A New Lanostane-type Triterpenoid from Chamaesyce Prostrata

Planta Medica. Jun, 1999  |  Pubmed ID: 17260274

A new triterpenoid, namely, lanost-25-en-3-beta-ol, and two known flavonoids (kaempferol-3,6-dimethyl ether and kaempferol 7- O-glucoside) were isolated from the aerial parts of Chamaesyce prostrate (Euphorbiaceae). The structure of the new compound was established based on spectral evidences.

EMSY Links the BRCA2 Pathway to Sporadic Breast and Ovarian Cancer

Cell. Nov, 2003  |  Pubmed ID: 14651845

The BRCA2 gene is mutated in familial breast and ovarian cancer, and its product is implicated in DNA repair and transcriptional regulation. Here we identify a protein, EMSY, which binds BRCA2 within a region (exon 3) deleted in cancer. EMSY is capable of silencing the activation potential of BRCA2 exon 3, associates with chromatin regulators HP1beta and BS69, and localizes to sites of repair following DNA damage. EMSY maps to chromosome 11q13.5, a region known to be involved in breast and ovarian cancer. We show that the EMSY gene is amplified almost exclusively in sporadic breast cancer (13%) and higher-grade ovarian cancer (17%). In addition, EMSY amplification is associated with worse survival, particularly in node-negative breast cancer, suggesting that it may be of prognostic value. The remarkable clinical overlap between sporadic EMSY amplification and familial BRCA2 deletion implicates a BRCA2 pathway in sporadic breast and ovarian cancer.

Shrapnell's Membrane in a Mammal Exposed to Extreme Pressure Variations: Morphological and Radiological Observations in the Hooded Seal

The Journal of Laryngology and Otology. Oct, 2003  |  Pubmed ID: 14653915

The function of Shrapnell's membrane (pars flaccida; PF) in middle-ear mechanics is still an enigma, though numerous proposals have been put forward, e.g. protection of pars tensa, equalizing of middle-ear pressure, sound transmission, and the site of origin of otitis media. In this study the PF was studied in a mammal (the hooded seal) which exposes itself to extreme pressure differences (from 1 to 100 atmospheres) when diving. Formaldehyde-fixed temporal bones obtained from newborn, one-year-old, and adult seals (three of each) were cleansed and decalcified in 10 per cent EDTA. The lateral wall of the middle-ear cavity, including the whole tympanic membrane with its bony surroundings, was then excised and photodocumented. Thin sections were cut parallel with, and perpendicular to, the handle of the malleus, stained with haematoxylin-eosin, toluidine blue or Giemsa stain and examined under a light microscope. One seal head was subjected to high resolution computerized tomography (HRCT) before sectioning. The PF was observed to be a narrow fissure measuring a maximum of 0.8 mm between processus brevis of the malleus and the notch of Rivinus in pars squamosa (pars tensa diameter 10-12 mm). It seems unlikely that the PF of the hooded seal participates in pressure equalization in the middle ear. The main function of the lateral wall of the attic, including the minimal PF, appears to be to protect the middle-ear ossicles and allow movement of the malleus.

Adults with Cystic Fibrosis: Meeting the Challenge!

Internal Medicine Journal. Dec, 2003  |  Pubmed ID: 14656234

The number of adults with cystic fibrosis (CF) is increasing. They are striving for independence and a fulfilling life with focus on career, relationships, education and finances at a time when lung function is likely to be declining and complications of this multi-system disease are increasing. Maintaining the quality and improving the duration of life are continuing challenges for the -clinician and the patient. Increased hope and greater expectations have been provided by a number of recent clinical advances and active research into novel treatments, including gene therapy. There has been increased recognition of the necessity for early diagnosis, adequate monitoring and effective intervention for complications such as diabetes and osteoporosis. Research into multi-resistant bacteria and clonal strains of Pseudomonas aeruginosa is ongoing and attention has focused on infection control policies. Although more high-level evidence is required on many issues confronting people with CF, a considerable effort has been made over the last decade to provide a more evidence-based approach to therapy with a number of large controlled clinical trials. For the adult with CF, there are also more decisions to be made. There is focus on reproductive health, with most couples enjoying the real possibility of having children. For those with advanced disease, the option for lung transplantation is well established. Maintenance of quality care will require adequate planning, effective transition programmes from paediatric to adult care, specialized training for doctors, nurses and allied health professionals and the allocation of sufficient resources to accommodate the inevitable increase in patient numbers.

Validation of the Quality of Life in Childhood Epilepsy Questionnaire in American Epilepsy Patients

Epilepsy & Behavior : E&B. Dec, 2003  |  Pubmed ID: 14698702

The aim of this study was to adapt the Australian Quality of Life in Childhood Epilepsy Questionnaire (QOLCE) and determine its psychometric properties in a North American population. Participants were North American families with children diagnosed with epilepsy. Parents were asked to complete the American QOLCE (USQOLCE) and the Child Health Questionnaire (CHQ). Seventy-one families completed the USQOLCE. The internal consistency reliability of the subscales was good. USQOLCE subscales correlated highly with theoretically similar subscales contained in the CHQ. Theoretically dissimilar subscales on the two instruments did not correlate as well. USQOLCE correlated significantly with a parental rating of seizure severity and an independent measure of degree of postoperative seizure control. This study demonstrated that the USQOLCE is suitable for a North American population with evidence of its reliability and validity including its sensitivity to seizure burden.

Granulomatous Diseases in a Patient with Cystic Fibrosis

Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society. Mar, 2003  |  Pubmed ID: 15463844

We report the case of an adult with Crohn's disease and pulmonary sarcoidosis on the background of cystic fibrosis (CF). There is a recognized association between Crohn's colitis and CF, but cases of pulmonary sarcoidosis in CF are rare. There may be a pathogenic link between the two granulomatous disorders and CF with chronic immune stimulation leading to hyperimmunoglobulinemia, circulating immune complexes and subsequent granuloma formation.

Improved Outcomes of Patients with Cystic Fibrosis Admitted to the Intensive Care Unit

Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society. Mar, 2004  |  Pubmed ID: 15463881

Invasive mechanical ventilation (IMV) has been previously associated with a poor outcome for patients with cystic fibrosis (CF), but with improved survival and the availability of lung transplantation intensive care unit (ICU) admission is being increasingly considered. This study aimed to review the outcomes of adult CF patients admitted to ICU, and to identify factors that may have influenced outcomes.

The Chemokine Fractalkine in Patients with Severe Traumatic Brain Injury and a Mouse Model of Closed Head Injury

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism. Oct, 2004  |  Pubmed ID: 15529011

The potential role of the chemokine Fractalkine (CX3CL1) in the pathophysiology of traumatic brain injury (TBI) was investigated in patients with head trauma and in mice after experimental cortical contusion. In control individuals, soluble (s)Fractalkine was present at low concentrations in cerebrospinal fluid (CSF) (12.6 to 57.3 pg/mL) but at much higher levels in serum (21,288 to 74,548 pg/mL). Elevation of sFractalkine in CSF of TBI patients was observed during the whole study period (means: 29.92 to 535.33 pg/mL), whereas serum levels remained within normal ranges (means: 3,100 to 59,159 pg/mL). Based on these differences, a possible passage of sFractalkine from blood to CSF was supported by the strong correlation between blood-brain barrier dysfunction (according to the CSF-/serum-albumin quotient) and sFractalkine concentrations in CSF (R = 0.706; P < 0.01). In the brain of mice subjected to closed head injury, neither Fractalkine protein nor mRNA were found to be augmented; however, Fractalkine receptor (CX3CR1) mRNA steadily increased peaking at 1 week postinjury (P < 0.05, one-way analysis of variance). This possibly implies the receptor to be the key factor determining the action of constitutively expressed Fractalkine. Altogether, these data suggest that the Fractalkine-CX3CR1 protein system may be involved in the inflammatory response to TBI, particularly for the accumulation of leukocytes in the injured parenchyma.

Antimycobacterial Compounds from Piper Sanctum

Journal of Natural Products. Dec, 2004  |  Pubmed ID: 15620234

Bioassay-guided chromatographic separation of the antimycobacterial extract of the leaves of Piper sanctum afforded 14 new compounds, identified as 2-oxo-12-(3',4'-methylenedioxyphenyl)dodecane (1), 2-oxo-14-(3',4'-methylenedioxyphenyl)tetradecane (2), 2-oxo-16-(3',4'-methylenedioxyphenyl)hexadecane (3), 2-oxo-18-(3',4'-methylenedioxyphenyl)octadecane (4), 2-oxo-14-(3',4'-methylenedioxyphenyl)-trans-13-tetradecene (5), 2-oxo-16-(3',4'-methylenedioxyphenyl)-trans-15-hexadecene (6), 2-oxo-18-(3',4'-methylenedioxyphenyl)-trans-17-octadecene (7), 2-oxo-16-phenyl-trans-3-hexadecene (8), methyl [6-(10-phenyldecanyl)tetrahydropyran-2-yl]acetate (9), methyl 2-(6-tridecyltetrahydro-2H-pyran-2-yl)acetate (10), methyl 2-(5-tetradecyltetrahydro-2-furanyl)acetate (11), 2-oxo-14-(3',4'-methylenedioxyphenyl)-trans-3-tetradecene (12), 2-oxo-16-(3',4'-methylenedioxyphenyl)-trans-3-hexadecene (13), and 2-oxo-16-phenyl-3-hexadecane (14). In addition, p-eugenol (15), methyleugenol (16), Z-piperolide (17), demethoxyyangonin (18), 5,6-dehydro-7,8-dihydromethysticin (19), cepharanone B (20), piperolactam A (21), cepharadione B (22), N-trans-feruloyltyramine (23), and N-trans-(p-coumaroyl)tyramine (24) were obtained from the anti-TBC stem extract of the plant. GC-MS and HPLC analyses of the essential oils of the leaves and stem revealed that safrol (25) was the major component of the oils. Compounds 2, 3, 6, 18-21, and 24 inhibited the growth of Mycobacterium tuberculosis when tested by the MABA assay, with MIC values ranging from 4 to 64 microg/mL.

Sequential Use of Oxygen and Bi-level Ventilation for Respiratory Failure in Cystic Fibrosis

Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society. Dec, 2004  |  Pubmed ID: 15698941

Supplemental nocturnal oxygen is widely used for hypoxaemic respiratory failure in adults with CF.

Memory Function in Childhood Epilepsy Syndromes

Journal of Paediatrics and Child Health. Jan-Feb, 2004  |  Pubmed ID: 14717999

Children with epilepsy are at risk of specific cognitive deficits. We aimed to compare and characterize the memory function of children with childhood absence epilepsy (CAE), frontal lobe epilepsy (FLE) and temporal lobe epilepsy (TLE).

EEG Power Spectra and Auditory P300 During Free Smoking and Enforced Smoking Abstinence

Pharmacology, Biochemistry, and Behavior. Jan, 2004  |  Pubmed ID: 14724047

We investigated resting EEG and auditory P300 during free smoking and 36 h of enforced smoking abstinence in 12 healthy volunteers. Resting EEG was recorded on 19 scalp leads and auditory P300 was obtained by an oddball paradigm task. Spectral analysis of EEG (absolute and relative power, mean frequency), latency and amplitude of auditory P300 were considered for statistical analysis. EEG changes were not significant during free smoking but were significant during smoking abstinence. Theta absolute power increased by +57% (P<.001), whereas alpha and delta absolute power increased by +26% (P<.01) and +19% (P<.01), respectively; theta absolute power change was delayed and prolonged. Alpha mean frequency reduced by -0.31 Hz (P<.001), whereas delta, theta and beta1 mean frequency increased by +0.13 Hz (P<.05), +0.09 Hz (P<.05) and +0.23 Hz (P<.01), respectively. Auditory P300 amplitude and latency were unaffected by smoking abstinence. Resting EEG, but not auditory P300, was sufficiently sensitive to detect changes during enforced smoking abstinence, and EEG bands had different temporal changes.

[Obstetric Brachial Plexus Injury]

Tidsskrift for Den Norske Lægeforening : Tidsskrift for Praktisk Medicin, Ny Række. Feb, 2004  |  Pubmed ID: 14983191

Antispasmodic Activity of Extracts and Compounds of Acalypha Phleoides Cav

Phytotherapy Research : PTR. Feb, 2004  |  Pubmed ID: 15022158

The aerial parts of Acalypha phleoides are usually prescribed in the Mexican traditional medicine for a variety of gastrointestinal complaints. The MeOH-CHCl(3) (1:1) extract of the aerial part of A. phleoides showed an inhibitory effect on the gastrointestinal propulsion of a charcoal meal in mice. In isolated guinea-pig ileum, this extract produced a concentration dependent inhibition of the contractions induced by 5-hydroxytryptamine, but it was unable to inhibit the contractions elicited by acetylcholine, histamine, KCl and BaCl(2). This extract produced also a concentration dependent inhibition of the spontaneous pendular movement of the isolated rabbit jejunum. This inhibitory activity was partially blocked by propranolol. The essential oil, obtained from the aerial part of this plant, was more potent than the MeOH-CHCl(3) (1:1) extract in inhibiting the spontaneous pendular movement of the rabbit jejunum. Thymol, camphor and gamma-terpinene were identified from the essential oil by GC-MS. These monoterpenes showed antispasmodic activity in the rabbit jejunum preparation, thymol was the most active compound, followed by camphor and gamma-terpinene. Thymol and camphor in high concentrations also showed tracheal relaxant properties, but gamma-terpinene did not. These in vivo and in vitro results tend to support the traditional use of A. phleoides as an antispasmodic agent.

Speech and Language Deterioration in Benign Rolandic Epilepsy

Journal of Child Neurology. Jan, 2004  |  Pubmed ID: 15032386

A 5-year-old boy presented with typical clinical and electrophysiologic features of benign rolandic epilepsy. His neurodevelopment, language, and behavior prior to the onset of epilepsy were appropriately normal. He demonstrated marked deterioration of language and cognitive function during the course to a mild and then a moderate disability range. Serial sleep electroencephalographic recordings initially showed continuous and bilateral rolandic discharges with evolution to localized left rolandic spikes. Language and cognitive improvements were subsequently seen. Educational support and evolution of the electroencephalogram to a localized focus could have been contributory. It is anticipated, however, that he will have significant long-term problems in complex language.

The Impact of Pan-resistant Bacterial Pathogens on Survival After Lung Transplantation in Cystic Fibrosis: Results from a Single Large Referral Centre

The Journal of Hospital Infection. Apr, 2004  |  Pubmed ID: 15066737

Reported actuarial one-year survival for patients with cystic fibrosis (CF) after lung transplant is 55-91%. Infection is the most common cause of early death. Colonization with Burkholderia cepacia complex is associated with reduced survival and international lung transplant referral guidelines support individual unit assessment policies for patients colonized with other pan-resistant bacteria. We examined local data on survival after transplant for CF to determine the impact of colonization with pan-resistant bacteria. A retrospective review of all CF patients from Royal Prince Alfred Hospital (RPAH), Sydney, who underwent lung transplantation at St Vincent's Hospital, Sydney, 1989-2002, was performed. Sixty-five patients were listed for lung transplantation with 54 (male: female=29:25) receiving transplants. Of the 11 patients (17%) who died on the waiting list, six were colonized with pan-resistant Pseudomonas aeruginosa. Thirty of the 54 transplanted patients had at least one pan-resistant organism before transplant. In 28 this included P. aeruginosa. Overall one-year survival was 92% with a median survival of 67 months. Overall survival for the pan-resistant group (N = 30) was not significantly different to survival in those with sensitive organisms (N = 24) (Logrank chi square = 1.6, P = 0.2). Three patients colonized with B. cepacia complex pre-transplant survive at 11, 40 and 60 months post-transplant. Infection contributed to 11 of the 18 post-transplant deaths, with pre-transplant-acquired bacterial pathogens responsible in two cases. Patients continued to acquire multiresistant bacteria post-transplantation. Lung transplant survival at St Vincent's Hospital for CF adults from RPAH compares favourably with international benchmarks. Importantly, colonization with pan-resistant bacteria pre-transplant did not appear to adversely affect survival post-transplant.

Unusual Case of Subcutaneous Panniculitis-like T-cell Lymphoma

The Australasian Journal of Dermatology. May, 2004  |  Pubmed ID: 15068459

An unusual case of subcutaneous panniculitis-like T-cell lymphoma is presented involving multiple organ systems, which eventually culminated in rapid demise from the haemophagocytic syndrome, after an initial protracted course. A 44-year-old man presented in April 2001 with bronchiolitis obliterans organising pneumonia that initially responded well to corticosteroids. However, the condition relapsed on attempted prednisone withdrawal in January 2002 and the patient was noted to have developed truncal subcutaneous nodules. Initial skin biopsy revealed lobular panniculitis, with negative microbiological culture. In July 2002, mononeuritis multiplex was diagnosed after the patient presented with paresthesiae and was treated with pulse cyclophosphamide therapy. By November 2002 there was ulceration of the subcutaneous nodules. Repeat skin biopsy revealed subcutaneous panniculitis-like T-cell lymphoma. The clinical manifestations were supportive of an unifying diagnosis of malignancy involving pulmonary, cutaneous and nervous systems. Combination chemotherapy with fludarabine, mitoxantrone and dexamethasone was commenced. However, the patient deteriorated, with fevers, weight loss, pancytopenia and laboratory features consistent with the haemophagocytic syndrome. Despite maximal supportive therapy the patient succumbed to his disease.

Sleep Disordered Breathing in Cystic Fibrosis

Sleep Medicine Reviews. Aug, 2004  |  Pubmed ID: 15233957

Cough, sleep fragmentation and oxyhaemoglobin desaturation have all been documented during sleep in patients with cystic fibrosis (CF). It has been proposed that repeated episodes of nocturnal hypoxia act as a stimulus for the development of pulmonary hypertension and right ventricular failure, a complication that is associated with a poor prognosis. In addition, sleep disturbance from these events could lead to poor daytime function and quality of life. This review provides a detailed description of the mechanisms underlying sleep disordered breathing in this population, what is known regarding its effects upon daytime function and current treatment options. Most importantly, we review what is needed from future research in this challenging area of care in patients with CF.

Origin of Extant Domesticated Sunflowers in Eastern North America

Nature. Jul, 2004  |  Pubmed ID: 15241413

Eastern North America is one of at least six regions of the world where agriculture is thought to have arisen wholly independently. The primary evidence for this hypothesis derives from morphological changes in the archaeobotanical record of three important crops--squash, goosefoot and sunflower--as well as an extinct minor cultigen, sumpweed. However, the geographical origins of two of the three primary domesticates--squash and goosefoot--are now debated, and until recently sunflower (Helianthus annuus L.) has been considered the only undisputed eastern North American domesticate. The discovery of 4,000-year-old domesticated sunflower remains from San Andrés, Tabasco, implies an earlier and possibly independent origin of domestication in Mexico and has stimulated a re-examination of the geographical origin of domesticated sunflower. Here we describe the genetic relationships and pattern of genetic drift between extant domesticated strains and wild populations collected from throughout the USA and Mexico. We show that extant domesticates arose in eastern North America, with a substantial genetic bottleneck occurring during domestication.

Cost of Using Levalbuterol in the Emergency Room

The Journal of Pediatrics. Sep, 2004  |  Pubmed ID: 15372720

State Level Classification of Serious Mental Illness: a Case for a More Uniform Standard

Journal of Health & Social Policy. 2004  |  Pubmed ID: 15774347

This study reports a national survey of U.S. states that was conducted from July of 1999 through March of 2001. The lack of consistent data on serious mental illness (SMI) provided the impetus for this study. Data was collected through a survey on states' definitions of SMI, on demographic information for patients with SMI, and on total annual per capita expenditures for SMI. Based on a 100% response rate, we found considerable variation among states in the definition used for SMI and the records kept on patients with SMI. This paper also involves a state-level statistical analysis of factors that may influence rates of per capita expenditures for SMI. The main finding using regression analysis was that per capita income and state definitions of mental illness that included DSM-III, DSM-IV, and ICD-9-CM diagnoses are significant and positively associated with a state's per capita expenditures for SMI. An additional finding is that accounting for all of the above factors, there still remains significant differences across major census divisions in per capita expenditures for the seriously mentally ill. Another major finding is that more consistent data collection is needed to take an epidemiological approach toward understanding the social conditions that contribute to SMI.

Reduction in Resting Energy Expenditure Following Lung Volume Reduction Surgery in Subjects with Chronic Obstructive Pulmonary Disease

Chronic Respiratory Disease. 2004  |  Pubmed ID: 16281646

Some subjects with COPD have an elevated resting energy expenditure (REE) which may be related to an increased work of breathing at rest. The purpose of this study was to examine the effect of lung volume reduction surgery (LVRS) on REE and body weight.

Quality of Life in Childhood Epilepsy: Validating the QOLCE

Journal of Paediatrics and Child Health. Mar, 2005  |  Pubmed ID: 15790332

The Effect of Infective Exacerbations on Sleep and Neurobehavioral Function in Cystic Fibrosis

American Journal of Respiratory and Critical Care Medicine. Jul, 2005  |  Pubmed ID: 15831839

Adults with cystic fibrosis (CF) are susceptible to hypoxemia, hypercapnia, arousal from sleep, and neurobehavioral impairment.

Spike Morphology, Location, and Frequency in Benign Epilepsy with Centrotemporal Spikes

Journal of Child Neurology. Mar, 2005  |  Pubmed ID: 15832607

The literature on benign epilepsy with centrotemporal spikes reports a constellation of neurophysiologic features in selected populations with heterogeneous methodologies. The aim of this study was to determine the specific electroencephalographic (EEG) features (spike morphology, location, and frequency and associated background slowing) in a broad population-based cohort identified through EEG laboratories. The mean spike frequency in the awake state was 9.3 per minute (95% confidence interval 6.5-12.0), in drowsiness, 21.2 per minute (16.7-25.6); and in sleep, 45.6 per minute (38.3-52.8), where 60% of patients had > 40 discharges per minute. In five patients, spike train rates occupied > 80% of the sleep record, and in nine patients, they occupied 61% to 80%. An ambulatory overnight record did not add new information comparing early-onset sleep with a mean spike frequency of 37.1 per minute (27.3-46.9) with slow-wave sleep, 36.0 per minute (27.3-44.7). Patients with benign epilepsy with centrotemporal spikes have a high spike burden, which can impact on cognitive function.

Glucocorticoid Regulation of Glial Responses During Hippocampal Neurodegeneration and Regeneration

Brain Research. Brain Research Reviews. Apr, 2005  |  Pubmed ID: 15850668

Glucocorticoids can prevent or accelerate neurodegeneration in the adult rat hippocampus. To investigate these actions of glucocorticoids, we previously cloned genes from the hippocampus. Adrenalectomy specifically increased glial fibrillary acidic protein and transforming growth factor (TGF)-beta1 mRNAs in the dentate gyrus and these effects were dependent on induced apoptosis. Corticosterone treatment prevented apoptosis, and decreased glial activation and the influx of activated microglia. Since these effects are opposite to injury and neurodegeneration, we propose that they represent adaptive actions of glucocorticoids, preventing cellular defense mechanisms from overshooting. We used adrenalectomy as a model to investigate how adult granule neurons die in vivo and the effects of neurotrophic factors in protecting against apoptosis. Neurotrophin-4/5 and TGF-beta1 protected granule neurons against adrenalectomy-induced apoptosis. Since neurogenesis is also greatly increased in the dentate gyrus following adrenalectomy, we compared the time course of birth and death with glial responses. TGF-beta1 mRNA increased before the detection of dying cells in the dentate gyrus, which was coincident with increased proliferation in the neurogenic zone. Glucocorticoids also increased Ndrg2 mRNA in glia in the neurogenic zone; Ndrg2 is a member of a novel gene family involved in neural differentiation and synapse formation. Therefore, studying the effects of glucocorticoid manipulation on the dentate gyrus is increasing our understanding of how mature neurons die by apoptosis and the role of glia in induced apoptosis and neurogenesis. Discovering how endocrine and inflammatory responses regulate neuron birth and survival is important for developing successful neuron replacement strategies to treat neurodegenerative diseases.

An Immunoproteomic Approach for Identification of Clinical Biomarkers for Monitoring Disease: Application to Cystic Fibrosis

Molecular & Cellular Proteomics : MCP. Aug, 2005  |  Pubmed ID: 15901828

Circulating antibodies can be used to probe protein arrays of body fluids, prepared by two-dimensional gel electrophoresis, for antigenic biomarker detection. However, detected proteins, particularly low abundance antigens, often remain unidentifiable due to proteome complexity and limiting sample amounts. Using a novel enrichment approach exploiting patient antibodies for isolation of antigenic biomarkers, we demonstrate how immunoproteomic strategies can accelerate biomarker discovery. Application of this approach as a means of identifying biomarkers was demonstrated for cystic fibrosis (CF) lung disease by isolation and identification of inflammatory-associated autoantigens, including myeloperoxidase and calgranulin B from sputum of subjects with CF. The approach was also exploited for isolation of proteins expressed by the Pseudomonas aeruginosa strain PA01. Capture of PA01 antigens using circulating antibodies from CF subjects implicated in vivo expression of Pseudomonas proteins. All CF subjects screened, but not controls, were immunoreactive against immunocaptured Pseudomonas proteins, representing stress (GroES and ferric iron-binding protein HitA), immunosuppressive (thioredoxin), and alginate synthetase pathway (nucleoside-diphosphate kinase) proteins, implicating their clinical relevance as biomarkers of infection.

Gene Finding in the Chicken Genome

BMC Bioinformatics. 2005  |  Pubmed ID: 15924626

Despite the continuous production of genome sequence for a number of organisms, reliable, comprehensive, and cost effective gene prediction remains problematic. This is particularly true for genomes for which there is not a large collection of known gene sequences, such as the recently published chicken genome. We used the chicken sequence to test comparative and homology-based gene-finding methods followed by experimental validation as an effective genome annotation method.

The Neuropsychological and Language Profile of Children with Benign Rolandic Epilepsy

Epilepsia. Jun, 2005  |  Pubmed ID: 15946332

Benign rolandic epilepsy (BRE) has an excellent prognosis for seizures, but recent research has raised concerns using cognition as an outcome measure. Methodologic problems related to recruitment bias and assessment processes are evident in previous studies. With well-defined criteria for inclusion and comprehensive assessment, the aim of this study was to define the cognitive profile of children with BRE and to assess the effect of interictal EEG activity.

Phytotoxins from Hofmeisteria Schaffneri: Isolation and Synthesis of 2'-(2' '-hydroxy-4' '-methylphenyl)-2'-oxoethyl Acetate1

Journal of Natural Products. Jun, 2005  |  Pubmed ID: 15974630

Activity-directed fractionation of a CH(2)Cl(2)-MeOH (1:1) extract of Hofmeisteria schaffneri led to the isolation of a new phytotoxin characterized as 2'-(2' '-hydroxy-4' '-methylphenyl)-2'-oxoethyl acetate and designated the trivial name of hofmeisterin (1). In addition, the known compounds beta-carotene, euparin, and 3',4',4a',9a'-tetrahydro-6,7'-dimethylspiro[benzofuran-3(2H),2'-pyrano[2,3-b]benzofuran]-2,4a'-diol (2) were obtained. The identification of the isolates was accomplished by spectroscopic methods. The structure of 1 was unequivocally confirmed by synthesis. The methyl derivative 1a was also synthesized following the same strategy. Compounds 1 and 2 inhibited radicle growth of Amaranthus hypochondriacus (IC(50) = 3.2 x 10(-4) and 1.2 x 10(-5) M, respectively) and significantly inhibited activation of the calmodulin (CaM)-dependent enzyme cAMP phosphodiesterase (PDE) with IC(50) values of 4.4 and 4.22 microM, respectively.

Gene Expression and Genotyping Studies Implicate the Interleukin 7 Receptor in the Pathogenesis of Primary Progressive Multiple Sclerosis

Journal of Molecular Medicine (Berlin, Germany). Oct, 2005  |  Pubmed ID: 16075257

Multiple sclerosis (MS) is an enigmatic disease of the central nervous system resulting in sclerotic plaques with the pathological hallmarks of demyelination and axonal damage, which can be directly or indirectly orchestrated by cells from the peripheral circulation. The majority of patients with MS follow a relapsing-remitting course in the early stages of the disease (RRMS) but most ultimately enter a secondary progressive phase (SPMS). About 10% of patients follow a primary progressive course from the onset (PPMS). We measured gene expression in whole blood of people with and without chronic progressive MS (CPMS), PPMS and SPMS, to discover genes which may be differentially expressed in peripheral blood in active disease, and so identify pathologically significant genes and pathways; and we investigated genetic differences in the promoters of dysregulated genes encoded in genomic regions associated with MS. If SPMS and PPMS were independently compared to the controls, there was little overlap in the set of most dysregulated genes. Ribosomal protein genes, whose expression is usually associated with cell proliferation and activation, were dramatically over-represented in the set of most down-regulated genes in PPMS compared to SPMS (P < 10(-4), chi(2)). The T cell proliferation gene IL7R (CD127) was also underexpressed in PPMS, but was up-regulated in SPMS compared to the controls. One interleukin 7 receptor (IL7R) promoter single nucleotide polymorphism (SNP), -504 C, was undertransmitted in PPMS trios (P = 0.05, TDT), and carriers of this allele were under-represented in PPMS cases from two independent patient cohorts (combined P = 0.006, FE). The four known IL7R promoter haplotypes were shown to have similar expression levels in healthy controls, but not in CPMS (P < 0.01, t test). These data support the hypothesis that PPMS has significant pathogenetic differences from SPMS, and that IL7R may be a useful therapeutic target in PPMS.

Combination Antibiotic Susceptibility Testing to Treat Exacerbations of Cystic Fibrosis Associated with Multiresistant Bacteria: a Randomised, Double-blind, Controlled Clinical Trial

Lancet. Aug 6-12, 2005  |  Pubmed ID: 16084254

We did a randomised, double-blind, controlled clinical trial to prospectively assess whether use of combination antibiotic susceptibility testing improved clinical outcomes in patients with acute pulmonary exacerbations of cystic fibrosis who were infected with multiresistant bacteria.

Antimycobacterial Agents from Selected Mexican Medicinal Plants

The Journal of Pharmacy and Pharmacology. Sep, 2005  |  Pubmed ID: 16105233

As part of the ICBG program Bioactive Agents from Dryland Biodiversity of Latin America, the present investigation was undertaken to explore the possible antimycobacterial potential of compounds derived from selected Mexican medicinal plants. Bioassay-guided fractionation of the crude extracts of Rumex hymenosepalus (Polygonaceae), Larrea divaricata (Zygophyllaceae), Phoradendron robinsonii (Loranthaceae) and Amphipteryngium adstringens (Julianiaceae) led to the isolation of several antimycobacterial compounds. Four stilbenoids, two flavan-3-ols and three anthraquinones were isolated from R. hymenosepalus. Two flavonols and nordihydroguaiaretic acid were obtained from L. divaricata. Sakuranetin was the antimycobacterial agent isolated from P. robinsonii. Two known triterpenoids and the novel natural product 3-dodecyl-1,8-dihydroxy-2-naphthoic acid were obtained from A. adstringens. In general, the isolates were identified by spectral means. The antimycobacterial activity of the secondary compounds isolated from the analysed species, as well as that of nine pure compounds previously isolated in our laboratories, was investigated; the MIC values ranged from 16 to 128 microg mL-1. Among the tested compounds, the glycolipids, sesquiterpenoids and triterpenoids showed the best antimycobacterial activity. The antimycobacterial property of the glycolipids is reported for the first time. Although the tested compounds showed moderate antimycobacterial activity, their presence in the analysed species provides the rationale for their traditional use in the treatment of tuberculosis.

Effect of Body Position on Maximal Expiratory Pressure and Flow in Adults with Cystic Fibrosis

Pediatric Pulmonology. Nov, 2005  |  Pubmed ID: 16130087

Maximum expiratory pressure (MEP) and peak expiratory flow rate (PEFR) are used as surrogate measures of cough and huff strength. Some body positions (particularly head-down tilt) significantly affect these measures in people with normal respiratory function and with chronic obstructive pulmonary disease. This may have implications for people with cystic fibrosis (CF), who use coughing and huffing and may use gravity-assisted drainage positions for airway clearance. Previous research concluded that body position does not affect MEP in people with CF, although head-down tilt was not examined and PEFR was not measured. This study investigated the effect of body position on MEP and PEFR in 20 adults with stable CF. Repeated measures of MEP and PEFR were performed across seven positions (standing, chair-sitting, sitting in bed with backrest vertical, sitting in bed with backrest at 45 degrees , supine, side-lying, and side-lying with head-down tilt 20 degrees ) in random order. During testing, reflux sensation and oxygenation were monitored. MEP was significantly reduced in side-lying and in the head-down tilt position. PEFRs were significantly reduced in the three-quarters sitting, supine, side-lying, and head-down positions. Oxygenation and reflux scores were worst in the head-down position. Despite statistical significance, the differences observed between positions in this stable population were of small magnitude. The effect of body position on MEP and PEFR may be more relevant during airway clearance treatments of the acutely unwell person with CF.

Tackling Obesity in Men -- Preliminary Evaluation of Men-only Groups Within a Commercial Slimming Organization

Journal of Human Nutrition and Dietetics : the Official Journal of the British Dietetic Association. Oct, 2005  |  Pubmed ID: 16150135

Over Slimming World's 36-year history men have always made up a small percentage of the slimming organization's membership. Past company research suggested that men would feel more comfortable in men-only groups rather than mixed. In 2002, Slimming World set a target to raise the awareness among men about the dangers of being overweight and made practical weight-management solutions more accessible through a national network of men's groups.

Effect of Sustained-release (SR) Bupropion on Craving and Withdrawal in Smokers Deprived of Cigarettes for 72 H

Psychopharmacology. Nov, 2005  |  Pubmed ID: 16160876

Sustained-release (SR) bupropion enhances quit rates of smokers, generally decreases tobacco withdrawal, and in some studies, reduces craving.

Proteomic Analysis of Sputum from Adults and Children with Cystic Fibrosis and from Control Subjects

American Journal of Respiratory and Critical Care Medicine. Dec, 2005  |  Pubmed ID: 16166615

Recurrent pulmonary exacerbations are associated with progressive lung disease in cystic fibrosis (CF). Current definitions of an exacerbation, although not precisely defined, include new/worsening symptoms, declining lung function, and/or changing radiologic appearance. Early diagnosis of exacerbations by rapid noninvasive means should expedite therapeutic intervention, thereby minimizing lung damage.

Antibiotic Susceptabilities of Pseudomonas Aeruginosa Isolates Derived from Patients with Cystic Fibrosis Under Aerobic, Anaerobic, and Biofilm Conditions

Journal of Clinical Microbiology. Oct, 2005  |  Pubmed ID: 16207967

Recent studies have determined that Pseudomonas aeruginosa can live in a biofilm mode within hypoxic mucus in the airways of patients with cystic fibrosis (CF). P. aeruginosa grown under anaerobic and biofilm conditions may better approximate in vivo growth conditions in the CF airways, and combination antibiotic susceptibility testing of anaerobically and biofilm-grown isolates may be more relevant than traditional susceptibility testing under planktonic aerobic conditions. We tested 16 multidrug-resistant isolates of P. aeruginosa derived from CF patients using multiple combination bactericidal testing to compare the efficacies of double and triple antibiotic combinations against the isolates grown under traditional aerobic planktonic conditions, in planktonic anaerobic conditions, and in biofilm mode. Both anaerobically grown and biofilm-grown bacteria were significantly less susceptible (P < 0.01) to single and combination antibiotics than corresponding aerobic planktonically grown isolates. Furthermore, the antibiotic combinations that were bactericidal under anaerobic conditions were often different from those that were bactericidal against the same organisms grown as biofilms. The most effective combinations under all conditions were colistin (tested at concentrations suitable for nebulization) either alone or in combination with tobramycin (10 microg ml(-1)), followed by meropenem combined with tobramycin or ciprofloxacin. The findings of this study illustrate that antibiotic sensitivities are dependent on culture conditions and highlight the complexities of choosing appropriate combination therapy for multidrug-resistant P. aeruginosa in the CF lung.

Effect of Airway Clearance Techniques on the Efficacy of the Sputum Induction Procedure

The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. Nov, 2005  |  Pubmed ID: 16264054

Sputum induction is used in the early identification of tuberculosis (TB) and pneumocystis infections of the lung. Although manual physiotherapy techniques to clear the airways are often incorporated in the sputum induction procedure, their efficacy in this setting is unknown. This randomised, crossover trial enrolled adults referred for sputum induction for suspected TB and pneumocystis infections of the lung. All participants underwent two sputum induction procedures, inhaling 3% saline via ultrasonic nebuliser. During one randomly allocated procedure, airway clearance techniques (chest wall percussion, vibration, huffing) were incorporated. In total, 59 participants completed the trial. The airway clearance techniques had no significant effect on how the test was tolerated, the volume expectorated or the quality of the sample obtained (assessed by the presence of alveolar macrophages). The techniques did not significantly affect how often the test identified a suspected organism, nor the sensitivity or specificity of sputum induction. In conclusion, the study was unable to demonstrate any effect of airway clearance techniques on the sputum induction procedure. The results provide some justification for not including airway clearance techniques as part of the sputum induction procedure.

Supported and Unsupported Arm Exercise Capacity Following Lung Volume Reduction Surgery: a Pilot Study

Chronic Respiratory Disease. 2005  |  Pubmed ID: 16279152

Lung volume reduction surgery (LVRS) has been shown to improve lung function, leg exercise capacity and quality of life in subjects with severe COPD. This is the first study to examine the effect of LVRS on supported and unsupported arm exercise capacity.

Determination of Some Toxic and Essential Metal Ions in Medicinal and Edible Plants from Mali

Journal of Agricultural and Food Chemistry. Mar, 2005  |  Pubmed ID: 15769174

Plants are used in different ways in Mali, among those as medicine and as food. The monitoring of metals in the plants is of great importance for protecting the public from the hazards of possible toxic effects and also for informing the population about the nutritional value of the plants. The concentrations of some toxic and essential metal ions were surveyed in seven medicinal and edible plants from Mali. Dry ashing of the plant material and subsequent use of atomic absorption spectrophotometry were the analytical methodologies used. Iron, manganese, and zinc were found in high concentrations in some of the plants, i.e., 1.4 and 1.5 mg/g iron in Cuminum cyminum and Bombax costatum, respectively, 243 microg/g manganese in Hibiscus sabdariffa, and 62.8 and 67.1 microg/g zinc in Spilanthes oleracaea and B. costatum, respectively, whereas cobalt and cadmium were not detected in any of the plant material studied. The other ions detected, Cr, Ni, Pb, and Cu, were present in minor amounts, in the ranges of 2.2-17.2 microg/g for Cr, 1.6-8.1 microg/g for Ni, 0.7-5.2 microg/g for Pb, and 2.4-17.1 microg/g for Cu. From a toxicological point of view, none of these plants would be harmful for the user by taking in the plant material in the traditional manner, which is preparing an infusion of the plant using amounts not adding up to those necessary to reach a harmful level of the metal ions detected. The plants B. costatum and C. cyminum could be of interest as sources for iron for humans in the case of too low of a level of hemoglobin.

The DNA Sequence of the Human X Chromosome

Nature. Mar, 2005  |  Pubmed ID: 15772651

The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise process that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a distribution that is consistent with their proposed role as way stations in the process of X-chromosome inactivation. We found 1,098 genes in the sequence, of which 99 encode proteins expressed in testis and in various tumour types. A disproportionately high number of mendelian diseases are documented for the X chromosome. Of this number, 168 have been explained by mutations in 113 X-linked genes, which in many cases were characterized with the aid of the DNA sequence.

Method for Detection of Respiratory Viruses in the Sputa of Patients with Cystic Fibrosis

European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. Jan, 2005  |  Pubmed ID: 15616837

Since the role of respiratory viruses in lung exacerbations of patients with cystic fibrosis has been hampered by the difficulty of detecting viruses in viscous sputum specimens, a multiplex reverse transcriptase PCR (RT-PCR) assay combined with colorimetric amplicon detection was tested for the identification of seven common respiratory viruses in the sputa of cystic fibrosis patients. Of 52 sputa from 38 patients, 12 (23%) samples from 12 patients were positive for a respiratory virus (4 for influenza B, 3 for parainfluenza 1, 3 for influenza A and 2 for respiratory syncytial virus). These results suggest that the RT-PCR method carried out on sputum may provide a convenient means of investigating the role of virus infection in lung exacerbations of cystic fibrosis patients.

Nitrification Parameter Measurement for Plant Design: Experience and Experimental Issues with New Methods

Water Science and Technology : a Journal of the International Association on Water Pollution Research. 2005  |  Pubmed ID: 16459822

Nitrification kinetics are important for process design, optimization, and capacity rating of activated sludge wastewater treatment plants. A Water Environment Research Foundation (WERF) project on Methods for Wastewater Characterization in Activated Sludge Modeling (WERF, 2003) focused significantly on the development of procedures for measuring the nitrifier maximum specific growth rate, micro(AUT). In addition, the importance of (and lack of data for) the nitrifier decay rate, b(AUT), was identified. This paper describes three bench-scale methods for measuring micro(AUT): the Low F/M SBR, Washout and High F/M methods. During the WERF project, the importance of pH and temperature control was investigated briefly; this paper summarizes further experimental work performed to address these issues. A summary of micro(AUT) measurements in a number of locations and using the different measurement techniques is provided.

Importance and Measurement of Decay Rate when Assessing Nitrification Kinetics

Water Science and Technology : a Journal of the International Association on Water Pollution Research. 2005  |  Pubmed ID: 16459823

Nitrification kinetics are important for process design, optimization and capacity rating of activated sludge wastewater treatment plants. Assessment of nitrification behaviour historically has focused on measuring the nitrifier maximum specific growth rate, micro(AUT). Very little attention has been directed at the of nitrifier organism rate has been assumed negligible. However, incorrect assessment of decay rate leads to errors in the micro(AUT) estimate; the magnitude of the error depends on the micro(AUT) measurement method employed. This paper illustrates why decay rate is important when measuring micro(AUT), and that the decay rate is significant. The paper also explains why measurement methods for nitrifier decay may have underestimated the decay rate. Results from an experiment incorporating improvements to previously suggested methods and data analysis are presented.

Using E-mail in the Management of Tuberculosis Patients, North-west Russia

The International Journal of Tuberculosis and Lung Disease : the Official Journal of the International Union Against Tuberculosis and Lung Disease. Dec, 2005  |  Pubmed ID: 16466060

Ten health care institutions in north-west Russia.

Airborne Fibres in the Norwegian Silicon Carbide Industry

The Annals of Occupational Hygiene. Apr, 2006  |  Pubmed ID: 16497830

Morphology of silicon carbide (SiC) fibres from the Norwegian SiC industry has been studied by scanning electron microscopy (SEM). The fibres are an unwanted side-product in SiC production. They represent a probable cause of the observed increased occurrence of lung diseases among SiC workers. The main aim of this work is to give a detailed description of the morphological variation of the fibres. Furthermore, it is important to study the occurrence of various morphological types with respect to job types and process parameters. SiC fibres accounted for >90% of all fibres observed. Eight categories of SiC fibres are described based on their morphology. The most frequent fibre category had a smooth surface and accounted for more than half of the observed SiC fibres. The diameter distributions of the eight fibre types were significantly different except for two of the categories. More than 99% of the SiC fibres observed were <3 microm in diameter, satisfying one WHO criterion for health relevant fibres. The aspect ratio and diameter of health-relevant fibres generally followed a lognormal distribution for different fibre categories, whereas fibre length did not. The proportions of SiC fibres (all categories) did not differ significantly between the plants. The proportions differed between plants for two SiC fibre categories including the most dominant type. For two SiC fibre categories and the SiC cleavage fragments differences were observed between job groups. Two other fibre categories were correlated with type of SiC produced (i.e. black or green SiC) and sawdust added to the raw material mix.

The Impact of Epilepsy Surgery on Quality of Life in Children

Neurology. Feb, 2006  |  Pubmed ID: 16505311

To determine if epilepsy surgery is effective in improving the quality of life (QOL) of children with intractable seizures using the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE).

Exercise Capacity and Quadriceps Muscle Metabolism Following Training in Subjects with COPD

Respiratory Medicine. Oct, 2006  |  Pubmed ID: 16516454

The aim of the study was to determine whether 16 sessions of exercise training, completed twice weekly, alters exercise capacity, quadriceps muscle metabolism, cross-sectional area (CSA) and strength in subjects with chronic obstructive pulmonary disease (COPD). We studied (a) 10 COPD subjects (mean age+/-sem = 71+/-2 years; FEV1 = 0.99+/-0.1 L) before and after 16 sessions of exercise training, and (b) 10 healthy subjects (age = 68+/-3 years). The COPD subjects underwent an incremental peak exercise test using a cycle ergometer and a 6-min walk test: both improved following exercise training (P < 0.05). Magnetic resonance spectroscopy measurements, in quadriceps muscle, of post-exercise phosphocreatinine (PCr) recovery kinetics were used to assess mitochondrial function in vivo: in the COPD subjects pre-training this was 19+/-8% lower than in healthy subjects (P = 0.03), but a 38+/-12% increase was seen in the COPD subjects following training (P = 0.003). Magnetic resonance imaging was used to assess quadriceps CSA: after training in the COPD subjects this showed a 7+/-2% increase (P = 0.03). Quadriceps strength, measured by the best of five maximum voluntary contractions, also showed a 32+/-11% increase in the COPD subjects (P = 0.007). Sixteen sessions of exercise training, performed twice weekly, increased exercise capacity as well as quadriceps mitochondrial capacity, CSA and strength in the subjects with COPD.

A Preliminary Investigation of Barriers to Achieving Patient-centered Communication with Patients Who Have Stroke-related Communication Disorders

Topics in Stroke Rehabilitation. 2006  |  Pubmed ID: 16581632

This article reports on research investigating barriers to achieving patient-centered communication (PCC) with patients who have stroke-related communication disorders. A focus group, including people who had strokes and their family members, identified PCC issues they encounter when communicating with health care providers. The two key themes that emerged from this research were the desire to be treated with respect and the importance of allowing adequate time for a person with a speech disorder to communicate. Suggestions are given for improving PCC with people who have stroke-related communication disorders.

The DNA Sequence and Biological Annotation of Human Chromosome 1

Nature. May, 2006  |  Pubmed ID: 16710414

The reference sequence for each human chromosome provides the framework for understanding genome function, variation and evolution. Here we report the finished sequence and biological annotation of human chromosome 1. Chromosome 1 is gene-dense, with 3,141 genes and 991 pseudogenes, and many coding sequences overlap. Rearrangements and mutations of chromosome 1 are prevalent in cancer and many other diseases. Patterns of sequence variation reveal signals of recent selection in specific genes that may contribute to human fitness, and also in regions where no function is evident. Fine-scale recombination occurs in hotspots of varying intensity along the sequence, and is enriched near genes. These and other studies of human biology and disease encoded within chromosome 1 are made possible with the highly accurate annotated sequence, as part of the completed set of chromosome sequences that comprise the reference human genome.

Fitting Back In: Adolescents Returning to School After Severe Acquired Brain Injury

Disability and Rehabilitation. Jun, 2006  |  Pubmed ID: 16754574

To explore the experiences of Australian adolescents with severe acquired brain injury (ABI) and their families as the adolescent returned to school. In particular, to understand the influence of services and support on the school return.

Nedd4-WW Domain-binding Protein 5 (Ndfip1) is Associated with Neuronal Survival After Acute Cortical Brain Injury

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. Jul, 2006  |  Pubmed ID: 16822981

Understanding the transcriptional response to neuronal injury after trauma is a necessary prelude to formulation of therapeutic strategies. We used Serial Analysis of Gene Expression (SAGE) to identify 50,000 sequence tags representing 18,000 expressed genes in the cortex 2 h after traumatic brain injury (TBI). A similar tag library was obtained from sham-operated cortex. The SAGE data were validated on biological replicates using quantitative real-time-PCR on multiple samples at 2, 6, 12, and 24 h after TBI. This analysis revealed that the vast majority of genes showed a downward trend in their pattern of expression over 24 h. This was confirmed for a subset of genes using in situ hybridization and immunocytochemistry on brain sections. Of the overexpressed genes in the trauma library, Nedd4-WW (neural precursor cell expressed, developmentally downregulated) domain-binding protein 5 (N4WBP5) (also known as Ndfip1) is strongly expressed in surviving neurons around the site of injury. Overexpression of N4WBP5 in cultured cortical neurons increased the number of surviving neurons after gene transfection and growth factor starvation compared with control transfections. These results identify N4WBP5 as a neuroprotective protein and, based on its known interaction with the ubiquitin ligase Nedd4, would suggest protein ubiquitination as a possible survival strategy in neuronal injury.

Sharing Responsibility for Education

Nursing New Zealand (Wellington, N.Z. : 1995). Jun, 2006  |  Pubmed ID: 16841541

Predictors of Pulmonary Exacerbations in Patients with Cystic Fibrosis Infected with Multi-resistant Bacteria

Thorax. Nov, 2006  |  Pubmed ID: 16844728

This study examined characteristics of adult and adolescent patients with cystic fibrosis (CF) to determine factors associated with an increased risk of pulmonary exacerbations.

Longitudinal Assessment of Neuropsychologic and Language Function in Children with Benign Rolandic Epilepsy

Journal of Child Neurology. Jun, 2006  |  Pubmed ID: 16948938

Previous studies of benign rolandic epilepsy have reported improvement in cognitive functioning over time. Their focus was the impact of paroxysmal electroencephalographic (EEG) activity on neuropsychologic function. Comprehensive longitudinal language assessment has not previously been undertaken. In a cross-sectional study, we demonstrated that some children with benign rolandic epilepsy have difficulties in verbal and visual memory and phonologic awareness. The current study evaluated a subgroup longitudinally to determine if difficulties improved. Twenty-eight patients underwent comprehensive longitudinal neuropsychologic and language assessments. The clinical features evaluated included seizure frequency, absolute age, medications, and a follow-up EEG. Differences in performance were analyzed using t-tests. Improvement in cognitive functioning, particularly in the areas of verbal memory, receptive language ability, and phonemic manipulation, was demonstrated. Visual memory and aspects of phonologic awareness showed no change. The improvements were not related to the clinical variables. It is important to recognize cognitive difficulties in children with benign rolandic epilepsy. Some difficulties can resolve; however, continued monitoring, particularly in areas of visual memory and phonologic awareness, is required.

Activin a Release into Cerebrospinal Fluid in a Subset of Patients with Severe Traumatic Brain Injury

Journal of Neurotrauma. Sep, 2006  |  Pubmed ID: 16958581

Activin A is a member of the transforming growth factor-beta superfamily and has been demonstrated to be elevated during inflammation and to have neuroprotective properties following neural insults. In this study, we examined whether traumatic brain injury (TBI) induced a response in activin A or in the concentrations of its binding protein, follistatin. Thirty-nine patients with severe TBI had daily, matched cerebrospinal fluid (CSF) and serum samples collected post-TBI and these were assayed for activin A and follistatin using specific immunoassays. Concentrations of both molecules were assessed relative to a variety of clinical parameters, such as the Glasgow Coma Score, computer tomography classification of TBI, measurement of injury markers, cell metabolism and membrane breakdown products. In about half of the patients, there was a notable increase in CSF activin A concentrations in the first few days post-TBI. There were only minor perturbations in either serum activin or in either CSF or serum follistatin concentrations. The CSF activin A response was not related to any of the common TBI indices, but was strongly correlated with two common markers of brain damage, neuronal specific enolase and S100-beta. Further, activin A levels were also associated with indices of metabolism, such as lactate and pyruvate, excitotoxicity (glutamate) and membrane lipid breakdown products such as glycerol. In one of the two patients who developed a CSF infection, activin A concentrations in CSF became markedly elevated. Thus, some TBI patients have an early release of activin A into the CSF that may result from activation of inflammatory and/or neuroprotective pathways.

Quality of Life of Children with Benign Rolandic Epilepsy

Pediatric Neurology. Oct, 2006  |  Pubmed ID: 16996395

The first objective of this study was to determine the quality of life of children with benign rolandic epilepsy. Secondly, this investigation aimed to predict the influence of cognition on quality of life, controlling for the emotional impact of the epilepsy on the parent. Initial recruitment was through the major electroencephalography laboratories of metropolitan Sydney. The syndrome was defined using the International League Against Epilepsy classification. Patients underwent a comprehensive cognitive assessment, and parents completed the Child Health Questionnaire, Child Behavior Checklist, and Quality of Life in Childhood Epilepsy Questionnaire. Parental emotional impact was assessed using a subscale from the Child Health Questionnaire. The cohort included 30 patients (22 males, 8 females), mean age 9.67 years. There was a higher incidence of competence problems compared with normative data. The average psychosocial score was significantly lower than normative data. Controlling for parental emotional impact, general intellectual ability predicted quality of life in the areas of self-esteem and language. Clinical variables had minimal impact and were not included in the regression models. Parental emotional impact, however, was a major independent predictor of quality of life. Quality of life may be compromised in children with benign rolandic epilepsy and is related to cognitive variables and emotional impact of the epilepsy on the parent.

Inhaled Hypertonic Saline As a Therapy for Cystic Fibrosis

Current Opinion in Pulmonary Medicine. Nov, 2006  |  Pubmed ID: 17053496

The beneficial effect of a short course of nebulized hypertonic saline on lung function for people with cystic fibrosis was first identified in 1996. At that time, competing hypotheses about the pathogenesis of cystic fibrosis lung disease predicted very different responses to long-term inhalation of hypertonic saline.

Profiling of the Resin Glycoside Content of Mexican Jalap Roots with Purgative Activity

Journal of Natural Products. Oct, 2006  |  Pubmed ID: 17067162

Mexican Jalap roots, a prehispanic medicinal plant complex still considered to be a useful laxative, can be found as an ingredient in some over-the-counter products sold by herbalists in contemporary Mexico. The drug is prepared from the dried roots of several morning glories, all of which have been identified as members of the genus Ipomoea. Analysis of several commercial samples was assessed by generating HPLC and 13C NMR spectroscopic profiles of the glycosidic acids obtained through saponification of the resin glycoside contents. These profiles distinguish the three Mexican jalaps currently in frequent use and can serve as analytical tools for the authentication and quality control of these purgative herbal drugs. Ipomoea purga, the authentic "jalap root", yielded two new hexasaccharides of convolvulinic and jalapinolic acids, purgic acids A (1) and B (2), respectively. Scammonic acid A (3), a tetrasaccharide, was produced from Ipomoea orizabensis, the Mexican scammony or false jalap. Operculinic acid B (4), a pentasaccharide, was identified in Ipomoea stans. Semipreparative HPLC was performed to obtain pure samples of new compounds 1 and 2 in sufficient quantity to elucidate their structure by high-field NMR spectroscopy. Purgic acid A (1) was identified as (11S)-hydroxytetradecanoic acid 11-O-beta-D-quinovopyranosyl-(1-->2)-O-beta-D-glucopyranosyl-(1-->3)-O-[beta-D-fucopyranosyl-(1-->4)]-O-alpha-L-rhamnopyranosyl-(1-->2)-O-beta-D-glucopyranosyl-(1-->2)-O-beta-D-quinovopyranoside, while purgic acid B (2) was characterized with (11S)-hydroxyhexadecanoic acid as its aglycon but having the same glycosidation sequence in the oligosaccharide core.

HIV Induces Maturation of Monocyte-derived Dendritic Cells and Langerhans Cells

Journal of Immunology (Baltimore, Md. : 1950). Nov, 2006  |  Pubmed ID: 17082627

In HIV infection, dendritic cells (DCs) may play multiple roles, probably including initial HIV uptake in the anogenital mucosa, transport to lymph nodes, and subsequent transfer to T cells. The effects of HIV-1 on DC maturation are controversial, with several recent conflicting reports in the literature. In this study, microarray studies, confirmed by real-time PCR, demonstrated that the genes encoding DC surface maturation markers were among the most differentially expressed in monocyte-derived dendritic cells (MDDCs), derived from human blood, treated with live or aldrithriol-2-inactivated HIV-1(BaL). These effects translated to enhanced cell surface expression of these proteins but differential expression of maturation markers was only partial compared with the effects of a conventional potent maturation stimulus. Such partially mature MDDCs can be converted to fully mature cells by this same potent stimulus. Furthermore, live HIV-1 stimulated greater changes in maturation marker surface expression than aldrithriol-2-inactivated HIV-1 and this enhanced stimulation by live HIV-1 was mediated via CCR5, thus suggesting both viral replication-dependent and -independent mechanisms. These partially mature MDDCs demonstrated enhanced CCR7-mediated migration and are also able to stimulate interacting T cells in a MLR, suggesting DCs harboring HIV-1 might prepare CD4 lymphocytes for transfer of HIV-1. Increased maturation marker surface expression was also demonstrated in native DCs, ex vivo Langerhans cells derived from human skin. Thus, HIV initiates maturation of DCs which could facilitate subsequent enhanced transfer to T cells.

Protease IV Production in Pseudomonas Aeruginosa from the Lungs of Adults with Cystic Fibrosis

Journal of Medical Microbiology. Dec, 2006  |  Pubmed ID: 17108265

Protease IV is important in the pathogenesis of Pseudomonas aeruginosa-induced microbial keratitis, but little is known of its role in cystic fibrosis (CF) lung infection. In this study protease IV production was examined in 43 P. aeruginosa isolates (24 non-clonal and 19 clonal) from the lungs of chronically infected adult patients attending the Royal Prince Alfred Hospital CF Clinic, Sydney, Australia. Overall, 32/43 (74 %) isolates were positive for protease IV protein by Western blotting and 22/43 (51 %) had evidence of active protease IV on gelatin zymography. Clonal strains were 1.6 times more likely than non-clonal strains to produce protease IV [18/19 (95 %) versus 14/24 (58 %), RR=1.6, CI 1.1-2.3, P=0.007] and 3 times more likely to secrete the protein [16/19 (84 %) versus 6/24 (25 %), RR=3.4, CI 1.6-6.9, P<0.001]. Nine of the ten strains negative by both Western blotting and zymography were non-clonal, and all but one of these was positive for the protease IV gene. There was a marked strain-to-strain variation in the amount of protease IV produced. Secretion of protease IV by clonal strains may enhance their infectivity and ability to adapt to the changing CF lung environment. Overall the findings suggest that protease IV plays an important role in the pathogenesis of P. aeruginosa infection in the CF lung.

A Controlled Trial of Long-term Inhaled Hypertonic Saline in Patients with Cystic Fibrosis

The New England Journal of Medicine. Jan, 2006  |  Pubmed ID: 16421364

Inhaled hypertonic saline acutely increases mucociliary clearance and, in short-term trials, improves lung function in people with cystic fibrosis. We tested the safety and efficacy of inhaled hypertonic saline in a long-term trial.

Transient Neuroprotection by Minocycline Following Traumatic Brain Injury is Associated with Attenuated Microglial Activation but No Changes in Cell Apoptosis or Neutrophil Infiltration

Experimental Neurology. Mar, 2007  |  Pubmed ID: 17188268

Cerebral inflammation and apoptotic cell death are two processes implicated in the progressive tissue damage that occurs following traumatic brain injury (TBI), and strategies to inhibit one or both of these pathways are being investigated as potential therapies for TBI patients. The tetracycline derivative minocycline was therapeutically effective in various models of central nervous system injury and disease, via mechanisms involving suppression of inflammation and apoptosis. We therefore investigated the effect of minocycline in TBI using a closed head injury model. Following TBI, mice were treated with minocycline or vehicle, and the effect on neurological outcome, lesion volume, inflammation and apoptosis was evaluated for up to 7 days. Our results show that while minocycline decreases lesion volume and improves neurological outcome at 1 day post-trauma, this response is not maintained at 4 days. The early beneficial effect is likely not due to anti-apoptotic mechanisms, as the density of apoptotic cells is not affected at either time-point. However, protection by minocycline is associated with a selective anti-inflammatory response, in that microglial activation and interleukin-1beta expression are reduced, while neutrophil infiltration and expression of multiple cytokines are not affected. These findings demonstrate that further studies on minocycline in TBI are necessary in order to consider it as a novel therapy for brain-injured patients.

Changes in Blood-brain Barrier Permeability to Large and Small Molecules Following Traumatic Brain Injury in Mice

The European Journal of Neuroscience. Jan, 2007  |  Pubmed ID: 17241284

The entry of therapeutic compounds into the brain and spinal cord is normally restricted by barrier mechanisms in cerebral blood vessels (blood-brain barrier) and choroid plexuses (blood-CSF barrier). In the injured brain, ruptured cerebral blood vessels circumvent these barrier mechanisms by allowing blood contents to escape directly into the brain parenchyma. This process may contribute to the secondary damage that follows the initial primary injury. However, this localized compromise of barrier function in the injured brain may also provide a 'window of opportunity' through which drugs that do not normally cross the blood-brain barriers are able to do so. This paper describes a systematic study of barrier permeability in a mouse model of traumatic brain injury using both small and large inert molecules that can be visualized or quantified. The results show that soon after trauma, both large and small molecules are able to enter the brain in and around the injury site. Barrier restriction to large (protein-sized) molecules is restored by 4-5 h after injury. In contrast, smaller molecules (286-10,000 Da) are still able to enter the brain as long as 4 days postinjury. Thus the period of potential secondary damage from barrier disruption and the period during which therapeutic compounds have direct access to the injured brain may be longer than previously thought.

Voxel-based Morphometry in the Detection of Dysplasia and Neoplasia in Childhood Epilepsy: Combined Grey/white Matter Analysis Augments Detection

Epilepsy Research. Dec, 2007  |  Pubmed ID: 17997078

Analysis of grey matter on MRI utilising voxel-based morphometry (VBM) may have insufficient sensitivity for routine clinical application. The aim of this exploratory study was to evaluate combined analysis of grey and white matter using VBM for detecting focal lesions underlying childhood epilepsy, and to establish the optimal statistical parameters in this context.

Telemedicine in Practice in Arkhangelsk Region, Russia: from a Blank Page to Routine Operation

International Journal of Circumpolar Health. Sep, 2007  |  Pubmed ID: 18018847

This article describes the telemedical activities in the Arkhangelsk region of north-west Russia from 1996 to 2004, and some of the outcomes of introducing telemedicine in health care.

Modulation of Immune Response by Head Injury

Injury. Dec, 2007  |  Pubmed ID: 18048036

Despite the fact that traumatic brain injury (TBI) is a silently growing epidemic, we are yet to understand its multifaceted pathogenesis, where various cellular pathways are initiated in response to both the primary mechanical insult and secondary physiologically mediated injury. Although the brain has traditionally been considered an immunologically privileged site, evidence to the contrary exists in studies of central nervous system (CNS) pathology, in particular TBI. Transmigration of leukocytes following blood brain barrier (BBB) disruption results in activation of resident cells of the CNS, such as microglia and astrocytes, to possess immunological function. Both infiltrating peripheral immune cells and activated resident cells subsequently engage in the intrathecal production of cytokines, important indicators of the presence of neuroinflammation. Cytokines can either promote this neurotoxicity, by encouraging excitotoxicity and propagating the inflammatory response, or attenuate the damage through neuroprotective and neurotrophic mechanisms, including the induction of cell growth factors. Certain cytokines perform both functions, for example, interleukin-6 (IL-6). This review article discusses the notion that the inflammatory response to TBI is no longer a peripherally mediated phenomenon, and that the CNS significantly influences the immunological sequence of events in the aftermath of injury.

Determination of Suitable Housekeeping Genes for Normalisation of Quantitative Real Time PCR Analysis of Cells Infected with Human Immunodeficiency Virus and Herpes Viruses

Virology Journal. 2007  |  Pubmed ID: 18053162

The choice of an appropriate housekeeping gene for normalisation purposes has now become an essential requirement when designing QPCR experiments. This is of particular importance when using QPCR to measure viral and cellular gene transcription levels in the context of viral infections as viruses can significantly interfere with host cell pathways, the components of which traditional housekeeping genes often encode. In this study we have determined the reliability of 10 housekeeping genes in context of four heavily studied viral infections; human immunodeficiency virus type 1, herpes simplex virus type 1, cytomegalovirus and varicella zoster virus infections using a variety of cell types and virus strains. This provides researchers of these viruses with a shortlist of potential housekeeping genes to use as normalisers for QPCR experiments.

Alcohol and Violence: Use of Possible Confounders in a Time-series Analysis

Addiction (Abingdon, England). Mar, 2007  |  Pubmed ID: 17298643

To assess the aggregate association between alcohol consumption and violence, while controlling for potential confounders.

Glycosylation of Sputum Mucins is Altered in Cystic Fibrosis Patients

Glycobiology. Jul, 2007  |  Pubmed ID: 17392389

Cystic fibrosis (CF) is characterized by chronic lung infection and inflammation, with periods of acute exacerbation causing severe and irreversible lung tissue damage. We used protein and glycosylation analysis of high-molecular mass proteins in saline-induced sputum from CF adults with and without an acute exacerbation, CF children with stable disease and preserved lung function, and healthy non-CF adult and child controls to identify potential biomarkers of lung condition. While the main high-molecular mass proteins in the sputum from all subjects were the mucins MUC5B and MUC5AC, these appeared degraded in CF adults with an exacerbation. The glycosylation of these mucins also showed reduced sulfation, increased sialylation, and reduced fucosylation in CF adults compared with controls. Despite improvements in pulmonary function after hospitalization, these differences remained. Two CF children showed glycoprotein profiles similar to those of CF adults with exacerbations and also presented with pulmonary flares shortly after sampling, while the remaining CF children had profiles indistinguishable from those of healthy non-CF controls. Sputum mucin glycosylation and degradation are therefore not inherently different in CF, and may also be useful predictive biomarkers of lung condition.

Phenotypic Characterization of Clonal and Nonclonal Pseudomonas Aeruginosa Strains Isolated from Lungs of Adults with Cystic Fibrosis

Journal of Clinical Microbiology. Jun, 2007  |  Pubmed ID: 17392437

The emergence of virulent Pseudomonas aeruginosa clones is a threat to cystic fibrosis (CF) patients globally. Characterization of clonal P. aeruginosa strains is critical for an understanding of its clinical impact and developing strategies to meet this problem. Two clonal strains (AES-1 and AES-2) are circulating within CF centers in eastern Australia. In this study, phenotypic characteristics of 43 (14 AES-1, 5 AES-2, and 24 nonclonal) P. aeruginosa isolates were compared to gain insight into the properties of clonal strains. All 43 isolates produced bands of the predicted size in PCRs for vfr, rhlI, rhlR, lasA, lasB, aprA, rhlAB, and exoS genes; 42 were positive for lasI and lasR, and none had exoU. Thirty-seven (86%) isolates were positive in total protease assays; on zymography, 24 (56%) produced elastase/staphylolysin and 22 (51%) produced alkaline protease. Clonal isolates were more likely than nonclonal isolates to be positive for total proteases (P = 0.02), to show elastase and alkaline protease activity by zymography (P = 0.04 and P = 0.01, respectively), and to show elastase activity by the elastin-Congo red assay (P = 0.04). There were no other associations with genotype. Overall, increasing patient age was associated with decreasing elastase activity (P = 0.03). Thirty-two (74%) isolates had at least one N-acylhomoserine lactone (AHL) by thin-layer chromatography. rhl-associated AHL detection was associated with the production and level of total protease and elastase activity (all P < 0.01). Thirty-three (77%) isolates were positive for ExoS by Western blot analysis, 35 (81%) produced rhamnolipids, and 34 (79%) showed chitinase activity. Findings suggest that protease activity during chronic infection may contribute to the transmissibility or virulence of these clonal strains.

Other Mucoactive Agents for Cystic Fibrosis

Paediatric Respiratory Reviews. Mar, 2007  |  Pubmed ID: 17419976

This review examines specific mucoactive agents from three classes: expectorants, which add water to the airway; ion-transport modifiers, which promote ion and water transport across the epithelium of the airway; and mucokinetics, which improve cough-mediated clearance by increasing airflow or reducing sputum adhesivity. The agents are isotonic and hypertonic saline, mannitol, denufosol and beta-agonists. Our understanding of these agents has recently improved through pre-clinical research, clinical trials and, in particular, extensive research into the nature of the liquid lining the surface of the airway, both in health and in cystic fibrosis (CF). For each agent, recent research is reviewed, highlighting the evidence for possible mechanisms of action and for clinical efficacy in CF, as well as the implications for the optimal clinical application of the agent.

Patient-centered Communication Survey of Nursing Homes and Rehabilitation Centers

Care Management Journals : Journal of Case Management ; The Journal of Long Term Home Health Care. 2007  |  Pubmed ID: 17491445

A surge of research has recently been published on the importance ofpatient-centered communication (P-CC). However, patients with communication disorders are rarely considered in these discussions. Health care workers in long-term care facilities (L-TCFs) and rehabilitation centers were surveyed in order to: (1) assess the level of P-CC used with people with communication disorders versus those without communication disorders; (2) identify the tools and strategies currently used by health care providers in long-term care facilities and rehabilitation centers to enhance P-CC with people with communication disorders; (3) assess the perceived level of efectiveness of these tools and strategies; and (4) identify the tools desired by health care providers in these settings. The results regarding P-CC levels were fairly consistent across settings. Health care providers reported that they achieve slightly higher P-CC with patients without communication disorders than with those with communication disorders. Respondents in both settings used similar tools and strategies, but the reported level of effectiveness varied greatly between the two settings, with rehabilitation centers indicating better success than L-TCFs. Interestingly, rehabilitation center respondents were more interested in obtaining additional tools than were L-TCF respondents, but the types of tools desired were similar.

Memory and Phonological Awareness in Children with Benign Rolandic Epilepsy Compared to a Matched Control Group

Epilepsy Research. Jun, 2007  |  Pubmed ID: 17531444

In a previous study we demonstrated children with Benign Rolandic Epilepsy have normal intelligence and language ability. However, difficulties in verbal and visual memory and aspects of phonological awareness were found compared to normative data. To address the methodological limitations related to the use of normative data, we compared the same cohort of children with Benign Rolandic Epilepsy to a matched control group.

A Biofilm Model for Engineering Design

Water Science and Technology : a Journal of the International Association on Water Pollution Research. 2007  |  Pubmed ID: 17547002

A biofilm model is presented for process engineering purposes--wastewater treatment plant design, upgrade and optimisation. The model belongs in the 1D dynamic layered biofilm model category, with modifications that allow it to be used with one parameter set for a large range of process situations. The biofilm model is integrated with a general activated sludge/anaerobic digestion model combined with a chemical equilibrium, precipitation and pH module. This allows the model to simulate the complex interactions that occur in the aerobic, anoxic and anaerobic layers of the biofilm. The model has been tested and is shown to match a variety of design guidelines, as well as experimental results from batch testing and full-scale plant operation. Both moving bed bioreactors (MBBR) and integrated fixed film activated sludge (IFAS) systems were simulated using the same model and parameter set. A new steady-state solver generates fast solutions and allows interactive design work with the complex model.

Superior Cardiovascular Effect of Aerobic Interval Training Versus Moderate Continuous Training in Heart Failure Patients: a Randomized Study

Circulation. Jun, 2007  |  Pubmed ID: 17548726

Exercise training reduces the symptoms of chronic heart failure. Which exercise intensity yields maximal beneficial adaptations is controversial. Furthermore, the incidence of chronic heart failure increases with advanced age; it has been reported that 88% and 49% of patients with a first diagnosis of chronic heart failure are >65 and >80 years old, respectively. Despite this, most previous studies have excluded patients with an age >70 years. Our objective was to compare training programs with moderate versus high exercise intensity with regard to variables associated with cardiovascular function and prognosis in patients with postinfarction heart failure.

Antidiabetic Properties of Selected Mexican Copalchis of the Rubiaceae Family

Phytochemistry. Aug, 2007  |  Pubmed ID: 17575991

The extracts prepared from the stem barks of several Mexican copalchis species, including Hintonia latiflora, Exostema caribaeum and a commercial mixture of Hintonia standleyana and E. caribaeum (CM) showed significant hypoglycemic and antihyperglycemic effects. The extracts were tested in three different in vivo models using normal and streptozotocin (STZ)-induced diabetic rats. From the active extract of H. latiflora, 25-O-acetyl-3-O-beta-D-glucopyranosyl-23,24-dihydrocucurbitacin F (1), an analog of 23,24-dihydrocucurbitacin F, and several known compounds (2-8) were isolated; cucurbitacin 1 was also isolated from H. standleyana. Oral administration of H. latiflora extract [100mg/kg of body weight (bw)] and 5-O-beta-D-glucopyranosyl-7,3',4'-trihydroxy-4-phenylcoumarin (5) (30 mg/kg of bw) to STZ-induced diabetic rats, for a 30 day duration, restored blood glucose levels to normal values. The groups treated either with the active principle 5, or the extract of H. latiflora, showed less body weight loss than glibenclamide-treated and diabetic control groups (p<0.05). It was also demonstrated that the extract of H. latiflora regulated hepatic glycogen and plasma insulin levels (p<0.05). These data suggest that its antihyperglycemic effect is due in part to stimulation of insulin secretion and regulation of hepatic glycogen metabolism.

Constituents, Biological Activities and Quality Control Parameters of the Crude Extract and Essential Oil from Arracacia Tolucensis Var. Multifida

Journal of Ethnopharmacology. Aug, 2007  |  Pubmed ID: 17582715

Bioassay guided fractionation of an antimycobacterial extract of Arracacia tolucensis var. multifida (Umbelliferae) led to the isolation of isoimperatorin (1), osthol (2), suberosin (3), 8-methoxypsoralen (8-MOP) (4), herniarin (5), scoparone (6), umbelliferone (7), dihydroxypeucedanin (8), 5-methoxypsoralen (5-MOP) (9), isoscopoletin (10) and scopoletin (11). The isolates were tested against Mycobacterium tuberculosis and only 1-4 showed significant activity with MIC values of 64, 32, 16 and 128 microg/mL, respectively. The essential oil showed moderate in vitro antibacterial activity against representative Gram-positive and Gram-negative bacteria. The volatile oil of Arracacia tolucensis var. multifida was analyzed by GC-MS and found to be composed mainly by 2 and 3. The essential oil (IC(50)=116.4+/-23.2 microg/mL) and the extract (IC(50)=1153.1+/-53.2 microg/mL) of the plant provoked concentration dependent inhibition of the tone and amplitude of the guinea-pig ileum spontaneous contractions; the latter activity was related with the high coumarin content of this species. A suitable (novel and rapid) HPLC method to quantify the major active coumarins of the plant was developed. The method provides also a reproducible fingerprint useful for identity tests of this plant.

Disparities in Smoking Between the Lesbian, Gay, and Bisexual Population and the General Population in California

American Journal of Public Health. Aug, 2007  |  Pubmed ID: 17600265

We conducted a large, population-based study to assess tobacco use in California's lesbian, gay, and bisexual (LGB) population.

Autobiographical Memory Specificity Predicts Social Problem-solving Ability in Old and Young Adults

Quarterly Journal of Experimental Psychology (2006). Sep, 2007  |  Pubmed ID: 17676558

Based on recent research with young, depressed adults, age-related cognitive declines and decreased autobiographical specificity were hypothesized to predict poorer social problem-solving ability in older than in younger healthy adults. Priming autobiographical memory (ABM) was hypothesized to improve social problem-solving performance for older adults. Subsequent to cognitive tests, old and young participants' specific ABMs were tested using a cued recall task, followed by a social problem-solving task. The order of the tasks was counterbalanced to test for a priming effect. Autobiographical specificity was related to cognitive ability and predicted social problem-solving ability for both age groups. However, priming of ABM did not improve social problem-solving ability for older or younger adults. This study provides support for the hypothesis that autobiographical memory serves a directive function across the life-span.

A Triangulated Approach to the Assessment of Teaching in Childhood Epilepsy

Medical Teacher. Mar, 2007  |  Pubmed ID: 17701642

A comprehensive methodology is needed to assess student teaching. The present study employed a triangulated approach evaluating participant perceptions of learning, critical reflection by the lecturer and peer observation to measure confidence, interest and usefulness of the subject matter.

Development and Validation of a Liquid Chromatography Method for Quantification of Xanthorrhizol in Roots of Iostephane Heterophylla (Cav.) Benth Ex Hemsl

Journal of AOAC International. Jul-Aug, 2007  |  Pubmed ID: 17760325

Roots of Iostephane heterophylla (Cav.) Benth ex Hemsl are used mainly in Mexican traditional medicine to heal skin problems. The development of a column high-performance liquid chromatography (LC)-UV detector method for the determination of xanthorrhizol, the major and active component of the roots of I. heterophylla, is described in this paper. The content of this compound was quantitatively determined employing a Symmetry C18 5 microm particle size column with the isocratic mobile phase acetonitrile-water (85 + 15). The flow rate was 1.0 mL/min, and UV detection was at 230 nm. The limits of detection and quantitation were 0.2 and 0.5 microg/mL, respectively. Quantities of xanthorrhizol measured by this method ranged between 1.8 to 10.94 mg/g of root of the plant in 11 different samples of I. heterophylla. Xanthorrhizol was not detected in a sample of I. madrensis, so xanthorrhizol could be used as a marker compound of I. heterophylla. The LC method described here was shown to be reliable, reproducible, and accurate.

Cigar and Smokeless Tobacco Use in the Lesbian, Gay, and Bisexual Population

Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. Sep, 2007  |  Pubmed ID: 17763109

Large population-based studies of alternative tobacco use in the lesbian, gay, and bisexual (LGB) population are needed to more fully measure tobacco use outcomes. This descriptive study used standard measures of alternative tobacco use from two separate, statewide household-based studies to compare basic prevalence rates in the LGB population and the general population in California. A total of 1,950 adult lesbians, bisexual women, heterosexual women who have sex with women, gay men, bisexual men, and heterosexual men who have sex with men, all living in California, completed surveys between 2003 and 2004. From a general population-based sample (California Tobacco Survey, 2002), a total of 11,037 adult women and 9,488 men were used as comparisons. The prevalence rates for lifetime and current cigar smoking and smokeless tobacco use were lower for all LGB subpopulations compared with the general population.

Regulation of Cuticle-degrading Subtilisin Proteases from the Entomopathogenic Fungi, Lecanicillium Spp: Implications for Host Specificity

Archives of Microbiology. Jan, 2008  |  Pubmed ID: 17805513

The ability to produce cuticle-degrading proteases to facilitate host penetration does not distinguish per se entomopathogenic fungi from saprophytes. However, adapted pathogens may produce host-protein specific enzymes in response to cues. This possibility prompted an investigation of the regulation of isoforms of the subtilisin Pr1-like proteases from five aphid-pathogenic isolates of Lecanicillium spp. Significant differences were found in substrate specificity and regulation of Pr1-like proteases between isoforms of the same isolate and between different isolates. For example, the pI 8.6 isoform from KV71 was considerably more active against aphid than locust cuticle and was induced specifically by N-acetylglucosamine (NAG). Isoform pI 9.1 from the same isolate was only produced on insect cuticle while most other isoforms were more prominent on chitin containing substrates but not induced by NAG. The ability to regulate isoforms independently may allow production at critical points in host penetration. Appearance of proteases (not subtilisins) with pI 4.2 and 4.4 only on aphid cuticle was a possible link with host specificity of KV71. The absence of C or N metabolite repression in subtilisins from KV42 is unusual for pathogen proteases and may help to account for differences in virulence strategy between aphid-pathogenic isolates of Lecanicillium longisporum (unpublished data).

Teaching Doctors How to Diagnose Paroxysmal Events: a Comparison of Two Educational Methods

Medical Education. Sep, 2008  |  Pubmed ID: 18715488

Two educational methods, facilitated case discussion and a computerised tutorial, were compared for teaching about childhood epilepsy. We used a comprehensive and clinically relevant assessment method to evaluate the hypothesis that a computerised tutorial more effectively increases knowledge acquisition than a facilitated case discussion.

The BUMP Model of Response Planning: Variable Horizon Predictive Control Accounts for the Speed-accuracy Tradeoffs and Velocity Profiles of Aimed Movement

Human Movement Science. Oct, 2008  |  Pubmed ID: 18774616

The BUMP model is a comprehensive discrete-time computational model of response planning. Developed within the Adaptive Model Theory framework, it is based on intermittent optimal control. The theory posits a basic unit of motor production (BUMP) that is determined by a planning system that operates intermittently at fixed intervals of time. Given sensory information about the position and velocity of the actual response as well as the predicted future state of the target, the response planning system generates an optimal response trajectory to reach the predicted future state of the target and to compensate for executional error. The ability to vary the duration, or prediction horizon, of the trajectory gives rise to the concept of variable horizon predictive control. We propose that the combination of signal-dependent noise in the nervous system and variable horizon predictive control accounts for the well-known speed-accuracy tradeoffs and velocity profiles in aimed movements. Conducting a simulation study, we found that on one extreme of variable horizon control, a receding horizon strategy reproduced Fitts' law and corresponding asymmetrical velocity profiles. On the other extreme, a fixed horizon strategy reproduced the linear tradeoff and corresponding symmetrical velocity profiles. We conclude that the BUMP model provides a unifying theoretical bridge between speed-accuracy tradeoffs and the accompanying velocity profiles of aimed movement.

Gene Expression Profiling of Skeletal Muscle in Exercise-trained and Sedentary Rats with Inborn High and Low VO2max

Physiological Genomics. Nov, 2008  |  Pubmed ID: 18780757

The relationship between inborn maximal oxygen uptake (VO(2max)) and skeletal muscle gene expression is unknown. Since low VO(2max) is a strong predictor of cardiovascular mortality, genes related to low VO(2max) might also be involved in cardiovascular disease. To establish the relationship between inborn VO(2max) and gene expression, we performed microarray analysis of the soleus muscle of rats artificially selected for high- and low running capacity (HCR and LCR, respectively). In LCR, a low VO(2max) was accompanied by aggregation of cardiovascular risk factors similar to the metabolic syndrome. Although sedentary HCR were able to maintain a 120% higher running speed at VO(2max) than sedentary LCR, only three transcripts were differentially expressed (FDR

Gas Exchange in Stable Patients with Moderate-to-severe Lung Disease from Cystic Fibrosis

Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society. Jul, 2008  |  Pubmed ID: 18785322

Studies using the multiple inert gas elimination technique (MIGET) to characterise the mechanisms of impaired gas exchange in CF, provide conflicting results on the importance of ventilation-perfusion (VA/Q) inequality over shunt. We hypothesise that the mechanisms of gas exchange abnormality have changed with changing CF management over the last two decades.

Batatinosides II-VI, Acylated Lipooligosaccharides from the Resin Glycosides of Sweet Potato

Journal of Agricultural and Food Chemistry. Oct, 2008  |  Pubmed ID: 18816059

Sweet potato ( Ipomoea batatas) belongs to the Convolvulaceae (morning glory family) and is native to Mexico and Central America. Its edible tuberous roots have been much appreciated since pre-Hispanic times in Mesoamerica and now play an important role as a basic diet staple and a medicinal plant worldwide. The hexane-soluble extract from roots, through preparative-scale recycling HPLC, yielded five new lipophilic oligosaccharides of jalapinolic acid, batatinosides II-VI ( 1- 5), as well as the known pescapreins I ( 6) and VII ( 7) and murucoidin I ( 8), which are part of the purgative resin glycoside mixture. NMR spectroscopy and FAB mass spectrometry were used to characterize their structures. Compounds 1 and 2 are tetraglycosidic lactones of operculinic acid C. The pentasaccharide structures for compounds 3 and 4 were confirmed to be macrolactones of simonic acid B, and that characterized for 5 was derived from operculinic acid A. The lactonization site of the aglycone was placed at C-3 of the second saccharide unit in all compounds except 4, where it was placed at C-2. All compounds contain an esterifying residue that is composed of a long-chain fatty acid, n-decanoic acid (capric) or n-dodecanoic acid (lauric). In compound 3, an additional short-chain fatty acid, (2 S)-methylbutyric acid, was also identified.

Transcriptome Analyses and Biofilm-forming Characteristics of a Clonal Pseudomonas Aeruginosa from the Cystic Fibrosis Lung

Journal of Medical Microbiology. Dec, 2008  |  Pubmed ID: 19018014

Transmissible Pseudomonas aeruginosa clones potentially pose a serious threat to cystic fibrosis (CF) patients. The AES-1 clone has been found to infect up to 40 % of patients in five CF centres in eastern Australia. Studies were carried out on clonal and non-clonal (NC) isolates from chronically infected CF patients, and the reference strain PAO1, to gain insight into the properties of AES-1. The transcriptomes of AES-1 and NC isolates, and of PAO1, grown planktonically and as a 72 h biofilm were compared using PAO1 microarrays. Microarray data were validated using real-time PCR. Overall, most differentially expressed genes were downregulated. AES-1 differentially expressed bacteriophage genes, novel motility genes, and virulence and quorum-sensing-related genes, compared with both PAO1 and NC. AES-1 but not NC biofilms significantly downregulated aerobic respiration genes compared with planktonic growth, suggesting enhanced anaerobic/microaerophilic growth by AES-1. Biofilm measurement showed that AES-1 formed significantly larger and thicker biofilms than NC or PAO1 isolates. This may be related to expression of the gene PA0729, encoding a biofilm-enhancing bacteriophage, identified by PCR in all AES-1 but few NC isolates (n=42). Links with the Liverpool epidemic strain included the presence of PA0729 and the absence of the bacteriophage gene cluster PA0632-PA0639. No common markers were found with the Manchester strain. No particular differentially expressed gene in AES-1 could definitively be ascribed a role in its infectivity, thus increasing the likelihood that AES-1 infectivity is multi-factorial and possibly involves novel genes. This study extends our understanding of the transcriptomic and genetic differences between clonal and NC strains of P. aeruginosa from CF lung.

Ex Vivo Mucoadhesion of Different Zinc-pectinate Hydrogel Beads

International Journal of Pharmaceutics. Jan, 2008  |  Pubmed ID: 17659852

The objective of this study was to investigate the mucoadhesive properties of pre-swelled hydrogel beads made of six types of pectin from three manufacturers. The types of pectin differed mainly in the degree of methoxylation and degree of amidation. Zinc ions were used as cross-linking agent. The mucoadhesive properties were tested on an inverted fresh porcine small intestine attached to a rotating cylinder. Beads made of pectin with a high degree of methoxylation (70%) showed superior mucoadhesive results compared to the other formulations, which could be correlated to the lower amount of zinc in this formulation, subsequently leading to a lower amount of cross-linking and higher mobility of the polymer chains of these beads. This study therefore also indicated the importance of doing mucoadhesive measurements on relevant formulations, and not basing the understanding solely on investigating polymer solutions. Samples from different manufacturers produced the same results.

Not Enough Time?

Tar Heel Nurse. Jul-Sep, 2008  |  Pubmed ID: 19051560

Physiological Responses to High Intensity, Constant-load Arm Exercise in COPD

Respiratory Medicine. Mar, 2008  |  Pubmed ID: 18063355

The aim of the study was to compare the metabolic, ventilatory and dyspnoea responses of a single bout of high intensity, constant-load arm exercise to peak arm exercise in people with chronic obstructive pulmonary disease (COPD). Thirty people with COPD (mean age+/-SD=65+/-8 years; FEV1% predicted=56+/-12%) were included. All subjects performed an incremental arm exercise test to peak work capacity on an arm ergometer and, on a separate day, a constant-load arm exercise test at 80% of the peak work rate achieved on the incremental test. Throughout both exercise tests, oxygen consumption (VO2), minute ventilation (VE), dyspnoea and rate of perceived exertion (RPE) were measured each minute. Peak work rate on the incremental test was 33.0+/-10.1 W with a mean duration of 6.6+/-2.0 min. The mean duration of the constant-load test of 7.1+/-2.9 min was not significantly different to the incremental test (p=0.3). At end exercise, VE, dyspnoea and RPE for the constant-load test was significantly higher compared to the incremental test (VE: 41.3+/-14.4 L/min and 38.3+/-11.8 L/min; dyspnoea: 5.6+/-2.7 and 4.6+/-2.1; RPE: 7.1+/-2.3 and 6.0+/-2.0; all p<0.05). Constant-load arm exercise at 80% peak work rate elicits higher ventilatory, dyspnoea and RPE responses at end exercise compared to incremental arm exercise in people with COPD. This finding suggests that an intensity of 80% peak work rate may be too high as an initial training intensity for supported arm exercise in people with COPD.

Aerobic Capacity-dependent Differences in Cardiac Gene Expression

Physiological Genomics. Mar, 2008  |  Pubmed ID: 18171719

Aerobic capacity is a strong predictor of cardiovascular mortality. To determine the relationship between inborn aerobic capacity and cardiac gene expression we examined genome-wide gene expression in hearts of rats artificially selected for high and low running capacity (HCR and LCR, respectively) over 16 generations. The artificial selection of LCR caused accumulation of risk factors of cardiovascular disease similar to the metabolic syndrome seen in human, whereas HCR had markedly better cardiac function. We also studied alterations in gene expression in response to exercise training in these animals. Left ventricle gene expression of both sedentary and exercise-trained HCR and LCR was characterized by microarray and gene ontology analysis. Out of 28,000 screened genes, 1,540 were differentially expressed between sedentary HCR and LCR. Only one gene was found differentially expressed by exercise training, but this gene had unknown name and function. Sedentary HCR expressed higher amounts of genes involved in lipid metabolism, whereas sedentary LCR expressed higher amounts of the genes involved in glucose metabolism. This suggests a switch in cardiac energy substrate utilization from normal mitochondrial fatty acid beta-oxidation in HCR to carbohydrate metabolism in LCR, an event that often occurs in diseased hearts. LCR were also associated with pathological growth signaling and cellular stress. Hypoxic conditions seemed to be a common source for several of these observations, triggering hypoxia-induced alterations of transcription. In conclusion, inborn high vs. low aerobic capacity was associated with differences in cardiac energy substrate, growth signaling, and cellular stress.

No Induction of Anti-avenin IgA by Oats in Adult, Diet-treated Coeliac Disease

Scandinavian Journal of Gastroenterology. 2008  |  Pubmed ID: 18224563

Coeliac disease is effectively treated with a gluten-free diet devoid of wheat, rye, barley and related cereals. Oats has until recently also been considered harmful but is now allowed in several countries. We have, however, identified three adult coeliac disease patients who developed a flare of active coeliac disease after ingestion of oats, which suggests that oats might not be entirely innocent in coeliac disease. It is known that patients with untreated coeliac disease have elevated IgA antibodies to oat prolamins. The objective of this study was to investigate whether levels of IgA against oats were increased in treated, adult coeliac disease patients.

Identifying Compliance Issues with Prescription Medicines Among Older People: a Pilot Study

Drugs & Aging. 2008  |  Pubmed ID: 18257602

Older people are at greater risk from polypharmacy and adverse effects due to interactions and altered pharmacokinetics. They may also have greater difficulty managing their medicines and complying with dosage regimens for various reasons.

Phytotoxic Activity and Conformational Analysis of Thymol Analogs from Hofmeisteria Schaffneri

Phytochemistry. Apr, 2008  |  Pubmed ID: 18328513

Bioassay-guided fractionation of two phytotoxic extracts (a CH(2)Cl(2)-MeOH (1:1) and an aqueous) prepared from the aerial parts of Hofmeisteria schaffneri led to isolation of thymol analogs 3-5, along with seven known compounds, 1, 2 and 6-10. Compounds 3-5 were identified by spectroscopic methods as 1,4-bis(2'-hydroxy-4'-methylphenyl)butane-1,4-dione (3), 2-isopropyl-5-methylphenyl (2Z)-2-methylbut-2-enoate (4) and 2-hydroxy-2-(2-hydroxy-4-methylphenyl)propane-1,3-diyl (2Z,2'Z)bis(2-methylbut-2-enoate) (5) and designated trivial names of hofmeisterins II-IV, respectively. Their conformational behavior was also studied by molecular modeling using density functional theory calculations at the B3LYP/DGDZVP level. Compounds 1-4 and 6-10 significantly inhibited radicle growth of seedlings of Amaranthus hypochondriacus and Echinochloa crus-galli in the Petri dish bioassay with IC(50)'s10(-4)M. Furthermore, the northymol analog 3 provoked significant bleaching of seedlings of A. hypochondriacus. However, none of the isolates affected either seedling growth or germination of Medicago sativa.

Both Aerobic Endurance and Strength Training Programmes Improve Cardiovascular Health in Obese Adults

Clinical Science (London, England : 1979). Nov, 2008  |  Pubmed ID: 18338980

Regular exercise training is recognized as a powerful tool to improve work capacity, endothelial function and the cardiovascular risk profile in obesity, but it is unknown which of high-intensity aerobic exercise, moderate-intensity aerobic exercise or strength training is the optimal mode of exercise. In the present study, a total of 40 subjects were randomized to high-intensity interval aerobic training, continuous moderate-intensity aerobic training or maximal strength training programmes for 12 weeks, three times/week. The high-intensity group performed aerobic interval walking/running at 85-95% of maximal heart rate, whereas the moderate-intensity group exercised continuously at 60-70% of maximal heart rate; protocols were isocaloric. The strength training group performed 'high-intensity' leg press, abdominal and back strength training. Maximal oxygen uptake and endothelial function improved in all groups; the greatest improvement was observed after high-intensity training, and an equal improvement was observed after moderate-intensity aerobic training and strength training. High-intensity aerobic training and strength training were associated with increased PGC-1alpha (peroxisome-proliferator-activated receptor gamma co-activator 1alpha) levels and improved Ca(2+) transport in the skeletal muscle, whereas only strength training improved antioxidant status. Both strength training and moderate-intensity aerobic training decreased oxidized LDL (low-density lipoprotein) levels. Only aerobic training decreased body weight and diastolic blood pressure. In conclusion, high-intensity aerobic interval training was better than moderate-intensity aerobic training in improving aerobic work capacity and endothelial function. An important contribution towards improved aerobic work capacity, endothelial function and cardiovascular health originates from strength training, which may serve as a substitute when whole-body aerobic exercise is contra-indicated or difficult to perform.

Inhaled Mannitol Improves Lung Function in Cystic Fibrosis

Chest. Jun, 2008  |  Pubmed ID: 18339790

The airways in patients with cystic fibrosis (CF) are characterized by the accumulation of tenacious, dehydrated mucus that is a precursor for chronic infection, inflammation, and tissue destruction. The clearance of mucus is an integral component of daily therapy. Inhaled mannitol is an osmotic agent that increases the water content of the airway surface liquid, and improves the clearance of mucus with the potential to improve lung function and respiratory health. To this end, this study examined the efficacy and safety of therapy with inhaled mannitol over a 2-week period.

Genes Implicated in Multiple Sclerosis Pathogenesis from Consilience of Genotyping and Expression Profiles in Relapse and Remission

BMC Medical Genetics. 2008  |  Pubmed ID: 18366677

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Although the pathogenesis of MS remains unknown, it is widely regarded as an autoimmune disease mediated by T-lymphocytes directed against myelin proteins and/or other oligodendrocyte epitopes.

Sleep-disordered Breathing Before and After Lung Transplantation

The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. May, 2008  |  Pubmed ID: 18442721

Sleep-disordered breathing (SDB) is common in patients with severe chronic respiratory failure, but there are no data describing the prevalence of SDB among patients listed for lung transplantation or the effect of transplantation on SDB. We sought to determine the prevalence and impact of SDB before and after lung transplantation.

Sunflower (Helianthus Annuus L.) As a Pre-Columbian Domesticate in Mexico

Proceedings of the National Academy of Sciences of the United States of America. Apr, 2008  |  Pubmed ID: 18443289

Mexico has long been recognized as one of the world's cradles of domestication with evidence for squash (Cucurbita pepo) cultivation appearing as early as 8,000 cal B.C. followed by many other plants, such as maize (Zea mays), peppers (Capsicum annuum), common beans (Phaseolus vulgaris), and cotton (Gossypium hirsutum). We present archaeological, linguistic, ethnographic, and ethnohistoric data demonstrating that sunflower (Helianthus annuus) had entered the repertoire of Mexican domesticates by ca. 2600 cal B.C., that its cultivation was widespread in Mexico and extended as far south as El Salvador by the first millennium B.C., that it was well known to the Aztecs, and that it is still in use by traditional Mesoamerican cultures today. The sunflower's association with indigenous solar religion and warfare in Mexico may have led to its suppression after the Spanish Conquest. The discovery of ancient sunflower in Mexico refines our knowledge of domesticated Mesoamerican plants and adds complexity to our understanding of cultural evolution.

Carbon Monoxide Levels Experienced by Heavy Smokers Impair Aerobic Capacity and Cardiac Contractility and Induce Pathological Hypertrophy

Inhalation Toxicology. May, 2008  |  Pubmed ID: 18464052

Cigarette smoke contains hundreds of potentially toxic compounds and is an important risk factor for cardiovascular disease. However, the key components responsible for endothelial and myocardial dysfunction have not been fully identified. The objective of the present study was to determine the cardiovascular effects of long-term inhalation of carbon monoxide (CO) administrated to give concentrations in the blood similar to those observed in heavy smokers. Female rats were exposed to either CO or air (control group) (n = 12). The CO group was exposed to 200 ppm CO (100 h/wk) for 18 mo. Rats exposed to CO had 24% lower maximal oxygen uptake, longer (145 vs. 123 microm) and wider (47 vs. 25 microm) cardiomyocytes, reduced cardiomyocyte fractional shortening (12 vs. 7%), and 26% longer time to 50% re-lengthening than controls. In addition, cardiomyocytes from CO-exposed rats had 48% lower intracellular calcium (Ca2 +) amplitude, 22% longer time to Ca2 + decay, 34% lower capacity of sarcoplasmic reticulum Ca2 +-ATPase (SERCA2a), and 37% less t-tubule area compared to controls. Phosphorylation levels of phospholamban at Ser16 and Thr17 were significantly reduced in the CO group, whereas total concentration of phospholamban and SERCA2a were unchanged. Cardiac atrial natriuretic peptide, vascular endothelial growth factor, cyclic guanosine monophosphate, calcineurin, calmodulin, pERK, and pS6 increased, whereas pAkt and pCaMKII delta remained unchanged by CO. Endothelial function and systemic blood pressure were not affected by CO exposure. Long-term CO exposure reduces aerobe capacity and contractile function and leads to pathological hypertrophy. Impaired Ca2 + handling and increased growth factor signaling seem to be responsible for these pathological changes.

A Retrospective Cohort Study of Pulmonary Function, Radiographic Measures, and Quality of Life in Children with Congenital Scoliosis: an Evaluation of Patient Outcomes After Early Spinal Fusion

Spine. May, 2008  |  Pubmed ID: 18469699

Retrospective cohort study.

CTLA-4 Polymorphisms Are Not Associated with Ocular Inflammatory Disease

Tissue Antigens. Jul, 2008  |  Pubmed ID: 18498289

Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) is regarded with other molecules such as HLA, PTPN22 and CARD15 as genetic master switches of autoimmunity. Single nucleotide polymorphisms (SNPs) in the genes encoding these molecules have been associated with autoimmune conditions. We analysed the SNPs -318C/T and 49A/G in CTLA-4 in patients with Behcet's disease (BD), patients with intermediate uveitis and appropriate controls. Blood was collected from 236 patients with BD from the UK and the Middle East (ME), all fulfilling the International Study Group criteria for the diagnosis of BD, and 143 patients with idiopathic intermediate uveitis were recruited from the Medical Eye Unit at St Thomas' Hospital. Samples from healthy individuals from each geographical centre were used as controls. DNA was prepared by standard methods, and SNPs -318 and 49 in CTLA-4 were detected by a polymerase chain reaction-sequence specific primers (PCR-SSP) assay using primer mixes. The results showed that there was no association with either polymorphism in patients with BD from the UK or the ME. Similarly, there was no association in patients with intermediate uveitis. Moreover, there was no association with SNP in CTLA-4 and disease manifestations in BD or outcome in patients with intermediate uveitis. Both BD and intermediate uveitis have HLA associations, but there is no difference in distribution of CTLA-4 polymorphisms that are associated with other autoimmune diseases. The lack of association with polymorphisms in CTLA-4 and other master controlling genes of autoimmunity suggests that mechanisms that mediate such a description for BD and intermediate uveitis have still to be elucidated.

Global Gene Expression Profiles of Ovarian Surface Epithelial Cells in Vivo

Journal of Molecular Endocrinology. Jun, 2008  |  Pubmed ID: 18502821

Epithelial ovarian cancer, the leading cause of death from gynecological malignancy in Western countries, is thought to arise from the ovarian surface epithelium (OSE). It has been postulated that the constant rounds of proliferation and repair following ovulation contributes to neoplastic transformation. However, there is little information on the genes and pathways which are involved in the normal functions of the ovarian epithelium, in particular genes that are hormone responsive and those central to functions such as proliferation and apoptosis during ovulation. We used laser microdissection and cDNA microarrays to profile gene expression specifically in mouse ovarian epithelial cells, first compared with other ovarian cells, and secondly between ovarian epithelium collected at different physiological stages. We identified over 1000 transcripts that were consistently more highly expressed in the ovarian epithelium compared with remaining ovarian cell types, including genes involved in cell growth, transcription, and cell adhesion. At the various physiological stages examined, the highest number of regulated genes was found during the estrous cycle, specifically on the evening of proestrus, coincident with the ovulatory surge of hormones and just prior to ovulation. The expression of several selected genes, identified by the microarray analysis, including Villin 2, Keratin 8, Arginine-rich mutated in epithelial tumors, and Tumor-associated calcium signal transducer 1, was validated by independent methods. The identification of genes expressed and regulated in the OSE, and characterization of the pathways involved, will contribute to a more detailed understanding of the ovarian epithelium transcriptome and ultimately lead to a better understanding of the aberrations leading to malignant transformation in the ovarian epithelium.

Exposure to Fibres, Crystalline Silica, Silicon Carbide and Sulphur Dioxide in the Norwegian Silicon Carbide Industry

The Annals of Occupational Hygiene. Jul, 2008  |  Pubmed ID: 18550624

The aim of this study was to assess personal exposure to fibres, crystalline silica, silicon carbide (SiC) and sulphur dioxide in the Norwegian SiC industry.

Endothelial Function in Highly Endurance-trained Men: Effects of Acute Exercise

Journal of Strength and Conditioning Research / National Strength & Conditioning Association. Mar, 2008  |  Pubmed ID: 18550971

Exercise training reverses endothelial dysfunction, but the effect in young, healthy subjects is less clear. We determined the influence of maximal oxygen uptake (VO2max) and a single bout of high-intensity exercise on flow-mediated dilatation (FMD), brachial artery diameter, peak blood flow, nitric oxide (NO) bioavailability, and antioxidant status in highly endurance-trained men and their sedentary counterparts. Ten men athletes (mean +/- SEM age 23.5 +/- 0.9 years, height 182.6 +/- 2.4 cm, weight 72.5 +/- 2.4 kg, VO2max 75.9 +/- 0.8 mL.kg.min) and seven healthy controls (age 25.4 +/- 1.2 years, height 183.9 +/- 3.74 cm, weight 92.8 +/- 3.9 kg, VO2max 47.7 +/- 1.7 mL.kg.min) took part in the study. FMD, brachial artery diameter, and peak blood flow were measured using echo-Doppler before, 1 hour, 24 hours, and 48 hours after a single bout of interval running for 5 x 5 minutes at 90% of maximal heart rate. NO bioavailability and antioxidant status in blood were measured at all time points. Maximal arterial diameter and peak flow were 10-15% (P < 0.02) and 28-35% (P < 0.02) larger, respectively, in athletes vs. controls at all time points, and similar FMD were observed, apart from a transient decay of FMD in athletes 1 hour post exercise. NO bioavailability increased significantly after exercise in both groups and decreased to baseline levels after 24 hours in controls but remained increased 80% and 93% above baseline 24 and 48 hours post exercise in athletes. Antioxidant status was equal in the two groups at baseline and increased by approximately 10% 1 hour post exercise, an effect that lasted for 24 hours. Athletes had larger arterial diameter but similar FMD as untrained subjects, i.e., athletes had larger capacity for blood transport compared with their untrained counterparts. The observed FMD, bioavailability of NO, and antioxidant status in blood were highly dependent on the time elapsed after the exercise session.

High Prevalence of a Class 1 Integron-associated AadB Gene Cassette in Pseudomonas Aeruginosa Isolates from an Australian Cystic Fibrosis Patient Population

Pathology. Aug, 2008  |  Pubmed ID: 18604741

Aerobic Interval Training Versus Continuous Moderate Exercise As a Treatment for the Metabolic Syndrome: a Pilot Study

Circulation. Jul, 2008  |  Pubmed ID: 18606913

Individuals with the metabolic syndrome are 3 times more likely to die of heart disease than healthy counterparts. Exercise training reduces several of the symptoms of the syndrome, but the exercise intensity that yields the maximal beneficial adaptations is in dispute. We compared moderate and high exercise intensity with regard to variables associated with cardiovascular function and prognosis in patients with the metabolic syndrome.

Heat Shock Increases Survival in Rats Exposed to Hyperbaric Pressure

Diving and Hyperbaric Medicine : the Journal of the South Pacific Underwater Medicine Society. Dec, 2008  |  Pubmed ID: 22692750

It has been shown that a single bout of exercise performed 20 hours prior to hyperbaric exposure reduces bubble formation and increases survival in rats. Heat shock proteins (HSPs) are stress proteins expressed in cells that are exposed to different stressors. HSPs are known to protect cells, by binding to proteins and stabilizing them. As it is known that a single bout of exercise induces HSPs, and that HSPs exert their protective effects 20-24 hours after the stimulus for induction, we hypothesized that HSPs might be one mechanism behind the observed exercise-induced protection. We hypothesized that rats that expressed HSPs would develop fewer bubbles and have a lower mortality than their non-stressed control group. Twenty-four female Sprague-Dawley rats (300-330 g) were divided into a heat-shock group and a control group and anaesthetized. The rats in the heat-shock group were heated to 42 ± 0.5 degrees Celsius for 15 min. The following day, all rats were compressed to 700 kPa for 45 min in a hyperbaric chamber. The right ventricles were insonated and bubbles were identified and graded. Six of 12 rats in the heat-shock group survive d, while 1 of 12 control rats survived (Chi square = 5.042, P = 0.034). There was no difference in bubble grade between the groups. The study suggests that the effect of heat shock on survival is not the same as observed after exercise, as the heat-shocked rats developed bubbles. However, heat shock appears to protect rats against the effects of bubbles by an independent mechanism.

Aerobic Interval Training Reduces Cardiovascular Risk Factors More Than a Multitreatment Approach in Overweight Adolescents

Clinical Science (London, England : 1979). Feb, 2009  |  Pubmed ID: 18673303

The aim of the present study was to compare the effects of a multidisciplinary approach (MTG) and aerobic interval training (AIT) on cardiovascular risk factors in overweight adolescents. A total of 62 overweight and obese adolescents from Trøndelag County in Norway, referred to medical treatment at St Olav's Hospital, Trondheim, Norway, were invited to participate. Of these, 54 adolescents (age, 14.0 +/- 0.3 years) were randomized to either AIT (4 x 4 min intervals at 90% of maximal heart rate, each interval separated by 3 min at 70%, twice a week for 3 months) or to MTG (exercise, dietary and psychological advice, twice a month for 12 months). Follow-up testing occurred at 3 and 12 months. VO(2max) (maximal oxygen uptake) increased more after AIT compared with MTG, both at 3 months (11 compared with 0%; P<0.01) and 12 months (12 compared with -1%; P<0.01). AIT enhanced endothelial function compared with MTG at both 3 months (absolute change, 5.1 compared with 3.9%; P<0.01) and 12 months (absolute change, 6.3 compared with 1.0%; P<0.01). AIT was favourable compared with MTG in reducing BMI (body mass index), percentage of fat, MAP (mean arterial blood pressure) and increasing peak oxygen pulse. In addition, AIT induced a more favourable regulation of blood glucose and insulin compared with MTG. In conclusion, the novel findings of the present proof-of-concept study was that 3 months of twice weekly high-intensity exercise sessions reduced several known cardiovascular risk factors in obese adolescents more than that observed after a multitreatment strategy, which was initiated as hospital treatment. Follow-up at 12 months confirmed that AIT improved or maintained these risk factors to a better degree than MTG.

Infection-triggered Familial or Recurrent Cases of Acute Necrotizing Encephalopathy Caused by Mutations in a Component of the Nuclear Pore, RANBP2

American Journal of Human Genetics. Jan, 2009  |  Pubmed ID: 19118815

Acute necrotizing encephalopathy (ANE) is a rapidly progressive encephalopathy that can occur in otherwise healthy children after common viral infections such as influenza and parainfluenza. Most ANE is sporadic and nonrecurrent (isolated ANE). However, we identified a 7 Mb interval containing a susceptibility locus (ANE1) in a family segregating recurrent ANE as an incompletely penetrant, autosomal-dominant trait. We now report that all affected individuals and obligate carriers in this family are heterozygous for a missense mutation (c.1880C-->T, p.Thr585Met) in the gene encoding the nuclear pore protein Ran Binding Protein 2 (RANBP2). To determine whether this mutation is the susceptibility allele, we screened controls and other patients with ANE who are unrelated to the index family. Patients from 9 of 15 additional kindreds with familial or recurrent ANE had the identical mutation. It arose de novo in two families and independently in several other families. Two other patients with familial ANE had different RANBP2 missense mutations that altered conserved residues. None of the three RANBP2 missense mutations were found in 19 patients with isolated ANE or in unaffected controls. We conclude that missense mutations in RANBP2 are susceptibility alleles for familial and recurrent cases of ANE.

Hypoglycemic Activity of Extracts and Compounds from the Leaves of Hintonia Standleyana and H. Latiflora: Potential Alternatives to the Use of the Stem Bark of These Species

Journal of Natural Products. Mar, 2009  |  Pubmed ID: 19140696

The CH(2)Cl(2)-MeOH (1:1) extract of the leaves of Hintonia standleyana and H. latiflora caused significant decrease in blood glucose levels in both normal and streptozotozin (STZ)-induced diabetic rats when compared with vehicle-treated groups (p < 0.05). These extracts were not toxic to mice according to the Lorke criteria. From the hypoglycemic extract of H. standleyana, two new 4-phenylcoumarins, namely, 6''-O-acetyl-5-O-beta-d-galactopyranosyl-7,4'-dihydroxy-4-phenylcoumarin (1) and 6''-O-acetyl-5-O-beta-d-galactopyranosyl-7,3',4'-trihydroxy-4-phenylcoumarin (2), were obtained. The analogous extract of H. latiflora yielded the new 5-O-[beta-d-xylopyranosyl-(1-->6)-beta-d-glucopyranosyl]-7,4'-dimethoxy-4-phenylcoumarin (3) along with several known compounds, including ursolic acid and desoxycordifolinic acid. Phenylcoumarins 1 and 2 showed hypoglycemic activity. HPLC profiles of the leaf extracts of both plants revealed the presence of known hypoglycemic phenylcoumarins as well as chlorogenic acid. The overall results have indicated that the leaves of H. standleyana and H. latiflora possess similar antidiabetic potential to their stem bark. Therefore, the leaves from these species could represent an alternative to the use of their stem bark, which, in turn, would contribute to the conservation of these Mexican medicinal plants.

Anti-Helicobacter Pylori Activity of Plants Used in Mexican Traditional Medicine for Gastrointestinal Disorders

Journal of Ethnopharmacology. Mar, 2009  |  Pubmed ID: 19162157

Helicobacter pylori is the major etiological agent of chronic active gastritis and peptic ulcer disease and is linked to gastric carcinoma. Treatment to eradicate the bacteria failed in many cases, mainly due to antibiotic resistance, hence the necessity of developing better therapeutic regimens. Mexico has an enormous unexplored potential of medicinal plants. This work evaluates the in vitro anti-H. pylori activity of 53 plants used in Mexican traditional medicine for gastrointestinal disorders.

Transcriptional Changes in Blood After Aerobic Interval Training in Patients with the Metabolic Syndrome

European Journal of Cardiovascular Prevention and Rehabilitation : Official Journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology. Feb, 2009  |  Pubmed ID: 19169141

Regular physical activity has beneficial effects on the metabolic syndrome. Eleven metabolic syndrome patients performing 16 weeks of aerobic interval training, significantly reduced their risk of cardiovascular disease, in terms of improved VO2max, endothelial function, blood pressure, insulin signaling, and plasma lipid composition. The knowledge on underlying mechanism of exercise-induced improvements is sparse, and a broad spectrum of methods is needed to gain more insight.

Genotype Analysis of Polymorphisms in Autoimmune Susceptibility Genes, CTLA-4 and PTPN22, in an Acute Anterior Uveitis Cohort

Molecular Vision. 2009  |  Pubmed ID: 19180256

Acute anterior uveitis (AAU) is the most common form of uveitis and is thought to be autoimmune in nature. Recent studies have described genes that act as master controllers of autoimmunity. Protein tyrosine phosphatase type 22 (PTPN22) and Cytotoxic T lymphocyte antigen-4 (CTLA-4) are two of these genes, and single nucleotide polymorphisms (SNPs) in the genes encoding these molecules have been associated with several autoimmune diseases. In this study we have analyzed SNPs in PTPN22 and CTLA-4 in patients with AAU.

Gene Expression Characteristics of a Cystic Fibrosis Epidemic Strain of Pseudomonas Aeruginosa During Biofilm and Planktonic Growth

FEMS Microbiology Letters. Mar, 2009  |  Pubmed ID: 19222585

Epidemic Pseudomonas aeruginosa have been identified in cystic fibrosis (CF) patients worldwide. The Australian Epidemic Strain-2 (AES-2) infects up to 40% of patients in three eastern Australian CF clinics. To investigate whether AES-2 isolates from chronically infected CF adults differentially express well-conserved genes potentially associated with transmissibility, we compared the transcriptomes of planktonic and biofilm-grown AES-2, infrequent P. aeruginosa clones and the reference P. aeruginosa PAO1 using the Affymetrix PAO1 array. The most interesting findings emerged from comparisons of planktonic and biofilm AES-2. AES-2 biofilms upregulated Type III secretion system genes, but downregulated quorum-sensing (QS)-regulatory genes, except lasR, QS-regulated, oxidative-stress and iron-storage genes. QS-regulated and iron-storage genes were downregulated to a greater extent in AES-2 biofilms compared with infrequent clone and PAO1 biofilms, suggesting enhanced anaerobic respiration in AES-2. Chitinase and chitin-binding protein maintained high expression in AES-2 biofilms compared with infrequent clone and PAO1 biofilms. Planktonic AES-2 upregulated QS regulators and QS-regulated genes, iron acquisition and aerobic respiration genes, and had high expression of Group III Type IV pilA compared with low expression of Group I Type IV pilA in infrequent clones. Together, these properties may enhance long-term survival of AES-2 in CF lung and contribute to its transmissibility.

Low Rates of Pseudomonas Aeruginosa Misidentification in Isolates from Cystic Fibrosis Patients

Journal of Clinical Microbiology. May, 2009  |  Pubmed ID: 19261796

Pseudomonas aeruginosa is an important cause of pulmonary infection in cystic fibrosis (CF). Its correct identification ensures effective patient management and infection control strategies. However, little is known about how often CF sputum isolates are falsely identified as P. aeruginosa. We used P. aeruginosa-specific duplex real-time PCR assays to determine if 2,267 P. aeruginosa sputum isolates from 561 CF patients were correctly identified by 17 Australian clinical microbiology laboratories. Misidentified isolates underwent further phenotypic tests, amplified rRNA gene restriction analysis, and partial 16S rRNA gene sequence analysis. Participating laboratories were surveyed on how they identified P. aeruginosa from CF sputum. Overall, 2,214 (97.7%) isolates from 531 (94.7%) CF patients were correctly identified as P. aeruginosa. Further testing with the API 20NE kit correctly identified only 34 (59%) of the misidentified isolates. Twelve (40%) patients had previously grown the misidentified species in their sputum. Achromobacter xylosoxidans (n = 21), Stenotrophomonas maltophilia (n = 15), and Inquilinus limosus (n = 4) were the species most commonly misidentified as P. aeruginosa. Overall, there were very low rates of P. aeruginosa misidentification among isolates from a broad cross section of Australian CF patients. Additional improvements are possible by undertaking a culture history review, noting colonial morphology, and performing stringent oxidase, DNase, and colistin susceptibility testing for all presumptive P. aeruginosa isolates. Isolates exhibiting atypical phenotypic features should be evaluated further by additional phenotypic or genotypic identification techniques.

Voxel-based Morphometry in the Detection of Dysplasia and Neoplasia in Childhood Epilepsy: Limitations of Grey Matter Analysis

Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia. Jun, 2009  |  Pubmed ID: 19303304

The purpose of this exploratory investigation was to evaluate voxel-based morphometry (VBM) in detecting lesions underlying childhood epilepsy, and to establish the optimal image processing and statistical parameters in this context. The patients were 16 children (10 boys) aged 5.9 to 15.2 years (mean 11.3 years) with epilepsy and focal cortical dysplasia (FCD) or neoplasia. The control group comprised 24 normal children (12 boys), age matched to the patients. MRI volumes were spatially normalised to a custom template and segmented into grey matter (GM) and white matter. Using statistical parametric mapping, the GM segment from each patient was then contrasted with the mean GM segment of the control group utilising different VBM post-processing methods. Maps showing increased/decreased areas of GM concentration or volume were generated and compared with visually identified lesions. The results indicated that conservative VBM parameters of linear normalisation with no modulation produced the highest rates of lesion detection, which were identical for FCD and neoplasia at 5/8 lesions. These preliminary data suggest that VBM analysis of GM using conservative parameters can usually detect FCD and neoplasia in the MRI of children with epilepsy, but sensitivity may be inadequate for routine clinical application. Further refinement of the technique may be necessary.

Quantitative Determination of Airborne Respirable Non-fibrous Alpha-silicon Carbide by X-ray Powder Diffractometry

The Annals of Occupational Hygiene. Jun, 2009  |  Pubmed ID: 19406909

The purpose of the present investigation was to establish a method for the determination of airborne respirable non-fibrous silicon carbide (SiC). The main application is within the industrial production of SiC.

HIV-1-infected Dendritic Cells Show 2 Phases of Gene Expression Changes, with Lysosomal Enzyme Activity Decreased During the Second Phase

Blood. Jul, 2009  |  Pubmed ID: 19436054

Dendritic cells (DCs) play a key role in the pathogenesis of HIV infection. HIV interacts with these cells through 2 pathways in 2 temporal phases, initially via endocytosis and then via de novo replication. Here the transcriptional response of human DCs to HIV-1 was studied in these phases and at different stages of the virus replication cycle using purified HIV-1 envelope proteins, and inactivated and viable HIV-1. No differential gene expression was detected in response to envelope. However, more than 100 genes were differentially expressed in response to entry of viable and inactivated HIV-1 in the first phase. A completely different set of genes was differentially expressed in the second phase, predominantly in response to viable HIV-1, including up-regulation of immune regulation genes, whereas genes encoding lysosomal enzymes were down-regulated. Cathepsins B, C, S, and Z RNA and protein decreased, whereas cathepsin L was increased, probably reflecting a concomitant decrease in cystatin C. The net effect was markedly diminished cathepsin activity likely to result in enhanced HIV-1 survival and transfer to contacting T lymphocytes but decreased HIV-1 antigen processing and presentation to these T cells.

Evaluation of the SenseWear Activity Monitor During Exercise in Cystic Fibrosis and in Health

Respiratory Medicine. Oct, 2009  |  Pubmed ID: 19464863

Determine the SenseWear Pro3 Armband (SWA) accuracy for estimating energy expenditure (EE) and step count during treadmill walking in cystic fibrosis (CF) compared to healthy adults.

Gene Expression in HIV-1/Mycobacterium Tuberculosis Co-infected Macrophages is Dominated by M. Tuberculosis

Tuberculosis (Edinburgh, Scotland). Jul, 2009  |  Pubmed ID: 19520608

The resurgence of tuberculosis worldwide has closely mirrored the HIV pandemic. In regions like sub-Saharan Africa, a large proportion of individuals are co-infected with Mycobacterium tuberculosis and HIV. Macrophages are the reservoir host cells for both pathogens, however the interactions between both pathogens in co-infected cells remain poorly understood. Thus, the global gene responses of primary human macrophages following productive co-infection with highly purified HIV and M. tuberculosis were analyzed using cDNA microarrays. A broad range of genes was up-regulated in response to co-infection or M. tuberculosis infection of primary macrophages, including those encoding pro-inflammatory chemokines and cytokines, their receptors, signalling associated genes, type I IFN signalling genes and genes of the tryptophan degradation pathway. Real-time RT-PCR analysis confirmed up-regulation of a wide variety of genes including indoleamine 2,3 dioxygenase and Sp110 in M. tuberculosis and co-infected samples. Downstream analysis confirmed significant elevation of the chemokines CCL3, CCL4 and CCL8 in M. tuberculosis and co-infected culture supernatants. In contrast, the changes seen in gene expression following HIV infection alone were fewer in number and significantly less in magnitude. Thus, the effects of M. tuberculosis infection on global gene expression dominated the effects of HIV-1 in co-infected primary human macrophages.

Sexual and Reproductive Health in Men with Cystic Fibrosis: Consistent Preferences, Inconsistent Practices

Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society. Jul, 2009  |  Pubmed ID: 19523883

Sexual and reproductive health (SRH) is increasingly relevant for men with CF. However, the extent of similarities or differences in SRH clinical practices across different centres or states is unknown as single clinic studies are not informative about variations in male preferences or clinical practices. We wished to determine the variability of male SRH knowledge and preferences, and clinical practices across different CF clinics.

Recombinant Activated Factor VII for Massive Hemoptysis in Patients with Cystic Fibrosis

Chest. Jul, 2009  |  Pubmed ID: 19584209

Massive hemoptysis is a common complication in patients with cystic fibrosis (CF) and is associated with significant morbidity and mortality. Conventional treatment with antibiotic therapy and early bronchial artery embolization (BAE) is usually successful in achieving hemostasis in the majority of patients. Recombinant activated factor VII (rFVIIa), originally developed for use in patients with hemophilia, has emerged as a general hemostatic agent that is potentially useful in the management of many life-threatening bleeding conditions. In this article, we present four patients with CF lung disease and massive hemoptysis who were treated successfully with rFVIIa. We suggest that in patients with CF who present with massive hemoptysis, the use of rFVIIa can be considered in patients with refractory hemoptysis despite conventional therapy or as a temporizing therapy when BAE is not immediately available.

Randomized Trial of a Decision Aid for Patients with Cystic Fibrosis Considering Lung Transplantation

American Journal of Respiratory and Critical Care Medicine. Oct, 2009  |  Pubmed ID: 19590021

We developed an evidence-based decision aid for patients with advanced cystic fibrosis considering referral for lung transplantation.

Multi-centre Research in Australia: Analysis of a Recent National Health and Medical Research Council-funded Project

Respirology (Carlton, Vic.). Sep, 2009  |  Pubmed ID: 19740265

Human research ethics committees provide essential review of research projects to ensure the ethical conduct of human research. Several recent reports have highlighted a complex process for successful application for human research ethics committee approval, particularly for multi-centre studies. Limited resources are available for the execution of human clinical research in Australia and around the world.

Dopamine D2 Receptor Knockout Mice Develop Features of Parkinson Disease

Annals of Neurology. Oct, 2009  |  Pubmed ID: 19847912

This study questions whether increased dopamine (DA) turnover in nigral neurons leads to formation of Lewy bodies (LBs), the characteristic alpha-synuclein-containing cytoplasmic inclusion of Parkinson disease (PD).

Teaching Paediatric Epilepsy to Medical Students: A Randomised Crossover Trial

Journal of Paediatrics and Child Health. Dec, 2009  |  Pubmed ID: 19863709

Research has shown computerised tutorial to be as effective as face-to-face teaching in promoting knowledge acquisition. Subsequently, the clinician must synthesise and interpret data (clinical reasoning). This study extends previous research and compares the effectiveness of interactive lecture and computerised tutorial in promoting observational skills and clinical reasoning in the evaluation of paroxysmal events.

The Genomic Profile of the Cerebral Cortex After Closed Head Injury in Mice: Effects of Minocycline

Journal of Neural Transmission (Vienna, Austria : 1996). Jan, 2009  |  Pubmed ID: 19018450

Microarray analysis was used to delineate gene expression patterns and profile changes following traumatic brain injury (TBI) in mice. A parallel microarray analysis was carried out in mice with TBI that were subsequently treated with minocycline, a drug proposed as a neuroprotectant in other neurological disorders. The aim of this comparison was to identify pathways that may be involved in secondary injury processes following TBI and potential specific pathways that could be targeted with second generation therapeutics for the treatment of neurotrauma patients. Gene expression profiles were measured with the compugen long oligo chip and real-time PCR was used to validate microarray findings. A pilot study of effect of minocycline on gene expression following TBI was also carried out. Gene ontology comparison analysis of sham TBI and minocycline treated brains revealed biological pathways with more genes differentially expressed than predicted by chance. Among 495 gene ontology categories, the significantly different gene ontology groups included chemokines, genes involved in cell surface receptor-linked signal transduction and pro-inflammatory cytokines. Expression levels of some key genes were validated by real-time quantitative PCR. This study confirms that multiple regulatory pathways are affected following brain injury and demonstrates for the first time that specific genes and molecular networks are affected by minocycline following brain injury.

Aerobic Interval Training Versus Continuous Moderate Exercise After Coronary Artery Bypass Surgery: a Randomized Study of Cardiovascular Effects and Quality of Life

American Heart Journal. Dec, 2009  |  Pubmed ID: 19958872

Peak oxygen uptake (Vo(2peak)) strongly predicts mortality in cardiac patients. We compared the effects of aerobic interval training (AIT) versus moderate continuous training (MCT) on Vo(2peak) and quality of life after coronary artery bypass grafting (CABG).

Phonetic Duration, Phonological Quantity and Prosodic Structure in Inari Saami

Phonetica. 2009  |  Pubmed ID: 20431321

Inari Saami, an endangered Finno-Ugric language of Northern Finland, is reported to have a three-way surface contrast in consonant length (short, halflong and long). We studied disyllabic words (C)V1CxV2(C) using data from 5 native speakers under two conditions, with short and long preceding vowel, V1, and found support for the claim that Inari Saami has a ternary contrast in consonant length. The three-way length contrast is more robust following a short V1. The duration of V2 correlates negatively with the length of the medial consonant. However, there is one major departure from this pattern. When both V1 and the medial consonant are long, V2 is also longer. This finding supports the idea that disyllables of this class differ from the others in their prosodic structure in having two metrical feet rather than one. This interpretation tallies with independent evidence from synchronic morphophonology and the historical development of the prosodic system of Inari Saami.

The Impact of Drinking Pattern on Alcohol-related Violence Among Adolescents: An International Comparative Analysis

Drug and Alcohol Review. Mar, 2010  |  Pubmed ID: 20447219

Drinking pattern seems to be an important mediator of the alcohol-violence association. Aggregate level studies have demonstrated that the alcohol-violence association is stronger in countries where intoxication occurs relatively more frequent to the overall drinking. However, this has not been tested against empirical data at the individual level or with respect to violence among young people. Thus, the aim of the present study was to test whether the association between alcohol consumption and prevalence of alcohol-related aggression in young people would be stronger in countries where intoxication is relatively more prevalent.

Clinical Profile of Adult Cystic Fibrosis Patients with Frequent Epidemic Clones of Pseudomonas Aeruginosa

Respirology (Carlton, Vic.). Aug, 2010  |  Pubmed ID: 20573059

Earlier reports suggested that Pseudomonas aeruginosa frequent epidemic clones circulating in cystic fibrosis (CF) centres had increased virulence. However, recent data show no consistent associations with virulence, and suggest attenuation of virulence in chronic infection. Changes to infection control programmes in relation to frequent epidemic clones should be based on their frequency, virulence across all age groups and mode of acquisition. The Australian epidemic strain-1 (AES-1) (or the Melbourne epidemic strain) and AES-2 are common in CF clinics in mainland eastern Australia, but not in the environment. Both have shown increased virulence, but there are no data specifically in adults. This study examines the frequency and virulence of P. aeruginosa frequent epidemic clones in the adult CF clinic at Royal Prince Alfred Hospital, Sydney, Australia.

Deficiency of the Chemokine Receptor CXCR2 Attenuates Neutrophil Infiltration and Cortical Damage Following Closed Head Injury

Neurobiology of Disease. Nov, 2010  |  Pubmed ID: 20621186

The contribution of infiltrated neutrophils to secondary damage following traumatic brain injury remains controversial. Chemokines that regulate neutrophil migration by signaling through the CXCR2 receptor are markedly elevated by brain injury and are associated with the propagation of secondary damage. This study thus investigated the function of CXCR2 in posttraumatic inflammation and secondary degeneration by examining Cxcr2-deficient (Cxcr2(-/-)) mice over 14 days following closed head injury (CHI). We demonstrate a significant attenuation of neutrophil infiltration in Cxcr2(-/-) mice at 12 hours and 7 days after CHI, despite increased levels of CXC neutrophil-attracting chemokines in the lesioned cortex. This coincides with reduced tissue damage, neuronal loss, and cell death in Cxcr2(-/-) mice compared to wild-type controls, with heterozygotes showing intermediate responses. In contrast, blood-brain barrier permeability and functional recovery did not appear to be affected by Cxcr2 deletion. This study highlights the deleterious contribution of neutrophils to posttraumatic neurodegeneration and demonstrates the importance of CXC chemokine signaling in this process. Therefore, CXCR2 antagonistic therapeutics currently in development for other inflammatory conditions may also be of benefit in posttraumatic neuroinflammation.

Antinociceptive Effect of Extracts and Compounds from Hofmeisteria Schaffneri

Journal of Ethnopharmacology. Sep, 2010  |  Pubmed ID: 20633627

Hofmeisteria schaffneri (Asteraceae) is a medicinal plant widely commercialized in the most important Markets of Mexico City for the treatment of gastro-intestinal complaints and skin afflictions.

The BUMP Model of Response Planning: Intermittent Predictive Control Accounts for 10 Hz Physiological Tremor

Human Movement Science. Oct, 2010  |  Pubmed ID: 20674054

Physiological tremor during movement is characterized by ∼10 Hz oscillation observed both in the electromyogram activity and in the velocity profile. We propose that this particular rhythm occurs as the direct consequence of a movement response planning system that acts as an intermittent predictive controller operating at discrete intervals of ∼100 ms. The BUMP model of response planning describes such a system. It forms the kernel of Adaptive Model Theory which defines, in computational terms, a basic unit of motor production or BUMP. Each BUMP consists of three processes: (1) analyzing sensory information, (2) planning a desired optimal response, and (3) execution of that response. These processes operate in parallel across successive sequential BUMPs. The response planning process requires a discrete-time interval in which to generate a minimum acceleration trajectory to connect the actual response with the predicted future state of the target and compensate for executional error. We have shown previously that a response planning time of 100 ms accounts for the intermittency observed experimentally in visual tracking studies and for the psychological refractory period observed in double stimulation reaction time studies. We have also shown that simulations of aimed movement, using this same planning interval, reproduce experimentally observed speed-accuracy tradeoffs and movement velocity profiles. Here we show, by means of a simulation study of constant velocity tracking movements, that employing a 100 ms planning interval closely reproduces the measurement discontinuities and power spectra of electromyograms, joint-angles, and angular velocities of physiological tremor reported experimentally. We conclude that intermittent predictive control through sequential operation of BUMPs is a fundamental mechanism of 10 Hz physiological tremor in movement.

Complex Exon-intron Marking by Histone Modifications is Not Determined Solely by Nucleosome Distribution

PloS One. 2010  |  Pubmed ID: 20808788

It has recently been shown that nucleosome distribution, histone modifications and RNA polymerase II (Pol II) occupancy show preferential association with exons ("exon-intron marking"), linking chromatin structure and function to co-transcriptional splicing in a variety of eukaryotes. Previous ChIP-sequencing studies suggested that these marking patterns reflect the nucleosomal landscape. By analyzing ChIP-chip datasets across the human genome in three cell types, we have found that this marking system is far more complex than previously observed. We show here that a range of histone modifications and Pol II are preferentially associated with exons. However, there is noticeable cell-type specificity in the degree of exon marking by histone modifications and, surprisingly, this is also reflected in some histone modifications patterns showing biases towards introns. Exon-intron marking is laid down in the absence of transcription on silent genes, with some marking biases changing or becoming reversed for genes expressed at different levels. Furthermore, the relationship of this marking system with splicing is not simple, with only some histone modifications reflecting exon usage/inclusion, while others mirror patterns of exon exclusion. By examining nucleosomal distributions in all three cell types, we demonstrate that these histone modification patterns cannot solely be accounted for by differences in nucleosome levels between exons and introns. In addition, because of inherent differences between ChIP-chip array and ChIP-sequencing approaches, these platforms report different nucleosome distribution patterns across the human genome. Our findings confound existing views and point to active cellular mechanisms which dynamically regulate histone modification levels and account for exon-intron marking. We believe that these histone modification patterns provide links between chromatin accessibility, Pol II movement and co-transcriptional splicing.

Massive Pulmonary Embolism in Children

The Journal of Pediatrics. Jan, 2010  |  Pubmed ID: 20006766

We present 3 children with massive pulmonary embolism and review 17 recent pediatric reports. Malignancies were a frequent cause (40%), and sudden death was common (60%). Compared with adults, diagnosis was more likely to be made at autopsy (P < .0001), more children were treated with embolectomy/thrombectomy (P = .0006), and mortality was greater (P = .03).

The Influence of Liposomal Formulation Factors on the Interactions Between Liposomes and Hydroxyapatite

Colloids and Surfaces. B, Biointerfaces. Mar, 2010  |  Pubmed ID: 20022224

Liposomes may have potentials as a drug delivery system in the oral cavity; hence, the adsorption to, oral tissues may be of importance. The aim of this study was to find an optimal liposomal formulation with appropriate in vitro stability and which liposomal formulation parameters may be of importance for the interaction to tooth enamel surfaces. Charged liposomes were adsorbed in vitro onto hydroxyapatite (HA), used as a model substance for human dental enamel. For a systematic approach of lipid selection, statistical experimental design and multivariate analysis were conducted to interpret the data. The factors investigated were the type of charge (positive, negative), type of main phospholipid (egg-PC, DPPC, DMPC), type of charged lipid (diacyl-TAP, -ethylPC, -PA, -PG, -PS), the amount of charged component (2.5, 10mol%) and the inclusion of cholesterol in the lipid bilayer. The results indicated that positively charged liposomes expressed significantly higher adsorption levels than the negatively charged ones. The effect of incorporating cholesterol did not turn out to be significant. Both positive egg-PC and DPPC liposomes exhibited high adsorption levels; however egg-PC liposomes were unstable during storage. For positively charged liposomes, the factor "type of main lipid" was found to be of significance for the adsorption, whereas, for negatively charged liposomes, no such important factors were found. Based on the adsorption profile to HA and the in vitro stability in phosphate buffer, the most promising liposomal formulation to target for human enamel in this study was the positively charged DPPC liposomes with 10mol% charged lipid included. However, more experiments are needed to determine the optimum mol% of positively charged lipid for the adsorption onto HA.

Role of CCL2 (MCP-1) in Traumatic Brain Injury (TBI): Evidence from Severe TBI Patients and CCL2-/- Mice

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism. Apr, 2010  |  Pubmed ID: 20029451

Cerebral inflammation involves molecular cascades contributing to progressive damage after traumatic brain injury (TBI). The chemokine CC ligand-2 (CCL2) (formerly monocyte chemoattractant protein-1, MCP-1) is implicated in macrophage recruitment into damaged parenchyma after TBI. This study analyzed the presence of CCL2 in human TBI, and further investigated the role of CCL2 in physiological and cellular mechanisms of secondary brain damage after TBI. Sustained elevation of CCL2 was detected in the cerebrospinal fluid (CSF) of severe TBI patients for 10 days after trauma, and in cortical homogenates of C57Bl/6 mice, peaking at 4 to 12 h after closed head injury (CHI). Neurological outcome, lesion volume, macrophage/microglia infiltration, astrogliosis, and the cerebral cytokine network were thus examined in CCL2-deficient (-/-) mice subjected to CHI. We found that CCL2-/- mice showed altered production of multiple cytokines acutely (2 to 24 h); however, this did not affect lesion size or cell death within the first week after CHI. In contrast, by 2 and 4 weeks, a delayed reduction in lesion volume, macrophage accumulation, and astrogliosis were observed in the injured cortex and ipsilateral thalamus of CCL2-/- mice, corresponding to improved functional recovery as compared with wild-type mice after CHI. Our findings confirm the significant role of CCL2 in mediating post-traumatic secondary brain damage.

Effects of Telmisartan on Office and 24-hour Ambulatory Blood Pressure: an Observational Study in Hypertensive Patients Managed in Primary Care

Vascular Health and Risk Management. 2010  |  Pubmed ID: 20191081

Although elevated blood pressure (BP) predicts future cardiovascular events, recommended BP targets often is not reached in the general community. In a clinical real-life setting we evaluated BP impact and tolerability of the angiotensin-II receptor blocker telmisartan in patients with essential hypertension.

Physical Characteristics Related to Bra Fit

Ergonomics. Apr, 2010  |  Pubmed ID: 20309747

Producing well-fitting garments has been a challenge for retailers and manufacturers since mass production began. Poorly fitted bras can cause discomfort or pain and result in lost sales for retailers. Because body contours are important factors affecting bra fit, this study analyses the relationship of physical characteristics to bra-fit problems. This study has used 3-D body-scanning technology to extract upper body angles from a sample of 103 college women; these data were used to categorise physical characteristics into shoulder slope, bust prominence, back curvature and acromion placement. Relationships between these physical categories and bra-fit problems were then analysed. Results show that significant main effects and two-way interactions of the physical categories exist in the fit problems of poor bra support and bra-motion restriction. The findings are valuable in helping the apparel industry create better-fitting bras. STATEMENT OF RELEVANCE: Poorly fitted bras can cause discomfort or pain and result in lost sales for retailers. The findings regarding body-shape classification provide researchers with a statistics method to quantify physical characteristics and the findings regarding the relationship analysis between physical characteristics and bra fit offer bra companies valuable information about bra-fit perceptions attributable to women with figure variations.

Tailoring the Photoluminescence Properties of Transition Metal Phosphonates

Dalton Transactions (Cambridge, England : 2003). Jul, 2010  |  Pubmed ID: 20383400

A series of phenylphosphonates, Zn(1-x)Mn(x)(O(3)PC(6)H(5)) x H(2)O, where x = 0, 0.005, 0.25, 0.5, 0.75 and 1.0, has been prepared and their photoluminescence responses studied. The presence of Mn in the sample results in a red emission, whilst when x = 0 the emission is green. Levels of Mn <1 mol% result in an orange emission. Ag(6)(m-O(3)PC(6)H(4)CO(2))(2) has been prepared by hydrothermal reaction of Ag(NO(3)) and m-phosphonobenzoic acid. The material has a 1D channel structure in which the channels are lined with the phenyl groups. Ag(6)(m-O(3)PC(6)H(4)CO(2))(2) shows a green luminescence response to laser excitation, whilst the related Zn material, Zn(3)(m-O(3)PC(6)H(4)CO(2))(2), shows an unusual yellow emission.

Pregnancy and Cystic Fibrosis

Paediatric Respiratory Reviews. Jun, 2010  |  Pubmed ID: 20416544

The management of a pregnancy in a woman with cystic fibrosis is usually achieved with successful outcomes for mother and child with appropriate multidisciplinary care. The process begins prior to conception and requires frequent monitoring of the mother's respiratory status, level of glycaemic control and obstetric wellbeing. Recent reports have suggested that pregnancy can be managed without a persisting decrement in lung function beyond what may be expected in women with cystic fibrosis who are not pregnant. With the increasingly positive outcomes for people with cystic fibrosis, it is likely that more couples will chose to pursue pregnancy, cognisant of the risks and longer term issues for mother, child and family. This review will address the current issues in the management of pregnancy in women with cystic fibrosis.

Animal Models of Traumatic Brain Injury: is There an Optimal Model to Reproduce Human Brain Injury in the Laboratory?

Injury. Jul, 2010  |  Pubmed ID: 20416875

Compared to other neurological diseases, the research surrounding traumatic brain injury (TBI) has a more recent history. The establishment and use of animal models of TBI remains vital to understand the pathophysiology of this highly complex disease. Such models share the ultimate goals of reproducing patterns of tissue damage observed in humans (thus rendering them clinically relevant), reproducible and highly standardised to allow for the manipulation of individual variables, and to finally explore novel therapeutics for clinical translation. There is no doubt that the similarity of cellular and molecular events observed in human and rodent TBI has reinforced the use of small animals for research. When confronted with the choice of the experimental model it becomes clear that the ideal animal model does not exist. This limitation derives from the fact that most models mimic either focal or diffuse brain injury, whereas the clinical reality suggests that each patient has an individual form of TBI characterised by various combinations of focal and diffuse patterns of tissue damage. This is additionally complicated by the occurrence of secondary insults such as hypotension, hypoxia, ischaemia, extracranial injuries, modalities of traumatic events, age, gender and heterogeneity of medical treatments and pre-existing conditions. This brief review will describe the variety of TBI models available for laboratory research beginning from the most widely used rodent models of focal brain trauma, to complex large species such as the pig. In addition, the models mimicking diffuse brain damage will be discussed in relation to the early primate studies until the use of most common rodent models to elucidate the intriguing and less understood pathology of axonal dysfunction. The most recent establishment of in vitro paradigms has complemented the in vivo modelling studies offering a further cellular and molecular insight of this pathology.

Psychosocial Stress During Pregnancy and Perinatal Outcomes: a Meta-analytic Review

Journal of Psychosomatic Obstetrics and Gynaecology. Dec, 2010  |  Pubmed ID: 21039328

The objective of this study was to evaluate the relationship between psychosocial stress in pregnancy and negative perinatal outcomes and to identify key moderators of this relationship. To evaluate this relationship, a meta-analytic review was conducted of studies that prospectively assessed the relationship between psychosocial stress in pregnancy and perinatal outcomes. A total of 35 studies, written or published between 1991 and 2009, involving 31,323 women were located. The overall association between psychosocial stress and negative perinatal outcomes was significant, but negligibly small in size (r (35) = -0.04, CI = -0.08, -0.01). Examining specific perinatal outcomes, only the associations with neonatal weight (r (14) = -0.07, CI = -0.03, -0.01) and risk for low birth weight (r (5) = 0.07, CI = 0.03, 0.10) were statistically significant, but again, very small. Results support that psychosocial stress explains a negligible to very small amount of the variability in perinatal outcomes. Future research should focus on identifying other psychosocial and lifestyle variables that alone or in interaction with other factors explain larger amounts of the variability in perinatal outcomes. Future research should also examine whether psychosocial stress increases risk for negative outcomes in combination with other biomedical and psychosocial risk factors.

Protein Disulphide Isomerase Protects Against Protein Aggregation and is S-nitrosylated in Amyotrophic Lateral Sclerosis

Brain : a Journal of Neurology. Jan, 2010  |  Pubmed ID: 19903735

Amyotrophic lateral sclerosis is a rapidly progressing fatal neurodegenerative disease characterized by the presence of protein inclusions within affected motor neurons. Endoplasmic reticulum stress leading to apoptosis was recently recognized to be an important process in the pathogenesis of sporadic human amyotrophic lateral sclerosis as well as in transgenic models of mutant superoxide dismutase 1-linked familial amyotrophic lateral sclerosis. Endoplasmic reticulum stress occurs early in disease, indicating a critical role in pathogenesis, and involves upregulation of an important endoplasmic reticulum chaperone, protein disulphide isomerase. We aimed to investigate the involvement of protein disulphide isomerase in endoplasmic reticulum stress induction, protein aggregation, inclusion formation and toxicity in amyotrophic lateral sclerosis. Motor neuron-like NSC-34 cell lines were transfected with superoxide dismutase 1 and protein disulphide isomerase encoding vectors and small interfering RNA, and examined by immunocytochemistry and immunoblotting. Expression of mutant superoxide dismutase 1 induced endoplasmic reticulum stress, predominantly in cells bearing mutant superoxide dismutase 1 inclusions but also in a proportion of cells expressing mutant superoxide dismutase 1 without visible inclusions. Over-expression of protein disulphide isomerase decreased mutant superoxide dismutase 1 aggregation, inclusion formation, endoplasmic reticulum stress induction and toxicity, whereas small interfering RNA targeting protein disulphide isomerase increased mutant superoxide dismutase 1 inclusion formation, indicating a protective role for protein disulphide isomerase against superoxide dismutase 1 misfolding. Aberrant modification of protein disulphide isomerase by S-nitrosylation of active site cysteine residues has previously been shown as an important process in neurodegeneration in Parkinson's and Alzheimer's disease brain tissue, but has not been described in amyotrophic lateral sclerosis. Using a biotin switch assay, we detected increased levels of S-nitrosylated protein disulphide isomerase in transgenic mutant superoxide dismutase 1 mouse and human sporadic amyotrophic lateral sclerosis spinal cord tissues. Hence, despite upregulation, protein disulphide isomerase is also functionally inactivated in amyotrophic lateral sclerosis, which may prevent its normal protective function and contribute to disease. We also found that a small molecule mimic of the protein disulphide isomerase active site, (+/-)-trans-1,2-bis(mercaptoacetamido)cyclohexane, protected against mutant superoxide dismutase 1 inclusion formation. These studies reveal that endoplasmic reticulum stress is important in the formation of mutant superoxide dismutase 1 inclusions, and protein disulphide isomerase has an important function in ameliorating mutant superoxide dismutase 1 aggregation and toxicity. Functional inhibition of protein disulphide isomerase by S-nitrosylation may contribute to pathophysiology in both mutant superoxide dismutase 1-linked disease and sporadic amyotrophic lateral sclerosis. Protein disulphide isomerase is therefore a novel potential therapeutic target in amyotrophic lateral sclerosis and (+/-)-trans-1,2-bis(mercaptoacetamido)cyclohexane and other molecular mimics of protein disulphide isomerase could be of benefit in amyotrophic lateral sclerosis and other neurodegenerative diseases related to protein misfolding.

Post-traumatic Hypoxia Exacerbates Brain Tissue Damage: Analysis of Axonal Injury and Glial Responses

Journal of Neurotrauma. Nov, 2010  |  Pubmed ID: 20822466

Traumatic brain injury (TBI) resulting in poor neurological outcome is predominantly associated with diffuse brain damage and secondary hypoxic insults. Post-traumatic hypoxia is known to exacerbate primary brain injury; however, the underlying pathological mechanisms require further elucidation. Using a rat model of diffuse traumatic axonal injury (TAI) followed by a post-traumatic hypoxic insult, we characterized axonal pathology, macrophage/microglia accumulation, and astrocyte responses over 14 days. Rats underwent TAI alone, TAI followed by 30 min of hypoxia (TAI + Hx), hypoxia alone, or sham-operation (n = 6/group). Systemic hypoxia was induced by ventilating rats with 12% oxygen in nitrogen, resulting in a ∼ 50% reduction in arterial blood oxygen saturation. Brains were assessed for axonal damage, macrophage/microglia accumulation, and astrocyte activation at 1, 7, and 14 days post-treatment. Immunohistochemistry with axonal damage markers (β-amyloid precursor protein [β-APP] and neurofilament) showed strong positive staining in TAI + Hx rats, which was most prominent in the corpus callosum (retraction bulbs 69.8 ± 18.67; swollen axons 14.2 ± 5.25), and brainstem (retraction bulbs 294 ± 118.3; swollen axons 50.3 ± 20.45) at 1 day post-injury. Extensive microglia/macrophage accumulation detected with the CD68 antibody was maximal at 14 days post-injury in the corpus callosum (macrophages 157.5 ± 55.48; microglia 72.71 ± 20.75), and coincided with regions of axonal damage. Astrocytosis assessed with glial fibrillary acidic protein (GFAP) antibody was also abundant in the corpus callosum and maximal at 14 days, with a trend toward an increase in TAI + Hx animals (18.99 ± 2.45 versus 13.56 ± 0.81; p = 0.0617). This study demonstrates for the first time that a hypoxic insult following TAI perpetuates axonal pathology and cellular inflammation, which may account for the poor neurological outcomes seen in TBI patients who experience post-traumatic hypoxia.

Effects of Exercise on Respiratory Flow and Sputum Properties in Patients with Cystic Fibrosis

Chest. Apr, 2011  |  Pubmed ID: 20829339

The physiologic mechanisms by which exercise may clear secretions in subjects with cystic fibrosis (CF) are unknown. The purpose of this study was to compare ventilation, respiratory flow, and sputum properties following treadmill and cycle exercise with resting breathing (referred to as "control").

Receptor Localization, Native Tissue Binding and Ex Vivo Occupancy for Centrally Penetrant P2X7 Antagonists in the Rat

British Journal of Pharmacology. Jan, 2011  |  Pubmed ID: 20840537

The P2X7 receptor is implicated in inflammation and pain and is therefore a potential target for therapeutic intervention. Here, the development of a native tissue radioligand binding, localization and ex vivo occupancy assay for centrally penetrant P2X7 receptor antagonists is described.

(Z)-3-butylidenephthalide from Ligusticum Porteri , an α-glucosidase Inhibitor

Journal of Natural Products. Mar, 2011  |  Pubmed ID: 20879744

An extract from the roots of Ligusticum porteri, orally administered to groups of normal and diabetic mice, showed significant hypoglycemic and antihyperglycemic effects. Experimental type-II DM was achieved by treating mice with streptozotocin 15 min after an injection of β-nicotinamide adenine dinucleotide. (Z)-6,6',7,3'α-diligustilide (1), (Z)-ligustilide (2), 3-(Z)-butylidenephthalide (3), myristicin (4), and ferulic acid (5) were isolated from the active extract. When tested In Vivo, compounds 1-3 showed antihyperglycemic activity, with 3 being the most active. Compound 3 (56.2 mg/kg) decreased blood glucose levels in NAD-STZ-diabetic mice after an oral sucrose load, suggesting that its antihyperglycemic effect is due to inhibition of α-glucosidase at the intestinal level. Furthermore, 3 inhibited the activity of yeast-α-glucosidase (IC(50) 2.35 mM) in a noncompetitive fashion with a K(i) of 4.86 mM. Docking analysis predicted that 3 binds to the enzyme in a pocket close to the catalytic site, but different from that for acarbose, with a K(i) of 11.48 mM. Compounds 1 and 2 did not affect α-glucosidase In Vivo, but altered glucose absorption by a mechanism yet to be determined. The stimulatory effect of 5 on insulin secretion, present in high amounts in the extract, has been demonstrated in previous investigations. The present study provides scientific support of the use of L. porteri in Mexican folk medicine for the treatment of diabetes.

Deep Brain Stimulation Can Suppress Pathological Synchronisation in Parkinsonian Patients

Journal of Neurology, Neurosurgery, and Psychiatry. May, 2011  |  Pubmed ID: 20935326

Although deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a highly effective therapeutic intervention in severe Parkinson's disease, its mechanism of action remains unclear. One possibility is that DBS suppresses local pathologically synchronised oscillatory activity.

Retroperitoneal Fibrosis Misinterpreted As an Abdominal Aortic Aneurysm on Ultrasound

BMJ Case Reports. 2011  |  Pubmed ID: 22679331

N2O Emissions: Modeling the Effect of Process Configuration and Diurnal Loading Patterns

Water Environment Research : a Research Publication of the Water Environment Federation. Dec, 2011  |  Pubmed ID: 22368954

The objective of this research was to develop a mechanistic model for quantifying N2O emissions from activated sludge plants and demonstrate how this may be used to evaluate the effects of process configuration and diurnal loading patterns. The model describes the mechanistic link between the factors recognized to correlate positively with N2O emissions. The primary factors are the presence of ammonia and nitrite accumulation. Low dissolved oxygen concentrations also may be implicated through differential impacts on ammonia-oxidizing bacteria (AOB) versus nitrite-oxidizing bacteria (NOB) activity. Factors promoting N2O emissions at treatment plants are discussed below. The model was applied to data from laboratory and pilot-scale systems. From a practical standpoint, plant configuration (e.g., plug-flow versus complete-mix), influent loading patterns (and peak load), and certain operating strategies (e.g., handling of return streams) are all important in determining N2O emissions.

Neuronal Activity Regulates Expression of Tyrosine Hydroxylase in Adult Mouse Substantia Nigra Pars Compacta Neurons

Journal of Neurochemistry. Feb, 2011  |  Pubmed ID: 21166807

Striatal delivery of dopamine (DA) by midbrain substantia nigra pars compacta (SNc) neurons is vital for motor control and its depletion causes the motor symptoms of Parkinson's disease. While membrane potential changes or neuronal activity regulates tyrosine hydroxylase (TH, the rate limiting enzyme in catecholamine synthesis) expression in other catecholaminergic cells, it is not known whether the same occurs in adult SNc neurons. We administered drugs known to alter neuronal activity to mouse SNc DAergic neurons in various experimental preparations and measured changes in their TH expression. In cultured midbrain neurons, blockade of action potentials with 1 μM tetrodotoxin decreased TH expression beginning around 20 h later (as measured in real time by green fluorescent protein (GFP) expression driven off TH promoter activity). By contrast, partial blockade of small-conductance, Ca(2+) -activated potassium channels with 300 nM apamin increased TH mRNA and protein between 12 and 24 h later in slices of adult midbrain. Two-week infusions of 300 nM apamin directly to the adult mouse midbrain in vivo also increased TH expression in SNc neurons, measured immunohistochemically. Paradoxically, the number of TH immunoreactive (TH+) SNc neurons decreased in these animals. Similar in vivo infusions of drugs affecting other ion-channels and receptors (L-type voltage-activated Ca(2+) channels, GABA(A) receptors, high K(+) , DA receptors) also increased or decreased cellular TH immunoreactivity but decreased or increased, respectively, the number of TH+ cells in SNc. We conclude that in adult SNc neurons: (i) TH expression is activity-dependent and begins to change ∼20 h following sustained changes in neuronal activity; (ii) ion-channels and receptors mediating cell-autonomous activity or synaptic input are equally potent in altering TH expression; and (iii) activity-dependent changes in TH expression are balanced by opposing changes in the number of TH+ SNc cells.

Ocular Loiasis in London 2008-2009: a Case Series

Eye (London, England). Mar, 2011  |  Pubmed ID: 21242984

To report three cases of Loa loa infestation presenting over the course of 12 months to ophthalmology departments in the South West Thames region around London. Methods: Case series (three case histories are described) and literature review.

Personalised Epilepsy Education Intervention for Adolescents and Impact on Knowledge Acquisition and Psychosocial Function

Journal of Paediatrics and Child Health. May, 2011  |  Pubmed ID: 21244556

Patients frequently have poor knowledge of epilepsy, and this is associated with low self-esteem in adolescence. There is a paucity of data determining whether education alone can improve psychosocial outcome. The study investigated whether an educational intervention in adolescence: 1 Increased understanding of epilepsy syndrome and general epilepsy knowledge. 2 Improved self-esteem, seizure self-efficacy and attitudes towards epilepsy.

Local Anesthesia Before IV Catheterization

The American Journal of Nursing. Feb, 2011  |  Pubmed ID: 21270583

Intradermal buffered lidocaine is known to be effective in producing local anesthesia prior to IV catheterization. Recently, intradermal bacteriostatic normal saline has been suggested as a possible alternative.

Antimicrobial Activity and Chemical Composition of the Essential Oil of Hofmeisteria Schaffneri

The Journal of Pharmacy and Pharmacology. Apr, 2011  |  Pubmed ID: 21401611

The aims of this study were to establish the antimicrobial potential of Hofmeisteria schaffneri essential oil and its chemical composition.

Wnt5a Regulates Midbrain Dopaminergic Axon Growth and Guidance

PloS One. 2011  |  Pubmed ID: 21483795

During development, precise temporal and spatial gradients are responsible for guiding axons to their appropriate targets. Within the developing ventral midbrain (VM) the cues that guide dopaminergic (DA) axons to their forebrain targets remain to be fully elucidated. Wnts are morphogens that have been identified as axon guidance molecules. Several Wnts are expressed in the VM where they regulate the birth of DA neurons. Here, we describe that a precise temporo-spatial expression of Wnt5a accompanies the development of nigrostriatal projections by VM DA neurons. In mice at E11.5, Wnt5a is expressed in the VM where it was found to promote DA neurite and axonal growth in VM primary cultures. By E14.5, when DA axons are approaching their striatal target, Wnt5a causes DA neurite retraction in primary cultures. Co-culture of VM explants with Wnt5a-overexpressing cell aggregates revealed that Wnt5a is capable of repelling DA neurites. Antagonism experiments revealed that the effects of Wnt5a are mediated by the Frizzled receptors and by the small GTPase, Rac1 (a component of the non-canonical Wnt planar cell polarity pathway). Moreover, the effects were specific as they could be blocked by Wnt5a antibody, sFRPs and RYK-Fc. The importance of Wnt5a in DA axon morphogenesis was further verified in Wnt5a-/- mice, where fasciculation of the medial forebrain bundle (MFB) as well as the density of DA neurites in the MFB and striatal terminals were disrupted. Thus, our results identify a novel role of Wnt5a in DA axon growth and guidance.

Neurogenesis and Glial Proliferation Are Stimulated Following Diffuse Traumatic Brain Injury in Adult Rats

Journal of Neuroscience Research. Jul, 2011  |  Pubmed ID: 21488090

Although increased neurogenesis has been described in rodent models of focal traumatic brain injury (TBI), the neurogenic response occurring after diffuse TBI uncomplicated by focal injury has not been examined to date, despite the pervasiveness of this distinct type of brain injury in the TBI patient population. Here we characterize multiple stages of neurogenesis following a traumatic axonal injury (TAI) model of diffuse TBI as well as the proliferative response of glial cells. TAI was induced in adult rats using an impact-acceleration model, and 5-bromo-2'-deoxyuridine (BrdU) was administered on days 1-4 posttrauma or sham operation to label mitotic cells. Using immunohistochemistry for BrdU combined with phenotype-specific markers, we found that proliferation was increased following TAI in the subventricular zone of the lateral ventricles and in the hippocampal subgranular zone, although the ultimate production of new dentate granule neurons at 8 weeks was not significantly enhanced. Also, abundant proliferating and reactive astrocytes, microglia, and polydendrocytes were detected throughout the brain following TAI, indicating that a robust glial response occurs in this model, although very few new cells in the nonneurogenic brain regions became mature neurons. We conclude that diffuse brain injury stimulates early stages of a neurogenic response similar to that described for models of focal TBI.

Difficult Asthma and Churg-Strauss-like Syndrome: a Cautionary Tale

Respirology (Carlton, Vic.). Jan, 2011  |  Pubmed ID: 21504509

Chemical Composition and Antimicrobial and Spasmolytic Properties of Poliomintha Longiflora and Lippia Graveolens Essential Oils

Journal of Food Science. Mar, 2011  |  Pubmed ID: 21535751

In the present study, we reported a comparative analysis of the chemical composition and pharmacological properties of the essential oils obtained from 2 Mexican oreganos, Poliomintha longiflora and Lippia graveolens. The gas chromatography-mass spectrometry (GC-MS) profiles of the oils showed high amounts of oxygenated monoterpenes, mainly carvacrol (%[mg/100 g dry matter]) (18.36 [459.0] in P. longiflora and 13.48 [164.7] in L. graveolens). In addition, these oils contained marked quantities of p-cymene (14.09 [352.2] and 7.46 [37.3], respectively), β-caryophyllene oxide, β-caryophyllene, and carvacrol acetate. Headspace analyses of the leaves of both species using different coated fibers revealed that γ-terpinene, eucalyptol, and p-cymene were the principal light volatile components. Chromatographic fingerprints and a suitable analytical method for quantifying the main components of both essences were established using high-performance liquid chromatography (HPLC) as analytical tool. The essential oils of both species were not toxic in the acute toxicity studies in mice performed according to the Lorke procedure (DL(50) > 5000 mg/kg). The oils and the major constituents, carvacrol and p-cymene, displayed a moderate in vitro antibacterial activity, with minimum inhibitory concentration values ranging from 128 to 512 μg/mL. In addition, these samples demonstrated a marginal antispasmodic activity in vivo and provoked a concentration-dependent inhibition of the carbachol- and histamine-induced contractions using the isolated guinea-pig ileum preparation. In particular, p-cymene exerts good selective inhibitory activity on the carbachol-induced contractions (IC(50) = 9.85 μg/mL). PRACTICAL APPLICATION: The analytical methods using GC-MS and HPLC techniques will be useful for establishing quality control as well as preclinical pharmacological and toxicological parameters of the crude drug P. longiflora, which is widely used as substitute of L. graveolens for medicinal and flavorings purposes. This overall information will be also useful for elaborating scientific and pharmacopoeic monographs of this very Mexican medicinal plant.

Pregnancy Outcomes in the Current Era of Cystic Fibrosis Care: a 15-year Experience

The Australian & New Zealand Journal of Obstetrics & Gynaecology. Jun, 2011  |  Pubmed ID: 21631440

With improvement in clinical care and longer survival of patients with cystic fibrosis (CF), pregnancy has become commonplace. However, the impact of pregnancy on maternal health and fetal outcomes requires ongoing review.

Using a Toolbox of Tailored Educational Lessons to Improve Fruit, Vegetable, and Physical Activity Behaviors Among African American Women in California

Journal of Nutrition Education and Behavior. Jul-Aug, 2011  |  Pubmed ID: 21683294

Evaluate the effectiveness of the Fruit, Vegetable, and Physical Activity Toolbox for Community Educators (Toolbox), an intervention originally designed for Spanish- and English-speaking audiences, in changing knowledge, attitudes, and behavior among low-income African American women.

Mechanisms and Applications of Hypertonic Saline

Journal of the Royal Society of Medicine. Jul, 2011  |  Pubmed ID: 21719889

Time Course of Endothelial Adaptation After Acute and Chronic Exercise in Patients with Metabolic Syndrome

Journal of Strength and Conditioning Research / National Strength & Conditioning Association. Sep, 2011  |  Pubmed ID: 21747296

Clustering of cardiovascular risk factors may lead to endothelial dysfunction. Physical exercise is an important factor in prevention and treatment of endothelial dysfunction. We wanted to determine the time course of adaptation to a single bout of exercise at either high or moderate intensity upon endothelial function both before and after a 16-week fitness program in patients with metabolic syndrome. Twenty-eight patients with metabolic syndrome participated in the study and were randomized and stratified (according to age and sex) into an aerobic interval exercise training group (AIT, n = 11), a continuously moderate-intensity exercise training group (CME, n = 8) or to a control group (n = 9). Flow-mediated dilatation (FMD) was determined at baseline, immediately, 24, 48, and 72 hours after 1 bout of exercise and repeated after 16 weeks of exercise. In the untrained state, FMD improved from 5 to 11% (p = 0.003) immediately after a single bout of aerobic interval training (AIT), an effect lasting 72 hours postexercise. In comparison, continuous moderate exercise (CME) improved FMD immediately after a single bout of exercise from 5 to 8% (p = 0.02), an effect lasting 24 hours postexercise (group difference, p < 0.001). In the trained state, a single bout of AIT resulted in a 2% (p = 0.007) acute increase of FMD lasting 48 hours postexercise. The CME increased FMD by 3% (p < 0.01), an effect lasting 24 hours postexercise (group difference p = 0.0012). Blood glucose level decreased after 1 single bout of AIT in the untrained state (p < 0.05), and the effect lasted at least 72 hours postexercise (p < 0.01). Acute CME decreased blood glucose with normalization of the values 24 hours postexercise (p < 0.01). A single bout of exercise in the trained state reduced fasting blood glucose by 10% (p < 0.05) after both AIT and CME. Exercise training, especially high intensity, thus appears to be highly beneficial in reducing blood glucose and improving endothelial function.

Sunflower Domestication Alleles Support Single Domestication Center in Eastern North America

Proceedings of the National Academy of Sciences of the United States of America. Aug, 2011  |  Pubmed ID: 21844335

Phylogenetic analyses of genes with demonstrated involvement in evolutionary transitions can be an important means of resolving conflicting hypotheses about evolutionary history or process. In sunflower, two genes have previously been shown to have experienced selective sweeps during its early domestication. In the present study, we identified a third candidate early domestication gene and conducted haplotype analyses of all three genes to address a recent, controversial hypothesis about the origin of cultivated sunflower. Although the scientific consensus had long been that sunflower was domesticated once in eastern North America, the discovery of pre-Columbian sunflower remains at archaeological sites in Mexico led to the proposal of a second domestication center in southern Mexico. Previous molecular studies with neutral markers were consistent with the former hypothesis. However, only two indigenous Mexican cultivars were included in these studies, and their provenance and genetic purity have been questioned. Therefore, we sequenced regions of the three candidate domestication genes containing SNPs diagnostic for domestication from large, newly collected samples of Mexican sunflower landraces and Mexican wild populations from a broad geographic range. The new germplasm also was genotyped for 12 microsatellite loci. Our evidence from multiple evolutionarily important loci and from neutral markers supports a single domestication event for extant cultivated sunflower in eastern North America.

Attenuated Neurological Deficit, Cell Death and Lesion Volume in Fas-mutant Mice is Associated with Altered Neuroinflammation Following Traumatic Brain Injury

Brain Research. Sep, 2011  |  Pubmed ID: 21871613

Progressive neurodegeneration following traumatic brain injury (TBI) involves the Fas and TNF-receptor1 protein systems which have been implicated in mediating delayed cell death. In this study, we used two approaches to assess whether inhibition of these pathways reduced secondary brain damage and neurological deficits after TBI. Firstly, we investigated whether the expression of non-functional Fas in lpr mice subjected to TBI altered tissue damage and neurological outcome. Compared to wild-type, lpr mice showed improved neurological deficit (p=0.0009), decreased lesion volume (p=0.017), number of TUNEL+ cells (p=0.011) and caspase-3+ cells (p=0.007). Changes in cellular inflammation and cytokine production were also compared between mouse strains. Accumulation of macrophages/microglia occurred earlier in lpr mice, likely due to enhanced production of the chemotactic mediators IL-12(p40) and MCP-1 (p<0.05). Cortical production of IL-1α and IL-6 increased after injury to a similar extent regardless of strain (p<0.05), while TNF and G-CSF were significantly higher in lpr animals (p<0.05). Secondly, we assessed whether therapeutic inhibition of FasL and TNF via intravenous injection of neutralizing antibodies in wild-type mice post-TBI could reproduce the beneficial effects observed in lpr animals. No differences were found with this approach in animals treated with anti-FasL and anti-TNF antibodies alone or the combination of both. Altogether, reduced neurological deficits and lesion volume in lpr mice was associated with altered cellular and humoral inflammation, possibly contributing to neuroprotection, whereas neutralization of FasL and TNF had no effect. In future studies, the lpr mouse strain may be utilized as a model to further characterize molecular and cellular mechanisms protecting against secondary brain damage after TBI.

The Role of Exercise in Maintaining Health in Cystic Fibrosis

Current Opinion in Pulmonary Medicine. Nov, 2011  |  Pubmed ID: 21881514

Consensus statements about the care of people with cystic fibrosis (CF) recommend exercise as part of a wider management strategy. Many of these recommendations are based on high-quality evidence that regular exercise improves some important clinical outcomes, such as lung function and quality of life. However, the evidence about the effect of exercise on other clinical outcomes is less extensive or lower in quality. This article will review the physiological effects of exercise on a range of outcomes in people with CF, the mechanisms by which exercise may improve these outcomes and the quality and findings of clinical research into the effects of exercise in the management of CF.

Population-specific Genetic Associations with Oesophageal Squamous Cell Carcinoma in South Africa

Carcinogenesis. Dec, 2011  |  Pubmed ID: 21926110

Genetic variants in multiple cellular pathways have been associated with an altered risk of oesophageal cancer. In this study, eight genes previously associated with an altered risk of oesophageal squamous cell carcinoma (OSCC) in European or Asian populations were investigated in two South African populations. We genotyped 12 single-nucleotide polymorphisms and one insertion/deletion variant in 1463 individuals from the Black and Mixed Ancestry populations. No polymorphisms were associated with OSCC in the Black population. In the Mixed Ancestry population, ALDH2 +82 G > A (rs886205) was significantly associated with a reduced risk of OSCC (odds ratio = 0.70, 95% confidence interval = 0.55-0.89; P = 0.0038). Several other polymorphisms showed a suggestive association (P < 0.05), including ADH1B Arg48His (rs1229984), COX-2 -1195G > A (rs689466), CASP8 Asp302His (rs1045485) and MGMT Leu84Phe (rs12917). Haplotype analysis indicated that the FAS polymorphisms -670 A > G (rs1800682) and -1377 G > A (rs2234767) were both associated with OSCC in the Mixed Ancestry population (P = 0.006 and P = 0.004, respectively), as well as the CASP8 (-652 6Ndel:302His) haplotype (P = 0.0013). This study indicates several instances of population-specific differences in the genetic etiology of OSCC between these two South African populations and between them and other high-risk populations, which may reflect differences in their ancestry and environmental exposures.

Pseudomonas Aeruginosa AES-1 Exhibits Increased Virulence Gene Expression During Chronic Infection of Cystic Fibrosis Lung

PloS One. 2011  |  Pubmed ID: 21935417

Pseudomonas aeruginosa, the leading cause of morbidity and mortality in people with cystic fibrosis (CF), adapts for survival in the CF lung through both mutation and gene expression changes. Frequent clonal strains such as the Australian Epidemic Strain-1 (AES-1), have increased ability to establish infection in the CF lung and to superimpose and replace infrequent clonal strains. Little is known about the factors underpinning these properties. Analysis has been hampered by lack of expression array templates containing CF-strain specific genes. We sequenced the genome of an acute infection AES-1 isolate from a CF infant (AES-1R) and constructed a non-redundant micro-array (PANarray) comprising AES-1R and seven other sequenced P. aeruginosa genomes. The unclosed AES-1R genome comprised 6.254Mbp and contained 6957 putative genes, including 338 not found in the other seven genomes. The PANarray contained 12,543 gene probe spots; comprising 12,147 P. aeruginosa gene probes, 326 quality-control probes and 70 probes for non-P. aeruginosa genes, including phage and plant genes. We grew AES-1R and its isogenic pair AES-1M, taken from the same patient 10.5 years later and not eradicated in the intervening period, in our validated artificial sputum medium (ASMDM) and used the PANarray to compare gene expression of both in duplicate. 675 genes were differentially expressed between the isogenic pairs, including upregulation of alginate, biofilm, persistence genes and virulence-related genes such as dihydroorotase, uridylate kinase and cardiolipin synthase, in AES-1M. Non-PAO1 genes upregulated in AES-1M included pathogenesis-related (PAGI-5) genes present in strains PACS2 and PA7, and numerous phage genes. Elucidation of these genes' roles could lead to targeted treatment strategies for chronically infected CF patients.

Cystic Fibrosis in Australia, 2009: Results from a Data Registry

The Medical Journal of Australia. Oct, 2011  |  Pubmed ID: 21978347

To describe the demographics, clinical features and outcomes among people with cystic fibrosis (CF) in Australia and to estimate incidence of the disease.

Results from 2 Randomized, Double-blind, Placebo-controlled Studies of the Novel NK1 Receptor Antagonist Casopitant in Patients with Major Depressive Disorder

Journal of Clinical Psychopharmacology. Dec, 2011  |  Pubmed ID: 22020354

Clinical study results for neurokinin (NK) receptor antagonists in the treatment of depression have been mixed, with Phase III studies failing to fulfill the early promise demonstrated in Phase II studies. Casopitant, a selective NK1 antagonist that achieves nearly complete receptor occupancy was studied in 2 randomized, placebo-controlled, double-blind, Phase II trials in depressed outpatients to test the hypothesis that nearly complete NK1 receptor occupancy is required to achieve antidepressant efficacy. Study 092 used an interactive voice response system to recruit depressed patients with baseline Hamilton Depression (17-item, HAMD17) total scores higher than 24 who were randomized to fixed-dose casopitant 30 mg/d, 80 mg/d, or placebo for 8 weeks (n = 356). Study 096 required Carroll Depression Scale-Revised self-assessment scores of higher than 24 for randomization to casopitant 120 mg/d, paroxetine 30 mg/d (both reached via forced titration), or placebo for 8 weeks (n = 362). In study 092, casopitant 80 mg but not 30 mg achieved statistically significant improvement versus placebo on the primary outcome measure, week 8 last observation carried forward change from baseline HAMD17 (difference = -2.7; 95% confidence interval, -5.1 to -0.4, P = 0.023). In study 096, neither casopitant nor paroxetine achieved statistical separation from placebo at end point on HAMD17 (casopitant difference = -1.7; 95% CI, -3.8 to 0.4, P = 0.282). Casopitant and paroxetine were generally well tolerated in most patients. These studies suggest that NK1 antagonists that have nearly complete receptor occupancy may be effective in the treatment of depression.

On the Causes of Variability in Amounts of Airborne Grass Pollen in Melbourne, Australia

International Journal of Biometeorology. Jul, 2011  |  Pubmed ID: 20814699

In Melbourne, Australia, airborne grass pollen is the predominant cause of hay fever (seasonal rhinitis) during late spring and early summer, with levels of airborne grass pollen also influencing hospital admissions for asthma. In order to improve predictions of conditions that are potentially hazardous to susceptible individuals, we have sought to better understand the causes of diurnal, intra-seasonal and inter-seasonal variability of atmospheric grass pollen concentrations (APC) by analysing grass pollen count data for Melbourne for 16 grass pollen seasons from 1991 to 2008 (except 1994 and 1995). Some of notable features identified in this analysis were that on days when either extreme (>100 pollen grains m(-3)) or high (50-100 pollen grains m(-3)) levels of grass pollen were recorded the winds were of continental origin. In contrast, on days with a low (<20 pollen grains m(-3)) concentration of grass pollen, winds were of maritime origin. On extreme and high grass pollen days, a peak in APC occurred on average around 1730 hours, probably due to a reduction in surface boundary layer turbulence. The sum of daily APC for each grass pollen season was highly correlated (r = 0.79) with spring rainfall in Melbourne for that year, with about 60% of a declining linear trend across the study period being attributable to a reduction of meat cattle and sheep (and hence grazing land) in rural areas around Melbourne. Finally, all of the ten extreme pollen events (3 days or more with APC > 100 pollen grains m(-3)) during the study period were characterised by an average downward vertical wind anomaly in the surface boundary layer over Melbourne. Together these findings form a basis for a fine resolution atmospheric general circulation model for grass pollen in Melbourne's air that can be used to predict daily (and hourly) APC. This information will be useful to those sectors of Melbourne's population that suffer from allergic problems.

Ent-trachyloban-19-oic Acid Isolated from Iostephane Heterophylla As a Promising Antibacterial Agent Against Streptococcus Mutans Biofilms

Fitoterapia. Apr, 2012  |  Pubmed ID: 22245083

From the roots of Iostephane heterophylla, six known compounds, namely, ent-trachyloban-19-oic acid (1), the mixture of ent-kaur-16-en-19-oic acid (2) and ent-beyer-15-en-19-oic acid (3), xanthorrhizol (4), 16α-hydroxy-ent-kaurane (5) and 16α-hydroxy-ent-kaur-11-en-19-oic acid (6) were isolated using a bioassay-guided fractionation method. The known compounds (1-6) were identified by comparison of their spectroscopic data with reported values in the literature. In an attempt to increase the resultant antimicrobial activity of 1 and 4, a series of reactions was performed on ent-trachyloban-19-oic acid (1) and xanthorrhizol (4), to obtain derivatives 1a, 1b, and 4a-4d. All the isolated compounds (1-6) and the derivatives 1a, 1b, and 4a-4d were evaluated for their antimicrobial activity against two oral pathogens, Streptococcus mutans and Porphyromonas gingivalis associated with caries and periodontal disease, respectively. Compounds 1, 1b, 2+3, 4 and 4d inhibited the growth of S. mutans with concentrations ranging from 4.1 μg/mL to 70.5 μg/mL. No significant activity was found on P. gingivalis except for 4 with an MIC of 6.8 μg/mL. The ability of 1, 1b, 2+3, 4 and 4d to inhibit biofilm formation by S. mutans was evaluated. It was found that 1, 1b, 4 and 4d interfered with the establishment of S. mutans biofilms, inhibiting their development at 32.5, 125.0, 14.1 and 24.4 μg/mL, respectively.

Attenuation of Microglial Activation with Minocycline is Not Associated with Changes in Neurogenesis After Focal Traumatic Brain Injury in Adult Mice

Journal of Neurotrauma. May, 2012  |  Pubmed ID: 22260446

Neurogenesis is stimulated following injury to the adult brain and could potentially contribute to tissue repair. However, evidence suggests that microglia activated in response to injury are detrimental to the survival of new neurons, thus limiting the neurogenic response. The aim of this study was to determine the effect of the anti-inflammatory drug minocycline on neurogenesis and functional recovery after a closed head injury model of focal traumatic brain injury (TBI). Beginning 30 min after trauma, minocycline was administered for up to 2 weeks and bromodeoxyuridine was given on days 1-4 to label proliferating cells. Neurological outcome and motor function were evaluated over 6 weeks using the Neurological Severity Score (NSS) and ledged beam task. Microglial activation was assessed in the pericontusional cortex and hippocampus at 1 week post-trauma, using immunohistochemistry to detect F4/80. Following immunolabeling of bromodeoxyuridine, double-cortin, and NeuN, cells undergoing distinct stages of neurogenesis, including proliferation, neuronal differentiation, neuroblast migration, and long-term survival, were quantified at 1 and 6 weeks in the hippocampal dentate gyrus, as well as in the subventricular zone of the lateral ventricles and the pericontusional cortex. Our results show that minocycline successfully reduced microglial activation and promoted early neurological recovery that was sustained over 6 weeks. We also show for the first time in the closed head injury model, that early stages of neurogenesis were stimulated in the hippocampus and subventricular zone; however, no increase in new mature neurons occurred. Contrary to our hypothesis, despite the attenuation of activated microglia, minocycline did not support neurogenesis in the hippocampus, lateral ventricles, or pericontusional cortex, with none of the neurogenic stages being affected by treatment. These data provide evidence that a general suppression of microglial activation is insufficient to enhance neuronal production, suggesting that further work is required to elucidate the relationship between microglia and neurogenesis after TBI.

Adults with Cystic Fibrosis Prefer Hypertonic Saline Before or During Airway Clearance Techniques: a Randomised Crossover Trial

Journal of Physiotherapy. 2012  |  Pubmed ID: 22341380

Among adults with cystic fibrosis, does the timing of hypertonic saline relative to airway clearance techniques affect lung function, perceived efficacy, tolerability, or satisfaction with the entire airway clearance regimen, and is the preferred timing regimen stable over time?

Therapeutic Identification of Depression in Young People: Lessons from the Introduction of a New Technique in General Practice

The British Journal of General Practice : the Journal of the Royal College of General Practitioners. Mar, 2012  |  Pubmed ID: 22429434

Mild-to-moderate depression in young people is associated with impaired social functioning and high rates of affective disorder in adult life. Earlier recognition of depression in young people has the potential to reduce the burden of depression in adulthood. However, depression in teenagers is underdiagnosed and undertreated.

A Novel Strategy for Retrospective Exposure Assessment in the Norwegian Silicon Carbide Industry

Journal of Occupational and Environmental Hygiene. 2012  |  Pubmed ID: 22448628

The objective was to construct a retrospective job-exposure matrix (JEM) for the Norwegian silicon carbide industry. More than 3300 historical total dust measurements were available (1967-2005); however, there were few measurements of other agents. Total dust measurements were therefore used as the basis for the JEM, and a novel method was developed to estimate exposure to other agents. Multiple linear regression models were developed to describe historical exposure to total dust. Exposure estimates were extrapolated backward to periods without exposure data by adjustments for process and work-hour related changes. An exposure assessment study was performed where total dust was sampled in parallel with fibers or respirable dust. The respirable dust was analyzed for the content of quartz, cristobalite, and silicon carbide. Mixed-effect models were developed to estimate the exposure to these agents from total dust exposure, plant, and job group. Exposure to asbestos and polycyclic aromatic hydrocarbons was assigned qualitatively. Multiple linear regression models of total dust described historical exposure best in the furnace department (R(2) (adj) = 0.49-0.74). Models in the other departments explained less variance (R(2) (adj) = 0.12-0.32). Exposure determinants and total dust explained a substantial proportion of the between- (70-100%) and within-worker (8.0-54%) variance in the mixed-effect models. The relative bias between available historical measurements and the estimated exposure to dust components varied between -39% (fiber) and 40% (quartz). However, corrections were not considered necessary due to limitations in the historical data. The component-specific metrices were sufficiently different from each other (r(Pearson) < 0.7), with the exception of total and respirable dust (r(Pearson) = 0.84) and total dust and cristobalite (r(Pearson) = 0.72), and will enable component-specific epidemiologic analyses in the future. Improved and less correlated estimates of exposure levels for the different components in the dust were obtained with the updated exposure assessment. Due to limitations in the measurement data, assumptions had to be made, especially in the period before 1967. [Supplementary materials are available for this article. Go to the publisher's online edition of Journal of Occupational and Environmental Hygiene for the following free supplemental resource: a file containing tables outlining multiple linear regression models for prediction of total dust exposure in the processing departments of Norwegian SiC producing plants, evaluation of the predictive abilities of the reduced total dust models, and mixed models for pedicting exposure to fibers and respirable quartz, cristobalite, non-fibrous silicon carbide and respirable dust from total dust exposure.].

Arm Exercise Training in Chronic Obstructive Pulmonary Disease: A Randomised Controlled Trial

Chronic Respiratory Disease. 2012  |  Pubmed ID: 22452973

The aim of this study was to compare the effects of arm endurance training, arm strength training, a combination of arm endurance and strength training, and no arm training on endurance arm exercise capacity. A randomised controlled trial was undertaken with chronic obstructive pulmonary disease subjects randomised into one of four groups to complete 8 weeks of training: (a) arm endurance training (endurance group) consisting of supported and unsupported arm exercises, (b) arm strength training (strength group) using weight machines, (c) a combination of arm endurance and arm strength training (combined group), or (d) no arm training (control group). The primary outcome measurement was endurance arm exercise capacity measured by an endurance arm crank test. Secondary outcomes included functional arm exercise capacity measured by the incremental unsupported arm exercise test and health-related quality of life. A total of 52 subjects were recruited and 38 (73%) completed the study. When comparing the arm endurance group to the control group, there was a significant increase in endurance time of 6 min (95% CI 2-10, p < 0.01) following the interventions. When comparing the combined group to each of the control, endurance and strength groups, there was a significantly greater reduction in dyspnoea and rate of perceived exertion at the end of the functional arm exercise test for the combined group following the interventions. The mode of training to be favoured to increase endurance arm exercise capacity is arm endurance training. However, combined arm endurance and strength training may also be very useful to reduce the symptoms during everyday arm tasks.

Inflammatory Regulators of Redirected Neural Migration in the Injured Brain

Neuro-Signals. 2012  |  Pubmed ID: 22456466

Brain injury following stroke or trauma induces the migration of neuroblasts derived from subventricular zone neural precursor cells (NPCs) towards the damaged tissue, where they then have the potential to contribute to repair. Enhancing the recruitment of new cells thus presents an enticing prospect for the development of new therapeutic approaches to treat brain injury; to this end, an understanding of the factors regulating this process is required. During the neuroinflammatory response to ischemic and traumatic brain injuries, a plethora of pro- and anti-inflammatory cytokines, chemokines and growth factors are released in the damaged tissue, and recent work indicates that a variety of these are able to influence injury-induced migration. In this review, we will discuss the contribution of specific chemokines and growth factors towards stimulating NPC migration in the injured brain.

A Qualitative Evaluation of General Practitioners' Perceptions Regarding Access to Medicines in New Zealand

BMJ Open. 2012  |  Pubmed ID: 22457477

The objective of this study was to evaluate general practitioners' (GPs) perceptions regarding access to medicines in New Zealand.

A Functional Description of CymA, an Electron-transfer Hub Supporting Anaerobic Respiratory Flexibility in Shewanella

The Biochemical Journal. Jun, 2012  |  Pubmed ID: 22458729

CymA (tetrahaem cytochrome c) is a member of the NapC/NirT family of quinol dehydrogenases. Essential for the anaerobic respiratory flexibility of shewanellae, CymA transfers electrons from menaquinol to various dedicated systems for the reduction of terminal electron acceptors including fumarate and insoluble minerals of Fe(III). Spectroscopic characterization of CymA from Shewanella oneidensis strain MR-1 identifies three low-spin His/His co-ordinated c-haems and a single high-spin c-haem with His/H(2)O co-ordination lying adjacent to the quinol-binding site. At pH 7, binding of the menaquinol analogue, 2-heptyl-4-hydroxyquinoline-N-oxide, does not alter the mid-point potentials of the high-spin (approximately -240 mV) and low-spin (approximately -110, -190 and -265 mV) haems that appear biased to transfer electrons from the high- to low-spin centres following quinol oxidation. CymA is reduced with menadiol (E(m) = -80 mV) in the presence of NADH (E(m) = -320 mV) and an NADH-menadione (2-methyl-1,4-naphthoquinone) oxidoreductase, but not by menadiol alone. In cytoplasmic membranes reduction of CymA may then require the thermodynamic driving force from NADH, formate or H2 oxidation as the redox poise of the menaquinol pool in isolation is insufficient. Spectroscopic studies suggest that CymA requires a non-haem co-factor for quinol oxidation and that the reduced enzyme forms a 1:1 complex with its redox partner Fcc3 (flavocytochrome c3 fumarate reductase). The implications for CymA supporting the respiratory flexibility of shewanellae are discussed.

Quantitative HPLC Method for Determining Two of the Major Active Phthalides from Ligusticum Porteri Roots

Journal of AOAC International. Jan-Feb, 2012  |  Pubmed ID: 22468345

Z-Ligustilide (1) and Z-6,6',7,3'-alpha-diligustilide (2), two of the major active phthalides of the medicinal plant Ligusticum porteri (osha), were chosen for the development and validation of an HPLC-diode array detection method suitable for QC of the crude drug. The method used gradient elution to achieve separation on a Hibar RT LiChrospher 100 C18 column. The LOD values were 29 and 45 microg/mL, and the LOQs were 89 and 125 microg/mL, respectively. The method showed good intraday precision (%RSD: 0.7 for 1 and 3.1 for 2) and interday precision (%RSD: 1.2 for 1 and 1.8 for 2). The method was used for the analysis of 1 and 2 in crude drug samples and several herbal preparations from Mexico and the United States. Quantitative analysis showed that the content of the two phthalides varied significantly among the samples. All the samples contained higher concentrations of 1 (0.15-2.5%) than 2 (0.002-1.0%). The profiles of volatile compounds in the essential oil obtained by hydrodistillation and solid-phase microextraction of L. porteri roots were analyzed by GC-MS. Thirty one chemical constituents (> 99.7% of the total content) were identified in the essential oil, which was characterized by the presence of a high percentage of phthalides (44.61%) and sesquiterpenes (10.69%). The major light volatile components extracted by solid-phase microextraction were monoterpenes.

Pseudomonas Aeruginosa Strains from the Chronically Infected Cystic Fibrosis Lung Display Increased Invasiveness of A549 Epithelial Cells over Time

Microbial Pathogenesis. Jul, 2012  |  Pubmed ID: 22516803

The invasive properties of Pseudomonas aeruginosa pose a serious threat to the wellbeing of cystic fibrosis (CF) patients; however the specific factors affecting invasiveness are not well understood, especially in chronic infection. This study characterises the invasive profiles of sequential isolates of the same P. aeruginosa strain collected five to eight years apart from five chronically infected adult CF patients. Strains from three patients were characterised as unique isolates and from two patients as the Australian Epidemic strain (AES-1) by pulsed field gel electrophoresis. The capacity of these strains to invade the human alveolar A549 cell line was examined. Later isolates were significantly more invasive than earlier counterparts from the same patient. Quantitative real-time PCR and Western blotting showed that the increase in invasiveness over time was independent of ExoS expression and secretion. A link between clonality and invasiveness was also identified, with AES-1 isolates more invasive than unique isolates. These results suggest that despite a reduction in some virulence factors such as the Type-3 Secretion System (T3SS) during chronic infection, a particular strain can become more invasive over time. Defining mechanisms behind the increased invasiveness during chronic infection may help identify new therapeutic targets for CF patients.

Birth Dating of Midbrain Dopamine Neurons Identifies A9 Enriched Tissue for Transplantation into Parkinsonian Mice

Experimental Neurology. Jul, 2012  |  Pubmed ID: 22524988

Clinical trials have provided proof of principle that new dopamine neurons isolated from the developing ventral midbrain and transplanted into the denervated striatum can functionally integrate and alleviate symptoms in Parkinson's disease patients. However, extensive variability across patients has been observed, ranging from long-term motor improvement to the absence of symptomatic relief and development of dyskinesias. Heterogeneity of the donor tissue is likely to be a contributing factor in the variable outcomes. Dissections of ventral midbrain used for transplantation will variously contain progenitors for different dopamine neuron subtypes as well as different neurotransmitter phenotypes. The overall impact of the resulting graft will be determined by the functional contribution from these different cell types. The A9 substantia nigra pars compacta dopamine neurons, for example, are known to be particularly important for motor recovery in animal models. Serotonergic neurons, on the other hand, have been implicated in unwanted dyskinesias. Currently little knowledge exists on how variables such as donor age, which have not been controlled for in clinical trials, will impact on the final neuronal composition of fetal grafts. Here we performed a birth dating study to identify the time-course of neurogenesis within the various ventral midbrain dopamine subpopulations in an effort to identify A9-enriched donor tissue for transplantation. The results show that A9 neurons precede the birth of A10 ventral tegmental area dopamine neurons. Subsequent grafting of younger ventral midbrain donor tissue revealed significantly larger grafts containing more mitotic dopamine neuroblasts compared to older donor grafts. These grafts were enriched with A9 neurons and showed significantly greater innervation of the target dorso-lateral striatum and DA release. Younger donor grafts also contained significantly less serotonergic neurons. These findings demonstrate the importance of standardized methods to improve cell therapy for Parkinson's disease and have significant implications for the generation and selectivity of dopamine neurons from stem cell based sources.

Gap Junctions and Connexin Hemichannels Underpin Hemostasis and Thrombosis

Circulation. May, 2012  |  Pubmed ID: 22528526

Connexins are a widespread family of membrane proteins that assemble into hexameric hemichannels, also known as connexons. Connexons regulate membrane permeability in individual cells or couple between adjacent cells to form gap junctions and thereby provide a pathway for regulated intercellular communication. We have examined the role of connexins in platelets, blood cells that circulate in isolation but on tissue injury adhere to each other and the vessel wall to prevent blood loss and to facilitate wound repair.

Profiling of Alkaloids and Eremophilanes in Miracle Tea (Packera Candidissima and P. Bellidifolia) Products

Journal of Natural Products. May, 2012  |  Pubmed ID: 22551074

Commercial preparations of the Mexican herbal drug known as "miracle tea" (Packera candidissima and P. bellidifolia) have been profiled qualitatively by HPLC and GC-MS. Eremophilanes (3-7) were the major components found in the hexane-soluble fraction, while pyrrolizidine alkaloids (PAs) were identified in the alkaloid extracts. The content of free PAs and their N-oxides was determined for a total of 22 samples, and the results showed that the amount of these hepatotoxic compounds (0.0005-0.94% free PAs; 0.0004-0.55% N-oxides), through the presence of retrorsine (1) and senesionine (2) as the main constituents, may reach toxic levels. Hexane-soluble extracts from commercial presentations (dried whole plants) of both species afforded neoadenostylone (3), 6-(2-methylbutanoyloxy)-9-oxo-1-(10)-furanoeremophilene (4), and epineoadenostylone (5), in addition to methyl-4-hydroxyphenylacetate (8) and methyl-2-(1-hydroxy-4-oxocyclohexyl)acetate (9). Also, epicacalone (6) and the new compound 2β-hydroxyneoadenostylone (7) were isolated from P. bellidifolia.

α-glucosidase Inhibitors from Brickellia Cavanillesii

Journal of Natural Products. May, 2012  |  Pubmed ID: 22587572

An aqueous extract from the aerial parts of Brickellia cavanillesii attenuated postprandial hyperglycemia in diabetic mice during oral glucose and sucrose tolerance tests. Experimental type-II DM was achieved by treating mice with streptozotocin (100 mg/kg) and β-nicotinamide adenine dinucleotide (40 mg/kg). These pharmacological results demonstrated that B. cavanillesii is effective for controlling fasting and postprandial blood glucose levels in animal models. The same aqueous extract also showed potent inhibitory activity (IC(50) = 0.169 vs 1.12 mg/mL for acarbose) against yeast α-glucosidase. Bioassay-guided fractionation of the active extract using the α-glucosidase inhibitory assay led to the isolation of several compounds including two chromenes [6-acetyl-5-hydroxy-2,2-dimethyl-2H-chromene (1) and 6-hydroxyacetyl-5-hydroxy-2,2-dimethyl-2H-chromene (2)], two sesquiterpene lactones [caleins B (3) and C (4)], several flavonoids [acacetin (5), genkwanin (6), isorhamnetin (7), kaempferol (8), and quercetin (9)], and 3,5-di-O-caffeoylquinic acid (10). Chromene 2 is a new chemical entity. Compounds 2, 4, 7, and 9 inhibited the activity of yeast α-glucosidase with IC(50) 0.42, 0.28, 0.16, and 0.53 mM, respectively, vs 1.7 mM for acarbose. Kinetic analysis revealed that compounds 4 and 7 behaved as mixed-type inhibitors with K(i) values of 1.91 and 0.41 mM, respectively, while 2 was noncompetititive, with a K(i) of 0.13 mM. Docking analysis predicted that these compounds, except 2, bind to the enzyme at the catalytic site.

HIV-1 Infection of Human Macrophages Directly Induces Viperin Which Inhibits Viral Production

Blood. Jul, 2012  |  Pubmed ID: 22677126

Macrophages are key target cells for HIV-1. HIV-1(BaL) induced a subset of interferon-stimulated genes in monocyte-derived macrophages (MDMs), which differed from that in monocyte-derived dendritic cells and CD4 T cells, without inducing any interferons. Inhibition of type I interferon induction was mediated by HIV-1 inhibition of interferon-regulated factor (IRF3) nuclear translocation. In MDMs, viperin was the most up-regulated interferon-stimulated genes, and it significantly inhibited HIV-1 production. HIV-1 infection disrupted lipid rafts via viperin induction and redistributed viperin to CD81 compartments, the site of HIV-1 egress by budding in MDMs. Exogenous farnesol, which enhances membrane protein prenylation, reversed viperin-mediated inhibition of HIV-1 production. Mutagenesis analysis in transfected cell lines showed that the internal S-adenosyl methionine domains of viperin were essential for its antiviral activity. Thus viperin may contribute to persistent noncytopathic HIV-1 infection of macrophages and possibly to biologic differences with HIV-1-infected T cells.

Symptoms in Advanced Pancreatic Cancer Are of Importance for Energy Intake

Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer. Jun, 2012  |  Pubmed ID: 22684989

PURPOSE: Cancer cachexia and low energy intake (EI) probably contribute to weight loss in advanced pancreatic cancer (PC). However, little is known about the actual EI in this disease. Aims were to assess EI, weight loss and symptoms during the disease course and investigate associations between symptoms and EI. METHODS: Thirty-nine patients (21 males) with advanced PC were consecutively included and followed every 4 weeks until the end of life. A 24-h dietary recall was used to assess EI. The Edmonton Symptom Assessment System (ESAS) and the PC-specific health-related quality of life questionnaire (QLQ-PAN26) were used for symptom assessment. RESULTS: Median age was 62 years (48-88), WHO performance status 1 (0-2) and survival 5 months (1-25). Seventeen (44 %) patients had unresectable cancer, 16 (41 %) metastatic and six (15 %) recurrent disease. Upon inclusion, 37 (95 %) reported weight loss (median 4.0 kg per month). During follow-up, median weight loss per month was <1.0 kg. Forty to 65 % had EI <29 kcal/kg/day (cut-off value for weight maintenance) during the observation period but they did not lose more weight than patients with EI ≥ 29 kcal. Strong negative correlations (r range) were found between EI and pain (0.51-0.61), fatigue (0.54-0.67), oral dryness (0.61-0.64) and loss of appetite (0.53-0.71). CONCLUSION: In this study, several symptoms influenced EI negatively. Low EI did not completely explain weight loss in this patient group, but careful monitoring and early follow-up of symptoms may be important interventions to reduce weight loss in advanced PC.

Fate of Dissolved Organic Nitrogen in Two Stage Trickling Filter Process

Water Research. Jul, 2012  |  Pubmed ID: 22835838

Dissolved organic nitrogen (DON) represents a significant portion of nitrogen in the final effluent of wastewater treatment plants (WWTPs). Biodegradable portion of DON (BDON) can support algal growth and/or consume dissolved oxygen in the receiving waters. The fate of DON and BDON has not been studied for trickling filter WWTPs. DON and BDON data were collected along the treatment train of a WWTP with a two-stage trickling filter process. DON concentrations in the influent and effluent were 27% and 14% of total dissolved nitrogen (TDN). The plant removed about 62% and 72% of the influent DON and BDON mainly by the trickling filters. The final effluent BDON values averaged 1.8 mg/L. BDON was found to be between 51% and 69% of the DON in raw wastewater and after various treatment units. The fate of DON and BDON through the two-stage trickling filter treatment plant was modeled. The BioWin v3.1 model was successfully applied to simulate ammonia, nitrite, nitrate, TDN, DON and BDON concentrations along the treatment train. The maximum growth rates for ammonia oxidizing bacteria (AOB) and nitrite oxidizing bacteria, and AOB half saturation constant influenced ammonia and nitrate output results. Hydrolysis and ammonification rates influenced all of the nitrogen species in the model output, including BDON.

De Novo Mutations in ATP1A3 Cause Alternating Hemiplegia of Childhood

Nature Genetics. Jul, 2012  |  Pubmed ID: 22842232

Alternating hemiplegia of childhood (AHC) is a rare, severe neurodevelopmental syndrome characterized by recurrent hemiplegic episodes and distinct neurological manifestations. AHC is usually a sporadic disorder and has unknown etiology. We used exome sequencing of seven patients with AHC and their unaffected parents to identify de novo nonsynonymous mutations in ATP1A3 in all seven individuals. In a subsequent sequence analysis of ATP1A3 in 98 other patients with AHC, we found that ATP1A3 mutations were likely to be responsible for at least 74% of the cases; we also identified one inherited mutation in a case of familial AHC. Notably, most AHC cases are caused by one of seven recurrent ATP1A3 mutations, one of which was observed in 36 patients. Unlike ATP1A3 mutations that cause rapid-onset dystonia-parkinsonism, AHC-causing mutations in this gene caused consistent reductions in ATPase activity without affecting the level of protein expression. This work identifies de novo ATP1A3 mutations as the primary cause of AHC and offers insight into disease pathophysiology by expanding the spectrum of phenotypes associated with mutations in ATP1A3.

Serum Levels of Choline-Containing Compounds Are Associated with Aerobic Fitness Level: The HUNT-Study

PloS One. 2012  |  Pubmed ID: 22860113

Cardiovascular disease (CVD) is a leading cause of death worldwide, and the number of people at risk is continuously growing. New methods for early risk prediction are therefore needed to actuate prevention strategies before the individuals are diagnosed with CVD. Several studies report that aerobic fitness level, measured as maximal oxygen uptake (VO(2max)), is the single best predictor of future CVD mortality in healthy people. Based on this, we wanted to study differences between healthy individuals with a large difference in VO(2max)-level to identify new biomarkers of low aerobic fitness that may also have potential as early biomarkers of CVD risk.

The RNA-binding E3 Ubiquitin Ligase MEX-3C Links Ubiquitination with MHC-I MRNA Degradation

The EMBO Journal. Aug, 2012  |  Pubmed ID: 22863774

RNA-binding E3 ubiquitin ligases were recently identified, though their function remains unclear. While studying the regulation of the MHC class I (MHC-I) pathway, we here characterize a novel role for ubiquitin in mRNA degradation. MHC-I molecules provide ligands for both cytotoxic T-lymphocytes as well as natural killer (NK) cells, and play a central role in innate and adaptive immunity. MHC-I cell-surface expression is closely monitored by NK cells, whose killer immunoglobulin-like receptors encode MHC-I-specific activatory and inhibitory receptors, implying that MHC-I expression needs to be tightly regulated. In a functional siRNA ubiquitome screen we identified MEX-3C, a novel RNA-binding ubiquitin E3 ligase, as responsible for the post-transcriptional, allotype-specific regulation of MHC-I. MEX-3C binds the 3'UTR of HLA-A2 mRNA, inducing its RING-dependent degradation. The RING domain of MEX-3C is not required for HLA-A2 cell-surface downregulation, but regulates the degradation of HLA-A2 mRNA. We have therefore uncovered a novel post-transcriptional pathway for regulation of HLA-A allotypes and provide a link between ubiquitination and mRNA degradation.

Distinct Genetic Association at the PLCE1 Locus with Oesophageal Squamous Cell Carcinoma in the South African Population

Carcinogenesis. Aug, 2012  |  Pubmed ID: 22865593

Oesophageal squamous cell carcinoma (OSCC) has a high prevalence in the Black and Mixed Ancestry populations of South Africa. Recently, three genome-wide association studies in Chinese populations identified five new OSCC susceptibility loci, including variants at PLCE1, C20orf54, PDE4D, RUNX1 and UNC5CL, but their contribution to disease risk in other populations is unknown. Here, we report testing variants from these five loci for association with OSCC in the South African Black (407 cases and 849 controls) and Mixed Ancestry (257 cases and 860 controls) populations. The RUNX1 variant rs2014300, which reduced risk in the Chinese population, was associated with an increased risk of OSCC in the Mixed Ancestry population (odds ratio (OR) = 1.33, 95% confidence interval (CI) = 1.09-1.63; P=0.0055), and none of the five loci were associated in the Black population. Since PLCE1 variants increased the risk of OSCC in all three Chinese studies, this gene was investigated further by sequencing in 46 Black South Africans. This revealed 48 variants, 10 of which result in amino acid substitutions, and much lower linkage disequilibrium across the PLCE1 locus than in the Chinese population. We genotyped five PLCE1 variants in cases and controls, and found association of Arg548Leu (rs17417407) with a reduced risk of OSCC (OR = 0.74, 95% CI = 0.60-0.93; P=0.008) in the Black population. These findings indicate several differences in the genetic contribution to OSCC between the South African and Chinese populations that may be related to differences in their genetic architecture.