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Find video protocols related to scientific articles indexed in Pubmed.
Diadenosine tetraphosphate contributes to carbachol-induced tear secretion.
Purinergic Signal.
PUBLISHED: 10-07-2014
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The purpose of this study is to investigate if the cholinergic stimulation by carbachol on tear secretion is a direct process or if it is also mediated by purinergic mechanisms. Experiments were performed in New Zealand male rabbits. The amount of tear secretion was measured with Schirmer's test and then analyzed by a HPLC protocol in order to study the nucleotide levels. Animal eyes were instilled with carbachol (a cholinergic agonist), pirenzepine, gallamine and 4-DAMP (muscarinic antagonists), PPADS, suramin and reactive blue 2 (purinergic antagonists), and a P2Y2 receptor small interfering RNA (siRNA). Tear secretion increased with the instillation of carbachol, approximately 84 % over control values 20 min after the instillation and so did Ap4A and ATP release. When we applied carbachol in the presence of muscarinic antagonists, tear volume only increased to 4 % with atropine, 12 % in the case of pirenzepine, 3 % with gallamine, and 8 % with 4-DAMP. In the presence of carbachol and purinergic antagonists, tear secretion was increased to 12 % (all values compared to basal tear secretion). By analyzing tear secretion induced with carbachol in presence of a P2Y2 receptor siRNA, we found that tear secretion was diminished to 60 %. The inhibition of tear secretion in the presence of carbachol and purinergic antagonists or P2Y2 siRNA occurred with no apparent change in the tear amount of Ap4A. These experiments demonstrated the participation of Ap4A in lacrimal secretion process.
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Enhanced near-infrared emission from holmium-ytterbium co-doped phosphate glasses containing silver nanoparticles.
Appl Spectrosc
PUBLISHED: 10-01-2014
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The fabrication and spectroscopic characterization of Ho(3+) and Yb(3+) co-doped phosphate glasses, also containing silver nanoparticles (SNPs), is reported. The nucleation and formation of nanoparticle structures in the samples are confirmed using transmission electron microscopy analyses. It is found that the Ho(3+)-Yb(3+)-SNP phosphate glasses exhibit an enhancement of both the resonant-absorption and the fluorescence properties when the SNP concentration is increased.
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[Progress of anticoagulation therapy in atrial fibrillation.]
Med Clin (Barc)
PUBLISHED: 09-02-2014
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Atrial fibrillation is currently a very prevalent disease and it represents one of the most common causes of disabling stroke. Antithrombotic therapies have reduced the incidence of this complication although they pose many limitations and difficulties. As a result, a large number of high risk patients do not receive an appropriate treatment. In recent years, four new oral anticoagulants (NOAC) with relevant advantages in comparison to vitaminK antagonists have been released. Four large phaseiii clinical trials have demonstrated that NOAC are at least as safe and efficacious as warfarin in stroke prevention in non-valve atrial fibrillation patients with moderate-high thrombotic risk, being their main advantage the reduction in intracranial hemorrhage. The arrival of these drugs has caused great expectations in the management of these patients but also new doubts. Lacking data in some subgroups of frail patients, the absence of specific antidotes available and specially their high cost represent nowadays the main limitations for their generalization.
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Two flat-backed polydesmidan millipedes from the Miocene Chiapas-amber Lagerstätte, Mexico.
PLoS ONE
PUBLISHED: 08-27-2014
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Two species of fossil polydesmidan millipedes (Diplopoda: Polydesmida) embedded in amber are described from Miocene strata near Simojovel, in the Chiapas Highlands, Mexico. Maatidesmus paachtun gen. et sp. nov., placed into Chelodesmidae Cook, 1895, and Anbarrhacus adamantis gen. et sp. nov., assigned in the family Platyrhacidae Pocock, 1895. Morphological data from fossil specimens have been recovered using 3D X-ray micro-computed tomography and regular to infrared-reflected microscopy. Both fossil species are recognizable as new primarily but not exclusively, by collum margin modification and remarkable paranotal and metatergite dorsal sculpture.
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Prediction of stable acenocoumarol dose by a pharmacogenetic algorithm.
Pharmacogenet. Genomics
PUBLISHED: 08-05-2014
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To develop an acenocoumarol (ACN) dosing algorithm for patients with atrial fibrillation or venous thromboembolism, considering the influence on the stable ACN dose of clinical factors and gene polymorphisms, including CYP2C9*2/*3, VKORC1, CYP4F2*3, ABCB1, APOE, CYP2C19*2/*17, and GGCX.
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Omental adipose tissue gene expression, gene variants, branched-chain amino acids, and their relationship with metabolic syndrome and insulin resistance in humans.
Genes Nutr
PUBLISHED: 07-21-2014
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Obesity is a complex disorder caused by several factors. Thus, the aim of the present study was to assess whether the expression of genes in the omental white adipose tissue (AT) of subjects with insulin resistance (IR) or metabolic syndrome (MetS) is associated with an elevation in serum branched-chain amino acids (BCAAs) and whether this response depends on specific genetic variants. Serum BCAA concentration, the adipocyte area, and gene variants of PPAR?, ABCA1, FTO, TCF7L2, GFOD2, BCAT2, and BCKDH were determined in 115 Mexican subjects. The gene expression in the AT and adipocytes of BCAT, BCKDH E1?, C/EBP?, PPAR?2, SREBP-1, PPAR?, UCP1, leptin receptor, leptin, adiponectin, and TNF? was measured in 51 subjects. Subjects with IR showed higher values for the BMI, HOMA-IR, and adipocyte area and higher levels of serum glucose, insulin, leptin, and C-reactive protein, as well as an elevation of the AT gene expression of SREBP-1, leptin, and TNF? and a significant reduction in the expression of adiponectin, BCAT2, and BCKDH E1?, compared with non-IR subjects. The presence of MetS was associated with higher HOMA-IR as well as higher serum BCAA concentrations. Subjects with the genetic variants for BCAT2 and BCKDH E1 ? showed a lower serum BCAA concentration, and those with the ABCA1 and FTO gene variant showed higher levels of insulin and HOMA-IR than non-IR subjects. AT dysfunction is the result of a combination of the presence of some genetic variants, altered AT gene expression, the presence of MetS risk factors, IR, and serum BCAA concentrations.
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Exposure to ozone induces a systemic inflammatory response: possible source of the neurological alterations induced by this gas.
Inhal Toxicol
PUBLISHED: 07-03-2014
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The World Health Organization identified urban outdoor air pollution as the eighth highest mortality risk factor in high-income countries. Exposure to ambient pollutants such as ozone (O3) increases the number of hospital admissions. O3 is a highly reactive gas that reacts with cells lining the airways, producing the formation of reactive oxygen species and inflammation. Beyond the respiratory system, O3 exposure also produces fatigue, lethargy, headaches, and significant decrease in rapid-eye-movement sleep related to an increase in slow-wave sleep. Interestingly, these sleep changes can be significantly mitigated by treatment with indomethacin, which suggests that an inflammatory mechanism may be responsible for these neurological symptoms. To characterize the inflammatory mechanisms by which O3 affects tissues outside the pulmonary system, we evaluated inflammatory factors in both lung and brain. Rats exposed to 1 part per million O3 for 1, 3 or 6 h, as well as rats exposed daily for 1 or 3 h over five consecutive days, showed increases in TNF-? and IL-6 levels within the lungs as well as increases in TNF-?, IL-6, NF-?B p50 and GFAP levels in the cerebral cortex. These results support the hypothesis that the neuroinflammatory response may be responsible for the central nervous system effects of O3 exposure.
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PET/MRI radiotracer beyond ¹?F-FDG.
PET Clin
PUBLISHED: 06-27-2014
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The recent development and introduction of new hybrid imaging devices combining positron emission tomography (PET) technology with magnetic resonance imaging (MRI) opens up new perspectives in clinical molecular imaging. Combining MRI and fluorine-18 choline PET would theoretically produce valuable clinical data in a single imaging session, which can be used for staging, prognosis, and assessment of treatment response. Fluorine-18-sodium fluoride (18F-NaF) is a highly sensitive PET tracer used as a marker of osteoblastic abnormalities. PET imaging with (68)Ga-DOTATATE or DOTATOC has demonstrated promising results for locating metastatic lesions, occasionally with superior sensitivity than whole-body MRI. l-DOPA PET adds data regarding l-DOPA metabolism, which may increase the specificity and sensibility of the study itself. Fluoromisonidazole is known to be not only a useful tracer for determining hypoxic cells but also an efficient hypoxic radiosensitizer.
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Granulocyte colony-stimulating factors as prophylaxis against febrile neutropenia.
Support Care Cancer
PUBLISHED: 06-09-2014
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Myelosuppression secondary to chemotherapy remains a serious adverse effect of cancer therapy that causes high morbidity and mortality. Several current European and American guidelines recommend consideration of primary prophylaxis with colony-stimulating factors (CSFs) when the risk of febrile neutropenia is higher than 20 %. The main factors associated with a high risk of febrile neutropenia include the chemotherapy regimen, tumor type, and patient-related factors such as old age and/or comorbidities. The purpose of this paper is to summarize the most relevant clinical trials and updated recommendations of the main guidelines on the role of granulocyte colony-stimulating factors (G-CSFs) in febrile neutropenia, examining whether the combination of G-CSF with chemotherapy improves overall survival. Future directions for G-CSF use are also discussed.
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Comparative study on the use of anthocyanin profile, color image analysis and near-infrared hyperspectral imaging as tools to discriminate between four autochthonous red grape cultivars from La Rioja (Spain).
Talanta
PUBLISHED: 05-16-2014
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Three independent methodologies were investigated to achieve the differentiation of red grapes from different grape varieties (Garnacha, Graciano, Mazuelo and Tempranillo) collected from five vineyards located in the D.O.Ca. Rioja. Anthocyanin chromatographic analysis, color image analysis and near infrared hyperspectral imaging were carried out for the grapes. Then, a Stepwise Linear Discriminant Analysis (SLDA) was developed for each data set in order to discriminate grapes according to their grape variety. As a result, using anthocyanin profile, color image analysis and near infrared hyperspectral imaging respectively, 88%, 54% and 100% of the samples were correctly classified in the internal validation process and 86%, 52% and 86% were correctly classified in the leave-one-out cross-validation process.
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Study of the effectiveness of first-line treatment in renal cell carcinoma.
Mol Clin Oncol
PUBLISHED: 05-13-2014
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The emergence of novel drugs corresponds with the determination of the effectiveness of the current treatments used in clinical practice. A retrospective observational study was conducted to evaluate the effectiveness of first-line treatments and to test the influence of the prognostic factors established using the Memorial Sloan-Kettering Cancer Center (MSKCC) and the analysis of Mekhail's study for two or more metastatic sites. The primary endpoints were median progression-free survival (mPFS) and median overall survival (mOS) times. A total of 65 patients were enrolled and the mPFS and mOS of the patients treated with sunitinib (n=51) were 9.0 and 20.1 months, respectively, and for the patients treated with temsirolimus (n=14) these were 3.0 and 6.2 months, respectively. In the poor-prognosis (PP) group, a difference of 1.2 months (P=0.049) was found in mPFS depending on the first-line treatment. A difference of 4.1 months (P=0.023) was also found in mPFS when classified by histology (clear verses non-clear cell) in the sunitinib-treatment group. When stratified by the prognostic group, differences of >7 months (P<0.001) were found between the groups. Therefore, it was concluded that the effectiveness of the treatments was reduced compared to previous studies and differences were found in the PP group when classified by first-line drug and histology. Additionally, the influence of prognostic factors on OS and the value of stratifying patients using these factors have been confirmed.
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Risks in the implementation and use of smart pumps in a pediatric intensive care unit: application of the failure mode and effects analysis.
Int J Technol Assess Health Care
PUBLISHED: 04-28-2014
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The aim of this study was to identify risk points in the different stages of the smart infusion pump implementation process to prioritize improvement measures.
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Comparison of clinical features of left-sided infective endocarditis involving previously normal versus previously abnormal valves.
Am. J. Cardiol.
PUBLISHED: 03-25-2014
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Native valve infective endocarditis (IE) in patients with normal valves has increased in the last decades. Whether patients with normal valves present a similar prognosis to those with pathologic valves is unresolved. Our aim is to describe epidemiologic and clinical differences between patients with left-sided IE and normal valves and those with native pathologic valves. We analyzed 945 consecutive episodes of IE, 435 of which involved left-sided nonprosthetic IE. They were classified into 2 groups: episodes in normal valves (normal group, n=173) and episodes in pathologic valves (abnormal group, n=262). Patients in the normal group were younger, Staphylococcus aureus and Streptococcus bovis were more frequently isolated, and vegetations were more frequently found. Heart failure, septic shock, and the need for surgery or death were more common. Multivariate analysis identified the following as factors independently associated with normal valve IE: age<65 years, S bovis, S aureus, heart failure, and vegetation detection. Factors independently associated with in-hospital events included S aureus, periannular complications, heart failure, and septic shock development. In conclusion, compared with patients with abnormal valve IE, patients with IE on normal valves were younger, had a more virulent microbiological profile, developed heart failure and septic shock more frequently, needed more surgical procedures, and had worse prognosis.
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Intensification treatment based on early FDG-PET in patients with high-risk diffuse large B-cell lymphoma: a phase II GELTAMO trial.
Br. J. Haematol.
PUBLISHED: 03-14-2014
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We conducted a multicentre, phase II study of interim positron emission tomography (PET) as a guide to risk-adapted therapy in high-risk patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). Patients achieving negative fluorodeoxyglucose (FDG)-PET after three courses of R-MegaCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) received three additional courses, whereas PET-positive patients received two courses of R-IFE (rituximab, ifosfamide, etoposide) followed by BEAM (BCNU, etoposide, cytarabine, melphalan) and autologous stem-cell transplantation. The primary endpoint was progression-free survival (PFS). 71 patients (median age 55 years, range 25-69) were enrolled. With a median follow-up of 42·8 months (range 7·2-58·4), the estimated 4-year PFS and overall survival (OS) were 67% and 78%, respectively, for the global series. Patients in complete remission after interim PET (N = 36) had significantly better 3-year PFS than those with partial response (N = 30) [81% vs. 57%, Hazard ratio (HR) = 2·6, 95% confidence interval (CI) = 1·02-6·65] but not a statistically significant longer OS. A retrospective PET central review was done for 51 patients. According to semiquantitative analysis, 3-year PFS (81% vs. 33%; HR = 6·9, 95% CI = 2·35-20·6) and OS (95% vs. 33%, HR = 19·4, 95% CI = 3·89-97·0) were significantly better for negative than for positive interim PET patients. Early PET assessment is valuable for risk stratification in DLBCL; for this purpose semiquantitative evaluation is a better predictor than visual criteria.
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Complete C4 vertebral body destruction: a dramatic finding in a patient with a new diagnosis of myeloma.
BMJ Case Rep
PUBLISHED: 02-22-2014
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We report the case of a 60-year-old woman who presented to accident and emergency with left arm and neck pain. She had reported these symptoms to her general practitioner over the preceding weeks but no imaging was obtained. Radiographs revealed a pathological lesion in her left humerus. On review in the Orthopaedic Fracture Clinic radiographs of the cervical spine were obtained and showed complete destruction of the C4 vertebral body. She underwent corpectomy and stabilisation. Tissue diagnosis confirmed myeloma and she is now under the care of the haematologists receiving chemotherapy and radiotherapy. Myeloma is known to cause severe destructive lesions. Through the dramatic radiographic images this case serves as a reminder to clinicians to obtain imaging of patients with a new or existing diagnosis of malignancy, who show symptoms of skeletal pain, as lesions requiring emergency management may be present.
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Sources of extracellular tau and its signaling.
J. Alzheimers Dis.
PUBLISHED: 02-18-2014
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The pathology associated with tau protein, tauopathy, has been recently analyzed in different disorders, leading to the suggestion that intracellular and extracellular tau may itself be the principal agent in the transmission and spreading of tauopathies. Tau pathology is based on an increase in the amount of tau, an increase in phosphorylated tau, and/or an increase in aggregated tau. Indeed, phosphorylated tau protein is the main component of tau aggregates, such as the neurofibrillary tangles present in the brain of Alzheimer's disease patients. It has been suggested that intracellular tau could be toxic to neurons in its phosphorylated and/or aggregated form. However, extracellular tau could also damage neurons and since neuronal death is widespread in Alzheimer's disease, mainly among cholinergic neurons, these cells may represent a possible source of extracellular tau. However, other sources of extracellular tau have been proposed that are independent of cell death. In addition, several ways have been proposed for cells to interact with, transmit, and spread extracellular tau, and to transduce signals mediated by this tau. In this work, we will discuss the role of extracellular tau in the spreading of the tau pathology.
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The incidence of pulmonary embolism and associated FDG-PET findings in IV contrast-enhanced PET/CT.
Acad Radiol
PUBLISHED: 02-12-2014
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Most fluorine-18 fluorodeoxyglucose (FDG)-positron emission tomography with computed tomography (PET/CT) studies are performed on cancer patients. These patients are at increased risk of pulmonary embolism (PE). In this retrospective review, we determined the rate of PE, and the prevalence of associated FDG-PET findings on intravenous (IV) contrast-enhanced PET/CT.
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P2X7 receptor inhibition interrupts the progression of seizures in immature rats and reduces hippocampal damage.
CNS Neurosci Ther
PUBLISHED: 02-12-2014
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Early-life seizures, particularly when prolonged, may be harmful to the brain. Current pharmacotherapy is often ineffective; therefore, novel neuro- and/or glio-transmitter systems should be explored for targeting. The P2X7 receptor is a cation-permeable channel with trophic and excitability effects on neurons and glia which is activated by high amounts of ATP that may be released in the setting of injury after severe seizures. Here, we tested the effects of A-438079, a potent and selective P2X7 receptor antagonist in a lesional model of early-life status epilepticus.
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Tau triggers tear secretion by interacting with muscarinic acetylcholine receptors in New Zealand white rabbits.
J. Alzheimers Dis.
PUBLISHED: 02-08-2014
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In recent years, in vitro experiments have shown that the spread of Alzheimer's disease is caused by a non-conventional activation of muscarinic receptors by dephosphorylated extracellular tau protein. However, so far, in vivo data to support this hypothesis has not been obtained. The eye provides a good model where cholinergic (muscarinic) transmission can be analyzed. The role of muscarinic receptors in the stimulation of lacrimal gland secretion has already been described, and it has been suggested that acetylcholine is the main transmitter controlling tear secretion. In this project, we have studied the interaction between tau and muscarinic receptors by analyzing tear secretion in the eyes of white rabbits. Our results show that tau protein increases tear secretion by 47.2% in a similar way to a muscarinic receptor agonist carbachol (84.3%). The use of muscarinic antagonists indicated that tau interacts with M1 and mainly M3 muscarinic receptors. In summary, tau can bind muscarinic receptors in vivo and this may explain the spread of the pathology.
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Determination of technological maturity of grapes and total phenolic compounds of grape skins in red and white cultivars during ripening by near infrared hyperspectral image: a preliminary approach.
Food Chem
PUBLISHED: 01-22-2014
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Hyperspectral images of intact grapes during ripening were recorded using a near infrared hyperspectral imaging system (900-1700 nm). Spectral data have been correlated with grape skin total phenolic concentration, sugar concentration, titratable acidity and pH by modified partial least squares regression (MPLS) using a number of spectral pre-treatments and different sets of calibration. The obtained results (RSQ and SEP, respectively) for the global model of red and white grape samples were: 0.89 and 1.23 mg g(-1) of grape skin for total phenolic concentration, 0.99 and 1.37 °Brix for sugar concentration, 0.98 and 3.88 g L(-1) for titratable acidity and for pH 0.94 and 0.12. Moreover, separate calibration models for red and white grape samples were also developed. The obtained results present a good potential for a fast and reasonably inexpensive screening of these parameters in intact grapes and therefore, for a fast control of technological and phenolic maturity.
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A novel method for evaluating flavanols in grape seeds by near infrared hyperspectral imaging.
Talanta
PUBLISHED: 01-15-2014
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Chemical composition of seeds changes during grape ripening and this affects the sensory properties of wine. In order to control the features of wines, the condition of seeds is becoming an important factor for deciding the moment of harvesting by winemakers. Sensory analysis is not easy to carry out and chemical analysis needs lengthy procedures, reagents, and it is destructive and time-consuming. In the present work, near infrared hyperspectral imaging has been used to determine flavanols in seeds of red (cv. Tempranillo) and white (cv. Zalema) grapes (Vitis vinifera L.). As reference measurements, the flavanol content was estimated using the p-dimethylaminocinnamaldehyde (DMACA) method. Not only total flavanol content was evaluated but also the quantity of flavanols that would be extracted into the wine during winemaking. A like-wine model solution was used for this purpose. Calibrations were performed by partial least squares regression and they provide coefficients of determination R(2)=0.73 for total flavanol content and R(2)=0.85 for predicting flavanols extracted with model solution. Values up to R(2)=0.88 were reached when cultivars were considered individually.
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Nature of Si-H interactions in a series of ruthenium silazane complexes using multinuclear solid-state NMR and neutron diffraction.
Inorg Chem
PUBLISHED: 01-06-2014
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Three new N-heterocyclic-silazane compounds, 1a-c, were prepared and employed as bidentate ligands to ruthenium, resulting in a series of [Ru(H){(?-Si,N-(SiMe2-N-heterocycle)}3] complexes (3a-c) featuring the same RuSi3H motif. Detailed structural characterization of the RuSi3H complexes with X-ray diffraction, and in the case of triazabicyclo complex [Ru(H){?-Si,N-(SiMe2)(C7H12N3)}3] (3a), neutron diffraction, enabled a reliable description of the molecular geometry. The hydride ligand of (3a) is located closer to two of the silicon atoms than it is to the third. Such a geometry differs from that of the previously reported complex [Ru(H){(?-Si,N-(SiMe2)N(SiMe2H)(C5H4N)}3] (3d), also characterized by neutron diffraction, where the hydride was found to be equidistant from all three silicon atoms. A DFT study revealed that the symmetric and less regular isomers are essentially degenerate. Information on the dynamics and on the Ru···H···Si interactions was gained from multinuclear solid-state ((1)H wPMLG, (29)Si CP MAS, and 2D (1)H-(29)Si dipolar HETCOR experiments) and solution NMR studies. The corresponding intermediate complexes, [Ru{?-Si,N-(SiMe2-N-heterocycle)}(?(4)-C8H12)(?(3)-C8H11)] (2a-c), involving a single silazane ligand were isolated and characterized by multinuclear NMR and X-ray diffraction. Protonation of the RuSi3H complexes was also studied. Reaction of 3a with NH4PF6 gave rise to [Ru(H)(?(2)-H -SiMe2)?-N-(C7H12N3){?-Si,N-(SiMe2)(C7H12N3)}2](+)[PF6](-)(4aPF6) which was isolated and characterized by NMR spectroscopy, X-ray crystallography, and DFT studies. The nature of the Si-H interactions in this silazane series was analyzed in detail.
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Toward a systems-level understanding of gene regulatory, protein interaction, and metabolic networks in cyanobacteria.
Front Genet
PUBLISHED: 01-01-2014
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Cyanobacteria are essential primary producers in marine ecosystems, playing an important role in both carbon and nitrogen cycles. In the last decade, various genome sequencing and metagenomic projects have generated large amounts of genetic data for cyanobacteria. This wealth of data provides researchers with a new basis for the study of molecular adaptation, ecology and evolution of cyanobacteria, as well as for developing biotechnological applications. It also facilitates the use of multiplex techniques, i.e., expression profiling by high-throughput technologies such as microarrays, RNA-seq, and proteomics. However, exploration and analysis of these data is challenging, and often requires advanced computational methods. Also, they need to be integrated into our existing framework of knowledge to use them to draw reliable biological conclusions. Here, systems biology provides important tools. Especially, the construction and analysis of molecular networks has emerged as a powerful systems-level framework, with which to integrate such data, and to better understand biological relevant processes in these organisms. In this review, we provide an overview of the advances and experimental approaches undertaken using multiplex data from genomic, transcriptomic, proteomic, and metabolomic studies in cyanobacteria. Furthermore, we summarize currently available web-based tools dedicated to cyanobacteria, i.e., CyanoBase, CyanoEXpress, ProPortal, Cyanorak, CyanoBIKE, and CINPER. Finally, we present a case study for the freshwater model cyanobacteria, Synechocystis sp. PCC6803, to show the power of meta-analysis, and the potential to extrapolate acquired knowledge to the ecologically important marine cyanobacteria genus, Prochlorococcus.
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Drug assessment by a Pharmacy and Therapeutics committee: from drug selection criteria to use in clinical practice.
Ther Clin Risk Manag
PUBLISHED: 01-01-2014
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In Spain, hospital medicines are assessed and selected by local Pharmacy and Therapeutics committees (PTCs). Of all the drugs assessed, cancer drugs are particularly important because of their budgetary impact and the sometimes arguable added value with respect to existing alternatives. This study analyzed the PTC drug selection process and the main objective was to evaluate the degree of compliance of prescriptions for oncology drugs with their criteria for use.
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Synthesis of phenylazonaphtol-?-D-O-glycosides, evaluation as substrates for beta-glycosidase activity and molecular studies.
Org Med Chem Lett
PUBLISHED: 01-01-2014
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Phenylazonaphtol-?-D-O-glycosides are alternative substrates for the detection of enzymatic activity of ?-glycosidases which are involved in various important processes. These azoic compounds are currently exploited as prodrugs for colonic disease due the presence of ?-glycosidase activity in the gut flora and therefore allowing the release of the drug at the specific site.
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Symptomatic peripheral mycotic aneurysms due to infective endocarditis: a contemporary profile.
Medicine (Baltimore)
PUBLISHED: 01-01-2014
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Peripheral mycotic aneurysms (PMAs) are a relatively rare but serious complication of infective endocarditis (IE). We conducted the current study to describe and compare the current epidemiologic, microbiologic, clinical, diagnostic, therapeutic, and prognostic characteristics of patients with symptomatic PMAs (SPMAs). A descriptive, comparative, retrospective observational study was performed in 3 tertiary hospitals, which are reference centers for cardiac surgery. From 922 definite IE episodes collected from 1996 to 2011, 18 patients (1.9%) had SPMAs. Because all SPMAs developed in left-sided IE, we performed a comparative study between 719 episodes of left-sided IE without SPMAs and 18 episodes with SPMAs. We found a higher frequency of intravenous drug abuse, native valve IE, intracranial bleeding, septic emboli, multiple embolisms, and IE diagnostic delay >30 days in patients with SPMAs than in patients without SPMAs. The causal microorganisms were gram-positive cocci (n =10), gram-negative bacilli (n = 2), gram-positive bacilli (n = 3), Bartonella henselae (n = 1), Candida albicans (n = 1), and negative culture (n = 1). The median IE diagnosis delay was 15 days (interquartile range [IQR], 13-33 d) in the case of high-virulence microorganisms versus 45 days (IQR, 30-240 d) in the case of low- to medium-virulence microorganisms. Twelve SPMAs were intracranial and 6 were extracranial. In 10 cases (8 intracranial and 2 extracranial), SPMAs were the initial presentation of IE; the remaining cases developed symptoms during or after finishing parenteral antibiotic treatment. The initial diagnosis of intracranial SPMAs was made by computed tomography (CT) or magnetic resonance imaging in 6 unruptured aneurysms and by angiography in 6 ruptured aneurysms. The initial test in extracranial SPMAs was Doppler ultrasonography in limbs, CT in liver, and coronary angiography in heart. Four (3 intracranial, 1 extracranial) of 7 (6 intracranial, 1 extracranial) patients treated only with antibiotics died. Surgical resection was performed in 7 (3 intracranial, 4 extracranial) and endovascular repair in 4 (3 intracranial, 1 extracranial) patients; all of them survived. In conclusion, we found that SPMAs were a rare complication of IE that developed only in left-sided IE, and especially in native valves. Intracranial hemorrhage, embolism, multiple embolisms, and diagnostic delay of IE were more common in patients with SPMAs. The microbiologic profile was diverse, but microorganisms of low-medium virulence were predominant, and had a greater delayed diagnosis of IE than those caused by microorganisms of high virulence. SPMAs were often the initial presentation of IE. The most common location of SPMAs was intracranial. Noninvasive radiologic imaging techniques were the initial imaging test in intracranial unruptured SPMAs and in most extracranial SPMAs. Surgical and endovascular treatments were safe and effective. Endovascular treatment could be the first line of treatment in selected cases. Mortality was high in those cases treated only with antibiotics.
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UniHI 7: an enhanced database for retrieval and interactive analysis of human molecular interaction networks.
Nucleic Acids Res.
PUBLISHED: 11-08-2013
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Unified Human Interactome (UniHI) (http://www.unihi.org) is a database for retrieval, analysis and visualization of human molecular interaction networks. Its primary aim is to provide a comprehensive and easy-to-use platform for network-based investigations to a wide community of researchers in biology and medicine. Here, we describe a major update (version 7) of the database previously featured in NAR Database Issue. UniHI 7 currently includes almost 350 000 molecular interactions between genes, proteins and drugs, as well as numerous other types of data such as gene expression and functional annotation. Multiple options for interactive filtering and highlighting of proteins can be employed to obtain more reliable and specific network structures. Expression and other genomic data can be uploaded by the user to examine local network structures. Additional built-in tools enable ready identification of known drug targets, as well as of biological processes, phenotypes and pathways enriched with network proteins. A distinctive feature of UniHI 7 is its user-friendly interface designed to be utilized in an intuitive manner, enabling researchers less acquainted with network analysis to perform state-of-the-art network-based investigations.
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Usefulness of bilateral bispectral index (BIS) monitoring in a comatose patient with myoclonic status epilepticus secondary to cefepime.
Epileptic Disord
PUBLISHED: 10-31-2013
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Background. Status epilepticus, particularly non-convulsive status epilepticus (NCSE), is a frequent complication in patients with altered renal function receiving treatment with intravenous cefepime. To the best of our knowledge, we report the first case, illustrated by video-EEG, of a critically ill patient receiving treatment with cefepime who developed an episode of confirmed symptomatic myoclonic status epilepticus (MSE). Methods. Case report and video-EEG. Results. A 60-year-old man, who had received a liver transplant due to alcoholic cirrhosis one year ago, was admitted to our intensive care unit due to septic shock. Computed tomography revealed a prostatic abscess as cause of his sepsis. On Day 27, a respiratory infection due to Pseudomona aeruginosa was diagnosed, and treatment with intravenous cefepime (2 g/8 hours) was initiated. On Day 32, his mental status deteriorated and he developed inattention, a reduced level of consciousness, and multifocal and generalised continuous myoclonic jerks. A video-EEG study was compatible with the diagnosis of symptomatic MSE. On Day 35, cefepime was stopped and general anaesthesia with midazolam was started in order to achieve a faster clinical improvement. We used the BIS-Vista™ monitor to guide general anaesthesia and detect potential episodes of NCSE. On Day 40, an EEG confirmed the existence of moderate diffuse encephalopathy. Finally, the patient died as a consequence of severe heart failure. Conclusions. Cefepime may be a cause of MSE in non-anoxic comatose patients. Clinicians should be aware of this possibility when evaluating comatose patients on cephalosporin therapy in order to establish a correct diagnostic approach and accurate prognosis. [Published with video sequences].
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Comparison of horse and rabbit anti-thymocyte globulin in immunosuppressive therapy for refractory cytopenia of childhood.
Haematologica
PUBLISHED: 10-25-2013
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Refractory cytopenia of childhood is the most common subtype of myelodysplastic syndrome in children. In this paper, we compared the outcome of immunosuppressive therapy using horse anti-thymocyte globulin (n = 46) with that using rabbit anti-thymocyte globulin (n = 49) in 95 patients with refractory cytopenia of childhood and hypocellular bone marrow. The response rate at 6 months was 74% for horse anti-thymocyte globulin and 53% for rabbit anti-thymocyte globulin (p = 0.04). The inferior response in the rabbit anti-thymocyte globulin group resulted in lower 4-year-transplantation-free (69% vs. 46%; p = 0.003) and failure-free (58% vs. 48%; p = 0.04) survival in this group compared with those in the horse anti-thymocyte globulin group. However, because of successful second-line hematopoietic stem cell transplantation, overall survival was comparable between groups (91% vs. 85%, p = ns). The cumulative incidence of relapse (15% vs. 9%, p = ns) and clonal evolution (12% vs. 4%, p = ns) at 4 years was comparable between groups. Our results suggest that the outcome of immunosuppressive therapy with rabbit anti-thymocyte globulin is inferior to that of horse anti-thymocyte globulin. Although immunosuppressive therapy is an effective therapy in selected patients with refractory cytopenia of childhood, the long-term risk of relapse or clonal evolution remains. (ClinicalTrial.gov identifiers: NCT00662090).
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Autologous stem cell transplantation after conditioning with Yttrium-90 ibritumomab tiuxetan plus beam in refractory non-Hodgkin diffuse large B-cell lymphoma: results of a prospective, multicenter, phase II clinical trial.
Haematologica
PUBLISHED: 10-25-2013
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In the rituximab era, lymphoma patients with persistent disease receiving autologous transplantation have a very poor outcome. The addition of radioimmunotherapy to the conditioning regimen may improve outcome for these patients. We have evaluated, in a prospective phase 2 study, the safety and efficacy of the addition of 90Y-Ibritumomab tiuxetan to the conditioning chemotherapy in refractory diffuse large B cell lymphoma patients. Thirty patients with induction failure (primary refractory; n=18) or refractory to salvage immunochemotherapy at relapse (n=12) were included in the study. Patients with a median age of 53 years (range, 25-67) received 90Y-Ibritumomab tiuxetan at a fixed dose of 0.4mCi/kg (maximum dose 32mCi) 14 days prior to the preparative chemotherapy regimen. Histology included de novo diffuse large B cell lymphoma (22) and transformed diffuse large B cell lymphoma (8). All patients had persistent disease at the time of transplantation, with 25 patients considered to be chemorefractory. Median time to neutrophil recovery (>500/ml) was 11 days (9-21), and to platelet recovery (>20.000/ml) was 13 days (11-35). Overall response at day +100 was 70% (95% CI, 53.6-86.4) with 60% (95% CI, 42.5-77.5) complete responses. After a median follow-up of 31 months for alive patients (range, 16-54), estimated 3-year overall and progression-free survival is 63% (95% CI, 48-82) and 61% (95% CI, 45-80), respectively. We conclude that autologous transplantation with conditioning including 90Y-Ibritumomab tiuxetan is safe, and results in a very high response rate with promising survival in this very poor prognosis group of refractory diffuse large B cell lymphoma patients. Study registered at European Union Drug Regulating Authorities Clinical Trials (EudraCT) No. 2007-003198-22.
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Impact of implementing smart infusion pumps in a pediatric intensive care unit.
Am J Health Syst Pharm
PUBLISHED: 10-17-2013
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The impact of smart infusion pumps on the interception of errors in the programming of i.v. drug administrations on a pediatric intensive care unit (PICU) is investigated.
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Feasibility study on the use of near-infrared hyperspectral imaging for the screening of anthocyanins in intact grapes during ripening.
J. Agric. Food Chem.
PUBLISHED: 10-03-2013
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The potential of near-infrared hyperspectral imaging to determine anthocyanins in intact grape has been evaluated. The hyperspectral images of intact grapes during ripening were recorded using a near-infrared hyperspectral imaging covering the spectral range between 900 and 1700 nm. Reference values of anthocyanins were obtained by HPLC-DAD. A number of spectral pretreatments and different mask development strategies were studied. Calibrations were performed by modified partial least-squares regression (MPLS) and present a good potential (RSQ of 0.86 and SEP values of 2.62 and 3.05 mg g(-1) of grape skin for nonacylated and total anthocyanins, respectively) for a fast and reasonably inexpensive screening of these compounds in intact grapes.
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Review of the novelties presented at the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (III).
Rev Neurol
PUBLISHED: 09-21-2013
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The most significant data presented at the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in France in October 2012, have been summarised in the fifth edition of the Post-ECTRIMS Experts Meeting, held in Madrid in October 2012. This led to the drafting of this review, which has been published in three parts. This third part of the Post-ECTRIMS review presents the findings from the latest studies conducted with disease-modifying treatments, more specifically with glatiramer acetate, laquinimod, ponesimod, BG-12, teriflunomide, daclizumab, natalizumab and secukinumab (AIN457). Likewise, we also address the reasons that justify the search for innovative treatments for multiple sclerosis, with antigen-specific therapy, cell therapy and therapy aimed at promoting remyelination being highlighted among other future therapeutic strategies. Access to new pharmacological agents and the complexity of the therapy of multiple sclerosis in the future will require new design strategies and directions in clinical trials, including the use of surrogate markers, new statistical applications, superiority, inferiority or equivalence clinical trials and adaptable designs.
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[Effect of administration of recombinant LH on the 5th day versus the 8th day in ovarian stimulation cycles].
Ginecol Obstet Mex
PUBLISHED: 09-21-2013
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Ovarian stimulation is a key component in assisted reproduction techniques. Supraphysiologic levels secondary to hormonal stimulation with high doses of exogenous hormones affect endometrial receptivity, the function of the corpus luteum, ovulation and embryo quality. The use of stimulation protocols called "minimal stimulation" may have a beneficial effect in achieving pregnancy.
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Renal autotransplant for subsequent endovascular exclusion of the thoracoabdominal aorta.
Ann Vasc Surg
PUBLISHED: 09-03-2013
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In the last 20 years, endovascular procedures have radically altered the treatment of diseases of the aorta. The objective of endovascular treatment of dissections is to close the entry point to redirect blood flow toward the true lumen, thereby achieving thrombosis of the false lumen. In extensive chronic dissections that have evolved with the formation of a large aneurysm, the dissection is maintained from the end of the endoprosthesis due to multiple orifices, or reentries, that communicate with the lumens. In addition, one of the primary limitations of this technique is when the visceral arteries have disease involvement. In this report we present a case where, despite having treated the entire length of the descending thoracic aorta, the dissection was maintained distally, leading to progression of the diameter of the aneurysm. After reviewing the literature, and to the best of our knowledge, we describe the first case in which renal autotransplant was performed to allow for subsequent exclusion of the aorta at the thoracoabdominal level using a fenestrated endoprosthesis for the celiac trunk and the superior mesenteric artery.
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Review of the novelties presented at the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (I).
Rev Neurol
PUBLISHED: 08-27-2013
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The most relevant data presented at the 28th edition of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in October 2012 in France, have been summarized in the fifth edition of the Post-ECTRIMS Expert Meeting held in Madrid in October 2012. The present review summarizes the views and results of the meeting and is being published in three parts. This first part of the Post-ECTRIMS review addresses the incidence and prevalence of multiple sclerosis (MS), which has increased at the global level, largely due to the increased incidence in women because the risk of developing the disease is increased in females, with minimal concurrent effect on the progression of MS. Sexual dimorphism is evident in MS, and all evidence points to an interaction between hormonal, genetic, and environmental factors. The paediatric population represents an ideal group to study susceptibility factors to the disease, which is why collaborative studies designed to increase the patient samples are being considered, given its low prevalence. In this review, inflammatory and neurodegenerative phenomena involved in the pathogenesis of the disease and that have a cause-and-effect or shared relationship with the disease are being discussed. Current hypotheses suggest a phenomenon of compartmentalization, presumably inaccessible to current immunomodulatory therapy. Among the possible mechanisms involved in these processes of inflammation and demyelination, the role of Th17 cells, mitochondrial dysfunction, early disruption of astrocytic processes, and chronic hypoxia are discussed.
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Phosphinodi(benzylsilane) PhP{(o-C6H4CH2)SiMe2H}2: a versatile "PSi2Hx" pincer-type ligand at ruthenium.
Inorg Chem
PUBLISHED: 08-13-2013
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The synthesis of the new phosphinodi(benzylsilane) compound PhP{(o-C6H4CH2)SiMe2H}2 (1) is achieved in a one-pot reaction from the corresponding phenylbis(o-tolylphosphine). Compound 1 acts as a pincer-type ligand capable of adopting different coordination modes at Ru through different extents of Si-H bond activation as demonstrated by a combination of X-ray diffraction analysis, density functional theory calculations, and multinuclear NMR spectroscopy. Reaction of 1 with RuH2(H2)2(PCy3)2 (2) yields quantitatively [RuH2{[?(2)-(HSiMe2)-CH2-o-C6H4]2PPh}(PCy3)] (3), a complex stabilized by two rare high order ?-agostic Si-H bonds and involved in terminal hydride/?(2)-Si-H exchange processes. A small free energy of reaction (?rG298 = +16.9 kJ mol(-1)) was computed for dihydrogen loss from 3 with concomitant formation of the 16-electron species [RuH{[?(2)-(HSiMe2)-CH2-o-C6H4]PPh[CH2-o-C6H4SiMe2]}(PCy3)] (4). Complex 4 features an unprecedented (29)Si NMR decoalescence process. The dehydrogenation process is fully reversible under standard conditions (1 bar, 298 K).
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The antidepressant-like effects of topiramate alone or combined with 17?-estradiol in ovariectomized Wistar rats submitted to the forced swimming test.
Psychopharmacology (Berl.)
PUBLISHED: 08-09-2013
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There is a significant delay in the clinical response of antidepressant drugs, and antidepressant treatments produce side effects.
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Lenalidomide plus dexamethasone for high-risk smoldering multiple myeloma.
N. Engl. J. Med.
PUBLISHED: 08-02-2013
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For patients with smoldering multiple myeloma, the standard of care is observation until symptoms develop. However, this approach does not identify high-risk patients who may benefit from early intervention.
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Isotope ratios of H, C, and O in CO2 and H2O of the martian atmosphere.
Chris R Webster, Paul R Mahaffy, Gregory J Flesch, Paul B Niles, John H Jones, Laurie A Leshin, Sushil K Atreya, Jennifer C Stern, Lance E Christensen, Tobias Owen, Heather Franz, Robert O Pepin, Andrew Steele, , Cherie Achilles, Christophe Agard, José Alexandre Alves Verdasca, Robert Anderson, Ryan Anderson, Doug Archer, Carlos Armiens-Aparicio, Ray Arvidson, Evgeny Atlaskin, Andrew Aubrey, Burt Baker, Michael Baker, Tonci Balic-Zunic, David Baratoux, Julien Baroukh, Bruce Barraclough, Keri Bean, Luther Beegle, Alberto Behar, James Bell, Steve Bender, Mehdi Benna, Jennifer Bentz, Gilles Berger, Jeff Berger, Daniel Berman, David Bish, David F Blake, Juan J Blanco Avalos, Diana Blaney, Jen Blank, Hannah Blau, Lora Bleacher, Eckart Boehm, Oliver Botta, Stephan Böttcher, Thomas Boucher, Hannah Bower, Nick Boyd, Bill Boynton, Elly Breves, John Bridges, Nathan Bridges, William Brinckerhoff, David Brinza, Thomas Bristow, Claude Brunet, Anna Brunner, Will Brunner, Arnaud Buch, Mark Bullock, Sönke Burmeister, Michel Cabane, Fred Calef, James Cameron, John Campbell, Bruce Cantor, Michael Caplinger, Javier Caride Rodríguez, Marco Carmosino, Isaías Carrasco Blázquez, Antoine Charpentier, Steve Chipera, David Choi, Benton Clark, Sam Clegg, Timothy Cleghorn, Ed Cloutis, George Cody, Patrice Coll, Pamela Conrad, David Coscia, Agnès Cousin, David Cremers, Joy Crisp, Alain Cros, Frank Cucinotta, Claude d'Uston, Scott Davis, Mackenzie Day, Manuel de la Torre Juarez, Lauren DeFlores, Dorothea DeLapp, Julia DeMarines, David DesMarais, William Dietrich, Robert Dingler, Christophe Donny, Bob Downs, Darrell Drake, Gilles Dromart, Audrey Dupont, Brian Duston, Jason Dworkin, M Darby Dyar, Lauren Edgar, Kenneth Edgett, Christopher Edwards, Laurence Edwards, Bethany Ehlmann, Bent Ehresmann, Jen Eigenbrode, Beverley Elliott, Harvey Elliott, Ryan Ewing, Cécile Fabre, Alberto Fairén, Ken Farley, Jack Farmer, Caleb Fassett, Laurent Favot, Donald Fay, Fedor Fedosov, Jason Feldman, Sabrina Feldman, Marty Fisk, Mike Fitzgibbon, Melissa Floyd, Lorenzo Flückiger, Olivier Forni, Abby Fraeman, Raymond Francis, Pascaline François, Caroline Freissinet, Katherine Louise French, Jens Frydenvang, Alain Gaboriaud, Marc Gailhanou, James Garvin, Olivier Gasnault, Claude Geffroy, Ralf Gellert, Maria Genzer, Daniel Glavin, Austin Godber, Fred Goesmann, Walter Goetz, Dmitry Golovin, Felipe Gómez Gómez, Javier Gómez-Elvira, Brigitte Gondet, Suzanne Gordon, Stephen Gorevan, John Grant, Jennifer Griffes, David Grinspoon, John Grotzinger, Philippe Guillemot, Jingnan Guo, Sanjeev Gupta, Scott Guzewich, Robert Haberle, Douglas Halleaux, Bernard Hallet, Vicky Hamilton, Craig Hardgrove, David Harker, Daniel Harpold, Ari-Matti Harri, Karl Harshman, Donald Hassler, Harri Haukka, Alex Hayes, Ken Herkenhoff, Paul Herrera, Sebastian Hettrich, Ezat Heydari, Victoria Hipkin, Tori Hoehler, Jeff Hollingsworth, Judy Hudgins, Wesley Huntress, Joel Hurowitz, Stubbe Hviid, Karl Iagnemma, Steve Indyk, Guy Israël, Ryan Jackson, Samantha Jacob, Bruce Jakosky, Elsa Jensen, Jaqueline Kløvgaard Jensen, Jeffrey Johnson, Micah Johnson, Steve Johnstone, Andrea Jones, Jonathan Joseph, Insoo Jun, Linda Kah, Henrik Kahanpää, Melinda Kahre, Natalya Karpushkina, Wayne Kasprzak, Janne Kauhanen, Leslie Keely, Osku Kemppinen, Didier Keymeulen, Myung-Hee Kim, Kjartan Kinch, Penny King, Laurel Kirkland, Gary Kocurek, Asmus Koefoed, Jan Köhler, Onno Kortmann, Alexander Kozyrev, Jill Krezoski, Daniel Krysak, Ruslan Kuzmin, Jean Luc Lacour, Vivian Lafaille, Yves Langevin, Nina Lanza, Jeremie Lasue, Stéphane Le Mouélic, Ella Mae Lee, Qiu-Mei Lee, David Lees, Matthew Lefavor, Mark Lemmon, Alain Lepinette Malvitte, Richard Léveillé, Éric Lewin-Carpintier, Kevin Lewis, Shuai Li, Leslie Lipkaman, Cynthia Little, Maxim Litvak, Eric Lorigny, Guenter Lugmair, Angela Lundberg, Eric Lyness, Morten Madsen, Justin Maki, Alexey Malakhov, Charles Malespin, Michael Malin, Nicolas Mangold, Gérard Manhes, Heidi Manning, Geneviève Marchand, Mercedes Marín Jiménez, César Martín García, Dave Martin, Mildred Martin, Jesus Martinez-Frias, Javier Martín-Soler, F Javier Martín-Torres, Patrick Mauchien, Sylvestre Maurice, Amy McAdam, Elaina McCartney, Timothy McConnochie, Emily McCullough, Ian McEwan, Christopher McKay, Scott McLennan, Sean McNair, Noureddine Melikechi, Pierre-Yves Meslin, Michael Meyer, Alissa Mezzacappa, Hayden Miller, Kristen Miller, Ralph Milliken, Douglas Ming, Michelle Minitti, Michael Mischna, Igor Mitrofanov, Jeff Moersch, Maxim Mokrousov, Antonio Molina Jurado, John Moores, Luis Mora-Sotomayor, John Michael Morookian, Richard Morris, Shaunna Morrison, Reinhold Mueller-Mellin, Jan-Peter Muller, Guillermo Muñoz Caro, Marion Nachon, Sara Navarro López, Rafael Navarro-González, Kenneth Nealson, Ara Nefian, Tony Nelson, Megan Newcombe, Claire Newman, Horton Newsom, Sergey Nikiforov, Brian Nixon, Eldar Noe Dobrea, Thomas Nolan, Dorothy Oehler, Ann Ollila, Timothy Olson, Miguel Ángel de Pablo Hernández, Alexis Paillet, Etienne Pallier, Marisa Palucis, Timothy Parker, Yann Parot, Kiran Patel, Mark Paton, Gale Paulsen, Alex Pavlov, Betina Pavri, Verónica Peinado-González, Laurent Peret, Rene Perez, Glynis Perrett, Joe Peterson, Cedric Pilorget, Patrick Pinet, Jorge Pla-García, Ianik Plante, Franck Poitrasson, Jouni Polkko, Radu Popa, Liliya Posiolova, Arik Posner, Irina Pradler, Benito Prats, Vasily Prokhorov, Sharon Wilson Purdy, Eric Raaen, Leon Radziemski, Scot Rafkin, Miguel Ramos, Elizabeth Rampe, François Raulin, Michael Ravine, Günther Reitz, Nilton Rennó, Melissa Rice, Mark Richardson, François Robert, Kevin Robertson, José Antonio Rodriguez Manfredi, Julio J Romeral-Planelló, Scott Rowland, David Rubin, Muriel Saccoccio, Andrew Salamon, Jennifer Sandoval, Anton Sanin, Sara Alejandra Sans Fuentes, Lee Saper, Philippe Sarrazin, Violaine Sautter, Hannu Savijärvi, Juergen Schieber, Mariek Schmidt, Walter Schmidt, Daniel Scholes, Marcel Schoppers, Susanne Schröder, Susanne Schwenzer, Eduardo Sebastian Martinez, Aaron Sengstacken, Ruslan Shterts, Kirsten Siebach, Tero Siili, Jeff Simmonds, Jean-Baptiste Sirven, Susie Slavney, Ronald Sletten, Michael Smith, Pablo Sobrón Sánchez, Nicole Spanovich, John Spray, Steven Squyres, Katie Stack, Fabien Stalport, Thomas Stein, Noel Stewart, Susan Louise Svane Stipp, Kevin Stoiber, Ed Stolper, Bob Sucharski, Rob Sullivan, Roger Summons, Dawn Sumner, Vivian Sun, Kimberley Supulver, Brad Sutter, Cyril Szopa, Florence Tan, Christopher Tate, Samuel Teinturier, Inge ten Kate, Peter Thomas, Lucy Thompson, Robert Tokar, Mike Toplis, Josefina Torres Redondo, Melissa Trainer, Allan Treiman, Vladislav Tretyakov, Roser Urqui-O'Callaghan, Jason Van Beek, Tessa Van Beek, Scott VanBommel, David Vaniman, Alexey Varenikov, Ashwin Vasavada, Paulo Vasconcelos, Edward Vicenzi, Andrey Vostrukhin, Mary Voytek, Meenakshi Wadhwa, Jennifer Ward, Eddie Weigle, Danika Wellington, Frances Westall, Roger Craig Wiens, Mary Beth Wilhelm, Amy Williams, Joshua Williams, Rebecca Williams, Richard B Williams, Mike Wilson, Robert Wimmer-Schweingruber, Mike Wolff, Mike Wong, James Wray, Megan Wu, Charles Yana, Albert Yen, Aileen Yingst, Cary Zeitlin, Robert Zimdar, María-Paz Zorzano Mier.
Science
PUBLISHED: 07-23-2013
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Stable isotope ratios of H, C, and O are powerful indicators of a wide variety of planetary geophysical processes, and for Mars they reveal the record of loss of its atmosphere and subsequent interactions with its surface such as carbonate formation. We report in situ measurements of the isotopic ratios of D/H and (18)O/(16)O in water and (13)C/(12)C, (18)O/(16)O, (17)O/(16)O, and (13)C(18)O/(12)C(16)O in carbon dioxide, made in the martian atmosphere at Gale Crater from the Curiosity rover using the Sample Analysis at Mars (SAM)s tunable laser spectrometer (TLS). Comparison between our measurements in the modern atmosphere and those of martian meteorites such as ALH 84001 implies that the martian reservoirs of CO2 and H2O were largely established ~4 billion years ago, but that atmospheric loss or surface interaction may be still ongoing.
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Update of the Mexican College of Rheumatology Guidelines for the Pharmacologic Treatment of Rheumatoid Arthritis.
Reumatol Clin
PUBLISHED: 07-16-2013
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The pharmacologic management of rheumatoid arthritis has progressed substantially over the past years. It is therefore desirable that existing information be periodically updated. There are several published international guidelines for the treatment of rheumatoid arthritis that hardly adapt to the Mexican health system because of its limited healthcare resources. Hence, it is imperative to unify the existing recommendations and to incorporate them to a set of clinical, updated recommendations; the Mexican College of Rheumatology developed these recommendations in order to offer an integral management approach of rheumatoid arthritis according to the resources of the Mexican health system.
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[Genetic variants associated to male infertility in Mexican patients].
Ginecol Obstet Mex
PUBLISHED: 07-04-2013
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Recently Mexican Federation of Obstetrics and Gynecology Colleges (Federación Mexicana de Colegios de Obstetricia y Ginecologia, FEMECOG) published the Mexican guideline forthe management of male infertility, which suggests performing genetic laboratory tests as part of diagnosis and management of infertile patients and states that these should receive genetic counseling. This paper reviews the genetic approach proposed by Mexican guideline. A systematic review of medical literature was performed in Pubmed and Web of Knowledge from 1980 to 2012 in order to find reports of genetic variants associated to male infertility in Mexican patients. Also it is discussed the current knowledge of these variants, their clinical implications and finally the guidelines and recommendations for their molecular diagnosis. Most genetic variants in Mexican infertile patients are chromosome abnormalities. In relation to other variants there is only a report of Y chromosome microdeletions, repeated CAG in androgen receptor and more common mutations in CFTR, and other article reporting mutations in CFTR in patients with congenital absence of vas deferens. Little is known about the genetics of Mexican infertile patients apart from chromosome abnormalities. However, the contribution of genetics as etiology of male infertility is taking more relevance and currently the consensual management of infertile male should include the screening of genetic background. This review pretends to be a quick guide for clinicians who want to know about reports of genetic variants related to male infertility in Mexican population and how to approach their diagnosis.
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Do planar tetracoordinate tin complexes really exist?
Dalton Trans
PUBLISHED: 06-29-2013
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New experimental and theoretical data show that the previously reported planar tetracoordinate Sn complexes [Sn(Ph?P(Se)N(Se)PPh?)?] (1-sq) and [Sn(iPr?P(Se)N(Se)PiPr?)?] (2-sq) were not isolated and rather confused with the selenium complexes [Se(Ph?P(Se)N(Se)PPh?)?] (3-sq) and [Se(iPr?P(Se)N(Se)PiPr?)?] (4-sq), respectively.
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18F-fluorodeoxyglucose positron emission tomography-computed tomography imaging in the management of Merkel cell carcinoma: a single-institution retrospective study.
Dermatol Surg
PUBLISHED: 06-18-2013
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Merkel cell carcinoma (MCC) is among the deadliest of cutaneous malignancies. A lack of consensus evaluation and treatment guidelines has hindered management of this disease. The utility of simultaneous positron emission tomography and computed tomography (PET/CT) has been demonstrated for a variety of tumors yet remains underinvestigated for MCC.
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Nicotinamide, a glucose-6-phosphate dehydrogenase non-competitive mixed inhibitor, modifies redox balance and lipid accumulation in 3T3-L1 cells.
Life Sci.
PUBLISHED: 06-11-2013
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Excessive energy uptake of dietary carbohydrates results in their storage as fat and requires glucose-6-phosphate dehydrogenase (G6PD)-mediated NADPH production. We sought to assess whether the nicotinamide-induced reduction of G6PD activity might modulate redox balance and lipid accumulation in 3T3-L1 cells.
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Clinical applicability and prognostic significance of molecular response assessed by fluorescent-PCR of immunoglobulin genes in multiple myeloma. Results from a GEM/PETHEMA study.
Br. J. Haematol.
PUBLISHED: 06-11-2013
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Minimal residual disease monitoring is becoming increasingly important in multiple myeloma (MM), but multiparameter flow cytometry (MFC) and allele-specific oligonucleotide polymerase chain reaction (ASO-PCR) techniques are not routinely available. This study investigated the prognostic influence of achieving molecular response assessed by fluorescent-PCR (F-PCR) in 130 newly diagnosed MM patients from Grupo Español Multidisciplinar de Melanoma (GEM)2000/GEM05 trials (NCT00560053, NCT00443235, NCT00464217) who achieved almost very good partial response after induction therapy. As a reference, we used the results observed with simultaneous MFC. F-PCR at diagnosis was performed on DNA using three different multiplex PCRs: IGH D-J, IGK V-J and KDE rearrangements. The applicability of F-PCR was 91·5%. After induction therapy, 64 patients achieved molecular response and 66 non-molecular response; median progression-free survival (PFS) was 61 versus 36 months, respectively (P = 0·001). Median overall survival (OS) was not reached (NR) in molecular response patients (5-year survival: 75%) versus 66 months in the non-molecular response group (P = 0·03). The corresponding PFS and OS values for patients with immunophenotypic versus non-immunophenotypic response were 67 versus 42 months (P = 0·005) and NR (5-year survival: 95%) versus 69 months (P = 0·004), respectively. F-PCR analysis is a rapid, affordable, and easily performable technique that, in some circumstances, may be a valid approach for minimal residual disease investigations in MM.
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Relationship between skin cell wall composition and anthocyanin extractability of Vitis vinifera L. cv. Tempranillo at different grape ripeness degree.
Food Chem
PUBLISHED: 06-03-2013
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The relationship between cell wall composition and extractability of anthocyanins from red grape skins was assessed in Tempranillo grape samples harvested at three stages of ripening (pre-harvest, harvest and over-ripening) and three different contents of soluble solids (22, 24 and 26 °Brix) within each stage. Cell wall material was isolated and analysed in order to determine cellulose, lignin, non-cellulosic polysaccharides, protein, total polyphenols index and the degree of esterification of pectins. Results showed the influence of ripeness degree and contents of soluble solids on cell wall composition. Furthermore, principal components analysis was applied to the obtained data set in order to establish relationships between cell wall composition and extractability of anthocyanins. Total insoluble material exhibits the biggest opposition to anthocyanin extraction, while the highest amounts of cellulose, rhamnogalacturonans-II and polyphenols were positively correlated with anthocyanin extraction. Moreover, multiple linear regression was performed to assess the influence of the cell wall composition on the extraction of anthocyanin compounds. A model connecting cell wall composition and anthocyanin extractabilities was built, explaining 96.2% of the observed variability.
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Increased neocortical expression of the P2X7 receptor after status epilepticus and anticonvulsant effect of P2X7 receptor antagonist A-438079.
Epilepsia
PUBLISHED: 05-21-2013
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ATP is an essential transmitter/cotransmitter in neuron function and pathophysiology and has recently emerged as a potential contributor to prolonged seizures (status epilepticus) through the activation of the purinergic ionotropic P2X7 receptor (P2X7R). Increased P2X7R expression has been reported in the hippocampus, and P2X7R antagonists reduced seizure-induced damage to this brain region. However, status epilepticus also produces damage to the neocortex. The present study was designed to characterize P2X7R in the neocortex and assess effects of P2X7R antagonists on cortical injury after status epilepticus.
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Co-occurrence of hemiscrotal agenesis with cutis marmorata telangiectatica congenita and hydronephrosis affecting the same side of the body.
Am. J. Med. Genet. A
PUBLISHED: 04-30-2013
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To our knowledge, there are nine previous reports of patients with congenital scrotal agenesis (CSA), seven of which were bilateral, and unilateral in two, also named as hemiscrotal agenesis (HSA). Here, we report a male infant with the previously undescribed co-occurrence of HSA with cutis marmorata telangiectatica congenita (CMTC), and hydronephrosis due to vesicoureteral reflux, all of them on the left side. CMTC is a segmental vascular malformation usually attributed to mosaicism of a postzygotic mutation, whereas the mechanisms in the CSA involve a failure on the labioscrotal fold (LSF) development due to a localized 5?-reductase deficiency and/or androgen insensitivity. Since the skin with HSA was affected also by CMTC and by the fact that it exhibited lack of response to the topical testosterone treatment, all this suggests to us an androgen insensitivity mosaicism in our patient restricted to the left LSF, because skin with intact androgen receptors normally shows some type of response. Since CSA and/or HSA have been also seen in patients with PHACES, popitleal pterygium syndrome, or as part of a recently proposed familial entity with CSA (or agenesis of labia majora as its female counterpart), developmental delay, visual impairment, and moderate hearing loss, further reports could confirm this manifest genetic heterogeneity, highly evocative of somatic mosaicism in our patient. © 2013 Wiley Periodicals, Inc.
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Value of true whole-body FDG-PET/CT scanning protocol in oncology: optimization of its use based on primary diagnosis.
Acta Radiol
PUBLISHED: 04-30-2013
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BackgroundNo standardized field of view (FOV) currently exists for whole-body (WB) positron emission tomography/computed tomography (PET/CT). Limited WB PET/CT FOV can exclude portions of the head, upper, and lower extremities, because there is little perceived clinical benefit to be gained from imaging these areas.PurposeTo determine how often utilizing WB PET/CT changes the clinical stage and management compared to each of the limited WB FOVs used for PET/CT.Material and MethodsWe retrospectively identified 556 oncologic patients (804 PET/CT studies) who underwent staging or restaging PET/CT between November 2010 and November 2011. Abnormal hypermetabolic areas that were suspicious for malignancy in areas that are outside of some of the limited fields of view including in the brain, scalp, and calvarium (above the orbital ridge), in the proximal upper extremity (distal to the humeral neck), distal upper extremity (beyond the elbow), proximal lower extremity (distal to the lesser trochanter), and distal lower extremity (beyond the knees) were recorded.ResultsA total of 8.5% (47/556) of patients had abnormal findings outside the most limited FOV (skull base to upper thighs) used in PET/CT. More patients had abnormal hypermetabolic lesions in the lower extremity (5.9%) than in the upper extremity (2.3%). Similarly, more patients had abnormal lesions in the proximal (6.5%) compared to the distal (1.4%) upper and lower extremities. The stage was only changed in one patient (0.2%), however new lesions noted in the brain changed management in six patients (1.1%). Melanoma, lymphoma, multiple myeloma, sarcomas and stage IV lung, breast, prostate, bladder, testicular, and renal cancer were more likely to have findings outside the most limited FOV (skull base to upper thighs).ConclusionWB FOV detects additional sites of disease compared to the limited WB FOV, and although these lesions rarely change stage, some of these lesions may change clinical management.
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Equity in specialist waiting times by socioeconomic groups: evidence from Spain.
Eur J Health Econ
PUBLISHED: 04-24-2013
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In countries with publicly financed health care systems, waiting time-rather than price-is the rationing mechanism for access to health care services. The normative statement underlying such a rationing device is that patients should wait according to need and irrespective of socioeconomic status or other non-need characteristics. The aim of this paper is to test empirically that waiting times for publicly funded specialist care do not depend on patients socioeconomic status. Waiting times for specialist care can vary according to the type of medical specialty, type of consultation (review or diagnosis) and the region where patients reside. In order to take into account such variability, we use Bayesian random parameter models to explain waiting times for specialist care in terms of need and non-need variables. We find that individuals with lower education and income levels wait significantly more time than their counterparts.
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Prediction of the type of milk and degree of ripening in cheeses by means of artificial neural networks with data concerning fatty acids and near infrared spectroscopy.
Talanta
PUBLISHED: 04-12-2013
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The present study addresses the prediction of the time of ripening and type of mixtures of milk (cows, ewes and goats) in cheeses of varying composition using artificial neural networks (ANN). To accomplish this aim, neural networks were designed using as input data the content of 19 fatty acids obtained with GC-FID of the cheese fat and scores obtained from principal component analysis (PCA) of NIR spectra. The best model of neuronal networks for the identification of the type of mixtures of milk was obtained using the information concerning the fatty acid concentration (80% of correct results in the training phase and 75% in the validation phase). Regarding the information of the near-infrared (NIR) spectra a neural network was designed. The aforesaid neural network predicted the ripening of cheeses with 100% accuracy in both training and in validation.
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Chilean flour and wheat grain: tracing their origin using near infrared spectroscopy and chemometrics.
Food Chem
PUBLISHED: 03-23-2013
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Instrumental techniques such a near-infrared spectroscopy (NIRS) are used in industry to monitor and establish product composition and quality. As occurs with other food industries, the Chilean flour industry needs simple, rapid techniques to objectively assess the origin of different products, which is often related to their quality. In this sense, NIRS has been used in combination with chemometric methods to predict the geographic origin of wheat grain and flour samples produced in different regions of Chile. Here, the spectral data obtained with NIRS were analysed using a supervised pattern recognition method, Discriminat Partial Least Squares (DPLS). The method correctly classified 76% of the wheat grain samples and between 90% and 96% of the flour samples according to their geographic origin. The results show that NIRS, together with chemometric methods, provides a rapid tool for the classification of wheat grain and flour samples according to their geographic origin.
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Heterogeneous 18F-FDG uptake in recurrent respiratory papillomatosis.
Clin Nucl Med
PUBLISHED: 03-15-2013
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Recurrent respiratory papillomatosis (RRP) describes an infection of the upper aerodigestive tract by the human papilloma virus most commonly affecting the larynx with rare lung involvement in 1%-2% of affected patients. We describe an unusual case of a 28-year-old male patient with a longstanding history of RRP where a whole-body PET/CT obtained for disease staging revealed multiple cavitary pulmonary nodules in addition to the more typical tracheobronchial papillomas. In the case described herein, we report heterogeneous uptake of 18F-FDG among these RRP lesions, suggesting significant unexpected variability in the underlying metabolic behavior of these lesions.
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The effects of ozone exposure and associated injury mechanisms on the central nervous system.
Rev Neurosci
PUBLISHED: 02-25-2013
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Ozone (O3) is a component of photochemical smog, which is a major air pollutant and demonstrates properties that are harmful to health because of the toxic properties that are inherent to its powerful oxidizing capabilities. Environmental O3 exposure is associated with many symptoms related to respiratory disorders, which include loss of lung function, exacerbation of asthma, airway damage, and lung inflammation. The effects of O3 are not restricted to the respiratory system or function - adverse effects within the central nervous system (CNS) such as decreased cognitive response, decrease in motor activity, headaches, disturbances in the sleep-wake cycle, neuronal dysfunctions, cell degeneration, and neurochemical alterations have also been described; furthermore, it has also been proposed that O3 could have epigenetic effects. O3 exposure induces the reactive chemical species in the lungs, but the short half-life of these chemical species has led some authors to attribute the injurious mechanisms observed within the lungs to inflammatory processes. However, the damage to the CNS induced by O3 exposure is not well understood. In this review, the basic mechanisms of inflammation and activation of the immune system by O3 exposure are described and the potential mechanisms of damage, which include neuroinflammation and oxidative stress, and the signs and symptoms of disturbances within the CNS caused by environmental O3 exposure are discussed.
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Frequency and clinical implications of incidental new primary cancers detected on true whole-body 18F-FDG PET/CT studies.
Nucl Med Commun
PUBLISHED: 02-15-2013
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To determine the frequency of additional primary malignancies in patients undergoing staging/restaging with PET/computed tomography (CT) and to determine the frequency with which these unsuspected findings change clinical management.
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Disentangling mechanisms involved in the adaptation of photosynthetic microorganisms to the extreme sulphureous water from Los Baños de Vilo (S Spain).
Microb. Ecol.
PUBLISHED: 02-11-2013
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Los Baños de Vilo (S Spain) is a natural spa characterized by extreme sulphureous waters; however, populations of chlorophyceans inhabit in the spa. The adaptation mechanisms allowing resistance by photosynthetic microorganisms to the extreme sulphureous waters were studied by using a modified Luria-Delbrück fluctuation analysis. For this purpose, the adaptation of the chlorophycean Dictyosphaerium chlorelloides and the cyanobacterium Microcystis aeruginosa (both isolated from non-sulphureous water) were analysed in order to distinguish between physiological adaptation (acclimation) and genetic adaptation by the selection of rare spontaneous mutations. Acclimation to the extreme water was achieved by D. chlorelloides; however, M. aeruginosa cells proliferated as a consequence of selection of favoured mutants (i.e. genetic adaptation). The resistant cells of M. aeruginosa appeared with a frequency of 7.1?×?10(-7) per cell per generation, and the frequency of the resistant allele, under non-selective conditions, was estimated to be 1.1?×?10(-6) per cells as a consequence of the balance mutation-selection. It could be hypothesized that the populations of eukaryotic algae living in the Los Baños de Vilo could be the descendants of chlorophyceans that arrived fortuitously at the spa in the past. On the other hand, cyanobacteria could quickly adapt by the selection of favoured mutants. The single mutation that allows resistance to sulphureous water from Baños de Vilo in M. aeruginosa represents a phenotypic burden impairing growth rate and photosynthetic performance. The resistant-variant cells of M. aeruginosa showed a lower acclimated growth rate and a decreased maximum quantum yield and photosynthetic efficiency, in comparison to the wild-type cells.
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FDG PET/CT evaluation of pathologically proven pulmonary lesions in an area of high endemic granulomatous disease.
Ann Nucl Med
PUBLISHED: 01-23-2013
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The goal of this study is to assess how reliable the threshold maximum standardized uptake value (maxSUV) of 2.5 on positron emission tomography-computed tomography (PET/CT) is for evaluation of solitary pulmonary lesions in an area of endemic granulomatous disease and to consider other imaging findings that may increase the accuracy of PET/CT.
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Non confirmatory electroencephalography in patients meeting clinical criteria for brain death: scenario and impact on organ donation.
Clin Neurophysiol
PUBLISHED: 01-19-2013
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To describe the causes and outcome of adult patients with preserved electroencephalographic activity despite clinical findings suggesting brain death (BD), and its impact on organ donation.
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[Cardiovascular disease: a view from global health perspective].
Med Clin (Barc)
PUBLISHED: 01-10-2013
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Globalization has facilitated the movement of large number of people around the world, leading modern clinicians to attend patients with rare or forgotten diseases. In the last few years many doctors are working in developing countries as volunteers or expatriates. The aim of this article is to summarize the basic epidemiological, clinical and therapeutic knowledge of the main cardiovascular diseases that a medical doctor from a developed country may attend in a tropical rural hospital, or with challenging diseases in patients coming from developing countries.
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Pharmacist-led medication reconciliation to reduce discrepancies in transitions of care in Spain.
Int J Clin Pharm
PUBLISHED: 01-02-2013
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Background Medication errors are one of the main causes of morbidity amongst hospital inpatients. More than half of medication errors occur at interfaces of care, when patients are discharged or transferred to the care of another physician. Medication reconciliation is the process of reviewing patients complete previous medication regimen, comparing it with current prescriptions, and analysing and resolving any discrepancies that the pharmacist does not believe to be intentional (unjustified discrepancies). Objective To quantify and analyse reconciliation unjustified discrepancies detected by a pharmacist in patients admitted to an internal medicine unit (IMU) over a 3-year period. Setting and method The hospital employs a pharmacist who acts as a link between the primary care services and the internal medicine specialist care unit. A retrospective descriptive study on the reconciliation discrepancies found was carried out. Medication reconciliation was performed upon admission in all patients transferred from the Accident and Emergency department (A&E) and admitted to the IMU, and also at the time of discharge. The interventions were categorised based on the consensus document on terminology and medication classification published by the Spanish Society of Hospital Pharmacy. Main outcome measure Number of patients with unjustified discrepancies, also known as reconciliation errors. Results 2,473 patients had their treatment reviewed at the time of admission and 1,150 at discharge. 866 reconciliation discrepancies were detected in 446 patients (1.94 per patient). 807 (93 %) were accepted by the prescribing physician and classified as reconciliation errors. 16.8 % of patients had at least one reconciliation error: 63.8 % of these errors were incomplete prescriptions, 16.6 % were medication omissions and 10.5 % were errors in dosage, administration method and/or frequency. Conclusion The rate of medication errors found in this study is low compared with other similar studies. The most common error was "incomplete prescriptions", most of them generated by the Accident and Emergency department. A computerised clinical history would help to decrease the number of reconciliation errors. Pharmacist interventions focused on medication reconciliation are well accepted by physicians, improving the quality of clinical histories and decreasing the number of medication errors that occur across transitions in patient care.
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P2X receptors as targets for the treatment of status epilepticus.
Front Cell Neurosci
PUBLISHED: 01-01-2013
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Prolonged seizures are amongst the most common neurological emergencies. Status epilepticus is a state of continuous seizures that is life-threatening and prompt termination of status epilepticus is critical to protect the brain from permanent damage. Frontline treatment comprises parenteral administration of anticonvulsants such as lorazepam that facilitate ?-amino butyric acid (GABA) transmission. Because status epilepticus can become refractory to anticonvulsants in a significant proportion of patients, drugs which act on different neurotransmitter systems may represent potential adjunctive treatments. P2X receptors are a class of ligand-gated ion channel activated by ATP that contributes to neuro- and glio-transmission. P2X receptors are expressed by both neurons and glia in various brain regions, including the hippocampus. Electrophysiology, pharmacology and genetic studies suggest certain P2X receptors are activated during pathologic brain activity. Expression of several members of the family including P2X2, P2X4, and P2X7 receptors has been reported to be altered in the hippocampus following status epilepticus. Recent studies have shown that ligands of the P2X7 receptor can have potent effects on seizure severity during status epilepticus and mice lacking this receptor display altered seizures in response to chemoconvulsants. Antagonists of the P2X7 receptor also modulate neuronal death, microglial responses and neuroinflammatory signaling. Recent work also found altered neuronal injury and inflammation after status epilepticus in mice lacking the P2X4 receptor. In summary, members of the P2X receptor family may serve important roles in the pathophysiology of status epilepticus and represent novel targets for seizure control and neuroprotection.
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Seizure suppression and neuroprotection by targeting the purinergic P2X7 receptor during status epilepticus in mice.
FASEB J.
PUBLISHED: 12-23-2011
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Prolonged seizures [status epilepticus (SE)] constitute a neurological emergency that can permanently damage the brain. SE results from a failure of the normal mechanisms to terminate seizures; in particular, ?-amino butyric acid-mediated inhibition, and benzodiazepine anticonvulsants are often incompletely effective. ATP acts as a fast neurotransmitter via ionotropic ligand-gated P2X receptors. Here we report that SE induced by intra-amygdala kainic acid in mice selectively increased hippocampal levels of P2X7 receptors relative to other P2X receptors. Using transgenic P2X7 reporter mice expressing enhanced green fluorescent protein, we identify dentate granule neurons as the major cell population transcribing the P2X7 receptor after SE. Pretreatment of mice with an intracerebroventricular microinjection of 1.75 nmol A438079, a P2X7 receptor antagonist, reduced seizure duration by 58% and reduced seizure-induced neuronal death by 61%. Injection of brilliant blue G (1 pmol), another selective antagonist, reduced seizure duration by 48% and was also neuroprotective. A438079 was seizure-suppressive when injected shortly after induction of SE, and coinjection of A438079 with lorazepam 60 min after triggering SE, when electrographic seizure-responsiveness to lorazepam had decreased, also terminated SE. Our results suggest that P2X7 receptor antagonists may be a promising class of drug for seizure abrogation and neuroprotection in SE.
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High-risk cytogenetics and persistent minimal residual disease by multiparameter flow cytometry predict unsustained complete response after autologous stem cell transplantation in multiple myeloma.
Blood
PUBLISHED: 11-29-2011
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The achievement of complete response (CR) after high-dose therapy/autologous stem cell transplantation (HDT/ASCT) is a surrogate for prolonged survival in multiple myeloma; however, patients who lose their CR status within 1 year of HDT/ASCT (unsustained CR) have poor prognosis. Thus, the identification of these patients is highly relevant. Here, we investigate which prognostic markers can predict unsustained CR in a series of 241 patients in CR at day +100 after HDT/ASCT who were enrolled in the Spanish GEM2000 (n = 140) and GEM2005 < 65y (n = 101) trials. Twenty-nine (12%) of the 241 patients showed unsustained CR and a dismal outcome (median overall survival 39 months). The presence of baseline high-risk cytogenetics by FISH (hazard ratio 17.3; P = .002) and persistent minimal residual disease by multiparameter flow cytometry at day +100 after HDT/ASCT (hazard ratio 8.0; P = .005) were the only independent factors that predicted unsustained CR. Thus, these 2 parameters may help to identify patients in CR at risk of early progression after HDT/ASCT in whom novel treatments should be investigated.
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Benefit from autologous stem cell transplantation in primary refractory myeloma? Different outcomes in progressive versus stable disease.
Haematologica
PUBLISHED: 11-04-2011
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Several studies of autologous stem cell transplantation in primary refractory myeloma have produced encouraging results. However, the outcome of primary refractory patients with stable disease has not been analyzed separately from the outcome of patients with progressive disease.
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?-Synuclein accumulates in huntingtin inclusions but forms independent filaments and its deficiency attenuates early phenotype in a mouse model of Huntingtons disease.
Hum. Mol. Genet.
PUBLISHED: 11-01-2011
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Huntingtons disease (HD) is the most common of nine inherited neurological disorders caused by expanded polyglutamine (polyQ) sequences which confer propensity to self-aggregate and toxicity to their corresponding mutant proteins. It has been postulated that polyQ expression compromises the folding capacity of the cell which might affect other misfolding-prone proteins. ?-Synuclein (?-syn) is a small neural-specific protein with propensity to self-aggregate that forms Parkinsons disease (PD) Lewy bodies. Point mutations in ?-syn that favor self-aggregation or ?-syn gene duplications lead to familial PD, thus indicating that increased ?-syn aggregation or levels are sufficient to induce neurodegeneration. Since polyQ inclusions in HD and other polyQ disorders are immunopositive for ?-syn, we speculated that ?-syn might be recruited as an additional mediator of polyQ toxicity. Here, we confirm in HD postmortem brains and in the R6/1 mouse model of HD the accumulation of ?-syn in polyQ inclusions. By isolating the characteristic filaments formed by aggregation-prone proteins, we found that N-terminal mutant huntingtin (N-mutHtt) and ?-syn form independent filamentous microaggregates in R6/1 mouse brain as well as in the inducible HD94 mouse model and that N-mutHtt expression increases the load of ?-syn filaments. Accordingly, ?-syn knockout results in a diminished number of N-mutHtt inclusions in transfected neurons and also in vivo in the brain of HD mice. Finally, ?-syn knockout attenuates body weight loss and early motor phenotype of HD mice. This study therefore demonstrates that ?-syn is a modifier of polyQ toxicity in vivo and raises the possibility that potential PD-related therapies aimed to counteract ?-syn toxicity might help to slow HD.
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Influence of the physiological stage and the content of soluble solids on the anthocyanin extractability of Vitis vinifera L. cv. Tempranillo grapes.
Anal. Chim. Acta
PUBLISHED: 08-01-2011
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The influence and the extent of the anthocyanin extractability from grape skins at different physiological stages and different soluble solids contents within each stage were investigated. For this purpose three different physiological stages (pre-harvest, harvest and over-ripening) and three soluble solids contents (22, 24 and 26°Brix) within each stage were taken into account using Vitis vinifera L. cv. Tempranillo. This study revealed the influence of physiological stages and soluble solids contents on the amounts of anthocyanins. The most important factor was the physiological stage although the soluble solid contents effect was also relevant, especially for anthocyanins monoglucosides. The highest contents in anthocyanins were found at pre-harvest, following by harvest and finally at over-ripening. Within each physiological stage, the relative abundance of acylated derivatives was influenced by the soluble solids contents. The percentages of acylated anthocyanins tend to decrease as the soluble solids contents. Differences in the anthocyanin extractabilities were highly influenced by the physiological stages and in a lesser extent by the soluble solids contents. The lowest extraction percentages were obtained in pre-harvest samples whatever soluble solids contents. Over-ripening samples present the lowest contents of anthocyanins but these compounds are easily released from tissues to the hydroalcoholic solution providing the highest extraction percentages. Generally, non-acylated anthocyanins were better extracted than the acylated anthocyanins.
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Utility of bilateral Bispectral index (BIS) monitoring in a comatose patient with focal nonconvulsive status epilepticus.
Seizure
PUBLISHED: 07-07-2011
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We report the case of a patient with an extensive right cerebral hematoma complicated by focal nonconvulsive status epilepticus (NCSE) in whom the use of the new bilateral BIS-Vista™ monitor was helpful in managing profound sedation and antiepileptic treatment in the absence of continuous EEG monitoring (CEEG). The analysis of color density spectral array (CDSA) showed stereotyped changes indicative of recurrent focal nonconvulsive seizures (NCSz) and NCSE. We noted a close correlation between NCSz and BIS value changes. EEGs during working hours always confirmed the persistence of focal NCSE. After several days of sedation, CDSA disclosed a gradual resolution of NCSE that was also confirmed by electroencephalography. The patient died of cardiorespiratory complications a few days later.
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