Survey of Primary Care Physicians and Home Care Clinicians

Journal of General Internal Medicine. Apr, 2002  |  Pubmed ID: 11972721

Providing home care in the United States is expensive, and significant geographic variation exists in the utilization of these services. However, few data exist on how well physicians and home care providers communicate and coordinate care for patients.

7-hydroxystaurosporine (UCN-01) and Ionizing Radiation Combine to Inhibit the Growth of Bcl-2-overexpressing U937 Leukemia Cells Through a Non-apoptotic Mechanism

International Journal of Oncology. Aug, 2002  |  Pubmed ID: 12118331

A clinically relevant dose (2.0 Gy) of ionizing radiation (IR) was employed to determine if subsequent exposure to the protein kinase C (PKC) and Chk 1 inhibitor UCN-01 for 24 h could abrogate IR-induced G2/M arrest and promote apoptosis in U937 leukemic cells ectopically expressing Bcl-2 (U937/Bcl-2). To this end, empty-vector control (U937/pCEP4) and U937/Bcl-2 cells were exposed to two UCN-01 concentrations following IR: i) a 50 nM concentration, which by itself was minimally toxic to both cell lines, and ii) a 150 nM concentration, which modestly induced apoptosis (e.g., ~19%) in control cells after 24 h. The effects of UCN-01 on IR responses were examined in relation to apoptosis induction, suspension culture growth inhibition, loss of clonogenic survival, and cell cycle perturbations. IR (2 Gy) alone minimally induced apoptosis in both U937 transfectant cell lines (e.g., <5% at 24 h in each case). Although UCN-01 failed to potentiate IR-mediated apoptosis at either early (e.g., 24 h) or late (e.g., 72 h) intervals, exposure to 50 or 150 nM UCN-01 resulted in a significant, albeit modest, reduction in proliferation and colony formation in irradiated U937/pCEP4 and U937/Bcl-2 cells. Despite failing to enhance apoptosis, UCN-01 treatment abrogated IR-induced G2/M arrest in both cell lines, an event associated with enhanced activation of cyclin-dependent kinase 1 (cdk1), promotion of G0/G1 arrest, and dephosphorylation of the retinoblastoma protein (pRb). Together, these findings indicate that exposure of U937 cells ectopically-expressing Bcl-2 to the combination of UCN-01 + IR leads to a further reduction in cell proliferation, and that this phenomenon appears to involve a non-apoptotic mechanism.

Active but Nonculturable Cells of Salmonella Enterica Serovar Typhimurium Do Not Infect or Colonize Mice

Microbiology (Reading, England). Sep, 2002  |  Pubmed ID: 12213918

The possibility that nonculturable cells of a normally culturable bacterial pathogen may constitute a source or reservoir for infective disease was investigated. In multiple experiments and with careful attention to the statistical limitations of the assays used, Salmonella enterica serovar Typhimurium cells rendered nonculturable by carbon and nitrogen stress in the presence of chloramphenicol were administered orally and intraperitoneally to over 300 female BALB/c mice. Neither infection nor colonization was detected in these studies, even when active but nonculturable (ABNC) cells, as defined by the Kogure cell elongation assay, were present in the inoculum. Doses of ABNC cells exceeding the oral and intraperitoneal LD(50) values by 3.5 and 2 orders of magnitude, respectively, were administered. It was concluded that ABNC cells of the salmonella strains used could not be considered potentially infective and that their detection in samples from material being evaluated as a potential source or reservoir of infection by the Kogure test does not specifically represent an infective hazard.

Indurated Plaques on the Arms

Archives of Dermatology. Oct, 2002  |  Pubmed ID: 12374546

Protein Kinase C-dependent Activation of the Tumor Necrosis Factor Receptor-mediated Extrinsic Cell Death Pathway Underlies Enhanced Apoptosis in Human Myeloid Leukemia Cells Exposed to Bryostatin 1 and Flavopiridol

Molecular Cancer Therapeutics. Jan, 2003  |  Pubmed ID: 12533676

Interactions between the protein kinase C activator bryostatin 1 and the cyclin-dependent kinase (CDK) inhibitor flavopiridol (FP) have been examined in human myeloid leukemia cells (U937 and HL-60). Previous studies have demonstrated synergistic induction of apoptosis in leukemic cells exposed to the potent differentiation-inducer phorbol 12-myristate 13-acetate (PMA) in conjunction with FP [L. Cartee et al., Cancer Res., 61: 2583-2591, 2001]. Although bryostatin 1 (10 nM) is a very weak inducer of differentiation compared with PMA in these cells, coadministration of a minimally toxic concentration of FP (100 nM) did not promote bryostatin 1-related maturation but instead caused a marked increase in mitochondrial damage (e.g., cytochrome c release; loss of Deltapsi(m)), caspase activation, poly(ADP-ribose) polymerase cleavage, and apoptosis. Bryostatin 1/FP-induced apoptosis was significantly diminished in cells ectopically expressing dominant-negative Fas-associated death domain or by coadministration of tumor necrosis factor (TNF)-alpha soluble receptors, implicating the extrinsic pathway in bryostatin 1/FP actions. Enhanced apoptosis in bryostatin 1/FP-treated cells was accompanied by down-regulation of Mcl-1 and a sustained increase in TNF-alpha release. The selective protein kinase C inhibitor GFX blocked TNF-alpha and cytochrome c release in bryostatin 1/FP-treated cells and attenuated apoptosis. Finally, coadministration of bryostatin 1 (or PMA) with FP induced a marked increase in apoptosis in U937 cells ectopically expressing an NH(2)-terminal phosphorylation loop-deleted Bcl-2 protein, which are otherwise highly resistant to FP-mediated lethality. Taken together, these findings suggest that synergistic induction of apoptosis by bryostatin 1 and FP does not stem from disruption of the leukemic cell maturation process but instead results from enhanced release of TNF-alpha and activation of the extrinsic apoptotic cascade, culminating in cell death.

Human Fasciolosis Acquired in an Australian Urban Setting

The Medical Journal of Australia. Mar, 2003  |  Pubmed ID: 12603192

Improvement in Diastolic Intraventricular Pressure Gradients in Patients with HOCM After Ethanol Septal Reduction

American Journal of Physiology. Heart and Circulatory Physiology. Dec, 2003  |  Pubmed ID: 12933340

We sought to validate measurement of intraventricular pressure gradients (IVPG) and analyze their change in patients with hypertrophic obstructive cardiomyopathy (HOCM) after ethanol septal reduction (ESR). Quantitative analysis of color M-mode Doppler (CMM) images may be used to estimate diastolic IVPG noninvasively. Noninvasive IVPG measurement was validated in 10 patients undergoing surgical myectomy. Echocardiograms were then analyzed in 19 patients at baseline and after ESR. Pulsed Doppler data through the mitral valve and pulmonary venous flow were obtained. CMM was used to obtain the flow propagation velocity (Vp) and to calculate IVPG off-line. Left atrial pressure was estimated with the use of previously validated Doppler equations. Data were compared before and after ESR. CMM-derived IVPG correlated well with invasive measurements obtained before and after surgical myectomy [r = 0.8, P < 0.01, Delta(CMM - invasive IVPG) = 0.09 +/- 0.45 mmHg]. ESR resulted in a decrease of resting LVOT systolic gradient from 62 +/- 10 to 29 +/- 5 mmHg (P < 0.001). There was a significant increase in the Vp and IVPG (from 48 +/- 5to 74 +/- 7 cm/s and from 1.5 +/- 0.2 to 2.6 +/- 0.3 mmHg, respectively, P < 0.001 for both). Estimated left atrial pressure decreased from 16.2 +/- 1.1 to 11.5 +/- 0.9 mmHg (P < 0.001). The increase in IVPG correlated with the reduction in the LVOT gradient (r = 0.6, P < 0.01). Reduction of LVOT obstruction after ESR is associated with an improvement in diastolic suction force. Noninvasive measurements of IVPG may be used as an indicator of diastolic function improvement in HOCM.

Using Memory Strategies to Improve 24-hour Dietary Recalls Among Older Adults

Journal of Allied Health. 2003  |  Pubmed ID: 14526903

Dietitians commonly use 24-hour recall to obtain estimates of the typical food intakes for a population. This study was designed to determine whether using an encoding strategy or support at the time of retrieval improves older adults' 24-hour recall of food items and amounts consumed. The study included 17 older adults ranging from 74 to 91 years of age. Lunch was served to these individuals, and 24-hour dietary recall and recognition of food items consumed at the meal were conducted the following day. Portion sizes for five food items served at the meal, as well as memory tests for recall and recognition and a visual perceptual test, were also administered. Among older adults, use of an encoding strategy did not enhance memory of food items and amounts consumed. However, when the adults were provided support with a visual recognition aid at the time of food item recall, individuals remembered more food items but not amounts consumed. Performance on the Wechsler Memory Scale I and II, Verbal Paired Associates, was found to be a predictor of subjects' performance on 24-hour recall.

Analysis of Normal Discourse Patterns

Brain and Cognition. Nov, 2003  |  Pubmed ID: 14607183

Twenty-five normal young adult college students provided speaking and writing samples using two elicitation procedures: picture description and personal narrative. Patterns of productivity, efficiency, and coherence were investigated while considering the demands imposed by mode of expression, task elicitation, cognitive distance, and verbal working memory. Samples were divided into top (S1) and bottom (S2) halves. Within group (S1/S2) and between group (pictured activity description/personal narrative) comparisons were made for oral vs. written samples, and performance measures were correlated with verbal working memory scores. Results indicated that the productivity measure was influenced by the type of elicitation task and was not related to verbal working memory scores. Efficiency was influenced by mode of expression and demonstrated a low correlation with verbal working memory scores. Coherence ratings were not influenced by type of elicitation task, mode of expression, or length of sample, and were not related to verbal working memory scores. Results are discussed in terms of the clinical utility of these discourse measures.

Trends of Behavioral Risk Factors in Motor Vehicle Crashes in Utah, 1992-1997

Accident; Analysis and Prevention. Mar, 2004  |  Pubmed ID: 14642879

Measure changes in the prevalence of behavioral factors including police-reported fatigue and alcohol intoxication, as well as self-reported seatbelt use, and assess their effect on hospitalization or death after a motor vehicle crash.

Use of Genome Level-informed PCR As a New Investigational Approach for Analysis of Outbreak-associated Mycobacterium Tuberculosis Isolates

Journal of Clinical Microbiology. May, 2004  |  Pubmed ID: 15131145

Mycobacterium tuberculosis strain CH, the index isolate linked to a major tuberculosis outbreak associated with high levels of transmissibility and virulence, was characterized by microarray analysis by use of a PCR product array representative of the genome of M. tuberculosis strain H37Rv. Seven potential genomic deletions were identified in CH, five of which were confirmed by PCR analysis across the predicted deletion points. The panel of five PCRs required to individually interrogate these loci was collectively referred to as the genome level-informed PCR (GLIP) assay. GLIP analysis was performed with CH, 12 other epidemiologically linked isolates, and 43 recent, non-outbreak-associated isolates derived from patients within the local area. All 13 outbreak-linked isolates showed a profile corresponding to the presence of all five deletions. These 13 isolates were also found to share common variable-number tandem repeat and mycobacterial interspersed repetitive unit profiles. None of the 43 non-outbreak-associated isolates exhibited the five-deletion profile. Although three individual deletions were present in upwards of 44% of the non-outbreak-associated isolates, no single-deletion isolates were detected. Interestingly, none of these deletions had been previously recognized, and sequence analysis of the immediate flanking regions in CH failed to identify a likely mechanism of deletion for four of the five loci. The GLIP assay also proved valuable in ongoing surveillance of the outbreak, rapidly identifying a further two outbreak-associated cases months after the initial cluster and, importantly, dismissing a further 12 epidemiologically suspect cases, which allowed the optimum deployment of public health resources.

Cerebral Areas Processing Swallowing and Tongue Movement Are Overlapping but Distinct: a Functional Magnetic Resonance Imaging Study

Journal of Neurophysiology. Oct, 2004  |  Pubmed ID: 15163677

Although multiple regions of the cerebral cortex have been implicated in swallowing, the functional contributions of each brain area remain unclear. The present study sought to clarify the roles of these cortical foci in swallowing by comparing brain activation associated with voluntary saliva swallowing and voluntary tongue elevation. Fourteen healthy right-handed subjects were examined with single-event-related functional magnetic resonance imaging (fMRI) while laryngeal movements associated with swallowing and tongue movement were simultaneously recorded. Both swallowing and tongue elevation activated 1) the left lateral pericentral and anterior parietal cortex, and 2) the anterior cingulate cortex (ACC) and adjacent supplementary motor area (SMA), suggesting that these brain regions mediate processes shared by swallowing and tongue movement. Tongue elevation activated a larger total volume of cortex than swallowing, with significantly greater activation within the ACC, SMA, right precentral and postcentral gyri, premotor cortex, right putamen, and thalamus. Although a contrast analysis failed to identify activation foci specific to swallowing, superimposed activation maps suggested that the most lateral extent of the left pericentral and anterior parietal cortex, rostral ACC, precuneus, and right parietal operculum/insula were preferentially activated by swallowing. This finding suggests that these brain areas may mediate processes specific to swallowing. Approximately 60% of the subjects showed a strong functional lateralization of the postcentral gyrus toward the left hemisphere for swallowing, whereas 40% showed a similar activation bias for the tongue elevation task. This finding supports the view that the oral sensorimotor cortices within the left and right hemispheres are functionally nonequivalent.

ArrayOme: a Program for Estimating the Sizes of Microarray-visualized Bacterial Genomes

Nucleic Acids Research. 2005  |  Pubmed ID: 15640440

ArrayOme is a new program that calculates the size of genomes represented by microarray-based probes and facilitates recognition of key bacterial strains carrying large numbers of novel genes. Protein-coding sequences (CDS) that are contiguous on annotated reference templates and classified as 'Present' in the test strain by hybridization to microarrays are merged into ICs (ICs). These ICs are then extended to account for flanking intergenic sequences. Finally, the lengths of all extended ICs are summated to yield the 'microarray-visualized genome (MVG)' size. We tested and validated ArrayOme using both experimental and in silico-generated genomic hybridization data. MVG sizing of five sequenced Escherichia coli and Shigella strains resulted in an accuracy of 97-99%, as compared to true genome sizes, when the comprehensive ShE.coli meta-array gene sequences (6239 CDS) were used for in silico hybridization analysis. However, the E.coli CFT073 genome size was underestimated by 14% as this meta-array lacked probes for many CFT073 CDS. ArrayOme permits rapid recognition of discordances between PFGE-measured genome and MVG sizes, thereby enabling high-throughput identification of strains rich in novel genes. Gene discovery studies focused on these strains will greatly facilitate characterization of the global gene pool accessible to individual bacterial species.

Effects of Seating Position and Appropriate Restraint Use on the Risk of Injury to Children in Motor Vehicle Crashes

Pediatrics. Mar, 2005  |  Pubmed ID: 15741356

Currently, many states are upgrading their child restraint laws to include provisions for the use of age-appropriate restraints through 6 to 8 years of age, with some also requiring rear seating for children, enabling the laws to be in closer alignment with best-practice recommendations.

Genetics in Occupational Therapy Education: a Survey of Professional Entry-level Programs

The American Journal of Occupational Therapy. : Official Publication of the American Occupational Therapy Association. Mar-Apr, 2005  |  Pubmed ID: 15830616

Advances in genetics indicate a need for occupational therapists to develop literacy and skills in genetics as it relates to lifestyle and occupation. The purpose of this study is to identify genetics content areas taught, instructional methods used, and the importance of teaching genetics at the entry-level in occupational therapy curricula.

Olfactory Bulb Mitral Cell Dendritic Pruning Abnormalities in a Mouse Model of the Fragile-X Mental Retardation Syndrome: Further Support for FMRP's Involvement in Dendritic Development

Brain Research. Developmental Brain Research. Jun, 2005  |  Pubmed ID: 15878626

The Fragile-X mental retardation syndrome is the leading form of inherited mental retardation. Dendritic analysis in a mouse model (FraX) found abnormal pruning in somatosensory cortex. To further characterize dendritic abnormalities and assess their occurrence in other brain regions, we examined mitral cells in FraX mice olfactory bulbs. FraX mice exhibited dendritic abnormalities consistent with somatosensory cortex, suggesting that deficient pruning is found in multiple brain regions.

Enhanced Toxicity to the Catecholamine Tyramine in Polyglutamine Transfected SH-SY5Y Cells

Neurochemical Research. Apr, 2005  |  Pubmed ID: 16076022

Huntington's disease (HD) is a progressive neurodegenerative disorder, of which the pathogenesis is not completely understood. In patients with Huntington's disease, there is a mutation in the gene encoding the protein huntingtin, which results in an expanded polyglutamine sequence leading to degeneration of the basal ganglia. There is mounting evidence that metabolism of the transmitter dopamine by the enzyme monoamine oxidase may contribute to striatal damage in mitochondrial toxin-induced models of HD. In this study, we have examined the role of the catecholamine tyramine in neural SH-SY5Y cells transfected with normal and expanded polyglutamine repeat numbers. Our findings demonstrate that cells containing a pathological number of polyglutamines are more sensitive to tyramine than cells with a non-pathological number. Tyramine-induced cell death was attenuated by MAO inhibitors as well as with catalase and the iron chelator deferoxamine, suggesting that H202 might mediate the observed toxicity. These observations support the notion that the metabolism of dopamine plays a role in neuron death in Huntington's disease.

Taste Preference and Rating of Commercial and Natural Thickeners

Rehabilitation Nursing : the Official Journal of the Association of Rehabilitation Nurses. Nov-Dec, 2005  |  Pubmed ID: 16294803

Dysphagia can negatively affect quality of life, nutritional status, and pulmonary status of individuals. The most common intervention for dysphagia is the use of thickening agents for liquids. This group study (n = 43) investigated the taste preference, taste ratings, and ranking for nectar-thick hot and cold beverages using three types of thickeners: SimplyThick, Thick-It, and noncommercially prepared natural thickeners. Results demonstrated a significant difference between the taste ratings of two commercial thickeners and between one commercial and the natural thickener for the ranking of taste with hot beverages. Every participant rated at least one of the thickener beverages as having an acceptable taste for the hot chocolate and fruit juice beverages. Exploring individual preferences is critical to selecting a beverage that increases compliance to clinical recommendations.

The Diabetes Prevention Program: a Worksite Experience

AAOHN Journal : Official Journal of the American Association of Occupational Health Nurses. Nov, 2005  |  Pubmed ID: 16309012

The purpose of this study was to determine if the U.S. National Institutes of Health Diabetes Prevention Program (DPP) could be successfully implemented in a worksite setting. Thirty-seven adult employees of BD Medical Systems of Sandy, Utah were enrolled in a single-group time-series study using the DPP. Two-hour oral glucose tolerance tests (OGTT) and other outcomes were measured at baseline, 6 months, and 12 months. Weight, body mass index, waist circumference, 2-hour OGTT, very low density lipoproteins, triglycerides, and aerobic fitness were significantly improved at 6 and 12 months and showed overall significant improvement across time. Fasting blood insulin, total cholesterol, low density lipoproteins, and total cholesterol/high density lipoproteins ratio were significantly improved at 6 months, but not at 12 months. Eighteen of the program participants (51%) were no longer in the pre-diabetes and diabetes categories after 1 year. Existing worksite health promotion and occupational health professionals can successfully offer the DPP and help employees improve glucose tolerance.

Bolus Location at the Initiation of the Pharyngeal Stage of Swallowing in Healthy Older Adults

Dysphagia. 2005  |  Pubmed ID: 16633870

This study characterized the vertical position of the bolus head at the onset of the pharyngeal swallow in healthy older adults. Lateral-view videofluoroscopic (VF) images were obtained from ten healthy volunteers (age-71.6 +/- 7.5 years, mean+/- SD) as they swallowed 5-cc thin liquid barium aliquots. For each swallow, the bolus head and several anatomic landmarks were digitally recorded from the image in which pharyngeal swallow-related hyoid bone elevation began. Vertical distance between the bolus head and the intersection of the tongue base and mandibular ramus (TMI) was computed. Bolus head position at swallow onset ranged from 47.4-mm above to 34.9-mm below the TMI (2.2 +/- 14.4-mm, mean +/- SD). Although the bolus head was below the level of the TMI for the majority of swallows, neither penetration nor aspiration occurred. For individual subjects, mean bolus head position ranged from 25.8 +/- 5.0-mm above to 15.5 +/- 6.5-mm below the TMI. Whereas five of ten subjects initiated the pharyngeal swallow with the bolus head consistently above or consistently below the TMI, five subjects initiated swallowing with the bolus head either above or below the TMI across trials. Older adults commonly initiate thin-liquid swallows with the bolus head well below the TMI without associated penetration or aspiration. Thus, bolus position alone does not differentiate between normal and pathologic swallowing within the healthy elderly. Bolus position at pharyngeal swallow onset can vary substantially from trial to trial within an individual, suggesting that the triggering of swallowing depends on multiple influences.

Effects of Swimming on Functional Recovery After Incomplete Spinal Cord Injury in Rats

Journal of Neurotrauma. Jun, 2006  |  Pubmed ID: 16774475

One of the most promising rehabilitation strategies for spinal cord injury is weight-supported treadmill training. This strategy seeks to re-train the spinal cord below the level of injury to generate a meaningful pattern of movement. However, the number of step cycles that can be accomplished is limited by the poor weight-bearing capability of the neuromuscular system after injury. We have begun to study swimming as a rehabilitation strategy that allows for high numbers of steps and a high step-cycle frequency in a standard rat model of contusive spinal cord injury. The purpose of the present study was to evaluate the effect of swimming as a rehabilitation strategy in rats with contusion injuries at T9. We used a swimming strategy with or without cutaneous feedback based on original work in the chick by Muir and colleagues. Adult female rats (n=27) received moderately-severe contusion injuries at T9. Walking and swimming performance were evaluated using the Open-Field Locomotor Scale (BBB; Basso et al., 1995) and a novel swimming assessment, the Louisville Swimming Scale (LSS). Rats that underwent swim-training with or without cutaneous feedback showed a significant improvement in hindlimb function during swimming compared to untrained animals. Rats that underwent swim-training without cutaneous feedback showed less improvement than those trained with cutaneous feedback. Rats in the non-swimming group demonstrated little improvement over the course of the study. All three groups showed the expected improvement in over-ground walking and had similar terminal BBB scores. These findings suggest that animals re-acquire the ability to swim only if trained and that cutaneous feedback improves the re-training process. Further, these data suggest that the normal course of recovery of over-ground walking following moderately-severe contusion injuries at T9 is the result of a re-training process.

The Genetic Portrait of an Outbreak Strain

Tuberculosis (Edinburgh, Scotland). Sep, 2006  |  Pubmed ID: 16360339

Unique events in the genome of Mycobacterium tuberculosis, including deletions and IS6110 insertions, have been proposed to be responsible for the virulence phenotype of outbreak strains. Based on this premise, we determined ten IS6110 insertion sites in the genome of the M. tuberculosis CH strain, which was responsible for a large outbreak in Leicestershire, England. Together with previous data on genomic deletions, it was found that 16 genes were mutated either by IS6110 insertions or deletions. The likely impact of these genomic events on the phenotype of the CH strain is discussed.

Multidimensional Scaling of Ferrous Sulfate and Basic Tastes

Physiology & Behavior. Feb, 2006  |  Pubmed ID: 16375932

The status of metallic sensations as a primary or basic taste category is controversial. Ferrous sulfate (FeSO4) has been suggested as a prototypical metallic chemosensory stimulus. At least part of the metallic sensation from FeSO4 arises from a metallic retronasal smell. The quality of this sensation was studied via multidimensional scaling (MDS) of taste similarities, with and without nasal closure to eliminate retronasal olfactory sensations. The metallic stimulus was embedded in a series containing classical "basic taste" stimuli, alum and monosodium glutamate. With olfaction available, the metallic stimulus plotted away from basic tastes and taste mixtures. Scaled ratings of sensory properties related to metallic taste (iron-nail, copper-penny-like, aftertaste) of FeSO4 decreased with nasal closure. Results are consistent with the idea that ferrous sulfate produces a distinctly different sensation from the traditional basic tastes, which includes both olfactory and oral sensations.

Commentary on Regehr C, Kjerulf M, Popova S & Baker A (2004) Trauma and Tribulation: the Experiences and Attitudes of Operating Room Nurses Working with Organ Donors. Journal of Clinical Nursing 13, 430-437

Journal of Clinical Nursing. Jan, 2006  |  Pubmed ID: 16390536

A Novel Strategy for the Identification of Genomic Islands by Comparative Analysis of the Contents and Contexts of TRNA Sites in Closely Related Bacteria

Nucleic Acids Research. 2006  |  Pubmed ID: 16414954

We devised software tools to systematically investigate the contents and contexts of bacterial tRNA and tmRNA genes, which are known insertion hotspots for genomic islands (GIs). The strategy, based on MAUVE-facilitated multigenome comparisons, was used to examine 87 Escherichia coli MG1655 tRNA and tmRNA genes and their orthologues in E.coli EDL933, E.coli CFT073 and Shigella flexneri Sf301. Our approach identified 49 GIs occupying approximately 1.7 Mb that mapped to 18 tRNA genes, missing 2 but identifying a further 30 GIs as compared with Islander [Y. Mantri and K. P. Williams (2004), Nucleic Acids Res., 32, D55-D58]. All these GIs had many strain-specific CDS, anomalous GC contents and/or significant dinucleotide biases, consistent with foreign origins. Our analysis demonstrated marked conservation of sequences flanking both empty tRNA sites and tRNA-associated GIs across all four genomes. Remarkably, there were only 2 upstream and 5 downstream deletions adjacent to the 328 loci investigated. In silico PCR analysis based on conserved flanking regions was also used to interrogate hotspots in another eight completely or partially sequenced E.coli and Shigella genomes. The tools developed are ideal for the analysis of other bacterial species and will lead to in silico and experimental discovery of new genomic islands.

A Wellness Class for Inpatients with Psychotic Disorders

Journal of Psychiatric Practice. Jan, 2006  |  Pubmed ID: 16432442

The purpose of this project was to educate inpatients with psychotic disorders, many of whom were taking second-generation antipsychotics, about lifestyle changes they can make to combat weight gain.

Parent Driver Characteristics Associated with Sub-optimal Restraint of Child Passengers

Traffic Injury Prevention. Dec, 2006  |  Pubmed ID: 17114095

To identify parent driver demographic and socioeconomic characteristics associated with the use of sub-optimal restraints for child passengers under nine years.

The Louisville Swim Scale: a Novel Assessment of Hindlimb Function Following Spinal Cord Injury in Adult Rats

Journal of Neurotrauma. Nov, 2006  |  Pubmed ID: 17115911

The majority of animal studies examining the recovery of function following spinal cord injury use the BBB Open-Field Locomotor Scale as a primary outcome measure. However, it is now well known that rehabilitation strategies can bring about significant improvements in hindlimb function in some animal models. Thus, improvements in walking following spinal cord injury in rats may be influenced by differences in activity levels and housing conditions during the first few weeks post-injury. Swimming is a natural form of locomotion that animals are not normally exposed to in the laboratory setting. We hypothesized that deficits in, and functional recovery of, swimming would accurately represent the locomotor capability of the nervous system in the absence of any retraining effects. To test this hypothesis, we have compared the recovery of walking and swimming in rats following a range of standardized spinal cord injuries and two different retraining strategies. In order to assess swimming, we developed a rating system we call the Louisville Swimming Scale (LSS) that evaluates three characteristics of swimming that are highly altered by spinal cord injury--namely, hindlimb movement, forelimb dependency, and body position. The data indicate that the LSS is a sensitive and reliable method of determining swimming ability and the improvement in hindlimb function after standardized contusion injury of the thoracic spinal cord. Furthermore, the data suggests that when used in conjunction with the BBB Open-field Locomotor Scale, the LSS assesses locomotor capabilities that are not influenced by a retraining effect.

An Interdisciplinary Approach to Introducing Professionalism

American Journal of Pharmaceutical Education. Aug, 2006  |  Pubmed ID: 17136200

To provide interdisciplinary structured activities in academic and clinical settings for introducing the concept of professionalism to health professions students.

A Mental Health Program for Ground Zero Rescue and Recovery Workers: Cases and Observations

Psychiatric Services (Washington, D.C.). Sep, 2006  |  Pubmed ID: 16968767

Clinical vignettes from the World Trade Center Worker and Volunteer Mental Health Monitoring and Treatment Program at the Mount Sinai Medical Center in New York City are presented. The hospital-based program pairs mental health screenings with federally funded occupational medical screenings to identify persons with mental health problems related to their rescue and recovery roles. The program also provides on-site mental health treatment. The cases illustrate the diverse mental health needs of the rescue and recovery workers, some of whom initially sought treatment years after September 11, 2001. The cases show that in addition to symptoms of posttraumatic stress disorder, workers experienced survivor guilt, distressing memories of childhood trauma, shame associated with intense feelings, substance abuse relapse, psychosis, and problems with family relationships.

Real-time Monitoring of Microwave-promoted Suzuki Coupling Reactions Using in Situ Raman Spectroscopy

Organic Letters. Sep, 2006  |  Pubmed ID: 16986957

The progress of microwave-promoted Suzuki reactions has been monitored using an in situ Raman spectroscopy apparatus assembled from commercially available components. It was possible to see if any reaction occurred and, if so, when it reached completion. In addition, the monitoring technique has given us an insight into the reaction, confirming that, when run in aqueous media, the coupling is in competition with the rapid deboronation of the boronic acid.

A Worksite Diabetes Prevention Program: Two-year Impact on Employee Health

AAOHN Journal : Official Journal of the American Association of Occupational Health Nurses. Sep, 2006  |  Pubmed ID: 17001837

The purpose of this study was to determine the 2-year impact of a worksite-based diabetes prevention program. Thirty-seven pre-diabetic and previously undiagnosed diabetic employees participating in a 12-month worksite diabetes prevention program were included. Weight, body mass index, waist circumference, oral glucose tolerance testing, fasting insulin, blood lipids, and aerobic fitness had improved significantly after 6 months. Much of this improvement continued through 12 months. One year following the intervention, oral glucose tolerance and aerobic fitness had improved significantly. Of the 22 employees remaining in the study through 24 months, more than half had normal results on glucose tolerance testing. Worksite diabetes prevention programs may reduce blood glucose below pre-diabetic and diabetic levels. Improvements in diabetes risk factors persisted for at least 2 years in most of these employees.

A Deletion Defining a Common Asian Lineage of Mycobacterium Tuberculosis Associates with Immune Subversion

Proceedings of the National Academy of Sciences of the United States of America. Oct, 2006  |  Pubmed ID: 17028173

Six major lineages of Mycobacterium tuberculosis appear preferentially transmitted amongst distinct ethnic groups. We identified a deletion affecting Rv1519 in CH, a strain isolated from a large outbreak in Leicester U.K., that coincidentally defines the East African-Indian lineage matching a major ethnic group in this city. In broth media, CH grew less rapidly and was less acidic and H2O2-tolerant than reference sequenced strains (CDC1551 and H37Rv). Nevertheless, CH was not impaired in its ability to grow in human monocyte-derived macrophages. When compared with CDC1551 and H37Rv, CH induced less protective IL-12p40 and more antiinflammatory IL-10 and IL-6 gene transcription and secretion from monocyte-derived macrophages. It thus appears that CH compensates microbiological attenuation by skewing the innate response toward phagocyte deactivation. Complementation of Rv1519, but none of nine additional genes absent from CH compared with the type strain, H37Rv, reversed the capacity of CH to elicit antiinflammatory IL-10 production by macrophages. The Rv1519 polymorphism in M. tuberculosis confers an immune subverting phenotype that contributes to the persistence and outbreak potential of this lineage.

Global Veterinary Opportunities and Responsibilities: Some Recent Graduates' Perspectives

Journal of Veterinary Medical Education. 2006  |  Pubmed ID: 17035217

The veterinary profession has critical global responsibilities. To help meet these responsibilities, it is critical that the training programs for veterinary graduates provide them with the skills, knowledge, understanding, and professional attributes pertinent to meeting these responsibilities. The programs at US veterinary schools, in the full range from admissions, to curriculum, to post-graduate opportunities, fall short in many critical arenas.

Seat Belt Use Among 13-15 Year Olds in Primary and Secondary Enforcement Law States

Accident; Analysis and Prevention. May, 2007  |  Pubmed ID: 17046700

Coverage and enforcement provisions of safety belt use laws vary by state. Most laws cover drivers and passengers age 16 and above. "Primary" enforcement laws allow police to stop and ticket a motorist for a safety belt law violation. With "secondary" enforcement laws, ticketing can only occur in the presence of another traffic infraction. Given the lower rates of restraint use among teen drivers and their passengers, the effect of primary enforcement laws on the restraint use of young teen passengers is of particular interest.

Development of a New, Combined Rapid Method Using Phage and PCR for Detection and Identification of Viable Mycobacterium Paratuberculosis Bacteria Within 48 Hours

Applied and Environmental Microbiology. Mar, 2007  |  Pubmed ID: 17259362

The FASTPlaqueTB assay is an established diagnostic aid for the rapid detection of Mycobacterium tuberculosis from human sputum samples. Using the FASTPlaqueTB assay reagents, viable Mycobacterium avium subsp. paratuberculosis cells were detected as phage plaques in just 24 h. The bacteriophage used does not infect M. avium subsp. paratuberculosis alone, so to add specificity to this assay, a PCR-based identification method was introduced to amplify M. avium subsp. paratuberculosis-specific sequences from the DNA of the mycobacterial cell detected by the phage. To give further diagnostic information, a multiplex PCR method was developed to allow simultaneous amplification of either M. avium subsp. paratuberculosis or M. tuberculosis complex-specific sequences from plaque samples. Combining the plaque PCR technique with the phage-based detection assay allowed the rapid and specific detection of viable M. avium subsp. paratuberculosis in milk samples in just 48 h.

Using in Situ Raman Monitoring As a Tool for Rapid Optimisation and Scale-up of Microwave-promoted Organic Synthesis: Esterification As an Example

Organic & Biomolecular Chemistry. Mar, 2007  |  Pubmed ID: 17315069

Microwave-promoted esterification reactions have been monitored using in situ Raman spectroscopy. Having optimised a reaction on a 23 mmol scale, it was transferred to a larger reaction vessel and scaled up to 0.26 mol, again with Raman monitoring. With conditions in hand, an automated stop-flow apparatus was used to prepare 5.7 moles of product.

Pili Mediate Specific Adhesion of Streptococcus Pyogenes to Human Tonsil and Skin

Cellular Microbiology. Jul, 2007  |  Pubmed ID: 17359232

Very little is known about the biological functions of pili that have recently been found to be expressed by important Gram-positive pathogens such as Corynebacterium diphtheriae, Streptococcus agalacticae, S. pneumoniae and S. pyogenes. Using various ex vivo tissue and cellular models, here we show that pili mediate adhesion of serotype M1 S. pyogenes strain SF370 to both human tonsil epithelium and primary human keratinocytes, which represent the two main sites of infection by this human-specific pathogen. Mutants lacking minor pilus subunits retained the ability to express cell-surface pili, but these were functionally defective. In contrast to above, pili were not required for S. pyogenes adhesion to either immortalized HEp-2 or A549 cells, highlighting an important limitation of these extensively used adhesion/invasion models. Adhering bacteria were internalized very effectively by both HEp-2 and A549 cells, but not by tonsil epithelium or primary keratinocytes. While pili acted as the primary adhesin, the surface M1 protein clearly enhanced adhesion to tonsil, but surprisingly, had the opposite effect on adhesion to keratinocytes. These studies provide clear evidence that S. pyogenes pili display an adhesive specificity for clinically relevant human tissues and are likely to play a critical role in the initial stages of infection.

Isolated Bilateral Abducens Nerve Palsy Associated with Traumatic Prepontine Hematoma

Seminars in Ophthalmology. Jan-Mar, 2007  |  Pubmed ID: 17366113

We describe a 15-year-old boy who developed isolated bilateral abducens nerve palsies immediately following a motor vehicle accident and who was found to have a pre-pontine extra-axial hematoma. We review the literature on isolated bilateral traumatic abducens palsies and discuss the alternate mechanisms for this injury.

Species Identification and Strain Differentiation of Clinical Candida Isolates Using the DiversiLab System of Automated Repetitive Sequence-based PCR

Journal of Medical Microbiology. Jun, 2007  |  Pubmed ID: 17510263

The DiversiLab system, which uses repetitive sequence-based PCR (rep-PCR) to genotype micro-organisms, was evaluated as a molecular typing tool for members of the genus Candida. Initially, 41 clinical Candida spp. (7 Candida krusei, 10 Candida parapsilosis, 7 Candida albicans, 10 Candida tropicalis and 7 Candida glabrata), previously identified at the species level by morphological and biochemical analysis, were analysed with the DiversiLab system. Species identification was confirmed by DNA sequence analysis of the contiguous internal transcribed spacer (ITS) region (ITS1-5.8S-ITS2). On the basis of an 80 % similarity threshold, rep-PCR consistently clustered like species and this set of isolates, along with five ATCC reference strains, was used to create a DNA fingerprint library with the DiversiLab software. Subsequently, an additional set of 115 clinical Candida isolates, identified biochemically as C. albicans (n=94), C. glabrata (n=8), C. parapsilosis (n=5), C. tropicalis (n=3), C. krusei (n=3) and Candida lusitaniae (n=2), isolated at a regional reference laboratory, were typed using DiversiLab. One hundred and six of these isolates clustered with members of the Candida library at >80 % similarity and thus could be assigned species identification, and initial calculations showed that identification via rep-PCR fingerprinting was 95 % concordant (101/106) with the biochemical/morphological identification. However, ITS region sequencing of the five discrepant samples, as well as the nine isolates that were <80 % similar to the database samples, showed that nine were misidentified with traditional biochemical/morphological methods. For the misidentified isolates, the sequence-based identification was in agreement with the DiversiLab clustering, yielding an actual correlation of >99 %. As traditional techniques can take several days to provide information about Candida at the genus/species level, genotyping with the DiversiLab system holds promise for more-rapid speciation of members of this genus. This system may also be useful for epidemiological studies such as source tracking that require Candida subspecies discrimination.

In Situ Raman Spectroscopy As a Probe for the Effect of Power on Microwave-promoted Suzuki Coupling Reactions

Organic & Biomolecular Chemistry. Sep, 2007  |  Pubmed ID: 17700844

We report the use of in situ Raman spectroscopy as a probe for the effect of power on microwave-promoted Suzuki coupling reactions. We find that increased initial microwave power leads to greater acceleration of the reaction but that the product yield obtained is essentially independent of initial microwave power. The application of simultaneous cooling lengthens the reaction time but does not alter the relative rates of the Suzuki coupling and deboronation processes. Performing the reaction at an initial microwave power of 5 W leads to an improvement in product yield.

Cerebral Cortical Processing of Swallowing in Older Adults

Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale. Jan, 2007  |  Pubmed ID: 16896984

While brain-imaging studies in young adults have implicated multiple cortical regions in swallowing, investigations in older subjects are lacking. This study examined the neural representations of voluntary saliva swallowing and water swallowing in older adults. Nine healthy females were examined with event-related functional magnetic resonance imaging (fMRI) while laryngeal swallow-related movements were recorded. Swallowing in the older adults, like young adults, activated multiple cortical regions, most prominently the lateral pericentral, perisylvian, and anterior cingulate cortex. Activation of the postcentral gyrus was lateralized to the left hemisphere for saliva and water swallowing, consistent with our findings in young female subjects. Comparison of saliva and water swallowing revealed a fourfold increase in the brain volume activated by the water swallow compared to the saliva swallow, particularly within the right premotor and prefrontal cortex. This task-specific activation pattern may represent a compensatory response to the demands of the water swallow in the face of age-related diminution of oral sensorimotor function.

Sensitivity of Polymerase Chain Reaction for Detection of Bovine Viral Diarrhea Virus in Pooled Serum Samples and Use of Pooled Polymerase Chain Reaction to Determine Prevalence of Bovine Viral Diarrhea Virus in Auction Market Cattle

Journal of Veterinary Diagnostic Investigation : Official Publication of the American Association of Veterinary Laboratory Diagnosticians, Inc. Jan, 2008  |  Pubmed ID: 18182514

Two reverse transcription-nested polymerase chain reaction tests, 1 quantitative (qRT-nPCR) and 1 standard (RT-nPCR), were evaluated to assess sensitivity for detection of bovine viral diarrhea virus (BVDV) of a single positive serum sample in a pool of 30. The RT-nPCR and qRT-nPCR each detected 95 of 100 known positives. The RT-nPCR was used to estimate the prevalence of BVDV in adult beef cows. Serum samples were obtained from the US Department of Agriculture brucellosis testing laboratories in 3 Midwestern states. Samples originated from auction markets and private treaty sales throughout the 3 states. A total of 2,990 serum samples were collected and randomly pooled into 100 pools for testing. Two of the 100 pools of field samples were positive, and each positive pool had a single positive individual sample upon confirmation. The estimate of BVDV prevalence in adult cows in this study was 0.07%. This study estimates the diagnostic sensitivity of RT-nPCR for BVDV and confirms that it is a useful diagnostic tool for pools of 30 serum samples and that prevalence of BVDV in adult cattle from auction markets is low.

Fasciola Hepatica and Fasciola Gigantica: Cloning and Characterisation of 70 KDa Heat-shock Proteins Reveals Variation in HSP70 Gene Expression Between Parasite Species Recovered from Sheep

Experimental Parasitology. Apr, 2008  |  Pubmed ID: 18190913

Fasciola hepatica and Fasciola gigantica are trematode parasites responsible for fasciolosis, a disease of ruminant animals which is also increasingly recognised as a disease in humans. By biochemical and in silico methods, we have cloned and characterised the 70 kDa heat-shock proteins (HSP70s) of F. hepatica and F. gigantica. The nucleotide and protein sequences for HSP70 were found to be 98% and 99% identical between liver fluke species, respectively, and to encode conserved amino acid motifs that are of putative functional importance. Western blot analysis demonstrated that HSP70 proteins were expressed at a higher level in F. gigantica recovered from sheep relative to F. hepatica, but HSP70 was not detected in the excretory-secretory products of these liver fluke samples. Real-time reverse-transcriptase PCR analysis of HSP70 expression in parasites from sheep, but not cattle, showed HSP70 expression to be higher in F. gigantica than F. hepatica. These results suggest that hosts refractory to F. gigantica are associated with higher HSP70 expression by this parasite and that HSP70 expression may represent a biochemical marker of the stress response of F. gigantica.

Trends in U.S. Emergency Department Visits for Anxiety-related Mental Health Conditions, 1992-2001

The Journal of Clinical Psychiatry. Feb, 2008  |  Pubmed ID: 18363455

To describe trends in anxiety-related mental health visits to U.S. emergency departments, an expanding portal of access for mental health care.

Cytological and Transcript Analyses Reveal Fat and Lazy Persister-like Bacilli in Tuberculous Sputum

PLoS Medicine. Apr, 2008  |  Pubmed ID: 18384229

Tuberculous sputum provides a sample of bacilli that must be eliminated by chemotherapy and that may go on to transmit infection. A preliminary observation that Mycobacterium tuberculosis cells contain triacylglycerol lipid bodies in sputum, but not when growing in vitro, led us to investigate the extent of this phenomenon and its physiological basis.

Nondestructive Optical Determination of Fiber Organization in Intact Myocardial Wall

Microscopy Research and Technique. Jul, 2008  |  Pubmed ID: 18393296

Mapping the myocardial fiber organization is important for assessing the electrical and mechanical properties of normal and diseased hearts. Current methods to determine the fiber organization have several limitations: histological sectioning mechanically distorts the tissue and is labor-intensive, while diffusion tensor imaging has low spatial resolution and requires expensive MRI scanners. Here, we utilized optical clearing, a fluorescent dye, and confocal microscopy to create three-dimensional reconstructions of the myocardial fiber organization of guinea pig and mouse hearts. We have optimized the staining and clearing procedure to allow for the nondestructive imaging of whole hearts with a thickness up to 3.5 mm. Myocardial fibers could clearly be identified at all depths in all preparations. We determined the change of fiber orientation across strips of guinea pig left ventricular wall. Our study confirms the qualitative result that there is a steady counterclockwise fiber rotation across the ventricular wall. Quantitatively, we found a total fiber rotation of 105.7+/-14.9 degrees (mean+/-standard error of the mean); this value lies within the range reported by previous studies. These results show that optical clearing, in combination with a fluorescent dye and confocal microscopy, is a practical and accurate method for determining myocardial fiber organization.

Commentary on Kim J, Fisher M & Elliott D (2006) Knowledge Levels of Korean Intensive Care Nurses Towards Brain Death and Organ Transplantation. Journal of Clinical Nursing 15, 574-580

Journal of Clinical Nursing. Jun, 2008  |  Pubmed ID: 18482147

Trends in US Emergency Department Visits for Suicide Attempts, 1992-2001

Crisis. 2008  |  Pubmed ID: 18664232

This article describes trends in suicide attempt visits to emergency departments in the United States (US). Data were obtained from the National Hospital Ambulatory Medical Care Survey using mental-health-related ICD-9-CM, E and V codes, and mental-health reasons for visit. From 1992 to 2001, mental-health-related visits increased 27.5% from 17.1 to 23.6 per 1000 (p < .001). Emergency Department (ED) visits for suicide attempt and self injury increased by 47%, from 0.8 to 1.5 visits per 1000 US population (p(trend) = .04). Suicide-attempt-related visits increased significantly among males over the decade and among females from 1992/1993 to 1998/1999. Suicide attempt visits increased in non-Hispanic whites, patients under 15 years or those between 50-69 years of age, and the privately insured. Hospitalization rates for suicide attempt-related ED visits declined from 49% to 32% between 1992 and 2001 (p = .04). Suicide attempt-related visits increased significantly in urban areas, but in rural areas suicide attempt visits stayed relatively constant, despite significant rural decreases in mental-health related visits overall. Ten-year regional increases in suicide attempt-related visits were significant for the West and Northeast only. US emergency departments have witnessed increasing rates of ED visits for suicide attempts during a decade of significant reciprocal decreases in postattempt hospitalization. Emergency departments are increasingly important sites for identifying, assessing and treating individuals with suicidal behavior.

Reconstructing Subsurface Electrical Wave Orientation from Cardiac Epi-fluorescence Recordings: Monte Carlo Versus Diffusion Approximation

Optics Express. Sep, 2008  |  Pubmed ID: 18772987

The development of voltage-sensitive dyes has revolutionized cardiac electrophysiology and made optical imaging of cardiac electrical activity possible. Photon diffusion models coupled to electrical excitation models have been successful in qualitatively predicting the shape of the optical action potential and its dependence on subsurface electrical wave orientation. However, the accuracy of the diffusion equation in the visible range, especially for thin tissue preparations, remains unclear. Here, we compare diffusion and Monte Carlo (MC) based models and we investigate the role of tissue thickness. All computational results are compared to experimental data obtained from intact guinea pig hearts. We show that the subsurface volume contributing to the epi-fluorescence signal extends deeper in the tissue when using MC models, resulting in longer optical upstroke durations which are in better agreement with experiments. The optical upstroke morphology, however, strongly correlates to the subsurface propagation direction independent of the model and is consistent with our experimental observations.

Enduring Mental Health Morbidity and Social Function Impairment in World Trade Center Rescue, Recovery, and Cleanup Workers: the Psychological Dimension of an Environmental Health Disaster

Environmental Health Perspectives. Sep, 2008  |  Pubmed ID: 18795171

The World Trade Center (WTC) attacks exposed thousands of workers to hazardous environmental conditions and psychological trauma. In 2002, to assess the health of these workers, Congress directed the National Institute for Occupational Safety and Health to establish the WTC Medical Monitoring and Treatment Program. This program has established a large cohort of WTC rescue, recovery, and cleanup workers. We previously documented extensive pulmonary dysfunction in this cohort related to toxic environmental exposures.

The Design and Evaluation of an Interprofessional Elective Course with a Cultural Competence Component

Journal of Allied Health. 2008  |  Pubmed ID: 19753404

Faculty from the Colleges of Nursing, Pharmacy, Social Work and Allied Health Sciences at the University of Cincinnati collaborated to create an elective course that focused on providing students the opportunity for interprofessional education (IPE) and cultural competence training. The course was designed around the educational principles described in the literature as most effective for IPE: interpersonal and small-group skills, face-to-face interaction, positive interdependence, individual accountability and group processing. Impact of the course was assessed using two questionnaires focusing on interdisciplinary interactions and cultural competence, respectively. The Student Attitude Questionnaire (SAQ) and Inventory for Assessing The Process of Cultural Competence Among Health Care Professionals-Revised (IAPCC-R) were administered to students prior to the start of the course and at the end of the course. The SAQ results indicated that students perceived the course to be beneficial in the following areas: interprofessional team work, professionalism, self-confidence, communication skills, and improved understanding of the roles of health professionals and the impact of each profession on patient care. The course also promoted students' progress on their personal and professional journeys toward cultural proficiency as noted by changes in their pre//post-course IAPCC-R scores. Students moved from being culturally aware to becoming culturally competent. The design and evaluation of this class can be used as a model by other universities to promote interdisciplinary team skills in health professions students and to provide additional opportunities for cultural competence training.

Spinal Cord Contusion Based on Precise Vertebral Stabilization and Tissue Displacement Measured by Combined Assessment to Discriminate Small Functional Differences

Journal of Neurotrauma. Oct, 2008  |  Pubmed ID: 18986224

Contusive spinal cord injury (SCI) is the most common type of spinal injury seen clinically. Several rat contusion SCI models have been described, and all have strengths and weaknesses with respect to sensitivity, reproducibility, and clinical relevance. We developed the Louisville Injury System Apparatus (LISA), which contains a novel spine-stabilizing device that enables precise and stable spine fixation, and is based on tissue displacement to determine the severity of injury. Injuries graded from mild to moderately severe were produced using 0.2-, 0.4-, 0.6-, 0.8-, 1.0-, and 1.2-mm spinal cord displacement in rats. Basso, Beattie, and Bresnahan (BBB) and Louisville Swim Score (LSS) could not significantly distinguish between 0.2-mm lesion severities, except those of 0.6- and 0.8-mm BBB scores, but could between 0.4-mm injury differences or if the data were grouped (0.2-0.4, 0.6-0.8, and 1.0-1.2). Transcranial magnetic motor evoked potential (tcMMEP) response amplitudes were decreased 10-fold at 0.2-mm displacement, barely detected at 0.4-mm displacement, and absent with greater displacement injuries. In contrast, somatosensory evoked potentials (SSEPs) were recorded at 0.2- and 0.4-mm displacements with normal amplitudes and latencies but were detected at lower amplitudes at 0.6-mm displacement and absent with more severe injuries. Analyzing combined BBB, tcMMEP, and SSEP results enabled statistically significant discrimination between 0.2-, 0.4-, 0.6-, and 0.8-mm displacement injuries but not the more severe injuries. Present data document that the LISA produces reliable and reproducible SCI whose parameters of injury can be adjusted to more accurately reflect clinical SCI. Moreover, multiple outcome measures are necessary to accurately detect small differences in functional deficits and/or recovery. This is of crucial importance when trying to detect functional improvement after therapeutic intervention to treat SCI.

Somatoform Dissociation in Depersonalization Disorder

Journal of Trauma & Dissociation : the Official Journal of the International Society for the Study of Dissociation (ISSD). 2008  |  Pubmed ID: 19042782

Along with psychoform dissociation, somatoform dissociation has been put forth as a core aspect of dissociative states, possibly as reliable as psychoform dissociation in the screening for dissociative disorders. The goal of this study was to investigate the prominence and correlates of somatoform dissociation in one of the major Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.) dissociative disorders, depersonalization disorder (DPD). A total of 54 adults with DPD and 47 healthy control participants free of lifetime Axis I and II disorders were administered the 20-item Somatoform Dissociation Questionnaire (SDQ) as well as the Dissociative Experiences Scale, the Cambridge Depersonalization Scale, and the Childhood Trauma Questionnaire-Short Form. Somatoform dissociation scores were statistically significantly, but clinically only modestly, elevated in the DPD as compared to the healthy control group. SDQ items significantly elevated in the DPD group were mostly perceptual in nature. Depersonalization scores were significantly correlated with somatoform dissociation in the DPD group, whereas absorption and amnesia scores were not. With respect to childhood interpersonal trauma, although emotional abuse was significantly associated with depersonalization severity, none of the 5 categories of trauma were significantly associated with somatoform dissociation in the DPD group. In conclusion, somatoform dissociation is modest in DPD, and the SDQ is a weak instrument for the screening of dissociation in this disorder, detecting only one third of the sample when using the traditional SDQ cutoff score of 30.

Toward Validation of the Diagnosis of Posttraumatic Stress Disorder

The American Journal of Psychiatry. Jan, 2009  |  Pubmed ID: 19047323

Unlike most psychiatric diagnoses, posttraumatic stress disorder (PTSD) is defined in relation to a potentially etiologic event (the traumatic "stressor criterion") that is fundamental to its conceptualization. The diagnosis of PTSD thus inherently depends on two separate but confounded processes: exposure to trauma and development of a specific pattern of symptoms that appear following the trauma. Attempts to define the range of trauma exposure inherent in the diagnosis of PTSD have generated controversy, as reflected in successive revisions of the criterion from DSM-III onward. It is still not established whether or not there are specific types of traumatic events and levels of exposure to them that are associated with a syndrome that is cohesive in clinical characteristics, biological correlates, familial patterns, and longitudinal diagnostic stability. On the other hand, the symptomatic description of PTSD is becoming more clear. Of three categories of symptoms associated with PTSD--intrusive memories, avoidance and numbing, and hyperarousal--avoidance and numbing appear to be the most specific for identification of PTSD. Research is now poised to answer questions about the relevance of traumatic events based on their relationship to symptomatic outcome. The authors recommend that future research begin with existing diagnostic criteria, testing and further refining them in accordance with the classic Robins and Guze strategy for validation of psychiatric diagnoses. In this process, diligent adherence to the criteria under examination is paramount to successful PTSD research, and changes in criteria are driven by empirical data rather than theory. Collaborations among trauma research biologists, epidemiologists, and nosologists to map the correspondence between the clinical and biological indicators of psychopathology are necessary to advance validation and further understanding of PTSD.

A Comparative Analysis of Multi-level Computer-assisted Decision Making Systems for Traumatic Injuries

BMC Medical Informatics and Decision Making. 2009  |  Pubmed ID: 19144188

This paper focuses on the creation of a predictive computer-assisted decision making system for traumatic injury using machine learning algorithms. Trauma experts must make several difficult decisions based on a large number of patient attributes, usually in a short period of time. The aim is to compare the existing machine learning methods available for medical informatics, and develop reliable, rule-based computer-assisted decision-making systems that provide recommendations for the course of treatment for new patients, based on previously seen cases in trauma databases. Datasets of traumatic brain injury (TBI) patients are used to train and test the decision making algorithm. The work is also applicable to patients with traumatic pelvic injuries.

Swimming As a Model of Task-specific Locomotor Retraining After Spinal Cord Injury in the Rat

Neurorehabilitation and Neural Repair. Jul-Aug, 2009  |  Pubmed ID: 19270266

The authors have shown that rats can be retrained to swim after a moderately severe thoracic spinal cord contusion. They also found that improvements in body position and hindlimb activity occurred rapidly over the first 2 weeks of training, reaching a plateau by week 4. Overground walking was not influenced by swim training, suggesting that swimming may be a task-specific model of locomotor retraining.

Epidemiological Trends in Psychosis-related Emergency Department Visits in the United States, 1992-2001

Schizophrenia Research. May, 2009  |  Pubmed ID: 19303744

Mental health visits represented an increasing fraction of all Emergency Department (ED) visits in the U.S. between 1992 and 2001. This study used the National Hospital Ambulatory Medical Care Survey, a 4-staged probability sample of ED visits from geographically diverse hospitals around the U.S., to assess the contribution of all psychosis-related visits to this overall trend. Unlike other mental-health-related ED visits, the rate of psychosis-related visits did not increase. This lack of change is notable in the context of dramatic changes in both healthcare financing and antipsychotic prescribing practices during this period. There was an unexpected decrease in Medicare-funded psychosis-related ED visits at a time of increasing Medicare enrollment overall. An important demographic trend over this decade was the increasing urbanization of psychosis-related ED visits coincident with a relative decrement in such visits within rural areas.

Swim Training Initiated Acutely After Spinal Cord Injury is Ineffective and Induces Extravasation in and Around the Epicenter

Journal of Neurotrauma. Jul, 2009  |  Pubmed ID: 19331515

Activity-based rehabilitation is a promising strategy for improving functional recovery following spinal cord injury (SCI). While results from both clinical and animal studies have shown that a variety of approaches can be effective, debate still exists regarding the optimal post-injury period to apply rehabilitation. We recently demonstrated that rats with moderately severe thoracic contusive SCI can be re-trained to swim when training is initiated 2 weeks after injury and that swim training had no effect on the recovery of overground locomotion. We concluded that swim training is a task-specific model of post-SCI activity-based rehabilitation. In the present study, we ask if re-training initiated acutely is more or less effective than when initiated at 2 weeks post-injury. Using the Louisville Swim Scale, an 18-point swimming assessment, supplemented by kinematic assessment of hindlimb movement during swimming, we report that acute re-training is less effective than training initiated at 2 weeks. Using the bioluminescent protein luciferase as a blood-borne macromolecular marker, we also show a significant increase in extravasation in and around the site of SCI following only 8 min of swimming at 3 days post-injury. Taken together, these results suggest that acute re-training in a rat model of SCI may compromise rehabilitation efforts via mechanisms that may involve one or more secondary injury cascades, including acute spinal microvascular dysfunction.

Genetic Predictors of Response to Antidepressants in the GENDEP Project

The Pharmacogenomics Journal. Aug, 2009  |  Pubmed ID: 19365399

The objective of the Genome-based Therapeutic Drugs for Depression study is to investigate the function of variations in genes encoding key proteins in serotonin, norepinephrine, neurotrophic and glucocorticoid signaling in determining the response to serotonin-reuptake-inhibiting and norepinephrine-reuptake-inhibiting antidepressants. A total of 116 single nucleotide polymorphisms in 10 candidate genes were genotyped in 760 adult patients with moderate-to-severe depression, treated with escitalopram (a serotonin reuptake inhibitor) or nortriptyline (a norepinephrine reuptake inhibitor) for 12 weeks in an open-label part-randomized multicenter study. The effect of genetic variants on change in depressive symptoms was evaluated using mixed linear models. Several variants in a serotonin receptor gene (HTR2A) predicted response to escitalopram with one marker (rs9316233) explaining 1.1% of variance (P=0.0016). Variants in the norepinephrine transporter gene (SLC6A2) predicted response to nortriptyline, and variants in the glucocorticoid receptor gene (NR3C1) predicted response to both antidepressants. Two HTR2A markers remained significant after hypothesis-wide correction for multiple testing. A false discovery rate of 0.106 for the three strongest associations indicated that the multiple findings are unlikely to be false positives. The pattern of associations indicated a degree of specificity with variants in genes encoding proteins in serotonin signaling influencing response to the serotonin-reuptake-inhibiting escitalopram, genes encoding proteins in norepinephrine signaling influencing response to the norepinephrine-reuptake-inhibiting nortriptyline and a common pathway gene influencing response to both antidepressants. The single marker associations explained only a small proportion of variance in response to antidepressants, indicating a need for a multivariate approach to prediction.

Assessing the Potential Impact of Salmonella Vaccines in an Endemically Infected Dairy Herd

Journal of Theoretical Biology. Aug, 2009  |  Pubmed ID: 19446567

Salmonella spp. in cattle contribute to bacterial foodborne disease for humans. Reduction of Salmonella prevalence in herds is important to prevent human Salmonella infections. Typical control measures are culling of infectious animals, vaccination, and improved hygiene management. Vaccines have been developed for controlling Salmonella transmission in dairy herds; however, these vaccines are imperfect and a variety of vaccine effects on susceptibility, infectiousness, Salmonella shedding level, and duration of infectious period were reported. To assess the potential impact of imperfect Salmonella vaccines on prevalence over time and the eradication criterion, we developed a deterministic compartmental model with both replacement (cohort) and lifetime (continuous) vaccination strategies, and applied it to a Salmonella Cerro infection in a dairy farm. To understand the uncertainty of prevalence and identify key model parameters, global parameter uncertainty and sensitivity analyses were performed. The results show that imperfect Salmonella vaccines reduce the prevalence of Salmonella Cerro. Among three vaccine effects that were being considered, decreasing the length of the infectious period is most effective in reducing the endemic prevalence. Analyses of contour lines of prevalence or the critical reproduction ratio illustrate that, reducing prevalence to a certain level or zero can be achieved by choosing vaccines that have either a single vaccine effect at relatively high effectiveness, or two or more vaccine effects at relatively low effectiveness. Parameter sensitivity analysis suggests that effective control measures through applying Salmonella vaccines should be adjusted at different stages of infection. In addition, lifetime (continuous) vaccination is more effective than replacement (cohort) vaccination. The potential application of the developed vaccination model to other Salmonella serotypes related to foodborne diseases was also discussed. The presented study may be used as a tool for guiding the development of Salmonella vaccines.

Moderation of Antidepressant Response by the Serotonin Transporter Gene

The British Journal of Psychiatry : the Journal of Mental Science. Jul, 2009  |  Pubmed ID: 19567893

There have been conflicting reports on whether the length polymorphism in the promoter of the serotonin transporter gene (5-HTTLPR) moderates the antidepressant effects of selective serotonin reuptake inhibitors (SSRIs). We hypothesised that the pharmacogenetic effect of 5-HTTLPR is modulated by gender, age and other variants in the serotonin transporter gene.

Alexithymia, Absorption, and Cognitive Failures in Depersonalization Disorder: a Comparison to Posttraumatic Stress Disorder and Healthy Volunteers

The Journal of Nervous and Mental Disease. Jul, 2009  |  Pubmed ID: 19597356

Alexithymia, absorption, and cognitive failures are traits that have been implicated in dissociative psychopathology. Forty-six participants with depersonalization disorder (DPD), 21 with posttraumatic stress disorder, and 35 healthy controls completed measures of dissociation, alexithymia, absorption, cognitive failures, and childhood trauma. The DPD and posttraumatic stress disorder groups had significantly and comparably elevated absorption and cognitive failures scores. Only the DPD group had significantly elevated alexithymia scores, specifically in "difficulty identifying feelings." Regression analyses revealed that "alexithymia-difficulty identifying feelings" was predictive of both DPD diagnosis and depersonalization scores. In contrast, amnesia scores were predicted by childhood trauma and absorption. In conclusion, the link between depersonalization and alexithymia appeared to be specific rather than broadly related to early trauma or to trauma-spectrum psychopathology.

Genetic Predictors of Increase in Suicidal Ideation During Antidepressant Treatment in the GENDEP Project

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. Nov, 2009  |  Pubmed ID: 19641488

The aim of this study was to investigate genetic predictors of an increase in suicidal ideation during treatment with a selective serotonin reuptake inhibitor or a tricyclic antidepressant. A total of 796 adult patients with major depressive disorder who were treated with a flexible dosage of escitalopram or nortriptyline in Genome-based Therapeutic Drugs for Depression (GENDEP) were included in the sample and provided data on suicidal ideation. Nine candidate genes involved in neurotrophic, serotonergic, and noradrenergic pathways were selected based on previous association studies with suicidal ideation or behavior. Using a logistic regression model, 123 polymorphisms in these genes were compared between subjects with an increase in suicidal ideation and those without any increase in suicidal ideation. Polymorphisms in BDNF, the gene encoding the brain-derived neurotrophic factor, were significantly associated with an increase in suicidal ideation. The strongest association was observed for rs962369 in BDNF (p=0.0015). Moreover, a significant interaction was found between variants in BDNF and NTRK2, the gene encoding the BNDF receptor (p=0.0003). Among men taking nortriptyline, suicidality was also associated with rs11195419 SNP in the alpha(2A)-adrenergic receptor gene (ADRA2A) (p=0.007). The associations observed with polymorphisms in BDNF suggest the involvement of the neurotrophic system in vulnerability to suicidality. Epistasis between BDNF and NTRK2 suggests that genetic variations in the two genes are involved in the same causal mechanisms leading to suicidality during antidepressant treatment. Among men, genetic variation in noradrenergic signaling may interact with norepinephrine reuptake-inhibiting antidepressants, thereby contributing to suicidality.

Weight Lifting in Women with Breast-cancer-related Lymphedema

The New England Journal of Medicine. Aug, 2009  |  Pubmed ID: 19675330

Weight lifting has generally been proscribed for women with breast-cancer-related lymphedema, preventing them from obtaining the well-established health benefits of weight lifting, including increases in bone density.

A Hierarchical Method Based on Active Shape Models and Directed Hough Transform for Segmentation of Noisy Biomedical Images; Application in Segmentation of Pelvic X-ray Images

BMC Medical Informatics and Decision Making. 2009  |  Pubmed ID: 19891796

Traumatic pelvic injuries are often associated with severe, life-threatening hemorrhage, and immediate medical treatment is therefore vital. However, patient prognosis depends heavily on the type, location and severity of the bone fracture, and the complexity of the pelvic structure presents diagnostic challenges. Automated fracture detection from initial patient X-ray images can assist physicians in rapid diagnosis and treatment, and a first and crucial step of such a method is to segment key bone structures within the pelvis; these structures can then be analyzed for specific fracture characteristics. Active Shape Model has been applied for this task in other bone structures but requires manual initialization by the user. This paper describes a algorithm for automatic initialization and segmentation of key pelvic structures - the iliac crests, pelvic ring, left and right pubis and femurs - using a hierarchical approach that combines directed Hough transform and Active Shape Models.

Automated Ventricular Systems Segmentation in Brain CT Images by Combining Low-level Segmentation and High-level Template Matching

BMC Medical Informatics and Decision Making. 2009  |  Pubmed ID: 19891798

Accurate analysis of CT brain scans is vital for diagnosis and treatment of Traumatic Brain Injuries (TBI). Automatic processing of these CT brain scans could speed up the decision making process, lower the cost of healthcare, and reduce the chance of human error. In this paper, we focus on automatic processing of CT brain images to segment and identify the ventricular systems. The segmentation of ventricles provides quantitative measures on the changes of ventricles in the brain that form vital diagnosis information.

Family Alert: Implementing Direct Family Activation of a Pediatric Rapid Response Team

Joint Commission Journal on Quality and Patient Safety / Joint Commission Resources. Nov, 2009  |  Pubmed ID: 19947334

A hospital's "no false alams" policy has been validated by staff's and families' appropriate activation of the rapid response team.

Advancing Paternal Age is Associated with Deficits in Social and Exploratory Behaviors in the Offspring: a Mouse Model

PloS One. 2009  |  Pubmed ID: 20041141

Accumulating evidence from epidemiological research has demonstrated an association between advanced paternal age and risk for several psychiatric disorders including autism, schizophrenia and early-onset bipolar disorder. In order to establish causality, this study used an animal model to investigate the effects of advanced paternal age on behavioural deficits in the offspring.

A Stochastic Model to Assess the Risk of Introduction of Bovine Viral Diarrhea Virus to Beef Cow-calf Herds

Preventive Veterinary Medicine. Feb, 2009  |  Pubmed ID: 18838184

A spreadsheet model using Monte Carlo simulation was designed to evaluate the introduction of bovine viral diarrhea virus (BVDV) to cow-calf farms and the effect of different testing strategies. Risks were modeled to include imports to the cow-calf herd and stocker calves imported to adjacent pastures. The number of persistently infected (PI) animals imported and the probability of BVDV introduction were monitored for three herd sizes, four import profiles, and six testing strategies. Importing stockers and importing pregnant heifers were the biggest risks for introduction of BVDV. Testing for PI animals in stockers decreased the risk they posed, but testing pregnant heifers was not sufficient to decrease risk unless their calves were also tested. Test sensitivity was more influential than PI prevalence on the likelihood of BVDV introduction, when all imports were tested. This model predicts the risk of BVDV introduction for individual herds based on management decisions, and should prove to be a useful tool to help cow-calf producers in controlling the risk of importing BVDV to a naïve herd.

Differentiating Effortful and Noneffortful Swallowing with a Neck Force Transducer: Implications for the Development of a Clinical Feedback System

Dysphagia. Mar, 2009  |  Pubmed ID: 18373122

This study sought to determine whether effortful saliva swallows could be differentiated from habitual, noneffortful saliva swallows on the basis of swallow-related changes in neck circumference in humans. Gender differences in swallow-related neck circumference were examined as a secondary question. Twenty-seven healthy adults (14 females; mean age = 26.6 years, SD = 3.9 years) participated in two experimental runs (run duration = 10 min) during which they produced single trials of three visually cued tasks in random order: effortful saliva swallowing, saliva swallowing, and a control task involving repetitive apposition of the dominant thumb and index finger. Neck and ribcage circumference were simultaneously collected from the output of force transducers positioned around the neck and ribcage, respectively. The primary outcome variables were the positive and negative voltage peak amplitudes associated with changes in neck circumference during single-swallow trials. Effects of the swallowing task on positive and negative voltage peaks were examined with separate two-way analysis of variance procedures. Results indicated that both positive (F = 6.49, p < 0.05) and negative (F = 12.05, p

Effectiveness of Predator Removal for Enhancing Bird Populations

Conservation Biology : the Journal of the Society for Conservation Biology. Jun, 2010  |  Pubmed ID: 20067492

Predation pressure on vulnerable bird species has made predator control an important issue for international nature conservation. Predator removal by culling or translocation is controversial, expensive, and time-consuming, and results are often temporary. Thus, it is important to assess its effectiveness from all available evidence. We used explicit systematic review methodology to determine the impact of predator removal on four measurable responses in birds: breeding performance (hatching success and fledging success) and population size (breeding and postbreeding). We used meta-analysis to summarize results from 83 predator removal studies from six continents. We also investigated whether characteristics of the prey, predator species, location, and study methodology explained heterogeneity in effect sizes. Removing predators increased hatching success, fledging success, and breeding populations. Removing all predator species achieved a significantly larger increase in breeding population than removing only a subset. Postbreeding population size was not improved on islands, or overall, but did increase on mainlands. Heterogeneity in effect sizes for the four population parameters was not explained by whether predators were native or introduced; prey were declining, migratory, or game species; or by the study methodology. Effect sizes for fledging success were smaller for ground-nesting birds than those that nest elsewhere, but the difference was not significant. We conclude that current evidence indicates that predator removal is an effective strategy for the conservation of vulnerable bird populations. Nevertheless, the ethical and practical problems associated with predator removal may lead managers to favor alternative, nonlethal solutions. Research is needed to provide and synthesize data to determine whether these are effective management practices for future policies on bird conservation.

A Two-tube Combined TaqMan/SYBR Green Assay to Identify Mycobacteria and Detect Single Global Lineage-defining Polymorphisms in Mycobacterium Tuberculosis

The Journal of Molecular Diagnostics : JMD. Mar, 2010  |  Pubmed ID: 20093392

We have developed a novel real-time PCR assay to identify and perform preliminary genotyping of mycobacteria in a manner tailored to our local service. Within a single thermocycler run, mycobacterial 16S rDNA and the Mycobacterium tuberculosis global lineage-defining RD750 polymorphism are targeted in separate reaction tubes, each of which includes both TaqMan and SYBR Green chemistries. The results of this 16S-RD assay differentiate M. tuberculosis complex (MTBC) from nontuberculous mycobacteria (NTM) and recognize whether or not MTBC isolates belong to the East African-Indian lineage, the single most frequently isolated global MTBC lineage in our service. If required, NTM amplicons may be sequenced to provide more specific identities. We report the technical performance of this assay on 88 mycobacteria-positive cultures and discuss its use in the initial management of mycobacterial infections. The 16S-RD assay correctly identified all 70 MTBC-positive cultures and 17 NTM-positive cultures while contemporaneously recognizing 26 MTBC isolates as within and 44 outside the East African-Indian lineage. In artificial samples, the combined assay also showed limited potential to detect mixed mycobacterial infections (MTBC/NTM) and tuberculosis infections involving more than one global MTBC lineage. The approach we have established can be readily tailored to targets of particular value for any mycobacterial diagnostic service, thereby optimizing the value of the results for local clinical and public health management of mycobacterial infections.

The Relationship Between Visual-spatial and Auditory-verbal Working Memory Span in Senegalese and Ugandan Children

PloS One. 2010  |  Pubmed ID: 20111706

Using the Kaufman Assessment Battery for Children (K-ABC) Conant et al. (1999) observed that visual and auditory working memory (WM) span were independent in both younger and older children from DR Congo, but related in older American children and in Lao children. The present study evaluated whether visual and auditory WM span were independent in Ugandan and Senegalese children.

Allelic Skewing of DNA Methylation is Widespread Across the Genome

American Journal of Human Genetics. Feb, 2010  |  Pubmed ID: 20159110

DNA methylation is assumed to be complementary on both alleles across the genome, although there are exceptions, notably in regions subject to genomic imprinting. We present a genome-wide survey of the degree of allelic skewing of DNA methylation with the aim of identifying previously unreported differentially methylated regions (DMRs) associated primarily with genomic imprinting or DNA sequence variation acting in cis. We used SNP microarrays to quantitatively assess allele-specific DNA methylation (ASM) in amplicons covering 7.6% of the human genome following cleavage with a cocktail of methylation-sensitive restriction enzymes (MSREs). Selected findings were verified using bisulfite-mapping and gene-expression analyses, subsequently tested in a second tissue from the same individuals, and replicated in DNA obtained from 30 parent-child trios. Our approach detected clear examples of ASM in the vicinity of known imprinted loci, highlighting the validity of the method. In total, 2,704 (1.5%) of our 183,605 informative and stringently filtered SNPs demonstrate an average relative allele score (RAS) change > or =0.10 following MSRE digestion. In agreement with previous reports, the majority of ASM ( approximately 90%) appears to be cis in nature, and several examples of tissue-specific ASM were identified. Our data show that ASM is a widespread phenomenon, with >35,000 such sites potentially occurring across the genome, and that a spectrum of ASM is likely, with heterogeneity between individuals and across tissues. These findings impact our understanding about the origin of individual phenotypic differences and have implications for genetic studies of complex disease.

A Stochastic Risk-analysis Model for the Spread of Bovine Viral Diarrhea Virus After Introduction to Naïve Cow-calf Herds

Preventive Veterinary Medicine. Jun, 2010  |  Pubmed ID: 20304508

A stochastic SIR model was developed to simulate the spread of bovine viral diarrhea virus (BVDV) through a cow-calf herd and estimate the effect of the virus on the herd, including abortions, calf morbidity, and calf mortality. The model was applied with three herd sizes (400, 100, and 50 head) and four control strategies (no intervention, vaccination of breeding stock, testing all calves pre-breeding and culling of persistently infected calves, and both vaccination of adults and testing and culling of calves). When no control strategy was implemented the BVDV reproductive rate (R(E-PI)) of persistently infected calves (PI's), vertical transmission rate from cows to calves and the mortality rate of PI's were influential in the number of PI's produced in the herd. When a vaccination program alone was implemented the vaccine efficacy was influential in the number of PI's produced in the herd. All control strategies decreased the effects of BVDV on the herd at both 1 and 10 years compared to no control. In most cases the combination of adult vaccination and calf testing and culling resulted in the largest decrease in the both the median and 95% prediction interval for the range of effects from BVDV. The effect of control strategies was most apparent in the 400 head herds. All control strategies increased the probability of early clearance of PI's from the herd for all herd sizes. Fifty and 100 head herds cleared infection by 4 and 9 years respectively even without a control program but 400 head herds did not always clear infection after 10 years unless a testing program was implemented. The model presented is valuable in assessing the effect of control strategies and the effects of disease parameters on BVDV spread in beef herds.

Stochastic Simulations of a Multi-group Compartmental Model for Johne's Disease on US Dairy Herds with Test-based Culling Intervention

Journal of Theoretical Biology. Jun, 2010  |  Pubmed ID: 20347851

Infection elimination may be an important goal of control programs. Only in stochastic infection models can true infection elimination be observed as a fadeout. The phenomena of fadeout and variable prevalence are important in understanding the transmission dynamics of infectious diseases and these phenomena are essential to evaluate the effectiveness of control measures. To investigate the stochastic dynamics of Mycobacterium avium subsp. paratuberculosis (MAP) infection on US dairy herds with test-based culling intervention, we developed a multi-group stochastic compartmental model (a continuous time Markov chain model) with both horizontal and vertical transmission. The stochastic model predicted fadeout and within-herd prevalence to have a large variance. Although test-based culling intervention generally decreased prevalence over time, it took longer than desired by producers to eliminate the endemic MAP infection from a herd. Uncertainty analysis showed that, using annual culture test and culling of only high shedders or culling of both low and high shedders with a 12-month delay in culling of low shedders, MAP infection persisted in many herds beyond 20 years. While using semi-annual culture test and culling of low and high shedders with a 6-month delay in culling of low shedders, MAP infection in many herds would be extinct within 20 years. Sensitivity analysis of the cumulative density function of fadeout suggested that combining test-based culling intervention and reduction of transmission rates through improved management between susceptible calves and shedding animals may be more effective than either alone in eliminating endemic MAP infection. We also discussed the effects of other factors such as herd size, heifer replacement, and adult cow infection on the probability of fadeout.

Modulation of UvrD Helicase Activity by Covalent DNA-protein Cross-links

The Journal of Biological Chemistry. Jul, 2010  |  Pubmed ID: 20444702

UvrD (DNA helicase II) has been implicated in DNA replication, DNA recombination, nucleotide excision repair, and methyl-directed mismatch repair. The enzymatic function of UvrD is to translocate along a DNA strand in a 3' to 5' direction and unwind duplex DNA utilizing a DNA-dependent ATPase activity. In addition, UvrD interacts with many other proteins involved in the above processes and is hypothesized to facilitate protein turnover, thus promoting further DNA processing. Although UvrD interactions with proteins bound to DNA have significant biological implications, the effects of covalent DNA-protein cross-links on UvrD helicase activity have not been characterized. Herein, we demonstrate that UvrD-catalyzed strand separation was inhibited on a DNA strand to which a 16-kDa protein was covalently bound. Our sequestration studies suggest that the inhibition of UvrD activity is most likely due to a translocation block and not helicase sequestration on the cross-link-containing DNA substrate. In contrast, no inhibition of UvrD-catalyzed strand separation was apparent when the protein was linked to the complementary strand. The latter result is surprising given the earlier observations that the DNA in this covalent complex is severely bent ( approximately 70 degrees ), with both DNA strands making multiple contacts with the cross-linked protein. In addition, UvrD was shown to be required for replication of plasmid DNAs containing covalent DNA-protein complexes. Combined, these data suggest a critical role for UvrD in the processing of DNA-protein cross-links.

Services Provided by Volunteer Psychiatrists After 9/11 at the New York City Family Assistance Center: September 12-November 20, 2001

Journal of Psychiatric Practice. May, 2010  |  Pubmed ID: 20485109

To characterize the experience of volunteer disaster psychiatrists who provided pro bono psychiatric services to 9/11 survivors in New York City, from September 12, 2001 to November 20, 2001.

Weight Lifting in Patients with Lower-extremity Lymphedema Secondary to Cancer: a Pilot and Feasibility Study

Archives of Physical Medicine and Rehabilitation. Jul, 2010  |  Pubmed ID: 20599045

To assess the feasibility of recruiting and retaining cancer survivors with lower-limb lymphedema into an exercise intervention study. To develop preliminary estimates regarding the safety and efficacy of this intervention. We hypothesized that progressive weight training would not exacerbate leg swelling and that the intervention would improve functional mobility and quality of life.

Multicenter Evaluation of the BD Max GBS Assay for Detection of Group B Streptococci in Prenatal Vaginal and Rectal Screening Swab Specimens from Pregnant Women

Journal of Clinical Microbiology. Nov, 2010  |  Pubmed ID: 20826650

A new integrated extraction and real-time PCR-based system for the detection of group B streptococci in antepartum screening samples enriched in Lim broth was compared to the CDC-recommended culture method. The BD Max GBS assay exhibited acceptable sensitivity (95%) and specificity (96.7%) compared to those of the culture method in this multisite evaluation.

Native Functions of the Androgen Receptor Are Essential to Pathogenesis in a Drosophila Model of Spinobulbar Muscular Atrophy

Neuron. Sep, 2010  |  Pubmed ID: 20869592

Spinobulbar muscular atrophy (SBMA) is a neurodegenerative disease caused by expansion of a polyglutamine tract in the androgen receptor (AR). This mutation confers toxic function to AR through unknown mechanisms. Mutant AR toxicity requires binding of its hormone ligand, suggesting that pathogenesis involves ligand-induced changes in AR. However, whether toxicity is mediated by native AR function or a novel AR function is unknown. We systematically investigated events downstream of ligand-dependent AR activation in a Drosophila model of SBMA. We show that nuclear translocation of AR is necessary, but not sufficient, for toxicity and that DNA binding by AR is necessary for toxicity. Mutagenesis studies demonstrated that a functional AF-2 domain is essential for toxicity, a finding corroborated by a genetic screen that identified AF-2 interactors as dominant modifiers of degeneration. These findings indicate that SBMA pathogenesis is mediated by misappropriation of native protein function, a mechanism that may apply broadly to polyglutamine diseases.

Weight Lifting for Women at Risk for Breast Cancer-related Lymphedema: a Randomized Trial

JAMA : the Journal of the American Medical Association. Dec, 2010  |  Pubmed ID: 21148134

Clinical guidelines for breast cancer survivors without lymphedema advise against upper body exercise, preventing them from obtaining established health benefits of weight lifting.

The GAS41-PP2Cbeta Complex Dephosphorylates P53 at Serine 366 and Regulates Its Stability

The Journal of Biological Chemistry. Apr, 2011  |  Pubmed ID: 21317290

The p53 tumor suppressor is principally regulated by post-translational modifications and proteasome-dependent degradation. Various kinases have been shown to phosphorylate p53, but little is known about the counteracting phosphatases. We demonstrate here that the newly identified complex GAS41-PP2Cβ, and not PP2Cβ alone, is specifically required for dephosphorylation of serine 366 on p53. Ectopic expression of GAS41 and PP2Cβ reduces UV radiation-induced p53 up-regulation, thereby increasing the cell survival upon genotoxic DNA damage. To our knowledge, the GAS41-PP2Cβ complex is the first example in which substrate specificity of a PP2C family member is controlled by an associated regulatory subunit. Because GAS41 is frequently amplified in human gliomas, our finding illustrates a novel oncogenic mechanism of GAS41 by p53 dephosphorylation.

A Drosophila Model of FUS-related Neurodegeneration Reveals Genetic Interaction Between FUS and TDP-43

Human Molecular Genetics. Jul, 2011  |  Pubmed ID: 21487023

Amyotrophic lateral sclerosis (ALS) is a late-onset neurodegenerative disorder characterized by the loss of motor neurons. Fused in sarcoma/translated in liposarcoma (FUS/TLS) and TAR DNA-binding protein (TDP)-43 are DNA/RNA-binding proteins found to be mutated in sporadic and familial forms of ALS. Ectopic expression of human ALS-causing FUS/TLS mutations in Drosophila caused an accumulation of ubiquitinated proteins, neurodegeneration, larval-crawling defect and early lethality. Mutant FUS/TLS localized to both the cytoplasm and nucleus, whereas wild-type FUS/TLS localized only to the nucleus, suggesting that the cytoplasmic localization of FUS/TLS is required for toxicity. Furthermore, we found that deletion of the nuclear export signal strongly suppressed toxicity, suggesting that cytoplasmic localization is necessary for neurodegeneration. Interestingly, we observed that FUS/TLS genetically interacts with TDP-43 in a mutation-dependent fashion to cause neurodegeneration in vivo. In summary, we demonstrate that ALS-associated mutations in FUS/TLS cause adult-onset neurodegeneration via a gain-of-toxicity mechanism that involves redistribution of the protein from the nucleus to the cytoplasm and is likely to involve an interaction with TDP-43.

The Effect of Cardiac Sympathetic Denervation Through Bilateral Stellate Ganglionectomy on Electrical Properties of the Heart

American Journal of Physiology. Heart and Circulatory Physiology. Jul, 2011  |  Pubmed ID: 21498778

The role of the cardiac sympathetic nerve activity in various cardiac diseases is typically evaluated using β-adrenergic receptor antagonists. However, these antagonists induce global denervation effects not only in the cardiovascular system, but also in the brain and kidney. The objective of this study was to detect the electrophysiological property changes due to 8 days of cardiac sympathetic denervation and investigate the possible mechanisms underlying these changes using a more cardiac-specific bilateral stellate ganglionectomy (SGX) rat model. High-resolution optical mapping using a voltage-sensitive dye was performed in isolated Langendorff-perfused sham and SGX hearts, which were paced at progressively reduced basic cycle lengths under several different conditions: control, pretreatment with isoproterenol, and administration of atenolol and esmolol. Several electrophysiological parameters were recorded during periodic pacing and ventricular fibrillation (VF). Our results demonstrate that cardiac sympathetic denervation by bilateral SGX shortens action potential duration (APD) and flattens the APD restitution curve, but does not significantly affect spatial dispersion of APD. We found that, although the vulnerability of sham and SGX hearts to VF is similar, the dynamics of VF are different. The maximum dominant frequency is higher, and the spatial distribution of VF is more complex in the SGX heart, resulting in different mechanisms of VF. We demonstrated that β(1)-adrenergic receptors are downregulated in the SGX compared with sham hearts. In addition, our data suggest that the mechanism of cardiac sympathetic denervation by SGX surgery is more similar to the administration of β-blocker esmolol than atenolol.

LPS Impairs Phospholipid Synthesis by Triggering Beta-transducin Repeat-containing Protein (beta-TrCP)-mediated Polyubiquitination and Degradation of the Surfactant Enzyme Acyl-CoA:lysophosphatidylcholine Acyltransferase I (LPCAT1)

The Journal of Biological Chemistry. Jan, 2011  |  Pubmed ID: 21068446

Acyl-CoA:lysophosphatidylcholine acyltransferase 1 (LPCAT1) is a relatively newly described and yet indispensable enzyme needed for generation of the bioactive surfactant phospholipid, dipalmitoylphosphatidylcholine (DPPtdCho). Here, we show that lipopolysaccharide (LPS) causes LPCAT1 degradation using the Skp1-Cullin-F-box ubiquitin E3 ligase component, β-transducin repeat-containing protein (β-TrCP), that polyubiquitinates LPCAT1, thereby targeting the enzyme for proteasomal degradation. LPCAT1 was identified as a phosphoenzyme as Ser(178) within a phosphodegron was identified as a putative molecular recognition site for glycogen synthase kinase-3β (GSK-3β) phosphorylation that recruits β-TrCP docking within the enzyme. β-TrCP ubiquitinates LPCAT1 at an acceptor site (Lys(221)), as substitution of Lys(221) with Arg abrogated LPCAT1 polyubiquitination. LPS profoundly reduced immunoreactive LPCAT1 levels and impaired lung surfactant mechanics, effects that were overcome by siRNA to β-TrCP and GSK-3β or LPCAT1 gene transfer, respectively. Thus, LPS appears to destabilize the LPCAT1 protein by GSK-3β-mediated phosphorylation within a canonical phosphodegron for β-TrCP docking and site-specific ubiquitination. LPCAT1 is the first lipogenic substrate for β-TrCP, and the results suggest that modulation of the GSK-3β-SCFβ(TrCP) E3 ligase effector pathway might be a unique strategy to optimize dipalmitoylphosphatidylcholine levels in sepsis.

FruitZotic: a Sensory Approach to Introducing Preschoolers to Fresh Exotic Fruits at Head Start Locations in Western Massachusetts

Journal of Nutrition Education and Behavior. May-Jun, 2011  |  Pubmed ID: 21550535

Acyl-CoA:lysophosphatidylcholine Acyltransferase I (Lpcat1) Catalyzes Histone Protein O-palmitoylation to Regulate MRNA Synthesis

The Journal of Biological Chemistry. Aug, 2011  |  Pubmed ID: 21685381

The enzyme acyl-CoA:lysophosphatidylcholine acyltransferase (Lpcat1) is a critical cytosolic enzyme needed for lung surfactant synthesis that catalyzes an acyltransferase reaction by adding a palmitate to the sn-2 position of lysophospholipids. Here we report that histone H4 protein is subject to palmitoylation catalyzed by Lpcat1 in a calcium-regulated manner. Cytosolic Lpcat1 was observed to shift into the nucleus in lung epithelia in response to exogenous Ca(2+). Nuclear Lpcat1 colocalizes with and binds to histone H4, where it catalyzes histone H4 palmitoylation. Mutagenesis studies demonstrated that Ser(47) within histone H4 serves as a putative acceptor site, indicative of Lpcat1-mediated O-palmitoylation. Lpcat1 knockdown or expression of a histone H4 Ser(47A) mutant protein in cells decreased cellular mRNA synthesis. These findings provide the first evidence of a protein substrate for Lpcat1 and reveal that histone lipidation may occur through its O-palmitoylation as a novel post-translational modification. This epigenetic modification regulates global gene transcriptional activity.

Modeling Binge-like Ethanol Drinking by Peri-adolescent and Adult P Rats

Pharmacology, Biochemistry, and Behavior. Nov, 2011  |  Pubmed ID: 21824488

Alcohol binge-drinking, especially among adolescents and young adults, is a serious public health concern. The present study examined ethanol binge-like drinking by peri-adolescent [postnatal days (PNDs 30-72)] and adult (PNDs 90-132) alcohol-preferring (P) rats with a drinking-in-the-dark-multiple-scheduled-access (DID-MSA) procedure used by our laboratory. Male and female P rats were provided concurrent access to 15% and 30% ethanol for three 1-h sessions across the dark cycle 5 days/week. For the 1st week, adolescent and adult female P rats consumed 3.4 and 1.6g/kg of ethanol, respectively, during the 1st hour of access, whereas for male rats the values were 3.5 and 1.1g/kg of ethanol, respectively. Adult intakes increased to ~2.0 g/kg/h and adolescent intakes decreased to ~2.5 g/kg/h across the 6 weeks of ethanol access. The daily ethanol intake of adult DID-MSA rats approximated or modestly exceeded that seen in continuous access (CA) rats or the selection criterion for P rats (≥5 g/kg/day). However, in general, the daily ethanol intake of DID-MSA peri-adolescent rats significantly exceeded that of their CA counterparts. BELs were assessed at 15-min intervals across the 3rd hour of access during the 4th week. Ethanol intake was 1.7 g/kg vs. 2.7 g/kg and BELs were 57 mg% vs. 100mg% at 15- and 60-min, respectively. Intoxication induced by DID-MSA in female P rats was assessed during the 1st vs. 4th week of ethanol access. Level of impairment did not differ between the 2 weeks (106 vs. 97 s latency to fall, 120 s criterion) and was significant (vs. naïve controls) only during the 4th week. Overall, these findings support the use of the DID-MSA procedure in rats, and underscore the presence of age- and sex-dependent effects mediating ethanol binge-like drinking in P rats.

Communication: the Key to Effective Interdisciplinary Collaboration in the Care of a Child with Complex Rehabilitation Needs

Rehabilitation Nursing : the Official Journal of the Association of Rehabilitation Nurses. Sep-Oct, 2011  |  Pubmed ID: 21882794

Healthcare providers have the unique opportunity to provide care and treatment to patients with complex medical needs. They learn early in their careers that the care they provide doesn't just include the patient. Communication is essential across the continuum and involves multiple providers and the family. An interdisciplinary team facilitates a comprehensive plan for recovery and treatment. This case study centers on the interdisciplinary approach to the rehabilitation continuum of care across the spectrum and its effects on patient outcomes.

Trauma Exposure and Posttraumatic Stress Disorder Among Employees of New York City Companies Affected by the September 11, 2001 Attacks on the World Trade Center

Disaster Medicine and Public Health Preparedness. Sep, 2011  |  Pubmed ID: 21900416

Several studies have provided prevalence estimates of posttraumatic stress disorder (PTSD) related to the September 11, 2001 (9/11) attacks in broadly affected populations, although without sufficiently addressing qualifying exposures required for assessing PTSD and estimating its prevalence. A premise that people throughout the New York City area were exposed to the attacks on the World Trade Center (WTC) towers and are thus at risk for developing PTSD has important implications for both prevalence estimates and service provision. This premise has not, however, been tested with respect to DSM-IV-TR criteria for PTSD. This study examined associations between geographic distance from the 9/11 attacks on the WTC and reported 9/11 trauma exposures, and the role of specific trauma exposures in the development of PTSD.

CYP2C19 Genotype Predicts Steady State Escitalopram Concentration in GENDEP

Journal of Psychopharmacology (Oxford, England). Sep, 2011  |  Pubmed ID: 21926427

In vitro work shows CYP2C19 and CYP2D6 contribute to the metabolism of escitalopram to its primary metabolite, N-desmethylescitalopram. We report the effect of CYP2C19 and CYP2D6 genotypes on steady state morning concentrations of escitalopram and N-desmethylescitalopram and the ratio of this metabolite to the parent drug in 196 adult patients with depression in GENDEP, a clinical pharmacogenomic trial. Subjects who had one CYP2D6 allele associated with intermediate metabolizer phenotype and one associated with poor metabolizer (i.e. IM/PM genotypic category) had a higher mean logarithm escitalopram concentration than CYP2D6 extensive metabolizers (EMs) (p = 0.004). Older age was also associated with higher concentrations of escitalopram. Covarying for CYP2D6 and age, we found those homozygous for the CYP2C19*17 allele associated with ultrarapid metabolizer (UM) phenotype had a significantly lower mean escitalopram concentration (2-fold, p = 0.0001) and a higher mean metabolic ratio (p = 0.0003) than EMs, while those homozygous for alleles conferring the PM phenotype had a higher mean escitalopram concentration than EMs (1.55-fold, p = 0.008). There was a significant overall association between CYP2C19 genotypic category and escitalopram concentration (p = 0.0003; p = 0.0012 Bonferroni corrected). In conclusion, we have demonstrated an association between CYP2C19 genotype, including the CYP2C19*17 allele, and steady state escitalopram concentration.

Rocky Mountain Spotted Fever in Panama: a Cluster Description

Journal of Infection in Developing Countries. Oct, 2011  |  Pubmed ID: 21997944

Rocky Mountain spotted fever (RMSF) is a tick-borne infection caused by Rickettsia rickettsii. We report a cluster of fatal cases of RMSF in 2007 in Panama, involving a pregnant woman and two children from the same family.  The woman presented with a fever followed by respiratory distress, maculopapular rash, and an eschar at the site from which a tick had been removed.  She died four days after disease onset.  This is the second published report of an eschar in a patient confirmed by PCR to be infected with R. rickettsii.  One month later, the children presented within days of one another with fever and rash and died three and four days after disease onset. The diagnosis was confirmed by immunohistochemistry, PCR and sequencing of the genes of R. rickettsii in tissues obtained at autopsy. 

A Role for Differential Variable Gene Pairing in Creating T Cell Receptors Specific for Unique Major Histocompatibility Ligands

Immunity. Nov, 2011  |  Pubmed ID: 22101158

A limited set of T cell receptor (TCR) variable (V) gene segments are used to create a repertoire of TCRs that recognize all major histocompatibility complex (MHC) ligands within a species. How individual αβTCRs are constructed to specifically recognize a limited set of MHC ligands is unclear. Here we have identified a role for the differential pairing of particular V gene segments in creating TCRs that recognized MHC class II ligands exclusively, or cross-reacted with classical and nonclassical MHC class I ligands. Biophysical and structural experiments indicated that TCR specificity for MHC ligands is not driven by germline-encoded pairwise interactions.Rather, identical TCRβ chains can have altered peptide-MHC (pMHC) binding modes when paired with different TCRα chains. The ability of TCR chain pairing to modify how V region residues interact with pMHC helps to explain how the same V genes are used to create TCRs specific for unique MHC ligands.

Extracting Surface Activation Time from the Optically Recorded Action Potential in Three-dimensional Myocardium

Biophysical Journal. Jan, 2012  |  Pubmed ID: 22225795

Optical mapping has become an indispensible tool for studying cardiac electrical activity. However, due to the three-dimensional nature of the optical signal, the optical upstroke is significantly longer than the electrical upstroke. This raises the issue of how to accurately determine the activation time on the epicardial surface. The purpose of this study was to establish a link between the optical upstroke and exact surface activation time using computer simulations, with subsequent validation by a combination of microelectrode recordings and optical mapping experiments. To simulate wave propagation and associated optical signals, we used a hybrid electro-optical model. We found that the time of the surface electrical activation (t(E)) within the accuracy of our simulations coincided with the maximal slope of the optical upstroke (t(F)*) for a broad range of optical attenuation lengths. This was not the case when the activation time was determined at 50% amplitude (t(F50)) of the optical upstroke. The validation experiments were conducted in isolated Langendorff-perfused rat hearts and coronary-perfused pig left ventricles stained with either di-4-ANEPPS or the near-infrared dye di-4-ANBDQBS. We found that t(F)* was a more accurate measure of t(E) than was t(F50) in all experimental settings tested (P = 0.0002). Using t(F)* instead of t(F50) produced the most significant improvement in measurements of the conduction anisotropy and the transmural conduction time in pig ventricles.

Relationship Between Hyperglycemia and Outcome in Children with Severe Traumatic Brain Injury

Pediatric Critical Care Medicine : a Journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. Jan, 2012  |  Pubmed ID: 21499170

To determine the relationship between hyperglycemia and outcome in infants and children after severe traumatic brain injury.