Microbial metabolomic responses to changes in temperature and salinity along the western Antarctic Peninsula.

Seasonal cycles within the marginal ice zones in polar regions include large shifts in temperature and salinity that strongly influence microbial abundance and physiology. However, the combined effects of concurrent temperature and salinity change on microbial community structure and biochemical composition during transitions between seawater and sea ice are not well understood. Coastal marine communities along the western Antarctic Peninsula were sampled and surface seawater was incubated at combinations of temperature and salinity mimicking the formation (cold, salty) and melting (warm, fresh) of sea ice to evaluate how these factors may shape community composition and particulate metabolite pools during seasonal transitions. Bacterial and algal community structures were tightly coupled to each other and distinct across sea-ice, seawater, and sea-ice-meltwater field samples, with unique metabolite profiles in each habitat. During short-term (approximately 10-day) incubations of seawater microbial communities under different temperature and salinity conditions, community compositions changed minimally while metabolite pools shifted greatly, strongly accumulating compatible solutes like proline and glycine betaine under cold and salty conditions. Lower salinities reduced total metabolite concentrations in particulate matter, which may indicate a release of metabolites into the labile dissolved organic matter pool. Low salinity also increased acylcarnitine concentrations in particulate matter, suggesting a potential for fatty acid degradation and reduced nutritional value at the base of the food web during freshening. Our findings have consequences for food web dynamics, microbial interactions, and carbon cycling as polar regions undergo rapid climate change.

Specimen Collection for Translational Studies in Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory disorder characterized by painful nodules, sinus tracts, and scars occurring predominantly in intertriginous regions. The prevalence of HS is currently 0.053-4%, with a predominance in African-American women and has been linked to low socioeconomic status. The majority of the reported literature is  retrospective, population based, epidemiologic studies. In this regard, there is a need to establish a repository of biospecimens, which represent appropriate gender and racial demographics amongst HS patients. These efforts will diminish knowledge gaps in understanding the disease pathophysiology. Hence, we sought to outline a step-by-step protocol detailing how we established our HS biobank to facilitate the formation of other HS tissue banks. Equipping researchers with carefully detailed processes for collection of HS specimens would accelerate the accumulation of well-organized human biological material. Over time, the scientific community will have access to a broad range of HS tissue biospecimens, ultimately leading to more rigorous basic and translational research. Moreover, an improved understanding of the pathophysiology is necessary for the discovery of novel therapies for this debilitating disease. We aim to provide high impact translational research methodology for cutaneous biology research and foster multidisciplinary collaboration and advancement of our understanding of cutaneous diseases.

A systematic review of cardiovascular responses associated with ambient black carbon and fine particulate matter.

BACKGROUND: Exposure to fine particulate matter (PM2.5), an ambient air pollutant with mass-based standards promulgated under the Clean Air Act, and black carbon (BC), a common component of PM2.5, are both associated with cardiovascular health effects. OBJECTIVES: To elucidate whether BC is associated with distinct, or stronger, cardiovascular responses compared to PM2.5, we conducted a systematic review. We evaluated the associations of short- and long-term BC, or the related component elemental carbon (EC), with cardiovascular endpoints including heart rate variability, heart rhythm, blood pressure and vascular function, ST segment depression, repolarization abnormalities, atherosclerosis and heart function, in the context of what is already known about PM2.5. DATA SOURCES: We conducted a stepwise systematic literature search of the PubMed, Web of Science and TOXLINE databases and applied Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines for reporting our results. STUDY ELIGIBILITY CRITERIA: Studies reporting effect estimates for the association of quantitative measurements of ambient BC (or EC) and PM2.5, with relevant cardiovascular endpoints (i.e. meeting inclusion criteria) were included in the review. Included studies were evaluated for risk of bias in study design and results. STUDY APPRAISAL AND SYNTHESIS METHODS: Risk of bias evaluations assessed aspects of internal validity of study findings based on study design, conduct, and reporting to identify potential issues related to confounding or other biases. Study results are presented to facilitate comparison of the consistency of associations with PM2.5 and BC within and across studies. RESULTS: Our results demonstrate similar associations for BC (or EC) and PM2.5 with the cardiovascular endpoints examined. Across studies, associations for BC and PM2.5 varied in their magnitude and precision, and confidence intervals were generally overlapping within studies. Where differences in the magnitude of the association between BC or EC and PM2.5 within a study could be discerned, no consistent pattern across the studies examined was apparent. LIMITATIONS: We were unable to assess the independence of the effect of BC, relative the effect of PM2.5, on the cardiovascular system, nor was information available to understand the impact of differential exposure misclassification. CONCLUSIONS: Overall, the evidence indicates that both BC (or EC) and PM2.5 are associated with cardiovascular effects but the available evidence is not sufficient to distinguish the effect of BC (or EC) from that of PM2.5 mass.

Immunohistological characterization of spinal TB granulomas from HIV-negative and -positive patients.

Tuberculosis (TB) is mainly a disease of the lungs, but Mycobacterium tuberculosis (Mtb) can establish infection in virtually any organ in the body. Rising rates of extrapulmonary (EP) TB have been largely associated with the HIV epidemic, as patients co-infected with HIV show a four-fold higher risk of EPTB. Spinal TB (Pott's Disease), one of the most debilitating extrapulmonary forms of disease, is difficult to diagnose and can cause deformity and/or neurological deficits. This study examined the histopathology and distribution of immune cells within spinal TB lesions and the impact of HIV on pathogenesis. The overall structure of the spinal granulomas resembled that seen in lung lesions from patients with pulmonary TB. Evidence of efficient macrophage activation and differentiation were detectable within organized structures in the spinal tissue, irrespective of HIV status. Interestingly, the granulomatous architecture and macroscopic features were similar in all samples examined, despite a reversal in the ratio of infiltrating CD4 to CD8 T cells in the lesions from HIV-infected patients. This study provides a foundation to understand the mechanism of tissue destruction and disease progression in Spinal TB, enabling the future development of novel therapeutic strategies and diagnostic approaches for this devastating disease.

Dendritic cell therapy in composite tissue allotransplantation.

Dendritic cells (DCs) are bone marrow-derived, professional antigen-presenting cells, with inherent tolerogenic function. The ability of immature or maturation-resistant DCs to regulate alloantigen-specific T-cell responses and to promote tolerance induction has been well demonstrated in organ and bone marrow transplantation. Recent data suggest that DCs can also promote long-term survival of composite tissue allografts in the absence of continued immunosuppressive drug therapy.

Dog bites: still a problem?

OBJECTIVE: To estimate the incidence of dog bites in the USA and compare it with similar estimates from 1994. DESIGN: Nationally representative cross-sectional, list-assisted, random-digit-dialed telephone survey conducted during 2001-2003. METHODS: Weighted estimates were generated from data collected by surveying 9684 households during 2001-2003 and compared with results from a similar survey conducted in 1994. Estimates for persons aged 15-17 years were extrapolated on the basis of rates for 10-14-year-olds. RESULTS: Whereas the incidence of dog bites among adults remained relatively unchanged, there was a significant (47%) decline in the incidence of dog bites among children compared with that observed in the 1994 survey, particularly among boys and among those aged 0-4 years. Between 2001 and 2003, an estimated 4 521 300 persons were bitten each year. Of these, 885 000 required medical attention (19%). Children were more likely than adults to receive medical attention for a dog bite. Among adults, bite rates decreased with increasing age. Among children and adults, having a dog in the household was associated with a significantly increased incidence of dog bites, with increasing incidence also related to increasing numbers of dogs. CONCLUSIONS: Dog bites continue to be a public health problem affecting 1.5% of the US population annually. Although comparison with similar data from 1994 suggests that bite rates for children are decreasing, there still appears to be a need for effective prevention programs.

Coronary artery and abdominal aortic calcification are associated with cardiovascular disease in type 2 diabetes.

AIMS/HYPOTHESIS: The goals of this study were to determine whether coronary calcium is associated with the presence of clinical cardiovascular disease in individuals with type 2 diabetes and if the measurement of abdominal aortic calcium may have an independent or added benefit as a surrogate marker for clinical vascular disease. METHODS: A cross-sectional study of subjects with type 2 diabetes enrolled in seven medical centres in the USA participating in a Veterans Affairs Cooperative Study of glycaemic control. Enrolled subjects included 309 veterans over 40 years of age with type 2 diabetes, with or without stable cardiovascular disease, who had inadequate glycaemic control (HbA(1)c>7.5%) on oral agents and/or insulin. The study assessed lifestyle behaviours, standard cardiovascular risk factors and coronary artery and abdominal aorta calcification by electron beam computed tomography. RESULTS: Subjects with coronary artery or abdominal aorta calcification present had a strikingly higher prevalence of peripheral artery disease, coronary artery disease and all combined cardiovascular disease. Prevalence of each condition increased from 5- to 13-fold with increasing quintiles of coronary artery calcification and from 2- to 3-fold with increasing abdominal aorta calcification. These associations persisted after adjustment for lifestyle behaviours and standard cardiovascular risk factors. CONCLUSIONS/INTERPRETATION: These results support the notion that vascular calcium in type 2 diabetes provides additional information beyond that of standard risk factors in identifying the presence of cardiovascular disease. Subclinical measures of atherosclerosis such as arterial calcification may help more precisely stratify these individuals and alert healthcare providers to those individuals who have particularly accelerated atherosclerosis.

Balancing benefit against risk in the choice of therapy for coronary artery disease. Lesson from prospective, randomized, clinical trials of percutaneous coronary intervention and coronary artery bypass graft surgery.

The ageing world population faces a coming pandemic of high-risk coronary artery disease (CAD). Patients with CAD have 3 therapeutic options, which are based on objective clinical outcome: medical therapy and risk factor modification (Medicine), and 2 forms of revascularization, coronary artery bypass graft surgery (CABG), and percutaneous coronary intervention (PCI). More than 50 large (>100 patients), multicenter, prospective, randomized clinical trials (RCT) have compared these treatment options in terms of clinical benefits and patient risks. The randomized trials which demonstrated hard outcome (survival, myocardial infarction, stroke) benefits from statins, angiotensin-converting enzyme inhibition and thienopyridines have all been completed subsequent to the publication of most Medicine versus revascularization trials. These medical therapies, plus aspirin, beta-blockers, and risk factor modification, should be made available to patients regardless of the decision to revascularize, or the decision by what means (CABG or PCI). This review integrates the information from these trials, comparing the clinical benefits against the risks inherent in the 3 therapeutic options. The results of our review show that: trials of medicine versus revascularization (either CABG or PCI) support the revascularization paradox, in that the patients at highest risk of adverse outcome, from myocardial ischemia, have a hard outcome benefit (survival, MI, or stroke) from revascularization. This paradox, first seen in the Medicine versus CABG trials of the 1970s, is evident in the trials comparing fibrinolysis and other medicines, with primary PCI for ST-elevation myocardial infarction (MI). The paradox is evident in the conservative versus invasive strategy trials of non-ST-elevation MI and unstable angina, where the benefit of revascularization occurs only in high-risk subsets. The paradox often results in sicker patients, who have more to gain from revascularization, being denied it because of the elevated perception of risk (comparable to a reperfusion paradox in ST-elevation MI, where patients most likely to benefit from thrombolytics are denied them because of the perception of risk). Trials that compared medicine with revascularization for the treatment of acute MI support the use of PCI as the preferred early stabilization strategy (90% of all PAMI trial patients). The majority of the PCI versus CABG trials enrolled populations that were at relatively low risk for ischemic clinical events. These trials demonstrated few hard outcome (survival, MI, or stroke) differences between CABG and PCI. On the basis of the results obtained the following conclusions may be drawn: medicines are the primary options for stable, low-risk CAD, and should be given to all CAD patients. Medically refractory is a useful high-risk marker of potential benefit from revascularization. CABG continues to be the complete revascularization option for patients with multivessel, multi-lesion CAD, in part because of its application to chronic occlusions. PCI is the acute stabilization method of choice for patients with on-going ischemia and acute MI, especially among patients with hemodynamic compromise, and/or major comorbidity.

Studying "exposure" to firearms: household ownership v access.

BACKGROUND: Firearm ownership has often been used to measure access to weapons. However, persons who own a firearm may not have access to it and conversely, persons who do not own a firearm may be able to access one quickly. OBJECTIVES: To examine whether using firearm ownership is a reasonable proxy for access by describing the demographic characteristics associated with ownership and access. METHODS: Data are from the 1994 Injury Control and Risk Survey, a national, random digit dial survey. Information about household firearm ownership and ready access to a loaded firearm were collected and weighted to provide national estimates. Adjusted odds ratios for three separate models were calculated using logistic regression. RESULTS: A total of 1353 (27.9%) respondents reported both having a firearm in the household and ready access to one. An additional 313 respondents (8.1%) reported having a firearm, but were not able to access these weapons. Another 421 respondents (7.2%) did not have a firearm in or around their home, yet reported being able to retrieve and fire one within 10 minutes. Based on the logistic regression findings, the demographic characteristics of this latter group are quite different from those who report ownership. Those who do not have a firearm, but report ready access to one, are more likely to be ethnic minorities, single, and living in attached homes. CONCLUSIONS: Asking only about the presence of a firearm in a household may miss some respondents with ready access to a loaded firearm. More importantly, those who do not own a firearm, but report ready access to one, appear to be qualitatively different from those who report ownership. Caution should be exercised when using measures of ownership as a proxy for access.

The construction and assessment of a statistical model for the prediction of protein assay data.

The focus of this work is the development of a statistical model for a bioinformatics database whose distinctive structure makes model assessment an interesting and challenging problem. The key components of the statistical methodology, including a fast approximation to the singular value decomposition and the use of adaptive spline modeling and tree-based methods, are described, and preliminary results are presented. These results are shown to compare favorably to selected results achieved using comparitive methods. An attempt to determine the predictive ability of the model through the use of cross-validation experiments is discussed. In conclusion a synopsis of the results of these experiments and their implications for the analysis of bioinformatic databases in general is presented.

State level estimates of the incidence and economic burden of head injuries stemming from non-universal use of bicycle helmets.

OBJECTIVE: To develop national and state level estimates for preventable bicycle related head injuries (BRHIs) and associated direct and indirect health costs from the failure to use bicycle helmets. METHODS: Information on the effectiveness and prevalence of use of bicycle helmets was combined to estimate the avoidable fraction, that is, the proportion of BRHIs that could be prevented through the use of bicycle helmets. The avoidable fraction multiplied by the expected number of BRHIs gives an estimate of the number of preventable cases. Direct and indirect health costs are estimated from a social perspective for the number of preventable BRHIs to assess potential cost savings that would be achieved if all riders wore helmets. RESULTS: Approximately 107,000 BRHIs could have been prevented in 1997 in the United States. These preventable injuries and deaths represent an estimated $81 million in direct and $2.3 billion in indirect health costs. Estimates range from 200 preventable BRHIs and $3 million in health costs in Wyoming (population 480,000) to 13,700 preventable BRHIs and $320 million in health costs in California (population 32.3 million). CONCLUSIONS: A number of successful approaches to increasing bicycle helmet use exist, including mandatory use laws and community based programs. The limited use of these strategies may be related to the fact that too little information is available to state agencies about the public health and economic burden of these preventable injuries. In conjunction with information on program costs, our estimates can assist state planners in better quantifying the number of preventable BRHIs and the costs and benefits of helmet promotion programs.

Ethical issues at the start of life.

In this article the fundamentals of a Jewish ethic are set out, through which today's pressing medical ethical questions are then broached. Ethics derive from a basic view of humanity. The Bible teaches that man is created in God's image, and every life is therefore sacrosanct. Second, since life is God-given we are its guarantors, not its owners. Finally, monotheism sees God as above nature and not in it, so nature itself is not holy--man can, and indeed should, try to improve upon it. With reference to specific medical issues, the need to be wary of the erosion of the family unit and of personal identity is stressed. Concerning abortion and stem cell research, the point is made that an embryo is not a person but is a potentiality and therefore not an object to be used. Regarding genetic intervention, a line is drawn between the therapeutic and the eugenic. Every technology carries with it the possibility of diminishing or enhancing human dignity. What matters is how we use it. The way to use it is in a covenant with God, honouring his image that is mankind.

Percutaneous coronary intervention versus coronary artery bypass graft surgery for patients with medically refractory myocardial ischemia and risk factors for adverse outcomes with bypass: a multicenter, randomized trial. Investigators of the Department of Veterans Affairs Cooperative Study #385, the Angina With Extremely Serious Operative Mortality Evaluation (AWESOME).

BACKGROUND: Percutaneous coronary intervention (PCI) and coronary artery bypass graft surgery (CABG) are being applied to high-risk populations, but previous randomized trials comparing revascularization methods have excluded a number of important high-risk groups. OBJECTIVES: This five-year, multicenter, randomized clinical trial was designed to compare long-term survival among patients with medically refractory myocardial ischemia and a high risk of adverse outcomes assigned to either a CABG or a PCI strategy, which could include stents. METHODS: Patients from 16 Veterans Affairs Medical Centers were screened to identify myocardial ischemia refractory to medical management and the presence of one or more risk factors for adverse outcome with CABG, including prior open-heart surgery, age >70 years, left ventricular ejection fraction <0.35, myocardial infarction within seven days or intraaortic balloon pump required. Clinically eligible patients (n = 2,431) underwent coronary angiography; 781 were angiographically acceptable; 454 (58% of eligible) patients consented to random assignment between CABG and PCI. RESULTS: A total of 232 patients was randomized to CABG and 222 to PCI. The 30-day survivals for CABG and PCI were 95% and 97%, respectively. Survival rates for CABG and PCI were 90% versus 94% at six months and 79% versus 80% at 36 months (log-rank test, p = 0.46). CONCLUSIONS: Percutaneous coronary intervention is an alternative to CABG for patients with medically refractory myocardial ischemia and a high risk of adverse outcomes with CABG.

Attitudinal acceptance of intimate partner violence among U.S. adults.

Attitudinal acceptance of intimate partner violence (IPV) is an important correlate of violent behavior. This study examined acceptance of IPV using data collected from a nationally representative telephone survey of 5,238 adults. Multivariable logistic regression analyses were used to test for associations between sociodemographic characteristics, exposure to violence, question order, and acceptance of hitting a spouse or boyfriend/girlfriend under specific circumstances. Depending on the circumstance examined, acceptance of IPV was significantly higher among participants who were male and younger than 35; were non-White; were divorced, separated, or had never married; had not completed high school; had a low household income; or were victims of violence within the past 12 months. Participants were more accepting of women hitting men; they also were consistently more likely to report tolerance of IPV if they were asked first about women hitting men rather than men hitting women. Reports of IPV tolerance need to be interpreted within the context of the survey. Efforts to change IPV attitudes can be tailored to specific IPV circumstances and subgroups, and these efforts should emphasize that the use of physical violence is unacceptable to both genders.

Trends and subgroup differences in transportation-related injury risk and safety behaviors among high school students, 1991-1997.

PURPOSE: To examine national trends in transportation-related injury risk and safety behaviors among U.S. high school students. METHODS: To examine secular trends in riding with a driver who had been drinking, driving after drinking, and using seat belts, bicycle helmets, and motorcycle helmets, we used logistic regression to analyze data from national Youth Risk Behavior Surveys (YRBS) conducted in 1991, 1993, 1995, and 1997. The YRBS is a self-administered, anonymous survey that uses a national probability sample of U.S. students in public and private schools from grades 9-12 (N = 55,734 for all years combined). RESULTS: The percentages of students who rode with a driver who had been drinking (36.6% in 1997), drove after drinking alcohol (16.9% in 1997), always wore seat belts (33.2% in 1997), and always wore a motorcycle helmet when riding a motorcycle (45.0% in 1997) remained stable between 1991 and 1997. From 1991 to 1997, the percentage of bicycle riders who always wore a helmet when bicycling showed a small but statistically significant increase (1.1% in 1991 to 3.8% in 1997), but helmet use remained low. CONCLUSION: Many young people place themselves at unnecessary risk for motor vehicle- and bicycle-related crash injuries and fatalities. Improved motor vehicle- and bicycle-related injury prevention strategies are needed that specifically target adolescents.

Measuring community bicycle helmet use among children.

Bicycling is a popular recreational activity and a principal mode of transportation for children in the United States, yet about 300 children die and 430,000 are injured annually. Wearing a bicycle helmet is an important countermeasure, since it reduces the risk of serious brain injury by up to 85%. The Centers for Disease Control and Prevention (CDC) have funded state health departments to conduct bicycle helmet programs, and their effectiveness has been evaluated by monitoring community bicycle helmet use. Although it would appear that measuring bicycle helmet use is easy, it is actually neither simple nor straightforward. The authors describe what they have learned about assessing helmet use and what methods have been most useful. They also detail several key practical decisions that define the current CDC position regarding helmet use assessment. Although important enough in their own right, the lessons learned in the CDC's bicycle helmet evaluation may serve as a model for evaluating other injury prevention and public health programs.

Breeds of dogs involved in fatal human attacks in the United States between 1979 and 1998.

OBJECTIVE: To summarize breeds of dogs involved in fatal human attacks during a 20-year period and to assess policy implications. ANIMALS: Dogs for which breed was reported involved in attacks on humans between 1979 and 1998 that resulted in human dog bite-related fatalities (DBRF). PROCEDURE: Data for human DBRF identified previously for the period of 1979 through 1996 were combined with human DBRF newly identified for 1997 and 1998. Human DBRF were identified by searching news accounts and by use of The Humane Society of the United States' registry databank. RESULTS: During 1997 and 1998, at least 27 people died of dog bite attacks (18 in 1997 and 9 in 1998). At least 25 breeds of dogs have been involved in 238 human DBRF during the past 20 years. Pit bull-type dogs and Rottweilers were involved in more than half of these deaths. Of 227 reports with relevant data, 55 (24%) human deaths involved unrestrained dogs off their owners' property, 133 (58%) involved unrestrained dogs on their owners' property, 38 (17%) involved restrained dogs on their owners' property, and 1 (< 1%) involved a restrained dog off its owner's property. CONCLUSIONS: Although fatal attacks on humans appear to be a breed-specific problem (pit bull-type dogs and Rottweilers), other breeds may bite and cause fatalities at higher rates. Because of difficulties inherent in determining a dog's breed with certainty, enforcement of breed-specific ordinances raises constitutional and practical issues. Fatal attacks represent a small proportion of dog bite injuries to humans and, therefore, should not be the primary factor driving public policy concerning dangerous dogs. Many practical alternatives to breed-specific ordinances exist and hold promise for prevention of dog bites.

Teaching a multidisciplinary approach to cancer treatment during surgical clerkship via an interactive board game.

BACKGROUND: Although educators agree that the approach to cancer management must be multidisciplinary, medical students usually observe cancer patients through the eyes of a single specialist at any given time. METHODS: In order to teach third-year medical students that cancer management is multidisciplinary, we developed the Oncology Game, an interactive, computer-assisted board game built on the principles of self-directed learning and student-student interaction. Eight "patients" with different histologic types of cancer are distributed randomly to 4 students, who play in teams of 2. The object is for the team to obtain the best treatment for its patients by advancing them via a roll of dice through surgical, medical, and radiation oncology clinics in the order most logical for the patient's particular cancer type. To test improvement in cognitive skills as a function of play, 16 students participated in a tournament taking parallel pretest and posttests before and after each round of play. RESULTS: Students demonstrated a statistically significant change in the total number of questions answered correctly each time they played the Oncology Game (F = 4.16, P = 0.018; Pretest Round 1: 8.88 +/- 0.58; Posttest Round 1: 9.63 +/- 0.42; Pretest Round 2: 10.75 +/- 0.62; Posttest Round 2: 11.5 +/- 0.85). Post hoc pairwise comparison revealed a significant improvement in student performance after playing two rounds of the Oncology Game. Based on the postgame survey, students felt they improved their understanding of oncologic principles (4.56 +/- 0.13), knowledge of malignancies (4.50 +/- 0.13), and appreciation for the multidisciplinary nature of cancer management (4.56 +/- 0.13). CONCLUSIONS: Improved test scores and postgame survey results demonstrate that third-year medical student students can learn about basic oncology principles and gain an appreciation for oncology as a multidisciplinary field of medicine through an interactive, computer-assisted board game.