Evidence That Mast Cells Are Not Required for Healing of Splinted Cutaneous Excisional Wounds in Mice

Wound healing is a complex biological process involving the interaction of many cell types to replace lost or damaged tissue. Although the biology of wound healing has been extensively investigated, few studies have focused on the role of mast cells. In this study, we investigated the possible role of mast cells in wound healing by analyzing aspects of cutaneous excisional wound healing in three types of genetically mast cell-deficient mice. We found that C57BL/6-Kit^W-sh/W-sh, WBB6F₁-Kit^W/W-v, and Cpa3-Cre; Mcl-1^fl/fl mice re-epithelialized splinted excisional skin wounds at rates very similar to those in the corresponding wild type or control mice. Furthermore, at the time of closure, scars were similar in the genetically mast cell-deficient mice and the corresponding wild type or control mice in both quantity of collagen deposition and maturity of collagen fibers, as evaluated by Masson’s Trichrome and Picro-Sirius red staining. These data indicate that mast cells do not play a significant non-redundant role in these features of the healing of splinted full thickness excisional cutaneous wounds in mice.     

Defensive Medicine among Obstetricians and Gynecologists in Tertiary Hospitals

Objective

To describe the daily work practice under the threat of defensive medicine among obstetricians and gynecologists.

Study Design

A prospective cross-sectional survey of obstetricians and gynecologists working at tertiary medical centers in Israel.

Results

Among the 117 obstetricians and gynecologists who participated in the survey, representing 10% of the obstetricians and gynecologists registered by the Israel Medical Association, 113 (97%) felt that their daily work practice is influenced by concern about being sued for medical negligence and not only by genuine medical considerations. As a result, 102 (87%) physicians are more likely to offer the cesarean section option, even in the absence of a clear medical indication, 70 (60%) follow court rulings concerning medical practices, and 85 (73%) physicians mentioned that discussions about medical negligence court rulings are included in their departments'' meetings.

Conclusions

Defensive medicine is a well-embedded phenomenon affecting the medical decision process of obstetricians and gynecologists.     

Neural Sensitivity to Absolute and Relative Anticipated Reward in Adolescents

Adolescence is associated with a dramatic increase in risky and impulsive behaviors that have been attributed to developmental differences in neural processing of rewards. In the present study, we sought to identify age differences in anticipation of absolute and relative rewards. To do so, we modified a commonly used monetary incentive delay (MID) task in order to examine brain activity to relative anticipated reward value (neural sensitivity to the value of a reward as a function of other available rewards). This design also made it possible to examine developmental differences in brain activation to absolute anticipated reward magnitude (the degree to which neural activity increases with increasing reward magnitude). While undergoing fMRI, 18 adolescents and 18 adult participants were presented with cues associated with different reward magnitudes. After the cue, participants responded to a target to win money on that trial. Presentation of cues was blocked such that two reward cues associated with $.20, $1.00, or $5.00 were in play on a given block. Thus, the relative value of the $1.00 reward varied depending on whether it was paired with a smaller or larger reward. Reflecting age differences in neural responses to relative anticipated reward (i.e., reference dependent processing), adults, but not adolescents, demonstrated greater activity to a $1 reward when it was the larger of the two available rewards. Adults also demonstrated a more linear increase in ventral striatal activity as a function of increasing absolute reward magnitude compared to adolescents. Additionally, reduced ventral striatal sensitivity to absolute anticipated reward (i.e., the difference in activity to medium versus small rewards) correlated with higher levels of trait Impulsivity. Thus, ventral striatal activity in anticipation of absolute and relative rewards develops with age. Absolute reward processing is also linked to individual differences in Impulsivity.     

A Bayesian Approach for Modeling Cattle Movements in the United States: Scaling up a Partially Observed Network

Networks are rarely completely observed and prediction of unobserved edges is an important problem, especially in disease spread modeling where networks are used to represent the pattern of contacts. We focus on a partially observed cattle movement network in the U.S. and present a method for scaling up to a full network based on Bayesian inference, with the aim of informing epidemic disease spread models in the United States. The observed network is a 10% state stratified sample of Interstate Certificates of Veterinary Inspection that are required for interstate movement; describing approximately 20,000 movements from 47 of the contiguous states, with origins and destinations aggregated at the county level. We address how to scale up the 10% sample and predict unobserved intrastate movements based on observed movement distances. Edge prediction based on a distance kernel is not straightforward because the probability of movement does not always decline monotonically with distance due to underlying industry infrastructure. Hence, we propose a spatially explicit model where the probability of movement depends on distance, number of premises per county and historical imports of animals. Our model performs well in recapturing overall metrics of the observed network at the node level (U.S. counties), including degree centrality and betweenness; and performs better compared to randomized networks. Kernel generated movement networks also recapture observed global network metrics, including network size, transitivity, reciprocity, and assortativity better than randomized networks. In addition, predicted movements are similar to observed when aggregated at the state level (a broader geographic level relevant for policy) and are concentrated around states where key infrastructures, such as feedlots, are common. We conclude that the method generally performs well in predicting both coarse geographical patterns and network structure and is a promising method to generate full networks that incorporate the uncertainty of sampled and unobserved contacts.     

Soluble Guanylate Cyclase α1–Deficient Mice: A Novel Murine Model for Primary Open Angle Glaucoma

Primary open angle glaucoma (POAG) is a leading cause of blindness worldwide. The molecular signaling involved in the pathogenesis of POAG remains unknown. Here, we report that mice lacking the α₁ subunit of the nitric oxide receptor soluble guanylate cyclase represent a novel and translatable animal model of POAG, characterized by thinning of the retinal nerve fiber layer and loss of optic nerve axons in the context of an open iridocorneal angle. The optic neuropathy associated with soluble guanylate cyclase α₁–deficiency was accompanied by modestly increased intraocular pressure and retinal vascular dysfunction. Moreover, data from a candidate gene association study suggests that a variant in the locus containing the genes encoding for the α₁ and β₁ subunits of soluble guanylate cyclase is associated with POAG in patients presenting with initial paracentral vision loss, a disease subtype thought to be associated with vascular dysregulation. These findings provide new insights into the pathogenesis and genetics of POAG and suggest new therapeutic strategies for POAG.     

Major Cardiovascular Risk Factors in Latin America: A Comparison with the United States. The Latin American Consortium of Studies in Obesity (LASO)

Background

Limited knowledge on the prevalence and distribution of risk factors impairs the planning and implementation of cardiovascular prevention programs in the Latin American and Caribbean (LAC) region.

Methods and Findings

Prevalence of hypertension, diabetes mellitus, abnormal lipoprotein levels, obesity, and smoking were estimated from individual-level patient data pooled from population-based surveys (1998–2007, n = 31,009) from eight LAC countries and from a national survey of the United States (US) population (1999–2004) Age and gender specific prevalence were estimated and age-gender adjusted comparisons between both populations were conducted. Prevalence of diabetes mellitus, hypertension, and low high-density lipoprotein (HDL)-cholesterol in LAC were 5% (95% confidence interval [95% CI]: 3.4, 7.9), 20.2% (95% CI: 12.5, 31), and 53.3% (95% CI: 47, 63.4), respectively. Compared to LAC region’s average, the prevalence of each risk factor tended to be lower in Peru and higher in Chile. LAC women had higher prevalence of obesity and low HDL-cholesterol than men. Obesity, hypercholesterolemia, and hypertriglyceridemia were more prevalent in the US population than in LAC population (31 vs. 16.1%, 16.8 vs. 8.9%, and 36.2 vs. 26.5%, respectively). However, the prevalence of low HDL-cholesterol was higher in LAC than in the US (53.3 vs. 33.7%).

Conclusions

Major cardiovascular risk factors are highly prevalent in LAC region, in particular low HDL-cholesterol. In addition, marked differences do exist in this prevalence profile between LAC and the US. The observed patterns of obesity-related risk factors and their current and future impact on the burden of cardiovascular diseases remain to be explained.     

False Positive HIV Diagnoses in Resource Limited Settings: Operational Lessons Learned for HIV Programmes

Background

Access to HIV diagnosis is life-saving; however the use of rapid diagnostic tests in combination is vulnerable to wrongly diagnosing HIV infection when both screening tests give a false positive result. Misclassification of HIV patients can also occur due to poor quality control, administrative errors and lack of supervision and training of staff. Médecins Sans Frontières discovered in 2004 that HIV negative individuals were enrolled in some HIV programmes. This paper describes the result of an audit of three sites to review testing practices, implement improved testing algorithms and offer re-testing to clients enrolled in the HIV clinic.

Findings

In the Democratic Republic of Congo (DRC), Burundi and Ethiopia patients were identified for HIV retesting. In total, 44 false-positive patients were identified in HIV programmes in DRC, two in Burundi and seven in Ethiopia. Some of those identified had been abandoned by partners or started on anti-retroviral therapy or prophylaxis. Despite potential damage to programme reputations, no impact in terms of testing uptake occurred with mean monthly testing volumes stable after introduction of re-testing. In order to prevent the problem, training, supervision and quality control of testing procedures were strengthened. A simple and feasible confirmation test was added to the test algorithm. Prevalence of false positives after introducing the changes varied from zero percent (95% CI 0%–8.2%) to 10.3 percent (95% CI: 7.2%–14.1%) in Burundi and DRC respectively.

Conclusion

False HIV diagnoses were found in a variety of programme settings and had devastating individual consequences. We re-tested individuals in our programmes while instituting improved testing procedures without a negative impact on test uptake. Considering the importance of correct diagnosis to the individual, as well as the resources needed to care for someone with HIV, it is critical to ensure that all patients registered in HIV programmes are accurately diagnosed.     

The Impact of Gene Duplication,Insertion, Deletion,Lateral Gene Transfer and Sequencing Error on Orthology Inference: A Simulation Study

The identification of orthologous genes, a prerequisite for numerous analyses in comparative and functional genomics, is commonly performed computationally from protein sequences. Several previous studies have compared the accuracy of orthology inference methods, but simulated data has not typically been considered in cross-method assessment studies. Yet, while dependent on model assumptions, simulation-based benchmarking offers unique advantages: contrary to empirical data, all aspects of simulated data are known with certainty. Furthermore, the flexibility of simulation makes it possible to investigate performance factors in isolation of one another.Here, we use simulated data to dissect the performance of six methods for orthology inference available as standalone software packages (Inparanoid, OMA, OrthoInspector, OrthoMCL, QuartetS, SPIMAP) as well as two generic approaches (bidirectional best hit and reciprocal smallest distance). We investigate the impact of various evolutionary forces (gene duplication, insertion, deletion, and lateral gene transfer) and technological artefacts (ambiguous sequences) on orthology inference. We show that while gene duplication/loss and insertion/deletion are well handled by most methods (albeit for different trade-offs of precision and recall), lateral gene transfer disrupts all methods. As for ambiguous sequences, which might result from poor sequencing, assembly, or genome annotation, we show that they affect alignment score-based orthology methods more strongly than their distance-based counterparts.     

Impaired Eye Region Search Accuracy in Children with Autistic Spectrum Disorders

To explore mechanisms underlying reduced fixation of eyes in autism, children with Autistic Spectrum Disorders (ASD) and typically developing children were tested in five visual search experiments: simple color feature; color-shape conjunction; face in non-face objects; mouth region; and eye region. No group differences were found for reaction time profile shapes in any of the five experiments, suggesting intact basic search mechanics in children with ASD. Contrary to early reports in the literature, but consistent with other more recent findings, we observed no superiority for conjunction search in children with ASD. Importantly, children with ASD did show reduced accuracy for eye region search (p = .005), suggesting that eyes contribute less to high-level face representations in ASD or that there is an eye region-specific disruption to attentional processes engaged by search in ASD.     

Can Inpatient Hospital Experiences Predict Central Line-Associated Bloodstream Infections?

Background

Factors that increase the risk of central line-associated bloodstream infections (CLABSIs) are not fully understood. Recently, Hospital Compare began compiling data from hospital-required reporting to the CDC''s National Healthcare Safety Network on CLABSIs in intensive care units (ICUs), at over 4,000 Medicare-certified hospitals in the United States, and made this data accessible on a central website. Also available on the same website are results from the Hospital Consumer Assessment of Healthcare Providers and Systems survey of patients'' hospital experiences. Utilizing both databases, our objective was to determine whether patients'' hospital experiences were significantly associated with increased risk for reported ICU CLABSI.

Methods and Findings

We conducted a zero-inflated Poisson regression analysis at the hospital level on CLABSI-observed cases by ICUs in acute care hospitals (n = 1987) in the United States between January 1, 2011, and December 31, 2011. During this period there were a total of 10,866 CLABSI cases and 9,543,765 central line days. In our final model, the percent of patients who reported that they “sometimes” or “never” received help as soon as they wanted was significantly associated with an increased risk for CLABSIs.

Conclusions

Using national datasets, we found that inpatients'' hospital experiences were significantly associated with an increased risk of ICU reported CLABSIs. This study suggests that hospitals with lower staff responsiveness, perhaps because of an understaffing of nurse and supportive personnel, are at an increased risk for CLABSIs. This study bolsters the evidence that patient surveys may be a useful surrogate to predicting the incidence of hospital acquired conditions, including CLABSIs. Moreover, our study found that poor staff responsiveness may be indicative of greater hospital problems and generally poorly performing hospitals; and that this finding may be a symptom of hospitals with a multitude of problems, including patient safety problems, and not a direct cause.