Sea anemone model has a single Toll-like receptor that can function in pathogen detection, NF-κB signal transduction, and development

In organisms from insects to vertebrates, Toll-like receptors (TLRs) are primary pathogen detectors that activate downstream pathways, specifically those that direct expression of innate immune effector genes. TLRs also have roles in development in many species. The sea anemone Nematostella vectensis is a useful cnidarian model to study the origins of TLR signaling because its genome encodes a single TLR and homologs of many downstream signaling components, including the NF-κB pathway. We have characterized the single N. vectensis TLR (Nv-TLR) and demonstrated that it can activate canonical NF-κB signaling in human cells. Furthermore, we show that the intracellular Toll/IL-1 receptor (TIR) domain of Nv-TLR can interact with the human TLR adapter proteins MAL and MYD88. We demonstrate that the coral pathogen Vibrio coralliilyticus causes a rapidly lethal disease in N. vectensis and that heat-inactivated V. coralliilyticus and bacterial flagellin can activate a reconstituted Nv-TLR–to–NF-κB pathway in human cells. By immunostaining of anemones, we show that Nv-TLR is expressed in a subset of cnidocytes and that many of these Nv-TLR–expressing cells also express Nv-NF-κB. Additionally, the nematosome, which is a Nematostella-specific multicellular structure, expresses Nv-TLR and many innate immune pathway homologs and can engulf V. coralliilyticus. Morpholino knockdown indicates that Nv-TLR also has an essential role during early embryonic development. Our characterization of this primitive TLR and identification of a bacterial pathogen for N. vectensis reveal ancient TLR functions and provide a model for studying the molecular basis of cnidarian disease and immunity.IOS-1354935 - National Science Foundation (NSF); GRFP - National Science Foundation (NSF); GRFP - National Science Foundation (NSF); 1262934 - National Science Foundation (NSF); 2014-BSP - Arnold and Mabel Beckman Foundatio

Can the United States Afford a “No-Fault” System of Compensation for Medical Injury?

One of the key issues separating US critics of a no-fault alternative to the tort system for compensating victims of medical injury from supporters is its anticipated cost. Results from a study are presented that estimate the costs of a no-fault system, one that is similar to the system now in operation in Sweden, within the context of the US health care system

Anabolic steroids, acute myocardial infarction and polycythemia: A case report and review of the literature

The association between testosterone-replacement therapy and cardiovascular risk remains unclear with most reports suggesting a neutral or possibly beneficial effect of the hormone in men and women. However, several cardiovascular complications including hypertension, cardiomyopathy, stroke, pulmonary embolism, fatal and nonfatal arrhythmias, and myocardial infarction have been reported with supraphysiologic doses of anabolic steroids. We report a case of an acute ST-segment elevation myocardial infarction in a patient with traditional cardiac risk factors using supraphysiologic doses of supplemental, intramuscular testosterone. In addition, this patient also had polycythemia, likely secondary to high-dose testosterone. The patient underwent successful percutaneous intervention of the right coronary artery. Phlebotomy was used to treat the polycythemia acutely. We suggest that the chronic and recent “stacked” use of intramuscular testosterone as well as the resultant polycythemia and likely increased plasma viscosity may have been contributing factors to this cardiovascular event, in addition to traditional coronary risk factors. Physicians and patients should be aware of the clinical consequences of anabolic steroid abuse

Cell-cell communication enhances the capacity of cell ensembles to sense shallow gradients during morphogenesis

Collective cell responses to exogenous cues depend on cell-cell interactions. In principle, these can result in enhanced sensitivity to weak and noisy stimuli. However, this has not yet been shown experimentally, and, little is known about how multicellular signal processing modulates single cell sensitivity to extracellular signaling inputs, including those guiding complex changes in the tissue form and function. Here we explored if cell-cell communication can enhance the ability of cell ensembles to sense and respond to weak gradients of chemotactic cues. Using a combination of experiments with mammary epithelial cells and mathematical modeling, we find that multicellular sensing enables detection of and response to shallow Epidermal Growth Factor (EGF) gradients that are undetectable by single cells. However, the advantage of this type of gradient sensing is limited by the noisiness of the signaling relay, necessary to integrate spatially distributed ligand concentration information. We calculate the fundamental sensory limits imposed by this communication noise and combine them with the experimental data to estimate the effective size of multicellular sensory groups involved in gradient sensing. Functional experiments strongly implicated intercellular communication through gap junctions and calcium release from intracellular stores as mediators of collective gradient sensing. The resulting integrative analysis provides a framework for understanding the advantages and limitations of sensory information processing by relays of chemically coupled cells.Comment: paper + supporting information, total 35 pages, 15 figure

Assessment of a new undergraduate module in musculoskeletal medicine.

BACKGROUND: Despite the high prevalence of musculoskeletal disorders seen by primary care physicians, numerous studies have demonstrated deficiencies in the adequacy of musculoskeletal education at multiple stages of medical education. The aim of this study was to assess a newly developed module in musculoskeletal medicine for use at European undergraduate level (i.e., the medical-school level). METHODS: A two-week module in musculoskeletal medicine was designed to cover common musculoskeletal disorders that are typically seen in primary care. The module incorporated an integrated approach, including core lectures, bedside clinical examination, and demonstration of basic practical procedures. A previously validated examination in musculoskeletal medicine was used to assess the cognitive knowledge of ninety-two students on completion of the module. A historical control group (seventy-two students) from a prior course was used for comparison. RESULTS: The new module group (2009) performed significantly better than the historical (2006) control group in terms of score (62.3% versus 54.3%, respectively; p \u3c 0.001) and pass rate (38.4% versus 12.5%, respectively; p = 0.0002). In a subgroup analysis of the new module group, students who enrolled in the graduate entry program (an accelerated four-year curriculum consisting of students who have already completed an undergraduate university degree) were more likely to perform better in terms of average score (72.2% versus 57%, respectively; p \u3c 0.001) and pass rates (70.9% versus 21.4%, respectively; p \u3c 0.001) compared with students who had enrolled via the traditional undergraduate route. In terms of satisfaction rates, the new module group reported a significantly higher satisfaction rate than that reported by the historical control group (63% versus 15%, respectively; p \u3c 0.001). CONCLUSIONS: In conclusion, the musculoskeletal module described in this paper represents an educational advance at undergraduate (i.e., medical-school) level as demonstrated by the improvement in scores in a validated examination. As pressure on medical curricula grows to accommodate advancing medical knowledge, it is important to continue to improve, assess, and consolidate the position of musculoskeletal medicine in contemporary medical education

Northern Bobwhite Age Ratios and Productivity at the Individual Property Scale in South Texas

Annual adult survival rate (Sˆ) and finite rate of population growth (k) are critical parameters that must be considered when subjecting a species to annual harvest. We used a data set of 148 estimates of northern bobwhite (Colinus virginianus) juvenile: adult age ratios (R) derived from hunter-harvested wings in the South Texas Plains to estimate these parameters. Data were collected from 1940 to 1976 and from 1983 to 2008. We used adjusted estimates of R to account for higher harvest vulnerability of juveniles, and the regional estimate of Sˆ (30.6% based on a stable population) to calculate estimates of k at the ranch (~800 2,000 ha) scale. Mean (6 SE) adjusted R was 2.79 6 0.13 juveniles: adult. Assuming a stable population (i.e., k 1⁄4 1), mean (6 SE) regional Sˆ was 30.6 6 0.1%. Given an annual Sˆ of 30.6%, mean regional k was 1.16 6 0.04, and single year k estimates ranged from 0.40 to 3.03 among individual properties. These data have important implications for bobwhite harvest management because they identify the potential for highly variable population growth rates (k) at a localized scale. There is an increased probability of overharvesting the population when local populations are declining. Our data indicate using only a regional estimate of k may mask local population trends, which has the potential for mismanagement of harvest within a given property by making harvest recommendations that are too high (overharvest) or too conservative (loss of opportunity)

A Simulation Model of Sustained-Yield Harvest for Northern Bobwhite in South Texas

Recommended sustainable harvest rates for northern bobwhite (Colinus virginianus) vary greatly and range from 25% to 70% of the prehunt population. Because northern bobwhite populations have declined across their geographic range, determining sustainable harvest levels is critical for effective management. Our objectives were to use simulation modeling to identify sustainable rates of bobwhite harvest, probability of population persistence, and minimum viable population estimates. We also conducted a sensitivity analysis to evaluate the impacts of harvest on northern bobwhite populations in Texas, USA. We constructed a simulation model using Program STELLA 9.0 for a hypothetical northern bobwhite population on 800 ha in the South Texas Plains USA and modeled population dynamics to 100 years over a range of harvest rates (0–40%). A 20% harvest rate produced the greatest average yields (mean ± standard error = 231 ± 10 bobwhites harvested/year). Given a quasi-extinction criterion of ≤40 bobwhites (≤0.05 bobwhite/ha), a 30% harvest rate resulted in a high probability of quasi-extinction (PE = 0.75) within 47.8 ± 2.3 years. A 40% harvest rate was not sustainable (PE = 1.0), with quasi-extinction occurring within 15.5 ± 2.6 years. Harvesting northern bobwhite populations in the South Texas Plains at rates of 20−25% of the prehunt population should maximize long-term harvest while minimizing the probability of population extinction. Spring densities of 0.60−0.80 bobwhite/ha may represent minimum viable spring densities for northern bobwhite populations in the South Texas Plains as these are the densities associated with sustainable 20-25% harvest rates. Harvest rates \u3e30% are likely to be excessive with respect to long-term population persistence for northern bobwhite populations in the South Texas Plains

Field Application of Sustained-Yield Harvest Management for Northern Bobwhite in Texas

Sustained-yield harvest (SYH) is considered a potentially viable strategy for managing harvest of northern bobwhites (Colinus virginianus). However, application of SYH has not been evaluated for northern bobwhites. We evaluated the application of using SYH as a harvest management strategy for bobwhite during the 2007 2008 and 2008 2009 hunting seasons in 2 ecoregions of Texas (Rolling Plains, South Texas Plains). We collected field data at 3 study sites/ecoregion (900 1,900 ha each; 2 hunted sites and 1 control) to estimate 4 demographic parameters (fall and spring density, overwinter survival in the absence of hunting, and harvest rate). We used these data to parameterize the additive harvest model for bobwhites and compare predictions of spring abundance of the model with field estimates. The additive harvest model, compared to field estimates, consistently underestimated spring population density (mean 6 SE) by 55.7 6 17.8% (2007 2008) and 34.1 6 4.9% (2008 2009) in the Rolling Plains, and by 26.4 6 25.3% (2007 2008) and 49.1 6 2.1% (2008 2009) in the South Texas Plains. Implementing SYH in the field, despite its potential benefits, will be challenging given the need for reliable estimates of 3 key population parameters (fall and spring density, and natural mortality in the absence of hunting) and the high variation often associated with them. Conservative harvest prescriptions based on the lower 95% CIs of fall density estimates may permit sustainable harvest despite variation in density estimates

Application of Metapopulation Theory to Northern Bobwhite Conservation

Northern bobwhite (Colinus virginianus) populations have declined throughout the majority of the species’ range, and have experienced the largest declines in fragmented habitats, suggesting landscape scale processes may be responsible for this decline. We used the results from a stochastic population dynamics model of South Texas bobwhites as conceptual justification for use of metapopulation theory in bobwhite management. Annual quasi-extinction probabilities for isolated bobwhite populations were 0.003 (95% CI: 0.001 0.006), 0.105 (95% CI: 0.083 0.126), and 0.773 (95% CI: 0.750 0.796) for simulated populations harvested at 20, 30, and 40% annually. The probability of regional persistence at 30% harvest increased to ~ 100% in scenarios where we modeled 5 occupied hypothetical 800-ha habitat patches; however, at 40% harvest rates, probability of regional metapopulation persistence did not reach 95% until 12 habitat patches were occupied. This suggests bobwhites probably require somewhere from 800 to 9,600 ha of available habitat space to maintain 95% probability of regional metapopulation persistence as harvest varies from 0 to 40% annually. Our results have strong implications for bobwhite harvest management given the high probability of quasi-extinction of isolated populations at rates of harvest 25%. Multiple patches of habitat (where individual patch size is 800 ha) must be available to ensure bobwhite metapopulation persistence