Exertional heat illness (EHI) in athletes

This issue of eMedRef provides information to clinicians on the pathophysiology, diagnosis, and therapeutics of exertional heat illness occurring in athletes

Low back pain

This issue of eMedRef provides information to clinicians on the pathophysiology, diagnosis, and therapeutics of low back pain

When should you suspect community-acquired MRSA? How should you treat it?

There are no clinical or epidemiologic features that will help you to clearly distinguish community-acquired methicillin-resistant Staphylococcus aureus infections (CA-MRSA) from methicillin-sensitive (CA-MSSA) infections (strength of recommendation [SOR]: B, prospective cohort studies). Incision and drainage is the primary therapy for purulent skin and soft tissue infections (SOR: B, randomized, controlled clinical trials [RCTs]). There are inadequate data evaluating the role of oral antibiotics for MRSA (SOR: B, single RCT)

Ablation of spinal cord estrogen receptor α-expressing interneurons reduces chemically induced modalities of pain and itch

Estrogens are presumed to underlie, at least in part, the greater pain sensitivity and chronic pain prevalence that women experience compared to men. Although previous studies revealed populations of estrogen receptor‐expressing neurons in primary afferents and in superficial dorsal horn neurons, there is little to no information as to the contribution of these neurons to the generation of acute and chronic pain. Here we molecularly characterized neurons in the mouse superficial spinal cord dorsal horn that express estrogen receptor α (ERα) and explored the behavioral consequences of their ablation. We found that spinal ERα‐positive neurons are largely excitatory interneurons and many coexpress substance P, a marker for a discrete subset of nociceptive, excitatory interneurons. After viral, caspase‐mediated ablation of spinal ERα‐expressing cells, we observed a significant decrease in the first phase of the formalin test, but in male mice only. ERα‐expressing neuron‐ablation also reduced pruritogen‐induced scratching in both male and female mice. There were no ablation‐related changes in mechanical or heat withdrawal thresholds or in capsaicin‐induced nocifensive behavior. In chronic pain models, we found no change in Complete Freund's adjuvant‐induced thermal or mechanical hypersensitivity, or in partial sciatic nerve injury‐induced mechanical allodynia. We conclude that ERα labels a subpopulation of excitatory interneurons that are specifically involved in chemically evoked persistent pain and pruritogen‐induced itch

Development of High Power Hall Thruster Systems to Enable the NASA Exploration Vision

The next phase of space exploration missions requires high power Solar Electric Propulsion (SEP) systems for large-scale science missions and cargo transportation. Development is underway at Aerojet Rocketdyne on Hall thruster systems that are intended to bracket the needs of future NASA SEP missions in support of space exploration. The Advanced Electric Propulsion System (AEPS) program is developing and qualifying a 13.3kW Hall thruster system to be demonstrated on the Power and Propulsion Element (PPE), which is intended to be the first element of a Lunar Outpost Platform - Gateway (LOP-G). The NextSTEP program is integrating a nested Hall thruster into a 100kW system and testing it for 100 hours. These two programs will provide a path to efficient in-space propulsion that will allow NASA to transfer the large amounts of cargo that is needed to support human missions - first to the moon and then on to Mars. The Advanced Electric Propulsion System (AEPS) program is completing development, qualification and delivery of five flight 13.3kW EP systems to NASA. The flight AEPS system includes a magnetically shielded long-life Hall thruster, Power Processing Unit (PPU) and a Xenon Flow Controller (XFC). The Hall thruster, developed and demonstrated by NASA, operates at input powers up to 12.5kW while providing a specific impulse over an estimated 2800s at an input voltage of 600V. The power processor is designed to accommodate an input voltage range of 95-140V, consistent with operation beyond the orbit of Mars. The integrated system input power is continuously throttleable between 3 and 13.3kW. Component level testing of the EP String has begun with prototype hardware. The NextSTEP program is developing a 100kW Electric Propulsion (EP) system using a nested Hall thruster designed for powers up to 250kW, a modular power processor and a modular mass flow controller. While the program objective is to operate the integrated EP system continuously at 100kW for 100hrs to demonstrate thermal stability and support the development of system life time models, it builds on decades of experience with long-life Hall thrusters and the design is evolvable to a capability of 250kW. Design upgrades that demonstrate the 100kW EP system have been completed and tested. Aerojet Rocketdyne (AR) is excited to support NASA as it extends human reach into deep space and believes that these programs will provide the propulsion to make such missions affordable and sustainable. These systems provide NASA with a range of options to power its deep space transport vehicles. This paper presents the mission requirements for supporting the NASA exploration vision, as well as the status for the high power Hall thruster systems in development

Dimensions of biodiversity in Chesapeake Bay demersal fishes: patterns and drivers through space and time

Biodiversity has typically been described in terms of species richness and composition, but theory and growing empirical evidence indicate that the diversity of functional traits, the breadth of evolutionary relationships, and the equitability with which individuals or biomass are distributed among species better characterize patterns and processes within ecosystems. Yet, the advantages of including such data come at the expense of measuring traits, sequencing genes, and counting or weighing individuals, and it remains unclear whether this greater resolution yields substantial benefits in describing diversity. We summarized a decade of high-resolution trawl data from a bimonthly trawl survey to investigate spatial and seasonal patterns of demersal fish diversity in the Chesapeake Bay, USA, with the goal of identifying areas and times of mismatch between different dimensions of diversity, and their response to environmental forcing. We found moderate to strong positive relationships among all metrics of diversity, and that functional and phylogenetic differences were well-reflected in an index derived from taxonomic (Linnaean) hierarchy. Compared with species richness and species diversity, functional, phylogenetic, and taxonomic indices peaked later in the year, which was a consequence of the distribution of biomass among functionally and evolutionarily divergent species. Generalized additive models revealed that spatial, temporal, and environmental variables explained roughly similar proportions of deviance across all aspects of diversity, suggesting that these three factors do not differentially affect the functional and phylogenetic aspects of community structure. We conclude that an index of diversity derived from taxonomic hierarchy served well as a practical surrogate for functional and phylogenetic diversity of the demersal fish community in this system. We also emphasize the importance of evenness in understanding diversity patterns, especially since most ecological communities in nature are dominated by one or few species

Genetic Stasis of Dominant West Nile Virus Genotype, Houston, Texas

The accumulation and fixation of mutations in West Nile virus (WNV) led to the emergence of a dominant genotype throughout North America. Subsequent analysis of 44 isolates, including 19 new sequences, from Houston, Texas, suggests that WNV has reached relative genetic stasis at the local level in recent years

Forces associated with launch into space do not impact bone fracture healing

Segmental bone defects (SBDs) secondary to trauma invariably result in a prolonged recovery with an extended period of limited weight bearing on the affected limb. Soldiers sustaining blast injuries and civilians sustaining high energy trauma typify such a clinical scenario. These patients frequently sustain composite injuries with SBDs in concert with extensive soft tissue damage. For soft tissue injury resolution and skeletal reconstruction a patient may experience limited weight bearing for upwards of 6 months. Many small animal investigations have evaluated interventions for SBDs. While providing foundational information regarding the treatment of bone defects, these models do not simulate limited weight bearing conditions after injury. For example, mice ambulate immediately following anesthetic recovery, and in most cases are normally ambulating within 1-3 days post-surgery. Thus, investigations that combine disuse with bone healing may better test novel bone healing strategies. To remove weight bearing, we have designed a SBD rodent healing study in microgravity (µG) on the International Space Station (ISS) for the Rodent Research-4 (RR-4) Mission, which launched February 19, 2017 on SpaceX CRS-10 (Commercial Resupply Services). In preparation for this mission, we conducted an end-to-end mission simulation consisting of surgical infliction of SBD followed by launch simulation and hindlimb unloading (HLU) studies. In brief, a 2 mm defect was created in the femur of 10 week-old C57BL6/J male mice (n = 9-10/group). Three days after surgery, 6 groups of mice were treated as follows: 1) Vivarium Control (maintained continuously in standard cages); 2) Launch Negative Control (placed in the same spaceflight-like hardware as the Launch Positive Control group but were not subjected to launch simulation conditions); 3) Launch Positive Control (placed in spaceflight-like hardware and also subjected to vibration followed by centrifugation); 4) Launch Positive Experimental (identical to Launch Positive Control group, but placed in qualified spaceflight hardware); 5) Hindlimb Unloaded (HLU, were subjected to HLU immediately after launch simulation tests to simulate unloading in spaceflight); and 6) HLU Control (single housed in identical HLU cages but not suspended). Mice were euthanized 28 days after launch simulation and bone healing was examined via micro-Computed Tomography (µCT). These studies demonstrated that the mice post-surgery can tolerate launch conditions. Additionally, forces and vibrations associated with launch did not impact bone healing (p = .3). However, HLU resulted in a 52.5% reduction in total callus volume compared to HLU Controls (p = .0003). Taken together, these findings suggest that mice having a femoral SBD surgery tolerated the vibration and hypergravity associated with launch, and that launch simulation itself did not impact bone healing, but that the prolonged lack of weight bearing associated with HLU did impair bone healing. Based on these findings, we proceeded with testing the efficacy of FDA approved and novel SBD therapies using the unique spaceflight environment as a novel unloading model on SpaceX CRS-10

Signature-Based Small Molecule Screening Identifies Cytosine Arabinoside as an EWS/FLI Modulator in Ewing Sarcoma

BACKGROUND: The presence of tumor-specific mutations in the cancer genome represents a potential opportunity for pharmacologic intervention to therapeutic benefit. Unfortunately, many classes of oncoproteins (e.g., transcription factors) are not amenable to conventional small-molecule screening. Despite the identification of tumor-specific somatic mutations, most cancer therapy still utilizes nonspecific, cytotoxic drugs. One illustrative example is the treatment of Ewing sarcoma. Although the EWS/FLI oncoprotein, present in the vast majority of Ewing tumors, was characterized over ten years ago, it has never been exploited as a target of therapy. Previously, this target has been intractable to modulation with traditional small-molecule library screening approaches. Here we describe a gene expression–based approach to identify compounds that induce a signature of EWS/FLI attenuation. We hypothesize that screening small-molecule libraries highly enriched for FDA-approved drugs will provide a more rapid path to clinical application. METHODS AND FINDINGS: A gene expression signature for the EWS/FLI off state was determined with microarray expression profiling of Ewing sarcoma cell lines with EWS/FLI-directed RNA interference. A small-molecule library enriched for FDA-approved drugs was screened with a high-throughput, ligation-mediated amplification assay with a fluorescent, bead-based detection. Screening identified cytosine arabinoside (ARA-C) as a modulator of EWS/FLI. ARA-C reduced EWS/FLI protein abundance and accordingly diminished cell viability and transformation and abrogated tumor growth in a xenograft model. Given the poor outcomes of many patients with Ewing sarcoma and the well-established ARA-C safety profile, clinical trials testing ARA-C are warranted. CONCLUSIONS: We demonstrate that a gene expression–based approach to small-molecule library screening can identify, for rapid clinical testing, candidate drugs that modulate previously intractable targets. Furthermore, this is a generic approach that can, in principle, be applied to the identification of modulators of any tumor-associated oncoprotein in the rare pediatric malignancies, but also in the more common adult cancers