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Contemporary anticancer therapies frequently have different efficacy and side effects in men and women. Yet, whether women are well‐represented in pivotal trials supporting contemporary anticancer drugs is unknown. Leveraging the Drugs@FDA database, clinicaltrials.gov, MEDLINE, and publicly available FDA‐drug‐reviews, we identified all pivotal (phase II and III) non‐sex specific trials supporting FDA‐approval of anticancer drugs (1998–2018). Observed‐enrollment‐rates were compared to expected‐population‐rates derived from concurrent US‐National‐Cancer‐Institute's Surveillance‐Epidemiology‐and‐End‐Results (SEER) reported rates and US‐Census databases. Primary outcome was the proportional representation of women across trials, evaluated by a participation‐to‐prevalence ratio (PPR), according to cancer type. Secondary outcome was the report of any sex‐specific analysis of efficacy and/or safety, irrespective of treatment‐arm. Overall, there were 148 trials, enrolling 60,216 participants (60.5 ± 4.0 years, 40.7% female, 79.1% biologic, targeted, or immune‐based therapies) evaluating 99 drugs. Sex was reported in 146 (98.6%) trials, wherein 40.7% (24,538) were women, compared to 59.3% (35,678) men (p <.01). Altogether, women were under‐represented in 66.9% trials compared to the proportional incidence of cancers by respective disease type; weight‐average PPR of 0.91 (relative difference: ‐9.1%, p <.01). Women were most under‐represented in gastric (PPR = 0.63), liver (PPR = 0.71), and lung (PPR =.81) cancer trials. Sex‐based safety data was reported in 4.0% trials. There was no association between adequate female enrollment and drug efficacy (HR: 0.616 vs. 0.613, p =.96). Over time, there was no difference in the percentage of women recruited into clinical trials. Among pivotal clinical trials supporting contemporary FDA‐approved cancer drugs, women were frequently under‐represented and sex‐specific‐efficacy and safety‐outcomes were commonly not reported. [ABSTRACT FROM AUTHOR]

A field biologist was bitten by a female Nikolsky's viper (Vipera berus nikolskii) in Kharkiv Oblast, Ukraine. Two months later, the patient began to experience cold-induced vasospasm of the affected digit diagnosed as acquired Raynaud phenomenon. The patient had more than 30 occurrences during the single winter following the bite, but the signs and symptoms of Raynaud phenomenon disappeared with the end of winter. This report describes the case and puts it into context with the literature on the topic of toxin-induced peripheral vasospastic disorders and their potential importance in snakebite envenoming. [ABSTRACT FROM AUTHOR]

Objective: Carrier screening with reflex to single‐gene noninvasive prenatal testing (sgNIPT) is an alternative approach for identifying pregnancies at risk for inherited autosomal recessive conditions without the need for a sample from the reproductive partner. This study is the largest clinical validation of this approach in a general population setting. Methods: The clinical performance of carrier screening with reflex to sgNIPT for cystic fibrosis, spinal muscular atrophy, alpha thalassemias, and beta hemoglobinopathies was assessed by collecting pregnancy outcome data on patients who underwent this testing and comparing the neonatal outcome to the assay‐predicted fetal risk. Results: Of 42,067 pregnant individuals who underwent screening, 7538 carriers (17.9%) had reflex sgNIPT, and neonatal or fetal outcomes were obtained for 528 cases, including 25 affected pregnancies. Outcomes demonstrated high concordance with sgNIPT, for example, all pregnancies with 9 in 10 personalized fetal risk results were affected (positive predictive value (PPV) of 100% for the sub‐group) and the sgNIPT assay showed a sensitivity of 96.0% (95% CI: 79.65%–99.90%), specificity of 95.2% (95% CI: 92.98%–96.92%), average PPV of 50.0% (95% CI: 35.23%–64.77%), and negative predictive value (NPV) of 99.8% (95% CI: 98.84%–99.99%). The end‐to‐end performance of carrier screening with reflex to sgNIPT was calculated to have a sensitivity of 92.4% and specificity of 99.9%, which are unaffected by partner carrier screening or misattributed paternity unlike a traditional carrier screening workflow, which has a 35% sensitivity and a maximum of 25% PPV (1 in 4) in a real‐life setting. Conclusion: This study builds upon earlier findings to confirm that carrier testing with reflex to sgNIPT is highly accurate for general population screening. Given this high accuracy and an NPV of 99.8%, this workflow should be considered as an option for most of the general pregnant population. When the biological partner sample is unavailable, this workflow should be recommended as the first‐line approach. Key points: What is already known about this topic? The utility of single‐gene NIPT to assess fetal risk of autosomal recessive (AR) conditions without the need for a partner sample is established. What does this study add? This study replicates and builds on a prior validation study by increasing the sample size four‐fold and restricting inclusion to general risk pregnancies—the population for which the test is intended.This study demonstrates the clinical validity of a quantitative approach to sgNIPT, demonstrating high sensitivity and specificity to identify affected pregnancies as high risk and unaffected pregnancies as low risk. [ABSTRACT FROM AUTHOR]

Antivenom is currently the standard-of-care treatment for snakebite envenoming, but its efficacy is limited by treatment delays, availability, and in many cases, species specificity. Many of the rapidly lethal effects of envenoming are caused by venom-derived toxins, such as phospholipase A2 (sPLA2); therefore, small molecule direct toxin inhibitors targeting these toxins may have utility as initial and adjunct therapies after envenoming. Varespladib (intravenous, IV) and varespladib-methyl (oral) have been shown to potently inhibit sPLA2s from snake venoms in murine and porcine models, thus supporting their further study as potential treatments for snakebite envenoming. In this pilot study, we tested the ability of these compounds to reverse neurotoxic effects of venom from the Australian and Papuan taipan (Oxyuranus scutellatus) subspecies in juvenile pigs (Sus domesticus). The mean survival time for control animals receiving Australian taipan venom (0.03 mg/kg, n = 3) was 331 min ± 15 min; for those receiving Papuan taipan venom (0.15 mg/kg, n = 3) it was 178 ± 31 min. Thirteen pigs received Australian taipan venom and treatment with either IV or oral varespladib (or with IV to oral transition) and all 13 survived the duration of the study (≥96 h). Eight pigs received Papuan taipan venom followed by treatment: Briefly: Two animals received antivenom immediately and survived to the end of the study. Two animals received antivenom treatment delayed 45 min from envenoming and died within 4 h. Two animals received similarly delayed antivenom treatment and were rescued by varespladib. Two animals were treated with varespladib alone after a 45-min delay. Treatment with varespladib only was effective but required repeat dosing over the course of the study. Findings highlight both the importance of early treatment and, as well, a half-life for the investigational inhibitors now in Phase II clinical trials for snakebite. Varespladib rapidly reversed weakness even when administered many hours post-envenoming and, overall, our results suggest that varespladib and varespladib-methyl could be efficacious tools in the treatment of sPLA2-induced weakness from Oxyuranus envenoming. Further clinical study as initial therapy and as potential method of rescue from some types of antivenom-resistant envenomings are supported by these data. [ABSTRACT FROM AUTHOR]

A late preterm infant with intrauterine growth restriction developed respiratory distress, tachypnoea and hypoxia after birth, requiring supplemental oxygen. Chest radiographs demonstrated persistent elevation of the right hemidiaphragm. Chest ultrasound initially demonstrated symmetrical bilateral diaphragm motion, but subsequent ultrasounds showed asymmetrical excursion with weaker movement of the right hemidiaphragm. Placental pathology demonstrated chronic infectious villitis secondary to cytomegalovirus (CMV), and subsequent CMV testing on the infant was positive. The infant was microcephalic and head imaging revealed intracranial calcifications, consistent with congenital CMV infection. CMV is the most common congenital infection and has a wide array of clinical manifestations. This report highlights the rarely described association between congenital CMV infection and respiratory distress due to underlying diaphragm dysfunction. In neonates with respiratory distress and features of congenital CMV infection, clinicians should have a high index of suspicion for diaphragm dysfunction. [ABSTRACT FROM AUTHOR]

Simple Summary: Dosimetry for preclinical radiotherapy research requires the standardization of dose validation and quality assurance procedures. Except for dose reference measurements, dosimetric quality control of image-guided small animal irradiation platforms is mostly performed with passive detectors (alanine and gafchromic films). This results in the inconvenient task of lengthy post-processing. In this paper, we carried out a dosimetric characterization of an active detection system based on inorganic scintillators in medium-energy X-rays. We implemented a cross-calibration framework based on international dosimetric protocols to assess the energy dependence of the detector. Additionally, we determined relative output factors for very small fields and compared them to other measurement systems (EBT3 film and CMOS sensor). We demonstrated the suitability of the inorganic scintillation system for the development of phantom-based end-to-end tests for dose verification in newly implemented preclinical radiotherapy irradiation techniques. The purpose of the study was to characterize a detection system based on inorganic scintillators and determine its suitability for dosimetry in preclinical radiation research. Dose rate, linearity, and repeatability of the response (among others) were assessed for medium-energy X-ray beam qualities. The response's variation with temperature and beam angle incidence was also evaluated. Absorbed dose quality-dependent calibration coefficients, based on a cross-calibration against air kerma secondary standard ionization chambers, were determined. Relative output factors (ROF) for small, collimated fields (≤10 mm × 10 mm) were measured and compared with Gafchromic film and to a CMOS imaging sensor. Independently of the beam quality, the scintillator signal repeatability was adequate and linear with dose. Compared with EBT3 films and CMOS, ROF was within 5% (except for smaller circular fields). We demonstrated that when the detector is cross-calibrated in the user's beam, it is a useful tool for dosimetry in medium-energy X-rays with small fields delivered by Image-Guided Small Animal Radiotherapy Platforms. It supports the development of procedures for independent "live" dose verification of complex preclinical radiotherapy plans with the possibility to insert the detectors in phantoms. [ABSTRACT FROM AUTHOR]

Introduction: Snakebite is an urgent, unmet global medical need causing significant morbidity and mortality worldwide. Varespladib is a potent inhibitor of venom secretory phospholipase A2 (sPLA2) that can be administered orally via its prodrug, varespladib-methyl. Extensive preclinical data support clinical evaluation of varespladib as a treatment for snakebite envenoming (SBE). The protocol reported here was designed to evaluate varespladib-methyl for SBE from any snake species in multiple geographies. Methods and Analysis: BRAVO (Broad-spectrum Rapid Antidote: Varespladib Oral for snakebite) is a multicenter, randomized, double-blind, placebo-controlled, phase 2 study to evaluate the safety, tolerability, and efficacy of oral varespladib-methyl plus standard of care (SoC) vs. SoC plus placebo in patients presenting with acute SBE by any venomous snake species. Male and female patients 5 years of age and older who meet eligibility criteria will be randomly assigned 1:1 to varespladib-methyl or placebo. The primary outcome is the Snakebite Severity Score (SSS) that has been modified for international use. This composite outcome is based on the sum of the pulmonary, cardiovascular, nervous, hematologic, and renal systems components of the updated SSS. Ethics and Dissemination: This protocol was submitted to regulatory authorities in India and the US. A Clinical Trial No Objection Certificate from the India Central Drugs Standard Control Organisation, Drug Controller General-India, and a Notice to Proceed from the US Food and Drug Administration have been obtained. The study protocol was approved by properly constituted, valid institutional review boards or ethics committees at each study site. This study is being conducted in compliance with the April 1996 ICH Guidance for Industry GCP E6, the Integrated Addendum to ICH E6 (R2) of November 2016, and the applicable regulations of the country in which the study is conducted. The trial is registered on Clinical trials.gov, NCT#04996264 and Clinical Trials Registry-India, 2021/07/045079 000062. [ABSTRACT FROM AUTHOR]

Background: Contemporary therapies improve breast cancer (BC) outcomes. Yet, many of these therapies have been increasingly linked with serious cardiotoxicity, including reports of profound hypertension. Yet, the incidence, predictors, and impacts of these events are largely unknown. Methods: Leveraging two large U.S.‐based registries, the National Inpatient Sample (NIS) and the Food and Drug Administration Adverse Event Reporting System (FAERS) databases, we assessed the incidence, factors, and outcomes of hypertensive events among BC patients from 2007 to 2015. Differences in baseline characteristics, hypertension‐related discharges, and complications were examined over time. Further, we performed a disproportionality analysis using reporting‐odds‐ratios (ROR) to determine the association between individual BC drugs and hypertensive events. Utilizing an ROR cutoff of >1.0, we quantified associations by drug‐class, and individual drugs with the likelihood of excess hypertension. Results: Overall, there were 5,464,401 BC‐admissions, of which 46,989 (0.8%) presented with hypertension. Hypertensive BC patients were older, and saw initially increased in‐hospital mortality, which equilibrated over time. The mean incidence of hypertension‐related admissions was 732 per 100,000 among BC patients, versus 96 per 100,000 among non‐cancer patients (RR 7.71, p < 0.001). Moreover, in FAERS, those with hypertension versus other BC‐treatment side‐effects were more frequently hospitalized (40.1% vs. 36.7%, p < 0.001), and were most commonly associated with chemotherapy (45.9%). Outside of Eribulin (ROR 3.36; 95% CI 1.37–8.22), no specific drug was associated with a higher reporting of hypertension; however, collectively BC drugs were associated with a higher odds of hypertension (ROR 1.66; 95% CI 1.09–2.53). Conclusions: BC therapies are associated with a substantial increase in limiting hypertension. [ABSTRACT FROM AUTHOR]

The African viperid snake genera Atheris, Cerastes, and Proatheris are closely related, similar in size, but occupy extremely divergent ecological niches (arboreal in tropical rainforests, fossorial in deserts, and swamp-dwelling, respectively). Their venoms have not previously been subjected to comparative analyses for their action upon the coagulation of blood, most notably with significant data deficiencies from Atheris and Proatheris. In contrast, the closely related genus Echis is well-documented as capable of producing potent procoagulant effects. In light of this, we set out to compare the coagulotoxic actions of Atheris ceratophora, A. chlorechis, A. desaixi, A. nitschei, A. squamigera, C. cerastes, C. cerastes gasperettii, C. vipera, and Proatheris superciliaris and explore potential pharmacological interventions to reestablish normal blood coagulation. All venoms displayed extremely potent procoagulant effects, over twice as fast as the most potent Echis reported to date. Although Cerastes is used in the immunising mixture of two different regionally available antivenoms (Inoserp-MENA with C. cerastes, C. cerastes gasperettii, C. vipera and Saudi Arabian polyvalent with C. cerastes), none of the other species in this study are included in the immunising mixture of any antivenom. Notably, all the Cerastes species were only neutralised by the Inoserp-MENA antivenom. C. cerastes venom was not neutralised well by the Saudi Arabian antivenom, with the low levels of recognition for any of the Cerastes venoms suggesting a strong regional variation in the venom of this species, as the C. cerastes venom tested was of African (Tunisian) origin versus Saudi locality used in that antivenom's production. The other antivenoms (Micropharm EchiTAbG, ICP EchiTAb-Plus-ICP, Inosan Inoserp Pan-Africa, Premium Serums PANAF Sub-Sahara Africa, South African Vaccine Producers Echis, South African Vaccine Producers Polyvalent) all displayed trivial-to-no ability to neutralise the procoagulant toxicity of any of the Atheris, Cerastes, or Proatheris venoms. Comparative testing of the enzyme inhibitors DMPS, marimastat, and prinomastat, revealed a very potent neutralising capacity of marimastat, with prinomastat showing lower but still significant potency at the same molar concentration, while a 5× molar concentration of DMPS had no apparent effect on procoagulant venom effects normalized by the other inhibitors. These results and methods contribute to the body of knowledge of potential clinical effects and data necessary for evidence-based advancement of clinical management strategies. [ABSTRACT FROM AUTHOR]

The availability of effective, reliably accessible, and affordable treatments for snakebite envenoming is a critical and long unmet medical need. Recently, small, synthetic toxin-specific inhibitors with oral bioavailability used in conjunction with antivenom have been identified as having the potential to greatly improve outcomes after snakebite. Varespladib, a small, synthetic molecule that broadly and potently inhibits secreted phospholipase A2 (sPLA2s) venom toxins has renewed interest in this class of inhibitors due to its potential utility in the treatment of snakebite envenoming. The development of varespladib and its oral dosage form, varespladib-methyl, has been accelerated by previous clinical development campaigns to treat non-envenoming conditions related to ulcerative colitis, rheumatoid arthritis, asthma, sepsis, and acute coronary syndrome. To date, twenty-nine clinical studies evaluating the safety, pharmacokinetics (PK), and efficacy of varespladib for non-snakebite envenoming conditions have been completed in more than 4600 human subjects, and the drugs were generally well-tolerated and considered safe for use in humans. Since 2016, more than 30 publications describing the structure, function, and efficacy of varespladib have directly addressed its potential for the treatment of snakebite. This review summarizes preclinical findings and outlines the scientific support, the potential limitations, and the next steps in the development of varespladib's use as a snakebite treatment, which is now in Phase 2 human clinical trials in the United States and India. [ABSTRACT FROM AUTHOR]

Background: Millions of Americans lost their jobs as a result of the COVID‐19 pandemic, placing immeasurable stress on families and making it difficult for parents to support their children's basic needs. Research shows that screening for social determinants of health is an important part of a child's well visit, noting that awareness of these factors leads to more holistic and improved quality of care. Due to increased precautions during the COVID‐19 pandemic and a significant decrease in well‐child visits and in‐person appointments, there was a marked decrease in the number of face‐to‐face opportunities for these screenings. In a time of increased need, methods such as telephone screenings represent an opportunity to assess needs and connect patients and families with helpful resources. Methods: This study occurred in Baltimore, Maryland at the University of Maryland Pediatrics at Midtown outpatient practice (PAM). Five paediatric resident physicians and 17 medical students developed a telephone welfare screening tool and called families receiving primary care at the clinic over a 9‐week period. The team documented identified needs and used a community resources database to provide resources to families over the phone. Data regarding the identified needs was collected and analysed throughout the screening process. Results: Volunteers contacted 671 families using our finalized screening tool. Of those, 349 answered the telephone call (52%), and 328 (49%) agreed to participate in the screening. Results showed that families commonly identified food insecurity (20%) and symptoms of depression (18%). This was consistent across families' home locations as analysed by postal ZIP code. Conclusions: This study suggests that telephone screening is a feasible and informative method for identifying and addressing the social needs of paediatric primary care patients and their families. Furthermore, our study supports the notion that there are significant and widespread social needs resulting from the COVID‐19 pandemic. [ABSTRACT FROM AUTHOR]

Within Neotropical pit-vipers, the Mexican/Central-American clade consisting of Atropoides, Cerrophidion, Metlapilcoatlus, and Porthidium is a wide-ranging, morphologically and ecologically diverse group of snakes. Despite their prevalence, little is known of the functional aspects of their venoms. This study aimed to fill the knowledge gap regarding coagulotoxic effects and to examine the potential of different therapeutic approaches. As a general trait, the venoms were shown to be anticoagulant but were underpinned by diverse biochemical actions. Pseudo-procoagulant activity (i.e., thrombin-like), characterized by the direct cleavage of fibrinogen to form weak fibrin clots, was evident for Atropoides picadoi, Cerrophidiontzotzilorum, Metlapilcoatlus mexicanus, M. nummifer, M. occiduus, M. olmec, and Porthidium porrasi. In contrast, other venoms cleaved fibrinogen in a destructive (non-clotting) manner, with C. godmani and C. wilsoni being the most potent. In addition to actions on fibrinogen, clotting enzymes were also inhibited. FXa was only weakly inhibited by most species, but Cerrophidion godmani and C. wilsoni were extremely strong in their inhibitory action. Other clotting enzymes were more widely inhibited by diverse species spanning the full taxonomical range, but in each case, there were species that had these traits notably amplified relatively to the others. C. godmani and C. wilsoni were the most potent amongst those that inhibited the formation of the prothrombinase complex and were also amongst the most potent inhibitors of Factor XIa. While most species displayed only low levels of thrombin inhibition, Porthidium dunni potently inhibited this clotting factor. The regional polyvalent antivenom produced by Instituto Picado Clodomiro was tested and was shown to be effective against the diverse anticoagulant pathophysiological effects. In contrast to the anticoagulant activities of the other species, Porthidium volcanicum was uniquely procoagulant through the activation of Factor VII and Factor XII. This viperid species is the first snake outside of the Oxyuranus/Pseudonaja elapid snake clade to be shown to activate FVII and the first snake venom of any kind to activate FXII. Interestingly, while small-molecule metalloprotease inhibitors prinomastat and marimastat demonstrated the ability to prevent the procoagulant toxicity of P. volcanicum, neither ICP antivenom nor inhibitor DMPS showed this effect. The extreme variation among the snakes here studied underscores how venom is a dynamic trait and how this can shape clinical outcomes and influence evolving treatment strategies. [ABSTRACT FROM AUTHOR]

Snakebite remains a significant public health burden globally, disproportionately affecting low-income and impoverished regions of the world. Recently, researchers have begun to focus on the use of small-molecule inhibitors as potential candidates for the neutralisation of key snake venom toxins and as potential field therapies. Bitis vipers represent some of the most medically important as well as frequently encountered snake species in Africa, with a number of species possessing anticoagulant phospholipase A2 (PLA2) toxins that prevent the prothrombinase complex from inducing clot formation. Additionally, species within the genus are known to exert pseudoprocoagulant activity, whereby kallikrein enzymatic toxins cleave fibrinogen to form a weak fibrin clot that rapidly degrades, thereby depleting fibrinogen levels and contributing to the net anticoagulant state. Utilising well-validated coagulation assays measuring time until clot formation, this study addresses the in vitro efficacy of three small molecule enzyme inhibitors (marimastat, prinomastat and varespladib) in neutralising these aforementioned activities. The PLA2 inhibitor varespladib showed the greatest efficacy for the neutralisation of PLA2 -driven anticoagulant venom activity, with the metalloproteinase inhibitors prinomastat and marimastat both showing low and highly variable degrees of cross-neutralisation with PLA2 anticoagulant toxicity. However, none of the inhibitors showed efficacy in neutralising the pseudo-procoagulant venom activity exerted by the venom of B. caudalis. Our results highlight the complex nature of snake venoms, for which single-compound treatments will not be universally effective, but combinations might prove highly effective. Despite the limitations of these inhibitors with regards to in vitro kallikrein enzyme pseudo-procoagulant venom activity, our results further support the growing body of literature indicating the potential use of small molecule inhibitors to enhance first-aid treatment of snakebite envenoming, particularly in cases where hospital and thus antivenom treatment is either unavailable or far away [ABSTRACT FROM AUTHOR]

A case study of 8-year-old girl is presented who transferred from an outside hospital for ophthalmology consult for concern of severe eye swelling. Topics include examines prior to presentation, the patient experienced 1 week of progressive right orbital swelling as she has photophobia, painful ophthalmoplegia, diplopia, as well as recent rhinorrhea, sore throat and subjective fevers.

African spitting cobras are unique among cobras for their potent anticoagulant venom activity arising from strong inhibition of Factor Xa. This anticoagulant effect is exerted by venom phospholipase A2 (Group I PLA2) toxins whose activity contributes to the lethality of these species. This anticoagulant toxicity is particularly problematic as it is not neutralized by current antivenoms. Previous work demonstrated this trait for Naja mossambica, N. nigricincta , N. nigricollis , and N. pallida. The present work builds upon previous research by testing across the full taxonomical range of African spitting cobras, demonstrating that N. ashei , N. katiensis , and N. nubiae are also potently anticoagulant through the inhibition of Factor Xa, and therefore the amplification of potent anticoagulant activity occurred at the base of the African spitting cobra radiation. Previous work demonstrated that the enzyme-inhibitor varespladib was able to neutralize this toxic action for N. mossambica, N. nigricincta , N. nigricollis , and N. pallida venoms. The current work demonstrates that varespladib was also able to neutralize N. ashei , N. katiensis , and N. nubiae. Thus varespladib is shown to have broad utility across the full range of African spitting cobras. In addition, we examined the cross-reactivity of the metalloprotease inhibitor prinomastat, which had been previously intriguingly indicated as being capable of neutralizing viperid venom PLA2 (Group II PLA2). In this study prinomastat inhibited the FXa-inhibiting PLA2 toxins of all the African spitting cobras at the same concentration at which it has been shown to inhibit metalloproteases, and thus was comparably effective in its cross-reactivity. In addition we showed that the metalloprotease-inhibitor marimastat was also able to cross-neutralize PLA2 but less effectively than prinomastat. Due to logistical (cold-chain requirement) and efficacy (cross-reactivity across snake species) limitations of traditional antivenoms, particularly in developing countries where snakebite is most common, these small molecule inhibitors (SMIs) might hold great promise as initial, field-based, treatments for snakebite envenoming as well as addressing fundamental limitations of antivenom in the clinical setting where certain toxin effects are unneutralized. [ABSTRACT FROM AUTHOR]

Palearctic vipers are medically significant snakes in the genera Daboia, Macrovipera, Montivipera , and Vipera which occur throughout Europe, Central Asia, Near and Middle East. While the ancestral condition is that of a small-bodied, lowland species, extensive diversification has occurred in body size, and niche specialization. Using 27 venom samples and a panel of in vitro coagulation assays, we evaluated the relative coagulotoxic potency of Palearctic viper venoms and compared their neutralization by three antivenoms (Insoserp Europe, VIPERFAV and ViperaTAb) and two metalloprotease inhibitors (prinomastat and DMPS). We show that variation in morphology parallels variation in the Factor X activating procoagulant toxicity, with the three convergent evolutions of larger body sizes (Daboia genus, Macrovipera genus, and Vipera ammodytes uniquely within the Vipera genus) were each accompanied by a significant increase in procoagulant potency. In contrast, the two convergent evolutions of high altitude specialization (the Montivipera genus and Vipera latastei uniquely within the Vipera genus) were each accompanied by a shift away from procoagulant action, with the Montivipera species being particularly potently anticoagulant. Inoserp Europe and VIPERFAV antivenoms were both effective against a broad range of Vipera species, with Inoserp able to neutralize additional species relative to VIPERFAV, reflective of its more complex antivenom immunization mixture. In contrast, ViperaTAb was extremely potent in neutralizing V. berus but, reflective of this being a monovalent antivenom, it was not effective against other Vipera species. The enzyme inhibitor prinomastat efficiently neutralized the metalloprotease-driven Factor X activation of the procoagulant venoms. In contrast, DMPS (2,3-dimercapto-1-propanesulfonic acid), which as been suggested as another potential treatment option in the absence of antivenom, DMPS failed against all venoms tested. Overall, our results highlight the evolutionary variations within Palearctic vipers and help to inform clinical management of viper envenomation. [ABSTRACT FROM AUTHOR]

Noonan syndrome (NS) is a genetic disorder with distinctive physical features and often multiple organ involvement. Bleeding disorders are reported in over half of patients with NS, including thrombocytopenia and platelet dysfunction. Neonatal alloimmune thrombocytopenia (NAIT) is an alloantigenic thrombocytopenia that can present with severe bleeding. Here, we present a case of intracranial hemorrhage and severe thrombocytopenia in a neonate found to have both NAIT and a de novo heterozygous pathogenic variant in PTPN11, consistent with Noonan syndrome. [ABSTRACT FROM AUTHOR]

BACKGROUND: Data describing antibiotic use in U.S. nursing homes remain limited. We report antibiotic use among skilled nursing facility residents from 29 U.S. nursing homes and assessed correlations between antibiotics prescribed to residents in skilled care and nursing home characteristics. DESIGN: Retrospective cohort study. SETTING: Twenty‐nine U.S. nursing homes in the same healthcare corporation. PARTICIPANTS: Residents receiving skilled care in 2016. MEASUREMENTS: We used pharmacy invoice and nursing home census data to calculate the days of antibiotic therapy per 1,000 days of skilled care (1,000 DOSC), the rate of antibiotic starts per 1,000 DOSC, the length of antibiotic therapy, and the average antibiotic spectrum index. We also assessed correlations between antibiotic use and nursing home characteristics. RESULTS: Antibiotics accounted for an average of 9.6% (±0.6%) of systemic medications prescribed among residents receiving skilled care. On average, 26.8% (±2.9%) of antibiotics were intravenous. Fluoroquinolones were prescribed at the highest rates (19% across all facilities), followed by beta‐lactam/beta‐lactamase inhibitors (11%), first‐ and second‐generation cephalosporins, sulfonamides, and oral tetracyclines (each at 9%). Both the proportion of residents using enrolled in Medicare and number of unique prescribers responsible for systemic prescriptions positively correlated with the rate of antibiotic starts. CONCLUSIONS: Our study demonstrates that pharmacy invoices represent a useful and preexisting source of data for assessing antibiotic prescriptions among individuals receiving skilled nursing care. The correlation between the number of unique prescribers and antibiotic starts suggests that prescribers are central to efforts to improve antibiotic use in nursing homes. [ABSTRACT FROM AUTHOR]

Fecal microbiota transplantation (FMT) is a successful therapeutic strategy for treating recurrent Clostridioides difficile infection. Despite remarkable efficacy, implementation of FMT therapy is limited and the mechanism of action remains poorly understood. Here, we demonstrate a critical role for the immune system in supporting FMT using a murine C. difficile infection system. Following FMT, Rag1 heterozygote mice resolve C. difficile while littermate Rag1−/− mice fail to clear the infection. Targeted ablation of adaptive immune cell subsets reveal a necessary role for CD4+ Foxp3+ T-regulatory cells, but not B cells or CD8+ T cells, in FMT-mediated resolution of C. difficile infection. FMT non-responsive mice exhibit exacerbated inflammation, impaired engraftment of the FMT bacterial community and failed restoration of commensal bacteria-derived secondary bile acid metabolites in the large intestine. These data demonstrate that the host's inflammatory immune status can limit the efficacy of microbiota-based therapeutics to treat C. difficile infection. Transfer of a host's microbiota by faecal microbiota transplantation has shown benefit in the context of recurrent Clostridioides difficle infection. Here the authors shows the inflammatory status of the recipient can impact on engraftment and the efficacy of the introduced microbiota in a model of C.difficile infection. [ABSTRACT FROM AUTHOR]

Background: Inferior vena cava filter (IVCF) use is common after a venous thromboembolic event (VTE). Cancer is associated with higher rates of VTEs and is also seen in a significant proportion of patients requiring IVCF. As hospital readmissions remain a frequently scrutinized metric, we sought to evaluate the impact of cancer on hospital-readmission rates and in-hospital outcomes among patients with VTEs who received an IVCF.Methods: Leveraging the 2013 to 2014 Nationwide Readmission Database, we identified adult patients presenting with a VTE in the United States and evaluated 30-day readmission rates and readmission in-hospital outcomes postindex-admission. Multivariable logistic regression was used to identify factors associated with readmission after an index-procedure, including traditional and nontraditional cardiovascular risk factors, as well as hospital-level characteristics.Results: Among the 619 241 patients presenting with a VTE at index-admission, 11.2% of patients received IVCF on index-admission, of which 30.9% had cancer. The 30-day readmission rate amongst IVCF recipients was 15.8% (N = 10 927), and 19.9% amongst those with cancer compared to 13.9% in patients without cancer (P < .001). Moreover, cancer patients had longer lengths of stay in the hospital (4.5 ± 0.2 vs 4.0 ± 0.1 days; P = .02), higher cost of care ($10 900 ± 308 vs $9242 ± 206; P = .007), but no difference in mortality (8.3% vs 6.3%; P = .70) during readmission compared to noncancer patients.Conclusion: Readmission after IVCF placement is common. In patients readmitted after an IVCF implantation, those with cancer have longer hospital stays and higher costs of care. However, in-hospital mortality is similar to those without cancer. [ABSTRACT FROM AUTHOR]

As health professionals develop health communication for coronavirus disease 2019 (COVID-19), we implore that these communication approaches do not include fear appeals. Fear appeals, also known as scare tactics, have been widely used to promote recommended preventive behaviors. We contend that unintended negative outcomes can result from fear appeals that intensify the already complex pandemic and efforts to contain it. We encourage public health professionals to reevaluate their desire to use fear appeals in COVID-19 health communication and recommend that evidence-based health communication be utilized to address the needs of a specific community, help people understand what they are being asked to do, explain step-by-step how to complete preventative behaviors, and consider external factors needed to support the uptake of behaviors. To aid health professionals in redirecting away from the use of fear appeals, we offer a phased approach to creating health communication messages during the COVID-19 crisis. [ABSTRACT FROM AUTHOR]

In carcinogenesis, the 14-3-3σ isoform (stratifin) is implicated by being downregulated in a mode of classic tumour suppression gene (TSG) loss and also via elevated oncogenic roles; with both scenarios appearing to be hallmarks of 14-3-3σ deregulation, depending on tumour stage or context. Mouse skin models highlight tumour-suppressive roles, as the Er/Er+/– repeated epilation stain possesses germline mutations that result in hyperplasia, failed follicular differentiation and susceptibility to squamous cell carcinoma (SCC). In transgenic models, 14-3-3σ knockout supports early roles, resulting in rapid papilloma formation in classic two-stage DMBA/TPA chemical carcinogenesis; however, our previous studies in this model demonstrated targeted overexpression of 14-3-3σ led to SCC of a follicular origin in collaboration with Fos and well-differentiated SCC in collaboration with rasHa. Therefore, to study mechanisms driving/inhibiting skin carcinogenesis, stage-specific expression of endogenous 14-3-3σ (stratifin) was analysed in early skin carcinogenesis driven by activated rasHa expression (HK1.ras) and subsequently via conditional RU486-inducible 14-3-3σ knockout (K14.creP-Δ14-3-3σ). Consistent with 14-3-3σ roles previously observed in epidermal differentiation, HK1.ras hyperplasia and early papillomas displayed elevated 14-3-3σ expression in suprabasal keratinocytes and in occasional K1-positive basal keratinocytes as they committed to differentiate. Older HK1.ras mice exhibited increasing 14-3-3σ positivity in papilloma basal layers, suggesting attempts to protect basal-layer p53 TSG function, given that 14-3-3σ acts as a chaperone protein to remove/relocate MDM2 for degradation, thus maintaining p53 levels. Indeed, such papillomas expressed activated p-MDM2166 confined to suprabasal layers, resulting in strong basal layer p53 expression and thus HK1.ras papillomas lacked malignant conversion. In mice where 14-3-3σ functions were ablated via an RU486-inducible Cre/loxP system expressed from a keratin 14 (K14) promoter (K14.creP-Δ14-3-3σ), treated HK1.ras-K14.Δ14-3-3σ mice exhibited a rapid papillomatogenesis and produced larger papillomas. These papillomas also exhibited rapid conversion to malignancy, associated with increased activated p-MDM2166 expression in basal layers and resultant p53 loss. These observations suggest that 14-3-3σ plays tumour suppressive roles involving p53 protection, where failure to regulate MDM2 activity led to p53 loss and susceptibility to malignant conversion. P11 Abstract withdrawn. [ABSTRACT FROM AUTHOR]

This essay considers the photographic encounter in Black New Orleans, focusing on a news image of a fire that destroyed several homes in the wake of Hurricane Katrina. I trace the circulation of this image, first published in Time, examining the devastation it documents as well as the race and class stereotypes it perpetuates. I simultaneously follow the homeowners as they renegotiate the photograph, asserting their true identity and position. Inspired by Roland Barthes and the search for a "just" image, the essay explores the possibilities of the photographic encounter for the reclamation of Black being and dwelling. [ABSTRACT FROM AUTHOR]

Trisomy 18 is an autosomal trisomy condition characterized by minor to major birth defects, severe disabilities, and high rates of pre‐ and postnatal mortality. Interventions for these infants have traditionally been withheld with focus instead on palliative support. The issues and attitudes surrounding corrective surgery of congenital heart defects, which is a birth defect that occurs in approximately 90% of infants with trisomy 18, is of our study's interest as recent literature has indicated that cardiac surgery is being performed and may lead to improved survival compared to palliative care. Thus, our study aimed to describe clinician attitudes toward cardiac surgery and trisomy 18. We surveyed 378 clinicians from multiple specialties, including genetic counselors, involved in the pre‐ and postnatal care of infants with trisomy 18. Descriptive statistics were performed to describe all clinicians' responses, and a secondary analysis with stratifications by clinician type was also performed. Forty‐eight percent (n = 378) of clinicians felt it was appropriate to discuss the option of cardiac surgery. Ethical concerns and insufficient outcome data were the most agreed upon reasons for not offering cardiac surgery. Trisomy 18 not being uniformly lethal and expressed parental wishes were the most agreed upon justifications for offering surgery. Clinicians felt the discussion of the option of cardiac surgery is appropriate, however are hesitant due to ethical concerns and insufficient outcome data. Results from this study aim to promote discussion and collaboration among clinicians to improve consistency in patient care. [ABSTRACT FROM AUTHOR]

Objective: Patients with BRAF-mutant colorectal cancer (CRC) have a poor prognosis. Molecular status is not currently used to select which drug to use in combination with radiotherapy. Our aim was to identify drugs that radiosensitise CRC cells with known BRAF status. Methods: We screened 298 oncological drugs with and without ionising radiation in colorectal cancer cells isogenic for BRAF. Hits from rank product analysis were validated in a 16-cell line panel of human CRC cell lines, using clonogenic survival assays and xenograft models in vivo. Results: Most consistently identified hits were drugs targeting cell growth/proliferation or DNA damage repair. The most effective class of drugs that radiosensitised wild-type and mutant cell lines was PARP inhibitors. In clonogenic survival assays, talazoparib produced a radiation enhancement ratio of 1.9 in DLD1 (BRAF-wildtype) cells and 1.8 in RKO (BRAF V600E) cells. In DLD1 xenografts, talazoparib significantly increased the inhibitory effect of radiation on tumour growth (P = 0.01). Conclusions: Our method for screening large drug libraries for radiosensitisation has identified PARP inhibitors as promising radiosensitisers of colorectal cancer cells with wild-type and mutant BRAF backgrounds. [ABSTRACT FROM AUTHOR]

As transgender and gender-expansive (TGE) youth and young adults (YYA) navigate challenging environments, they often seek spaces for safety and acceptance. This study explores ways in which a group of TGE YYA who were engaged with a community-based service organization make sense of their experiences, challenges, and successes in ways that illuminate the factors and processes associated with resilience. Secondary data analysis was conducted on qualitative responses from 85 TGE YYA ages 13–24. The themes that emerged provide insight into the ways community-based programs and providers can understand and support the resilience of TGE YYA. [ABSTRACT FROM AUTHOR]

Le Kèr Creole: Creole Compositions & Stories from Louisiana This musical ethnography of Louisiana Creole arrives in troubled times - in the midst of a multilayered public health crisis, fueled by a global pandemic alongside persistent police violence with disproportionate and deadly impact for Black people. Accepting this approach, the book succeeds in laying out the history and cultural context of Louisiana Creole from the essays, archival letters, photographs, and architectural drawings it contains. [Extracted from the article]

Background: Cancer inducing a hypercoagulable state, venous thromboembolism (VTE) remains a leading cause of morbidity and mortality globally. We assessed the impacts of cancer on the likelihood for readmission after a VTE-targeted procedure.Methods: We created a new cohort using discharge-level data from all hospitalizations from State Inpatient Databases of geographically dispersed participating states (18-27 states).Results: In those presenting with VTE during index-admission (619 241), 2.4% patients underwent catheter directed thrombolytic therapy (CDL) on index admission and among those 20.3% had cancer. Moreover, the 30-day readmission rate amongst CDL recipients (10 776 overall) was 14.3% in those with cancer compared to 8.8% in those with no cancer history (P < .0001). Additionally, in-hospital mortality (5.7% vs 1.1%; P = 0.009) and cost-of-care ($11 014 ± 914 vs $10 520 ± 534; P = .04) was significantly higher in cancer compared to noncancer.Conclusion: The use of CDL does not appear to reduce the risk of returning for a VTE-related admission in cancer. [ABSTRACT FROM AUTHOR]

The social and religious work of African-American women in New Orleans who mourn and memorialise the dead attends primarily to sons and grandsons, the young black men who are most frequently the victims of homicide. Based on ethnographic and historical research in two Christian congregations, this article examines the forms of relatedness that women have developed to support and advocate for each other, the displaced, and the deceased. Tracing more broadly the development of vulnerability and violence at the urban margins, I argue that this work unfolds in a continued context of social death, predicated on dominant and still racist determinations of human value. I thus examine the transformative potential of African-American religious women’s relational practices, highlighting in particular their assertion of black social and spiritual value, in the kingdom of God if not yet in the inclusive, just, and sustainable city and world they envision. [ABSTRACT FROM AUTHOR]

The inclusion of lesbian, gay, bisexual, transgender, and queer (LGBTQ) perspectives and experiences in the social work classroom is necessary to adequately include LGBTQ students and prepare graduates to practice effectively. Drawing from queer theory as a theoretical framework and the authors’ experiences in practice and teaching/learning spaces with LGBTQ youth, this article offers practical strategies for creating classrooms inclusive of LGBTQ persons. Queering the classroom builds skills in students beyond practice with LGBTQ people and communities, thereby enhancing their capacity to engage diversity in practice more generally and to advance human rights and social justice. [ABSTRACT FROM AUTHOR]

The objective of the present study was to evaluate the changes in blood metabolites, AA profile, and oxidative stress markers in American Foxhound dogs fed a nutrient-fortified endurance diet while undergoing unstructured endurance exercise over several months. Thirty-six adult American Foxhound dogs (mean age: 4.5, range 2 to 10 yr and mean BW: 34.7, range: 23.1 to 46.9 kg) were selected to participate in the study. Prior to the study, all dogs consumed a commercial diet for 16 wk. After collecting baseline blood samples, dogs were assigned to a standard commercial performance diet (control) or a nutrient-fortified dog food (test). Dogs were balanced by gender, age, body weight, and athletic performance between diets. During the study, dogs underwent 78 bouts of exercise, with approximately 22 km/bout. Blood samples were collected after 40, 75, 138, and 201 d on study (October 2012 to March 2013). All blood metabolites were similar at baseline and serum chemistry profile remained within normal ranges throughout the study. Over time, plasma taurine and vitamin E concentrations decreased (P < 0.05) in dogs fed the control diet but were maintained or increased (P < 0.05) in dogs fed the treatment diet. Also, plasma creatinine and triglycerides were lower (P < 0.05) and blood phosphorus and alkaline phosphatase were higher (P < 0.05) in dogs fed the treatment diet. Vitamin E and taurine status of dogs appear to be affected by extended endurance exercise. These data suggest dogs undergoing endurance exercise may benefit from supplementation of vitamin E and taurine to minimize oxidation and maintain taurine status. [ABSTRACT FROM AUTHOR]

People living with the human immunodeficiency virus (HIV) should receive pneumococcal vaccinations as part of their routine health maintenance. Our goal was to create a “virtual clinic” to help increase rates of pneumococcal vaccination among people living with HIV without adding substantially to the workload of primary providers. We used administrative data from our Veterans Affairs (VA) medical center to identify a cohort of veterans living with HIV who were not current with either the 13-valent pneumococcal conjugate vaccine (PCV13), the 23-valent pneumococcal polysaccharide vaccine (PPSV23) or both. We enrolled these individuals (n = 99) into a virtual clinic, notified providers via the electronic medical record and mailed letters to the veterans recommending they receive a pneumococcal vaccine. We also wrote orders for the appropriate pneumococcal vaccine that expired after 90 days. Among the virtual clinic cohort, 38% (38/99) of patients received the recommended vaccine within 180 days. Concurrent with our intervention, the Veterans Health Administration deployed a system-wide pneumococcal vaccine clinical reminder that incorporated recent PCV13 recommendations. To discern any effect of the virtual clinic beyond that of the clinical reminder, we compared the rate of PCV13 vaccinations among all HIV-positive veterans at our institution to the equivalent population from 2 other VA medical centers in Ohio. With consideration of the VHA’s system-wide clinical reminder, the proportion of HIV-positive patients who received PCV13 in the first 90 days following the virtual clinic intervention was greater at our facility compared to another Ohio VA medical center (P < 0.05). The virtual clinic improved the pneumococcal vaccine coverage among HIV-positive veterans. These outcomes suggest that even in conjunction with a system-wide clinical reminder, the virtual clinic strategy improves vaccination rates among a high-risk population. [ABSTRACT FROM PUBLISHER]

Triceps tendon ruptures are rare injuries and are frequently missed on initial presentation to the emergency department. In cases of complete rupture, surgical repair is recommended but no guidelines exist on the optimum reconstructive technique or rehabilitation. We present a surgical technique and rehabilitation programme for the management of these injuries. A midline posterior incision is performed, the ruptured triceps tendon is identified and mobilized, and the tendon footprint is prepared. The tendon is then repaired using bone suture anchors, with a parachute technique, and held in 40° of flexion. The rehabilitation programme is divided into five phases, over a period of 12 weeks. Range of movement is gradually increased in a brace for the first 6 weeks. Rehabilitation is gradually increase in intensity, progressing from isometric extension exercises to weight-resisted exercises, and finally plyometrics and throwing exercises. Our surgical technique provides a solid tendon repair without the need for further metalwork removal. The graduated rehabilitation programme also helps to protect the integrity of the repair at the same time as enabling patients to gradually increase the strength of the triceps tendon and ultimately return to sport activities. [ABSTRACT FROM AUTHOR]

Objectives To identify features of community nursing home ( NH) environments associated with lower rates of overall antibiotic use. Design This pilot study used an explanatory sequential design that incorporated comparative feedback about antibiotic use to inform a discussion about antimicrobial stewardship practices in community NHs. Setting NHs. Participants Clinical leadership of five NHs. Measurements For the quantitative phase, the number of antibiotic prescriptions, length of therapy, and days of therapy/1,000 days of care were measured at six NHs. For the qualitative phase, semistructured interviews were conducted with healthcare workers in leadership positions at five community NHs. Transcripts from the recorded interviews were assessed using emergent thematic analysis. For the triangulation phase, themes from the semistructured interviews were evaluated in the context of each NH's antibiotic use. Results The number of antibiotic prescriptions ranged from 172 to 1,244, with 50% to 83% written for 7 days or fewer. All NHs reported a similar proportion of fluoroquinolone use (27-32% of days of therapy). Triangulation yielded six themes for which the environment at each facility ranged from less- to more-supportive antimicrobial stewardship: practice patterns, external influences, infection control, leadership, communication, and facility culture. All NHs reported pressure from well-intentioned family members to prescribe antibiotics. NHs with shorter lengths of therapy and lower overall antibiotic use were consonant with an environment more supportive of antimicrobial stewardship. Conclusion These findings suggest several features of NHs that are supportive of antimicrobial stewardship: practice patterns grounded in established diagnostic criteria, proactive infection control and prevention, open communication and interconnectedness among staff. [ABSTRACT FROM AUTHOR]

While migration has been shown to be a risk factor for HIV, variation in HIV prevalence by subgroups of migrants needs further exploration. This paper documents the HIV prevalence and key characteristics among male foreign migrants in Cape Town, South Africa and the effectiveness of respondent-driven sampling (RDS) to recruit this population. Participants in this cross-sectional study completed a behavioral risk-factor questionnaire and provided a dried blood sample for HIV analysis. Overall HIV prevalence was estimated to be 8.7 % (CI 5.4-11.8) but varied dramatically by country of origin. After adjusting for country of origin, HIV sero-positivity was positively associated with older age (p = 0.001), completing high school (p = 0.025), not having enough money for food (p = 0.036), alcohol use (p = 0.049), and engaging in transactional sex (p = 0.022). RDS was successful in recruiting foreign migrant men. A better understanding of the timing of HIV acquisition is needed to design targeted interventions for migrant men. [ABSTRACT FROM AUTHOR]

Religion and spirituality (R/S) are important components of many individuals' lives, and spirituality is often employed by women coping with pregnancy complications. To characterize how prenatal genetic counselors might address spiritual issues with patients, 283 English and Spanish speaking women receiving prenatal genetic counseling in Houston, Texas were surveyed post-counseling using both the Brief RCope and questions regarding interest in spiritual exploration. Genetic counselors were concurrently surveyed to identify religious/spiritual language used within sessions and perceived importance of R/S. Genetic counselors were significantly more likely to identify R/S as important to a patient when patients used religious/spiritual language ( p < 0.001). Conversely, when no religious/spiritual terms were present, the counselor felt uncertain about the importance of R/S 63 % of the time. However, 67 % of patients reported that they felt comfortable sharing their faith as it relates to their pregnancy, and 93 % reported using positive religious coping. Less than 25 % reported a desire for overt religious actions such as prayer or scripture exploration. Therefore, most patients' desires for spiritual exploration center in the decision making and coping processes that are in line with the genetic counseling scope of practice. Thus, counselors should feel empowered to incorporate spiritual exploration into their patient conversations. [ABSTRACT FROM AUTHOR]

Background. Little is known about the American public's perceptions or knowledge about antibiotic-resistant bacteria or antibiotic misuse. We hypothesized that although many people recognize antibiotic resistance as a problem, they may not understand the relationship between antibiotic consumption and selection of resistant bacteria. Methods. We developed and tested a survey asking respondents about their perceptions and knowledge regarding appropriate antibiotic use. Respondents were recruited with the Amazon Mechanical Turk crowdsourcing platform. The survey, carefully designed to assess a crowd-sourced population, asked respondents to explain "antibiotic resistance" in their own words. Subsequent questions were multiple choice. Results. Of 215 respondents, the vast majority agreed that inappropriate antibiotic use contributes to antibiotic resistance (92%), whereas a notable proportion (70%) responded neutrally or disagreed with the statement that antibiotic resistance is a problem. Over 40% of respondents indicated that antibiotics were the best choice to treat a fever or a runny nose and sore throat. Major themes from the free-text responses included that antibiotic resistance develops by bacteria, or by the infection, or the body (ie, an immune response). Minor themes included antibiotic overuse and antibiotic resistance caused by bacterial adaptation or an immune response. Conclusions. Our findings indicate that the public is aware that antibiotic misuse contributes to antibiotic resistance, but many do not consider it to be an important problem. The free-text responses suggest specific educational targets, including the difference between an immune response and bacterial adaptation, to increase awareness and understanding of antibiotic resistance. [ABSTRACT FROM AUTHOR]

The article presents a study on the correlation of murine norovirus infection with vancomycin-resistant Enterococcus faecium (VRE) reduced density in the intestinal tract of mice having antibiotic-induced loss of colonization resistance. The findings show that an orally bioavailable Toll-like receptor 7 (TLR-7) ligand which stimulates the intestine's innate immune pathways restores colonization resistance over an antibiotic-resistant bacterial pathogen.

With the rapidly evolving field of prenatal testing, there is a growing need to provide support for women pursuing termination of pregnancy following the discovery of a fetal anomaly. Previous studies have documented that women in this situation often feel unsupported, but the type of resources desired by this population remains undetermined. We studied the awareness and utilization of support resources in 51 women at the time of the procedure, at 6 weeks, and at 3 months following the event. Though largely knowledgeable of existing resources at the time of the procedure, only 50 % admitted contemplating their individualized need for support. Most expected to rely on the support of family and friends. Additionally, 50 % expressed the desire to commemorate the pregnancy, though none wanted direct contact with their healthcare provider(s). Responses from the 6 weeks and 3 months assessments were consistent with previous literature as many women indicated not coping as expected and were unprepared for the psychological consequences following the procedure. Our findings indicate that women in these situations may not realize what their long-term support needs will be. They further indicate that guidelines for routine follow-up care should be established among healthcare providers that respect this population's initial desires to avoid reminders of the pregnancy and promote a flexible timeframe for support uptake. Additional support resources that promote flexible uptake as well as meet the desires of anonymity and ease of access need to be developed for this population. [ABSTRACT FROM AUTHOR]