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Critical care nurses occasionally confront patient conditions that are not common. One such condition is hepatorenal syndrome (HRS). Three primary processes contribute to regional alterations in circulation in the renal and splanchnic beds. These processes include effective hypovolemia from the massive release of vasoactive mediators, thereby underfilling circulation, systemic and splanchnic vasodilation along with renal vasoconstriction, and hyperdynamic circulation. A 'second-hit' hypothesis, whereby a triggering event causes intravascular volume depletion, likely initiates the development of HRS. The idea of a second hit focuses the attention of the health care team on surveillance strategies to prevent or limit HRS in patients with advanced cirrhosis and ascites. The treatment goal is to restore systemic and splanchnic vasoconstriction, while promoting renal vasodilation, balance sodium, and achieve euvolemia. The critical care nurse must maintain ongoing education to care for the patient with this complex syndrome in order to prevent complications and death. [ABSTRACT FROM AUTHOR]

Critical care nurses assess and treat clinical conditions associated with inadequate oxygenation. Changes in regional organ (gut) blood flow are believed to occur in response to a decrease in oxygenation. Although the stomach is a widely accepted monitoring site, there are multiple methodological and measurement issues associated with the gastric environment that limit the accuracy of P CO2 detection. The rectum may provide nurses with an alternative site for monitoring changes in P CO2 without the limitations associated with gastric monitoring. This pilot study used a repeated measures design to examine changes in gastric and rectal P CO2 during elective coronary artery bypass grafting with cardiopulmonary bypass (CPB) and in the immediate 4-hr postoperative period in 26 subjects. The systemic indicators explained little variation in the regional indicators during protocol. A comparison of rectal and gastric P CO2 revealed no statistically significant differences in the direction or magnitude of change over any phase of cardiac surgery (baseline, CPB, post-CPB). A reduction in both rectal and gastric P CO2 occurred during CPB, and both values trended upward during the post-CPB phase. However, poor correlation and agreement was found between the measures of P CO2 at the two sites. Although clinically important, the cause is unclear. Possible explanations include variation in CO2 production between the gastric and rectal site, differences in sensitivity of the two monitoring instruments, or the absence of hemodynamic complications, which limited the extent of change in P CO2. Further investigation using patients with more profound changes in oxygenation are needed to identify response patterns and possible mechanisms. [ABSTRACT FROM AUTHOR]

Abstract Background Malaria treatment-seeking practices vary worldwide and Bangladesh is no exception. Individuals from 88 villages in Rajasthali were asked about their treatment-seeking practices. A portion of these households preferred malaria treatment from the National Control Programme, but still a large number of households continued to use drug vendors and approximately one fourth of the individuals surveyed relied exclusively on non-control programme treatments. The risks of low-control programme usage include incomplete malaria treatment, possible misuse of anti-malarial drugs, and an increased potential for drug resistance. Methods The spatial patterns of treatment-seeking practices were first examined using hot-spot analysis (Local Getis-Ord Gi statistic) and then modelled using regression. Ordinary least squares (OLS) regression identified key factors explaining more than 80% of the variation in control programme and vendor treatment preferences. Geographically weighted regression (GWR) was then used to assess where each factor was a strong predictor of treatment-seeking preferences. Results Several factors including tribal affiliation, housing materials, household densities, education levels, and proximity to the regional urban centre, were found to be effective predictors of malaria treatment-seeking preferences. The predictive strength of each of these factors, however, varied across the study area. While education, for example, was a strong predictor in some villages, it was less important for predicting treatment-seeking outcomes in other villages. Conclusion Understanding where each factor is a strong predictor of treatment-seeking outcomes may help in planning targeted interventions aimed at increasing control programme usage. Suggested strategies include providing additional training for the Building Resources across Communities (BRAC) health workers, implementing educational programmes, and addressing economic factors.

Protective clothing standards, such as test methods published by ASTM International, play an integral role in ensuring the performance of personal protective equipment. The standard tests are not without limitations and are periodically reviewed and often updated. Some tests may not be reflective of in-use conditions. A new test cell was designed using sanitary fixtures to evaluate the effect of glove stretch on barrier performance using fluorescein solution as the challenge agent for enhanced visualization and fluorometer detection. Domed-shaped and flat screens were developed to permit and limit glove stretch within the test cell. The barrier performance of glove swatches was evaluated for both stretched and unstretched states. Latex, nitrile, and vinyl glove models of various thicknesses were evaluated. The tests were conducted following pressure and time parameters specified in ASTM F903, ASTM F1670, and ASTM F1671. Fluorescein solution movement, which may occur through penetration, was measured using a fluorometer. Glove stretch caused a reduction in glove thickness ranging from 16% to 40%. Overall, 21 sample failures were found (16.7%; n = 126) regardless of test condition. Nitrile gloves provided better barrier efficacy with the lowest failure rates (2.38%; 1 failure out of 42) compared to latex (19.4%; 7 failures out of 36) and vinyl gloves (27.1%; 13 failures out of 48). Differences in failure rates between stretched and unstretched gloves were insignificant; however, the latex material showed a 2.5 times increase in failures when stretched compared to unstretched. The new test apparatus was able to differentiate between the barrier performance of different glove materials. The use of a domed screen allowed the gloves to stretch, a condition that better represents the state of gloves when in use. Analysis of samples collected from the glove surface opposite to the exposure may provide a way to assess chemical permeation in addition to penetration., (Published by Oxford University Press on behalf of The British Occupational Hygiene Society 2024.)

The National Institute for Occupational Safety and Health recommends the use of nitrile gloves with a minimum thickness of 5.0 ± 2.0 mil [0.127 ± 0.051 millimeters] in situations where it is suspected or known that fentanyl or other illicit drugs are present. However, there is limited data available on fentanyl permeation through gloves. Current test methods used to measure fentanyl permeation do not consider the effect of glove fit and flexion. Furthermore, first responders need to have PPE readily available in the field, and storage conditions may affect the protective performance of the gloves. The objective of this study was to evaluate the effects of glove stretch and storage temperatures on glove durability and barrier performance against fentanyl. Nine nitrile glove models previously shown to be resistant to fentanyl permeation were selected for this investigation. These nine models were stretched 25% in one linear direction, to consider glove fit and flexion, and tested against fentanyl hydrochloride permeation. Additionally, four of the nine glove models were stored at 48 °C, 22 °C, and -20 °C, and evaluated for tensile strength, ultimate elongation, and puncture resistance after up to 16 wk of storage and fentanyl permeation after up to 8 wk of storage. At least one sample for six of the nine tested models had maximum permeation over the test method fail threshold when stretched. The tested storage temperatures showed no effect on glove tensile strength, ultimate elongation, and puncture resistance. The findings of this study can be used to inform PPE recommendations, with consideration to storage practices and proper sizing for first responders with potential exposure to fentanyl and other illicit drugs. The results of this study can be used to assess the need for new standard test methods to evaluate the barrier performance of gloves and shelf-life determination with consideration to glove fit.

The Nearctic species of Saropogon Loew, 1847 north of Mexico are reviewed, with 19 species recognized and one described as new: Saropogonpyrodes sp. nov. from Arizona. This previously recognized new species has awaited description since its first collection in 1964. Only after a community scientist posted photographs taken in nature to an online database did its description become a priority. All species of Saropogon occurring in the Nearctic Region north of the Mexican border have been reexamined. Photographs and diagnoses of all species are provided with a distribution map of the included specimens studied. An updated key to the Nearctic species north of Mexico is provided. Finally, the need for a review of the diverse Mexican fauna is expressed., (Charlotte H. E. Alberts, Eric M. Fisher.)

In response to the shortage of N95 filtering facepiece respirators for healthcare workers during the COVID-19 pandemic, the Centers for Disease Control and Prevention issued guidance for extended use and limited reuse of N95 FFRs to conserve supply. Previously worn N95 filtering facepiece respirators can serve as a source of pathogens, which can be transferred to the wearer while doffing and donning a respirator when practicing reuse. When practicing limited filtering facepiece respirators reuse, to reduce the risk of self-contamination, the Centers for Disease Control and Prevention recommends storing filtering facepiece respirators for five days between uses to allow for the decay of viable pathogens including SARS-CoV-2. This study assesses the persistence of the SARS-CoV-2 strain USA-WA1/2020 on N95 filtering facepiece respirators under controlled storage conditions for up to 5 days to inform the Centers for Disease Control and Prevention guidance. Coupons excised from six N95 filtering facepiece respirator models and glass slide coverslips were inoculated with the virus in a defined culture medium and in human saliva and stored at 20 °C and 20%, 45%, and 75% relative humidity. Statistically significant differences in SARS-CoV-2 half-lives were measured among the tested humidity levels with half-lives decreasing from an average of approximately 30 hr at 20% relative humidity to approximately 2 hr at 75% relative humidity. Significant differences in virus half-lives were also observed between the culture medium and saliva suspension media at 20% and 45% relative humidity with half lives up to 2.9 times greater when the virus was suspended in cell culture medium. The 5-day storage strategy, assessed in this study, resulted in a minimum of 93.4% reduction in viable virus for the most challenging condition (20% relative humidity, cell culture medium) and exceeding 99% reduction in virus at all other conditions.

Existing tactile stimulation technologies powered by small actuators offer low-resolution stimuli compared to the enormous mechanoreceptor density of human skin. Arrays of soft pneumatic actuators initially show promise as small-resolution (1- to 3-mm diameter), highly conformable tactile display strategies yet ultimately fail because of their need for valves bulkier than the actuators themselves. In this paper, we demonstrate an array of individually addressable, soft fluidic actuators that operate without electromechanical valves. We achieve this by using microscale combustion and localized thermal flame quenching. Precisely, liquid metal electrodes produce sparks to ignite fuel lean methane-oxygen mixtures in a 5-mm diameter, 2-mm tall silicone cylinder. The exothermic reaction quickly pressurizes the cylinder, displacing a silicone membrane up to 6 mm in under 1 ms. This device has an estimated free-inflation instantaneous stroke power of 3 W. The maximum reported operational frequency of these cylinders is 1.2 kHz with average displacements of ∼100 µm. We demonstrate that, at these small scales, the wall-quenching flame behavior also allows operation of a 3 × 3 array of 3-mm diameter cylinders with 4-mm pitch. Though we primarily present our device as a tactile display technology, it is a platform microactuator technology with application beyond this one., Competing Interests: Competing interest statement: R.F.S., C.A.A., and R.H.H. are coauthors on a patent filed by Cornell University on August 19, 2020, titled “Microscale Combustion for High-Density Soft Actuation,” claiming priority to US Provisional Application No. 62/888,836, filed on August 19, 2019, by the same authors.

The Community Care Connections (CCC) program aims to align social and healthcare services to improve health outcomes in older adults with complex medical and social needs. This study assessed changes in healthcare utilization before and after CCC program participation. Between June 2016 and March 2019, 1214 adults with complete data who provided informed consent participated in the CCC program. CCC client data were linked with data on hospitalizations, emergency department (ED) visits, and observation stays 90 days before and after program start. Data analysis examined changes in health care utilization 90 days after program start, compared to 90 days before. Hospitalizations decreased by 30% (Change = -0.029, 95% Confidence Interval (CI) = -0.053, -0.005), ED visits decreased by 29% (Change = -0.114, 95% CI = -0.163, -0.066), and observation stays decreased by 23% (Change = -0.041, 95% CI = -0.073, -0.009) during the post period. ED visits decreased by 37% (Change = -0.140, 95% CI = -0.209, -0.070) for those with hypertension and by 30% (Change = -0.109, 95% CI = -0.199, -0.020) for those with high cholesterol, while observation stays decreased by 46% (Change = -0.118, 95% CI = -0.185, -0.052) for those with diabetes and by 44% (Change = -0.082, 95% CI = -0.150, -0.014) for those with high cholesterol during the post period. Connecting older adults with social services through the healthcare delivery system may lead to decreases in hospitalizations, ED visits, and observation stays. Implementation of cross-sector partnerships that address non-clinical factors that impact the health of older adults may reduce the use of costly healthcare services., (Copyright © 2020 Elsevier Inc. All rights reserved.)

RESUMENLas mascarillas respiratorias autofiltrantes ( filtering facepiece respirators , FFR) N95 certificadas por el Instituto Nacional de Seguridad y Salud Laborales (National Institute for Occupational Safety and Health, NIOSH) se utilizan en los centros de atención sanatoria como medida de control para mitigar las exposiciones a partículas atmosféricas infecciosas. Cuando la superficie externa de una FFR se contamina, supone un riesgo de transmisión para el usuario. La guía de los Centros para el Control y Prevención de Enfermedades (Centers for Disease Control and Prevention, CDC) recomienda que el personal sanitario retire las FFR agarrando las tiras en la parte posterior de la cabeza para evitar el contacto con la superficie posiblemente contaminada. Al parecer, la adherencia a la técnica de retirada adecuada es baja, debido a numerosos factores que incluyen la dificultad para ubicar y agarrar las tiras. En este estudio se compara el impacto de lengüetas ubicadas en las tiras de la FFR con el de mascarillas comparativas (sin lengüetas) sobre la retirada adecuada, la facilidad de uso, la comodidad y la reducción de la transmisión de la contaminación al usuario. El uso de un agente fluorescente como rastreador de contactos para explorar la contaminación de las FFR en manos y áreas de la cabeza de 20 sujetos humanos demostró que no hubo diferencia entre las tiras de la FFR con lengüetas y las mascarillas comparativas en el sentido de estimular la retirada adecuada de las mismas (p = 0.48), pero la hizo más fácil (p = 0.04), según indican siete de ocho sujetos que usaron las lengüetas. Siete de 20 sujetos opinaron que las FFR con lengüetas son más fáciles de retirar, mientras que solo dos de 20 sujetos indicaron que las FFR sin lengüetas son más fáciles de retirar. La incomodidad no fue un factor relevante para ninguno de los tipos de tiras de las FFR. Al retirar una FFR con las manos contaminadas, el uso de lengüetas redujo de forma importante la cantidad del rastreador de contactos transferida en comparación con las tiras sin lengüetas (p = 0.012). Las FFR con lengüetas en las tiras están asociadas con la facilidad de la retirada y una transferencia notablemente menor del rastreador de contactos fluorescente.

No treatment for frontotemporal dementia (FTD), the second most common type of early-onset dementia, is available, but therapeutics are being investigated to target the 2 main proteins associated with FTD pathological subtypes: TDP-43 (FTLD-TDP) and tau (FTLD-tau). Testing potential therapies in clinical trials is hampered by our inability to distinguish between patients with FTLD-TDP and FTLD-tau. Therefore, we evaluated truncated stathmin-2 (STMN2) as a proxy of TDP-43 pathology, given the reports that TDP-43 dysfunction causes truncated STMN2 accumulation. Truncated STMN2 accumulated in human induced pluripotent stem cell-derived neurons depleted of TDP-43, but not in those with pathogenic TARDBP mutations in the absence of TDP-43 aggregation or loss of nuclear protein. In RNA-Seq analyses of human brain samples from the NYGC ALS cohort, truncated STMN2 RNA was confined to tissues and disease subtypes marked by TDP-43 inclusions. Last, we validated that truncated STMN2 RNA was elevated in the frontal cortex of a cohort of patients with FTLD-TDP but not in controls or patients with progressive supranuclear palsy, a type of FTLD-tau. Further, in patients with FTLD-TDP, we observed significant associations of truncated STMN2 RNA with phosphorylated TDP-43 levels and an earlier age of disease onset. Overall, our data uncovered truncated STMN2 as a marker for TDP-43 dysfunction in FTD.

In 2018, the Centers for Disease Control and Prevention reported that opioid overdose deaths (including fentanyl and carfentanil) comprised 46,802 (69%) of the 67,367 total drug overdose deaths. The opioid overdose epidemic affects Americans not only at home but also in the workplace. First responders may be at risk of opioid exposure during incidents such as vehicle searches and responses to overdose calls. To reduce direct exposure to opioids and other hazardous drugs, first responders rely in part on personal protective equipment (PPE) as their last line of defense. First responders seek guidance from the National Institute for Occupational Safety and Health (NIOSH) regarding appropriate PPE selection for potential opioid exposure. There is limited empirical glove performance data for illicit drugs. Empirical data are needed to validate NIOSH's current recommendations regarding gloves to help prevent exposure to illicit drugs (i.e., powder-free nitrile gloves with a minimum thickness of 5 ± 2 mil [0.127 ± 0.051 millimeters]); however, no industry standard or test method currently exists for specifically evaluating PPE performance against fentanyl and its analogs. To understand the permeation qualities of gloves when challenged against fentanyl and carfentanil solutions, the ASTM International (formerly American Society for Testing and Materials) ASTM D6978-19 standard for chemotherapy drug glove permeation was adapted to test fentanyl and carfentanil hydrochloride solution permeation through twelve disposable glove models, including five models in which the manufacturers claim fentanyl protection. No nitrile glove models showed fentanyl or carfentanil permeation rates above the chemotherapy drug threshold criterion of 0.01 µg/cm 2 /min (i.e., thereby meeting the performance requirement) as calculated using the ASTM D6978-19 standard within the 240-min test. Latex and vinyl glove materials exhibited fentanyl and carfentanil permeation with permeation rates above this threshold. These findings are among the first empirical data to support NIOSH's current opioid glove recommendations and define procedures that could be used to support industry standards for evaluating opioid permeation through air-impermeable PPE materials.

During the current COVID-19 infectious disease pandemic, the demand for NIOSH-approved filtering facepiece respirators (FFR) has exceeded supplies and decontamination and reuse of FFRs has been implemented by various user groups. FFR decontamination and reuse is only intended to be implemented as a crisis capacity strategy. This paper provides a review of decontamination procedures in the published literature and calls attention to their benefits and limitations. In most cases, the data are limited to a few FFR models and a limited number of decontamination cycles. Institutions planning to implement a decontamination method must understand its limitations in terms of the degree of inactivation of the intended microorganisms and the treatment's effects on the fit and filtration of the device.

During epidemics and pandemics healthcare personnel (HCP) are on the front line of disease containment and mitigation. Personal protective equipment (PPE), such as NIOSH-approved N95 filtering facepiece respirators (FFRs), serve an important role in minimizing HCP risks and are in high demand during public health emergencies. Because PPE demand can exceed supply, various public health strategies have been developed to reduce the rate of PPE consumption as supply dwindles. Extended use and limited reuse of N95 FFRs are strategies advocated by many governmental agencies used to increase the number of times a device can be used. Increased use of respirators designed for reuse-such as powered air-purifying respirators (PAPRs) and elastomeric half-mask and full facepiece air-purifying respirators- is another option designed to reduce the continuous need for new devices as the daily need for respirator use increases. Together, these strategies are designed to reduce the number of PPE units that must be discarded daily and, therefore, extend the longevity of available supply. The purpose of this paper is to theoretically estimate the impact of extended use and limited reuse strategies for N95 FFRs and the increased use of reusable respirator options on PPE consumed. The results suggest that a considerable reduction in PPE consumption would result from extended use and limited reuse of N95 FFRs and the increased use of respirators designed for reuse; however, the practical benefits must be balanced with the risks and economic costs. In addition, extended use and reuse strategies must be accompanied by proper procedures to reduce risk. The study is designed to support epidemic and pandemic PPE supply and demand planning efforts.

Recent high-profile infectious disease outbreaks illustrate the importance of selecting appropriate control measures to protect a wider range of employees, other than those in healthcare settings. In such settings, where routine exposure risks are often high, control measures may be more available, routinely implemented, and studied for effectiveness. In the absence of evidence-based guidelines or established best practices for selecting appropriate control measures, employers may unduly rely on personal protective equipment (PPE) because of its wide availability and pervasiveness as a control measure, circumventing other effective options for protection. Control banding is one approach that may be used to assign job tasks into risk categories and prioritize the application of controls. This article proposes an initial control banding framework for workers at all levels of risk and incorporates a range of control options, including PPE. Using the National Institutes of Health (NIH) risk groups as a surrogate for toxicity and combining the exposure duration with the exposure likelihood, we can generate the risk of a job task to the worker.

Domestic violence (DV) emergency shelters play a vital role in supporting victims who seek to leave abusive partners and gain independence. Research indicates that numerous positive outcomes for victims and their children are associated with utilization of DV shelter programs. Yet, research also suggests that DV shelter programs may be unable to comprehensively meet the needs of all victims, and many choose to leave shelters soon after their arrival. To better understand the ways in which DV shelter programs support victims but also fail to meet their needs, this article explores the factors that influence victims' decisions to stay or leave a DV emergency shelter program through qualitative interviews with 33 DV shelter residents. Study participants indicate that three types of factors influence their decision to stay or leave the shelter program: (a) contextual factors, (b) partner or family relationship factors, and (c) shelter-specific factors. Shelter-specific factors cited as important contributors to satisfaction or dissatisfaction with shelter living include policies, staff and services, displacement from one's home community, and facilities. Findings provide information from the perspective of victims on the factors that influence one's decision to stay or leave a DV program and can be used to support service providers and advocates in building programs that are both supportive of victims' needs and conductive to longer shelter stays.

Healthcare workers (HCWs) are at significantly higher risk of exposure to influenza virus during seasonal epidemics and global pandemics. During the 2009 influenza pandemic, some healthcare organizations recommended that HCWs wear respiratory protection such as filtering facepiece respirators, while others indicated that facemasks such as surgical masks (SMs) were sufficient. To assess the level of exposure a HCW may possibly encounter, the aim of this study was to (1.) evaluate if SMs and N95 respirators can serve as "personal bioaerosol samplers" for influenza virus and (2.) determine if SMs and N95 respirators contaminated by influenza laden aerosols can serve as a source of infectious virus for indirect contact transmission. This effort is part of a National Institute for Occupational Safety and Health 5-year multidisciplinary study to determine the routes of influenza transmission in healthcare settings. A coughing simulator was programmed to cough aerosol particles containing influenza virus over a wide concentration range into an aerosol exposure simulation chamber virus/L of exam room air), and a breathing simulator was used to collect virus on either a SM or N95 respirator. Extraction buffers containing nonionic and anionic detergents as well as various protein additives were used to recover influenza virus from the masks and respirators. The inclusion of 0.1% SDS resulted in maximal influenza RNA recovery (41.3%) but with a complete loss of infectivity whereas inclusion of 0.1% bovine serum albumin resulted in reduced RNA recovery (6.8%) but maximal retention of virus infectivity (17.9%). Our results show that a HCW's potential exposure to airborne influenza virus can be assessed in part through analysis of their SMs and N95 respirators, which can effectively serve as personal bioaerosol samplers., (Published by Elsevier B.V.)

Increased understanding of influenza transmission is critical for pandemic planning and selecting appropriate controls for healthcare personnel safety and health. The goals of this pilot study were to assess environmental contamination in different areas and at two time periods in the influenza season and to determine the feasibility of using surgical mask contamination to evaluate potential exposure to influenza virus. Bioaerosol samples were collected over 12 days (two 6-day sessions) at 12 locations within a student health center using portable two-stage bioaerosol samplers operating 8 hr each day. Surface samples were collected each morning and afternoon from common high-contact non-porous hard surfaces from rooms and locations where bioaerosol samplers were located. Surgical masks worn by participants while in contact with patients with influenza-like illness were collected. A questionnaire administered to each of the 12 participants at the end of each workday and another at the end of each workweek assessed influenza-like illness symptoms, estimated the number of influenza-like illness patient contacts, hand hygiene, and surgical mask usage. All samples were analyzed using qPCR. Over the 12 days of the study, three of the 127 (2.4%) bioaerosol samples, 2 of 483 (0.41%) surface samples, and 0 of 54 surgical masks were positive for influenza virus. For the duration of contact that occurred with an influenza patient on any of the 12 days, nurse practitioners and physicians reported contacts with influenza-like illness patients >60 min, medical assistants reported 15-44 min, and administrative staff reported <30 min. Given the limited number of bioaerosol and surface samples positive for influenza virus in the bioaerosol and surface samples, the absence of influenza virus on the surgical masks provides inconclusive evidence for the potential to use surgical masks to assess exposure to influenza viruses. Further studies are needed to determine feasibility of this approach in assessing healthcare personnel exposures. Information learned in this study can inform future field studies on influenza transmission.

Introduction: Healthcare personnel are at high risk for exposure to influenza by direct and indirect contact, droplets and aerosols, and by aerosol generating procedures. Information on air and surface influenza contamination is needed to assist in developing guidance for proper prevention and control strategies. To understand the vulnerabilities of healthcare personnel, we measured influenza in the breathing zone of healthcare personnel, in air and on surfaces within a healthcare setting, and on filtering facepiece respirators worn by healthcare personnel when conducting patient care., Methods: Thirty participants were recruited from an adult emergency department during the 2015 influenza season. Participants wore personal bioaerosol samplers for six hours of their work shift, submitted used filtering facepiece respirators and medical masks and completed questionnaires to assess frequency and types of interactions with potentially infected patients. Room air samples were collected using bioaerosol samplers, and surface swabs were collected from high-contact surfaces within the adult emergency department. Personal and room bioaerosol samples, surface swabs, and filtering facepiece respirators were analyzed for influenza A by polymerase chain reaction., Results: Influenza was identified in 42% (53/125) of personal bioaerosol samples, 43% (28/ 96) of room bioaerosol samples, 76% (23/30) of pooled surface samples, and 25% (3/12) of the filtering facepiece respirators analyzed. Influenza copy numbers were greater in personal bioaerosol samples (17 to 631 copies) compared to room bioaerosol samples (16 to 323 copies). Regression analysis suggested that the amount of influenza in personal samples was approximately 2.3 times the amount in room samples (Wald χ2 = 16.21, p<0.001)., Conclusions: Healthcare personnel may encounter increased concentrations of influenza virus when in close proximity to patients. Occupations that require contact with patients are at an increased risk for influenza exposure, which may occur throughout the influenza season. Filtering facepiece respirators may become contaminated with influenza when used during patient care., Competing Interests: The authors have declared that no competing interests exist.

TDP-43 (encoded by the gene TARDBP ) is an RNA binding protein central to the pathogenesis of amyotrophic lateral sclerosis (ALS). However, how TARDBP mutations trigger pathogenesis remains unknown. Here, we use novel mouse mutants carrying point mutations in endogenous Tardbp to dissect TDP-43 function at physiological levels both in vitro and in vivo Interestingly, we find that mutations within the C-terminal domain of TDP-43 lead to a gain of splicing function. Using two different strains, we are able to separate TDP-43 loss- and gain-of-function effects. TDP-43 gain-of-function effects in these mice reveal a novel category of splicing events controlled by TDP-43, referred to as "skiptic" exons, in which skipping of constitutive exons causes changes in gene expression. In vivo , this gain-of-function mutation in endogenous Tardbp causes an adult-onset neuromuscular phenotype accompanied by motor neuron loss and neurodegenerative changes. Furthermore, we have validated the splicing gain-of-function and skiptic exons in ALS patient-derived cells. Our findings provide a novel pathogenic mechanism and highlight how TDP-43 gain of function and loss of function affect RNA processing differently, suggesting they may act at different disease stages., (© 2018 The Authors. Published under the terms of the CC BY 4.0 license.)

Purpose: A good 'fit' with an organization is critical to a leader's success yet when searching for a new position assessment an evaluation of many aspects may be overlooked, such as culture. This paper presents key considerations around 'fit' that applicants for leadership positions should consider prior to, during, and after the interview. Suggestions are provided on how to approach an evaluation of 'fit'., Conclusion: The importance of assessing individual fit with an organization prior to accepting a leadership position cannot be over-emphasized., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Rationale: The prevalence of Alzheimer's disease is increased in people with Down syndrome. The pathology appears much earlier than in the general population, suggesting a predisposition to develop Alzheimer's disease. Down syndrome results from trisomy of human chromosome 21, leading to overexpression of possible Alzheimer's disease candidate genes, such as amyloid precursor protein gene. To better understand how the Down syndrome context results in increased vulnerability to Alzheimer's disease, we analysed amyloid-β [25-35] peptide toxicity in the Tc1 mouse model of Down syndrome, in which ~75% of protein coding genes are functionally trisomic but, importantly, not amyloid precursor protein., Results: Intracerebroventricular injection of oligomeric amyloid-β [25-35] peptide in three-month-old wildtype mice induced learning deficits, oxidative stress, synaptic marker alterations, activation of glycogen synthase kinase-3β, inhibition of protein kinase B (AKT), and apoptotic pathways as compared to scrambled peptide-treated wildtype mice. Scrambled peptide-treated Tc1 mice presented high levels of toxicity markers as compared to wildtype mice. Amyloid-β [25-35] peptide injection in Tc1 mice induced significant learning deficits and enhanced glycogen synthase kinase-3β activity in the cortex and expression of apoptotic markers in the hippocampus and cortex. Interestingly, several markers, including oxidative stress, synaptic markers, glycogen synthase kinase-3β activity in the hippocampus and AKT activity in the hippocampus and cortex, were unaffected by amyloid-β [25-35] peptide injection in Tc1 mice., Conclusions: Tc1 mice present several toxicity markers similar to those observed in amyloid-β [25-35] peptide-treated wildtype mice, suggesting that developmental modifications in these mice modify their response to amyloid peptide. However, amyloid toxicity led to severe memory deficits in this Down syndrome mouse model.

Contact transmission of pathogens from personal protective equipment is a concern within the healthcare industry. During public health emergency outbreaks, resources become constrained and the reuse of personal protective equipment, such as N95 filtering facepiece respirators, may be needed. This study was designed to characterize the transfer of bacteriophage MS2 and fluorescein between filtering facepiece respirators and the wearer's hands during three simulated use scenarios. Filtering facepiece respirators were contaminated with MS2 and fluorescein in droplets or droplet nuclei. Thirteen test subjects performed filtering facepiece respirator use scenarios including improper doffing, proper doffing and reuse, and improper doffing and reuse. Fluorescein and MS2 contamination transfer were quantified. The average MS2 transfer from filtering facepiece respirators to the subjects' hands ranged from 7.6-15.4% and 2.2-2.7% for droplet and droplet nuclei derived contamination, respectively. Handling filtering facepiece respirators contaminated with droplets resulted in higher levels of MS2 transfer compared to droplet nuclei for all use scenarios (p = 0.007). MS2 transfer from droplet contaminated filtering facepiece respirators during improper doffing and reuse was greater than transfer during improper doffing (p = 0.008) and proper doffing and reuse (p = 0.042). Droplet contamination resulted in higher levels of fluorescein transfer compared to droplet nuclei contaminated filtering facepiece respirators for all use scenarios (p = 0.009). Fluorescein transfer was greater for improper doffing and reuse (p = 0.007) from droplet contaminated masks compared to droplet nuclei contaminated filtering facepiece respirators and for improper doffing and reuse when compared improper doffing (p = 0.017) and proper doffing and reuse (p = 0.018) for droplet contaminated filtering facepiece respirators. For droplet nuclei contaminated filtering facepiece respirators, the difference in MS2 and fluorescein transfer did not reach statistical significance when comparing any of the use scenarios. The findings suggest that the results of fluorescein and MS2 transfer were consistent and highly correlated across the conditions of study. The data supports CDC recommendations for using proper doffing techniques and discarding filtering facepiece respirators that are directly contaminated with secretions from a cough or sneeze.

With increasingly large numbers of mouse models of human disease dedicated to MRI studies, compromises between in vivo and ex vivo MRI must be fully understood in order to inform the choice of imaging methodology. We investigate the application of high resolution in vivo and ex vivo MRI, in combination with tensor-based morphometry (TBM), to uncover morphological differences in the rTg4510 mouse model of tauopathy. The rTg4510 mouse also offers a novel paradigm by which the overexpression of mutant tau can be regulated by the administration of doxycycline, providing us with a platform on which to investigate more subtle alterations in morphology with morphometry. Both in vivo and ex vivo MRI allowed the detection of widespread bilateral patterns of atrophy in the rTg4510 mouse brain relative to wild-type controls. Regions of volume loss aligned with neuronal loss and pathological tau accumulation demonstrated by immunohistochemistry. When we sought to investigate more subtle structural alterations in the rTg4510 mice relative to a subset of doxycycline-treated rTg4510 mice, ex vivo imaging enabled the detection of more regions of morphological brain changes. The disadvantages of ex vivo MRI may however mitigate this increase in sensitivity: we observed a 10% global shrinkage in brain volume of the post-mortem tissues due to formalin fixation, which was most notable in the cerebellum and olfactory bulbs. However, many central brain regions were not adversely affected by the fixation protocol, perhaps due to our "in-skull" preparation. The disparity between our TBM findings from in vivo and ex vivo MRI underlines the importance of appropriate study design, given the trade-off between these two imaging approaches. We support the utility of in vivo MRI for morphological phenotyping of mouse models of disease; however, for subtler phenotypes, ex vivo offers enhanced sensitivity to discrete morphological changes.

NIOSH-certified N95 filtering facepiece respirators (FFRs) are used in healthcare settings as a control measure to mitigate exposures to airborne infectious particles. When the outer surface of an FFR becomes contaminated, it presents a contact transmission risk to the wearer. The Centers for Disease Control and Prevention (CDC) guidance recommends that healthcare workers (HCWs) doff FFRs by grasping the straps at the back of the head to avoid contact with the potentially contaminated surface. Adherence to proper doffing technique is reportedly low due to numerous factors including difficulty in locating and grasping the straps. This study compares the impact of tabs placed on FFR straps to controls (without tabs) on proper doffing, ease of use and comfort, and reduction of transfer of contamination to the wearer. Utilizing a fluorescent agent as a tracer to track contamination from FFRs to hand and head areas of 20 human subjects demonstrated that there was no difference in tabbed FFR straps and controls with respect to promoting proper doffing (p = 0.48), but did make doffing easier (p = 0.04) as indicated by 7 of 8 subjects that used the tabs. Seven of the 20 subjects felt that FFRs with tabs were easier to remove, while only 2 of 20 indicated that FFRs without tabs were easier to remove. Discomfort was not a factor for either FFR strap type. When removing an FFR with contaminated hands, the use of the tabs significantly reduced the amount of tracer transfer compared to straps without tabs (p = 0.012). FFRs with tabs on the straps are associated with ease of doffing and significantly less transfer of the fluorescent tracer.

Evolutionary differences in gene regulation between humans and lower mammalian experimental systems are incompletely understood, a potential translational obstacle that is challenging to surmount in neurons, where primary tissue availability is poor. Rodent-based studies show that activity-dependent transcriptional programs mediate myriad functions in neuronal development, but the extent of their conservation in human neurons is unknown. We compared activity-dependent transcriptional responses in developing human stem cell-derived cortical neurons with those induced in developing primary- or stem cell-derived mouse cortical neurons. While activity-dependent gene-responsiveness showed little dependence on developmental stage or origin (primary tissue vs. stem cell), notable species-dependent differences were observed. Moreover, differential species-specific gene ortholog regulation was recapitulated in aneuploid mouse neurons carrying human chromosome-21, implicating promoter/enhancer sequence divergence as a factor, including human-specific activity-responsive AP-1 sites. These findings support the use of human neuronal systems for probing transcriptional responses to physiological stimuli or indeed pharmaceutical agents., Competing Interests: The authors declare that no competing interests exist.

We describe a fully automated pipeline for the morphometric phenotyping of mouse brains from μMRI data, and show its application to the Tc1 mouse model of Down syndrome, to identify new morphological phenotypes in the brain of this first transchromosomic animal carrying human chromosome 21. We incorporate an accessible approach for simultaneously scanning multiple ex vivo brains, requiring only a 3D-printed brain holder, and novel image processing steps for their separation and orientation. We employ clinically established multi-atlas techniques-superior to single-atlas methods-together with publicly-available atlas databases for automatic skull-stripping and tissue segmentation, providing high-quality, subject-specific tissue maps. We follow these steps with group-wise registration, structural parcellation and both Voxel- and Tensor-Based Morphometry-advantageous for their ability to highlight morphological differences without the laborious delineation of regions of interest. We show the application of freely available open-source software developed for clinical MRI analysis to mouse brain data: NiftySeg for segmentation and NiftyReg for registration, and discuss atlases and parameters suitable for the preclinical paradigm. We used this pipeline to compare 29 Tc1 brains with 26 wild-type littermate controls, imaged ex vivo at 9.4T. We show an unexpected increase in Tc1 total intracranial volume and, controlling for this, local volume and grey matter density reductions in the Tc1 brain compared to the wild-types, most prominently in the cerebellum, in agreement with human DS and previous histological findings., Competing Interests: The authors have declared that no competing interests exist.

Type 2 diabetes (T2D) is a complex metabolic disease associated with obesity, insulin resistance and hypoinsulinemia due to pancreatic β-cell dysfunction. Reduced mitochondrial function is thought to be central to β-cell dysfunction. Mitochondrial dysfunction and reduced insulin secretion are also observed in β-cells of humans with the most common human genetic disorder, Down syndrome (DS, Trisomy 21). To identify regions of chromosome 21 that may be associated with perturbed glucose homeostasis we profiled the glycaemic status of different DS mouse models. The Ts65Dn and Dp16 DS mouse lines were hyperglycemic, while Tc1 and Ts1Rhr mice were not, providing us with a region of chromosome 21 containing genes that cause hyperglycemia. We then examined whether any of these genes were upregulated in a set of ~5,000 gene expression changes we had identified in a large gene expression analysis of human T2D β-cells. This approach produced a single gene, RCAN1, as a candidate gene linking hyperglycemia and functional changes in T2D β-cells. Further investigations demonstrated that RCAN1 methylation is reduced in human T2D islets at multiple sites, correlating with increased expression. RCAN1 protein expression was also increased in db/db mouse islets and in human and mouse islets exposed to high glucose. Mice overexpressing RCAN1 had reduced in vivo glucose-stimulated insulin secretion and their β-cells displayed mitochondrial dysfunction including hyperpolarised membrane potential, reduced oxidative phosphorylation and low ATP production. This lack of β-cell ATP had functional consequences by negatively affecting both glucose-stimulated membrane depolarisation and ATP-dependent insulin granule exocytosis. Thus, from amongst the myriad of gene expression changes occurring in T2D β-cells where we had little knowledge of which changes cause β-cell dysfunction, we applied a trisomy 21 screening approach which linked RCAN1 to β-cell mitochondrial dysfunction in T2D.

The present study examined memory function in Tc1 mice, a transchromosomic model of Down syndrome (DS). Tc1 mice demonstrated an unusual delay-dependent deficit in recognition memory. More specifically, Tc1 mice showed intact immediate (30sec), impaired short-term (10-min) and intact long-term (24-h) memory for objects. A similar pattern was observed for olfactory stimuli, confirming the generality of the pattern across sensory modalities. The specificity of the behavioural deficits in Tc1 mice was confirmed using APP overexpressing mice that showed the opposite pattern of object memory deficits. In contrast to object memory, Tc1 mice showed no deficit in either immediate or long-term memory for object-in-place information. Similarly, Tc1 mice showed no deficit in short-term memory for object-location information. The latter result indicates that Tc1 mice were able to detect and react to spatial novelty at the same delay interval that was sensitive to an object novelty recognition impairment. These results demonstrate (1) that novelty detection per se and (2) the encoding of visuo-spatial information was not disrupted in adult Tc1 mice. The authors conclude that the task specific nature of the short-term recognition memory deficit suggests that the trisomy of genes on human chromosome 21 in Tc1 mice impacts on (perirhinal) cortical systems supporting short-term object and olfactory recognition memory., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Mouse models of Alzheimer's disease have served as valuable tools for investigating pathogenic mechanisms relating to neurodegeneration, including tau-mediated and neurofibrillary tangle pathology-a major hallmark of the disease. In this work, we have used multiparametric magnetic resonance imaging (MRI) in a longitudinal study of neurodegeneration in the rTg4510 mouse model of tauopathy, a subset of which were treated with doxycycline at different time points to suppress the tau transgene. Using this paradigm, we investigated the sensitivity of multiparametric MRI to both the accumulation and suppression of pathologic tau. Tau-related atrophy was discernible from 5.5 months within the cortex and hippocampus. We observed markedly less atrophy in the treated rTg4510 mice, which was enhanced after doxycycline intervention from 3.5 months. We also observed differences in amide proton transfer, cerebral blood flow, and diffusion tensor imaging parameters in the rTg4510 mice, which were significantly less altered after doxycycline treatment. We propose that these non-invasive MRI techniques offer insight into pathologic mechanisms underpinning Alzheimer's disease that may be important when evaluating emerging therapeutics targeting one of more of these processes., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Immunization is the best way to prevent seasonal epidemics and pandemics of influenza. There are two kinds of influenza vaccines available in the United States: an inactivated vaccine (TIV) and an attenuated vaccine; however, only TIV is approved for immunization of the elderly population. While the aged population has the highest rate of influenza vaccination, the protective efficacy is low as evidenced by elderly individuals having the highest mortality associated with influenza. Recently, we reported that an adjuvant derived from the helminth parasite Onchocerca volvulus, named O. volvulus activation-associated secreted protein-1 (Ov-ASP-1), can significantly enhance the protective efficacy of an inactivated vaccine (TIV) in young adult mice. In the current study, we examined whether this recombinant Ov-ASP-1 (rOv-ASP-1) can enhance the efficacy of TIV in aged mice as well. While primary immunization with TIV alone produced only a low level of influenza-specific antibodies (total IgG, IgG1, and IgG2c) in aged mice, the antibody levels were significantly increased after immunization with TIV+rOv-ASP-1. More importantly, the level of the total IgG in aged mice administered TIV+rOv-ASP-1 was comparable to that of young adult mice immunized with TIV alone. Co-administration of rOv-ASP-1 induced a low level of cross-reactive antibody and enhanced the protective efficacy of TIV in aged mice, reflected by significantly increased survival after challenge with a heterologous influenza virus. rOv-ASP-1 was also superior to the conventional adjuvant alum in inducing specific IgG after TIV immunization in aged mice, and in conferring protection after challenge. These results demonstrate that rOv-ASP-1 may serve as a potential adjuvant for influenza vaccine to improve the efficacy of protection in the elderly., (Copyright © 2016 Elsevier Ltd. All rights reserved.)