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Purpose: Age- and disease-related changes in oropharyngeal anatomy and physiology may be identified through quantitative videofluoroscopic measures of pharyngeal area and dynamics. Pixel-based measures of nonconstricted pharyngeal area (PhAR) are typically taken during oral bolus hold tasks or on postswallow rest frames. A recent study in 87 healthy adults reported mean postswallow PhAR of 62%(C2-4) 2 , (range: 25%-135%), and significantly larger PhAR in males. The fact that measures were taken after initial bolus swallows without controlling for the presence of subsequent clearing swallows was identified as a potential source of variation. A subset of study participants had completed a protocol including additional static nonswallowing tasks, enabling us to explore variability across those tasks, taking sex differences into account., Method: Videofluoroscopy still shots were analyzed for 20 healthy adults (10 males, 10 females, M age = 26 years) in head-neutral position, chin-down and chin-up positions, a sustained /a/ vowel vocalization, and oral bolus hold tasks (1-cc, 5-cc). Trained raters used ImageJ software to measure PhAR in %(C2-4) 2 units. Measures were compared to previously reported mean postswallow PhAR for the same participants: (a) explorations of sex differences; (b) pairwise linear mixed-model analyses of variance (ANOVAs) of PhAR for each nonswallowing task versus postswallow measures, controlling for sex; and (c) a combined mixed-model ANOVA to confirm comparability of the subset of tasks showing no significant differences from postswallow measures in Step 2., Results: Overall, PhAR measures were significantly larger in male participants; however, most pairwise task comparisons did not differ by sex. No significant differences from postswallow measures were seen for 5-cc bolus hold, chin-down and chin-up postures, and the second (but not the first) of two repeated head neutral still shots. PhAR during a 5-cc bolus hold was most similar to postswallow measures: mean ± standard deviation of 51 ± 13%(C2-4) 2 in females and 64 ± 16%(C2-4) 2 in males., Conclusions: PhAR is larger in men than in women. Oral bolus hold tasks with a 5-cc liquid bolus yield similar measures to those obtained from postswallow rest frames.

Objective: The pharyngeal swallow typically begins within 400 ms following the arrival of a liquid bolus in the pharynx. By contrast, processed food particles aggregate in the valleculae prior to swallow initiation. With solid foods, swallow reaction time (SRT), the interval between bolus passing the ramus of mandible and hyoid burst onset (HYB) can be subdivided into components of vallecular aggregation time (VAT) and the subsequent end of aggregation to hyoid burst interval (EOA-to-HYB). However, expected durations of these timing measures remain unclear. We aimed to study bolus aggregation in healthy swallowing for International Dysphagia Diet Standardisation Initiative Food Levels 5 (minced and moist [MM5]), 6 (soft and bite-sized [SB6]), and 7 (regular [RG7]). Understanding typical patterns and durations of vallecular aggregation with solids in healthy swallowing will inform the identification of impaired swallow timing in patient populations., Design: Twenty healthy adults (10 males, M age = 28 years, range: 23-55 years) swallowed two boluses each of MM5, SB6, and RG7 foods in videofluoroscopy. Blinded duplicate ratings determined bolus location at swallow onset, SRT, VAT, and EOA-to-HYB. Texture-based differences were measured using Friedman's tests. Bolus location was at/above the valleculae at swallow onset for 85% of boluses, with no differences by texture. SRT, VAT, and EOA-to-HYB did not vary by texture, with overall median values (interquartile range) of 99 ms (-66 to 743 ms) for SRT, 347 ms (66 to 891 ms) for VAT, and -132 ms (-231 to -83 ms) for EOA-to-HYB., Conclusions: These data corroborate prior evidence that it is not unusual for food particles to aggregate in the valleculae prior to swallow initiation in healthy swallowing. However, durations of vallecular aggregation are typically < 1 s in healthy adults.

Literature shows that Latinos who drink are more likely to experience alcohol-related consequences and less likely to seek care for alcohol misuse than Whites. We aim to understand characteristics, consumption patterns, and openness to treatment among Latino first-time offenders driving under the influence. Latino participants were significantly younger (29.0 years) than non-Latinos (37.7 years). In adjusted models, Latino participants were significantly more likely than non-Latinos to binge drink, but there were no significant group differences in amount of alcohol consumed in a typical week. There was no significant difference in incidence of alcohol-related consequences, readiness to change drinking, and driving behaviors in this sample.

Purpose: Videofluoroscopic (VFSS) measurements of pharyngeal swallow mechanics can differentiate age- and disease-related changes in swallowing. Pharyngeal area at rest (PhAR) may differ in people with dysphagia, although its impact is not clear. Before the role of PhAR in dysphagia can be explored, it is important to establish whether PhAR remains stable across repeated measures in healthy adults, and varies as a function of sex or age. We hypothesized that healthy adults would show stable PhAR across repeated measures, but that larger PhAR would be seen in men versus women and in older versus younger adults., Method: We collected VFSS data from 87 healthy adults (44 men, M age = 46 years, range: 21-82). Trained raters identified the swallow rest frame after the initial swallow of each bolus and measured unobliterated pharyngeal area on these frames, in %(C2-4) 2 units. Repeated-measures analyses of variance with a factor of sex, a covariate of age, and a repeated factor of task repetition were performed across the first 12 available measures per participant ( N = 1,044 swallows)., Results: There were no significant variations in PhAR across repeated measures. A significant Sex × Age interaction was seen ( p = .04): Males had significantly larger PhAR than females ( p = .001), but females showed larger PhAR with advancing age ( R = .47)., Conclusions: These data confirm stability in PhAR across repeated measurements in healthy individuals. However, significant sex and age differences should be taken into consideration in future studies exploring the role of PhAR in people with dysphagia., Supplemental Material: https://doi.org/10.23641/asha.22043543.

For almost two decades, the United States has been engaged in continuous combat operations in Iraq, Afghanistan, and other theaters. Some service members have sustained injuries or developed medical conditions as a consequence of military service that affect their ability to perform their military duties. The process by which the U.S. Department of Defense (DoD) evaluates service members and determines whether they should be medically discharged has changed considerably since 2001. In particular, beginning in 2007, major changes to the Disability Evaluation System (DES) were implemented in response to concern about inefficiencies and confusion resulting from the practice of having DoD and the U.S. Department of Veterans Affairs (VA) conduct separate evaluations according to different criteria, thus producing different disability determinations. In 2008, DoD launched a pilot program to streamline the disability evaluation process, with VA conducting medical exams to be used by both DoD and VA. This system, the Integrated Disability Evaluation System (IDES), was formally adopted military-wide in 2011. Changes to DES also reflected changes in understanding of traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD), the signature injuries of the Iraq and Afghanistan wars. The authors review changes to disability evaluation policy and changes in the diagnosis and treatment of PTSD and TBI since 2001., (Copyright © 2022 RAND Corporation.)

"In September 2017, Puerto Rico was struck by two major hurricanes-Irma and Maria-that intensified existing challenges in Puerto Rico's health and social services infrastructure. In the aftermath, the government of Puerto Rico created a long-term recovery plan built on an evidence-based assessment of the damage from the hurricanes and the ongoing needs across Puerto Rico. Development of the recovery plan was supported by the Federal Emergency Management Agency, other federal agencies, local stakeholders, and analysis from the Homeland Security Operational Analysis Center (HSOAC), operated by RAND Corporation under contract with the U.S. Department of Homeland Security. HSOAC research provided the foundation for the 31 courses of action in the recovery plan addressing the health and social services sector. These actions are a mix of social, governmental, fiscal, and economic policies and reforms. This collection of actions presents an opportunity to build a more resilient health and social services infrastructure and regional health care networks to ensure reliable access to services, promote health and well-being, and more efficiently and effectively respond to public health crises and future disasters. The actions span the areas of health care, public health and emergency preparedness, environmental health, mental and behavioral health, and social services. The damage and needs assessment and courses of actions cover four major themes: building system capacity to respond both during disasters and routine times; strengthening the health and social services workforce; strengthening support services for at-need populations; and creating health-promoting communities., (Copyright © 2021 RAND Corporation.)

Transmissible spongiform encephalopathy (TSE) surveillance in goats relies on tests initially approved for cattle, subsequently assessed for sheep, and approval extrapolated for use in "small ruminants." The current EU-approved immunodetection tests employ antibodies against various epitopes of the prion protein PrP Sc , which is encoded by the host PRNP gene. The caprine PRNP gene is polymorphic, mostly at codons different from the ovine PRNP . The EU goat population is much more heterogeneous than the sheep population, with more PRNP -related polymorphisms, and with marked breed-related differences. The ability of the current tests to detect disease-specific PrP Sc generated against these different genetic backgrounds is currently assumed, rather than proven. We examined whether common polymorphisms within the goat PRNP gene might have any adverse effect on the relative performance of EU-approved rapid tests. The sample panel comprised goats from the UK, Cyprus, France, and Italy, with either experimental or naturally acquired scrapie at both the preclinical and/or unknown and clinical stages of disease. Test sensitivity was significantly lower and more variable when compared using samples from animals that were preclinical or of unknown status. However, all of the rapid tests included in our study were able to correctly identify all samples from animals in the clinical stages of disease, apart from samples from animals polymorphic for serine or aspartic acid at codon 146, in which the performance of the Bio-Rad tests was profoundly affected. Our data show that some polymorphisms may adversely affect one test and not another, as well as underline the dangers of extrapolating from other species.

Background: Between 12,000 and 16,000 veterans leave incarceration annually. As is known to be the case for justice-involved populations in general, mental health disorders (MHDs) and substance use disorders (SUDs) are highly prevalent among incarcerated veterans, and individuals with MHDs and SUDs reentering the community are at increased risk of deteriorating health and recidivism. We sought to identify opportunities to better coordinate care/services across correctional, community, and VA systems for reentry veterans with MHDs and SUDs., Methods: We interviewed 16 veterans post-incarceration and 22 stakeholders from reentry-involved federal/state/community organizations. We performed a grounded thematic analysis, and recognizing consistencies between the emergent themes and the evidence-based Collaborative Chronic Care Model (CCM), we mapped findings to the CCM's elements - work role redesign (WRR), patient self-management support (PSS), provider decision support (PDS), clinical information systems (CIS), linkages to community resources (LCR), and organizational/leadership support (OLS)., Results: Emergent themes included (i) WRR - coordination challenges among organizations involved in veterans' reentry; (ii) PSS - veterans' fear of reentering society; (iii) PDS - uneven knowledge by reentry support providers regarding available services when deciding which services to connect a reentry veteran to and whether he/she is ready and/or willing to receive services; (iv) CIS - lapses in MHD/SUD medications between release and a first scheduled health care appointment, as well as challenges in transfer of medical records; (v) LCR - inconsistent awareness of existing services and resources available across a disparate reentry system; and (vi) OLS - reentry plans designed to address only immediate transitional needs upon release, which do not always prioritize MHD/SUD needs., Conclusions: Applying the CCM to coordinating cross-system health care and reentry support may contribute to reductions in mental health crises and overdoses in the precarious first weeks of the reentry period.

The European Commission asked EFSA for a Scientific Opinion: to revise the state of knowledge about the differences between the chronic wasting disease (CWD) strains found in North America (NA) and Europe and within Europe; to review new scientific evidence on the zoonotic potential of CWD and to provide recommendations to address the potential risks and to identify risk factors for the spread of CWD in the European Union. Full characterisation of European isolates is being pursued, whereas most NA CWD isolates have not been characterised in this way. The differing surveillance programmes in these continents result in biases in the types of cases that can be detected. Preliminary data support the contention that the CWD strains identified in Europe and NA are different and suggest the presence of strain diversity in European cervids. Current data do not allow any conclusion on the implications of strain diversity on transmissibility, pathogenesis or prevalence. Available data do not allow any conclusion on the zoonotic potential of NA or European CWD isolates. The risk of CWD to humans through consumption of meat cannot be directly assessed. At individual level, consumers of meat, meat products and offal derived from CWD-infected cervids will be exposed to the CWD agent(s). Measures to reduce human dietary exposure could be applied, but exclusion from the food chain of whole carcasses of infected animals would be required to eliminate exposure. Based on NA experiences, all the risk factors identified for the spread of CWD may be associated with animals accumulating infectivity in both the peripheral tissues and the central nervous system. A subset of risk factors is relevant for infected animals without involvement of peripheral tissues. All the risk factors should be taken into account due to the potential co-localisation of animals presenting with different disease phenotypes., (© 2019 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

This study explored patterns of clinical need among homeless individuals with dual diagnoses, and explored whether certain profiles are characteristic of different demographic groups. Data were drawn from two larger studies conducted with dually diagnosed, homeless individuals (n = 373). Hierarchical cluster analysis identified four subgroups: (1) Clinically least severe, characterized by less frequent psychological symptoms and no history of physical or sexual abuse; (2) Moderate clinical needs, including shorter history of substance use and less frequent psychological symptoms, but symptoms consistent with severe mental illness; (3) Clinically severe, with frequent anxiety, depression, past and recent physical or sexual abuse, and long history of substance use; (4) Least frequent psychological symptoms, but frequent history of physical or sexual abuse and long history of drug use. Women veterans were mostly likely to be classified in cluster 3, and male civilians in cluster 2. Subgroups of homeless individuals with dual diagnoses demonstrated different clusters of clinical needs, having implications for service delivery to the population.

Prions are highly resistant to the decontamination procedures normally used to inactivate conventional pathogens. This is a challenging problem not only in the medical and veterinary fields for minimizing the risk of transmission from potentially infective sources but also for ensuring the safe disposal or subsequent use of animal by-products. Specific pressure autoclaving protocols were developed for this purpose, but different strains of prions have been reported to have differing resistance patterns to established prion decontamination procedures, and as additional TSE strains are identified it is necessary to determine the effectiveness of such procedures. In this study we assessed the efficacy of sterilization using the EU recommended autoclave procedure for prions (133°C, 3 Bar for 20 min) on the atypical or Nor98 (AS/Nor98) scrapie strain of sheep and goats. Using a highly sensitive murine mouse model (tg338) that overexpresses ovine PrP C , we determined that this method of decontamination reduced the infectivity titre by 10 10 . Infectivity was nonetheless still detected after applying the recommended autoclaving protocol. This shows that AS/Nor98 can survive the designated legislative decontamination conditions, albeit with a significant decrease in titre. The infectivity of a classical scrapie isolate subjected to the same decontamination conditions was reduced by 10 6 suggesting that the AS/Nor98 isolate is less sensitive to decontamination than the classical scrapie source., (© 2019 Blackwell Verlag GmbH.)

Background: Between 12,000 and 16,000 veterans leave incarceration every year, yet resources are limited for reentry support that helps veterans remain connected to VA and community health care and services after leaving incarceration. Homelessness and criminal justice recidivism may result when such follow-up and support are lacking. In order to determine where gaps exist in current reentry support efforts, we developed a novel methodological adaptation of process mapping (a visualization technique being increasingly used in health care to identify gaps in services and linkages) in the context of a larger implementation study of a peer-support intervention to link veterans to health-related services after incarceration ( https://clinicaltrials.gov/ , NCT02964897, registered November 4, 2016) to support their reentry into the community., Methods: We employed process mapping to analyze qualitative interviews with staff from organizations providing reentry support. Interview data were used to generate process maps specifying the sequence of events and the multiple parties that connect veterans to post-incarceration services. Process maps were then analyzed for uncertainties, gaps, and bottlenecks., Results: We found that reentry programs lack systematic means of identifying soon-to-be released veterans who may become their clients; veterans in prisons/jails, and recently released, lack information about reentry supports and how to access them; and veterans' whereabouts between their release and their health care appointments are often unknown to reentry and health care teams. These system-level shortcomings informed our intervention development and implementation planning of peer-support services for veterans' reentry., Conclusions: Systematic information sharing that is inherent to process mapping makes more transparent the research needed, helping to engage participants and operational partners who are critical for successful implementation of interventions to improve reentry support for veterans leaving incarceration. Even beyond our immediate study, process mapping based on qualitative interview data enables visualization of data that is useful for 1) verifying the research team's interpretation of interviewee's accounts, 2) specifying the events that occur within processes that the implementation is targeting (identifying knowledge gaps and inefficiencies), and 3) articulating and tracking the pre- to post-implementation changes clearly to support dissemination of evidence-based health care practices for justice-involved populations.

The prion hypothesis proposes a causal relationship between the misfolded prion protein (PrPSc) molecular entity and the disease transmissible spongiform encephalopathy (TSE). Variations in the conformation of PrPSc are associated with different forms of TSE and different risks to animal and human health. Since the discovery of atypical forms of bovine spongiform encephalopathy (BSE) in 2003, scientists have progressed the molecular characterisation of the associated PrPSc in order to better understand these risks, both in cattle as the natural host and following experimental transmission to other species. Here we report the development of a mass spectrometry based assay for molecular characterisation of bovine proteinase K (PK) treated PrPSc (PrPres) by quantitative identification of its N-terminal amino acid profiles (N-TAAPs) and tryptic peptides. We have applied the assay to classical, H-type and L-type BSE prions purified from cattle, transgenic (Tg) mice expressing the bovine (Tg110 and Tg1896) or ovine (TgEM16) prion protein gene, and sheep brain. We determined that, for classical BSE in cattle, the G96 N-terminal cleavage site dominated, while the range of cleavage sites was wider following transmission to Tg mice and sheep. For L-BSE in cattle and Tg bovinised mice, a C-terminal shift was identified in the N-TAAP distribution compared to classical BSE, consistent with observations by Western blot (WB). For L-BSE transmitted to sheep, both N-TAAP and tryptic peptide profiles were found to be changed compared to cattle, but less so following transmission to Tg ovinised mice. Relative abundances of aglycosyl peptides were found to be significantly different between the atypical BSE forms in cattle as well as in other hosts. The enhanced resolution provided by molecular analysis of PrPres using mass spectrometry has improved insight into the molecular changes following transmission of atypical BSE to other species., Competing Interests: The authors have declared that no competing interests exist.

The epizootic prion disease of cattle, bovine spongiform encephalopathy (BSE), causes variant Creutzfeldt-Jakob disease (vCJD) in humans following dietary exposure. While it is assumed that all cases of vCJD attributed to a dietary aetiology are related to cattle BSE, sheep and goats are susceptible to experimental oral challenge with cattle BSE prions and farmed animals in the UK were undoubtedly exposed to BSE-contaminated meat and bone meal during the late 1980s and early 1990s. Although no natural field cases of sheep BSE have been identified, it cannot be excluded that some BSE-infected sheep might have entered the European human food chain. Evaluation of the zoonotic potential of sheep BSE prions has been addressed by examining the transmission properties of experimental brain isolates in transgenic mice that express human prion protein, however to-date there have been relatively few studies. Here we report that serial passage of experimental sheep BSE prions in transgenic mice expressing human prion protein with methionine at residue 129 produces the vCJD phenotype that mirrors that seen when the same mice are challenged with vCJD prions from patient brain. These findings are congruent with those reported previously by another laboratory, and thereby strongly reinforce the view that sheep BSE prions could have acted as a causal agent of vCJD within Europe., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

This report presents the results of experimental challenges of goats with scrapie by both the intracerebral (i.c.) and oral routes, exploring the effects of polymorphisms at codon 146 of the goat PRNP gene on resistance to disease. The results of these studies illustrate that while goats of all genotypes can be infected by i.c. challenge, the survival distribution of the animals homozygous for asparagine at codon 146 was significantly shorter than those of animals of all other genotypes (chi-square value, 10.8; P = 0.001). In contrast, only those animals homozygous for asparagine at codon 146 (NN animals) succumbed to oral challenge. The results also indicate that any cases of infection in non-NN animals can be detected by the current confirmatory test (immunohistochemistry), although successful detection with the rapid enzyme-linked immunosorbent assay (ELISA) was more variable and dependent on the polymorphism. Together with data from previous studies of goats exposed to infection in the field, these data support the previously reported observations that polymorphisms at this codon have a profound effect on susceptibility to disease. It is concluded that only animals homozygous for asparagine at codon 146 succumb to scrapie under natural conditions. IMPORTANCE In goats, like in sheep, there are PRNP polymorphisms that are associated with susceptibility or resistance to scrapie. However, in contrast to the polymorphisms in sheep, they are more numerous in goats and may be restricted to certain breeds or geographical regions. Therefore, eradication programs must be specifically designed depending on the identification of suitable polymorphisms. An initial analysis of surveillance data suggested that such a polymorphism in Cypriot goats may lie in codon 146. In this study, we demonstrate experimentally that NN animals are highly susceptible after i.c. inoculation. The presence of a D or S residue prolonged incubation periods significantly, and prions were detected in peripheral tissues only in NN animals. In oral challenges, prions were detected only in NN animals, and the presence of a D or S residue at this position conferred resistance to the disease. This study provides an experimental transmission model for assessing the genetic susceptibility of goats to scrapie., (© Crown copyright 2017.)

Background: Approximately 600,000 persons are released from prison annually in the United States. Relatively few receive sufficient re-entry services and are at risk for unemployment, homelessness, poverty, substance abuse relapse and recidivism. Persons leaving prison who have a mental illness and/or a substance use disorder are particularly challenged. This project aims to create a peer mentor program to extend the reach and effectiveness of reentry services provided by the Department of Veterans' Affairs (VA). We will implement a peer support for reentry veterans sequentially in two states. Our outcome measures are 1) fidelity of the intervention, 2) linkage to VA health care and, 3) continued engagement in health care. The aims for this project are as follows: (1) Conduct contextual analysis to identify VA and community reentry resources, and describe how reentry veterans use them. (2) Implement peer-support, in one state, to link reentry veterans to Veterans' Health Administration (VHA) primary care, mental health, and SUD services. (3) Port the peer-support intervention to another, geographically, and contextually different state., Design: This intervention involves a 2-state sequential implementation study (Massachusetts, followed by Pennsylvania) using a Facilitation Implementation strategy. We will conduct formative and summative analyses, including assessment of fidelity, and a matched comparison group to evaluate the intervention's outcomes of veteran linkage and engagement in VHA health care (using health care utilization measures). The study proceeds in 3 phases., Discussion: We anticipate that a peer support program will be effective at improving the reentry process for veterans, particularly in linking them to health, mental health, and SUD services and helping them to stay engaged in those services. It will fill a gap by providing veterans with access to a trusted individual, who understands their experience as a veteran and who has experienced justice involvement. The outputs from this project, including training materials, peer guidebooks, and implementation strategies can be adapted by other states and regions that wish to enhance services for veterans (or other populations) leaving incarceration. A larger cluster-randomized implementation-effectiveness study is planned., Trial Registration: This protocol is registered with clinicaltrials.gov on November 4, 2016 and was assigned the number NCT02964897 .

Context:   Ice hockey is a high-speed, full-contact sport with a high risk of head/face/neck (HFN) injuries. However, men's and women's ice hockey differ; checking is allowed only among men., Objectives:   To describe the epidemiology of HFN injuries in collegiate men's and women's ice hockey during the 2009-2010 through 2013-2014 academic years., Design:   Descriptive epidemiology study., Setting:   Ice hockey data from the National Collegiate Athletic Association (NCAA) Injury Surveillance Program during the 2009-2010 through 2013-2014 academic years., Patients or Other Participants:   Fifty-seven men's and 26 women's collegiate ice hockey programs from all NCAA divisions provided 106 and 51 team-seasons of data, respectively., Main Outcome Measure(s):   Injury rates per 1000 athlete-exposures and rate ratios with 95% confidence intervals (CIs)., Results:   The NCAA Injury Surveillance Program reported 496 and 131 HFN injuries in men's and women's ice hockey, respectively. The HFN injury rate was higher in men than in women (1.75 versus 1.16/1000 athlete-exposures; incidence rate ratio = 1.51; 95% CI = 1.25, 1.84). The proportion of HFN injuries from checking was higher in men than in women for competitions (38.5% versus 13.6%; injury proportion ratio = 2.82; 95% CI = 1.64, 4.85) and practices (21.9% versus 2.3%; injury proportion ratio = 9.41; 95% CI = 1.31, 67.69). The most common HFN injury diagnosis was concussion; most concussions occurred in men's competitions from player contact while checking (25.9%). Player contact during general play comprised the largest proportion of concussions in men's practices (25.9%), women's competitions (25.0%), and women's practices (24.0%). While 166 lacerations were reported in men, none were reported in women. In men, most lacerations occurred from player contact during checking in competitions (41.8%) and player contact during general play in practices (15.0%)., Conclusions:   A larger proportion of HFN injuries in ice hockey occurred during checking in men versus women. Concussion was the most common HFN injury and was most often due to player contact. Lacerations were reported only among men and were mostly due to checking. Injury-prevention programs should aim to reduce checking-related injuries.

Background: Homeless veterans often have multiple health care and psychosocial needs, including assistance with access to housing and health care, as well as support for ongoing treatment engagement. The Department of Veterans Affairs (VA) developed specialized Homeless Patient Alignment Care Teams (HPACT) with the goal of offering an integrated, "one-stop program" to address housing and health care needs of homeless veterans. However, while 70% of HPACT's veteran enrollees have co-occurring mental health and substance use disorders, HPACT does not have a uniform, embedded treatment protocol for this subpopulation. One wraparound intervention designed to address the needs of homeless veterans with co-occurring mental health and substance use disorders which is suitable to be integrated into HPACT clinic sites is the evidence-based practice called Maintaining Independence and Sobriety through Systems Integration, Outreach, and Networking-Veterans Edition, or MISSION-Vet. Despite the promise of MISSION-Vet within HPACT clinics, implementation of an evidence-based intervention within a busy program like HPACT can be difficult. The current study is being undertaken to identify an appropriate implementation strategy for MISSION-Vet within HPACT. The study will test the implementation platform called Facilitation and compared to implementation as usual (IU). The aims of this study are as follows: (1) Compare the extent to which IU or Facilitation strategies achieve fidelity to the MISSION-Vet intervention as delivered by HPACT homeless provider staff. (2) Compare the effects of Facilitation and IU strategies on the National HPACT Performance Measures. (3) Compare the effects of IU and Facilitation on the permanent housing status. (4) Identify and describe key stakeholders' (patients, providers, staff) experiences with, and perspectives on, the barriers to, and facilitators of implementing MISSION., Design: Type III Hybrid modified stepped wedge implementation comparing IU to Facilitation across seven HPACT teams in three sites in the greater Los Angeles VA system. This is a cluster randomized trial., Discussion: Integrating MISSION-Vet within HPACT has the potential to improve the health of thousands of veterans, but it is crucial to implement the intervention appropriately in order for it to succeed. The lessons learned in this protocol could assist with a larger roll-out of MISSION within HPACT. This protocol is registered with clinicaltrials.gov and was assigned the number NCT 02942979.

Aims: Prion diseases exist in classical and atypical disease forms. Both forms are characterized by disease-associated accumulation of a host membrane sialoglycoprotein known as prion protein (PrP d ). In classical forms of prion diseases, PrP d can accumulate in the extracellular space as fibrillar amyloid, intracellularly within lysosomes, but mainly on membranes in association with unique and characteristic membrane pathology. These membrane changes are found in all species and strains of classical prion diseases and consist of spiral, branched and clathrin-coated membrane invaginations on dendrites. Atypical prion diseases have been described in ruminants and man and have distinct biological, biochemical and pathological properties when compared to classical disease. The purpose of this study was to determine whether the subcellular pattern of PrP d accumulation and membrane changes in atypical scrapie were the same as those found in classical prion diseases., Methods: Immunogold electron microscopy was used to examine brains of atypical scrapie-affected sheep and Tg338 mice., Results: Classical prion disease-associated membrane lesions were not found in atypical scrapie-affected sheep, however, white matter PrP d accumulation was localized mainly to the inner mesaxon and paranodal cytoplasm of oligodendroglia. Similar lesions were found in myelinated axons of atypical scrapie Tg338-infected mice. However, Tg338 mice also showed the unique grey matter membrane changes seen in classical forms of disease., Conclusions: These data show that atypical scrapie infection directs a change in trafficking of abnormal PrP to axons and oligodendroglia and that the resulting pathology is an interaction between the agent strain and host genotype., (© 2016 Crown copyright. Neuropathology and Applied Neurobiology © 2016 British Neuropathological Society. This article Altered trafficking of abnormal prion protein in atypical scrapie: prion protein accumulation in oligodendroglial inner mesaxons is written by M. Jeffrey et al. It is published with the permission of the Controller of HMSO and the Queen's Printer for Scotland.)

Pathology is the study of the structural and functional changes produced by diseases or - more specifically - the lesions they cause. To achieve this pathologists employ various approaches. These include description of lesions that are visible to the naked eye which are the subject of anatomic pathology and changes at the cellular level that are visible under the microscope, the subject of histopathology. Changes at the molecular level which are identified by probes that target specific molecules - mainly proteins that are detected using immunohistochemistry (IHC). As transmissible spongiform encephalopathies (TSEs) do not cause visible lesions anatomic pathology is not applicable to their study. For decades the application of histopathology to detect vacuoles or plaques was the only means of confirming TSE disease. The subsequent discovery of the cellular prion protein (PrP C ) and its pathogenic isoform, PrP Sc , which is a ubiquitous marker of TSEs, led to the production of anti-PrP antibodies, and enabled the development of PrP Sc detection techniques such as immunohistochemistry, Histoblot and PET-blot that have evolved in parallel with similar biochemical methods such as Western blot and ELISA. These methods offer greater sensitivity than histopathology in TSE diagnosis and crucially they can be applied to analyze various phenotypic aspects of single TSE sources increasing the amount of data and offering higher discriminatory power. The above principles are applied to diagnose and define TSE phenotypes which form the basis of strain characterisation., Competing Interests: Conflict of interest statement: The authors had no conflicts of interest to declare in this article., (©2016 Food Safety Commission, Cabinet Office, Government of Japan.)

The results of the study reported here are part of an ongoing integrated research programme aimed at producing additional, robust, evidence on the genetic resistance to classical scrapie in goats, with particular reference to codon 146. The study targeted animals aged ⩾6 years, which were born and raised in infected herds and were being culled for management reasons. A total of 556 animals were tested, and all positive animals (n = 117) were of the susceptible NN genotype. A total of 246 goats heterozygous or homozygous for putatively resistant alleles (S146 and D146) were screened with no positive results. The outcome of this study supports the hypothesis that the D146 and S146 alleles could be used as the basis for a nationwide strategy for breeding for resistance in the Cypriot goat population.

Many mammalian species can be affected by prion diseases, also known as transmissible spongiform encephalopathies (TSEs). "Classical" bovine spongiform encephalopathy (C-BSE) was the first prion disease recognized in cattle and it is the only known zoonotic prion disease, having caused variant Creutzfeldt-Jakob disease (vCJD) in humans. Based on the biochemical signatures of disease-associated prion protein (PrP Sc ), two distinct forms of atypical bovine spongiform encephalopathies (H-BSE and L-BSE) have been distinguished from C-BSE since 2004. To date there is no comprehensive information about the origin of atypical BSEs (sporadic vs. acquired) and this has an influence on the interpretation of the knowledge gathered from experimental studies, regarding how well such models may represent the real distribution of the agent in the body of naturally affected animals. Moreover, there are only very limited data available concerning the pathogenesis of both atypical BSE forms, as compared to C-BSE. Thus, precautions that are presently taken to minimize the risk of prion contamination of the food supply might not be as effective at preventing the spread of these recently recognized strains. In the last few years a wide range of experimental transmission studies of atypical strains in different animal hosts have been performed. The most recent data on classical and atypical BSE studies concerning characteristics, pathogenesis and transmissions in cattle will be summarized in this review., Competing Interests: Conflict of interest statement: The authors had no conflicts of interest to declare in this article., (©2016 Food Safety Commission, Cabinet Office, Government of Japan.)

Apart from prion protein genotype, the factors determining the host range and susceptiblity for specific transmissible spongiform encephalopathy agents remain unclear. It is known that bovine atypical L-BSE can transmit to a range of species including primates and humanised transgenic mice. It is important, therefore, that there is as broad an understanding as possible of how such isolates might present in food animal species and how robust they are on inter- and intra-species transmission to inform surveillance sytems and risk assessments. This paper demonstrates that L-BSE can be intracerebrally transmitted to sheep of several genotypes, with the exception of ARR/ARR animals. Positive animals mostly present with a cataplectic form of disease characterized by collapsing episodes and reduced muscle tone. PrP accumulation is confined to the nervous system, with the exception of one animal with lymphoreticular involvement. In Western blot there was maintenance of the low molecular mass and glycoform profile associated with L-BSE, irrespective of ovine host genotype, but there was a substantially higher N-terminal antibody signal relative to the core-specific antibody, which is similar to the ratio associated with classical scrapie. The disease phenotype was maintained on experimental subpassage, but with a shortened survival time indicative of an original species barrier and subsequent adaptation. Passive surveillance approaches would be unlikely to identify such cases as TSE suspects, but current statutory active screening methods would be capable of detecting such cases and classifying them as unusual and requiring further investigation if they were to occur in the field.

Background: Previous studies confirmed that classical scrapie can be transmitted via milk in sheep. The current study aimed to investigate whether scrapie can also be transmitted via goat milk using in vivo (new-born lambs fed milk from scrapie-affected goats due to the unavailability of goat kids from guaranteed scrapie-free herds) and in vitro methods (serial protein misfolding cyclic amplification [sPMCA] on milk samples)., Results: In an initial pilot study, new-born lambs of two different prion protein gene (PRNP) genotypes (six VRQ/VRQ and five ARQ/ARQ) were orally challenged with 5 g brain homogenate from two scrapie-affected goats to determine susceptibility of sheep to goat scrapie. All sheep challenged with goat scrapie brain became infected based on the immunohistochemical detection of disease-associated PrP (PrP(sc)) in lymphoid tissue, with an ARQ/ARQ sheep being the first to succumb. Subsequent feeding of milk to eight pairs of new-born ARQ/ARQ lambs, with each pair receiving milk from a different scrapie-affected goat, resulted in scrapie in the six pairs that received the largest volume of milk (38-87 litres per lamb), whereas two pairs fed 8-9 litres per lamb, and an environmental control group raised on sheep milk from healthy ewes, did not show evidence of infection when culled at up to 1882 days of age. Infection in those 12 milk recipients occurred regardless of the clinical status, PrP(sc) distribution, caprine arthritis-encephalitis virus infection status and PRNP polymorphisms at codon 142 (II or IM) of the donor goats, but survival time was influenced by PRNP polymorphisms at codon 141. Serial PMCA applied to a total of 32 milk samples (four each from the eight donor goats collected throughout lactation) detected PrP(sc) in one sample each from two goats., Conclusions: The scrapie agent was present in the milk from infected goats and was able to transmit to susceptible species even at early preclinical stage of infection, when PrP(sc) was undetectable in the brain of the donor goats. Serial PMCA as a PrP(sc) detection method to assess the risk of scrapie transmission via milk in goats proved inefficient compared to the bioassay.

Scrapie is transmissible spongiform encephalopathy (TSE), which causes neurological signs in sheep, but confirmatory diagnosis is usually made postmortem on examination of the brain for TSE-associated markers like vacuolar changes and disease-associated prion protein (PrP(Sc)). The objective of this study was to evaluate whether testing of brainstem auditory evoked potentials (BAEPs) at two different sound levels could aid in the clinical diagnosis of TSEs in sheep naturally or experimentally infected with different TSE strains [classical and atypical scrapie and bovine spongiform encephalopathy (BSE)] and whether any BAEP abnormalities were associated with TSE-associated markers in the auditory pathways. BAEPs were recorded from 141 clinically healthy sheep of different breeds and ages that tested negative for TSEs on postmortem tests to establish a reference range and to allow comparison with 30 sheep clinically affected or exposed to classical scrapie (CS) without disease confirmation (test group 1) and 182 clinically affected sheep with disease confirmation (test group 2). Abnormal BAEPs were found in 7 sheep (23%) of group 1 and 42 sheep (23%) of group 2. The proportion of sheep with abnormalities did not appear to be influenced by TSE strain or PrP(Sc) gene polymorphisms. When the magnitude of TSE-associated markers in the auditory pathways was compared between a subset of 12 sheep with and 12 sheep without BAEP abnormalities in group 2, no significant differences in the total PrP(Sc) or vacuolation scores in the auditory pathways could be found. However, the data suggested that there was a difference in the PrP(Sc) scores depending on the TSE strain because PrP(Sc) scores were significantly higher in sheep with BAEP abnormalities infected with classical and L-type BSE, but not with CS. The results indicated that BAEPs may be abnormal in sheep infected with TSEs but the test is not specific for TSEs and that neither vacuolation nor PrP(Sc) accumulation appears to be responsible for the clinical abnormalities.

Objectives: In the United States, state firearm ownership has been correlated with homicide rates. More than 90% of homicides of law enforcement officers (LEOs) are committed with firearms. We examined the relationship between state firearm ownership rates and LEO occupational homicide rates., Methods: We obtained the number LEOs killed from 1996 to 2010 from a Federal Bureau of Investigation (FBI) database. We calculated homicide rates per state as the number of officers killed per number of LEOs per state, obtained from another FBI database. We obtained the mean household firearm ownership for each state from the Behavioral Risk Factor Surveillance System., Results: Using Poisson regression and controlling for factors known to affect homicide rates, we associated firearm ownership with the homicide rates for LEOs (incidence rate ratio = 1.044; P = .005); our results were supported by cross-sectional and longitudinal sensitivity analyses. LEO homicide rates were 3 times higher in states with high firearm ownership compared with states with low firearm ownership., Conclusions: High public gun ownership is a risk for occupational mortality for LEOs in the United States. States could consider methods for reducing firearm ownership as a way to reduce occupational deaths of LEOs.

Current European Commission (EC) surveillance regulations require discriminatory testing of all transmissible spongiform encephalopathy (TSE)-positive small ruminant (SR) samples in order to classify them as bovine spongiform encephalopathy (BSE) or non-BSE. This requires a range of tests, including characterization by bioassay in mouse models. Since 2005, naturally occurring BSE has been identified in two goats. It has also been demonstrated that more than one distinct TSE strain can coinfect a single animal in natural field situations. This study assesses the ability of the statutory methods as listed in the regulation to identify BSE in a blinded series of brain samples, in which ovine BSE and distinct isolates of scrapie are mixed at various ratios ranging from 99% to 1%. Additionally, these current statutory tests were compared with a new in vitro discriminatory method, which uses serial protein misfolding cyclic amplification (sPMCA). Western blotting consistently detected 50% BSE within a mixture, but at higher dilutions it had variable success. The enzyme-linked immunosorbent assay (ELISA) method consistently detected BSE only when it was present as 99% of the mixture, with variable success at higher dilutions. Bioassay and sPMCA reported BSE in all samples where it was present, down to 1%. sPMCA also consistently detected the presence of BSE in mixtures at 0.1%. While bioassay is the only validated method that allows comprehensive phenotypic characterization of an unknown TSE isolate, the sPMCA assay appears to offer a fast and cost-effective alternative for the screening of unknown isolates when the purpose of the investigation was solely to determine the presence or absence of BSE., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Introduction: Scrapie and bovine spongiform encephalopathy (BSE) are transmissible spongiform encephalopathies (TSEs) which naturally affect small and large ruminants respectively. However, small ruminants, which are susceptible to BSE under experimental conditions, have been exposed to the same or similar contaminated food additives as cattle. To date two natural cases of BSE in small ruminants have been reported. As a result surveillance projects, combined with appropriate control measures, have been established throughout the European Union (EU) to minimize the overall incidence of small ruminant TSEs. Although BSE can be differentiated from classical scrapie (subsequently referred to as scrapie) if appropriate discriminatory tests are applied, the value of these tests in BSE/scrapie co-infection scenarios has not been evaluated fully. Mouse bioassay is regarded as the gold standard regarding differentiation of distinct TSE strains and has been used as to resolve TSE cases were laboratory tests produced equivocal results. However, the ability of this method to discriminate TSE strains when they co-exist has not been examined systematically. To address this issue we prepared in vitro mixtures of ovine BSE and scrapie and used them to challenge RIII, C57BL/6 and VM mice., Results: Disease phenotype analysis in all three mouse lines indicated that most phenotypic parameters (attack rates, incubation periods, lesion profiles and Western blots) were compatible with scrapie phenotypes as were immunohistochemistry (IHC) data from RIII and C57BL/6 mice. However, in VM mice that were challenged with BSE/scrapie mixtures a single BSE-associated IHC feature was identified, indicating the existence of BSE in animals where the scrapie phenotype was dominant., Conclusions: We conclude that wild type mouse bioassay is of limited value in detecting BSE in the presence of scrapie particularly if the latter is in relative excess.

Previous studies have shown the association between the polymorphisms serine (S) or aspartic acid (D) at codon 146 of the PRNP gene and resistance to scrapie. All goats aged >12 months (a total of 1075 animals) from four herds with the highest prevalence of scrapie in the country were culled and tested, of which 234 (21·7%) were positive by either the rapid test or immunohistochemistry (IHC) for any of the tissues tested. The odds of scrapie infection occurring in NN146 goats was 101 [95% credible interval (CrI) 19-2938] times higher than for non-NN146 or unknown genotypes. IHC applied to lymphoreticular tissue produced the highest sensitivity (94%, 95% CrI 90-97). The presence of putatively resistant non-NN146 alleles in the Cypriot goat population, severely affected by scrapie, provides a potential tool to reduce/eradicate scrapie provided that coordinated nationwide breeding programmes are implemented and maintained over time.

The interactions of host and infecting strain in ovine transmissible spongiform encephalopathies are known to be complex, and have a profound effect on the resulting phenotype of disease. In contrast to classical scrapie, the pathology in naturally-occurring cases of atypical scrapie appears more consistent, regardless of genotype, and is preserved on transmission within sheep homologous for the prion protein (PRNP) gene. However, the stability of transmissible spongiform encephalopathy phenotypes on passage across and within species is not absolute, and there are reports in the literature where experimental transmissions of particular isolates have resulted in a phenotype consistent with a different strain. In this study, intracerebral inoculation of atypical scrapie between two genotypes both associated with susceptibility to atypical forms of disease resulted in one sheep displaying an altered phenotype with clinical, pathological, biochemical and murine bioassay characteristics all consistent with the classical scrapie strain CH1641, and distinct from the atypical scrapie donor, while the second sheep did not succumb to challenge. One of two sheep orally challenged with the same inoculum developed atypical scrapie indistinguishable from the donor. This study adds to the range of transmissible spongiform encephalopathy phenotype changes that have been reported following various different experimental donor-recipient combinations. While these circumstances may not arise through natural exposure to disease in the field, there is the potential for iatrogenic exposure should current disease surveillance and feed controls be relaxed. Future sheep to sheep transmission of atypical scrapie might lead to instances of disease with an alternative phenotype and onward transmission potential which may have adverse implications for both public health and animal disease control policies.