Alabama Veterans Rural Health Initiative: A Preliminary Evaluation of Unmet Health Care Needs

The Alabama Veterans Rural Health Initiative aims to better understand the health care needs, health status, and barriers to care for rural veterans. Following extensive community outreach, Veteran Community Outreach Health Workers assessed 203 veterans residing in rural counties of Alabama who either: 1) had never enrolled in VA health services, or 2) had not used those services in at least two years. While 71.4 percent of participants reported having utilized non-VHA primary care within the past year, 33.5 percent reported an inability or delay in obtaining needed health care for one or more services: primary care, specialty care, mental health care, addictions treatment, dental care, or prescription medication. The most commonly cited barrier was cost. Among all participants, 56 percent screened positive for at least one Axis I mental disorder. Rurally residing, non-VHA utilizing veterans appear to have fairly good access to primary care, but need dental care, prescription medication, and mental health care

Shifted phase of EEG cross-frequency coupling in individuals with Phelan-McDermid syndrome

Background Phelan-McDermid Syndrome (PMS) is a rare condition caused by deletion or mutation of the SHANK3 gene. Individuals with PMS frequently present with intellectual disability, autism spectrum disorder, and other neurodevelopmental challenges. Electroencephalography (EEG) can provide a window into network-level function in PMS. Methods Here, we analyze EEG data collected across multiple sites in individuals with PMS (n = 26) and typically developing individuals (n = 15). We quantify oscillatory power, alpha-gamma phase-amplitude coupling strength, and phase bias, a measure of the phase of cross frequency coupling thought to reflect the balance of feedforward (bottom-up) and feedback (top-down) activity. Results We find individuals with PMS display increased alpha-gamma phase bias (U = 3.841, p < 0.0005), predominantly over posterior electrodes. Most individuals with PMS demonstrate positive overall phase bias while most typically developing individuals demonstrate negative overall phase bias. Among individuals with PMS, strength of alpha-gamma phase-amplitude coupling was associated with Sameness, Ritualistic, and Compulsive behaviors as measured by the Repetitive Behavior Scales-Revised (Beta = 0.545, p = 0.011). Conclusions Increased phase bias suggests potential circuit-level mechanisms underlying phenotype in PMS, offering opportunities for back-translation of findings into animal models and targeting in clinical trials

"People don't have the answers": A qualitative exploration of the experiences of young people with Long COVID

Young people living with Long COVID are learning to navigate life with a constellation of poorly understood symptoms. Most qualitative studies on experiences living with Long COVID focus on adult populations. This study aimed to understand the experiences of young people living with Long COVID. Qualitative, semi-structured interviews were conducted (n = 16); 11 young people (aged 13-19) and five parents were recruited from the Children and Young People with Long COVID (CLoCk) study (n = 11) or its patient and public involvement and engagement (PPIE) group (n = 5). Thematic analysis generated four themes: (i) Unravelling Long COVID: Exploring Symptom Journeys and Diagnostic Dilemmas; (ii) Identity Disruption and Adjustment; (iii) Long COVID's Ripple Effect: the impact on Mental Health, Connections, and Education; and (iv) Navigating Long COVID: barriers to support and accessing services. Treatment options were perceived as not widely available or ineffective, emphasising the need for viable and accessible interventions for young people living with Long COVID

Temperatures of the Lacus Mortis Region of the Moon

Over 11&nbsp;years of data acquired by the Diviner Lunar Radiometer Experiment instrument aboard Lunar Reconnaissance Orbiter have been compiled into a comprehensive data set of surface temperatures in the Lacus Mortis region which includes the landing ellipse of the Astrobotic Mission One lander mission. These data provide diurnal brightness temperatures at 128 pixels per degree (ppd) spatial resolution and 0.1&nbsp;hr of local time resolution. From this data set, we highlight several features that display variations in radiative and thermophysical properties in the Lacus Mortis region and characterize the temperatures of the Astrobotic Mission One landing ellipse. We identify distinctly contrasting properties of materials in the walls of B&uuml;rg crater, hummocks of materials on the southeast margin of the mare basalts, and materials exposed or excavated by impacts. Additionally, we describe an exceptionally rocky fault scarp that predates the formation of B&uuml;rg crater suggesting the observed boulders are replenished on a timescale &lt;1&nbsp;Ga. Within the Astrobotic landing ellipse, temperatures are observed to range from &sim;88 to &sim;359&nbsp;K with sunrise and sunset local times constrained to 5.8&ndash;6.3&nbsp;hr and 17.8 and 18.1&nbsp;hr respectively. &nbsp;</p

Wnt-reporter expression pattern in the mouse intestine during homeostasis

<p>Abstract</p> <p>Background</p> <p>The canonical Wnt signaling pathway is a known regulator of cell proliferation during development and maintenance of the intestinal epithelium. Perturbations in this pathway lead to aberrant epithelial proliferation and intestinal cancer. In the mature intestine, proliferation is confined to the relatively quiescent stem cells and the rapidly cycling transient-amplifying cells in the intestinal crypts. Although the Wnt signal is believed to regulate all proliferating intestinal cells, surprisingly, this has not been thoroughly demonstrated. This important determination has implications on intestinal function, especially during epithelial expansion and regeneration, and warrants an extensive characterization of Wnt-activated cells.</p> <p>Methods</p> <p>To identify intestinal epithelial cells that actively receive a Wnt signal, we analyzed intestinal Wnt-reporter expression patterns in two different mouse lines using immunohistochemistry, enzymatic activity, <it>in situ </it>hybridization and qRT-PCR, then corroborated results with reporter-independent analyses. Wnt-receiving cells were further characterized for co-expression of proliferation markers, putative stem cell markers and cellular differentiation markers using an immunohistochemical approach. Finally, to demonstrate that Wnt-reporter mice have utility in detecting perturbations in intestinal Wnt signaling, the reporter response to gamma-irradiation was examined.</p> <p>Results</p> <p>Wnt-activated cells were primarily restricted to the base of the small intestinal and colonic crypts, and were highest in numbers in the proximal small intestine, decreasing in frequency in a gradient toward the large intestine. Interestingly, the majority of the Wnt-reporter-expressing cells did not overlap with the transient-amplifying cell population. Further, while Wnt-activated cells expressed the putative stem cell marker Musashi-1, they did not co-express DCAMKL-1 or cell differentiation markers. Finally, gamma-irradiation stimulated an increase in Wnt-activated intestinal crypt cells.</p> <p>Conclusion</p> <p>We show, for the first time, detailed characterization of the intestine from Wnt-reporter mice. Further, our data show that the majority of Wnt-receiving cells reside in the stem cell niche of the crypt base and do not extend into the proliferative transient-amplifying cell population. We also show that the Wnt-reporter mice can be used to detect changes in intestinal epithelial Wnt signaling upon physiologic injury. Our findings have an important impact on understanding the regulation of the intestinal stem cell hierarchy during homeostasis and in disease states.</p

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine

A journey in capacity building: Revisiting the mullins framework for meaningfully engaging patients in patient centered outcomes research

This paper reviews the implementation of the UNITE for Better Health Outcomes Eugene Washington PCORI Engagement Award project using Mullins and colleagues\u27 Framework for Meaningfully Engaging Patients in Patient Centered Outcomes Research (PCOR) and the advantages and disadvantages of this framework. We combine Mullins\u27 framework with the ten themes for guiding future studies in PCOR also developed by Mullins\u27 research group. We interviewed patient stakeholders at the end of the engagement award and include patient stakeholder perspectives of how well we performed each of these steps. Despite some breakdowns in trust, which were eventually repaired, we successfully identified patient and family stakeholders; built partnerships with patients, researchers, providers, and community groups; explained the purpose of our project and the importance of PCOR; developed training materials for patients and providers; and updated our key constituents throughout the process. Overall, we believe combining Mullins\u27 framework with the ten themes provides a solid roadmap for implementing a PCORI engagement award. Our main challenge was recruiting and keeping hard-to-reach patients and caregivers involved in the project. We believe this was due to our limitations more so than the framework. Based on the lessons we learned, we provide concrete recommendations for others who want to engage hard-to-reach patients using the Mullins framework