Autophagy, aging, and age-related neurodegeneration.

Autophagy is a conserved mechanism that degrades damaged or superfluous cellular contents and enables nutrient recycling under starvation conditions. Many neurodegeneration-associated proteins are autophagy substrates, and autophagy upregulation ameliorates disease in many animal models of neurodegeneration by enhancing the clearance of toxic proteins, proinflammatory molecules, and dysfunctional organelles. Autophagy inhibition also induces neuronal and glial senescence, a phenomenon that occurs with increasing age in non-diseased brains as well as in response to neurodegeneration-associated stresses. However, aging and many neurodegeneration-associated proteins and mutations impair autophagy. This creates a potentially detrimental feedback loop whereby the accumulation of these disease-associated proteins impairs their autophagic clearance, facilitating their further accumulation and aggregation. Thus, understanding how autophagy interacts with aging, senescence, and neurodegenerative diseases in a temporal, cellular, and genetic context is important for the future clinical application of autophagy-modulating therapies in aging and neurodegeneration.

Mental health provider perspectives on a mobile health application to support remote measurement-based care: Challenges and impacts.

Measurement-based care (MBC) comprises collecting patient-reported outcomes data using validated assessments and using that information to support treatment. The Veterans Health Administration (VHA) has developed technology platforms to support MBC, including the Mental Health Checkup (MHC) mobile health application (app). Our objective was to examine VHA mental health provider perspectives on the MHC app. We completed a mixed-methods, sequential explanatory evaluation of MHC. We surveyed 284 VHA mental health providers who used MHC, then conducted semistructured telephone interviews with a purposefully selected subset of survey respondents (n = 20). Approximately half of survey respondents agreed that MHC allowed them to collect assessment data from veterans more frequently than before (51%) and that they more frequently discussed assessment results with veterans because of MHC (50%) and used those results to inform goal-setting discussions (50%) and treatment decision making (51%). Bivariate analyses indicated a positive relationship between frequency of MHC use and the aforementioned impacts on care. Interview data conveyed both advantages (e.g., increased treatment efficiency, improved treatment decision making) and challenges (e.g., limited assessment availability, difficulties engaging veterans in completing assessments through the app) to using MHC. This evaluation demonstrated how MHC supported providers working to implement MBC. The app enhanced their ability to reach and engage veterans and incorporate assessment data into clinical encounters. Still, many did not perceive that MHC was impactful on mental health care delivery; given that providers who used MHC more frequently reported more positive impressions of MHC, this may be related to how frequently they used the app. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The role of economic factors in shaping and constituting the household burden of neglected tropical diseases of the skin: Qualitative findings from Ghana and Ethiopia.

Tracers of health system equity, neglected tropical diseases (NTDs) disproportionately affect marginalized populations. NTDs that manifest on the skin - "skin NTDs" - are associated with scarring, disfigurement, physical disability, social exclusion, psychological distress, and economic hardship. To support development and evaluation of appropriate intervention strategies, we aimed to improve understanding of the role of economic factors in shaping and constituting the burden that skin NTDs place on households. We collected data in 2021 in two predominantly rural districts: Atwima Mponua in Ghana (where Buruli ulcer, yaws, and leprosy are endemic) and Kalu in Ethiopia (where cutaneous leishmaniasis and leprosy are endemic). We conducted interviews (n = 50) and focus group discussions (n = 14) that explored economic themes with affected individuals, caregivers, and community members and analysed the data thematically using a pre-defined framework. We found remarkable commonalities across countries and diseases. We developed a conceptual framework which illustrates skin NTDs' negative economic impact, including financial costs of care-seeking and reductions in work and schooling; categorises coping strategies by their degree of risk-pooling; and clarifies the mechanisms through which skin NTDs disproportionately affect the poorest. Despite health insurance schemes in both countries, wide-ranging, often harmful coping strategies were reported. Traditional healers were often described as more accessible, affordable and offering more flexible payment terms than formal health services, except for Ethiopia's well-established leprosy programme. Our findings are important in informing strategies to mitigate the skin NTD burden and identifying key drivers of household costs to measure in future evaluations. To reduce skin NTDs' impact on households' physical, mental, and economic wellbeing, intervention strategies should address economic constraints to prompt and effective care-seeking. While financial support and incentives for referrals and promotion of insurance enrolment may mitigate some constraints, structural interventions that decentralise care may offer more equitable and sustainable access to skin NTD care.

A positive yet complicated case of gender-based violence coordination: a qualitative study of Lebanon's protracted humanitarian emergency, 2012-22.

Gender-based violence (GBV), a global health and human rights concern, often intensifies during emergencies. This paper explores the evolution of GBV coordination in Lebanon's protracted Syrian refugee crisis from 2012-22. Utilising 38 in-depth interviews and a document review, the findings were analysed using the framework for effective GBV coordination. Lebanon provides a positive yet complicated example of GBV coordination. Initially established to address the refugee crisis, it matured into a collaborative national coordination mechanism, fostering trust and advancing localisation amidst sectarian complexities. However, the volatile, restrictive policy context hindered government co-leadership and engagement with refugee-led organisations. While essential GBV response services were expanded nationwide, lack of an interagency strategy on GBV risk mitigation and prevention compromised lasting change. The paper emphasises the importance of dedicated GBV coordinators, multi-year funding, and increased attention to GBV prevention. The findings underscore the transformative potential of humanitarian responses and advocate for enhanced engagement with national stakeholders to promote sustainability in protracted crises.

Improving experiences of neglected tropical diseases of the skin: Mixed methods formative research for development of a complex intervention in Atwima Mponua District, Ghana.

Integrated approaches to managing co-endemic neglected tropical diseases (NTDs) of the skin within primary healthcare services are complex and require tailoring to local contexts. We describe formative research in Atwima Mponua District in Ghana's Ashanti Region designed to inform the development of a sustainable intervention to improve access to skin NTD care. We employed a convergent, parallel, mixed-methods design, collecting data from February 2021 to February 2022. We quantitatively assessed service readiness using a standardised checklist and reviewed outpatient department registers and condition-specific case records in all government health facilities in the district. Alongside a review of policy documents, we conducted 49 interviews and 7 focus group discussions with purposively selected affected persons, caregivers, community members, health workers, and policy-makers to understand skin NTD care-seeking practices and the policy landscape. Outside the district hospital, skin NTD reporting rates in the surveyed facilities were low; supply chains for skin NTD diagnostics, consumables, and medicines had gaps; and health worker knowledge of skin NTDs was limited. Affected people described fragmented care, provided mostly by hospitals (often outside the district) or traditional healers, resulting in challenges obtaining timely diagnosis and treatment and high care-seeking costs. Affected people experienced stigma, although the extent to which stigma influenced care-seeking behaviour was unclear. National actors were more optimistic than district-level actors about local resource availability for skin NTD care and were sceptical of including traditional healers in interventions. Our findings indicate that improvement of the care cascade for affected individuals to reduce the clinical, economic, and psychosocial impact of skin NTDs is likely to require a complementary set of interventions. These findings have informed the design of a strategy to support high-quality, integrated, decentralised care for skin NTDs in Atwima Mponua, which will be assessed through a multidisciplinary evaluation.

Veteran Experiences With an mHealth App to Support Measurement-Based Mental Health Care: Results From a Mixed Methods Evaluation.

BACKGROUND: Mental health conditions are highly prevalent among US veterans. The Veterans Health Administration (VHA) is committed to enhancing mental health care through the integration of measurement-based care (MBC) practices, guided by its Collect-Share-Act model. Incorporating the use of remote mobile apps may further support the implementation of MBC for mental health care. OBJECTIVE: This study aims to evaluate veteran experiences with Mental Health Checkup (MHC), a VHA mobile app to support remote MBC for mental health. METHODS: Our mixed methods sequential explanatory evaluation encompassed mailed surveys with veterans who used MHC and follow-up semistructured interviews with a subset of survey respondents. We analyzed survey data using descriptive statistics. We then compared responses between veterans who indicated having used MHC for ≥3 versus <3 months using χ2 tests. We analyzed interview data using thematic analysis. RESULTS: We received 533 surveys (533/2631, for a 20% response rate) and completed 20 interviews. Findings from these data supported one another and highlighted 4 key themes. (1) The MHC app had positive impacts on care processes for veterans: a majority of MHC users overall, and a greater proportion who had used MHC for ≥3 months (versus <3 months), agreed or strongly agreed that using MHC helped them be more engaged in their health and health care (169/262, 65%), make decisions about their treatment (157/262, 60%), and set goals related to their health and health care (156/262, 60%). Similarly, interviewees described that visualizing progress through graphs of their assessment data over time motivated them to continue therapy and increased self-awareness. (2) A majority of respondents overall, and a greater proportion who had used MHC for ≥3 months (versus <3 months), agreed/strongly agreed that using MHC enhanced their communication (112/164, 68% versus 51/98, 52%; P=.009) and rapport (95/164, 58% versus 42/98, 43%; P=.02) with their VHA providers. Likewise, interviewees described how MHC helped focus therapy time and facilitated trust. (3) However, veterans also endorsed some challenges using MHC. Among respondents overall, these included difficulty understanding graphs of their assessment data (102/245, 42%), not receiving enough training on the app (73/259, 28%), and not being able to change responses to assessment questions (72/256, 28%). (4) Interviewees offered suggestions for improving the app (eg, facilitating ease of log-in, offering additional reminder features) and for increasing adoption (eg, marketing the app and its potential advantages for veterans receiving mental health care). CONCLUSIONS: Although experiences with the MHC app varied, veterans were positive overall about its use. Veterans described associations between the use of MHC and engagement in their own care, self-management, and interactions with their VHA mental health providers. Findings support the potential of MHC as a technology capable of supporting the VHA's Collect-Share-Act model of MBC.

Stigma experiences, effects and coping among individuals affected by Buruli ulcer and yaws in Ghana.

BACKGROUND: Stigma related to skin neglected tropical diseases like Buruli ulcer (BU) and yaws has remained underexplored and existing studies are limited to individual diseases despite the WHO call for integration in disease management. Within two districts in central Ghana, we explored stigma associated with BU and yaws to understand overlaps and disease-specific nuances to help guide integrated interventions. METHODOLOGY/PRINCIPAL FINDINGS: In-depth interviews were conducted with 31 current or formerly affected individuals to assess the experiences, effects and coping strategies adopted to manage disease related stigma. Data were analysed along broad themes based on the sociological construct of macro and micro interaction and Goffman's treatise on stigma. Disapproving community labels fueled by misconceptions were noted among BU participants which contributed to macro stigma experiences, including exclusion, discrimination and avoidance. In contrast, a high level of social acceptance was reported among yaws participants although some micro-level stigma (anticipated, felt and self-stigma) were noted by individuals with both diseases. While younger participants experienced name-calling and use of derogatory words to address affected body parts, older participants and caregivers discussed the pain of public staring. Stigma experiences had negative consequences on psychosocial well-being, schooling, and social relations, particularly for BU affected people. Problem-focused strategies including confrontation, selective disclosure and concealment as well as emotion-focused strategies (religious coping and self-isolation) were noted. CONCLUSIONS AND SIGNIFICANCE: The types and levels of stigma varied for BU and yaws. Stigma experiences also differed for adults and children in this setting and these differences should be accounted for in integrated interventions for these skin NTDs. School health programs need to prioritize educating school teachers about skin NTDs and the negative impact of stigma on the wellbeing of children.

Health-seeking behaviour and beliefs around sore throat in The Gambia: A qualitative study.

Group A Streptococcus (Strep A) bacteria causes a broad spectrum of diseases. The most common manifestations of Strep A infection are sore throat and pus-producing skin infections such as impetigo. Complications of Strep A infection can lead to inflammation in the bones, muscles, joints, and internal organs causing acute rheumatic fever and rheumatic heart disease (RHD). In The Gambia, the RHD burden is thought to be very high. However, epidemiological data is minimal, and Strep A control programmes do not exist. This study aimed to explore common beliefs and practices related to sore throats among primary caregivers of children, and healthcare providers in a community with a high Strep A disease burden. Four informal conversations with providers and fifteen semi-structured interviews with caregivers were conducted in the peri-urban area of Sukuta, The Gambia. Sampling was purposive and gradual, beginning from households identified to have recently experienced sore throat through a parallel cohort study. Themes explored in qualitative analysis included: sore throat causal attributions and diagnoses, care practises, health-seeking behaviour, and perceived barriers to using the biomedical sector. We found that sore throats were typically perceived to affect one child in a family, disproportionately or exclusively. Sore throats were rarely perceived as life-threatening, and awareness of links between sore throat and ARF or RHD was not reported among caregivers or providers in this study population. Most cases of sore throat were initially managed at home using traditional medicine which delayed resort to antibiotics, though in two instances of severe pain with the presence of exudate, fear that the child's life was at risk prompted care-seeking through the formal health system. Our findings can inform the development of tailored strategies to increase community knowledge of the potential long-term consequences of sore throats and appropriate care-seeking, alongside improvements in the health system, to prevent Strep A sequelae effectively.

From humanitarian crisis to employment crisis: The lives and livelihoods of South Sudanese refugee health workers in Uganda.

Despite the many benefits of refugee health workers for health systems, they commonly face challenges integrating into host country workforces. The Global Code of Practice on International Recruitment of Health Personnel, which should monitor and protect migrant health workers, offers little guidance for refugees and research is needed to inform strategy. Based on interviews with 34 refugee health workers and 10 leaders across two settlements supporting populations fleeing the humanitarian crisis in South Sudan since 2013, we describe the governance and social dynamics affecting South Sudanese refugee health worker employment in Uganda. Refugees in Uganda legally have the right to work but face an employment crisis. Refugee health workers report that systemic discrimination, competition from underemployed domestic workers, unclear work permit rules and expensive credentialling processes exclude them from meaningful work in public health facilities and good jobs in the humanitarian response. This pushes them into unchallenging roles in private clinics, poorly remunerated positions on village health teams or out of the health sector altogether. Health system strengthening initiatives in Uganda to integrate humanitarian and government services and to deter the domestic workforce from emigration have overlooked the potential contributions of refugee health workers and the employment crisis they face. More effort is needed to increase fairness in public sector recruitment practices for refugee health workers, support credentialling, training opportunities for professional and non-professional cadres, job placements, and to draw attention to the public benefits of refugee health worker employment alongside higher spending on human resources for health.

Development of an integrated and decentralised skin health strategy to improve experiences of skin neglected tropical diseases and other skin conditions in Atwima Mponua District, Ghana.

Integrated strategies are recommended to tackle neglected tropical diseases of the skin (skin NTDs), which pose a substantial health and economic burden in many countries, including Ghana. We describe the development of an integrated and decentralised skin health strategy designed to improve experiences of skin NTDs in Atwima Mponua district in Ashanti Region. A multidisciplinary research team led an iterative process to develop an overall strategy and specific interventions, based on a theory of change informed by formative research conducted in Atwima Mponua district. The process involved preparatory work, four co-development workshops (August 2021 to November 2022), collaborative working groups to operationalise intervention components, and obtaining ethical approval. Stakeholders including affected individuals, caregivers, other community members and actors from different levels of the health system participated in co-development activities. We consulted these stakeholders at each stage of the research process, including discussion of study findings, development of our theory of change, identifying implementable solutions to identified challenges, and protocol development. Participants determined that the intervention should broadly address wounds and other skin conditions, rather than only skin NTDs, and should avoid reliance on non-governmental organisations and research teams to ensure sustainable implementation by district health teams and transferability elsewhere. The overall strategy was designed to focus on a decentralised model of care for skin conditions, while including other interventions to support a self-care delivery pathway, community engagement, and referral. Our theory of change describes the pathways through which these interventions are expected to achieve the strategy's aim, the assumptions, and problems addressed. This complex intervention strategy has been designed to respond to the local context, while maximising transferability to ensure wider relevance. Implementation is expected to begin in 2023.

Safety considerations for dietary supplement manufacturers in the United States.

Due to significant dietary supplement use in the US, product manufacturers must understand the importance of implementing a robust approach to establishing safety for all ingredients, including dietary ingredients, components, and finished dietary supplement products. Different regulatory pathways exist by which the safety of dietary ingredients can be established, and thus allowed to be marketed in a dietary supplement. For individual dietary ingredients, safety information may come from a variety of sources including history of safe use, presence of the ingredient in foods, and/or non-clinical and clinical data. On occasion safety data gaps are identified for a specific ingredient, particularly those of botanical origin. Modern toxicological methods and models can prove helpful in satisfying data gaps and are presented in this review. For finished dietary supplement products, issues potentially impacting safety to consider include claims, product labeling, overages, contaminants, residual solvents, heavy metals, packaging, and product stability. In addition, a safety assessment does not end once a product is marketed. It is important that manufacturers actively monitor and record the occurrence of adverse events reported in association with the use of their products, in accordance with the law. Herein, we provide a comprehensive overview of considerations for assessing dietary supplement safety.

Chronic Toxoplasma gondii infection is associated with decreased working memory performance in women / Infecção crônica por Toxoplasma gondii está associada à diminuição de desempenho da memória de trabalho em mulheres

Objective The present study sought to investigate changes in mood, inhibitory control, and working memory associated with T. gondii infection in a sample of Brazilian women. Method Twenty-eight female participants were equally distributed into two groups, according to the serology for chronic infection by T. gondii. The participants answered a Sociodemographic questionnaire, the CES-D, and performed Simon and N-Back tasks. Results Infected participants presented less accuracy and longer response time in N-Back tasks. No significant differences were found in the Simon task performance or in the depression levels. Conclusion Our findings suggest that chronic infection by T. gondii may result in impaired working memory and point out the importance of public policies aiming at preventing this infection.

Objetivo O presente estudo investigou alterações de humor, controle inibitório e memória de trabalho associadas à infecção por T. gondii em uma amostra de mulheres brasileiras. Método Vinte e oito participantes foram distribuídas igualmente em dois grupos de acordo com a sorologia para infecção crônica por T. gondii. As participantes responderam a um questionário sociodemográfico, à CES-D e realizaram as tarefas Simon e N-Back. Resultados As participantes infectadas apresentaram menor acurácia e maior tempo de resposta na tarefa N-Back. Nenhuma diferença significativa foi encontrada na tarefa Simon ou na escala de depressão. Conclusão Nossos achados sugerem que a infecção crônica por T. gondii pode resultar em comprometimento da memória de trabalho, e apontam para a importância de políticas públicas de prevenção dessa infecção.

Neuroproteomic Analysis after SARS-CoV-2 Infection Reveals Overrepresented Neurodegeneration Pathways and Disrupted Metabolic Pathways.

Besides respiratory illness, SARS-CoV-2, the causative agent of COVID-19, leads to neurological symptoms. The molecular mechanisms leading to neuropathology after SARS-CoV-2 infection are sparsely explored. SARS-CoV-2 enters human cells via different receptors, including ACE-2, TMPRSS2, and TMEM106B. In this study, we used a human-induced pluripotent stem cell-derived neuronal model, which expresses ACE-2, TMPRSS2, TMEM106B, and other possible SARS-CoV-2 receptors, to evaluate its susceptibility to SARS-CoV-2 infection. The neurons were exposed to SARS-CoV-2, followed by RT-qPCR, immunocytochemistry, and proteomic analyses of the infected neurons. Our findings showed that SARS-CoV-2 infects neurons at a lower rate than other human cells; however, the virus could not replicate or produce infectious virions in this neuronal model. Despite the aborted SARS-CoV-2 replication, the infected neuronal nuclei showed irregular morphology compared to other human cells. Since cytokine storm is a significant effect of SARS-CoV-2 infection in COVID-19 patients, in addition to the direct neuronal infection, the neurons were treated with pre-conditioned media from SARS-CoV-2-infected lung cells, and the neuroproteomic changes were investigated. The limited SARS-CoV-2 infection in the neurons and the neurons treated with the pre-conditioned media showed changes in the neuroproteomic profile, particularly affecting mitochondrial proteins and apoptotic and metabolic pathways, which may lead to the development of neurological complications. The findings from our study uncover a possible mechanism behind SARS-CoV-2-mediated neuropathology that might contribute to the lingering effects of the virus on the human brain.

Rural Veterans' Experiences with Social Risk Factors: Impacts, Challenges, and Care System Recommendations.

BACKGROUND: Social risk factors, such as food insecurity and financial needs, are associated with increased risk of cardiovascular diseases, health conditions that are highly prevalent in rural populations. A better understanding of rural Veterans' experiences with social risk factors can inform expansion of Veterans Health Administration (VHA) efforts to address social needs. OBJECTIVE: To examine social risk and need from rural Veterans' lived experiences and develop recommendations for VHA to address social needs. DESIGN: We conducted semi-structured interviews with participants purposively sampled for racial diversity. The interview guide was informed by Andersen's Behavioral Model of Health Services Use and the Outcomes from Addressing Social Determinants of Health in Systems framework. PARTICIPANTS: Rural Veterans with or at risk of cardiovascular disease who participated in a parent survey and agreed to be recontacted. APPROACH: Interviews were recorded and transcribed. We analyzed transcripts using directed qualitative content analysis to identify themes. KEY RESULTS: Interviews (n = 29) took place from March to June 2022. We identified four themes: (1) Social needs can impact access to healthcare, (2) Structural factors can make it difficult to get help for social needs, (3) Some Veterans are reluctant to seek help, and (4) Veterans recommended enhancing resource dissemination and navigation support. CONCLUSIONS: VHA interventions should include active dissemination of information on social needs resources and navigation support to help Veterans access resources. Community-based organizations (e.g., Veteran Service Organizations) could be key partners in the design and implementation of future social need interventions.

Gender based violence (GBV) coordination in a complex, multi-crisis context: a qualitative case study of Lebanon's compounded crises (2019-2023).

BACKGROUND: Since 2019 Lebanon has faced multiple compounded crises. Political and social instability, the COVID-19 pandemic, and the Beirut Port explosion, alongside the influx of refugees related to the ongoing Syrian conflict, have resulted in a nationwide economic emergency. In the context of the humanitarian response to the Syrian conflict, the UN and government-led gender-based violence (GBV) task force has coordinated the sub-sector since 2012. The compounded crisis, however, created new challenges for GBV coordination and service delivery, which we explore in this paper. We highlight lessons for strengthening GBV coordination in Lebanon and other complex emergencies. METHODS: We conducted 29 remote in-depth interviews, reviewed key policy documents and observed seven GBV task force meetings. We analysed and presented our findings across three key themes: context-relevant and adaptable coordination mechanisms; coordination to support GBV service delivery; and stakeholders' roles, legitimacy and power. RESULTS: Parallel response frameworks developed to address the multiple crises, created a complex humanitarian architecture within an increasingly challenging operating context, with some perceived inefficiencies. Positively, coordination was integrated under the established government-UN interagency system and the GBV task force maintained GBV sub-sector coordination. The task force was commended for effectively adapting to the evolving context, including working remotely, maintaining essential GBV services, assessing the compounded crises' impact on programming and adjusting accordingly, and harmonising guidance, tools and approaches. The importance of ensuring a government co-led response was highlighted by both UN and government informants, who pointed to examples where marginalising government leadership compromised coordination effectiveness and sustainability. The participation of local actors had become increasingly important but more difficult, with the impact of the various crises, and remote modalities, challenging service delivery and staff wellbeing. CONCLUSION: Experiences from Lebanon highlight the essential role of government leadership in coordination; the value of investing in local GBV capacity; the significance of effective national, subnational and intersectoral coordination to support service delivery and address cross-cutting GBV issues; the importance of targeted interventions to support marginalised populations; and the need to prioritize the well-being of front-line staff during crisis response. In Lebanon, and other complex crises, donors are encouraged to increase flexible, multiyear funding for GBV coordination and services, while women-led organizations should be at the forefront of recovery efforts, contributing to a more equitable society.

Addressing clinician moral distress: Implications from a mixed methods evaluation during Covid-19.

Clinician moral distress has been documented over the past several decades as occurring within numerous healthcare disciplines, often in relation to clinicians' involvement in patients' end-of-life decision-making. The resulting harms impact clinician well-being, patient well-being, and healthcare system functioning. Given Covid-19's catastrophic death toll and associated demands on end-of-life decision-making processes, the pandemic represents a particularly important context within which to understand clinician moral distress. Thus, we conducted a convergent mixed methods study to examine its prevalence, associations with clinicians' demographic and professional characteristics, and contributing circumstances among Veterans Health Administration (VA) clinicians. The study, conducted in April 2021, consisted of a cross-sectional on-line survey of VA clinicians at 20 VA Medical Centers with professional jurisdiction to place life-sustaining treatment orders working who were from a number of select specialties. The survey collected quantitative data on respondents' demographics, clinical practice characteristics, attitudes and behaviors related to goals of care conversations, intensity of moral distress during "peak-Covid," and qualitative data via an open-ended item asking for respondents to describe contributing circumstances if they had indicated any moral distress. To understand factors associated with heightened moral distress, we analyzed quantitative data using bivariate and multivariable regression analyses and qualitative data using a hybrid deductive/inductive thematic approach. Mixed methods analysis followed, whereby we compared the quantitative and qualitative datasets and integrated findings at the analytic level. Out of 3,396 eligible VA clinicians, 323 responded to the survey (9.5% adjusted response rate). Most respondents (81%) reported at least some moral distress during peak-Covid. In a multivariable logistic regression, female gender (OR 3.35; 95% CI 1.53-7.37) was associated with greater odds of moral distress, and practicing in geriatrics/palliative care (OR 0.40; 95% CI 0.18-0.87) and internal medicine/family medicine/primary care (OR 0.46; 95% CI 0.22-0.98) were associated with reduced odds of moral distress compared to medical subspecialties. From the 191 respondents who completed the open-ended item, five qualitative themes emerged as moral distress contributors: 1) patient visitation restrictions, 2) anticipatory actions, 3) clinical uncertainty related to Covid, 4) resource shortages, and 5) personal risk of contracting Covid. Mixed methods analysis found that quantitative results were consistent with these last two qualitative themes. In sum, clinician moral distress was prevalent early in the pandemic. This moral distress was associated with individual-, system-, and situation-level contributors. These identified contributors represent leverage points for future intervention to mitigate clinician moral distress and its negative outcomes during future healthcare crises and even during everyday clinical care.

Production of Mare Chorionic Girdle Organoids That Secrete Equine Chorionic Gonadotropin.

The equine chorionic girdle is comprised of specialized invasive trophoblast cells that begin formation approximately 25 days after ovulation (day 0) and invade the endometrium to become endometrial cups. These specialized trophoblast cells transition from uninucleate to differentiated binucleate trophoblast cells that secrete the glycoprotein hormone equine chorionic gonadotropin (eCG; formerly known as pregnant mare serum gonadotropin or PMSG). This eCG has LH-like activity in the horse but variable LH- and FSH-like activity in other species and has been utilized for these properties both in vivo and in vitro. To produce eCG commercially, large volumes of whole blood must be collected from pregnant mares, which negatively impacts equine welfare due to repeated blood collections and the birth of an unwanted foal. Attempts to produce eCG in vitro using long-term culture of chorionic girdle explants have not been successful beyond 180 days, with peak eCG production at 30 days of culture. Organoids are three-dimensional cell clusters that self-organize and can remain genetically and phenotypically stable throughout long-term culture (i.e., months). Human trophoblast organoids have been reported to successfully produce human chorionic gonadotropin (hCG) and proliferate long-term (>1 year). The objective of this study was to evaluate whether organoids derived from equine chorionic girdle maintain physiological functionality. Here we show generation of chorionic girdle organoids for the first time and demonstrate in vitro production of eCG for up to 6 weeks in culture. Therefore, equine chorionic girdle organoids provide a physiologically representative 3D in vitro model for chorionic girdle development of early equine pregnancy.

Characterization of Depressive Symptoms in Dementia and Examination of Possible Risk Factors.

Background: Depression in individuals with Alzheimer's disease (AD) is common, distressing, difficult to treat, and inadequately understood. It occurs more frequently in AD than in older adults without dementia. The reasons why some patients develop depression during AD and others do not remain obscure. Objective: We aimed to characterize depression in AD and to identify risk factors. Methods: We used data from three large dementia focused cohorts: ADNI (n = 665 with AD, 669 normal cognition), NACC (n = 698 with AD, 711 normal cognition), and BDR (n = 757 with AD). Depression ratings were available using the GDS and NPI and in addition for BDR the Cornell. A cut-off of≥8 was used for the GDS and the Cornell Scale for Depression in Dementia,≥6 for the NPI depression sub-scale, and≥2 for the NPI-Q depression sub-scale. We used logistic regression to examine potential risk factors and random effects meta-analysis and an interaction term to look for interactions between each risk factor and the presence of cognitive impairment. Results: In individual studies there was no evidence of a difference in risk factors for depressive symptoms in AD. In the meta-analysis the only risk factor which increased the risk of depressive symptoms in AD was previous depression, but information on this was only available from one study (OR 7.78 95% CI 4.03-15.03). Conclusion: Risk factors for depression in AD appear to differ to those for depression per se supporting suggestions of a different pathological process, although a past history of depression was the strongest individual risk factor.

Impact of the COVID-19 Pandemic on Providing Recommendations During Goals-of-Care Conversations: A Multisite Survey.

Background: Goals-of-care conversations (GoCCs) are essential for individualized end-of-life care. Shared decision-making (SDM) that elicits patients' goals and values to collaboratively make life sustaining treatment (LST) decisions is best practice. However, it is unknown how the COVID-19 pandemic onset and associated changes to care delivery, stress on providers, and clinical uncertainty affected SDM and recommendation-making during GoCCs. Aim: To assess providers' attitudes and behaviors related to GoCCs during the COVID-19 pandemic and identify factors associated with provision of LST recommendations. Design: Survey of United States Veterans Health Administration (VA) health care providers. Setting/Participants: Health care providers from 20 VA facilities with high COVID-19 caseloads early in the pandemic who had authority to place LST orders and practiced in select specialties (n = 3398). Results: We had 323 respondents (9.5% adjusted response rate). Most were age ≥50 years (51%), female (63%), non-Hispanic white (64%), and had ≥1 GoCC per week during peak-COVID-19 (78%). Compared with pre-COVID-19, providers believed it was less appropriate and felt less comfortable giving an LST recommendation during peak-COVID-19 (p < 0.001). One-third (32%) reported either "never" or "rarely" giving an LST recommendation during GoCCs at peak-COVID-19. In adjusted regression models, being a physician and discussing patients' goals and values were positively associated with giving an LST recommendation (B = 0.380, p = 0.031 and B = 0.400, p < 0.001, respectively) at peak-COVID-19. Conclusion: Providers who discuss patients' preferences and values are more likely to report giving a recommendation; both behaviors are markers of SDM during GoCCs. Our findings suggest potential areas for training in conducting patient-centered GoCCs.

Critical appraisal in rapid systematic reviews of COVID-19 studies: implementation of the Quality Criteria Checklist (QCC).

In this letter, we briefly describe how we selected and implemented the quality criteria checklist (QCC) as a critical appraisal tool in rapid systematic reviews conducted to inform public health advice, guidance and policy during the COVID-19 pandemic. As these rapid reviews usually included a range of study designs, it was key to identify a single tool that would allow for reliable critical appraisal across most experimental and observational study designs and applicable to a range of topics. After carefully considering a number of existing tools, the QCC was selected as it had good interrater agreement between three reviewers (Fleiss kappa coefficient 0.639) and was found to be easy and fast to apply once familiar with the tool. The QCC consists of 10 questions, with sub-questions to specify how it should be applied to a specific study design. Four of these questions are considered as critical (on selection bias, group comparability, intervention/exposure assessment and outcome assessment) and the rating of a study (high, moderate or low methodological quality) depends on the responses to these four critical questions. Our results suggest that the QCC is an appropriate critical appraisal tool to assess experimental and observational studies within COVID-19 rapid reviews. This study was done at pace during the COVID-19 pandemic; further reliability analyses should be conducted, and more research is needed to validate the QCC across a range of public health topics.