Research with Refugee Populations in North America: Applying the NIH Guiding Principles for Ethical Research.

This article examines the ethics of research design and the initiation of a study (e.g., recruitment of participants) involving refugee participants. We aim to equip investigators and members of IRBs with a set of ethical considerations and pragmatic recommendations to address challenges in refugee-focused research as it is developed and prepared for IRB review. We discuss challenges including how refugees are being defined and identified; their vulnerabilities before, during, and following resettlement that impacts their research participation; recruitment; consent practices including assent and unaccompanied minors; and conflicts of interest. Ethical guidance and regulatory oversight provided by international bodies, federal governments, and IRBs are important for enforcing the protection of participants. We describe the need for additional ethical guidance and awareness, if not special protections for refugee populations as guided by the National Institutes of Health (NIH) Guiding Principles for Ethical Research.

Cell type-specific modulation of metabolic, immune-regulatory, and anti-microbial pathways by CD101.

T lymphocytes and myeloid cells express the immunoglobulin-like glycoprotein cluster of differentiation (CD)101, notably in the gut. Here, we investigated the cell-specific functions of CD101 during dextran sulfate sodium (DSS)-induced colitis and Salmonella enterica Typhimurium infection. Similar to conventional CD101-/- mice, animals with a regulatory T cell-specific Cd101 deletion developed more severe intestinal pathology than littermate controls in both models. While the accumulation of T helper 1 cytokines in a CD101-deficient environment entertained DSS-induced colitis, it impeded the replication of Salmonella as revealed by studying CD101-/- x interferon-g-/- mice. Moreover, CD101-expressing neutrophils were capable to restrain Salmonella infection in vitro and in vivo. Both cell-intrinsic and -extrinsic mechanisms of CD101 contributed to the control of bacterial growth and spreading. The CD101-dependent containment of Salmonella infection required the expression of Irg-1 and Nox2 and the production of itaconate and reactive oxygen species. The level of intestinal microbial antigens in the sera of inflammatory bowel disease patients correlated inversely with the expression of CD101 on myeloid cells, which is in line with the suppression of CD101 seen in mice following DSS application or Salmonella infection. Thus, depending on the experimental or clinical setting, CD101 helps to limit inflammatory insults or bacterial infections due to cell type-specific modulation of metabolic, immune-regulatory, and anti-microbial pathways.

Medical Interpreting Services for Refugees in Canada: Current State of Practice and Considerations in Promoting this Essential Human Right for All.

Language barriers, specifically among refugees, pose significant challenges to delivering quality healthcare in Canada. While the COVID-19 pandemic accelerated the emergence and development of innovative alternatives such as telephone-based and video-conferencing medical interpreting services and AI tools, access remains uneven across Canada. This comprehensive analysis highlights the absence of a cohesive national strategy, reflected in diverse funding models employed across provinces and territories, with gaps and disparities in access to medical interpreting services. Advocating for medical interpreting, both as a moral imperative and a prudent investment, this article draws from human rights principles and ethical considerations, justified in national and international guidelines, charters, codes and regulations. Substantiated by a cost-benefit analysis, it emphasizes that medical interpreting enhances healthcare quality and preserves patient autonomy. Additionally, this article illuminates decision-making processes for utilizing interpreting services; recognizing the pivotal roles of clinicians, interpreters, patients and caregivers within the care circle; appreciating intersectional considerations such as gender, culture and age, underscoring the importance of a collaborative approach. Finally, it provides recommendations at provider, organizational and system levels to ensure equitable access to this right and to promote the health and well-being of refugees and other individuals facing language barriers within Canada's healthcare system.

L-arginine metabolism as pivotal interface of mutual host-microbe interactions in the gut.

L-arginine (L-arg) is a versatile amino acid and a central intestinal metabolite in mammalian and microbial organisms. Thus, L-arg participates as precursor of multiple metabolic pathways in the regulation of cell division and growth. It also serves as a source of carbon, nitrogen, and energy or as a substrate for protein synthesis. Consequently, L-arg can simultaneously modify mammalian immune functions, intraluminal metabolism, intestinal microbiota, and microbial pathogenesis. While dietary intake, protein turnover or de novo synthesis usually supply L-arg in sufficient amounts, the expression of several key enzymes of L-arg metabolism can change rapidly and dramatically following inflammation, sepsis, or injury. Consequently, the availability of L-arg can be restricted due to increased catabolism, transforming L-arg into an essential amino acid. Here, we review the enzymatic pathways of L-arg metabolism in microbial and mammalian cells and their role in immune function, intraluminal metabolism, colonization resistance, and microbial pathogenesis in the gut.

On Psychological Continuity and Dementia.

This letter responds to the article "On the Authority of Advance Euthanasia Directives for People with Severe Dementia: Reflections on a Dutch Case," by Henri Wijsbek and Thomas Nys, in the September-October 2022 issue of the Hastings Center Report.

Caring for refugees and newcomers in the post-COVID-19 era: Evidence review and guidance for FPs and health providers.

OBJECTIVE: To guide clinicians working in a range of primary care clinical settings on how to provide effective care and support for refugees and newcomers during and after the coronavirus disease 2019 (COVID-19) pandemic. SOURCES OF INFORMATION: The described approach integrates recommendations from evidence-based clinical guidelines on refugee health and COVID-19, practical lessons learned from Canadian Refugee Health Network clinicians working in a variety of primary care settings, and contributions from persons with lived experience of forced migration. MAIN MESSAGE: The COVID-19 pandemic has amplified health and social inequities for refugees, asylum seekers, undocumented migrants, transient migrant workers, and other newcomers. Refugees and newcomers face front-line exposure risks, difficulties accessing COVID-19 testing, exacerbation of mental health concerns, and challenges accessing health care, social, and settlement supports. Existing guidelines for clinical care of refugees are useful, but creative case-by-case strategies must be employed to overcome additional barriers in the context of COVID-19 and new care environments, such as the need for virtual interpretation and digital literacy skills. Clinicians can address inequities and advocate for improved services in collaboration with community partners. CONCLUSION: The COVID-19 pandemic is amplifying structural inequities. Refugees and newcomers require and deserve effective health care and support during this challenging time. This article outlines practical approaches and advocacy priorities for providing care in the COVID-19 context.

Soigner les réfugiés et les nouveaux arrivants à l'ère post-COVID-19: Revue des données probantes et conseils pour les MF et les professionnels de la santé.

OBJECTIF: Guider les cliniciens qui travaillent dans divers milieux cliniques de soins primaires quant aux façons de prodiguer des soins et du soutien efficaces aux réfugiés et aux nouveaux arrivants, durant et après la pandémie de la maladie à coronavirus 2019 (COVID-19). SOURCES D'INFORMATION: L'approche décrite intègre les recommandations tirées de guides de pratique clinique fondés sur des données probantes portant sur la santé des réfugiés et la COVID-19, de leçons concrètes apprises de cliniciens du Réseau canadien sur la santé des réfugiés (Canadian Refugee Health Network) qui travaillent dans divers milieux de soins primaires, ainsi que de contributions de personnes ayant vécu l'expérience d'une migration forcée. MESSAGE PRINCIPAL: La pandémie de la COVID-19 a amplifié les iniquités sociales et de santé pour les réfugiés, les demandeurs d'asile, les migrants sans papiers, les travailleurs transitoires de l'étranger et d'autres nouveaux arrivants. Les réfugiés et les nouveaux arrivants sont confrontés à des risques d'exposition en première ligne, à des problèmes d'accès aux tests de dépistage de la COVID-19, à l'exacerbation des préoccupations liées à la santé mentale, et aux difficultés d'accéder aux soins de santé et aux services sociaux et d'établissement. Les lignes directrices existantes sur les soins cliniques aux réfugiés sont utiles, mais des stratégies créatives au cas par cas doivent être utilisées pour surmonter les obstacles additionnels dans le contexte de la COVID-19 et des nouveaux environnements de soins, comme la nécessité d'une traduction simultanée virtuelle et d'habiletés en littératie numérique. Les cliniciens peuvent lutter contre les iniquités et plaider en faveur de meilleurs services en collaboration avec des partenaires communautaires. CONCLUSION: La pandémie de la COVID-19 amplifie les iniquités structurelles. Les réfugiés et les nouveaux arrivants nécessitent et méritent des soins de santé et du soutien efficaces durant ces moments éprouvants. Cet article présente des approches pratiques et les priorités en matière de défense des droits pour offrir des soins dans le contexte de la COVID-19.

Access to Refugee and Migrant Mental Health Care Services during the First Six Months of the COVID-19 Pandemic: A Canadian Refugee Clinician Survey.

The COVID-19 pandemic has had a major impact on the mental health of refugees and migrants. This study aimed to assess refugee clinician perspectives on mental health care during the COVID-19 pandemic, specifically access to and delivery of community mental health care services. We utilized a mixed methods design. We surveyed members of a national network of Canadian clinicians caring for refugees and migrants. Seventy-seven clinicians with experience caring for refugee populations, representing an 84% response rate, participated in the online survey, 11 of whom also participated in semi-structured interviews. We report three major themes: exacerbation of mental health issues and inequities in social determinants of health, and decreased access to integrated primary care and community migrant services. Clinicians reported major challenges delivering care during the first 6 months of the pandemic related to access to care and providing virtual care. Clinicians described perspectives on improving the management of refugee mental health, including increasing access to community resources and virtual care. The majority of clinicians reported that technology-assisted psychotherapy appears feasible to arrange, acceptable and may increase health equity for their refugee patients. However, major limitations of virtual care included technological barriers, communication and global mental health issues, and privacy concerns. In summary, the COVID-19 pandemic has exacerbated social and health inequities within refugee and migrant populations in Canada and challenged the way mental health care is traditionally delivered. However, the pandemic has provided new avenues for the delivery of care virtually, albeit not without additional and unique barriers.

Millennial storage of near-Moho magma.

The lower crust plays a critical role in the processing of mantle melts and the triggering of volcanic eruptions by supply of magma from greater depth. Our understanding of the deeper parts of magmatic systems is obscured by overprinting of deep signals by shallow processes. We provide a direct estimate of magma residence time in basaltic systems of the deep crust by studying ultramafic nodules from the Borgarhraun eruption in Iceland. Modeling of chromium-aluminum interdiffusion in spinel crystals provides a record of long-term magmatic storage on the order of 1000 years. This places firm constraints on the total crustal residence time of mantle-derived magmas and has important implications for modeling the growth and evolution of transcrustal magmatic systems.

Efficacy and Safety of MED2005, a Topical Glyceryl Trinitrate Formulation, in the Treatment of Erectile Dysfunction: A Randomized Crossover Study.

BACKGROUND: Current treatments for erectile dysfunction (ED) have some limitations. AIM: This study evaluated the efficacy and tolerability of MED2005, a 0.2% glyceryl trinitrate topical gel, formulated into an enhanced absorption topical delivery system (DermaSys), administered on demand, in the treatment of ED. METHODS: This randomized, double-blinded, placebo-controlled, phase II crossover trial involved 232 men with ED (231 treated, 230 assessed for efficacy) and their partners. After a 4-week run-in period, patients were randomized to 1 of 2 treatment sequences, MED2005-placebo or placebo-MED2005. Each treatment was given for 4 weeks, separated by a 1-week washout interval. Efficacy was assessed by the International Index of Erectile Function (IIEF), the Sexual Encounter Profile, a Global Assessment Questionnaire (GAQ), and specific questions about the onset and offset of action and treatment preferences (patients and partners). OUTCOMES: The primary outcome measure was the IIEF erectile function domain (IIEF-EF) score. Other efficacy assessments were secondary outcomes. RESULTS: The mean baseline IIEF-EF score was 17.1 (SD = 5.7), and this increased to 19.6 (SD = 7.5) after MED2005 treatment and 18.5 (SD = 6.7) after placebo (P = .0132). Overall, 23.1% of patients showed a clinically relevant (≥4-point) increase in IIEF-EF scores after treatment with MED2005 only compared with 14.5% who responded after MED2005 and placebo, 14.0% who responded after placebo only, and 48.4% who did not respond after either treatment (P = .0272). MED2005 also was associated with significant improvements compared with placebo in the other IIEF domains, and this was consistent with patients' and partners' responses to the GAQ. For all assessments, significant effects of MED2005 were seen primarily in patients with mild ED. The start of erection was noticed within 5 and 10 minutes in 44.2% and 69.5%, respectively, of all intercourse attempts with MED2005. Patients and partners showed significant preferences for MED2005 over placebo. The most commonly reported adverse events during MED2005 treatment were headache (patients, n = 18 [7.9%]; partners, n = 3 [1.3%]) and nasopharyngitis (patients, n = 13 [5.7%]; partners, n = 2 [0.9%]). CLINICAL IMPLICATIONS: These findings suggest that topical glyceryl trinitrate could be a useful treatment option in ED. STRENGTHS AND LIMITATIONS: Strengths of this study include the use of a validated outcome measure. Limitations include the use of only 1 dosage. CONCLUSION: Further studies are warranted to investigate the efficacy of topical glyceryl trinitrate to include higher doses, thereby improving clinical significance, especially in cases of moderate and severe ED. Ralph DJ, Eardley I, Taubel J, et al. Efficacy and Safety of MED2005, a Topical Glyceryl Trinitrate Formulation, in the Treatment of Erectile Dysfunction: A Randomized Crossover Study. J Sex Med 2018;15:167-175.

A cross-national analysis of how economic inequality predicts biodiversity loss.

We used socioeconomic models that included economic inequality to predict biodiversity loss, measured as the proportion of threatened plant and vertebrate species, across 50 countries. Our main goal was to evaluate whether economic inequality, measured as the Gini index of income distribution, improved the explanatory power of our statistical models. We compared four models that included the following: only population density, economic footprint (i.e., the size of the economy relative to the country area), economic footprint and income inequality (Gini index), and an index of environmental governance. We also tested the environmental Kuznets curve hypothesis, but it was not supported by the data. Statistical comparisons of the models revealed that the model including both economic footprint and inequality was the best predictor of threatened species. It significantly outperformed population density alone and the environmental governance model according to the Akaike information criterion. Inequality was a significant predictor of biodiversity loss and significantly improved the fit of our models. These results confirm that socioeconomic inequality is an important factor to consider when predicting rates of anthropogenic biodiversity loss.

An exceptional Devonian fish from Australia sheds light on tetrapod origins.

The transition from fishes to tetrapods was one of the most dramatic events in the evolution of vertebrates, but many pivotal fossils are incomplete, resulting in gaps in the data that are used for phylogenetic reconstruction. Here we present new observations from the most complete, acid-prepared Devonian tetrapodomorph fish yet discovered, Gogonasus, which was previously placed just crownward of Kenichthys and rhizodontids, the most primitive taxa on the tetrapod lineage. Unexpectedly, Gogonasus shows a mosaic of plesiomorphic and derived tetrapod-like features. Whereas the braincase and dermal cranial skeleton exhibit generalized morphologies with respect to Eusthenopteron or Panderichthys, taxa that are traditionally considered to be phyletically close to tetrapods, the presence of a deeply invaginated, wide spiracle, advanced internal spiracular architecture and near-horizontal hyomandibula are specialized features that are absent from Eusthenopteron. Furthermore, the pectoral fin skeleton of Gogonasus shares several features with that of Tiktaalik, the most tetrapod-like fish. A new phylogenetic analysis places Gogonasus crownward of Eusthenopteron as the sister taxon to the Elpistostegalia. Aspects of the basic tetrapod limb skeleton and middle ear architecture can now be traced further back within the tetrapodomorph radiation.