Implementation of a remote behavioral intervention for older adults with asthma - a pilot study.

OBJECTIVE: Older adults with asthma (OAA) have elevated asthma morbidity rates. A six-session intervention based on self-regulation theory was shown to improve outcomes. However, wide-spread implementation was difficult due to the in-person design. Our objective was to determine the feasibility and acceptability of an updated intervention for OAA that is completely remote, includes a physician component, and utilizes shared decision-making (SDM). METHODS: A pilot study of 12 OAA with uncontrolled asthma and their asthma providers was conducted at three health centers. The remote intervention (titled SOAR) consisted of 4 sessions (2 groups and 2 individual). Asthma providers (both specialists and primary care) were sent updates of progress along with information on how to incorporate SDM into the visit. Implementation (feasibility, acceptability, and appropriateness) and clinical (asthma control, asthma quality of life, perceived control, depression, and self-confidence) outcomes were measured. RESULTS: SOAR was found to be feasible, acceptable, and appropriate, with values on validated implementation scales similar to those of in-person behavioral interventions. Asthma providers found the program helpful and intended to change care based on the updates. Asthma control scores improved significantly from baseline (14.2 to 16.8, p = 0.04), as did asthma quality of life (4.2 to 4.9, p = 0.03) and self-confidence to manage asthma (7.1 to 8.5, p = 0.02). There was no change in depression nor perceived control scores. CONCLUSION: A remote behavioral intervention appeared feasible and acceptable for OAA and their health care providers, and can improve outcomes. Larger scale implementation trials are warranted.

Convalescent Plasma as Adjunctive Therapy for Hospitalized Patients with COVID-19: The Co-CLARITY Trial.

Background and Objective: Convalescent plasma therapy (CPT) may reduce the risk of disease progression among patients with COVID-19. This study was undertaken to evaluate the efficacy and safety of CPT in preventing ICU admission among hospitalized COVID-19 patients. Methods: In this open-label randomized controlled trial, we randomly assigned hospitalized adult patients with COVID-19 in a 1:1 ratio to receive convalescent plasma as an adjunct to standard of care or standard of care alone. The primary endpoint was ICU admission within first 28 days of enrolment. Primary safety endpoints include rapid deterioration of respiratory or clinical status within four hours of convalescent plasma transfusion and cumulative incidence of serious adverse events during the study period including transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO), severe allergic reactions, and transfusion-related infections. Results: A total of 22 patients were assigned to receive convalescent plasma as an adjunct to standard of care and 22 to receive standard of care alone. The median time from onset of COVID-19 symptoms to study enrolment was eight days (IQR, 4 to 10). Two patients (9.1%) in the CPT group and one patient (4.5%) in the control group were admitted to the ICU. The primary outcome measure, ICU admission, was not different between the two groups (q-value >0.9). No patient who received convalescent plasma had rapid deterioration of respiratory/clinical status within four hours of transfusion and none developed TRALI, TACO, anaphylaxis, severe allergic reactions, or transfusion-related infections. There was also no significant difference in the secondary outcomes of 28-day mortality (two patients in the CPT group and none in the control group, q-value >0.90), dialysis-free days, vasopressor-free days, and ICU-free days. Conclusions: Among hospitalized COVID-19 patients, no significant differences were observed in the need for ICU admission between patients given CPT as adjunct to standard of care and those who received standard of care alone. Interpretation is limited by early termination of the trial which may have been underpowered to detect a clinically important difference.

National and regional population attributable fractions for anemia risk factors (iron, folate, and vitamin B12) in Belize: potential impact of fortification.

Objective: To estimate the national and regional population attributable fraction (PAF) and potential number of preventable anemia cases for three nutritional risk factors (iron, red blood cell folate [RBCF], and vitamin B12 deficiencies) among women of childbearing age in Belize. Methods: A national probability-based household and micronutrient survey capturing sociodemographic and health information was conducted among 937 nonpregnant Belizean women aged 15-49 years. Blood samples were collected to determine hemoglobin, ferritin, alpha-1-glycoprotein (AGP), RBCF, and vitamin B12 status. All analyses used sample weights and design variables to reflect a complex sample survey. Logistic regression was used to determine adjusted prevalence risk (aPR) ratios, which were then used to estimate national and regional PAF for anemia. Results: The overall prevalence of anemia (hemoglobin <12 g/dL) was 21.2% (95% CI [18.7, 25.3]). The prevalence of anemia was significantly greater among women with iron deficiency (59.5%, 95% CI [48.7, 69.5]) compared to women without iron deficiency (15.2%, 95% CI [12.2, 18.3]; aPR 3.9, 95% CI [2.9, 5.1]). The three nutritional deficiencies examined contributed to 34.6% (95% CI [22.1, 47.1]) of the anemia cases. If all these nutritional deficiencies could be eliminated, then an estimated 5 953 (95% CI [3 807, 8 114]) anemia cases could be prevented. Conclusions: This study suggests that among women of child-bearing age in Belize, anemia cases might be reduced by a third if three modifiable nutritional risk factors (iron, RBCF, and vitamin B12 deficiencies) could be eliminated. Fortification is one potential strategy to improve nutritional status and reduce the burden of anemia in this population.

National and regional population attributable fractions for anemia risk factors (iron, folate, and vitamin B12) in Belize: potential impact of fortification / Fracciones atribuibles poblacionales nacionales y regionales de factores de riesgo de anemia (hierro, folato y vitamina B12) en Belice: posible impacto del enriquecimiento de los alimentos con suplementos / Frações atribuíveis populacionais nacionais e regionais de fatores de risco para anemia (ferro, ácido fólico e vitamina B12) em Belize: potencial impacto da fortificação

[ABSTRACT]. Objective. To estimate the national and regional population attributable fraction (PAF) and potential number of preventable anemia cases for three nutritional risk factors (iron, red blood cell folate [RBCF], and vitamin B12 deficiencies) among women of childbearing age in Belize. Methods. A national probability-based household and micronutrient survey capturing sociodemographic and health information was conducted among 937 nonpregnant Belizean women aged 15–49 years. Blood samples were collected to determine hemoglobin, ferritin, alpha-1-glycoprotein (AGP), RBCF, and vitamin B12 status. All analyses used sample weights and design variables to reflect a complex sample survey. Logistic regression was used to determine adjusted prevalence risk (aPR) ratios, which were then used to estimate national and regional PAF for anemia. Results. The overall prevalence of anemia (hemoglobin <12 g/dL) was 21.2% (95% CI [18.7, 25.3]). The prevalence of anemia was significantly greater among women with iron deficiency (59.5%, 95% CI [48.7, 69.5]) compared to women without iron deficiency (15.2%, 95% CI [12.2, 18.3]; aPR 3.9, 95% CI [2.9, 5.1]). The three nutritional deficiencies examined contributed to 34.6% (95% CI [22.1, 47.1]) of the anemia cases. If all these nutritional deficiencies could be eliminated, then an estimated 5 953 (95% CI [3 807, 8 114]) anemia cases could be prevented. Conclusions. This study suggests that among women of child-bearing age in Belize, anemia cases might be reduced by a third if three modifiable nutritional risk factors (iron, RBCF, and vitamin B12 deficiencies) could be eliminated. Fortification is one potential strategy to improve nutritional status and reduce the burden of anemia in this population.

[RESUMEN]. Objetivo. Calcular la fracción atribuible poblacional a nivel nacional y regional y el número de casos de anemia que podrían prevenirse para tres factores de riesgo nutricional (deficiencia de hierro, folato eritrocitario y vitamina B12) en las mujeres en edad reproductiva en Belice. Metodología. Se llevó a cabo una encuesta probabilística nacional sobre características de los hogares y micronutrientes en la que se recopiló información sociodemográfica y de salud de 937 mujeres beliceñas no embarazadas de entre 15 y 49 años. Se extrajeron muestras de sangre para determinar los niveles de hemoglobina, ferritina, alfa–1–glucoproteína, folato eritrocitario y vitamina B12. En todos los análisis se emplearon ponderaciones muestrales y variables calculadas para tener en cuenta que se trataba de una encuesta con una muestra compleja. Se estimaron mediante regresión logística las razones de riesgos de prevalencia ajustados, que posteriormente se utilizaron para calcular la fracción atribuible poblacional con respecto a la anemia a nivel nacional y regional. Resultados. La prevalencia global de la anemia (hemoglobina <12 g/dl) fue del 21,2% (IC del 95%: 18,7– 25,3). La prevalencia de la anemia fue significativamente mayor en las mujeres con ferropenia (59,5%, IC del 95%: 48,7–69,5) que en las que no tenían ferropenia (15,2%, IC del 95%: 12,2, 18,3); razón de riesgos de prevalencia ajustados = 3.9, IC del 95%; 2,9–5,1). Las tres deficiencias nutricionales examinadas explicaban al 34,6% (IC del 95%: 22,1–47,1) de los casos de anemia. Se estima que si pudieran eliminarse todas estas deficiencias nutricionales, se prevendrían unos 5953 (IC del 95%: 3807–8114) casos de anemia. Conclusiones. Los resultados de este estudio sugieren que los casos de anemia en las mujeres en edad reproductiva de Belice podrían reducirse en un tercio si se pudieran eliminar tres factores de riesgo nutricionales modificables (deficiencias de hierro, folato eritrocitario y vitamina B12). Una posible estrategia para mejorar el estado nutricional y reducir la carga de la anemia en este grupo poblacional es en el enriquecimiento de los alimentos con suplementos.

[RESUMO]. Objetivo. Estimar a fração atribuível populacional (FAP) nacional e regional e o potencial número de casos preveníveis de anemia para três fatores de risco nutricionais (deficiência de ferro, ácido fólico eritrocitário e vitamina B12) entre mulheres em idade fértil em Belize. Métodos. Realizou-se um inquérito probabilístico domiciliar nacional sobre micronutrientes, que coletou informações sociodemográficas e de saúde de 937 mulheres belizenhas não grávidas com idade entre 15 e 49 anos. Coletaram-se amostras de sangue para dosagem de hemoglobina, ferritina, alfa-1-glicoproteína (AGP), ácido fólico eritrocitário e vitamina B12. Todas as análises usaram variáveis de delineamento e ponderações amostrais para refletir um inquérito amostral complexo. Aplicou-se regressão logística para determinar razões ajustadas de risco de prevalência (RPa), que foram usadas para estimar a FAP nacional e regional para anemia. Resultados. A prevalência geral de anemia (hemoglobina <12 g/dL) foi de 21,2% (IC 95% [18,7–25,3]). A prevalência de anemia foi significativamente maior em mulheres com deficiência de ferro (59,5%, IC 95% [48,7–69,5]) que em mulheres sem deficiência de ferro (15,2%, IC 95% [12,2–18,3]); RPa 3,9, IC 95% [2,9– 5,1]). As três deficiências nutricionais analisadas contribuíram para 34,6% (IC 95% [22,1–47,1]) dos casos de anemia. Caso se eliminassem todas essas deficiências nutricionais, seria possível evitar cerca de 5.953 (IC 95% [3.807–8.114]) casos de anemia. Conclusões. Este estudo sugere que, nas mulheres belizenhas em idade fértil, os casos de anemia poderiam ser reduzidos em um terço caso fosse possível eliminar três fatores de risco nutricionais modificáveis (deficiência de ferro, ácido fólico eritrocitário e vitamina B12). A fortificação é uma possível estratégia para melhorar o estado nutricional e reduzir a carga de anemia nessa população.

Interdisciplinary assessment and treatment of paediatric drooling: two decades of experience by the Nijmegen saliva control team reflected in a stepwise algorithm.

Anterior and posterior drooling are prevalent comorbidities in children with neurodevelopmental disabilities. Considering the heterogeneity of the patient population and the multifactorial aetiology of drooling, an interdisciplinary and individualised treatment approach is indispensable. However, no tool for stepwise decision-making in the treatment of paediatric drooling has been developed previously. Within the Radboudumc Amalia Children's Hospital, care for children with anterior and/or posterior drooling secondary to neurodevelopmental disabilities is coordinated by a saliva control team with healthcare professionals from six disciplines. In alignment with international literature, published guidelines, and evidence gained from two decades of experience and research by our team, this paper proposes an algorithm reflecting the assessment and treatment approach applied in our clinic. First, directions are provided to decide on the necessity of saliva control treatment, taking type of drooling, the child's age, and the severity and impact of drooling into account. Second, the algorithm offers guidance on the choice between available treatment options, highlighting the importance of accounting for child characteristics and child and caregiver preferences in clinical (shared) decision-making. CONCLUSIONS: With this algorithm, we aim to emphasise the importance of repeated stepwise decision-making in the assessment and treatment of drooling in children during their childhood, encouraging healthcare professionals to apply a holistic approach. WHAT IS KNOWN: • Children with anterior or posterior drooling secondary to neurodevelopmental disabilities comprise a heterogeneous group, necessitating an individualised treatment approach. • No stepwise decision-making tool is available for the treatment of paediatric drooling. WHAT IS NEW: • Deciding on the necessity of saliva control treatment should be a conscious process, based on type of drooling, age, and drooling severity and impact. • Type of drooling, age, cognition, oral motor skills, self-awareness, posture, diagnosis, and child/caregiver preferences need to be considered to decide on the optimal treatment.

Bacterial sepsis triggers stronger transcriptomic immune responses in larger primates.

Empirical data relating body mass to immune defence against infections remain limited. Although the metabolic theory of ecology predicts that larger organisms would have weaker immune responses, recent studies have suggested that the opposite may be true. These discoveries have led to the safety factor hypothesis, which proposes that larger organisms have evolved stronger immune defences because they carry greater risks of exposure to pathogens and parasites. In this study, we simulated sepsis by exposing blood from nine primate species to a bacterial lipopolysaccharide (LPS), measured the relative expression of immune and other genes using RNAseq, and fitted phylogenetic models to determine how gene expression was related to body mass. In contrast to non-immune-annotated genes, we discovered hypermetric scaling in the LPS-induced expression of innate immune genes, such that large primates had a disproportionately greater increase in gene expression of immune genes compared to small primates. Hypermetric immune gene expression appears to support the safety factor hypothesis, though this pattern may represent a balanced evolutionary mechanism to compensate for lower per-transcript immunological effectiveness. This study contributes to the growing body of immune allometry research, highlighting its importance in understanding the complex interplay between body size and immunity over evolutionary timescales.

The when, why, and how of using glycopyrronium to diminish drooling in children with neurodevelopmental disabilities: Implications for clinical practice.

BACKGROUND: Despite the established efficacy of glycopyrronium bromide in reducing drooling among children with neurodevelopmental disabilities, evidence on its impact on the daily lives of children and parents and effectiveness in a real-world setting are scarce, especially among long-term users. This study explored timing and duration of glycopyrronium treatment, effect and impact on daily life, and occurrence of side effects to inform clinical practice. METHODS: This was a retrospective cohort study at a national referral centre for drooling, including 61 children with nonprogressive neurodevelopmental disabilities, treated with glycopyrronium for anterior and/or posterior drooling between 2011 and 2021. Data were obtained from medical records and supplemented by structured telephone interviews with parents. RESULTS: Anterior drooling severity decreased in 82% of the included children. Changes in the impact of drooling on burden of care, social interaction, and self-esteem were reported in 55%, 31%, and 36%, respectively. Side effects were noted for 71% of cases, yet only 36% of parents deemed these as outweighing the positive impact of treatment. A substantial majority (77%) of the included children were long-term users (≥6 months). Among these, 38% of parents reported decreasing effectiveness and 27% noticed more prominent side effects over time. CONCLUSIONS: Glycopyrronium demonstrated potential in mitigating the impact of drooling on daily life, although variations were observed in the specific aspects and extent of improvement. The real-world context of our study provides important insights for refining clinical practices, emphasizing the need for balanced consideration of treatment benefits and potential side effects to facilitate shared decision-making.

Exploring the relationship between school-supervised asthma therapy and social determinants of health in pediatric asthma care.

BACKGROUND: Social determinants of health (SDoH), including access to care, economic stability, neighborhood factors, and social context, strongly influence pediatric asthma outcomes. School-supervised asthma therapy (SST) is an evidence-based strategy that improves asthma outcomes, particularly for historically marginalized children, by providing support for daily medication adherence in school. However, little is known about the relationship between these programs and the adverse SDoH commonly affecting underrepresented minority and marginalized children with asthma. METHODS: We examined qualitative data from interviews (n = 52) conducted between 2017 and 2020 with diverse multi-level partners involved in Asthma Link, a SST intervention. Participants included end-users (children and their parents), deliverers (school nurses and pediatric providers), and systems-level partners (e.g., insurers, legislators, and state officials). We used inductive coding to determine themes and subthemes and deductive coding using the Healthy People 2030 SDoH framework. RESULTS: Three themes emerged: (1) SST mitigates adverse SDoH (improves access to preventive healthcare and asthma health literacy), (2) SST benefits children experiencing specific adverse SDoH (provides a consistent medication routine to children with unstable family/housing situations) and (3) specific adverse SDoH impede SST implementation (economic instability, culture and language barriers). CONCLUSION: This study suggests an important relationship between SDoH and SST that warrants further evaluation in our future work on this community-based asthma intervention. Moreover, our findings underscore the importance of measuring SDoH in the implementation and evaluation of pediatric asthma interventions, particularly given the strong influence of these social factors on child health outcomes.

Qualitative Study to Explore the Occupational and Reproductive Health Challenges among Women Tobacco Farm Laborers in Mysore District, India.

Tobacco farm laborers are primarily women and children working for very low wages. The aim of this study was to explore occupational and reproductive health challenges faced by women tobacco farm laborers in Mysore District, India. We conducted interviews and six focus group discussions among 41 women tobacco farm laborers. Codes and themes were generated based on deductive and inductive approaches using the socioecological model. Participants reported symptoms of green tobacco sickness including headaches, back pain, gastric problems, weakness, and allergies during menstruation, pre-natal, and post-natal periods. Participants had poor awareness about the health effects of tobacco farming, and there were gender inequalities in wages and the use of personal protective equipment. Participants received support from family and community health workers during their pregnancy and post-natal period. Women reported wanting maternity benefits from the tobacco board, as well as monetary support and nutritional supplements. There is a need for health education about the environmental dangers of tobacco among farm laborers, and more supportive policies for women farmworkers during pregnancy and post-natal periods.

Beyond bNAbs: Uses, Risks, and Opportunities for Therapeutic Application of Non-Neutralising Antibodies in Viral Infection.

The vast majority of antibodies generated against a virus will be non-neutralising. However, this does not denote an absence of protective capacity. Yet, within the field, there is typically a large focus on antibodies capable of directly blocking infection (neutralising antibodies, NAbs) of either specific viral strains or multiple viral strains (broadly-neutralising antibodies, bNAbs). More recently, a focus on non-neutralising antibodies (nNAbs), or neutralisation-independent effects of NAbs, has emerged. These can have additive effects on protection or, in some cases, be a major correlate of protection. As their name suggests, nNAbs do not directly neutralise infection but instead, through their Fc domains, may mediate interaction with other immune effectors to induce clearance of viral particles or virally infected cells. nNAbs may also interrupt viral replication within infected cells. Developing technologies of antibody modification and functionalisation may lead to innovative biologics that harness the activities of nNAbs for antiviral prophylaxis and therapeutics. In this review, we discuss specific examples of nNAb actions in viral infections where they have known importance. We also discuss the potential detrimental effects of such responses. Finally, we explore new technologies for nNAb functionalisation to increase efficacy or introduce favourable characteristics for their therapeutic applications.

Geographic variation in breast reconstruction surgery after mastectomy for females with breast cancer in Alberta, Canada.

BACKGROUND: Breast cancer is the most common cancer affecting females in Canada, and about half of females with breast cancer are treated with mastectomy. We sought to evaluate geographic variation in breast reconstruction surgery in Alberta, Canada. METHODS: Using linked population-based administrative databases, we extracted data on all Alberta females aged 18 years and older who were diagnosed with breast cancer and treated with mastectomy during 2004-2017. Analyses included regression modelling of odds of reconstruction at 1 year and a spatial scan to identify geographic clusters of lower numbers of reconstruction. RESULTS: A total of 16 198 females diagnosed with breast cancer were treated with a mastectomy, and 1932 (11.9%) had reconstruction within 1 year postmastectomy. Those with reconstruction were more likely to be younger (adjusted odds ratio [OR] 16.7, 95% confidence interval [CI] 13.7-20.3; aged 21-44 yr v. ≥ 65 yr) and were less likely to be from lower-income neighbourhoods. They were more likely to have at least 1 comorbidity and were more likely to have advanced stages of cancer and to require chemotherapy (adjusted OR 0.55, 95% CI 0.47-0.65) or radiotherapy after mastectomy (adjusted OR 0.59, 95% CI 0.39-0.87) than females without reconstruction. We identified rural northern and southeastern clusters with frequencies of reconstruction that were 69.6% and 41.6% of what was expected, respectively. CONCLUSION: We found an overall postmastectomy rate of breast reconstruction of 11.9%, and we identified geographic variation. Predictors of reconstruction in Alberta were similar to those previously described in the literature, specifically with patients in rural communities having lower rates of reconstruction than their urban counterparts. These results suggest that further interventions are required to identify the specific barriers to reconstruction within rural communities and to create strategies to ensure equitable access to all residents.

Occupational exposures among women beedi workers in Mysore District, India: A mixed-methods study protocol.

Beedi is the most common smoking form of tobacco used in India. The rolling of beedis is performed primarily by women in settings that lack occupational safeguards. The aims of this protocol are to establish methods for the study of occupational exposures among women beedi workers and their experiences and challenges working with unburnt tobacco. This protocol employs a convergent parallel mixed-methods approach. Qualitatively, we plan to explore the experiences and challenges faced by women beedi workers using photovoice, a community based participatory method. Occupational exposures to pesticides will be assessed through the use of silicone wristbands worn for seven days by workers, and exposure to toxic metals and metalloids will be assessed in dust samples collected in the homes of workers. The outcomes will be analyzed to form policy recommendations to improve the occupational health of women beedi workers.

Immune gene expression and epigenetic potential affect the consumption of risky food by female house sparrows.

When organisms move into new areas, they are likely to encounter novel food resources. Even if they are nutritious, these foods can also be risky, as they might be contaminated by parasites. The behavioural immune system of animals could help them avoid the negative effects of contaminated resources, but our understanding of behavioural immunity is limited, particularly whether and how behavioural immunity interacts with physiological immunity. Here, we asked about the potential for interplay between these two traits, specifically how the propensity of an individual house sparrow (Passer domesticus) to take foraging risks was related to its ability to regulate a key facet of its immune response to bacterial pathogens. Previously, we found that sparrows at expanding geographic range edges were more exploratory and less risk-averse to novel foods; in those same populations, birds tended to over-express Toll-like receptor 4 (TLR4), a pattern-recognition receptor that distinguishes cell-wall components of Gram-negative bacteria, making it the major sensor of potentially lethal gut microbial infections including salmonellosis. When we investigated how birds would respond to a typical diet (i.e., mixed seeds) spiked with domesticated chicken faeces, birds that expressed more TLR4 or had higher epigenetic potential for TLR4 (more CpG dinucleotides in the putative gene promoter) ate more food, spiked or not. Females expressing abundant TLR4 were also willing to take more foraging risks and ate more spiked food. In males, TLR4 expression was not associated with risk-taking. Altogether, our results indicate that behaviour and immunity covary among individual house sparrows, particularly in females where those birds that maintain more immune surveillance also are more disposed to take foraging risks.

School Connectedness and Suicide Among High School Youth: A Systematic Review.

BACKGROUND: Suicide is a leading cause of death for adolescents, and school connectedness is a potential, modifiable protective factor for suicide. We sought to examine if school connectedness protected against suicide among high school students and if potential moderators affected the relationship between school connectedness and suicide. METHODS: We searched online databases (PubMed, EMBASE, CINAHL, and PsycINFO) on December 12, 2021, for studies that examined the effects of school connectedness on suicide among high school students. RESULTS: This systematic review identified 34 studies that examined the effects of school connectedness on adolescent suicidality. Results indicated mixed findings of school connectedness on suicidality. Among studies that assessed a suicide ideation outcome, 73.3% found that school connectedness protected against suicide. Among studies that assessed a suicide attempts outcome, 50% found that school connectedness protected against suicide. Most included studies did not control for notable variables in their final models, such as sleep, impulsivity, substance use, or depression. No studies examined moderators of school connectedness and suicide. CONCLUSIONS: School connectedness is somewhat protective of suicidality, and more protective of suicidal ideation than suicide attempts. Researchers should examine the construct of school connectedness among modern youth to better understand school connectedness and suicide.

Shared genomic segments analysis identifies MHC class I and class III molecules as genetic risk factors for juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is a complex rheumatic disease encompassing several clinically defined subtypes of varying severity. The etiology of JIA remains largely unknown, but genome-wide association studies (GWASs) have identified up to 22 genes associated with JIA susceptibility, including a well-established association with HLA-DRB1. Continued investigation of heritable risk factors has been hindered by disease heterogeneity and low disease prevalence. In this study, we utilized shared genomic segments (SGS) analysis on whole-genome sequencing of 40 cases from 12 multi-generational pedigrees significantly enriched for JIA. Subsets of cases are connected by a common ancestor in large extended pedigrees, increasing the power to identify disease-associated loci. SGS analysis identifies genomic segments shared among disease cases that are likely identical by descent and anchored by a disease locus. This approach revealed statistically significant signals for major histocompatibility complex (MHC) class I and class III alleles, particularly HLA-A∗02:01, which was observed at a high frequency among cases. Furthermore, we identified an additional risk locus at 12q23.2-23.3, containing genes primarily expressed by naive B cells, natural killer cells, and monocytes. The recognition of additional risk beyond HLA-DRB1 provides a new perspective on immune cell dynamics in JIA. These findings contribute to our understanding of JIA and may guide future research and therapeutic strategies.

Recruitment strategies in marginalized industries for occupational health research: an example in a pilot study of cleaning staff during COVID-19.

This commentary describes challenges in recruiting workers from marginalized industries with examples from a pilot study of janitors, custodians, and maids and their experiences of cleaning and disinfection protocols during COVID-19 and potentially associated respiratory symptoms. Recruitment strategies included contacting a local hospital, national workers' unions, and a large Arizona employer; using online Facebook groups; and contacting Arizona maid service companies and a school district. English and Spanish online and hard copy surveys about cleaning protocols and respiratory symptoms were used. Participants could also participate in online/phone interviews. Worker's compensation, liability, and confidentiality were concerns across organizations. Online surveys yielded unreliable data. Hard copy surveys were used due to workers' limited technology access. We reflect upon these challenges and discuss other strategies for recruiting from marginalized populations for occupational health research. Building trust with organizations and workers and considering technology access may ultimately increase recruitment feasibility.

HPA flexibility and FKBP5: promising physiological targets for conservation.

Hypothalamic-pituitary-adrenal axis (HPA) flexibility is an emerging concept recognizing that individuals that will cope best with stressors will probably be those using their hormones in the most adaptive way. The HPA flexibility concept considers glucocorticoids as molecules that convey information about the environment from the brain to the body so that the organismal phenotype comes to complement prevailing conditions. In this context, FKBP5 protein appears to set the extent to which circulating glucocorticoid concentrations can vary within and across stressors. Thus, FKBP5 expression, and the HPA flexibility it causes, seem to represent an individual's ability to regulate its hormones to orchestrate organismal responses to stressors. As FKBP5 expression can also be easily measured in blood, it could be a worthy target of conservation-oriented research attention. We first review the known and likely roles of HPA flexibility and FKBP5 in wildlife. We then describe putative genetic, environmental and epigenetic causes of variation in HPA flexibility and FKBP5 expression among and within individuals. Finally, we hypothesize how HPA flexibility and FKBP5 expression should affect organismal fitness and hence population viability in response to human-induced rapid environmental changes, particularly urbanization. This article is part of the theme issue 'Endocrine responses to environmental variation: conceptual approaches and recent developments'.

A conceptual framework for understanding stress-induced physiological and transgenerational effects on population responses to climate change.

Organisms are experiencing higher average temperatures and greater temperature variability because of anthropogenic climate change. Some populations respond to changes in temperature by shifting their ranges or adjusting their phenotypes via plasticity and/or evolution, while others go extinct. Predicting how populations will respond to temperature changes is challenging because extreme and unpredictable climate changes will exert novel selective pressures. For this reason, there is a need to understand the physiological mechanisms that regulate organismal responses to temperature changes. In vertebrates, glucocorticoid hormones mediate physiological and behavioral responses to environmental stressors and thus are likely to play an important role in how vertebrates respond to global temperature changes. Glucocorticoids have cascading effects that influence the phenotype and fitness of individuals, and some of these effects can be transmitted to offspring via trans- or intergenerational effects. Consequently, glucocorticoid-mediated responses could affect populations and could even be a powerful driver of rapid evolutionary change. Here, we present a conceptual framework that outlines how temperature changes due to global climate change could affect population persistence via glucocorticoid responses within and across generations (via epigenetic modifications). We briefly review glucocorticoid physiology, the interactions between environmental temperatures and glucocorticoid responses, and the phenotypic consequences of glucocorticoid responses within and across generations. We then discuss possible hypotheses for how glucocorticoid-mediated phenotypic effects might impact fitness and population persistence via evolutionary change. Finally, we pose pressing questions to guide future research. Understanding the physiological mechanisms that underpin the responses of vertebrates to elevated temperatures will help predict population-level responses to the changing climates we are experiencing.