Associations Between Sociodemographic Variables, Social Determinants of Health, and Diabetes: Findings From a Congregational Health Needs Assessment.

PURPOSE: To examine associations between sociodemographic variables, social determinants of health (SDOHs) and diabetes using health needs assessment data. DESIGN: Cross-sectional study. SETTING: Faith-based communities in the Mid-South U.S. SAMPLE: Of the 378 churches, 92 participated in the study (24% response rate); N = 828 church leaders and members completed the survey. MEASURE: The Mid-South Congregational Health Survey assessed perceived health-related needs of congregations and the communities they serve. ANALYSIS: Generalized linear mixed modeling examined the associations between sociodemographic variables (age, sex, race/ethnicity, educational level), SDOHs (affordable healthcare, healthy food, employment), and diabetes. RESULTS: Individuals with less education had lower odds of reporting all SDOHs as health needs compared to individuals with more education (ORrange = .59-.63). Men had lower odds of reporting diabetes as a health need or concern compared to women (OR = .70; 95% CI = .50, .97). African Americans had greater odds of reporting diabetes as a health need compared to individuals in the 'Other' race/ethnicity category (OR = 3.91; 95% CI = 2.20, 6.94). Individuals who reported affordable healthcare (OR = 2.54; 95% CI = 1.73, 3.72), healthy food (OR = 2.24; 95% CI = 1.55, 3.24), and employment (OR = 3.33; 95% CI = 2.29, 4.84) as health needs had greater odds of reporting diabetes as a health need compared to those who did not report these SDOHs as needs. CONCLUSIONS: Future studies should evaluate strategies to merge healthcare and faith-based organizations' efforts to address SDOHs impacting diabetes.

Perceived Health Needs of Church Leaders and Members: A Secondary Data Analysis of the Mid-South Congregational Health Survey.

Needs assessments have been successful in helping communities and congregations focus their health ministry efforts; however, most have used leader perceptions of congregational health needs. The purpose of this study was to examine and compare the self-reported needs of both church leaders and members to be addressed by their congregation. Church leaders (n = 369) and members (n = 459) from 92 congregations completed the 2019 Mid-South Congregational Health Survey. Frequencies and generalized linear mixed models (GLMM) were performed to examine the top 10 self-reported needs and associations by church role, respectively. Of the top 10 congregational needs, anxiety or depression, high blood pressure, stress, and healthy foods were ranked identically regardless of church role. Church leaders perceived obesity and diabetes to be important congregational health needs, whereas members perceived affordable health care and heart disease to be important congregational health needs. GLMM, controlling for within-church clustering and covariates, revealed church leaders were more likely than members to report obesity (odds ratio [OR]: 1.93, 95% confidence interval [CI] = [1.39, 2.67], p < .0001) and diabetes (OR: 1.73, 95% CI = [1.24, 2.41], p = .001) as congregational needs. Findings display similarities and differences in needs reported by church role. Including many perspectives when conducting congregational health needs assessments will assist the development of effective faith-based health promotion programs.

Perceptions of mindfulness practices as a support for individuals managing caregiving responsibilities and chronic disease: A qualitative study.

OBJECTIVES: Explore the lived experience of individuals managing and/or caregiving for someone with a chronic disease and their perceptions of developing a mindfulness program for stress reduction. METHODS: Sixteen participants with chronic disease and/or caregivers participated. Participants completed eligibility screening, demographic questionnaires, and semi-structured interviews (30-60 min each) online or by phone. Interviews (n = 16) were audio recorded, transcribed, and analyzed using thematic analysis and NVivo® 12. Survey data were analyzed using SPSS® 28. RESULTS: Four themes emerged: (a) Chronic disease management and stress-perspectives on life's stressors; (b) Stress reduction techniques/perceptions of mindfulness-knowledge and implementation of stress reduction practices and familiarity with mindfulness; (c) Mindfulness program acceptability, barriers, and facilitators-interest, barriers, and facilitators to attending; (d) Mindfulness program structure-logistics to increase access and appeal to diverse audiences. DISCUSSION: Mindfulness has the potential for addressing the complexities of stress associated with disease management. Targeting mindfulness programs for populations with chronic disease management and caregiving responsibilities should include: Consideration of group formats with participation limited to this population, structuring programs to overcome barriers (i.e., culturally appropriate location), and equipping members of the community being served as instructors to ensure culturally relevant instruction.

Activation of the Interleukin-18 Signaling Pathway via Direct Receptor Dimerization in the Absence of Interleukin-18.

Interleukin 18 (IL-18) is a key cytokine involved in the activation of T and NK cells, which are major effector cells in tumor killing. However, recombinant IL-18 showed limited efficacy in clinical trials. A recent study showed the lack of efficacy was largely due to the existence of IL-18BP, a soluble decoy receptor for IL-18. It was shown that engineered IL-18 variants that maintained pathway activation, but avoided IL-18BP binding, could exert potent antitumor effects. In this study, we demonstrated an alternative strategy to activate IL-18 signaling through direct receptor dimerization. These results provide evidences that the IL-18 pathway can be activated by directly bridging the receptors and, therefore, bypassing the IL-18BP-mediated inhibition.

A Scoping Review of Self-Care Within the Context of Obesity-Related Outcomes Among Faith Leaders.

OBJECTIVE: Faith leaders often serve as health-related role models yet many struggle with obesity and self-care engagement. The purpose of this scoping review was to examine how the faith leader literature has defined self-care and examined obesity and obesity-related chronic disease. DATA SOURCE: Studies were identified through database (eg, PubMed, CINAHL, PsycINFO), backward, and grey literature (eg, dissertations) searches. INCLUSION/EXCLUSION CRITERIA: Studies published in English with participants who were 18 years or older and examined leaders across all faiths. Studies also included an examination of self-care behaviors among faith leaders within the context of obesity or obesity-related chronic diseases. DATA EXTRACTION/SYNTHESIS: Data synthesis was qualitative and informed by the six-step framework developed by Arksey and O'Malley (2005) as well as updated recommendations by Daudt et al (2013). Of the 418 studies identified and screened, 20 met the eligibility criteria. RESULTS: Studies were primarily cross-sectional and participants Christian faith-leaders in the US. Most studies did not define self-care or incorporate theory, but focused on vegetarian diets and physical activity engagement. Other self-care related behaviors (eg, sleep, days off), some unique to faith leaders (eg, sabbatical), were included but not systematically. CONCLUSIONS: Research with more diverse faith leaders and that uses theory is needed to guide development of strategies for engaging this population in self-care to reduce obesity and related chronic diseases.

Nickel-catalyzed ester carbonylation promoted by imidazole-derived carbenes and salts.

Millions of tons of acetyl derivatives such as acetic acid and acetic anhydride are produced each year. These building blocks of chemical industry are elaborated into esters, amides, and eventually polymer materials, pharmaceuticals, and other consumer products. Most acetyls are produced industrially using homogeneous precious metal catalysts, principally rhodium and iridium complexes. We report here that abundant nickel can be paired with imidazole-derived carbenes or the corresponding salts to catalyze methyl ester carbonylation with turnover frequency (TOF) exceeding 150 hour-1 and turnover number (TON) exceeding 1600, benchmarks that invite comparisons to state-of-the-art rhodium-based systems and considerably surpass known triphenylphosphine-based nickel catalysts, which operate with TOF ~7 hour-1 and TON ~100 under the same conditions.

A myeloid program associated with COVID-19 severity is decreased by therapeutic blockade of IL-6 signaling.

Altered myeloid inflammation and lymphopenia are hallmarks of severe infections. We identified the upregulated EN-RAGE gene program in airway and blood myeloid cells from patients with acute lung injury from SARS-CoV-2 or other causes across 7 cohorts. This program was associated with greater clinical severity and predicted future mechanical ventilation and death. EN-RAGEhi myeloid cells express features consistent with suppressor cell functionality, including low HLA-DR and high PD-L1. Sustained EN-RAGE program expression in airway and blood myeloid cells correlated with clinical severity and increasing expression of T cell dysfunction markers. IL-6 upregulated many EN-RAGE program genes in monocytes in vitro. IL-6 signaling blockade by tocilizumab in a placebo-controlled clinical trial led to rapid normalization of EN-RAGE and T cell gene expression. This identifies IL-6 as a key driver of myeloid dysregulation associated with worse clinical outcomes in COVID-19 patients and provides insights into shared pathophysiological mechanisms in non-COVID-19 ARDS.

Fit with Faith: An Exploratory Study Examining a Behavior Change Intervention for African-American Clergy and Their Spouses.

Fit with Faith is a 10-week, diet, physical activity, and stress reduction intervention for African-American clergy and spouses, which included: meetings, phone calls, a behavior tracking app. Survey, 24-h recall, accelerometer, anthropometric, and blood pressure data were collected. Wilcoxon signed ranked tests were used for analyses. In this one-arm study, clergy and spouses (n = 20) attended most meetings and calls, but only half posted daily goals or tracked behaviors using the app. Spouses' body mass index (BMI) decreased and physical activity self-regulation cognitive scores increased pre-post intervention. Statistically significant changes in BMI, systolic blood pressure, and self-regulations scores also were seen among younger (< 51 years) participants (n = 8). As positive changes were seen mostly among women and younger participants, more research is needed on how to engage all clergy in behavior change programs.

Congregational health needs by key demographic variables: Findings from a congregational health needs assessment tool.

Health needs assessments identify important issues to be addressed and assist organizations in prioritizing resources. Using data from the Mid-South Congregational Health Survey, top health needs (physical, mental, social determinants of health) were identified, and differences in needs by key demographic variables (age, sex, race/ethnicity, education) were examined. Church leaders and members (N = 828) from 92 churches reported anxiety/depression (65 %), hypertension/stroke (65 %), stress (62 %), affordable healthcare (60 %), and overweight/obesity (58 %) as the top health needs in their congregations. Compared to individuals < 55 years old and with a college degree, individuals ≥ 55 years old (ORrange=1.50-1.86) and with ≤ high school degree (ORrange=1.55-1.91) were more likely to report mental health needs (anxiety/depression; stress). African Americans were less likely to report physical health needs (hypertension/stroke; overweight/obesity) than individuals categorized as Another race/ethnicity (ORrange=0.38-0.60). Individuals with ≤ high school degree were more likely to report affordable healthcare as a need compared to individuals with some college or a college degree (ORrange=1.58). This research highlights the need for evaluators and planners to design programs that are comprehensive in their approach to addressing the health needs of congregations while also considering demographic variation that may impact program participation and engagement.

Examination of Associations between Physical Activity and Eating Identities among College-aged Adults Living in Hawai'i.

While physical activity and diet behaviors are correlated, mechanisms underlying associations have rarely been examined. This study examined associations between physical activity identity and eating identity among college-aged adults in Hawai'i to provide guidance for future multiple behavior change interventions. This study was a cross-sectional analysis of data collected between September 2013 and January 2014. Participants were 40 college students attending 4-year and 2-year institutions within the University of Hawai'i system. Total physical activity identity score and dimensions were measured using the Athlete Identity Questionnaire. Eating identity subtypes were measured using the Eating Identity Type Inventory. Associations between physical activity identity total score, 4 physical activity identity dimensions (appearance, importance, competence, and encouragement), and 4 eating identity subtypes (healthy, emotional, meat, and picky) were examined using multiple linear regressions. A significant positive association was found between total physical activity identity score and the healthy eating subtype and a negative association with the picky eating subtype. The physical activity dimension importance had a significant positive association with the healthy eating subtype, appearance a negative association with the emotional eating subtype, and competence a positive association with the meat eating subtype but a negative association with the picky eating subtype. The findings suggest important overlap in identities for physical activity and diet. Measurement of physical activity identity and eating identity as well as tailored intervention strategies should be incorporated into more behavior change research.

Responding to the COVID-19 pandemic: The experiences of South Australia's Rescue, Retrieval and Aviation Services.

COVID-19 poses significant challenges to pre-hospital and retrieval medicine (PHRM) clinicians - and many are unique to this area of clinical practice. We share the experiences of the South Australian Ambulance Service (SAAS) MedSTAR Emergency Medical Retrieval Service in preparing for the COVID-19 pandemic in the pre-hospital and retrieval setting - including the role of a multidisciplinary leadership team; challenges and potential approaches to screening for COVID-19; personal protective equipment for pre-hospital and aeromedical taskings; issues arising with interstate retrievals; and the role of telehealth. Although novel solutions allowed SAAS MedSTAR to continue to deliver high-quality care, considering the resource implications involved in undertaking the transfer of patients with COVID-19, it is clear that significant community disease transmission threatens to overwhelm any PHRM service. Should Australia face a significant future outbreak, it is conceivable that some PHRM operations may need to be reduced or suspended entirely.

Strategies for Designing Clergy and Spouse Obesity-Related Programs.

PURPOSE: Clergy have influence on the health of congregations and communities yet struggle with health behaviors. Interventions tailored to their occupation-specific demands and unique needs may provide a solution. Qualitative methods were used to identify opportunities and resources for the development of an effective obesity-related program for clergy. APPROACH: Ninety-minute focus groups were held with clergy (3 groups) and spouses (3 separate groups). Discussion explored: Program target(s); Opportunities and barriers that influence diet, physical activity, and stress-reduction practices; Empowering and culturally relevant health promotion strategies. SETTING: All study activities took place in Memphis, TN. PARTICIPANTS: Eighteen clergy and fourteen spouses participated. All clergy were male, all spouses were female. METHOD: Previous research with clergy informed the interview guide and the PEN-3 framework aided in organizing the coding of clergy and spouse focus groups. Focus groups were audio recorded and transcripts analyzed using NVivo® 12. RESULTS: Themes included: 1) Intervention targets-clergy, spouses, congregations; 2) Opportunities and barriers-making time, establishing boundaries, church traditions, individuals who support and hinder behavior change; 3) Intervention strategies-tools for healthy eating, goal setting, camaraderie, combining face-to-face with eHealth modalities. CONCLUSION: The relationship between clergy, spouse, and congregation make it important for obesity-related programs to target the unique needs of both clergy and spouses. Strategies should focus on healthy eating and personal connections no matter the modality used.

Early impact of the implementation of Medicaid episode-based payment reforms in Arkansas.

OBJECTIVE: To evaluate episode-based payments for upper respiratory tract infections (URI) and perinatal care in Arkansas's Medicaid population. STUDY SETTING: Upper respiratory infection and perinatal episodes among Medicaid-covered individuals in Arkansas and comparison states from fiscal year (FY) 2011 to 2014. STUDY DESIGN: Cross-sectional observational analysis using a difference-in-difference design to examine outcomes associated with URI and perinatal episodes of care (EOC) from 2011 to 2014. Key dependent variables include antibiotic use, emergency department visits, physician visits, hospitalizations, readmission, and preventive screenings. DATA COLLECTION: Claims data from the Medicaid Analytic Extract for Arkansas, Mississippi, and Missouri from 2010 to 2014 with supplemental county-level data from the Area Health Resource File (AHRF). PRINCIPAL FINDINGS: The URI EOC reduced the probability of antibiotic use (marginal effect [ME] = -1.8, 90% CI: -2.2, -1.4), physician visits (ME = 0.6, 90% CI: -0.8, -0.4), improved the probability of strep tests for children diagnosed with pharyngitis (ME = 9.4, 90% CI: 8.5, 10.3), but also increased the probability of an emergency department (ED) visit (ME = 0.1, 90% CI: 0.1, 0.2), relative to the comparison group. For perinatal EOCs, we found a reduced probability of an ED visit during pregnancy (ME = 0.1, 90% CI: -0.2, -0.0), an increased probability of screening for HIV (ME = 6.2, 90% CI: 4.0, 8.5), chlamydia (ME = 9.5, 90% CI: 7.2, 11.8), and group B strep-test (ME = 2.6, 90% CI: 0.5, 4.6), relative to the comparison group. Predelivery and postpartum hospitalizations also increased (ME = 1.2, 90% CI: 0.4, 2.0; ME = 0.4, 90% CI: 0.0, 0.8, respectively), relative to the comparison group. CONCLUSION: Upper respiratory infection and perinatal EOCs for Arkansas Medicaid beneficiaries produced mixed results. Aligning shared savings with quality metrics and cost-thresholds may help achieve quality targets and disincentivize over utilization within the EOC, but may also have unintended consequences.

Did Arkansas' Medicaid Patient-Centered Medical Home Program Have Spillover Effects on Commercially Insured Enrollees?

Patient-centered medical homes are increasingly being implemented by state Medicaid programs to incentivize high-quality, coordinated care and ultimately lower health care spending. This study examined whether the Arkansas Medicaid Patient-Centered Medical Home Program's practice-wide transformation activities had spillover effects on commercial beneficiaries. We used difference-in-differences to compare utilization and expenditures of commercially insured enrollees as their practices received Medicaid patient-centered medical home certification on a rolling basis between 2014 and 2016. We found a 5.7% increase in outpatient visits and 13% higher expenditures among early adopting practices. Even without associated reductions in costly emergency department visits or inpatient hospital admissions, decisionmakers should not lose sight of the potential value of increased engagement in and coordination of professional services for a population with high unmet health needs. Our results also emphasize that states can leverage Medicaid to spur system-wide transformation, and the investments generate spillover effects beyond those covered directly by Medicaid.

Effect of Obesity-Linked FTO rs9939609 Variant on Physical Activity and Dietary Patterns in Physically Active Men and Women.

Single nucleotide polymorphisms (SNPs) in the fat mass and obesity-associated (FTO) locus are associated with obesity, but lifestyle factors may modulate the obesity risk related to FTO. This study examined the physical activity and dietary patterns of 528 physically active white men and women (mean (SD): 34.9 (9.5) years, 26.6 (4.3) kg·m-2) carrying different risk variants of FTO SNP rs9939609. Sex, age, and anthropometric measurements (stature, body mass, and waist circumference) were self-reported using an online questionnaire, and body mass index and waist-to-height ratio were calculated. Physical activity and eating behaviour were assessed using the International Physical Activity Questionnaire (IPAQ) and Three-Factor Eating Questionnaire (TFEQ), respectively. Body mass, body mass index (BMI), waist circumference, and waist-to-height ratio were not significantly different between individuals expressing different FTO rs9939609 risk variants (all P ≥ 0.66). The cohort was physically active (4516 (3043) total MET min·week-1), although homozygous risk allele carriers (AA) displayed higher TFEQ cognitive restraint compared with nonrisk allele carriers (TT) (ES = 0.33 and P=0.03). In conclusion, obesity-related parameters were not different in physically active individuals expressing different risk variants of FTO rs9939609, although homozygous risk allele carriers exhibited higher cognitive restraint.

Discovery of selective small-molecule HDAC6 inhibitor for overcoming proteasome inhibitor resistance in multiple myeloma.

Multiple myeloma (MM) has proven clinically susceptible to modulation of pathways of protein homeostasis. Blockade of proteasomal degradation of polyubiquitinated misfolded proteins by the proteasome inhibitor bortezomib (BTZ) achieves responses and prolongs survival in MM, but long-term treatment with BTZ leads to drug-resistant relapse in most patients. In a proof-of-concept study, we previously demonstrated that blocking aggresomal breakdown of polyubiquitinated misfolded proteins with the histone deacetylase 6 (HDAC6) inhibitor tubacin enhances BTZ-induced cytotoxicity in MM cells in vitro. However, these foundational studies were limited by the pharmacologic liabilities of tubacin as a chemical probe with only in vitro utility. Emerging from a focused library synthesis, a potent, selective, and bioavailable HDAC6 inhibitor, WT161, was created to study the mechanism of action of HDAC6 inhibition in MM alone and in combination with BTZ. WT161 in combination with BTZ triggers significant accumulation of polyubiquitinated proteins and cell stress, followed by caspase activation and apoptosis. More importantly, this combination treatment was effective in BTZ-resistant cells and in the presence of bone marrow stromal cells, which have been shown to mediate MM cell drug resistance. The activity of WT161 was confirmed in our human MM cell xenograft mouse model and established the framework for clinical trials of the combination treatment to improve patient outcomes in MM.

Immunotherapy Not Working? Check Your Microbiota.

Gut microbes have ascended to prominence as key modulators of host immunity, raising the possibility that they could influence the outcome of cancer immunotherapy. Two recent studies address this question by identifying specific gut-resident bacteria as drivers of checkpoint blockade immunotherapy in pre-clinical tumor models.

Emerging cytokine networks in colorectal cancer.

Cytokine networks are crucial aspects of tumour immunology, particularly for colorectal cancer (CRC), in which inflammation and antitumour immunity are key determinants of disease progression. In this Review, we highlight new insights into the functions of well-known cytokines in CRC, describe recently discovered roles for a growing number of novel players, and emphasize the complexity and therapeutic implications of the cytokine milieu. We also discuss how cancer mutations and epigenetic adaptations influence the oncogenic potential of cytokines, a relatively unexplored area that could yield crucial insights into tumour immunology and facilitate the effective application of cytokine-modulatory therapies for CRC.

Cytotoxicity of thiazolidinedione-, oxazolidinedione- and pyrrolidinedione-ring containing compounds in HepG2 cells.

Liver damage occurred in some patients who took troglitazone (TGZ) for type II diabetes. The 2,4-thiazolidinedione (TZD) ring in TGZ's structure has been implicated in its hepatotoxicity. To further examine the potential role of a TZD ring in toxicity we used HepG2 cells to evaluate two series of compounds containing different cyclic imides. N-phenyl analogues comprised 3-(3,5-dichlorophenyl)-2,4-thiazolidinedione (DCPT); 3-(3,5-dichlorophenyl)-2,4-oxazolidinedione (DCPO) and N-(3,5-dichlorophenyl)succinimide (NDPS). Benzylic compounds, which closely resemble TGZ, included 5-(3,5-dichlorophenylmethyl)-2,4-thiazolidinedione (DCPMT); 5-(4-methoxyphenylmethyl)-2,4-thiazolidinedione (MPMT); 5-(4-methoxyphenylmethylene)-2,4-thiazolidinedione (MPMT-I); 5-(4-methoxyphenylmethyl)-2,4-oxazolidinedione (MPMO); 3-(4-methoxyphenylmethyl)succinimide (MPMS) and 3-(4-methoxyphenylmethylene)succinimide (MPMS-I). Cytotoxicity was assessed using the MTS assay after incubating the compounds (0-250µM) with HepG2 cells for 24h. Only certain TZD derivatives (TGZ, DCPT, DCPMT and MPMT-I) markedly decreased cell viability, whereas MPMT had low toxicity. In contrast, analogues without a TZD ring (DCPO, NDPS, MPMO, MPMS and MPMS-I) were not cytotoxic. These findings suggest that a TZD ring may be an important determinant of toxicity, although different structural features, chemical stability, cellular uptake or metabolism, etc., may also be involved. A simple clustering approach, using chemical fingerprints, assigned each compound to one of three classes (each containing one active compound and close homologues), and provided a framework for rationalizing the activity in terms of structure.

Intratumoural inflammation and endocrine resistance in breast cancer.

It is becoming clear that inflammation-associated mechanisms can affect progression of breast cancer and modulate responses to treatment. Estrogen receptor alpha (ERα (ESR1)) is the principal biomarker and therapeutic target for endocrine therapies in breast cancer. Over 70% of patients are ESR1-positive at diagnosis and are candidates for endocrine therapy. However, ESR1-positive tumours can become resistant to endocrine therapy. Multiple mechanisms of endocrine resistance have been proposed, including suppression of ESR1. This review discusses the relationship between intratumoural inflammation and endocrine resistance with a particular focus on inflammation-mediated suppression of ESR1.