α-IRAK-4 Suppresses the Activation of RANK/RANKL Pathway on Macrophages Exposed to Endodontic Microorganisms.

Periapical lesions are common pathologies affecting the alveolar bone, often initiated by intraradicular lesions resulting from microbial exposure to dental pulp. These microorganisms trigger inflammatory and immune responses. When endodontic treatment fails to eliminate the infection, periapical lesions persist, leading to bone loss. The RANK/RANKL/OPG pathway plays a crucial role in both the formation and the destruction of the bone. In this study, the objective was to inhibit the RANK/RANKL pathway in vitro within exposed Thp-1 macrophages to endodontic microorganisms, specifically Enterococcus faecalis, which was isolated from root canals of 20 patients with endodontic secondary/persistent infection, symptomatic and asymptomatic, and utilizing an α-IRAK-4 inhibitor, we introduced endodontic microorganisms and/or lipoteichoic acid from Streptococcus spp. to cellular cultures in a culture plate, containing thp-1 cells and/or PBMC from patients with apical periodontitis. Subsequently, we assessed the percentages of RANK+, RANKL+, and OPG+ cells through flow cytometry and measured the levels of several inflammatory cytokines (IL-1ß, TNF-α, IL-6, IL-8, IL-10, and IL-12p70) in the cellular culture supernatant through a CBA kit and performed analysis by flow cytometry. A significant difference was observed in the percentages of RANK+RANKL+, OPG+ RANKL+ cells in thp-1 cells and PBMCs from patients with apical periodontitis. The findings revealed significant differences in the percentages of the evaluated cells, highlighting the novel role of the IRAK-4 inhibitor in addressing this oral pathology, apical periodontitis, where bone destruction is observed.

Role of the sympathetic nervous system in cancer-associated cachexia and tumor progression in tumor-bearing BALB/c mice.

BACKGROUND: Adipose and muscle tissue wasting outlines the cachectic process during tumor progression. The sympathetic nervous system (SNS) is known to promote tumor progression and research suggests that it might also contribute to cancer-associated cachexia (CAC) energetic expenditure through fat wasting. METHODS: We sympathectomized L5178Y-R tumor-bearing male BALB/c mice by intraperitoneally administering 6-hydroxydopamine to evaluate morphometric, inflammatory, and molecular indicators of CAC and tumor progression. RESULTS: Tumor burden was associated with cachexia indicators, including a 10.5% body mass index (BMI) decrease, 40.19% interscapular, 54% inguinal, and 37.17% visceral adipose tissue loss, a 12% food intake decrease, and significant (p = 0.038 and p = 0.0037) increases in the plasmatic inflammatory cytokines IL-6 and IFN-γ respectively. Sympathectomy of tumor-bearing mice was associated with attenuated BMI and visceral adipose tissue loss, decreased interscapular Ucp-1 gene expression to basal levels, and 2.6-fold reduction in Mmp-9 relative gene expression, as compared with the unsympathectomized mice control group. CONCLUSION: The SNS contributes to CAC-associated morphometric and adipose tissue alterations and promotes tumor progression in a murine model.

Cancer mortality among Colombian and foreign populations over a 15-year period.

Purpose: We aimed to compare cancer mortality among foreign- and Colombian populations in Colombia during the period of 2006-2020. Methods: This retrospective study utilized vital statistics from the Colombian National Department of Statistics (DANE). The dataset included variables such as age group, sex, country of permanent residency, insurance, education level, marital status, ethnicity, and cause of death. The population data to calculate rates was obtained from the Colombian census and the United Nations. Crude and adjusted rates as well as proportional mortality rates were calculated. Results: A total of 561,932 cancer deaths occurred in Colombia from 2006 to 2020. The foreign population (country of permanent residency different to Colombia) had a lower crude cancer mortality rate (31.1 per 100,000 inhabitants) than the Colombian population (81.9 per 100,000 inhabitants). However, the age-adjusted cancer mortality rate among the foreign population was 253.6 per 100,000, compared to 86.1 per 100,000 among the Colombian population. The proportional cancer mortality was 10.4 % among foreign population compared to 17.4 % among Colombian population. Conclusions: The proportional cancer mortality shows that the proportion of cancer-related deaths is greater among the Colombian population compared to the immigrant population. However, immigrants in Colombia have a higher age-adjusted cancer mortality rate than Colombians, indicating that immigrants have worse cancer outcomes than the Colombians even though the immigrant population is younger. This is likely due to the frequent barriers that immigrants encounter in accessing health care in Colombia. Future research needs to focus on access to care for the immigrant population by investigating cancer-related risk factors among immigrants and addressing their barriers to cancer prevention and treatment.

Endothelial c-Myc knockout disrupts metabolic homeostasis and triggers the development of obesity.

Introduction: Obesity is a major risk factor associated with multiple pathological conditions including diabetes and cardiovascular disease. Endothelial dysfunction is an early predictor of obesity. However, little is known regarding how early endothelial changes trigger obesity. In the present work we report a novel endothelial-mediated mechanism essential for regulation of metabolic homeostasis, driven by c-Myc. Methods: We used conditional knockout (EC-Myc KO) and overexpression (EC-Myc OE) mouse models to investigate the endothelial-specific role of c-Myc in metabolic homeostasis during aging and high-fat diet exposure. Body weight and metabolic parameters were collected over time and tissue samples collected at endpoint for biochemical, pathology and RNA-sequencing analysis. Animals exposed to high-fat diet were also evaluated for cardiac dysfunction. Results: In the present study we demonstrate that EC-Myc KO triggers endothelial dysfunction, which precedes progressive increase in body weight during aging, under normal dietary conditions. At endpoint, EC-Myc KO animals showed significant increase in white adipose tissue mass relative to control littermates, which was associated with sex-specific changes in whole body metabolism and increase in systemic leptin. Overexpression of endothelial c-Myc attenuated diet-induced obesity and visceral fat accumulation and prevented the development of glucose intolerance and cardiac dysfunction. Transcriptome analysis of skeletal muscle suggests that the protective effects promoted by endothelial c-Myc overexpression are associated with the expression of genes known to increase weight loss, energy expenditure and glucose tolerance. Conclusion: Our results show a novel important role for endothelial c-Myc in regulating metabolic homeostasis and suggests its potential targeting in preventing obesity and associated complications such as diabetes type-2 and cardiovascular dysfunction.

Hepatic Steatosis Can Be Partly Generated by the Gut Microbiota-Mitochondria Axis via 2-Oleoyl Glycerol and Reversed by a Combination of Soy Protein, Chia Oil, Curcumin and Nopal.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a serious health problem, and recent evidence indicates that gut microbiota plays a key role in its development. It is known that 2-oleoyl glycerol (2-OG) produced by the gut microbiota is associated with hepatic fibrosis, but it is not known whether this metabolite is involved in the development of hepatic steatosis. The aim of this study was to evaluate how a high-fat-sucrose diet (HFS) increases 2-OG production through gut microbiota dysbiosis and to identify whether this metabolite modifies hepatic lipogenesis and mitochondrial activity for the development of hepatic steatosis as well as whether a combination of functional foods can reverse this process. Wistar rats were fed the HFS diet for 7 months. At the end of the study, body composition, biochemical parameters, gut microbiota, protein abundance, lipogenic and antioxidant enzymes, hepatic 2-OG measurement, and mitochondrial function of the rats were evaluated. Also, the effect of the consumption of functional food with an HFS diet was assessed. In humans with MASLD, we analyzed gut microbiota and serum 2-OG. Consumption of the HFS diet in Wistar rats caused oxidative stress, hepatic steatosis, and gut microbiota dysbiosis, decreasing α-diversity and increased Blautia producta abundance, which increased 2-OG. This metabolite increased de novo lipogenesis through ChREBP and SREBP-1. 2-OG significantly increased mitochondrial dysfunction. The addition of functional foods to the diet modified the gut microbiota, reducing Blautia producta and 2-OG levels, leading to a decrease in body weight gain, body fat mass, serum glucose, insulin, cholesterol, triglycerides, fatty liver formation, and increased mitochondrial function. To use 2-OG as a biomarker, this metabolite was measured in healthy subjects or with MASLD, and it was observed that subjects with hepatic steatosis II and III had significantly higher 2-OG than healthy subjects, suggesting that the abundance of this circulating metabolite could be a predictor marker of hepatic steatosis.

Unsupervised Clustering Analysis of Regimen and HLA Characteristics in Pediatric Umbilical Cord Blood Transplantation.

HLA matching is a critical factor in allogeneic unrelated hematopoietic cell transplantation (HCT) because of its impact on post-transplantation survival and quality of life. Umbilical cord blood transplantation (UCBT) offers unique advantages, but determining the optimal approach to graft selection and immunosuppression remains challenging. Unsupervised clustering, a machine learning technique, has potential for analyzing transplantation outcomes, but its application in investigating leukemia outcomes has been limited. This study aimed to identify optimal combinations of HLA/ killer immunoglobulin receptor (KIR) donor-patient pairing, conditioning, and immunosuppressive regimens in pediatric patients with acute lymphoblastic leukemia (ALL) or acute myeloblastic leukemia (AML) undergoing UCBT. Outcome data for single, unmanipulated UCBT in pediatric AML (n = 708) and ALL (n = 1034) patients from the Eurocord/EBMT registry were analyzed using unsupervised clustering. Resulting clusters were used to inform post hoc competing risks and Kaplan-Meier analyses. In AML, single HLA-C mismatches with other loci fully matched (7/8) were associated with poorer relapse-free survival (RFS) (P = .039), but a second mismatch at any other locus counteracted this effect. In ALL, total body irradiation (TBI) effectively prevented relapse mortality (P = .007). KIR/HLA-C match status affected RFS in AML (P = .039) but not in ALL (P = .8). Administration of antithymocyte globulin (ATG) substantially increased relapse, with no relapses occurring in the 85 patients who did not receive ATG. Our unsupervised clustering analyses generate several key statistical and mechanistic hypotheses regarding the relationships between HLA matching, conditioning regimens, immunosuppressive therapies, and transplantation outcomes in pediatric AML and ALL patients. HLA-C and KIR combinations significantly impact RFS in pediatric AML but not in ALL. ATG use in fully matched pediatric patients is associated with late-stage relapse. TBI regimens appear to be beneficial in ALL, with efficacy largely independent of histocompatibility variables. These findings reflect the distinct genetic and biological profiles of AML and ALL.

Methodological and Practical Challenges in Synthesizing Occupational Cancer Studies.

Studies examining occupational exposures and cancer risk frequently report mixed findings; it is thus imperative for researchers to synthesize study results and identify any potential sources that explain such variabilities in study findings. However, when synthesizing study results using meta-analytic techniques, researchers often encounter a number of practical and methodological challenges. These challenges include (1) an incomparability of effect size measures due to large variations in research methodology; (2) a violation of the independence assumption for meta-analysis; (3) a violation of the normality assumption of effect size measures; and (4) a variation in cancer definitions across studies and changes in coding standards over time. In this paper, we first demonstrate these challenges by providing examples from a real dataset collected for a large meta-analysis project that synthesizes cancer mortality and incidence rates among firefighters. We summarize how each of these challenges has been handled in our meta-analysis. We conclude this paper by providing practical guidelines for handling challenges when synthesizing study findings from occupational cancer literature.

Impact of the universal health insurance benefits on cervical cancer mortality in Colombia.

BACKGROUND: Cervical cancer patients in Colombia have a lower likelihood of survival compared to breast cancer patients. In 1993, Colombia enrolled citizens in one of two health insurance regimes (contributory-private insurance and subsidized- public insurance) with fewer benefits in the subsidized regime. In 2008, the Constitutional Court required the Colombian government to unify services of both regimes by 2012. This study evaluated the impact of this insurance change on cervical cancer mortality before and after 2012. METHODS: We accessed 24,491 cervical cancer mortality records for 2006-2020 from the vital statistics of Colombia's National Administrative Department of Statistics (DANE). We calculated crude mortality rates by health insurance type and departments (geopolitical division). Changes by department were analyzed by rate differences between 2006 and 2012 and 2013-2020, for each health insurance type. We analyzed trends using join-point regressions by health insurance and the two time-periods. RESULTS: The contributory regime (private insurance) exhibited a significant decline in cervical cancer mortality from 2006 to 2012, characterized by a noteworthy average annual percentage change (AAPC) of -3.27% (P = 0.02; 95% CI [-5.81, -0.65]), followed by a marginal non-significant increase from 2013 to 2020 (AAPC 0.08%; P = 0.92; 95% CI [-1.63, 1.82]). In the subsidized regime (public insurance), there is a non-significant decrease in mortality between 2006 and 2012 (AAPC - 0.29%; P = 0.76; 95% CI [-2.17, 1.62]), followed by a significant increase from 2013 to 2020 (AAPC of 2.28%; P < 0.001; 95% CI [1.21, 3.36]). Examining departments from 2013 to 2020 versus 2006 to 2012, the subsidized regime showed fewer cervical cancer-related deaths in 5 out of 32 departments, while 6 departments had higher mortality. In 21 departments, mortality rates remained similar between both regimes. CONCLUSION: Improvement of health benefits of the subsidized regime did not show a positive impact on cervical cancer mortality in women enrolled in this health insurance scheme, possibly due to unresolved administrative and socioeconomic barriers that hinder access to quality cancer screening and treatment.

Epigenetic reprogramming of H3K4me3 in adipose-derived stem cells by HFS diet consumption leads to a disturbed transcriptomic profile in adipocytes.

Adipose tissue metabolism is actively involved in the regulation of energy balance. Adipose-derived stem cells (ASCs) play a critical role in maintaining adipose tissue function through their differentiation into mature adipocytes (Ad). This study aimed to investigate the impact of an obesogenic environment on the epigenetic landscape of ASCs and its impact on adipocyte differentiation and its metabolic consequences. Our results showed that ASCs from rats on a high-fat sucrose (HFS) diet displayed reduced adipogenic capacity, increased fat accumulation, and formed larger adipocytes than the control (C) group. Mitochondrial analysis revealed heightened activity in undifferentiated ASC-HFS but decreased respiratory and glycolytic capacity in mature adipocytes. The HFS diet significantly altered the H3K4me3 profile in ASCs on genes related to adipogenesis, mitochondrial function, inflammation, and immunomodulation. After differentiation, adipocytes retained H3K4me3 alterations, confirming the upregulation of genes associated with inflammatory and immunomodulatory pathways. RNA-seq confirmed the upregulation of genes associated with inflammatory and immunomodulatory pathways in adipocytes. Overall, the HFS diet induced significant epigenetic and transcriptomic changes in ASCs, impairing differentiation and causing dysfunctional adipocyte formation.NEW & NOTEWORTHY Obesity is associated with the development of chronic diseases like metabolic syndrome and type 2 diabetes, and adipose tissue plays a crucial role. In a rat model, our study reveals how an obesogenic environment primes adipocyte precursor cells, leading to epigenetic changes that affect inflammation, adipogenesis, and mitochondrial activity after differentiation. We highlight the importance of histone modifications, especially the trimethylation of histone H3 to lysine 4 (H3K4me3), showing its influence on adipocyte expression profiles.

[Impact of bariatric surgery on maternal-fetal outcomes during pregnancy compared to non-operated obese women]. / Impacto de la cirugía bariátrica en los resultados materno-fetales de la gestación en comparación con mujeres con obesidad no operadas.

Introduction: Objective: the aim of our study was to assess the effect of bariatric surgery on obstetric outcomes. Material and methods: a retrospective cohort study was conducted, including 54 pregnancies post-bariatric surgery and 219 pregnancies in non-operated obese women, from December 2018 to January 2023. Various maternal and obstetric characteristics were evaluated, ranging from baseline data to antepartum, intrapartum, postpartum, and neonatal outcomes. Results: bariatric surgery showed a significant 69 % reduction in the risk of gestational diabetes (GDM) (p = 0.045) and a 63.1 % reduction in cesarean sections (p = 0.014), but also a notable increase in the risk of miscarriage (3.5 times more, p = 0.046) and intrauterine growth restriction (35 times more, p = 0.009). Bariatric surgery was associated with a significant prolongation of postpartum hospital stay (7.5 times more, p = 0.001) and a decrease in the average weight of the newborn (213.71 g, p = 0.006). Conclusion: pregnancy after bariatric surgery presents benefits, such as a reduced risk of gestational diabetes (GDM) and cesarean section, but also presents challenges, such as an increased risk of miscarriage and intrauterine growth restriction (IUGR). These results highlight the importance of specialized obstetric care to optimize maternal-fetal outcomes in pregnant women with a history of bariatric surgery.

Introducción: Objetivo: el objetivo de nuestro estudio es evaluar el efecto de la cirugía bariátrica en los resultados obstétricos. Material y métodos: se realizó un estudio de cohortes retrospectivo que incluyó 47 gestaciones postcirugía bariátrica y 219 gestaciones en mujeres con obesidad no operadas, reclutadas en el Hospital Álvaro Cunqueiro de Vigo (Galicia, noroeste de España), en el periodo comprendido entre diciembre de 2018 y enero de 2023. Se evaluaron diversas características, tanto maternas como obstétricas, abarcando desde datos basales hasta los resultados anteparto, intraparto, posparto y neonatales. Resultados: la cirugía bariátrica mostró una significativa reducción del riesgo de diabetes gestacional (DMG) en un 69 % (p = 0,045) y del riesgo de cesáreas en un 63,1 % (p = 0,014), pero también un aumento notable del riesgo de aborto (3,5 veces más, p = 0,046) y del retraso del crecimiento intrauterino (35 veces más, p = 0,009). La cirugía bariátrica se asoció a una prolongación significativa de la estancia hospitalaria posparto (7,5 veces más, p = 0,001) y a una disminución del peso promedio del recién nacido (213,71 g, p = 0,006). Conclusión: la gestación postcirugía bariátrica presenta beneficios, como una reducción del riesgo de diabetes gestacional (DMG) y de cesárea, pero presenta desafíos, como un mayor riesgo de aborto y un retraso del crecimiento intrauterino (CIR). Estos resultados resaltan la importancia de una atención obstétrica especializada para optimizar los resultados materno-fetales en las gestantes con antecedentes de cirugía bariátrica.

Characterisation of RAET1E/ULBP4 exon 4 and 3' untranslated region genetic architecture reveals further diversity and allelic polymorphism.

NKG2D is a natural killer cell activating receptor recognising ligands on infected or tumorigenic cells, leading to their cytolysis. There are eight known genes encoding NKG2D ligands: MICA, MICB and ULBP1-6. MICA and MICB are highly polymorphic and well characterised, whilst ULBP ligands are less polymorphic and the functional implication of their diversity is not well understood. Using International HLA and Immunogenetics Workshop (IHIW) cell line DNA, we previously characterised alleles of the RAET1E gene (encoding ULBP4 proteins), including the 5' UTR promoter region and exons 1-3. We found 11 promoter haplotypes associating with alleles based on exons 1-3, revealing 19 alleles overall. The current study extends this analysis using 87 individual DNA samples from IHIW cell lines or cord blood to include RAET1E exon 4 and the 3' UTR, as polymorphism in these regions have not been previously investigated. We found two novel exon 4 polymorphisms encoding amino acid substitutions altering the transmembrane domain. An amino acid substitution at residue 233 was unique to the RAET1E*008 allele whereas the substitution at residue 237 was shared between groups of alleles. Additionally, four haplotypes were found based on 3' UTR sequences, which were unique to certain alleles or shared with allele groups based on exons 1-4 polymorphisms. Furthermore, putative microRNAs were identified that may interact with these polymorphic sites, repressing transcription and potentially affecting expression levels.

Distinct Prostate Cancer Survival Outcomes in Firefighters: A Population-Based Study.

Introduction: Survival outcomes for prostate cancer among specific occupational groups prone to regular medical check-ups vis-à-vis the general population have been understudied. For firefighters, a demographic subject to rigorous medical evaluations, possessing above-average medical expertise, and exposed to specific carcinogens of interest, prostate cancer survival in the US has never been studied. Methods: We conducted a retrospective study, utilizing data from the Florida Cancer Data System spanning 2004 to 2014, coupled with firefighter certification records from the Florida State Fire Marshal's Office. Our study cohort consisted of 1058 prostate cancer cases among firefighters as well as prostate cases for the Florida general population (n = 150,623). We compared cause-specific survival between the two using Cox regression models adjusted for demographics and clinical characteristics, including PSA levels, Gleason scores, and treatment modalities. Results: Firefighters demonstrated a higher five-year cause-specific survival rate (96.1%, 95% CI: 94.7-97.1%) than the general population (94.2%, 95%CI: 94.1-94.3%). Overall, firefighters' diagnoses were established at younger ages (median age 63 vs. 67 in the general population), exhibited a higher proportion of localized stage cancers (84.7% vs. 81.1%), and had a greater utilization of surgery (46.4% vs. 37.6%), a treatment modality with a high success rate but potential side effects. In multivariable analysis, firefighters displayed a survival advantage for localized stage (adjusted hazard ratio [aHR] = 0.53; 95%CI: 0.34-0.82). However, for regional or distant stages, firefighters aged 65 and above exhibited a higher risk of death (aHR = 1.84; 95% CI: 1.18-2.86) than the general population. Conclusion: Firefighters experience enhanced prostate cancer survival, primarily in cases diagnosed at localized stages, likely due to increased PSA testing. Nonetheless, for regional or distant stage, survival among older firefighters' lags behind that of the general population. Further investigations are warranted to unravel factors influencing the development of aggressive disease beyond PSA and Gleason scores in this population, as well as to assess the impact of a higher rate of surgical treatment on firefighters' quality of life.

Medical History and Preoperative Coagulation Profile as Predictors of Outcomes in Elective Spinal Surgery: A Meta-Analysis.

BACKGROUND: In patients with unremarkable medical history, comprehensive preoperative hemostasis screening in elective neurosurgery remains debated. Comprehensive medical history has shown to be noninferior to coagulation profile to evaluate surgical outcomes. This study aims to evaluate the predictiveness of preoperative coagulation screening and medical history for surgical outcomes. METHODS: Databases were searched until April 2023 for observational cohort studies that reported preoperative hemostasis screening and clinical history prior to elective neurosurgical procedures. Outcomes of interest included postoperative transfusion, mortality, and complications. Pooled relative risk ratios (RRs) were analyzed using random-effects models. RESULTS: Out of 604 studies, 3 cohort studies met our inclusion criteria, adding a patient population of 83,076. Prolonged partial thromboplastin time (PTT; RR=1.42, 95% confidence interval [CI] =1.14, 1.77, P=0.002), elevated international normalized ratio (INR; RR=2.01, 95% CI=1.14, 3.55, P=0.02), low platelet count (RR=1.58, 95% CI=1.34, 1.86, P<0.00001), and positive bleeding history (RR=2.14, 95% CI=1.16, 3.93, P=0.01) were associated with postoperative transfusion risk. High PTT (RR=2.42, 95% CI=1.24, 4.73, P=0.010), High INR (RR=8.15, 95% CI=5.97, 11.13; P<0.00001), low platelet count (RR=4.89, 95% CI=3.73, 6.41, P<0.00001), and bleeding history (RR=7.59, 95% CI=5.84, 9.86, P<0.00001) were predictive of mortality. Prolonged PTT (RR=1.53, 95% CI=1.25, 1.86, P=<0.0001), a high INR (RR=3.41, 95% CI=2.63, 4.42, P=< 0.00001), low platelets (RR=1.63, 95% CI=1.40, 1.90, P=<0.00001), and medical history (RR=2.15, 95% CI=1.71, 2.71, P=<0.00001) were predictive of complications. CONCLUSIONS: Medical history was a noninferior predictor to coagulation profile for postoperative transfusion, mortality, and complications. However, our findings are mostly representative of elective spinal procedures. Cost-effective alternatives should be explored to promote affordable patient care in patients with unremarkable history.

Post-stroke Cognition is Associated with Stroke Survivor Quality of Life and Caregiver Outcomes: A Systematic Review and Meta-analysis.

Disability arising from post-stroke cognitive impairment is a likely contributor to the poor quality of life (QoL) stroke survivors and their carers frequently experience, but this has not been summarily quantified. A systematic literature review and meta-analysis was completed examining the association between general and domain-specific post-stroke cognitive functioning and adult stroke survivor QoL, caregiver QoL, and caregiver burden. Five databases were systematically searched, and eligibility for inclusion, data extraction, and study quality were evaluated by two reviewers using a standardised protocol. Effects sizes (r) were estimated using a random effects model. Thirty-eight studies were identified, generating a sample of 7365 stroke survivors (median age 63.02 years, range 25-93) followed for 3 to 132 months post-stroke. Overall cognition (all domains combined) demonstrated a significant small to medium association with QoL, r = 0.23 (95% CI 0.18-0.28), p < 0.001. The cognitive domains of speed, attention, visuospatial, memory, and executive skills, but not language, also demonstrated a significant relationship with QoL. Regarding caregiver outcomes, 15 studies were identified resulting in a sample of 2421 caregivers (median age 58.12 years, range 18-82) followed for 3 to 84 months post-stroke. Stroke survivor overall cognitive ability again demonstrated a significant small to medium association with caregiver outcomes (QoL and burden combined), r = 0.17 (95% CI 0.10-0.24), p < 0.001. In conclusion, lower post-stroke cognitive performance is associated with significant reductions in stroke survivor QoL and poorer caregiver outcomes. Cognitive assessment is recommended early to identify those at risk and implement timely interventions to support both stroke survivors and their caregivers.

Indoor Temperature and Energy Insecurity: Implications for Prenatal Health Disparities in Extreme Heat Events.

BACKGROUND: Extreme heat events are a major public health concern and are only expected to increase in intensity and severity as climate change continues to accelerate. Pregnant people are physiologically more vulnerable to the effects of extreme heat, and exposure can induce harm on both the pregnant person and the fetus. OBJECTIVES: This commentary argues that there is a need for greater epidemiological research on indoor heat exposure and energy insecurity as potential drivers of maternal and child environmental health disparities. DISCUSSION: While there is substantial evidence linking ambient (outdoor) high temperature to pregnancy-related outcomes, there is a lack of epidemiological evidence to date on pregnant people's exposure to high indoor temperature and adverse maternal and/or child health outcomes. Energy insecurity is disproportionately experienced by people with low incomes and/or people of color, and indoor temperature may play a role in shaping socioeconomic and racial/ethnic disparities in maternal and child health in the United States. Further research is needed to understand the relationship between indoor heat exposure, energy insecurity, and pregnancy outcomes in both parents and children and to inform potential policies and practices to enhance resilience and reduce maternal/child health disparities. https://doi.org/10.1289/EHP13706.

Improving Sleep Using Mentored Behavioral and Environmental Restructuring (SLUMBER).

OBJECTIVES: To evaluate the impact of a mentoring program to encourage staff-delivered sleep-promoting strategies on sleep, function, depression, and anxiety among skilled nursing facility (SNF) residents. DESIGN: Modified stepped-wedge unit-level intervention. SETTING AND PARTICIPANTS: Seventy-two residents (mean age 75 ± 15 years; 61.5% female, 41% non-Hispanic white, 35% Black, 20% Hispanic, 3% Asian) of 2 New York City urban SNFs. METHODS: Expert mentors provided SNF staff webinars, in-person workshops, and weekly sleep pearls via text messaging. Resident data were collected at baseline, post-intervention (V1), and 3-month follow-up (V2), including wrist actigraphy, resident behavioral observations, Pittsburgh Sleep Quality Index (PSQI), Patient Health Questionnaire-9 (PHQ-9) depression scale, Brief Anxiety and Depression Scale (BADS), Brief Cognitive Assessment Tool (BCAT), and select Minimum Data Set 3.0 (MDS 3.0) measures. Linear mixed models were fit for continuous outcomes and mixed-effects logistic models for binary outcomes. Outcomes were modeled as a function of time. Planned contrasts compared baseline to V1 and V2. RESULTS: There was significant improvement in PSQI scores from baseline to V1 (P = .009), and from baseline to V2 (P = .008). Other significant changes between baseline and V1 included decreased depression (PHQ-9) (P = .028), increased daytime observed out of bed (P ≤ .001), and increased daytime observed being awake (P < .001). At V2 (vs baseline) being observed out of bed decreased (P < .001). Daytime sleeping by actigraphy increased from baseline to V1 (P = .004), but not V2. MDS 3.0 activities of daily living and pain showed improvements by the second quarter following implementation of SLUMBER (P's ≤ .034). There were no significant changes in BADS or BCAT between baseline and V1 or V2. CONCLUSIONS AND IMPLICATIONS: SNF residents had improvements in sleep quality and depression with intervention, but improvements were not sustained at 3-month follow-up. The COVID-19 pandemic led to premature study termination, so full impacts remain unknown.

Implementation Outcomes for the SLUMBER Sleep Improvement Program in Long-Term Care.

OBJECTIVES: To describe the implementation of a mentored staff-delivered sleep program in nursing facilities. DESIGN: Modified stepped-wedge unit-level intervention. SETTING AND PARTICIPANTS: This program was implemented in 2 New York City nursing facilities, with partial implementation (due to COVID-19) in a third facility. METHODS: Expert mentors provided staff webinars, in-person workshops, and weekly sleep pearls via text messaging. We used the integrated Promoting Action on Research Implementation in Health Services (i-PARiHS) framework as a post hoc approach to describe key elements of the SLUMBER implementation. We measured staff participation in unit-level procedures and noted their commentary during unit workshops. RESULTS: We completed SLUMBER within 5 units across 2 facilities and held 15 leadership meetings before and during program implementation. Sessions on each unit included 3 virtual webinar presentations and 4 in-person workshops for each nursing shift, held over a period of 3 to 4 months. Staff attendance averaged >3 sessions per individual staff member. Approximately 65% of staff present on each unit participated in any given session. Text messaging was useful for engagement, educational reinforcement, and encouraging attendance. We elevated staff as experts in the care of their residents as a strategy for staff engagement and behavior change and solicited challenging cases from staff during workshops to provide strategies to address resident behavior and encourage adoption when successful. CONCLUSIONS AND IMPLICATIONS: Engaging staff, leadership, residents, and family of nursing facilities in implementing a multicomponent sleep quality improvement program is feasible for improving nursing facilities' sleep environment. The program required gaining trust at multiple levels through presence and empathy, and reinforcement mechanisms (primarily text messages). To improve scalability, SLUMBER could evolve from an interdisciplinary investigator-based approach to internal coaches in a train-the-trainer model to effectively and sustainably implement this program to improve sleep quality for facility residents.

Impact of donor NKG2D and MICA gene polymorphism on clinical outcomes of adult and paediatric allogeneic cord blood transplantation for malignant diseases.

OBJECTIVES: NKG2D is an activating receptor expressed by natural killer (NK) and CD8+ T cells and activation intensity varies by NKG2D expression level or nature of its ligand. An NKG2D gene polymorphism determines high (HNK1) or low (LNK1) expression. MICA is the most polymorphic NKG2D ligand and stronger effector cell activation associates with methionine rather than valine at residue 129. We investigated correlation between cord blood (CB) NKG2D and MICA genotypes and haematopoietic stem cell (HSC) transplant outcome. METHODS: We retrospectively studied 267 CB HSC recipients (178 adult and 87 paediatric) who underwent transplant for malignant disease between 2007 and 2018, analysing CB graft DNA for NKG2D and MICA polymorphisms using Sanger sequencing. Multivariate analysis was used to correlate these results with transplant outcomes. RESULTS: In adult patients, LNK1 homozygous CB significantly improved 60-day neutrophil engraftment (hazard ratio (HR) 0.6; 95% confidence interval (CI) 0.4-0.9; p = .003). In paediatrics, HNK1 homozygous CB improved 60-day engraftment (HR 0.4; 95% CI 0.2-0.7; p = .003), as did MICA-129 methionine+ CB grafts (HR 1.7 95% CI 1.1-2.6; p = .02). CONCLUSION: CB NKG2D and MICA genotypes potentially improve CB HSC engraftment. However, results contrast between adult and paediatric recipients and may reflect transplant procedure disparities between cohorts.

Energy Insecurity Indicators Associated With Increased Odds Of Respiratory, Mental Health, And Cardiovascular Conditions.

Energy insecurity, defined as the inability to meet household energy needs, has multiple economic, physical, and coping dimensions that affect health. We conducted the first citywide representative survey of energy insecurity and health in a sample of 1,950 New York City residents in 2022. We compiled ten indicators that characterize energy insecurity as experienced in New York City housing settings and then examined associations between number and types of indicators and health conditions. Nearly 30 percent of residents experienced three or more indicators, with significantly higher levels among Black non-Latino/a and Latino/a residents compared with White non-Latino/a residents, renters compared with owners, recent immigrants compared with those living in the United States for longer, and those in households with children compared with those with no children. Residents with three or more indicators of energy insecurity had higher odds of respiratory, mental health, and cardiovascular conditions and electric medical device dependence than residents with no indicators. Our study demonstrates that broadening the understanding of energy insecurity with context-specific metrics can help guide interventions and policies that address disparities relevant to health and energy equity.

Whoever wants better healthcare simply pays more: citizens' perception about voluntary private health insurance in Colombia.

OBJECTIVES: To explore the perceptions that Colombians have about voluntary private health insurance plans (VPHI) in the health system to identify the tensions that exist between the public and private systems. METHODS: A qualitative case study approach with 46 semi structured interviews of patients, healthcare workers, healthcare administrators, decision-makers, and citizens. Interviews were recorded, transcribed, anonymized, digitally stored, and analyzed following grounded theory guidelines. RESULTS: We developed a paradigmatic matrix that explores how, in a context mediated by both the commodification of health and social stratification, perceptions about the failures in the public health system related to lack of timely care, extensive administrative procedures, and the search for privileged care led to positioning VPHI as a solution to these failures. The interviewees identified three consequences of using VPHI: first, the worsening of problems of timely access to care in the public system; second, higher costs for citizens translated into double payment for technologies and services to which they are entitled; third, the widening of inequity gaps in access to health services between people with similar needs but different payment capacities. CONCLUSIONS: These findings can help decision makers to understand citizens´ perceptions about the implications that VPHI may have in worsening equity gaps in the Colombian health system. It also shows, how VPHI is perceived as a double payment for services covered within social security plans and suggests that the perceived lack of timely access to care in the public systems and the fear that citizens have for themselves or their family members when using suboptimal healthcare are important drivers to purchase these private insurances.

RESUMEN: OBJETIVOS: Explorar las percepciones que tienen los colombianos sobre los planes de seguro de salud privados voluntarios (VPHI) en el sistema de salud para identificar las tensiones que existen entre los sistemas público y privado. MéTODOS: Un estudio cualitativo de caso con 46 entrevistas semiestructuradas a pacientes, trabajadores de la salud, administradores de salud, tomadores de decisiones y ciudadanos. Las entrevistas se grabaron, transcribieron y almacenaron de manera anónima. El análisis se hizo siguiendo conceptos de la teoría fundamentada. RESULTADOS: Desarrollamos una matriz paradigmática que explora cómo, en un contexto mediado tanto por la mercantilización de la salud como por la estratificación social, las percepciones sobre las fallas en el sistema de salud público relacionadas con la falta de atención oportuna, procedimientos administrativos extensos y la búsqueda de atención privilegiada llevaron a posicionar los VPHI como una solución a estas fallas. Los entrevistados identificaron tres consecuencias del uso de los VPHI: primero, el empeoramiento de los problemas de acceso oportuno a la atención en el sistema público; segundo, mayores costos para los ciudadanos, traducidos en un pago doble por tecnologías y servicios a los que tienen derecho; tercero, el aumento de las brechas de equidad en el acceso a los servicios de salud entre personas con necesidades similares pero diferentes capacidades de pago. CONCLUSIONES: Estos hallazgos pueden ayudar a los tomadores de decisiones a comprender las percepciones de los ciudadanos sobre las implicaciones que el VPHI puede tener en el empeoramiento de las brechas de equidad en el sistema de salud colombiano. También muestra cómo el VPHI se percibe como un pago doble por servicios cubiertos dentro de los planes de seguridad social y sugiere que la falta percibida de acceso oportuno a la atención en los sistemas públicos y el miedo que los ciudadanos tienen por sí mismos o por sus familiares cuando utilizan una atención sanitaria subóptima son factores importantes para adquirir estos seguros privados.