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.

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.

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.

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.

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.

The CHANGE (Climate Health ANalysis Grading Evaluation) tool for weight of evidence reviews on climate change and health research.

BACKGROUND: Climate change has been identified as one of the biggest threats to human health. Despite this claim, there are no standardized tools that assess the rigor of published literature for use in weight of evidence (WOE) reviews. Standardized assessment tools are essential for creating clear and comparable WOE reviews. As such, we developed a standardized tool for evaluating the quality of climate change and health studies focused on evaluating studies that quantify exposure-response relationships and studies that implement and/or evaluate adaptation interventions. METHODS: The authors explored systematic-review methodology to enhance transparency and increase efficiency in summarizing and synthesizing findings from studies on climate change and health research. The authors adapted and extended existing WOE methods to develop the CHANGE (Climate Health ANalysis Grading Evaluation) tool. The resulting assessment tool has been refined through application and subsequent team input. RESULTS: The CHANGE tool is a two-step standardized tool for systematic review of climate change and health studies of exposure-response relationships and adaptation intervention studies. Step one of the CHANGE tool aims to classify studies included in weight-of-evidence reviews and step two assesses the quality and presence of bias in the climate change and health studies. CONCLUSION: The application of the CHANGE tool in WOE reviews of climate change and health will lead to increased comparability, objectivity, and transparency within this research area.

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.

Early Estrogen Replacement Therapy Attenuates Cardiac Dysfunction Caused by Aging and Ovariectomy in Female Wistar Rats.

BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of women's mortality, linked to aging and reduced estrogen during menopause. Estrogen replacement therapy (ERT) is suggested for CVDs prevention. Yet, its timing initiation remains contentious. Thus, we aimed to evaluate the effect of early and late estrogen therapy on cardiac function and lipid metabolism in ovariectomized old female Wistar rats. METHODS: Fifty randomized female Wistar rats were included in 5 groups (n = 10, 18 months old): (1) Sham, (2) 10 weeks post ovariectomy (Ovx-10 w), (3) 10 weeks post Ovx + early estrogen replacement therapy (Ovx 10 w-early ERT), (4) 20 weeks post Ovx (Ovx-20 w) and (5) Ovx 20 w-late ERT. Three days (early ERT) or 10 weeks (late ERT) after surgery 17-ß estradiol was given (5 µg/kg/day), and 10 weeks after the start of ERT, we assessed cardiac function by echocardiography, electrocardiography, and cardiac catheterization. Estradiol, cholesterol, triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels were determined. Cardiac histology was performed with Masson's staining. RESULTS: Ovariectomy (Ovx) increases left ventricle internal systolic diameter (0.4 vs 0.3 cm, *p = 0.020) and decreases shortening fraction (40 vs 54 %, *p = 0.030) regardless of therapy. ERT prevents the increase in left ventricle mass after 10 weeks post-Ovx and the ejection fractionreduction after 20 weeks. Lower P wave amplitudes (18.8 vs 24.2 ms, *p = 0.013) were found in the Ovx-20 w group. A longer duration of the QRS complex after 20 weeks post-Ovx with and without ERT was found (32.5 and 32.1 vs 28.3 ms, *p = 0.003; *p = 0.007). Diastolic blood pressure was higher 20 weeks post-Ovx (86 vs 76 mmHg, *p = 0.047), regardless of ERT. The left ventricle (LV) -dP/dt was decreased in Ovx groups without ERT (-750 vs -1320 mmHg, *p = 0.034). An increase in LV collagen deposition was found in the Ovx 10 w group vs Sham (9.58 vs 4.54 %, *p = 0.028). Early ERT avoids the increase in body weight, cholesterol and LDL caused by Ovx. CONCLUSIONS: Ovariectomy causes time-dependent alterations in lipid metabolism, morphology, electrical activity, and heart contractile function. Early but not late ERT prevents some of these effects.

Sexual orientation and gender identity inequities in cervical cancer screening by race and ethnicity.

BACKGROUND: In the United States, inequities in preventive health behaviors such as cervical cancer screening have been documented. Sexual orientation, gender identity, and race/ethnicity all individually contribute to such disparities. However, little work has investigated their joint impact on screening behavior. METHODS: Using sampling weighted data from the 2016 and 2018 Behavioral Risk Factor Surveillance System, we assessed differences in two metrics via chi-square statistics: 1) lifetime uptake, and 2) up-to-date cervical cancer screening by sexual orientation and gender identity, within and across racial/ethnic classifications. RESULTS: Within all races, individuals who identify as members of sexual and gender minority (SGM) communities reported higher rates of never being screened (except for Black transgender men) than straight or cisgender individuals (p < 0.0001). [*START* Across all races, the Asian/Pacific Islander transgender population (32.4%; weighted n (w.n.) = 1,313) had the lowest proportion of lifetime screening, followed by the Asian/Pacific Islander gay/lesbian (53.0%, w.n. = 21,771), Hispanic transgender (58.7%; w.n. = 24,780), Asian/Pacific Islander bisexual (61.8%, w.n. = 54,524), and Hispanic gay/lesbian (69.6%, w.n. = 125,781) populations. *END*] Straight or cisgender Non-Hispanic White (w.n. = 40,664,476) individuals had the highest proportion of lifetime screening (97.7% and 97.5%, respectively). However, among individuals who had been screened at least once in their lifetime, identifying as SGM was not associated with a decreased proportion of up-to-date screening within or between races. CONCLUSIONS: Due to small sample sizes, especially among Asian/Pacific Islander and Hispanic populations, confidence intervals were wide. Heterogeneity in screening participation by SGM status within and across racial/ethnic groups were observed. IMPACT: These screening disparities reveal the need to disaggregate data to account for intersecting identities and for studies with larger sample sizes to increase estimate reliability.

Impact and Equity of New York City's Tobacco Retail Reduction Initiative.

INTRODUCTION: High levels of tobacco retailer density in communities is associated with a range of tobacco use behaviors and is a key structural driver of tobacco-related disparities. This study evaluates the impacts of New York City's (NYC) novel policy intervention to cap tobacco retail licenses on tobacco retailer density levels and neighborhood inequities in tobacco access. METHODS: Using geocoded tobacco retail licensing data from 2010 to 2022, Bayesian conditional autoregressive Poisson panel models estimated the association between policy implementation in 2018 and retailer density per 1,000 population, controlling for neighborhood-level sociodemographic factors. Data were analyzed in 2023. RESULTS: The number of tobacco retail licenses decreased from 9,304 in 2010 to 5,107 in 2022, with the rate of decline significantly accelerating post-policy (-14·2% versus -34·2%). Policy effects were stronger in districts with lower income and greater proportions of non-Hispanic Black residents. CONCLUSIONS: NYC's policy substantially reduced tobacco retailer density and appeared to close longstanding patterns of inequity in tobacco access, serving as a rare example of a tobacco control policy that may effectively reduce tobacco-related disparities. This emergent approach to restructure tobacco retail in communities may reach populations that have not benefitted from traditional tobacco control policies and should be considered by other localities.

Increased IL-12p70 and IL-8 Produced by Monocytes in Response to Streptococcus spp. and Actinomyces spp. Causals of Endodontic Primary Infections.

We sought to evaluate the effect of endodontic-causative microorganisms of primary infections on mononuclear cells such as CD14+, CD4+, CD8+, CD19+ and Tregs Foxp3+. Facultative anaerobic microorganisms were isolated from radicular conducts and peripheral blood samples, which were taken from patients with primary infections. Cellular cultures were performed with peripheral blood mononuclear cells (PBMC) with and without Actinomyces spp. and Streptococcus spp. during 48, 72, and 96 h of contact in culture (concentration 5 × 105 cells/well) in a round plate bound with 48 wells. Later, PBMC was collected for analysis by flow cytometry, with the monoclonal antibodies αCD14, αCD4, αCD8, αCD19 and αFoxp3, and acquired using an FACSCanto II cytometer. The supernatant of cellular cultures was analyzed for the quantification of inflammatory cytokines. Data analysis was performed in FlowJo v10.8.2 and FCAPArray software, and statistical analysis was performed using GraphPad v5.0. software. We observed an increase in the percentage of CD14+ cells in patients at different hours of cellular culture in the presence of both Actinomyces spp. and Streptococcus spp. microorganisms, compared to healthy controls. This study demonstrates the role played by the innate immune system in the pathogeny of endodontic primary infections, explaining the effects that generate the more common microorganisms in this oral pathology.

Chronic Bi-Maxillary Osteomyelitis Caused by Actinomycetes in a Patient with Severe COVID-19 / Osteomyelitis bi-maxilar crónica causada por Actinomycetes en un paciente con COVID-19 severo

Abstract Osteomyelitis is defined as the inflammation of the either medullary, cortical, or cancellous bone, including nerves and blood vessels, causing necrosis and bone sequestrum formation; this condition has become a rare pathology, and odontogenic infections are considered the most frequent causal factor. This case shows a patient with bi-maxillary osteomyelitis caused by Actinomyces spp, which was worsened for severe COVID-19 infection. Patient was submitted at surgery as, amplified total bilateral maxillectomy through the surgical technique Weber-Fergusson, and prolonged use of combination of antibiotics, achieved a good recovery. Two years later follow- up, the patient no show imaging or clinical evidence of the infection of osteomyelitis. The present case shows an interesting relationship between a rare infection and its association with COVID-19.

Resumen La osteomielitis se define como la inflamación del hueso medular, cortical o esponjoso, incluyendo nervios y vasos sanguíneos, causando necrosis y formación de secuestro óseo; esta condición es una patología rara, y las infecciones odontogénicas son consideradas como el factor causal más frecuente. En este caso, se muestra un paciente con osteomielitis bi-maxilar causada por Actinomyces spp, la cual empeoró por la infección de COVID-19 severo. El paciente fue sometido a una cirugía, maxilectomía bilateral total amplificada, a través de la técnica quirúrgica de Weber- Fergusson, y el uso prolongado de una combinación de antibióticos, logrando una buena recuperación. A los 2 años de seguimiento, el paciente no mostró evidencia clínica o imagenológica de la infección de osteomielitis. El presente caso muestra una interesante relación entre una infección rara y su asociación con COVID-19.

Timing Matters: Effects of Early and Late Estrogen Replacement Therapy on Glucose Metabolism and Vascular Reactivity in Ovariectomized Aged Wistar Rats.

Cardiovascular disease incidence increases after menopause due to the loss of estrogen cardioprotective effects. However, there are conflicting data regarding the timing of estrogen therapy (ERT) and its effect on vascular dysfunction associated with impaired glucose metabolism. The aim of this work was to evaluate the effect of early and late ERT on blood glucose/insulin balance and vascular reactivity in aged ovariectomized Wistar rats. Eighteen-month-old female Wistar rats were randomized as follows: (1) sham, (2) 10-week postovariectomy (10 w), (3) 10 w postovariectomy+early estradiol therapy (10 w-early E2), (4) 20-week postovariectomy (20 w), and (5) 20-week postovariectomy+late estradiol therapy (20 w-late E2). Early E2 was administered 3 days after ovariectomy and late therapy after 10 weeks, in both groups. 17ß-Estradiol (E2) was administered daily for 10 weeks (5 µg/kg/day). Concentration-response curves to angiotensin II, KCl, and acetylcholine (ACh) were performed. Heart rate (HR), diastolic and systolic blood pressure (DBP and SBP), glucose, insulin, HOMA-IR, and nitric oxide (NO) levels were determined. Higher glucose levels were found in all groups compared to the sham group, except the 20 w-late E2 group. Insulin was increased in all ovariectomized groups compared to sham. The HOMA-IR index showed insulin resistance in all ovariectomized groups, except for the 10 w-early E2 group. The 10 w-early E2 group increased NO levels vs. the 10 w group. After 10 w postovariectomy, the vascular response to KCl and Ach increases, despite early E2 administration. Early and late E2 treatment decreased vascular reactivity to Ang II. At 20-week postovariectomy, DBP increased, even with E2 administration, while SBP and HR remained unchanged. The effects of E2 therapy on blood glucose/insulin balance and vascular reactivity depend on the timing of therapy. Early ERT may provide some protective effects on insulin resistance and vascular function, whereas late ERT may not have the same benefits.

Pleoardoris graminearum, gen. et sp. nov., a new member of Pleosporales from North American Plains, its biogeography and effects on a foundation grass species.

Diverse fungi colonize plant roots worldwide and include species from many orders of the phylum Ascomycota. These fungi include taxa with dark septate hyphae that colonize grass roots and may modulate plant responses to stress. We describe a novel group of fungal isolates and evaluate their effects on the grass Bouteloua gracilis in vitro. We isolated fungi from roots of six native grasses from 24 sites spanning replicated latitudinal gradients in the south-central US grasslands and characterized isolates phylogenetically using a genome analysis. We analyzed 14 isolates representing a novel clade within the family Montagnulaceae (order Pleosporales), here typified as Pleoardoris graminearum, closely related to the genera Didymocrea and Bimuria. This novel species produces asexual, light brown pycnidium-like conidioma, hyaline hyphae, and chlamydospores when cultured on quinoa and kiwicha agar. To evaluate its effects on B. gracilis, seeds were inoculated with one of three isolates (DS304, DS334, and DS1613) and incubated at 25 C for 20 d. We also tested the effect of volatile organic compounds (VOCs) produced by the same isolates on B. gracilis root and stem lengths. Isolates had variable effects on plant growth. One isolate increased B. gracilis root length up to 34% compared with uninoculated controls. VOCs produced by two isolates increased root and stem lengths (P < 0.05) compared with controls. Internal transcribed spacer ITS2 metabarcode data revealed that P. graminearum is distributed across a wide range of sites in North America (22 of 24 sites sampled), and its relative abundance is influenced by host species identity and latitude. Host species identity and site were the most important factors determining P. graminearum relative abundance in drought experiments at the Extreme Drought in the Grasslands Experiment (EDGE) sites. Variable responses of B. gracilis to inoculation highlight the potential importance of nonmycorrhizal root-associated fungi on plant survival in arid ecosystems.

Lung cancer survival among Florida male firefighters.

Introduction: Lung cancer is a leading cause of cancer incidence and death in the United States. Although most firefighters are fit and do not smoke, they are exposed to many known carcinogens during and in the aftermath of firefighting activities. Comprehensive epidemiologic investigations on lung cancer survival for both career and volunteer firefighters have not been undertaken. Methods: Data from the Florida Cancer Data System (1981-2014) were linked with firefighter certification records from the Florida State Fire Marshal's Office to identify all patients of this occupational group; lung cancer cause-specific survival data were compared with other occupational groups using Cox regression models with occupation as the main effect. Adjusted hazard ratios (aHR) and 95% confidence intervals (95% CI) were calculated. Results: Out of 210,541 male lung cancer cases diagnosed in Florida (1981-2014), 761 were firefighters (604 career, 157 volunteer). Lung cancer death was similar between volunteer (75.2%) and career firefighters (74.0%) but lower than non-firefighters (80.0%). Survival at 5 years was higher among firefighters (29.7%; career: 30.3%; volunteer: 27.4%) than non-firefighters (23.8%). In a multivariable model, compared with non-firefighters, firefighters have significantly higher cause-specific survival (aHR = 0.84; 95% CI: 0.77-0.91; p < 0.001). However, there were no significant survival differences between career and volunteer firefighters (1.14; 0.93-1.39; p = 0.213). In a separate multivariable model with firefighters as the comparator, other broad occupational groups had significantly lower cause-specific survival [white collar: 1.11 (1.02-1.21); blue collar: 1.15 (1.05-1.25); service: 1.13 (1.03-1.25); others/unknown: 1.21 (1.12-1.32); all p-values < 0.02]. Conclusion: Lung cancer survival is significantly higher among firefighters compared with non-firefighters, but there is no significant difference between career and volunteer firefighters. Improved survival for firefighters might be due to a healthy worker effect, lower smoking prevalence relative to other worker groups, and possibly superior treatment adherence and compliance. Many firefighters are cross-trained as EMTs/paramedics and possess a level of medical knowledge that may favorably impact treatment engagement and better navigation of complex cancer care.

Disparities in preterm birth following the July 1995 Chicago heat wave.

PURPOSE: To evaluate if changes in preterm birth (PTB, <37 weeks of gestation) incidence differed between non-Hispanic (NH) Black and NH white births following the July 1995 Chicago heat wave-among the most severe U.S. heat waves since 1950. METHODS: We used an ecologic study design. We obtained birth data from January 1990-December 1996 from the National Vital Statistics File to calculate the mean monthly PTB incidence in Chicago's Cook County, Illinois. Births between July 1995 and February 1996 were potentially exposed to the heat wave in utero. We generated time series models for NH Black and NH white births, which incorporated synthetic controls of Cook County based on unexposed counties. We ran a secondary analysis considering socioeconomic status (SES). RESULTS: From 1990-1996, the mean monthly PTB incidence among NH Black births was 18.6% compared to 7.8% among NH white births. The mean monthly PTB incidence among NH Black births from August 1995-January 1996 was 16.7% higher than expected (three additional PTBs per 100 live births per month [95% confidence interval (CI): 1, 5]). A similar increase occurred among low-SES NH Black births. No increase appeared among NH white births. CONCLUSIONS: Severe heat waves may increase racial disparities in PTB incidence.