Association between early echocardiography screening of low systemic blood flow and intraventricular hemorrhage in preterm infants: a multicenter cohort study.

OBJECTIVE: To determine whether early echocardiography screening of low systemic blood flow reduces intraventricular hemorrhage in preterm infants. STUDY DESIGN: Prospective multicenter study in preterm infants below 33 weeks of gestational age at nine neonatal units. Five units performed early echocardiography screening for low systemic blood flow and guided clinical management (exposure group) and 4 units did not (control group). Our main outcome was ≥grade II intraventricular hemorrhage or death within the first 7 days of life. The main analysis used the inverse probability of treatment weighting. RESULTS: Three hundred and thirty-two preterm infants (131 in the exposure group and 201 in the control group) were included. Exposure to early echocardiography screening was associated with a significant reduction in ≥grade II intraventricular hemorrhage or early death [odds ratio 0.285 (95% CI: 0.133-0.611); p = 0.001]. CONCLUSIONS: Early echocardiography screening for low systemic blood flow may reduce the incidence of intraventricular hemorrhage in preterm infants.

Knowledge, attitudes and perceptions of Latin American healthcare workers relating to antibiotic stewardship and antibiotic use: a cross-sectional multi-country study.

BACKGROUND: The burden of antimicrobial resistance (AMR) in Latin America is high. Little is known about healthcare workers' (HCWs) knowledge, attitudes, and perceptions of antimicrobial stewardship (AS), AMR, and antibiotic use (AU) in the region. METHODS: HCWs from 42 hospitals from 5 Latin American countries were invited to take an electronic, voluntary, anonymous survey regarding knowledge, attitudes, and perceptions of AS, AMR, and AU between March-April 2023. FINDINGS: Overall, 996 HCWs completed the survey (52% physicians, 32% nurses, 11% pharmacists, 3% microbiologists, and 2% "other"). More than 90% of respondents indicated optimizing AU was a priority at their healthcare facility (HCF), 69% stated the importance of AS was communicated at their HCF, and 23% were unfamiliar with the term "antibiotic stewardship". Most (> 95%) respondents acknowledged that appropriate AU can reduce AMR; however, few thought AU (< 30%) or AMR (< 50%) were a problem in their HCF. Lack of access to antibiogram and to locally endorsed guidelines was reported by 51% and 34% of HCWs, respectively. Among prescribers, 53% did not consider non-physicians' opinions to make antibiotic-related decisions, 22% reported not receiving education on how to select antibiotics based on culture results and 60% stated patients and families influence their antibiotic decisions. CONCLUSIONS: Although HCWs perceived improving AU as a priority, they did not perceive AU or AMR as a problem in their HCF. AS opportunities include improved access to guidelines, access to AMR/AU data, teamwork, and education on AS for HCWs and patients and families.

Ansiedad y estrategias de afrontamiento en personas privadas de la libertad en Barranquilla, Colombia / Anxiety and coping strategies in persons deprived of liberty in Barranquilla, Colombia / Ansiedade e estratégias de enfrentamento em pessoas privadas de liberdade em Barranquilla, Colômbia

El presente estudio tuvo como propósito principal determinar la relación entre la ansiedad y las estrategias de afrontamiento empleadas por personas privadas de la libertad (PPL) en el EPMSC Establecimiento de Reclusión Especial Barranquilla-Cárcel del Bosque. Para ello se siguió una ruta de investigación cuantitativa, de diseño no experimental, transversal y de alcance correlacional. La muestra estuvo conformada por 98 PPL, en edades entre 19 y 73 años, a quienes se aplicaron los instrumentos Escala de Valoración de la Ansiedad de Hamilton y Escala de Estrategias de Afrontamiento de Coping Modificada. Los resultados señalan niveles moderados de ansiedad, siendo los PPL más jóvenes (19-27 años) los que presentan mayor ansiedad psíquica; las personas mayores de 50 años tienden más a buscar solución a los problemas. Se concluye que a mayores niveles de ansiedad mayor relación con la estrategia de afrontamiento reacción agresiva.

The main purpose of this study was to determine the relationship between anxiety and the coping strategies employed by persons deprived of liberty (PPL) in the EPMSC Establecimiento de Reclusión Especial Barranquilla-Cárcel del Bosque. For this purpose, a quantitative, non-experimental, cross-sectional and correlational research route was followed. The sample consisted of 98 PPL, aged between 19 and 73 years, who were administered the Hamilton Anxiety Rating Scale and the Modified Coping Strategies Scale of Coping Modified. The results indicate moderate levels of anxiety, with younger PPL (19-27 years old) showing higher levels of psychological anxiety; people over 50 years old tend more to seek solutions to problems. It is concluded that the higher the level of anxiety, the greater the relationship with the coping strategy aggressive reaction.

O principal objetivo deste estudo foi determinar a relação entre ansiedade e estratégias de enfrentamento usadas por pessoas privadas de liberdade (PPL) no EPMSC Establecimiento de Reclusión Especial Barranquilla-Cárcel del Bosque. Para isso, foi seguido um roteiro de pesquisa quantitativo, não experimental, transversal e correlacional. A amostra consistiu em 98 PPL, com idades entre 19 e 73 anos, que receberam a Escala de Avaliação de Ansiedade de Hamilton e a Escala de Estratégias de Enfrentamento Modificada de Enfrentamento Modificada. Os resultados indicam níveis moderados de ansiedade, sendo que as PPL mais jovens (19 a 27 anos) apresentam níveis mais altos de ansiedade psicológica; as pessoas com mais de 50 anos tendem a buscar mais soluções para os problemas. Conclui-se que quanto maior o nível de ansiedade, maior a relação com a estratégia de enfrentamento reação agressiva.

Molecular, biochemical, and sensorial characterization of cocoa (Theobroma cacao L.) beans: A methodological pathway for the identification of new regional materials with outstanding profiles.

Cocoa is an economically important product in Colombia. On-farm germplasm evaluations enable the selection of superior genotypes for propagation and distribution across the country. This study examined 12 cocoa samples from Antioquia along with five reference materials, employing 96 single nucleotide polymorphism (SNP) markers. Furthermore, these genetic findings were correlated with physical, chemical, and sensory attributes. Primary coordinate analysis revealed that the majority of samples were hybrids derived from five original germplasm pools, including Criollo, Amelonado, and three Upper Amazon Forastero cocoas. The integral profile of the 12 selected materials was classified into Modern Criollo (Rodriguez-Medina et al., 2019) [3], Forasteros (Rodriguez-Medina et al., 2019) [3], and Trinitarios (Borja Fajardo et al., 2022) [6]. Three key factors were identified to best account for the sample classification: type of variety, functional properties, and quality.

Advancing precision in histocompatibility and immunogenetics: a comprehensive review of the UCLA exchange program.

Precise typing of human leukocyte antigens (HLA) is crucial for clinical hematopoietic stem cell and solid organ transplantations, transfusion medicine, HLA-related disease association, and drug hypersensitivity analysis. The UCLA Cell Exchange program has played a vital role in providing educational and proficiency testing surveys to HLA laboratories worldwide for the past 5 decades. This article highlights the significant contribution of the UCLA Cell and DNA Exchange Programs in advancing HLA antibody testing, genotyping, crossmatches, and, more recently, virtual crossmatches. Additionally, we discuss future directions of the UCLA Cell Exchange program to support histocompatibility testing to adapt to the fast-evolving field of immunotherapy, tolerance and xenotransplantation.

Inflammation as a New Therapeutic Target among Older Patients with Ischemic Heart Disease.

Cardiovascular (CV) diseases remain a global health challenge, with ischemic heart disease (IHD) being the primary cause of both morbidity and mortality. Despite optimal pharmacological therapy, older patients with IHD exhibit an increased susceptibility to recurrent ischemic events, significantly impacting their prognosis. Inflammation is intricately linked with the aging process and plays a pivotal role in the evolution of atherosclerosis. Emerging anti-inflammatory therapies have shown promise in reducing ischemic events among high-risk populations. This review aims to explore the potential of targeted anti-inflammatory interventions in improving clinical outcomes and the quality of life for older patients with IHD.

How does arch form and interproximal contact size affect the 3D displacements and rotations of teeth: a finite element analysis.

OBJECTIVE: The objective of this study was to determine how arch form and interproximal contact size displace mandibular teeth subjected to an anterior component of force (ACF). METHODS: Nine finite element models (FEM) of the mandibular arch were developed using Ansys® v. 16.0 software. They were designed to evaluate the effects of three arch forms (triangular, oval, and square) and three contact sizes (point-to-point, 1 mm diameter, and 2 mm diameter). All nine models were subjected to an ACF of 53.8 N (5486 gm). Three-dimensional tooth rotations and displacements of the mandibular teeth were evaluated, from the right first molar to the left first molar. RESULTS: Arch form had a greater effect on tooth movements than contact size. Triangular arches and point-to-point contacts produced the greatest displacements and rotations of teeth. Oval arches with 2 mm wide interproximal contact points showed the greatest stability. The right first premolar showed the greatest displacements in all of the models. CONCLUSIONS: Arch form and contact size affect interproximal tooth stability. Teeth are least stable in narrow arches with point-to-point interproximal contacts, and most stable in wider arches with larger contacts.

Factors Associated with Longitudinal Changes in Mammographic Density in a Multiethnic Breast Screening Cohort of Postmenopausal Women.

Background: Breast density is an important risk factor for breast cancer and is known to be associated with characteristics such as age, race, and hormone levels; however, it is unclear what factors contribute to changes in breast density in postmenopausal women over time. Understanding factors associated with density changes may enable a better understanding of breast cancer risk and facilitate potential strategies for prevention. Methods: This study investigated potential associations between personal factors and changes in mammographic density in a cohort of 3,392 postmenopausal women with no personal history of breast cancer between 2011 and 2017. Self-reported information on demographics, breast and reproductive history, and lifestyle factors, including body mass index (BMI), alcohol intake, smoking, and physical activity, was collected by an electronic intake form, and breast imaging reporting and database system (BI-RADS) mammographic density scores were obtained from electronic medical records. Factors associated with a longitudinal increase or decrease in mammographic density were identified using Fisher's exact test and multivariate conditional logistic regression. Results: 7.9% of women exhibited a longitudinal decrease in mammographic density, 6.7% exhibited an increase, and 85.4% exhibited no change. Longitudinal changes in mammographic density were correlated with age, race/ethnicity, and age at menopause in the univariate analysis. In the multivariate analysis, Asian women were more likely to exhibit a longitudinal increase in mammographic density and less likely to exhibit a decrease compared to White women. On the other hand, obese women were less likely to exhibit an increase and more likely to exhibit a decrease compared to normal weight women. Women who underwent menopause at age 55 years or older were less likely to exhibit a decrease in mammographic density compared to women who underwent menopause at a younger age. Besides obesity, lifestyle factors (alcohol intake, smoking, and physical activity) were not associated with longitudinal changes in mammographic density. Conclusions: The associations we observed between Asian race/obesity and longitudinal changes in BI-RADS density in postmenopausal women are paradoxical in that breast cancer risk is lower in Asian women and higher in obese women. However, the association between later age at menopause and a decreased likelihood of decreasing in BI-RADS density over time is consistent with later age at menopause being a risk factor for breast cancer and suggests a potential relationship between greater cumulative lifetime estrogen exposure and relative stability in breast density after menopause. Our findings support the complexity of the relationships between breast density, BMI, hormone exposure, and breast cancer risk.

Deep Dive Into Gaps and Barriers to Implementation of Antimicrobial Stewardship Programs in Hospitals in Latin America.

BACKGROUND: Antimicrobial resistance has worsened in Latin America. There is an urgent need to understand the development of antimicrobial stewardship programs (ASPs) and the barriers to implementing effective ASPs in light of limited national action plans or policies to promote ASPs in the region. METHODS: We performed a descriptive mixed-methods study of ASPs in 5 Latin American countries in March-July 2022. An electronic questionnaire with an associated scoring system (hospital ASP self-assessment) was used, and ASP development was classified based on the scores (inadequate, 0-25; basic, 26-50; intermediate, 51-75; or advanced, 76-100). Interviews among healthcare workers (HCWs) involved in antimicrobial stewardship (AS) inquired about behavioral and organizational factors that influence AS activities. Interview data were coded into themes. Results from the ASP self-assessment and interviews were integrated to create an explanatory framework. RESULTS: Twenty hospitals completed the self-assessment, and 46 AS stakeholders from these hospitals were interviewed. ASP development was inadequate/basic in 35% of hospitals, intermediate in 50%, and advanced in 15%. For-profit hospitals had higher scores than not-for-profit hospitals. Interview data validated the self-assessment findings and provided further insight into ASP implementation challenges, which included limited formal hospital leadership support, inadequate staffing and tools to perform AS work more efficiently, limited awareness of AS principles by HCWs, and limited training opportunities. CONCLUSIONS: We identified several barriers to ASP development in Latin America, suggesting the need to create accurate business cases for ASPs to obtain the necessary funding for their effective implementation and sustainability.

Urinary glyphosate and AMPA levels in a cross-sectional study of postmenopausal women: Associations with organic eating behavior and dietary intake.

Animal and epidemiologic studies suggest that there may be adverse health effects from exposure to glyphosate, the most highly used pesticide in the world, and its metabolite aminomethylphosphonic acid (AMPA). Meanwhile, consumption of organic foods (presumably grown free of chemical pesticides) has increased in recent years. However, there have been limited biomonitoring studies assessing the levels of human glyphosate and AMPA exposure in the United States. We examined urinary levels of glyphosate and AMPA in the context of organic eating behavior in a cohort of healthy postmenopausal women residing in Southern California and evaluated associations with demographics, dietary intake, and other lifestyle factors. 338 women provided two first-morning urine samples and at least one paired 24-h dietary recall reporting the previous day's dietary intake. Urinary glyphosate and AMPA were measured using LC-MS/MS. Participants reported on demographic and lifestyle factors via questionnaires. Potential associations were examined between these factors and urinary glyphosate and AMPA concentrations. Glyphosate was detected in 89.9% of urine samples and AMPA in 67.2%. 37.9% of study participants reported often or always eating organic food, 30.2% sometimes, and 32.0% seldom or never. Frequency of organic food consumption was associated with several demographic and lifestyle factors. Frequent organic eaters had significantly lower urinary glyphosate and AMPA levels, but not after adjustment for covariates. Grain consumption was significantly associated with higher urinary glyphosate levels, even among women who reported often or always eating organic grains. Soy protein and alcohol consumption as well as high frequency of eating fast food were associated with higher urinary AMPA levels. In conclusion, in the largest study to date examining paired dietary recall data and measurements of first-void urinary glyphosate and AMPA, the vast majority of subjects sampled had detectable levels, and significant dietary sources in the American diet were identified.

Sex-Related Differences in Heart Failure Diagnosis.

PURPOSE OF REVIEW: The literature on the importance of sex in heart failure diagnosis is scarce. This review aims to summarize current knowledge on sex differences regarding the diagnosis of heart failure. RECENT FINDINGS: Comorbidities are frequent in patients with heart failure, and their prevalence differs between sexes; some differences in symptomatology and diagnostic imaging techniques were also found. Biomarkers also usually show differences between sexes but are not significant enough to establish sex-specific ranges. This article outlines current information related to sex differences in HF diagnosis. Research in this field remains to be done. Maintaining a high diagnostic suspicion, actively searching for the disease, and considering the sex is relevant for early diagnosis and better prognosis. In addition, more studies with equal representation are needed.

Infecciones periamigdalinas en el área de salud de León los años previos a la pandemia, durante la misma y posterior a ella. Estudio de un periodo de 6 años / Trend of peritonsillar infections in the León Health Area in the years before, during and after the pandemic. Study of a 6-year period

Introducción y objetivo: La COVID-19 ha tenido diversas consecuencias para el sistema sanitario de salud. Centrándonos en nuestro Servicio de Otorrinolaringología, hemos observado un descenso en la aparición de infecciones periamigdalinas (IPA). El objetivo de este estudio es evaluar aspectos epidemiológicos de las IPA a lo largo de un período de 6 años. Método: Estudio descriptivo retrospectivo y longitudinal con datos obtenidos del registro hospitalario informatizado de León durante un período de 6 años. Resultados: Un total de 327 pacientes fueron incluidos, prepandemia 201 (61.47%), en pandemia 64 (19.54%) y postpandemia 62 (18.96%), con una disminución de 48.58% en la incidencia de IPA. Discusión: Encontramos resultados similares a los analizados en otras series sobre la incidencia de los abscesos periamigdalinos durante la pandemia, sin embargo, tenemos una mayor estancia media hospitalaria en los ingresos por dicha patología. Conclusiones: La pandemia ha repercutido y cambiado la forma de atender ciertas patologías. En nuestro caso, en lo referente a los abscesos periamigdalinos observamos un claro descenso. (AU)

Introduction and objective: COVID-19 has had various consequences for the health care system. Focusing on our ENT Service, we have observed a decrease in the occurrence of peritonsillar infections (PTI). The aim of this study is to evaluate epidemiological aspects of PTIs over a 6-year period. Method: Retrospective and longitudinal descriptive study with data obtained from the computerized hospital registry of León over a 6-year period. Results: A total of 327 patients were included, pre-pandemic 201 (61.47%), pandemic 64 (19.54%) and post-pandemic 62 (18.96%), with a decrease of 48.58% in the incidence of IPA. Discussion: We found similar results to those analyzed in other series about the incidence of peritonsillar abscesses during the pandemic, however, we have a longer mean hospital stay in admissions for this pathology. Conclusions: The pandemic has affected and changed the way we look at certain conditions. In our case, when looking at peritonsillar abscesses we have observed a clear decrease. (AU)

How does arch form and interproximal contact size affect the 3D displacements and rotations of teeth: a finite element analysis

ABSTRACT Objective: The objective of this study was to determine how arch form and interproximal contact size displace mandibular teeth subjected to an anterior component of force (ACF). Methods: Nine finite element models (FEM) of the mandibular arch were developed using Ansys® v. 16.0 software. They were designed to evaluate the effects of three arch forms (triangular, oval, and square) and three contact sizes (point-to-point, 1 mm diameter, and 2 mm diameter). All nine models were subjected to an ACF of 53.8 N (5486 gm). Three-dimensional tooth rotations and displacements of the mandibular teeth were evaluated, from the right first molar to the left first molar. Results: Arch form had a greater effect on tooth movements than contact size. Triangular arches and point-to-point contacts produced the greatest displacements and rotations of teeth. Oval arches with 2 mm wide interproximal contact points showed the greatest stability. The right first premolar showed the greatest displacements in all of the models. Conclusions: Arch form and contact size affect interproximal tooth stability. Teeth are least stable in narrow arches with point-to-point interproximal contacts, and most stable in wider arches with larger contacts.

RESUMO Objetivo: O objetivo deste estudo foi determinar como o formato da arcada e o tamanho do contato interproximal deslocam os dentes inferiores submetidos a um componente anterior de força (CAF). Métodos: Nove modelos de elementos finitos (MEF) da arcada inferior foram desenvolvidos utilizando o software Ansys® v. 16.0. Eles foram projetados para avaliar os efeitos de três formatos de arcada (triangular, oval e quadrado) e três tamanhos de contato interproximal (ponto a ponto, 1 mm de diâmetro e 2 mm de diâmetro). Todos os nove modelos foram submetidos a um CAF de 53,8 N (5486 gm). Foram avaliados tridimensionalmente as rotações dentárias e os deslocamentos dos dentes inferiores, do primeiro molar direito ao primeiro molar esquerdo. Resultados: A forma da arcada teve um efeito maior no movimento dos dentes do que o tamanho do contato interproximal. Arcadas triangulares e contatos ponto a ponto produziram os maiores deslocamentos e rotações dos dentes. Arcadas ovais com pontos de contato interproximal de 2 mm de largura apresentaram maior estabilidade. O primeiro pré-molar direito apresentou os maiores deslocamentos em todos os modelos. Conclusões: O formato da arcada e o tamanho do contato interproximal afetam a estabilidade dos dentes. Os dentes foram menos estáveis nas arcadas estreitas com contatos interproximais ponto a ponto, e mais estáveis nas arcadas mais largas com contatos maiores.

Asociación del uso de ivermectina en la mortalidad de pacientes con la COVID-19 / Association of Ivermectin use on mortality in patients with COVID-19

RESUMEN Introducción: La ivermectina ha sido utilizada para prevenir y tratar pacientes con la COVID-19, sin embargo, investigaciones han demostrado que su eficacia no justifica el uso. Objetivo: Determinar la asociación del uso de ivermectina, mortalidad y otros 3 indicadores en pacientes con la COVID-19. Métodos: Estudio observacional de cohorte retrospectiva. Se revisaron las historias clínicas que estuvieron hospitalizados entre abril y octubre de 2020, quienes además del tratamiento estándar (oxigenoterapia, corticoide y enoxaparina), recibieron tratamiento con ivermectina por neumonía grave o crítica por la COVID-19. Se midieron 4 variables resultado: mortalidad, indicación de pase a la unidad de cuidados intensivos, días de hospitalización y tiempo de requerimiento de oxigenoterapia a alto flujo. Resultados: El 42 % (126) de los pacientes falleció y el 52 % (159) tuvo indicación de pase a la unidad de cuidados intensivos. En el análisis multivariado, quienes tomaron una mayor dosis tuvieron mayor indicación de pase a cuidados intensivos (RRa: 1,10; IC 95 %: 1,01-1,20; valor p= 0,035), días de hospitalización (coeficiente: 5,07; IC 95 %: 2,15-11,92; valor p< 0,001) y tiempo de requerimiento de oxigenoterapia con alto flujo (coeficiente: 3,33; IC 95 %: 1,56-7,09; valor p= 0,002). Conclusión: Los pacientes que recibieron ivermectina tuvieron mayor probabilidad de indicación de pase a la unidad de cuidados intensivos, mayor tiempo de hospitalización y mayor tiempo de requerimiento de oxígeno a alto flujo, sin hallar relación con la mortalidad de los pacientes hospitalizados por la COVID-19. La administración de ivermectina antes o durante la hospitalización no tuvo beneficios.

ABSTRACT Introduction: Ivermectin has been used to prevent and treat COVID-19 patients, however, research has shown that its efficacy does not justify its use. Objective: To determine the association between the use of Ivermectin, mortality and 3 other indicators in patients with COVID-19. Methods: Observational retrospective cohort study. We reviewed the medical records of patients who were hospitalized between April and October 2020, who in addition to standard treatment (oxygen therapy, corticosteroid and enoxaparin), received treatment with Ivermectin for severe or critical COVID-19 pneumonia. Four outcome variables were measured: mortality, indication for transfer to the Intensive Care Unit days of hospitalization and time required for high-flow oxygen therapy. Results: Of patients, 42 % (126) died and 52 % (159) had indication for transfer to the Intensive Care Unit. In the multivariate analysis those who took a higher dose had a greater indication for transfer to Intensive Care Unit (RRa: 1.10; IC 95 %: 1.01-1.20; p-value= 0.035), days of hospitalization (coefficient: 5,07; IC 95 %: 2.15-11.92; p-value< 0.001) and time requiring high-flow oxygen therapy (coefficient: 3.33; IC 95 %: 1.56-7.09; p-value= 0.002). Conclusion: Patients who received Ivermectin were more likely to be referred to the Intensive Care Unit, had a longer hospital stay, and required more time on high-flow oxygen, without finding a relationship with mortality in patients hospitalized for SARS-CoV-2. The administration of Ivermectin before or during hospitalization had no benefit.

Neuronal F-Box protein FBXO41 regulates synaptic transmission and hippocampal network maturation.

FBXO41 is a neuron-specific E3 ligase subunit implicated in epileptic encephalopathies. Fbxo41 null mutant (KO) mice show behavioral deficits and early lethality. Here, we report that loss of FBXO41 causes defects in synaptic transmission and brain development. Cultured Fbxo41 KO neurons had normal morphology and showed no signs of degeneration. Single-cell electrophysiology showed a lower synaptic vesicle release probability in excitatory neurons. Inhibitory neurons exhibited reduced synaptophysin expression, a smaller readily releasable pool, and decreased charge transfer during repetitive stimulation. In Fbxo41 KO hippocampal slices at postnatal day 6, the dentate gyrus was smaller with fewer radial-glial-like cells and immature neurons. In addition, neuronal migration was delayed. Two-photon calcium imaging showed a delayed increase in network activity and synchronicity. Together, our findings point toward a role for FBXO41 in synaptic transmission and postnatal brain development, before behavioral deficits are detected in Fbxo41 KO mice.

Association of Glyphosate Exposure with Blood DNA Methylation in a Cross-Sectional Study of Postmenopausal Women.

BACKGROUND: Glyphosate is the most commonly used herbicide in the world and is purported to have a variety of health effects, including endocrine disruption and an elevated risk of several types of cancer. Blood DNA methylation has been shown to be associated with many other environmental exposures, but to our knowledge, no studies to date have examined the association between blood DNA methylation and glyphosate exposure. OBJECTIVE: We conducted an epigenome-wide association study to identify DNA methylation loci associated with urinary glyphosate and its metabolite aminomethylphosphonic acid (AMPA) levels. Secondary goals were to determine the association of epigenetic age acceleration with glyphosate and AMPA and develop blood DNA methylation indices to predict urinary glyphosate and AMPA levels. METHODS: For 392 postmenopausal women, white blood cell DNA methylation was measured using the Illumina Infinium MethylationEPIC BeadChip array. Glyphosate and AMPA were measured in two urine samples per participant using liquid chromatography-tandem mass spectrometry. Methylation differences at the probe and regional level associated with glyphosate and AMPA levels were assessed using a resampling-based approach. Probes and regions that had an false discovery rate q<0.1 in ≥90% of 1,000 subsamples of the study population were considered differentially methylated. Differentially methylated sites from the probe-specific analysis were combined into a methylation index. Epigenetic age acceleration from three epigenetic clocks and an epigenetic measure of pace of aging were examined for associations with glyphosate and AMPA. RESULTS: We identified 24 CpG sites whose methylation level was associated with urinary glyphosate concentration and two associated with AMPA. Four regions, within the promoters of the MSH4, KCNA6, ABAT, and NDUFAF2/ERCC8 genes, were associated with glyphosate levels, along with an association between ESR1 promoter hypomethylation and AMPA. The methylation index accurately predicted glyphosate levels in an internal validation cohort. AMPA, but not glyphosate, was associated with greater epigenetic age acceleration. DISCUSSION: Glyphosate and AMPA exposure were associated with DNA methylation differences that could promote the development of cancer and other diseases. Further studies are warranted to replicate our results, determine the functional impact of glyphosate- and AMPA-associated differential DNA methylation, and further explore whether DNA methylation could serve as a biomarker of glyphosate exposure. https://doi.org/10.1289/EHP10174.

Outcomes from the medication assisted treatment pilot program for adults with opioid use disorders in rural Colorado.

BACKGROUND: As Colorado ranked among the top nationally in non-medical use of opioids, a pilot medication for opioid use disorder (MOUD) program was developed to increase the number of NPs and PAs providing MOUD in order to bring this evidence- based treatment to 2 counties showing disproportionally high opioid overdose deaths. Over the first 18 months, the MOUD Pilot Program led to 15 new health care providers receiving MOUD waiver training and 1005 patients receiving MOUD from the 3 participating organizations. Here we evaluate patient centered clinical and functional outcomes of the pilot MOUD program implemented in 2 rural counties severely affected by the opioid crisis. METHODS: Under state-funded law (Colorado Senate Bill 17-074), three rural agencies submitted de-identified patient-level data at baseline (N = 1005) and after 6 months of treatment (N = 190, 25%) between December 2017 and January 2020. The Addiction Severity Index, PhQ9 and GAD-7 with McNemar-Bowker, and Wilcoxon Signed Rank tests analysis were used to measure patient outcomes across after participation in the program. . RESULTS: Patients in treatment reported using less heroin (52.1% vs 20.4%), opioids (22.3% vs 11.0%), and alcohol (28.6% vs 13.1%, all P < 0.01). Patients reported improved health (53.4% vs. 68.2%, P = 0.04), less frequency of disability (8.69 vs. 6.51, P = 0.02), symptoms (29.8% vs 21.3%), pain (67.5% to 53.6), worry (45.3% vs 62.3%), anxiety (49.7% vs 23.2%), depression (54.1% vs 23.3%, all P < 0.02) after treatment. CONCLUSIONS: This study shows decreased substance use, improved physical and mental health, and reduced symptoms after 6 months of MOUD. Although more research on retention and long-term effects is needed, data shows improved health outcomes after 6 months of MOUD. Lessons learned from implementing this pilot program informed program expansion into other rural areas in need to address some of Colorado' major public health crises.

Association of mammographic density with blood DNA methylation.

BACKGROUND: Altered DNA methylation may be an intermediate phenotype between breast cancer risk factors and disease. Mammographic density is a strong risk factor for breast cancer. However, no studies to date have identified an epigenetic signature of mammographic density. We performed an epigenome-wide association study of mammographic density. METHODS: White blood cell DNA methylation was measured for 385 postmenopausal women using the Illumina Infinium MethylationEPIC BeadChip array. Differential methylation was assessed using genome-wide, probe-level, and regional analyses. We implemented a resampling-based approach to improve the stability of our findings. RESULTS: On average, women with elevated mammographic density exhibited DNA hypermethylation within CpG islands and gene promoters compared to women with lower mammographic density. We identified 250 CpG sites for which DNA methylation was significantly associated with mammographic density. The top sites were located within genes associated with cancer, including HDLBP, TGFB2, CCT4, and PAX8, and were more likely to be located in regulatory regions of the genome. We also identified differential DNA methylation in 37 regions, including within the promoters of PAX8 and PF4, a gene involved in the regulation of angiogenesis. Overall, our results paint a picture of epigenetic dysregulation associated with mammographic density. CONCLUSION: Mammographic density is associated with differential DNA methylation throughout the genome, including within genes associated with cancer. Our results suggest the potential involvement of several genes in the biological mechanisms behind differences in breast density between women. Further studies are warranted to explore these potential mechanisms and potential links to breast cancer risk.

Tale of a Black Heart!

Alkaptonuria is a rare condition of inborn error of metabolism. Association with aortic stenosis has been described; however, diagnosis at the time of valve replacement is infrequent. Recognition of this condition has potential management implications as the durability of prosthetic valves in such cases is unknown. We describe a case report that depicts these unique aspects.

Vascular dysfunction in HFpEF: Potential role in the development, maintenance, and progression of the disease.

Heart failure with preserved ejection fraction (HFpEF) is a complex, heterogeneous disease characterized by autonomic imbalance, cardiac remodeling, and diastolic dysfunction. One feature that has recently been linked to the pathology is the presence of macrovascular and microvascular dysfunction. Indeed, vascular dysfunction directly affects the functionality of cardiomyocytes, leading to decreased dilatation capacity and increased cell rigidity, which are the outcomes of the progressive decline in myocardial function. The presence of an inflammatory condition in HFpEF produced by an increase in proinflammatory molecules and activation of immune cells (i.e., chronic low-grade inflammation) has been proposed to play a pivotal role in vascular remodeling and endothelial cell death, which may ultimately lead to increased arterial elastance, decreased myocardium perfusion, and decreased oxygen supply to the tissue. Despite this, the precise mechanism linking low-grade inflammation to vascular alterations in the setting of HFpEF is not completely known. However, the enhanced sympathetic vasomotor tone in HFpEF, which may result from inflammatory activation of the sympathetic nervous system, could contribute to orchestrate vascular dysfunction in the setting of HFpEF due to the exquisite sympathetic innervation of both the macro and microvasculature. Accordingly, the present brief review aims to discuss the main mechanisms that may be involved in the macro- and microvascular function impairment in HFpEF and the potential role of the sympathetic nervous system in vascular dysfunction.