Implementation of a roadmap for the comprehensive diagnosis, follow-up, and research of childhood leukemias in vulnerable regions of Mexico: results from the PRONAII Strategy.

The main objective of the National Project for Research and Incidence of Childhood Leukemias is to reduce early mortality rates for these neoplasms in the vulnerable regions of Mexico. This project was conducted in the states of Oaxaca, Puebla, and Tlaxcala. A key strategy of the project is the implementation of an effective roadmap to ensure that leukemia patients are the target of maximum benefit of interdisciplinary collaboration between researchers, clinicians, surveyors, and laboratories. This strategy guarantees the comprehensive management of diagnosis and follow-up samples of pediatric patients with leukemia, centralizing, managing, and analyzing the information collected. Additionally, it allows for a precise diagnosis and monitoring of the disease through immunophenotype and measurable residual disease (MRD) studies, enhancing research and supporting informed clinical decisions for the first time in these regions through a population-based study. This initiative has significantly improved the diagnostic capacity of leukemia in girls, boys, and adolescents in the regions of Oaxaca, Puebla, and Tlaxcala, providing comprehensive, high-quality care with full coverage in the region. Likewise, it has strengthened collaboration between health institutions, researchers, and professionals in the sector, which contributes to reducing the impact of the disease on the community.

Sexually Transmitted Infections in the Emergency Department.

As the United States faces a worsening epidemic of sexually transmitted infections (STIs), emergency departments (EDs) play a critical role in identifying and treating these infections. The growing health inequities in the distribution and disproportionate impact of STIs add to the urgency of providing high-quality sexual health care through the ED. Changes in population health are reflected in the new Centers for Disease Control recommendations on screening, diagnostic testing, and treatment of STIs. This review covers common, as well as and less common or emerging STIs, and discusses the state-of-the-art guidance on testing paradigms, extragenital sampling, and antimicrobial treatment and prevention of STIs.

Connecting epigenetics and inflammation in vascular senescence: state of the art, biomarkers and senotherapeutics.

Vascular diseases pose major health challenges, and understanding their underlying molecular mechanisms is essential to advance therapeutic interventions. Cellular senescence, a hallmark of aging, is a cellular state characterized by cell-cycle arrest, a senescence-associated secretory phenotype macromolecular damage, and metabolic dysregulation. Vascular senescence has been demonstrated to play a key role in different vascular diseases, such as atherosclerosis, peripheral arterial disease, hypertension, stroke, diabetes, chronic venous disease, and venous ulcers. Even though cellular senescence was first described in 1961, significant gaps persist in comprehending the epigenetic mechanisms driving vascular senescence and its subsequent inflammatory response. Through a comprehensive analysis, we aim to elucidate these knowledge gaps by exploring the network of epigenetic alterations that contribute to vascular senescence. In addition, we describe the consequent inflammatory cascades triggered by these epigenetic modifications. Finally, we explore translational applications involving biomarkers of vascular senescence and the emerging field of senotherapy targeting this biological process.

Dorsal motor vagal neurons can elicit bradycardia and reduce anxiety-like behavior.

Cardiovagal neurons (CVNs) innervate cardiac ganglia through the vagus nerve to control cardiac function. Although the cardioinhibitory role of CVNs in nucleus ambiguus (CVNNA) is well established, the nature and functionality of CVNs in dorsal motor nucleus of the vagus (CVNDMV) is less clear. We therefore aimed to characterize CVNDMV anatomically, physiologically, and functionally. Optogenetically activating cholinergic DMV neurons resulted in robust bradycardia through peripheral muscarinic (parasympathetic) and nicotinic (ganglionic) acetylcholine receptors, but not beta-1-adrenergic (sympathetic) receptors. Retrograde tracing from the cardiac fat pad labeled CVNNA and CVNDMV through the vagus nerve. Using whole-cell patch-clamp, CVNDMV demonstrated greater hyperexcitability and spontaneous action potential firing ex vivo despite similar resting membrane potentials, compared to CVNNA. Chemogenetically activating DMV also caused significant bradycardia with a correlated reduction in anxiety-like behavior. Thus, DMV contains uniquely hyperexcitable CVNs and is capable of cardioinhibition and robust anxiolysis.

Efficient generation of human cerebral organoids directly from adherent cultures of pluripotent stem cells.

Human cerebral organoids (hCOs) offer the possibility of deepening the knowledge of human brain development, as well as the pathologies that affect it. The method developed here describes the efficient generation of hCOs by going directly from two-dimensional (2D) pluripotent stem cell (PSC) cultures to three-dimensional (3D) neuroepithelial tissue, avoiding dissociation and aggregation steps. This has been achieved by subjecting 2D cultures, from the beginning of the neural induction step, to dual-SMAD inhibition in combination with CHIR99021. This is a simple and reproducible protocol in which the hCOs generated develop properly presenting proliferative ventricular zones (VZs) formed by neural precursor and radial glia (RG) that differentiate to give rise to mature neurons and glial cells. The hCOs present additional cell types such as oligodendrocyte precursors, astrocytes, microglia-like cells, and endothelial-like cells. This new approach could help to overcome some of the existing limitations in the field of organoid biotechnology, facilitating its execution in any laboratory setting.

Human Trypanosoma cruzi infection in the Argentinean Chaco: risk factors and identification of households with infected children for treatment.

BACKGROUND: Chagas disease is a neglected tropical disease (NTD). Cost-effective strategies for large-scale implementation of diagnosis and etiological treatment are urgently needed to comply with NTD control goals. We determined the seroprevalence of Trypanosoma cruzi infection and associated risk factors in a well-defined rural population of Pampa del Indio municipality including creole and indigenous (Qom) households and developed two indices to identify houses harboring infected children. METHODS: We serodiagnosed and administered a questionnaire to 1337 residents (48.2% of the listed population) in two sections of the municipality (named Areas II and IV) 6-9 years after deploying sustained vector control interventions. Multiple logistic regression models were used to evaluate the relationship between human infection and a priori selected predictors. Two risk indices were constructed based on environmental and serostatus variables, and we used spatial analysis to test whether households harboring T. cruzi-seropositive children were randomly distributed. RESULTS: The global seroprevalence of T. cruzi infection was 24.8%. Human infection was positively and significantly associated with exposure time to triatomines, the household number of seropositive co-inhabitants, maternal seropositivity for T. cruzi, recent residence at the current house and the presence of suitable walls for triatomine colonization in the domicile. The pre-intervention mean annual force of infection (FOI) was 1.23 per 100 person-years. Creoles from Area IV exhibited the highest seroprevalence and FOI; Qom people from both areas displayed intermediate ones and creoles from Area II the lowest. Three hotspots of infected children were spatially associated with hotspots of triatomine abundance at baseline and persistent house infestation. No child born after vector control interventions was T. cruzi seropositive except for one putative transplacental case. Two simple risk indices (based on self-reported inhabiting an infested house and suitable walls for triatomines or maternal serostatus) identified 97.3-98.6% of the households with at least one T. cruzi-seropositive child. CONCLUSIONS: We showed strong heterogeneity in the seroprevalence of T. cruzi infection within and between ethnic groups inhabiting neighboring rural areas. Developed indices can be used for household risk stratification and to improve access of rural residents to serodiagnosis and treatment and may be easily transferred to primary healthcare personnel.

A newly identified ferritin L-subunit variant results in increased proteasomal subunit degradation, impaired complex assembly, and severe hypoferritinemia.

Ferritin is a hetero-oligomeric nanocage, composed of 24 subunits of two types, FTH1 and FTL. It protects the cell from excess reactive iron, by storing iron in its cavity. FTH1 is essential for the recruitment of iron into the ferritin nanocage and for cellular ferritin trafficking, whereas FTL contributes to nanocage stability and iron nucleation inside the cavity. Here we describe a female patient with a medical history of severe hypoferritinemia without anemia. Following inadequate heavy IV iron supplementation, the patient developed severe iron overload and musculoskeletal manifestations. However, her serum ferritin levels rose only to normal range. Genetic analyses revealed an undescribed homozygous variant of FTL (c.92A > G), which resulted in a Tyr31Cys substitution (FTLY31C ). Analysis of the FTL structure predicted that the Y31C mutation will reduce the variant's stability. Expression of the FTLY31C variant resulted in significantly lower cellular ferritin levels compared with the expression of wild-type FTL (FTLWT ). Proteasomal inhibition significantly increased the initial levels of FTLY31C , but could not protect FTLY31C subunits from successive degradation. Further, variant subunits successfully incorporated into hetero-polymeric nanocages in the presence of sufficient levels of FTH1. However, FTLY31C subunits poorly assembled into nanocages when FTH1 subunit levels were low. These results indicate an increased susceptibility of unassembled monomeric FTLY31C subunits to proteasomal degradation. The decreased cellular assembly of FTLY31C -rich nanocages may explain the low serum ferritin levels in this patient and emphasize the importance of a broader diagnostic approach of hypoferritinemia without anemia, before IV iron supplementation.

Correlates of Toddlers' Physical Activity Levels and Sedentary Behavior During Unstructured Outdoor Play in Early Childhood Education and Daycare Settings.

Despite recent research showing that early childhood education and daycare settings (ECEC) have an important role in promoting toddlers' physical activity (PA), crucial information gaps remain regarding toddlers' PA and sedentary behavior (SB) in these outdoor settings. We aimed in this study to: (a) analyze PA patterns and SB during unstructured outdoor play time in preschool and daycare environments using accelerometry and systematic observation; (b) provide concurrent accelerometry and observational data to help validate the Observational System for Recording Physical Activity in Children-Preschool Version (OSRAC-P); and (c) examine individual, social and environmental correlates of PA and SB during toddlers' unstructured outdoor play time. We found that: (a) toddlers displayed high amounts of PA with no sex, BMI, and/or age differences in PA and SB levels,; (b) environmental variables (e.g., fixed equipment and playground density) were not associated with PA levels or SB intensity; (c) the OSRAC-P was a reliable and valid means of observing and analyzing toddlers' PA patterns during unstructured outdoor play time; and (e) different social patterns between boys and girls did not impact PA levels or patterns. Combining different measurement methods permitted an improved understanding of unstructured outdoor play in preschool and daycare settings.

Cut-off points of neck and waist circumference as predictors of obstructive sleep apnea in the Colombian population: a comparison with polysomnography

ABSTRACT BACKGROUND: Neck circumference (NC) is a useful anthropometric measure for predicting obstructive sleep apnea (OSA). Ethnicity and sex also influence obesity phenotypes. NC cut-offs for defining OSA have not been established for the Latin American population. OBJECTIVES: To evaluate NC, waist circumference (WC), and body mass index (BMI) as predictors of OSA in the Colombian population and to determine optimal cut-off points. DESIGN AND SETTING: Diagnostic tests were conducted at the Javeriana University, Bogota. METHODS: Adults from three cities in Colombia were included. NC, WC, and BMI were measured, and a polysomnogram provided the reference standard. The discrimination capacity and best cut-off points for diagnosing OSA were calculated. RESULTS: 964 patients were included (57.7% men; median age, 58 years) and 43.4% had OSA. The discrimination capacity of NC was similar for men and women (area under curve, AUC 0.63 versus 0.66, P = 0.39) but better for women under 60 years old (AUC 0.69 versus 0.57, P < 0.05). WC had better discrimination capacity for women (AUC 0.69 versus 0.57, P < 0.001). There were no significant differences in BMI. Optimal NC cut-off points were 36.5 cm for women (sensitivity [S]: 71.7%, specificity [E]: 55.3%) and 41 cm for men (S: 56%, E: 62%); and for WC, 97 cm for women (S: 65%, E: 69%) and 99 cm for men (S: 53%, E: 58%). CONCLUSIONS: NC and WC have moderate discrimination capacities for diagnosing OSA. The cut-off values suggest differences between Latin- and North American as well as Asian populations.

Cut-off points of neck and waist circumference as predictors of obstructive sleep apnea in the Colombian population: a comparison with polysomnography.

BACKGROUND: Neck circumference (NC) is a useful anthropometric measure for predicting obstructive sleep apnea (OSA). Ethnicity and sex also influence obesity phenotypes. NC cut-offs for defining OSA have not been established for the Latin American population. OBJECTIVES: To evaluate NC, waist circumference (WC), and body mass index (BMI) as predictors of OSA in the Colombian population and to determine optimal cut-off points. DESIGN AND SETTING: Diagnostic tests were conducted at the Javeriana University, Bogota. METHODS: Adults from three cities in Colombia were included. NC, WC, and BMI were measured, and a polysomnogram provided the reference standard. The discrimination capacity and best cut-off points for diagnosing OSA were calculated. RESULTS: 964 patients were included (57.7% men; median age, 58 years) and 43.4% had OSA. The discrimination capacity of NC was similar for men and women (area under curve, AUC 0.63 versus 0.66, P = 0.39) but better for women under 60 years old (AUC 0.69 versus 0.57, P < 0.05). WC had better discrimination capacity for women (AUC 0.69 versus 0.57, P < 0.001). There were no significant differences in BMI. Optimal NC cut-off points were 36.5 cm for women (sensitivity [S]: 71.7%, specificity [E]: 55.3%) and 41 cm for men (S: 56%, E: 62%); and for WC, 97 cm for women (S: 65%, E: 69%) and 99 cm for men (S: 53%, E: 58%). CONCLUSIONS: NC and WC have moderate discrimination capacities for diagnosing OSA. The cut-off values suggest differences between Latin- and North American as well as Asian populations.

[Depression in health personnel associated with exposure to COVID-19]. / Depresión en personal de salud asociado a la exposición de la COVID-19.

Background: There are many working factors to do with depression. Objective: To determine the association between the exposure to COVID-19 and depression in physicians and nurses from the four hospitals at "Centro Médico Nacional Siglo XXI" (CMN SXXI) took part in: Oncology, Specialties, Cardiology and Pediatrics. Material and Methods: A cross-sectional study of 856 participants took place in January 2022, excluding workers, such as physicians and nurses from the CMN SXXI, disabled workers, staff with a union agreement, support staff and/or staff with less than one year of work labour. Through a self-administered questionnaire, the degree of occupational exposure to patients care with COVID-19, a history of COVID-19 infection, and the patient's health quiz were asked (PHQ-9). The analysis included simple frequency measurements, odds ratio (OR), Chi squared and multiple logistics regression with p ≤ 0.05. Results: The prevalence of depression in the medical and nursing staff at CMN SXXI was 32.2% (moderate to severe degree); In the multiple regression, an association was identified with not identifying support by the Institute (OR: 1.60, CI95%: 1.08-2.39, p = 0.02), high occupational exposure (OR: 8.35, CI95%: 3.02-23.09, p ˂ 0.0001), and more than 5 working days a week serving the COVID-19 patients (OR: 2.51, CI95%: 1.35-4.49, p = 0.004) and as a protective factor the fact that they have never had the COVID-19 (OR: 0.61, CI95%: 0.43-0.86, p = 0.01). Conclusions: The prevalence of depression was higher than expected being associated with the degree of occupational exposure in the COVID-19 patients´ assistance.

Introducción: existen factores laborales que influyen en la presencia de la depresión. Objetivo: determinar la asociación entre la exposición a la COVID-19 y la depresión en médicos y enfermeras de los cuatro hospitales del Centro Médico Nacional Siglo XXI (CMN SXXI): Oncología, Especialidades, Cardiología y Pediatría. Material y métodos: se realizó un estudio transversal, en enero del 2022, con 870 participantes pertenecientes a la población de médicos y enfermeras que laboraban en el CMN SXXI, se excluyó a los trabajadores que se encontraban con incapacidad, al personal temporal y/o con menos de un año de antigüedad laboral. A través de un cuestionario autoaplicable se interrogó sobre el grado de exposición laboral a la atención de pacientes con COVID-19, antecedentes de infección por la COVID-19 y el cuestionario de salud del paciente (PHQ-9). El análisis incluyo medidas de frecuencia simple y razón de Momios (RM), Chi cuadrada y regresión logística múltiple con p ≤ 0.05. Resultados: la prevalencia de depresión en personal médico y de enfermería del CMN SXXI fue del 32.2% (grado moderado a severo). En la regresión múltiple se encontró asociación con no identificar apoyo por parte del Instituto (RM: 1.60, IC95%: 1.08-2.39, p = 0.02), alta exposición laboral (RM: 8.35, IC95%: 3.02-23.09, p ˂ 0.0001) y más de 5 días laborados a la semana atendiendo pacientes con la COVID-19 (RM: 2.51, IC95%: 1.35-4.49, p = 0.004) y como factor protector el que nunca hayan enfermado de la COVID-19 (RM: 0.61, IC95%: 0.43-0.86, p = 0.01). Conclusiones: la prevalencia de depresión fue mayor a la esperada y se asoció con el grado de exposición laboral en la atención de pacientes con la COVID-19.

Dorsal Motor Vagal Neurons Can Elicit Bradycardia and Reduce Anxiety-Like Behavior.

Cardiovagal neurons (CVNs) innervate cardiac ganglia through the vagus nerve to control cardiac function. Although the cardioinhibitory role of CVNs in nucleus ambiguus (CVNNA) is well established, the nature and functionality of CVNs in dorsal motor nucleus of the vagus (CVNDMV) is less clear. We therefore aimed to characterize CVNDMV anatomically, physiologically, and functionally. Optogenetically activating cholinergic DMV neurons resulted in robust bradycardia through peripheral muscarinic (parasympathetic) and nicotinic (ganglionic) acetylcholine receptors, but not beta-1-adrenergic (sympathetic) receptors. Retrograde tracing from the cardiac fat pad labeled CVNNA and CVNDMV through the vagus nerve. Using whole cell patch clamp, CVNDMV demonstrated greater hyperexcitability and spontaneous action potential firing ex vivo despite similar resting membrane potentials, compared to CVNNA. Chemogenetically activating DMV also caused significant bradycardia with a correlated reduction in anxiety-like behavior. Thus, DMV contains uniquely hyperexcitable CVNs capable of cardioinhibition and robust anxiolysis.

[Occupational disease by COVID-19 in healthcare workers]. / Enfermedad de trabajo por COVID-19 en trabajadores de la salud.

Background: 1 out of 5 cases of COVID-19 in Mexico occurred in health workers, and the high risk of contagion in these workers caused absenteeism due to temporary leave from work (TLfW), as well as the need to establish qualification criteria for COVID-19 as an occupational disease (OD). There are no quantitative data about the labor population to whom this benefit has been provided, nor on the economic impact of not being qualified as OD. Objective: To estimate the prevalence of qualification of OD by COVID-19 in health workers from a tertiary care hospital (TCH). Material and methods: Descriptive, cross-sectional, and retrospective study carried out from March 2020 to April 2021, which included health workers from a TCH who had TLfW due to COVID-19 and were working 14 days before it was issued. Variables such as OD, days of TLfW, category, among others, were analyzed, as well as the economic income lost by remaining as a general disease (GD). It was used descriptive statistics. Results: A total of 654 health workers had TLfW due to COVID-19, with a prevalence of OD of 18.5%; 17 days of TLfW were granted on average. Nurses were classified with the high number of OD, and the category with the highest prevalence was cleaning and hygiene assistant (36%). 5310 days of TLfW were subsidized as GD, equivalent to $510,385.60 (Mexican pesos) that were not granted as an economic benefit to the population that did not have an OD qualification due to COVID-19. Conclusions: The prevalence of recognition of COVID-19 as OD was low; most of TLfWs were subsidized as GDs.

Introducción: 1 de cada 5 casos de COVID-19 en México se presentó en trabajadores de la salud (TS) y la alta tasa de contagio provocó ausentismo por incapacidad temporal para el trabajo (ITT), así como la necesidad de establecer criterios para calificar la COVID-19 como enfermedad de trabajo (ET). No hay datos cuantitativos sobre la población laboral a la que se le ha dado esta prestación, ni sobre el impacto económico de que no sea calificada como ET. Objetivo: estimar la prevalencia de calificación de ET por COVID-19 en trabajadores de un hospital de tercer nivel (HTC). Material y métodos: estudio descriptivo, transversal y retrospectivo llevado a cabo de marzo de 2020 a abril de 2021, que incluyó trabajadores de la salud de un HTC que generaron una ITT por COVID-19 y estaban laborando 14 días antes de su expedición. Se analizaron las variables ET, días de ITT, categoría e ingreso económico perdido al permanecer como enfermedad general (EG). Se usó estadística descriptiva. Resultados: 654 trabajadores generaron ITT por COVID-19, con una prevalencia de ET del 18.5%; se otorgaron en promedio 17 días de ITT. A enfermería se le calificó el mayor número de ET y auxiliar de limpieza e higiene tuvo mayor prevalencia de ET (36%). Se generaron 5310 días de ITT subsidiados como EG, equivalentes a $510,385.60 pesos, que no fueron otorgados como prestación económica a la población que no contó con calificación de ET por la COVID-19. Conclusiones: la prevalencia del reconocimiento de la COVID-19 como ET fue baja; más del 80% de las ITT permanecieron y fueron subsidiadas como EG.

Is Insulin Receptor Substrate4 (IRS4) a Platform Involved in the Activation of Several Oncogenes?

The IRS (insulin receptor substrate) family of scaffold proteins includes insulin receptor substrate-4 (IRS4), which is expressed only in a few cell lines, including human kidney, brain, liver, and thymus and some cell lines. Its N-terminus carries a phosphotyrosine-binding (PTB) domain and a pleckstrin homology domain (PH), which distinguishes it as a member of this family. In this paper, we collected data about the molecular mechanisms that explain the relevance of IRS4 in the development of cancer and identify IRS4 differences that distinguish it from IRS1 and IRS2. Search engines and different databases, such as PubMed, UniProt, ENSEMBL and SCANSITE 4.0, were used. We used the name of the protein that it encodes "(IRS-4 or IRS4)", or the combination of these terms with the word "(cancer)" or "(human)", for searches. Terms related to specific tumor pathologies ("breast", "ovary", "colon", "lung", "lymphoma", etc.) were also used. Despite the lack of knowledge on IRS4, it has been reported that some cancers and benign tumors are characterized by high levels of IRS-4 expression. Specifically, the role of IRS-4 in different types of digestive tract neoplasms, gynecological tumors, lung cancers, melanomas, hematological tumors, and other less common types of cancers has been shown. IRS4 differs from IRS1 and IRS2 in that can activate several oncogenes that regulate the PI3K/Akt cascade, such as BRK and FER, which are characterized by tyrosine kinase-like activity without regulation via extracellular ligands. In addition, IRS4 can activate the CRKL oncogene, which is an adapter protein that regulates the MAP kinase cascade. Knowledge of the role played by IRS4 in cancers at the molecular level, specifically as a platform for oncogenes, may enable the identification and validation of new therapeutic targets.

Amyloid Precursor Protein (APP) Regulates Gliogenesis and Neurogenesis of Human Neural Stem Cells by Several Signaling Pathways.

Numerous studies have focused on the pathophysiological role of amyloid precursor protein (APP) because the proteolytic processing of APP to ß-amyloid (Aß) peptide is a central event in Alzheimer's disease (AD). However, many authors consider that alterations in the physiological functions of APP are likely to play a key role in AD. Previous studies in our laboratory revealed that APP plays an important role in the differentiation of human neural stem cells (hNSCs), favoring glial differentiation (gliogenesis) and preventing their differentiation toward a neuronal phenotype (neurogenesis). In the present study, we have evaluated the effects of APP overexpression in hNSCs at a global gene level by a transcriptomic analysis using the massive RNA sequencing (RNA-seq) technology. Specifically, we have focused on differentially expressed genes that are related to neuronal and glial differentiation processes, as well as on groups of differentially expressed genes associated with different signaling pathways, in order to find a possible interaction between them and APP. Our data indicate a differential expression in genes related to Notch, Wnt, PI3K-AKT, and JAK-STAT signaling, among others. Knowledge of APP biological functions, as well as the possible signaling pathways that could be related to this protein, are essential to advance our understanding of AD.

The pivotal role of HbA1c assay to detect hemoglobinopathies: A 5-year observational retrospective study in the population of Southern France.

Background and Aims: Mobility and migration flows are growing from different countries of the world to European countries, including France and in particular the Mediterranean basin. This study aimed to investigate the presence of hemoglobin (Hb) variants in outpatients/inpatients of the Montpellier Hospital (France) in whom an HbA1c assay had been performed and for which the country of birth had been informed. Methods: This is a retrospective study from January 2016 to December 2020 based on all high-performance liquid chromatography (HPLC) chromatograms (Tosoh Bioscience HLC-723G8) having an alarm of suspected Hb variant during HbA1c measurement. The corresponding samples were systematically sent to the hematology laboratory for confirmation and identification of Hb variant. Patient's medical history, clinical and demographic data were extracted from each medical chart. Statistical analyses were performed using XLSTAT® software, version 2016.06.35661. Results: Three hundred sixty-three patients were confirmed with Hb variant exhibiting 17 different Hb profiles, highlighting the pivotal role of glycated hemoglobin (HbA1c) as a detection step. The prevalence of Hb variant in this southern French population was 0.71%, with the highest frequency for the beta-globin variants (n = 342/363; i.e., 94.2%), including the most common: S, C, E, and D in 200/342 (58.5%), 83/342 (24.3%), 29/342 (8.5%), and 11/342 (3.2%), respectively. Among patients with Hb variants, almost half (165/363; i.e., 45.4%) were born in the African continent with a predominance for Morocco (32/165; i.e., 19.3%) and Algeria (29/165; i.e., 17.5%). Conclusion: HbA1c assay is a useful tool to detect Hb variants. Hemoglobinopathies are a public health issue in the current French population which is a multiethnic society. Despite the monocentric nature of our study, we note a high frequency of Hb variants in the south of France, which underlines the importance of screening for Hb variants in the whole population.

Report from the extended HLA-DPA1 ~ promoter ~ HLA-DPB1 haplotype of the 18th international HLA and immunogenetics workshop.

The primary goal of the HLA-DPA1 ~ promoter ~ HLA-DPB1 haplotype component of the 18th IHIWS was to characterise the extended haplotypes within the HLA-DP region and survey the extent of genetic diversity in this region across human populations. In this report, we analysed single-nucleotide polymorphisms (SNPs) in 255 subjects from 6 different cohorts. The results from the HLA-DP haplotype component have validated findings from the initial pilot study. SNPs in this region were inherited in strong linkage, particularly HLA-DPA1, SNP-linked promoter haplotypes and motifs in exon 2 of HLA-DPB1. We reported 17 SNP-linked haplotypes in the promoter region. Together with HLA-DPA1 and HLA-DPB1 alleles, they formed 74 distinct extended HLA-DP haplotypes in 438 sequences. We also observed the presence of region-specific alleles and promoter haplotypes. Our approach involved phasing extended SNPs including promoter SNPs, HLA-DPA1 and HLA-DPB1 alleles, in a 22 kb region, GRCh38/hg38 (chr6:33,064,111-33,086,679), followed by clustering of these SNPs as one extended haplotype. This hierarchical clustering revealed four major clades, suggesting that haplotypes within each clade may have diverged from a common ancestral haplotype and undergone similar evolutionary processes. The correlation between HLA-DPA1 and the promoter region raises questions about the role of HLA-DPA1 antigen in the heterodimer. This finding requires validation on a larger sample size specifically designed for anthropological analysis. Nevertheless, the results from this study highlight the clinical potential of selecting better-matched donors for patients awaiting haematopoietic stem cell transplants from genetically overlapping groups that share common ancestral haplotypes.

A Multifaceted Educational Intervention in the Doctor-Patient Relationship for Medical Students to Incorporate Patient Agendas in Simulated Encounters.

From the beginning of their clinical training, medical students demonstrate difficulties when incorporating patient perspectives. This study aimed to assess if students, after an instructional programme, increased their sensitivity towards patients' needs and carried out bidirectional conversations. An observational study involving 109 medical students prior to their clerkships was designed. They attended a five-step training programme designed to encourage the use of communication skills (CSs) to obtain patients' perspectives. The course developed experiential and reflective educational strategies. The students improved their use of CSs throughout three sessions, and the overall score for these patient consultations went up in the opinions of both the external observer (EO) (5; 6.6; 7.5) and the simulated patients SPs (5.3; 6.6; 7.8). Most of the students (83.9%) considered that the CSs addressed were useful for clinical practice, particularly the interviews and the feedback received by the SP and the lecturer. The programme seems to help the students use CSs that facilitate a more bidirectional conversation in a simulated learning environment. It is feasible to integrate these skills into a broader training programme. More research is needed to assess whether the results are applicable to students in real settings and whether they influence additional outcomes.

Sleep Quality, Insomnia, and Perceived Stress among Colombian Healthcare Workers during the COVID-19 Pandemic.

Objective The COVID-19 pandemic has imposed a great burden on healthcare workers worldwide. The aim of the present study was to assess sleep quality, insomnia, and perceived stress in healthcare workers of a high complexity hospital located in Bogota, Colombia. Methods Cross-sectional study in which 1,155 healthcare workers at the Hospital Universitario San Ignacio in Bogotá, Colombia were included, between September and October 2020. Using an online-based survey, self-reported variables were assessed including demographics, Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), and 10 item Perceived Stress Scale (PSS-10). Associations between these variables were evaluated. Results Fifty percent of the respondents were between 31 and 45 years old, and 76 percent were women. Most of the surveyed were the nursing staff. Poor sleep quality, insomnia, and high perceived stress was found in 74.9, 12.4, and 13.2%, respectively. Poor sleep quality was predominantly found in females, in the 31 to 45 years old group and in married personnel. Also, poor sleep quality was found in relation to a moderate to high perceived risk of COVID-19 infection by the family of the workers surveyed. Discussion Poor sleep quality, moderate rates of insomnia, and perceived stress were found among healthcare workers committed to COVID-19 infected patients in Colombia. The identification of workers at greater risk and the implementation of targeted interventions are called upon as the results.

Biomarkers for the severity of periodontal disease in patients with obstructive sleep apnea:IL-1 ß, IL-6, IL-17A, and IL-33.

Objective: This study aims to compare the salivary and gingival crevicular fluid (GCF) concentrations of five cytokines: IL-1ß, IL-6, IL-17A, IL-33, and Tumor Necrosis Factor-alpha (TNF-α) in patients with OSA and their association with periodontitis. Methods: Samples of saliva and GCF were obtained from 84 patients classified into four groups according to periodontal and OSA diagnosis: G1(H) healthy patients, G2(P) periodontitis and non-OSA patients, G3(OSA) OSA and non-periodontitis patients, and G4(P-OSA) periodontitis and OSA patients. The cytokines in the samples were quantified using multiplexed bead immunoassays. Data were analyzed with the Kruskal-Wallis test, Dunn's multiple comparisons test, and the Spearman correlation test. Results: Stage III periodontitis was the highest in patients with severe OSA (69%; p=0.0142). Similar levels of IL-1ß and IL-6 in saliva were noted in G2(P) and G4(P-OSA). The IL-6, IL-17A and IL-33 levels were higher in the GCF of G4(P-OSA). There was a significant positive correlation between IL-33 in saliva and stage IV periodontitis in G4(P-OSA) (r s  = 0.531). The cytokine profile of the patients in G4(P-OSA) with Candida spp. had an increase of the cytokine's levels compared to patients who did not have the yeast. Conclusions: OSA may increase the risk of developing periodontitis due to increase of IL-1ß and IL-6 in saliva and IL-6, IL-17A and IL-33 in GCF that share the activation of the osteoclastogenesis. Those cytokines may be considered as biomarkers of OSA and periodontitis.