Epigenetics dysfunction in morbid obesity with or without obstructive sleep apnoea: the EPIMOOSA study.

BACKGROUND: Obstructive sleep apnoea (OSA) and morbid obesity (MO), defined by a body mass index ≥35 kg/m2, are two closely related conditions. Recent studies suggest that circulating microRNA (miRNA) plays a potential role in the physiopathology of both conditions. To date, circulating miRNA expression has been studied separately in both conditions, but never jointly. The primary treatment of OSA is continuous positive airway pressure (CPAP), whereas bariatric surgery (BS) is the treatment of choice for MO. We have thus initiated the Epigenetics modification in Morbid Obesity and Obstructive Sleep Apnoea (EPIMOOSA) study (ClinicalTrials.gov identifier: NCT03995836). METHODS/DESIGN: EPIMOOSA is a prospective non-interventional cohort study aiming to recruit 45 MO patients who are candidates for BS. Three groups will be formed: MO without OSA, MO with OSA without CPAP and MO with OSA and CPAP. All of them will be followed up in 4 visits: baseline, 6 months prior to BS and 3, 6 and 12 months post-BS. At baseline, OSA status will be assessed by home sleep polygraphy (HSP), and CPAP will be adopted according to national guidelines. A specific standardized questionnaire (including medical conditions and AOS-related symptoms) and anthropometrical examination will be performed at each visit. Blood samples will be obtained at each visit for immediate standard biochemistry, haematology and inflammatory cytokines. For bio-banking, serum, plasma, and circulating exosomes will also be obtained. Twenty-four hours of blood pressure and electrocardiogram (ECG) Holter monitoring will be performed at all visits. A new HSP will be performed at the last visit. Finally, the three groups will be sex- and age- matched with participants in the EPIOSA study, an ongoing study aimed at understanding epigenetic changes in non-obese OSA patients. DISCUSSION: EPIMOOSA will evaluate changes in circulating miRNA in MO with or without OSA for the first time. In addition, EPIMOOSA will be able to elucidate the influence of OSA in MO patients and how specific and combined treatments alter miRNA expression.

Sensitivity of a sequential model based on a questionnaire (STOP-Bang vs Dixon) and nocturnal pulse oximetry for screening obstructive sleep apnea in patients with morbid obesity candidates for bariatric surgery. / Sensibilidad de un modelo secuencial basado en cuestionario (STOP-Bang vs. Dixon) y pulsioximetría nocturna para el screening de apnea obstructiva del sueño en pacientes obesos mórbidos candidatos a cirugía bariátrica.

INTRODUCTION: Obstructive sleep apnea (OSA) has a high incidence in patients with morbid obesity who are candidates for bariatric surgery (BS). Adequate screening would decrease the number of respiratory polygraphies (RPs). OBJECTIVE: To analyze the value of a sequential model consisting of a questionnaire (modified Dixon [DXM] vs STOP-Bang) and nocturnal pulse oximetry in patients who were candidates for BS. METHODS: A prospective study was conducted from July 1, 2014 to July 1, 2015 on candidates for BS, excluding those who have already undergone RP. VARIABLES: questionnaires (Epworth, STOP-Bang, and DXM), anthropometric measurements, RP, and blood and gas tests. The sample was divided into patients with no or mild OSA (no OSA) and those with moderate to severe OSA (AHI>15). RESULTS: A total of 70 patients were analyzed, 46 (65.7%) of them females. Moderate to severe OSA was diagnosed in 26 (37.1%) patients. STOP-Bang and DXM were compared using ROC curves, and greater area under the curve (AUC) was found for the latter (0.873 [0.74 -0.930] vs 0.781 [0.673-0.888]). STOP-Bang had greater sensitivity, 100%, as compared to 73.1% for DXM. ODI3% showed greater diagnostic yield (AUC=0.982 [0.970-1]). Use of the sequential model with STOP-Bang>3, DXM>5, and DXM>3 would have avoided 41 (58.5%), 50 (71.4%), and 41 (58.5%) RPs and 0, 7 (10%), and 0 false negatives, respectively. CONCLUSION: Use of a sequential model based on the STOP-Bang and nocturnal pulse oximetry is a useful tool for screening OSA in patients with morbid obesity candidates for BS, decreasing the number of RPs.

Interaction of apolipoprotein E gene polymorphisms on miscarriage risk in black and white American women.

OBJECTIVE: To evaluate whether [1] apolipoprotein E (APOE) polymorphisms can differentially regulate miscarriage risk and [2] whether this genotype effect could also be modulated by the race within populations. DESIGN: Data were derived from the Coronary Artery Risk Development in Young Adults (CARDIA), a longitudinal study with black and white participants from four U.S. SETTING: Not applicable. PATIENT(S): Women without miscarriages (controls) and women who miscarried at least once (cases). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): A group of women (n = 1,372) successfully followed for 25 years and with their APOE alleles identified were analyzed for miscarriage risk throughout their reproductive life. Additionally, a larger longitudinal analysis encompassing all the participants who had their APOE characterized (n = 2,140) was also performed for the association between APOE and miscarriage risk. RESULT(S): In white women followed up for 25 years, the odds ratio for miscarriage associated with APOE*2 allele presence was 1.61 (95% confidence interval, 1.04-2.50) compared with APOE*33 carriers. This was a race-dependent phenomenon as no associations between APOE alleles and miscarriage was observed in black women. Likewise, Cox regression analysis showed that cumulative miscarriage risk in white women was 37.2% in the APOE*2 carriers compared with 27.8% and 24.8% in APOE*33 and APOE*4 carriers, respectively. With APOE*33 as the reference, the age-adjusted hazard ratio associated with carrying the APOE*2 allele was 1.47 (95 confidence interval, 1.06-2.05). CONCLUSION(S): This variable miscarriage risk, produced by an interaction between genotype and race, may reconcile, at least partially, the conflicting reports of the association of APOE and miscarriage risk.

Influencia del error diagnóstico en el pronóstico de la hemorragia subaracnoidea aneurismática en uruguay: analisis de una serie de 149 pacientes en un período de tiempo prepandemia y durante la pandemia SARS-Cov2 / Influence of diagnostic error on the prognosis of aneurysmal subarachnoid hemorrhage in Uruguay: analysis of a series of 149 patients in a pre-pandemic period and during the SARS-Cov2 pandemic

Introducción:La hemorragia subaracnoidea espontánea (HSA) presenta aproximadamente el 5% de todos los ACV, siendo una patología de alto impacto en la sociedad por su elevada morbi-mortalidad. La clínica de presentación es variada, lo cual lleva múltiples veces a dificultades en el diagnóstico. El objetivo de este trabajo es analizar el error diagnóstico que existe en esta patología y evaluar si el mismo se vio modificado por la interposición de la Emergencia Sanitaria declarada en el país por la pandemia del SARS-Cov2. Materiales y Métodos: es un estudio prospectivo y multicéntrico, incluyendo a todos los pacientes que presentaron HSA en el Uruguay entre el 1 de noviembre del 2019 y el 31 de julio de 2020. Se analizaron acuerdo con 3 períodos: 1) pre-pandemia, 2) cuarentena general, y 3) nueva normalidad. Se incluyeron todos los pacientes mayores de 18 años que consultaron y se les diagnosticó una HSA espontánea aneurismática. Se definió́ error diagnóstico a la imposibilidad de reconocer esta patología en la consulta médica inicial otorgándole el alta. El análisis se procesó utilizando el software SPSS versión 22. La investigación fue aprobada por todos los Comité de Ética de los diferentes centros que participaron del estudio. Resultados: de un total de 149 pacientes, la edad media fue de 57,23 años, con mayor frecuencia en el sexo femenino. Se constató error diagnóstico en 38 pacientes (25,5%), con mayor porcentaje durante la cuarentena general. El retraso en el diagnóstico por problemas asistenciales fue de un 2,6%. Se evidenció un 22,8% de complicaciones por el tratamiento indicado, y un 71,1% por la HSA, con una mortalidad global del 51,7%. Conclusiones: en el presente trabajo se observó un error diagnóstico elevado, evidenciando una relación directa y significativa con la cefalea y la HSA leve (HyH 1 y 2) como formas de presentación. Hubo un porcentaje mayor de HSA graves en comparación a la literatura, con una relación directa y significativa entre la presencia de vasoespasmo y la mortalidad con el error diagnóstico. También es claro que la crisis sanitaria determinó que ese error diagnóstico aumentara durante los primeros meses de la pandemia en Uruguay.

Introduction: Spontaneous subarachnoid hemorrhage (SAH) represents approximately 5% of all strokes, being a pathology of high impact in society, due to its high morbidity and mortality. The clinical presentation is varied, which leads many times to difficulties in diagnosis. The objective of this work is to analyze the diagnostic error that exists in this pathology, and to assess whether it was modified by the introduction of the Health Emergency declared in the country by the SARS-Cov2 pandemic. Materials and Methods: it is a prospective and multicenter study, including all patients who presented SAH in Uruguay between November 1, 2019 and July 31, 2020. They were analyzed according to 3 periods: 1) pre-pandemic, 2) general quarantine, and 3) new normality. All patients over 18 years of age who consulted and were diagnosed with spontaneous aneurysmal SAH were included. Diagnostic error was defined as the inability to recognize this pathology in the initial medical consultation and discharge. The analysis was processed using SPSS version 22 software. The research was approved by all the Ethics Committees of the different centers that participated in the study. Results: of a total of 149 patients, the mean age was 57.23 years, more frequently in the female sex. Diagnostic error was found in 38 patients (25.5%), with a higher percentage during general quarantine. The delay in diagnosis due to healthcare problems was 2.6%. There were 22.8% complications due to the indicated treatment, and 71.1% due to SAH, with an overall mortality of 51.7%. Conclusions: in the present work, a high diagnostic error was observed, showing a significant direct relationship with headache and mild SAH (HyH 1 and 2) as forms of presentation. There was a higher percentage of severe SAH compared to the literature, with a direct and significant relationship between the presence of vasospasm and mortality with diagnostic error. It is also clear that the health crisis determined that this diagnostic error increased during the first months of the pandemic in Uruguay

Effects of adipocyte-secreted factors on decidualized endometrial cells: modulation of endometrial receptivity in vitro.

Obesity is defined as an excessive accumulation of adipose tissue that may lead to health complications. Mounting evidence indicates that obesity has a negative impact on fertility. Yet, the link between adipose tissue biology and infertility remains unclear. We aimed to investigate the communication between the adipose tissue and the reproductive system and the importance of this cross talk for the development of a receptive endometrium. To that end, we generated an in vitro model with endometrial and adipocyte cell lines. Sexual hormones, progesterone and estradiol, were used to decidualize endometrial cells and sensitize adipocytes. Decidualization produced a simultaneous increase of adipokine receptors in endometrial cells paralleling changes in their receptivity status. Furthermore, sensitization of 3T3-L1 adipocytes increased mRNA levels of leptin and resistin and decreased the expression of adiponectin and chemerin levels. This was accompanied by increased isoproterenol-induced lipolysis and reduced insulin-stimulated glucose uptake. Lastly, conditioned culture medium of those sensitized adipocytes was used to feed endometrial cells. This treatment resulted in (i) upregulation of genes previously identified as positive regulators of endometrial receptivity, such as leukemia inhibitory factor and glutathione peroxidase 3, and (ii) downregulation of interleukin-15 and mucin1, both genes negatively related with endometrial receptivity. Our results indicate that the endocrine communication between adipose tissue and the reproductive system is bidirectional and stress the importance of the adipose tissue to modulate the reproductive fitness.

Memory clinic experience under a social security health system in Costa Rica.

Dementia and mild cognitive impairment (MCI) are an increasingly prevalent clinical entity in our field, showing an increasing incidence with age. OBJECTIVE: The purpose of this study was to identify the main types of dementia and MCI treated in a memory disorders unit in Costa Rica. METHODS: A consecutive and standardized register of patients diagnosed with dementia and MCI at the memory disorders unit of the National Geriatrics and Gerontology Hospital (NGGH) was analyzed. RESULTS: Dementia was diagnosed in 63.5% of the 3572 cases, whereas 10.6% met criteria for MCI. The most frequent type of dementia was Alzheimer's disease (47.1%), followed by vascular pathology (28.9%), mixed forms (17.2%) and other types (6.8%). In MCI, 69.5% were of amnestic multiple domain type and 14.3% were non-amnestic multiple domain, while 41.3% were of vascular and 35.8% of neurodegenerative etiology. Mean age was 79.6±6.7 years and 64.7% were women in dementia cases whereas mean age was 76.4±6.9 years and 62.1% were women in MCI. Mean years of schooling was 4.95±4.09 years and 6.87±4.71, while mean time between onset of symptoms and clinical diagnosis was 3.2±2.6 years and 2.67±2.69 years, in dementia and MCI, respectively. CONCLUSION: The determination of the main types of dementia and MCI in Costa Rica and their main features has allowed the registration of comprehensive, hitherto unavailable information that will be useful for the management and strategic planning of public health care.

Demência e transtorno cognitivo leve (CCL) é uma entidade clínica cada vez mais prevalente, mostrando uma incidência crescente com a idade. OBJETIVO: O objetivo deste estudo foi o de identificar os principais tipos de demência e CCL tratados em uma unidade de transtornos da memória de Costa Rica. MÉTODOS: Um registo consecutivo e padronizado de pacientes com diagnóstico de demência e CCL na unidade de transtorno de memória do Hospital Geral de Geriatria e Gerontologia. RESULTADOS: Demência foi diagnosticada em 63,5% dos 3.572 casos, enquanto 10,6% tiveram diagnóstico de CCL. O tipo mais frequente de demência foi a doença de Alzheimer (47,1%), seguido de doença vascular (28,9%), formas mistas (17,2%) e outros tipos (6,8%). No CCL, 69,5% eram de tipo amnéstico de múltiplos domínios e 14,3% eram não-amnéstcios de múltiplos domínios, enquanto 41,3% eram de etiologia vascular e 35,8% de etiologia neurodegenerativa. A média de idade foi de 79,6±6,7 anos e 64,7% eram mulheres em casos de demência ao passo que a média de idade foi de 76,4±6,9 anos e 62,1% eram mulheres nos casos de CCL. A média de anos de estudo foi de 4,95±4,09 anos e 6,87±4,71, o tempo entre o início dos sintomas eo diagnóstico clínico médio foi de 3,2±2,6 anos e 2,67±2,69 anos em demência e CCL, respectivamente. CONCLUSÃO: A determinação dos principais tipos de demência e CCL na Costa Rica e as suas principais características permitiu o registro de informação abundante que era desconhecida e que será útil para a gestão e planejamento estratégico da saúde pública.

Sensibilidad de un modelo secuencial basado en cuestionario (STOP-Bang vs. Dixon) y pulsioximetría nocturna para el screening de apnea obstructiva del sueño en pacientes obesos mórbidos candidatos a cirugía bariátrica / Sensitivity of a sequential model based on a questionnaire (STOP-Bang vs Dixon) and nocturnal pulse oximetry for screening obstructive sleep apnea in patients with morbid obesity candidates for bariatric surgery

INTRODUCCIÓN: La apnea obstructiva del sueño (AOS) tiene una elevada incidencia en obesos mórbidos candidatos a cirugía bariátrica (CB). Un screening adecuado reduciría el número de poligrafías (PR). OBJETIVO: Analizar la utilidad de un modelo secuencial con un cuestionario (Dixon modificado [DXM] vs. STOP-Bang) y pulsioximetría nocturna en pacientes candidatos a CB. MÉTODOS: Estudio prospectivo, desde el 1 de julio de 2014 hasta el 1 de julio de 2015. Se incluyeron candidatos a CB, excluyéndose aquellos que ya se habían sometido a una PR. VARIABLES: cuestionarios (Epworth, STOP-Bang y DXM), medidas antropométricas, PR y analítica de sangre y gases. Se dividió la muestra entre los que no tenían AOS o era leve (No AOS) y los que tuvieron una AOS moderada-grave (IAH>15). RESULTADOS: Se analizaron 70 pacientes, de los cuales 46 (65,7%) eran mujeres. Se diagnosticaron 26 (37,1%) de AOS moderada-grave. Comparamos STOP-Bang y DXM mediante curvas ROC con una mayor área bajo la curva (AUC) para este último (0,873 [0,74-0,930] vs. 0,781 [0,673-0,888]). La sensibilidad fue superior para el STOP-Bang con un 100% vs. 73,1% de DXM. El IDO3% presentó mayor rentabilidad diagnóstica AUC=0,982 (0,970-1). La aplicación del modelo secuencial con STOP-Bang>3, DXM>5 y DXM>3 hubiese evitado 41 (58,5%), 50 (71,4%) y 41 (58,5%) PR y 0, 7 (10%) y 0 falsos negativos, respectivamente. CONCLUSIÓN: La aplicación de un modelo secuencial basado en el STOP-Bang y pulsioximetría nocturna es una herramienta útil para el screening de AOS en obesos mórbidos candidatos a CB, reduciendo el número de PR

INTRODUCTION: Obstructive sleep apnea (OSA) has a high incidence in patients with morbid obesity who are candidates for bariatric surgery (BS). Adequate screening would decrease the number of respiratory polygraphies (RPs). OBJECTIVE: To analyze the value of a sequential model consisting of a questionnaire (modified Dixon [DXM] vs STOP-Bang) and nocturnal pulse oximetry in patients who were candidates for BS. METHODS: A prospective study was conducted from July 1, 2014 to July 1, 2015 on candidates for BS, excluding those who have already undergone RP. VARIABLES: questionnaires (Epworth, STOP-Bang, and DXM), anthropometric measurements, RP, and blood and gas tests. The sample was divided into patients with no or mild OSA (no OSA) and those with moderate to severe OSA (AHI>15). RESULTS: A total of 70 patients were analyzed, 46 (65.7%) of them females. Moderate to severe OSA was diagnosed in 26 (37.1%) patients. STOP-Bang and DXM were compared using ROC curves, and greater area under the curve (AUC) was found for the latter (0.873 [0.74 -0.930] vs 0.781 [0.673-0.888]). STOP-Bang had greater sensitivity, 100%, as compared to 73.1% for DXM. ODI3% showed greater diagnostic yield (AUC=0.982 [0.970-1]). Use of the sequential model with STOP-Bang>3, DXM>5, and DXM>3 would have avoided 41 (58.5%), 50 (71.4%), and 41 (58.5%) RPs and 0, 7 (10%), and 0 false negatives, respectively. CONCLUSION: Use of a sequential model based on the STOP-Bang and nocturnal pulse oximetry is a useful tool for screening OSA in patients with morbid obesity candidates for BS, decreasing the number of RPs

Effects of adipocyte-secreted factors on decidualized endometrial cells: modulation of endometrial receptivity in vitro

Obesity is defined as an excessive accumulation of adipose tissue that may lead to health complications. Mounting evidence indicates that obesity has a negative impact on fertility. Yet, the link between adipose tissue biology and infertility remains unclear. We aimed to investigate the communication between the adipose tissue and the reproductive system and the importance of this cross talk for the development of a receptive endometrium. To that end, we generated an in vitro model with endometrial and adipocyte cell lines. Sexual hormones, progesterone and estradiol, were used to decidualize endometrial cells and sensitize adipocytes. Decidualization produced a simultaneous increase of adipokine receptors in endometrial cells paralleling changes in their receptivity status. Furthermore, sensitization of 3T3-L1 adipocytes increased mRNA levels of leptin and resistin and decreased the expression of adiponectin and chemerin levels. This was accompanied by increased isoproterenol-induced lipolysis and reduced insulin-stimulated glucose uptake. Lastly, conditioned culture medium of those sensitized adipocytes was used to feed endometrial cells. This treatment resulted in (i) upregulation of genes previously identified as positive regulators of endometrial receptivity, such as leukemia inhibitory factor and glutathione peroxidase 3, and (ii) downregulation of interleukin-15 and mucin1, both genes negatively related with endometrial receptivity. Our results indicate that the endocrine communication between adipose tissue and the reproductive system is bidirectional and stress the importance of the adipose tissue to modulate the reproductive fitness