Increased production of functional small extracellular vesicles in senescent endothelial cells.

Small extracellular vesicles (EVs) are novel players in vascular biology. However, a thorough understanding of their production and function remains elusive. Endothelial senescence is a key feature of vascular ageing and thus, is an attractive therapeutic target for the treatment of vascular disease. In this study, we sought to characterize the EV production of senescent endothelial cells. To achieve this, Human Umbilical Vascular Endothelial Cells (HUVECs) were replicated until they reached senescence, as determined by measurement of Senescence-Associated ß-Galactosidase activity via microscopy and flow cytometry. Expression of the endosomal marker Rab7 and the EV marker CD63 was determined by immunofluorescence. Small EVs were isolated by ultracentrifugation and characterized using electron microscopy, nanoparticle tracking analysis and immunoassays to assess morphology, size, concentration and expression of exosome markers CD9 and CD81. Migration of HUVECs in response to EVs was studied using a transwell assay. The results showed that senescent endothelial cells express higher levels of Rab7 and CD63. Moreover, senescent endothelial cells produced higher levels of CD9- and CD81-positive EVs. Additionally, small EVs from both young and senescent endothelial cells promoted HUVEC migration. Overall, senescent endothelial cells produce an increased number of functional small EVs, which may have a role in vascular physiology and disease.

A lower duodenal immune response is associated with an increase of insulin resistance in patients with morbid obesity.

OBJECTIVE: The intestinal immune response could play an important role in obesity-related comorbidities. We aim to study the profile of duodenal cytokines and chemokines in patients with morbid obesity (MO), its relation with insulin resistance (IR) and the intake of metformin, and with the evolution of MO after sleeve gastrectomy (SG). RESEARCH DESIGN AND METHODS: Duodenal levels of 24 cytokines and 9 chemokines were analyzed in 14 nonobese and in 54 MO who underwent SG: with lower IR (MO-lower-IR), with higher IR (MO-higher-IR), and with type 2 diabetes treated with metformin (MO-metf-T2DM). RESULTS: MO-lower-IR had higher levels of cytokines related to Th1, Th2, Th9, Th17, Th22, M1 macrophages, and chemokines involved in the recruitment of macrophages and T-lymphocytes (p < 0.05), and total (CD68 expression) and M1 macrophages (ITGAX expression) (p < 0.05) when compared with nonobese patients, but with a decrease in M2 macrophages (MRC1 expression) (p < 0.05). In MO-higher-IR, these chemokines and cytokines decreased and were similar to those found in nonobese patients. In MO-metf-T2DM, only IL-4 (Th2) and IL-22 (Th22) increased their levels with regard to MO-higher-IR (p < 0.05). In MO-higher-IR and MO-metf-T2DM, there was a decrease of CD68 expression (p < 0.05) while ITGAX and MRC1 were similar with regard to MO-lower-IR. We found an association between CXCL8, TNFß and IL-2 with the evolution of body mass index (BMI) after SG (p < 0.05). CONCLUSIONS: There is an association between a higher IR and a lower duodenal immune response in MO, with a slight increase in those patients with metformin treatment. Intestinal immune response could be involved in the evolution of BMI after SG.

Overexpression of scavenger receptor and infiltration of macrophage in epicardial adipose tissue of patients with ischemic heart disease and diabetes.

BACKGROUND: Oxidized low-density lipoproteins and scavenger receptors (SRs) play an important role in the formation and development of atherosclerotic plaques. However, little is known about their presence in epicardial adipose tissue (EAT). The objective of the study was to evaluate the mRNA expression of different SRs in EAT of patients with ischemic heart disease (IHD), stratifying by diabetes status and its association with clinical and biochemical variables. METHODS: We analyzed the mRNA expression of SRs (LOX-1, MSR1, CXCL16, CD36 and CL-P1) and macrophage markers (CD68, CD11c and CD206) in EAT from 45 patients with IHD (23 with type 2 diabetes mellitus (T2DM) and 22 without T2DM) and 23 controls without IHD or T2DM. RESULTS: LOX-1, CL-P1, CD68 and CD11c mRNA expression were significantly higher in diabetic patients with IHD when compared with those without T2DM and control patients. MSR1, CXCL16, CD36 and CD206 showed no significant differences. In IHD patients, LOX-1 (OR 2.9; 95% CI 1.6-6.7; P = 0.019) and CD68 mRNA expression (OR 1.7; 95% CI 0.98-4.5; P = 0.049) were identified as independent risk factors associated with T2DM. Glucose and glycated hemoglobin were also shown to be risk factors. CONCLUSIONS: SRs mRNA expression is found in EAT. LOX-1 and CD68 and were higher in IHD patients with T2DM and were identified as a cardiovascular risk factor of T2DM. This study suggests the importance of EAT in coronary atherosclerosis among patients with T2DM.

Increased PON lactonase activity in morbidly obese patients is associated with impaired lipid profile.

AIMS: The paraoxonase-1 (PON1) enzyme could play an important role in the anti-oxidant capacity of high-density lipoprotein. However, there are no studies which analyse the evolution of the three activities of PON1 (PON arylesterase, PON paraoxonase and PON lactonase) after Roux-en-Y Gastric Bypass (RYGB) in morbidly obese subjects. We analysed the association of PON concentration and activities with the evolution of morbidly obese subjects who underwent RYGB, and its relationship with biochemical variables and different atherogenic indices. METHODS: Twenty-seven non-obese and 82 morbidly obese subjects were studied before and 6 months after RYGB. RESULTS: Before RYGB, morbidly obese subjects had a lower PON1 concentration (P < 0.05) and higher PON lactonase activity (P < 0.001) than non-obese subjects, with no differences in PON arylesterase and PON paraoxonase activities. After RYGB, PON1 concentration (P < 0.05) and PON lactonase activity (P < 0.001) decreased with regard to the presurgery state. PON lactonase activity correlated with the atherogenic index of plasma before (r = 0.19, P = 0.047) and after RYGB (r = 0.27, P = 0.035). In different multiple lineal regression analysis models, presurgery PON lactonase activity was associated with total cholesterol (ß = 0.909, P < 0.001), LDL (ß = 0.632, P = 0.006) and DBP (ß = 0.230, P = 0.030) (R2  = 0.295), postsurgery PON lactonase activity was associated with esterified cholesterol (ß = 0.362, P = 0.011) (R2  = 0.131), and the change (Δ) in PON lactonase activity after RYGB was associated with Δesterified cholesterol (ß = 0.304, P = 0.030) (R2  = 0.093). CONCLUSIONS: PON lactonase activity is associated with the presence of morbid obesity and with an impaired lipid profile. All associations found could indicate the relationship between PON lactonase activity and the development of atherosclerosis.

Novel intragenic deletions within the UBE3A gene in two unrelated patients with Angelman syndrome: case report and review of the literature.

BACKGROUND: Patients with Angelman syndrome (AS) are affected by severe intellectual disability with absence of speech, distinctive dysmorphic craniofacial features, ataxia and a characteristic behavioral phenotype. AS is caused by the lack of expression in neurons of the UBE3A gene, which is located in the 15q11.2-q13 imprinted region. Functional loss of UBE3A is due to 15q11.2-q13 deletion, mutations in the UBE3A gene, paternal uniparental disomy and genomic imprinting defects. CASE PRESENTATION: We report here two patients with clinical features of AS referred to our hospital for clinical follow-up and genetic diagnosis. Methylation Specific-Multiplex Ligation-Dependent Probe Amplification (MS-MLPA) of the 15q11.2-q13 region was carried out in our laboratory as the first diagnostic tool detecting two novel UBE3A intragenic deletions. Subsequently, the MLPA P336-A2 kit was used to confirm and determine the size of the UBE3A deletion in the two patients. A review of the clinical features of previously reported patients with whole UBE3A gene or partial intragenic deletions is presented here together with these two new patients. CONCLUSION: Although rare, UBE3A intragenic deletions may represent a small fraction of AS patients without a genetic diagnosis. Testing for UBE3A intragenic exonic deletions should be performed in those AS patients with a normal methylation pattern and no mutations in the UBE3A gene.

Expression of epicardial adipose tissue thermogenic genes in patients with reduced and preserved ejection fraction heart failure.

Epicardial adipose tissue has been proposed to participate in the pathogenesis of heart failure. The aim of our study was to assess the expression of thermogenic genes (Uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), and PR-domain-missing 16 (PRDM16) in epicardial adipose tissue in patients with heart failure, stablishing the difference according to left ventricular ejection fraction (reduced or preserved). Among the 75 patients in our study, 42.7% (n=32) had reduced left ventricular ejection fraction. UCP1, PGC1α and PRDM16 mRNA in EAT were significantly lower in patients with reduced left ventricular ejection fraction. Multiple regression analysis showed that age, male gender, body max index, presence of obesity, type-2-diabetes mellitus, hypertension and coronary artery disease and left ventricular ejection fraction were associated with the expression levels of UCP1, PGC1α and PRDM16 mRNA. Thermogenic genes expressions in epicardial adipose tissue (UCP1: OR 0.617, 95%CI 0.103-0.989, p=0.042; PGC1α: OR 0.416, 95%CI 0.171-0.912, p=0.031; PRDM16: OR 0.643, 95%CI 0.116-0.997, p=0.044) were showed as protective factors against the presence of heart failure with reduced left ventricular ejection fraction, and age (OR 1.643, 95%CI 1.001-3.143, p=0.026), presence of coronary artery disease (OR 6.743, 95%CI 1.932-15.301, p<0.001) and type-2-diabetes mellitus (OR 4.031, 95%CI 1.099-7.231, p<0.001) were associated as risk factors. The adequate expression of thermogenic genes has been shown as possible protective factors against heart failure with reduced ejection fraction, suggesting that a loss of functional epicardial adipose tissue brown-like features would participate in a deleterious manner on heart metabolism. Thermogenic genes could represent a future novel therapeutic target in heart failure.

Masked polycythaemia vera: presenting features, response to treatment and clinical outcomes.

Masked polycythaemia vera (PV) has been proposed as a new entity with poorer outcome than overt PV. In this study, the initial clinical and laboratory characteristics, response to treatment and outcome of masked and overt PV were compared using red cell mass and haemoglobin or haematocrit levels for the distinction between both entities. Sixty-eight of 151 PV patients (45%) were classified as masked PV according to World Health Organisation diagnostic criteria, whereas 16 (11%) were classified as masked PV using the British Committee for Standards in Haematology (BCSH). In comparison with overt PV, a higher platelet count and a lower JAK2V617F allele burden at diagnosis were observed in masked PV. Patients with masked PV needed lower phlebotomies and responded faster to hydroxcarbamide than those with overt PV. Complete haematological response was more frequently achieved in masked than in overt PV (79% vs. 58%, P = 0.001). There were no significant differences in the duration of haematological response, the rate of resistance or intolerance to hydroxycarbamide and the probability of molecular response according to type of PV (masked vs. overt). Overall survival, rate of thrombosis and major bleeding, and probability of transformation was superimposable among patients with masked and overt PV.

PXK locus in systemic lupus erythematosus: fine mapping and functional analysis reveals novel susceptibility gene ABHD6.

OBJECTIVES: To perform fine mapping of the PXK locus associated with systemic lupus erythematosus (SLE) and study functional effects that lead to susceptibility to the disease. METHODS: Linkage disequilibrium (LD) mapping was conducted by using 1251 SNPs (single nucleotide polymorphism) covering a 862 kb genomic region on 3p14.3 comprising the PXK locus in 1467 SLE patients and 2377 controls of European origin. Tag SNPs and genotypes imputed with IMPUTE2 were tested for association by using SNPTEST and PLINK. The expression QTLs data included three independent datasets for lymphoblastoid cells of European donors: HapMap3, MuTHER and the cross-platform eQTL catalogue. Correlation analysis of eQTLs was performed using Vassarstats. Alternative splicing for the PXK gene was analysed on mRNA from PBMCs. RESULTS: Fine mapping revealed long-range LD (>200 kb) extended over the ABHD6, RPP14, PXK, and PDHB genes on 3p14.3. The highly correlated variants tagged an SLE-associated haplotype that was less frequent in the patients compared with the controls (OR=0.89, p=0.00684). A robust correlation between the association with SLE and enhanced expression of ABHD6 gene was revealed, while neither expression, nor splicing alterations associated with SLE susceptibility were detected for PXK. The SNP allele frequencies as well as eQTL pattern analysed in the CEU and CHB HapMap3 populations indicate that the SLE association and the effect on ABHD6 expression are specific to Europeans. CONCLUSIONS: These results confirm the genetic association of the locus 3p14.3 with SLE in Europeans and point to the ABHD6 and not PXK, as the major susceptibility gene in the region. We suggest a pathogenic mechanism mediated by the upregulation of ABHD6 in individuals carrying the SLE-risk variants.

Hypoxia is associated with a lower expression of genes involved in lipogenesis in visceral adipose tissue.

BACKGROUND: A key role for HIF-1α in the promotion and maintenance of dietary obesity has been proposed. We analyzed the association between hypoxia and de novo lipogenesis in human adipose tissue. METHODS: We studied HIF-1α mRNA and protein expression in fasting status in visceral adipose tissue (VAT) from non-obese and morbidly obese subjects, and in VAT from wild-type and ob/ob C57BL6J mice in both fasting and feeding status. We also analyzed the effect of hypoxia on the VAT mRNA expression of genes involved in lipogenesis. RESULTS: HIF-1α was increased in VAT from morbidly obese subjects. In fasting status, C57BL6J ob/ob mice had a higher VAT HIF-1α mRNA expression than C57BL6J wild-type mice. In feeding status, VAT HIF-1α mRNA expression significantly increased in C57BL6J wild-type, but not in C57BL6J ob/ob mice. In humans, HIF-1α mRNA expression correlated positively with body mass index and insulin resistance. VAT HIF-1α mRNA expression correlated negatively with ACC1, PDHB and SIRT3 mRNA expression, and positively with PPAR-γ. VAT explants incubated in hypoxia showed reduced SIRT3 and increased PPAR-γ, SREBP-1c, ACLY, ACC1 and FASN mRNA expression. CONCLUSIONS: Morbidly obese subjects have a higher level of VAT HIF-1α. Postprandial status is associated with an increase in HIF-1α mRNA expression in C57BL6J wild-type mice. Hypoxia alters the mRNA expression of genes involved in de novo lipogenesis in human VAT.

Stroke incidence and risk factors in Havana and Matanzas, Cuba.

INTRODUCTION: Cerebrovascular disease is the third-leading cause of death and the second-leading cause of disability and dementia. OBJECTIVE: Determine stroke incidence and risk factors in a population of adults aged 65 and over in Cuba (Havana and Matanzas). MATERIAL AND METHODS: This prospective longitudinal study, completed between April 2008 and Abril 2011, re-evaluated 2916 elderly adults with an average follow-up time of 4 years. Cases included 2316 living subjects and 600 verbal autopsies. Study variables were age, sex, educational level, self-reported health, and description of chronic diseases and substance abuse. Laboratory tests included genotyping APOE. Stroke was diagnosed based on the World Health Organization definition. We calculated the global incidence rate for stroke, broken down by sex, age group, and risk factors for incident stroke. RESULTS: Stroke incidence was 786.2 in 100000 persons/year (95% CI: 672.3-906.4). History of alcohol consumption (HR: 3.5; 95% CI: 3.3-3.7), dementia (HR: 3.0; 95% CI, 1.6-5.5) and male sex (HR: 1.8; 95% CI, 1.2-2.8) were shown to be risk factors for incident stroke. CONCLUSIONS: Stroke incidence was similar to rates reported in developed countries and lower than that in low- to middle-income countries. Given that diabetes mellitus, heart disease, arterial hypertension, smoking, APOE4, etc. are associated with higher mortality rates, they will require separate analysis in a study of stroke risk factors.

Characteristics of culprit atheromatous plaques obtained in vivo by intravascular ultrasound radiofrequency analysis: results from the CULPLAC study.

OBJECTIVES: We used virtual histology-intravascular ultrasound (VH-IVUS) to investigate the characteristics of culprit lesions in acute coronary syndromes (ACS). BACKGROUND: Autopsy studies of patients who died of ACS have shown that culprit atheromatous plaques almost always contain a large lipid-necrotic core covered by a ruptured thin fibrous cap. There are no studies of sufficient size that have assessed the in vivo characterization of plaques responsible for ACS. METHODS: Patients undergoing angiography for stable ischemic heart disease and ACS (with and without ST-segment elevation) were enrolled in a prospective study. Lesions in patients with stable angina were classified as stable and those in patients with ACS as culprit or nonculprit. RESULTS: The study included 189 patients: VH-IVUS was used to assess 253 lesions (73 stable, 82 nonculprit, and 98 culprit lesions). The thin-cap fibroatheroma phenotype (VH-TCFA) was more frequent among lesions in patients with ACS (55.1% in culprit lesions, 36.6% in nonculprit lesions and 14.4% in stable lesions; P = .007). The arc of the VH-TCFA exposed to the vessel lumen was significantly greater in culprit lesions than in nonculprit lesions (122.28° ± 58 vs 89.46° ± 52; respectively; P = .007). Multivariate analysis showed that VH-TCFA (OR 2.1; P = .033), calcified nodules (OR 2.1; P = .046), positive remodeling (OR 3.5; P < .001) and necrotic core volume (OR 1.02;P = .009) were independently associated with a clinically identified culprit lesion. CONCLUSIONS: Plaque phenotype, rather than the proportion of each tissue, appears to be associated with plaque instability. VH-TCFA, particularly subtype IV, is associated with lesions responsible for ACS.

The use of ultrasound elastography in the assessment of malignancy risk in thyroid nodules and multinodular goitres.

OBJECTIVE: The objective of our work is to use a surgical series to analyse the validity of elastography in evaluating the malignancy of thyroid nodules and multinodular goitres. PATIENTS AND METHODS: The study examined 156 patients, 134 women (85·9%) and 22 men (14·1%), who underwent surgery for nodular thyroid disease between October 2008, and November 2010. The average age of the patients was 52 years (±14·42). Thirty-six patients (23·1%) presented with a single nodule, and 120 (76·9%) exhibited multinodular goitres. Prior to surgical intervention, all patients underwent colour eco-elastography using a qualitative five-point ordinal scale for nodule classifications. Test results were analysed using a receiver operating characteristic (ROC) curve, and an anatomical pathologic examination of surgical specimens was used as a gold standard diagnostic tool for comparison. RESULTS: Of the 192 nodules analysed, 28 (14·6%) were malignant. Using elastography data, an ROC curve was obtained with an area under the curve of 0·662 (±0·060) and a 95% confidence interval (CI 95%) between 0·545 and 0·779 (P = 0·006). By establishing a cut-off point that classified thyroid nodules with an elastographic value greater than or equal to 3 as malignant, we achieved a sensitivity of 75%, specificity of 45·73%, positive predictive value of 19·1% and negative predictive value of 91%. The positive and negative likelihood ratios were 1·38 and 0·55, respectively. CONCLUSIONS: Ultrasound elastography can provide information regarding malignancy risk in thyroid nodules and multinodular goitres. However, the sensitivity and specificity values obtained in our study are below those reported by other groups, a finding that calls into question the current clinical utility of ultrasound elastography.

Reliability and validity of a Spanish version of the Impact of Pediatric Epilepsy Scale in a Cuban population.

The Impact of Pediatric Epilepsy Scale (IPES) is a brief, accurate, and acceptable measurement scale of the impact of pediatric epilepsy on the health-related quality of life (HRQOL) of both the child and the child's family as perceived by the child's parent(s). The aim of this study was to validate a Spanish language version of the IPES in Cuban children with epilepsy. The IPES was translated and adapted to Cuban culture and administered to 76 parents of children with epilepsy. The principal component analysis indicated that two factors accounted for 72% of the variance of the IPES (family relationships and health and social well-being). The IPES was also able to detect differences in HRQOL between subjects according to epilepsy severity. The internal consistency coefficient was 0.962, and the test-retest reliability was 0.979. The Cuban version of IPES can be used to measure a child's epilepsy-specific HRQOL in Cuba.

Absence of diabetes mellitus type 2 in obese children and adolescents in the north of Spain.

BACKGROUND: The worldwide epidemic of childhood obesity has been accompanied by an increase in the incidence of carbohydrate metabolism disorders. OBJECTIVE: To determine the prevalence of type 2 diabetes mellitus (T2DM) and other carbohydrate metabolism disorders in obese young people in the Basque Country (Spain). DESIGN: Prospective observational study. PATIENTS: We studied 136 obese Caucasian children and adolescents (body mass index ≥2 SDS above the mean). MEASUREMENTS: Their severity of obesity was classified as mild <3 SDS or moderate-to-severe ≥3 SDS. Data were collected on clinical and metabolic parameters; insulin resistance (IR) was calculated using the homeostasis model assessment, and an oral glucose tolerance test (OGTT) was carried out. RESULTS: T2DM was not found. Impaired glucose tolerance (IGT) was found in 9.6% of patients being higher in moderate-to-severe obesity (12.8% vs. 2.4%; p=0.048) and in patients with acanthosis nigricans (27.8% vs. 6.8%; p=0.016). No differences were detected by sex or pubertal development in metabolic results as a function of OGTT's response. IR (13.5%) was higher among those with moderate-to-severe obesity, in patients with acanthosis nigricans and was associated with other cardiovascular disease risk factors. CONCLUSIONS: We found no children with T2DM. The prevalence of IGT and IR was related to severity of obesity, to the association of acanthosis nigricans and was associated with cardiovascular risk.

[Emotional overload of health personnel of the Navarra Health Service during the SARS-CoV-2 pandemic]. / Sobrecarga emocional del personal sanitario del Servicio Navarro de Salud durante la pandemia del SARS-CoV-2.

INTRODUCTION: Health care workers faced unprecedented levels of emotional burden related to the COVID-19 pandemic.. This study aims to find out the self-perception of the state of emotional overload of the professionals of the Navarre Osasunbidea Health Service (SNS-O) at two moments during the pandemic and its associated factors. METHOD: Cross-sectional study using a questionnaire that includes the Emotional Overload Self-Assessment Scale sent by email to all SNS-O health professionals at two moments of the pandemic, in October 2020 and October 2021. Results of the global scale and of the subscales '"fear-anxiety"' and ""affective response"' were compared between the two moments of measurement according to position, field, area and service using ANCOVA models. RESULTS: The number of responding participants in the 2020 survey was 1 485 (11,3%) and 950 in the 2021 survey (7,3%). The mean difference for overall score between 2020 and 2021 was -1.87 (95% CI: -2.38, -1.35), indicating less worrying results with the passage of time since the start of the pandemic, with some differences accross occupational categories. CONCLUSIONS: The year 2020 had a great impact on the emotional overload that decreased the following year. One of the greatest fears of health personnel during their occupational exposure to epidemic infectious diseases continues to be the fear of contracting the disease and transmitting it to their family members and social environment. As the proximity to the patient and their environment increases, the probability of psycho-emotional affectation increases.

OBJETIVO: Los trabajadores de la salud se enfrentaron a niveles sin precedentes de carga emocional relacionada con la pandemia de la COVID-19. Este estudio pretende conocer la autopercepción del estado de sobrecarga emocional de los profesionales del Servicio Navarro de Salud-Osasunbidea (SNS-O) en dos momentos durante la pandemia y sus factores asociados. Método: Estudio transversal mediante el uso de un cuestionario que incluye la Escala de Autoevaluación de Sobrecarga Emocional, enviado por correo electrónico a todos los profesionales sanitarios del SNS-O en dos momentos de la pandemia, en octubre de 2020 y octubre de 2021. Los resultados de la escala global y de las subescalas '"miedos-ansiedad"' y '"respuesta afectiva"' se compararon entre los dos momentos de medición según puesto de trabajo, ámbito, área y servicio, mediante modelos ANCOVA?.  Resultados: Participaron en la encuesta de 2020 1.485 (11,3%) sanitarios y 950 (7,3%) en la encuesta de 2021 de. La diferencia media para el score global entre 2020 y 2021 fue -1.87 (95% IC: -2.38, -1.35), indicando una reducción de la sobrecarga emocional con la evolución de la pandemia, con algunas diferencias entre categorías profesionales. CONCLUSIONES: El año 2020 tuvo gran impacto en la sobrecarga emocional que disminuyó al año siguiente. Uno de los mayores temores del personal sanitario durante su exposición laboral a enfermedades infecciosas epidémicas sigue siendo el miedo a contraer la enfermedad y transmitirla a sus familiares y entorno social. Conforme aumenta la proximidad con el paciente y su entorno, incrementa la probabilidad de afectación psicoemocional.

EVOO Promotes a Less Atherogenic Profile Than Sunflower Oil in Smooth Muscle Cells Through the Extracellular Vesicles Secreted by Endothelial Cells.

Background: Little is known about the effect of extra virgin olive (EVOO) and sunflower oil (SO) on the composition of extracellular vesicles (EVs) secreted by endothelial cells and the effects of these EVs on smooth muscle cells (SMCs). These cells play an important role in the development of atherosclerosis. Methods: We evaluated the effects of endothelial cells-derived EVs incubated with triglyceride-rich lipoproteins obtained after a high-fat meal with EVOO (EVOO-EVs) and SO (SO-EVs), on the transcriptomic profile of SMCs. Results: We found 41 upregulated and 19 downregulated differentially expressed (DE)-miRNAs in EVOO-EVs. Afterwards, SMCs were incubated with EVOO-EVs and SO-EVs. SMCs incubated with SO-EVs showed a greater number of DE-mRNA involved in pathways related to cancer, focal adhesion, regulation of actin cytoskeleton, and MAPK, toll-like receptor, chemokine and Wnt signaling pathways than in SMCs incubated with EVOO-EVs. These DE-mRNAs were involved in biological processes related to the response to endogenous stimulus, cell motility, regulation of intracellular signal transduction and cell population proliferation. Conclusion: EVOO and SO can differently modify the miRNA composition of HUVEC-derived EVs. These EVs can regulate the SMCs transcriptomic profile, with SO-EVs promoting a profile more closely linked to the development of atherosclerosis than EVOO-EVs.

Breastfeeding experiences during the COVID-19 pandemic in Spain:a qualitative study.

BACKGROUND: The pandemic caused by COVID-19 has affected reproductive and perinatal health both through the infection itself and, indirectly, as a consequence of changes in medical care, social policy or social and economic circumstances. The objective of this study is to explore the impact of the pandemic and of the measures adopted on breastfeeding initiation and maintenance. METHODS: A qualitative descriptive study was conducted by means in-depth semi-structured interviews, until reaching data saturation. The study was conducted between the months of January to May 2021. Participants were recruited by midwives from the Primary Care Centres of the Andalusian provinces provinces of Seville, Cádiz, Huelva, Granada, and Jaén. The interviews were conducted via phone call and were subsequently transcribed and analysed by means of reflexive inductive thematic analysis, using Braun and Clarke's thematic analysis. RESULTS: A total of 30 interviews were conducted. Five main themes and ten subthemes were developed, namely: Information received (access to the information, figure who provided the information), unequal support from the professionals during the pandemic (support to postpartum hospitalization, support received from Primary Health Care during the postpartum period), social and family support about breastfeeding (support groups, family support), impact of confinement and of social restriction measures (positive influence on breastfeeding, influence on bonding with the newborn), emotional effect of the pandemic (insecurity and fear related to contagion by coronavirus, feelings of loneliness). CONCLUSION: The use of online breastfeeding support groups through applications such as WhatsApp®, Facebook® or Instagram® has provided important breastfeeding information and support sources. The main figure identified that has provided formal breastfeeding support during this period was that of the midwife. In addition, the social restrictions inherent to the pandemic have exerted a positive effect for women in bonding and breastfeeding, as a consequence of the increase in the time spent at their homes and in the family nucleus co-living.

Morbid Obesity in Women Is Associated with an Altered Intestinal Expression of Genes Related to Cancer Risk and Immune, Defensive, and Antimicrobial Response.

BACKGROUND: Little is known about the relation between morbid obesity and duodenal transcriptomic changes. We aimed to identify intestinal genes that may be associated with the development of obesity regardless of the degree of insulin resistance (IR) of patients. MATERIAL AND METHODS: Duodenal samples were assessed by microarray in three groups of women: non-obese women and women with morbid obesity with low and high IR. RESULTS: We identified differentially expressed genes (DEGs) associated with morbid obesity, regardless of IR degree, related to digestion and lipid metabolism, defense response and inflammatory processes, maintenance of the gastrointestinal epithelium, wound healing and homeostasis, and the development of gastrointestinal cancer. However, other DEGs depended on the IR degree. We mainly found an upregulation of genes involved in the response to external organisms, hypoxia, and wound healing functions in women with morbid obesity and low IR. CONCLUSIONS: Regardless of the degree of IR, morbid obesity is associated with an altered expression of genes related to intestinal defenses, antimicrobial and immune responses, and gastrointestinal cancer. Our data also suggest a deficient duodenal immune and antimicrobial response in women with high IR.

Safety and effectiveness of surgery for epilepsy in children. Experience of a tertiary hospital in Ecuador. / Efectividad y seguridad de la cirugía para la epilepsia en niños. Experiencia de un hospital terciario en Ecuador.

INTRODUCTION: There is sufficient evidence on the usefulness of surgery as a therapeutic alternative for patients with drug-resistant epilepsy; however this treatment is underutilized, especially in developing countries. METHODS: We describe the outcomes of epilepsy surgery in 27 paediatric patients at Hospital Baca Ortiz in Quito, Ecuador. Our analysis considered the following variables: reduction in seizure frequency, surgery outcome according to the Engel classification, improvement in quality of life, and serious complications due to surgery. RESULTS: 21 corpus callosotomies and 6 resective surgeries were performed. The mean seizure frequency decreased from 465 per month before surgery to 37.2 per month thereafter (p<.001); quality of life scale scores increased from 12.6 to 37.2 (p<.001), and quality of life improved in 72.7% of patients. Regarding resective surgery, 2 patients with temporal lobe epilepsy and one with posterior quadrant epilepsy achieved Engel class IA, and one patient undergoing hemispherotomy due to Rasmussen encephalitis achieved Engel class IIA. Two patients underwent surgery for hypothalamic hamartoma: one achieved Engel III and the other, Engel IA; however, the latter patient died in the medium term due to a postoperative complication. The other major complication was a case of hydrocephalus, which led to the death of a patient with refractory infantile spasms who underwent corpus callosotomy. CONCLUSIONS: Favourable outcomes were observed in 92.5% of patients.

Oxidized LDL Increase the Proinflammatory Profile of Human Visceral Adipocytes Produced by Hypoxia.

BACKGROUND: Little is known about the effects of hypoxia on scavenger receptors (SRs) levels in adipocytes. We analyzed the effect of morbid obesity and hypoxia on SRs and inflammation markers in human visceral adipocytes and whether ox-LDL modify the inflammatory profile produced by hypoxia. METHODS: We studied in 17 non-obese and 20 subjects with morbid obesity (MO) the mRNA expression of HIF-1α, SRs (LOX-1, MSR1, CL-P1 and CXCL16), IL6 and TNFα in visceral adipocytes and the effect of hypoxia with or without ox-LDL on visceral in vitro-differentiated adipocytes (VDA). RESULTS: HIF-1α, TNFα, IL6, LOX-1, MSR1 and CXCL16 expression in adipocytes was increased in MO when compared with those in non-obese subjects (p < 0.05). The expression of most of the inflammatory markers and SRs gene correlated with HIF-1α. In VDA, hypoxia increased TNFα, IL6, MSR1, CXCL16 and CL-P1 (p < 0.05) in non-obese subjects, and TNFα, IL6, MSR1 and CXCL16 (p < 0.05) in MO. Silencing HIF-1α prevented the increase of TNFα, IL6, LOX-1, MSR1, CL-P1 and CXCL16 expression (p < 0.05). The combination of hypoxia and ox-LDL produced higher TNFα expression (p = 0.041). CONCLUSIONS: Morbid obesity and hypoxia increased SRs and inflammatory markers in visceral adipocytes. In a hypoxic state, ox-LDL increased the proinflammatory response of visceral adipocytes to hypoxia.