Epigenetic modulation of Nrf2 and Ogg1 gene expression in testicular germ cells by methyl parathion exposure.

Methyl parathion (Me-Pa) is an oxidizing organophosphate (OP) pesticide that generates reactive oxygen species (ROS) through its biotransformation. Some studies have also suggested that OP pesticides have the capacity to alkylate biomolecules, including DNA. In general, DNA methylation in gene promoters represses transcription. NRF2 is a key transcription factor that regulates the expression of antioxidant, metabolic and detoxifying genes through the antioxidant response element (ARE) situated in promoters of regulated genes. Furthermore, DNA repair genes, including 8-oxoguanine DNA glycosidase (OGG1), have been proposed as NRF2 target genes. Me-Pa exposure produces poor semen quality, genetic and oxidative damage in sperm cells, and reduced fertility. However, the Me-Pa effects on the methylation status and the expression of antioxidant (Nrf2) or DNA repair (Ogg1) genes in male germ cells have not been investigated. Therefore, mice were exposed to Me-Pa to evaluate the global (%5-mC) and specific methylation of Nrf2 and Ogg1 genes using pyrosequencing, gene expression, and total protein carbonylation in male germ cells. The results showed that Me-Pa significantly decreased the global DNA methylation pattern and significantly increased the methylation of two CpG sites within Ogg1 promoter and one CpG site within Nrf2 promoter. In addition, Ogg1 or Nrf2 expression did not change after Me-Pa exposure despite the oxidative damage produced. Altogether, our data suggest that Me-Pa toxicity alters Ogg1 and Nrf2 promoter methylation in male germ cells that may be modulating their gene expression.

Psychotherapeutic and psychosocial interventions for managing stress in multiple sclerosis: the contribution of mindfulness-based interventions.

Depression or anxiety in multiple sclerosis (MS) has been linked to a more severe course of the disease and higher numbers of relapses, in addition to poorer treatment adherence and exacerbated immune system dysregulation. Recent investigations indicate that psychotherapeutic interventions for stress management, such as mindfulness-based interventions (MBIs), could improve quality of life, depression, anxiety, and fatigue in MS patients. Mindfulness fosters the ability to slow down and observe experiences as they truly are, which improves affect regulation. Mindfulness is acquired through training; its advantage over other psychotherapeutic interventions is that effects may remain over time, since cultivating mindfulness depends on regular practising of abilities learned during training. The objective of this article is to review the current evidence of psychotherapeutic and psychosocial interventions, including MBIs for stress management, and their beneficial effects on MS patients.

The JAK2 46/1 haplotype does not predispose to CALR-mutated myeloproliferative neoplasms.

Somatic mutations in the CALR gene were recently discovered in a substantial proportion of Philadelphia-negative chronic myeloproliferative neoplasm (cMPN) patients lacking JAK2 and MPL mutations. Somatically acquired defects are not the only pathogenic mechanism involved in these disorders. Since germline JAK2 46/1 haplotype predisposes to cMPN-associated mutations, including JAK2V617F and MPLW515K7L, we evaluated whether the 46/1 haplotype also confers susceptibility to CALR-mutated cMPN, both in sporadic and familial cases. The single-nucleotide polymorphism rs10974944, which tags 46/1, was investigated in 155 sporadic MPN patients and 270 unrelated controls, as well as in 11 familial cMPN cases and 36 unaffected relative controls. As described elsewhere, the 46/1 haplotype was overrepresented, both in sporadic and familial cMPN. In sporadic cMPN, the JAK2 46/1 haplotype was closely associated with JAK2V617F (p = 0.0003) but not with JAK2-nonmutated cases. Analysis of CALR-mutated sporadic cMPN (n = 22) showed no association between CALR mutations and 46/1 haplotype (p = 0.87). Regarding the familial cMPN, the prevalence of carriers of the G allele was higher in familial (81.8%) than in sporadic (62%) cMPN, but it did not differ significantly (p = 0.3). Although we described a family with carriers of both JAK2V617F and CALR mutations, due to the low number of CALR-mutated familial cases, we could not determinate whether the JAK2 46/1 haplotype predisposes or does not to CALR-mutated familial cMPN. We conclude, for the first time, that the 46/1 haplotype, unlike JAK2V617F and MPLW515K7L, is not associated with CALR-mutated cMPN.

Extracellular vesicles and their synthetic analogues in aging and age-associated brain diseases.

Multicellular organisms rely upon diverse and complex intercellular communications networks for a myriad of physiological processes. Disruption of these processes is implicated in the onset and propagation of disease and disorder, including the mechanisms of senescence at both cellular and organismal levels. In recent years, secreted extracellular vesicles (EVs) have been identified as a particularly novel vector by which cell-to-cell communications are enacted. EVs actively and specifically traffic bioactive proteins, nucleic acids, and metabolites between cells at local and systemic levels, modulating cellular responses in a bidirectional manner under both homeostatic and pathological conditions. EVs are being implicated not only in the generic aging process, but also as vehicles of pathology in a number of age-related diseases, including cancer and neurodegenerative and disease. Thus, circulating EVs-or specific EV cargoes-are being utilised as putative biomarkers of disease. On the other hand, EVs, as targeted intercellular shuttles of multipotent bioactive payloads, have demonstrated promising therapeutic properties, which can potentially be modulated and enhanced through cellular engineering. Furthermore, there is considerable interest in employing nanomedicinal approaches to mimic the putative therapeutic properties of EVs by employing synthetic analogues for targeted drug delivery. Herein we describe what is known about the origin and nature of EVs and subsequently review their putative roles in biology and medicine (including the use of synthetic EV analogues), with a particular focus on their role in aging and age-related brain diseases.

The in vitro immunomodulatory effect of extracellular products (ECPs) of Vagococcus fluvialis L21 on European sea bass (Dicentrarchus labrax) leucocytes.

The immune associated genes, interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor-α (TNF-α), ciclo-oxigenase-2 (COX-2), and Mx gene were studied by real-time PCR in head-kidney leucocytes of sea bass after incubation with the extracellular products (ECPs) of the probiotic strain Vagococcus fluvialis L21 and polyinosinic:polycytidylic acid (POLY I:C), at different times (T1.5, T6, T12, T24, T48 and T72). In general, we can observe how pro-inflammatory cytokines IL-1ß, TNF-α, IL-6 and COX-2 studied displayed a strong peak after stimulation with 1.5 h of ECPs of V. fluvialis L21, significant differences (P < 0.05) exist with other periods and with the POLY I: C at the same time. Similarly to the case of IL-10 also produced a statistically significant (P < 0.05) peak of expression on leukocytes that were stimulated with the ECPs of V. fluvialis L21. In the case of Mx gene expression, we note that in almost all sampling times there is an up-regulation of the Mx gene in leucocytes incubated with ECPs and POLY I:C compared to the control and Mx expression was higher in leucocytes that were stimulated with the ECPs of V. fluvialis for all times, except in T24. With these results we can consider that the ECPs of V. fluvialis L21 have a great power of stimulating the in vitro expression of immune-related genes and may even be useful as adjuvants for vaccine in aquaculture.

Immunization of sea bream (Sparus aurata) juveniles against Photobacterium damselae subsp. piscicida by short bath: Effect on some pro-inflammatory molecules and the Mx gene expression.

Cytokines are a family of proteins derived from macrophages, lymphocytes, granulocytes, mast cells and epithelial cells and can be divided into interferons (IFNs), Interleukins (ILs) and Tumor Necrosis factors (TNFs) among others. The presence of cytokines in a wide number of fish species has been proved and several molecules types have been already cloned and sequenced. In this work some proinflamatory molecules and Mx gene were detected in the liver of vaccinated sea bream juveniles with an average body weight of 5 g. The method of immunization was by short bath and three different bacterins against the marine pathogen Photobacterium damselae subsp. piscicida were designed and used to immunize fish. Five genes encoding for five different molecules were analyzed by real time PCR: IL-1ß, IL Ir-2, Cox-2, Mx and TNFα. Gene expression was quantified along four days after fish immunization and results were compared among groups. Results show that the heat-inactivated vaccine stimulates the up-regulation of IL-1ß, IL Ir-2, Cox-2 and TNFα genes whereas the UV-light inactivated vaccine was the unique vaccine which stimulates the expression of Mx gene. The present is a novel study that shows by the first time the effect of the inactivation process of vaccines on the expression levels of genes involved in the defense against Photobacterium damselae subsp piscicida.

Mindfulness-based narrative therapy for depression in cancer patients.

UNLABELLED: Mindfulness-based narrative therapy (MBNT) is a therapeutic intervention for the treatment of depression in cancer patients. In a previous randomized controlled trial, MBNT was found to ameliorate anxiety and depression, improve functional dimensions of quality of life, and enhance treatment adherence. In this review, we describe MBNT and its technical characteristics in the context of other psychotherapeutic interventions for depression in cancer patients. We highlight needed adjustments to other narrative approaches and recommend clinical modifications tailored to the needs of cancer patients that are intended to encompass the client's initial depressive narrative. The narrative construction is supported by emotional regulation and attachment relationships on the one hand and by individual and social linguistic capabilities on the other. Through destabilization of the depressive narrative, MBNT facilitates the emergence of new meanings using both verbal and non-verbal techniques based on mindfulness. The attitude and practice of mindfulness are integrated throughout the therapeutic process. In summary, MBNT makes use of linguistic interventions, promotes mindfulness and emotional regulation, and can be adapted specifically for use with cancer patients. KEY PRACTITIONER MESSAGE: In this review, we describe mindfulness-based narrative therapy (MBNT) for the treatment of depression in cancer patients. In a previous controlled trial, we found significant benefits of MBNT in terms of reducing depressive symptoms and improving treatment adherence and quality of life in depressed, non-metastatic cancer patients. Narrative construction is socially and neurobiologically derived. MBNT makes use of linguistic interventions, promotes mindfulness and emotional regulation, and can be adapted specifically for use with cancer patients. MBNT is proposed as an interesting and promising intervention, particularly for patients with somatic pathologies.

The mediating role of reflective functioning in the association between childhood trauma and suicide attempt.

BACKGROUND: Childhood trauma is intimately related with suicidal behaviour. Patients who have suffered childhood trauma develop impaired Reflective Functioning (RF), which refers to the capacity to understand ourselves and others in terms of intentional mental states. An improvement in RF has been associated with a reduction in suicidal attempts, but the mediating role of RF between childhood trauma and suicidal behaviour has not been addressed so far. OBJECTIVE: We aim to examine the potential mediating effect of RF among childhood trauma and suicide attempts. METHOD: We included 748 patients who had attempted suicide at least once. They were asked to complete the Reflective Functioning Questionnaire (RFQ-8), the Columbia-Suicide Severity Rating scale (CSSRS), and the Childhood Trauma Questionnaire-Short Form (CTQ-SF). We conducted linear regressions by simple mediating model to examine the role of RF in the indirect association between childhood trauma and the number of suicide attempts. RESULTS: Our results show significant indirect effects through hypo and hypermentalizing between Emotional Abuse (EA) and Sexual Abuse (SA) in childhood and the number of suicide attempts in lifetime. These results indicate that ineffective RF significantly mediates the association between childhood trauma and suicidality. CONCLUSION: This is the first study supporting the mediational role of RF in the relationship between EA and SA, and the number of suicide attempt in lifetime. These findings have important implications for reducing suicide rates and preventing future re-attempts. Further studies analysing this mediating role and focusing efforts on increasing RF-based interventions are required.

Studies on the fibre surfaces modified with xylan polyelectrolytes.

Xylan was isolated from birch wood chips by using pressurized hot water extraction (PHWE). The extracted xylan was chemically modified yielding three different xylan derivatives (XDs): xylan sulfate (XS), carboxymethyl xylan (CMX) and xylan-4-[N,N,N-trimethylammonium]butyrate chloride (XTMAB). The structure and molecular weight of XDs was determined by using NMR spectroscopy and size exclusion chromatography (SEC). The potential utilization of xylan polyelectrolytes for modifying fibre surfaces was assessed by sorption experiments using bleached pine Kraft pulp as substrate. Polyelectrolyte titration method was chosen for estimating the amount of sorbed XDs onto the fibres. The cationic xylan derivative XTMAB had a strong interaction with fibres while the anionic derivatives did not show any sorption. X-ray photoelectron spectroscopy (XPS) and time of flight secondary ion mass spectrometry (ToF-SIMS) were selected as advanced surface analyses for studying the amount of surface anionic groups and the surface distribution of the XTMAB. XPS and polyelectrolyte titration results suggested that the XTMAB is sorbed onto the fibre surfaces. ToF-SIMS imaging showed that XTMAB was evenly distributed on fibre surfaces.

[Retrospective observational study of the persistence of SARS-CoV-2 infection in patients previously treated with rituximab]. / Estudio observacional retrospectivo de persistencia de infección por SARS-CoV-2 en pacientes tratados previamente con rituximab.

OBJECTIVE: Rituximab-induced immunosuppression could be a risk factor for mortality from COVID-19. The aim of the study was to describe the prevalence of SARS-CoV-2 infection in patients who have received rituximab and its association with a persistent viral infection. METHODS: Retrospective observational study of patients who received rituximab in the 6 months before to the onset of the pandemic. We analyzed the presence of infection and associated them with demographic variables, pathological history related to an increased risk of developing severe COVID-19, the doses of rituximab received, the type of ventilatory support, thromboembolic events, and the treatment received. A descriptive analysis of all the variables was carried out and infected and uninfected patients were compared. RESULTS: We screened a total of 68 patients who had received rituximab (median cumulative dose: 4,161mg (2,611-8,187.5)). 54.4% men, mean age 60.8 years (15.7; 25-87)). C + was confirmed for 22 patients. Of these, 45.5% had high blood pressure, 36.4% Diabetes Mellitus, 31.8% smokers/ex-smoker, 22.7% lung disease, 13.6% heart disease and 4.5% obesity. There were no statistically significant differences between C+ and C-. Only 2 patients developed immunity. For 10 patients (45.5%) did not have a negative CRP until the end of the follow-up. There was no association with cumulative dose of rituximab. The mortality rate was 22.7% in the C+. CONCLUSIONS: We observe that the persistence of the infection leads to a worse evolution of COVID-19. The use of alternatives should be considered during the pandemic, because of patients with decreased B-cell function may have high risk of fatal progression from COVID-19.

Combined therapy versus usual care for the treatment of depression in oncologic patients: a randomized controlled trial.

OBJECTIVE: To compare narrative therapy (NT) plus escitalopram versus escitalopram plus usual care on quality of life and depressive symptomatology of depressed patients with oncologic disease. METHODS: A total of 72 subjects (mean age 54.6 years), predominantly female with non-metastatic breast, lung and colon cancer and depressive disorder (DSM-IV-TR) were randomized to receive treatment with NT plus escitalopram (n=39) or escitalopram (10-20 mg QD) plus usual care (n=33). Main endpoints were improvement in dimensions of quality of life measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C-30 and reduction of depressive symptoms using the Hospital Anxiety and Depression Scale at weeks 12 and 24. RESULTS: The combined therapy group showed significantly greater improvement in all the functioning dimensions (p<0.01), pain scale (p=0.02), global health (p=0.02), and global quality of life (p=0.007) at weeks 12 and 24. There were no statistically significant differences in depressive symptomatology between the groups. From week 12 to week 24 study retention was higher in the combined treatment group (p=0.01). CONCLUSIONS: Brief NT in combination with escitalopram was superior to usual care and escitalopram in improving functioning dimensions of quality life.

Organophosphorous pesticides research in Mexico: epidemiological and experimental approaches.

Non-persistent pesticides, such as organophosphorous (OP) insecticides have been extensively used in Mexico, and becoming a public health problem. This review presents data of OP use and related toxicity from epidemiological and experimental studies conducted in Mexico. Studies in agricultural workers from several regions of the country reported moderate to severe cholinergic symptoms, including decreased acetylcholinesterase (AChE) activity (the main acute OP toxic effect that causes an over accumulation of the neurotransmitter acetylcholine), revealing the potential risk of intoxication of Mexican farmers. OP exposure in occupational settings has been associated with decreased semen quality, sperm DNA damage and as endocrine disrupter, particularly in agricultural workers. Alterations in female reproductive function have also been observed, as well as adverse effects on embryo development by prenatal exposure in agricultural communities. This illustrates that OP exposure represents a risk for reproduction and offspring well-being in Mexico. The genotoxic effects of this group of pesticides in somatic and sperm cells are also documented. Lastly, we present data about gene-environmental interactions regarding OP metabolizing enzymes, such as paraoxonase-1 (PON1) and its role in modulating their toxicity, particularly on semen quality and sperm DNA integrity. In summary, readers will see the important health problems associated with OP exposure in Mexican populations, thereby the need of capacitation programs to communicate farmers the proper handling of agrochemicals to prevent their toxic effects and of more well designed human studies to support data of the current situation of workers and communities dedicated to agriculture activities.

The effects of altered neurogenic microRNA levels and their involvement in the aggressiveness of periventricular glioblastoma. / Efecto de la alteración de los niveles de expresión de microARN neurogénicos y su implicación en la agresividad de glioblastomas localizados en la región paraventricular.

INTRODUCTION: Glioblastoma multiforme is the most common primary brain tumour, with the least favourable prognosis. Despite numerous studies and medical advances, it continues to be lethal, with an average life expectancy of 15 months after chemo-radiotherapy. DEVELOPMENT: Recent research has addressed several factors associated with the diagnosis and prognosis of glioblastoma; one significant factor is tumour localisation, particularly the subventricular zone, which represents one of the most active neurogenic niches of the adult human brain. Glioblastomas in this area are generally more aggressive, resulting in unfavourable prognosis and a shorter life expectancy. Currently, the research into microRNAs (miRNA) has intensified, revealing different expression patterns under physiological and pathophysiological conditions. It has been reported that the expression levels of certain miRNAs, mainly those related to neurogenic processes, are dysregulated in oncogenic events, thus favouring gliomagenesis and greater tumour aggressiveness. This review discusses some of the most important miRNAs involved in subventricular neurogenic processes and their association with glioblastoma aggressiveness. CONCLUSIONS: MiRNA regulation and function play an important role in the development and progression of glioblastoma; understanding the alterations of certain miRNAs involved in both differentiation and neural and glial maturation could help us to better understand the malignant characteristics of glioblastoma.

Methyl-parathion decreases sperm function and fertilization capacity after targeting spermatocytes and maturing spermatozoa.

Paternal germline exposure to organophosphorous pesticides (OP) has been associated with reproductive failures and adverse effects in the offspring. Methyl-parathion (Me-Pa), a worldwide-used OP, has reproductive adverse effects and is genotoxic to sperm, possibly via oxidative damage. This study investigated the stages of spermatogenesis susceptible to be targeted by Me-Pa exposure that impact on spermatozoa function and their ability to fertilize. Male mice were exposed to Me-Pa (20 mg/kg bw, i.p.) and spermatozoa from epididymis-vas deferens were collected at 7 or 28 days post-treatment (dpt) to assess the effects on maturing spermatozoa and spermatocytes, respectively. Spermatozoa were examined for DNA damage by nick translation (NT-positive cells) and SCSA (%DFI), lipoperoxidation (LPO) by malondialdehyde production, sperm function by spontaneous- and induced-acrosome reactions (AR), mitochondrial membrane potential (MMP) by using the JC-1 fluorochrome, and fertilization ability by an in vitro assay and in vivo mating. Alterations on DNA integrity (%DFI and NT-positive cells) in spermatozoa collected at 7 and 28 dpt, and decreases in sperm quality and induced-AR were observed; reduced MMP and LPO were observed at 7 dpt only. Negative correlations between LPO and sperm alterations were found. Altered sperm functional parameters evaluated either in vitro or in vivo were associated with reduced fertilization rates at both times. These results show that Me-Pa exposure of maturing spermatozoa and spermatocytes affects many sperm functional parameters that result in a decreased fertilizing capacity. Oxidative stress seems to be a likely mechanism of the detrimental effects of Me-Pa exposure in male germ cells.

Prenatal exposure to metals modified DNA methylation and the expression of antioxidant- and DNA defense-related genes in newborns in an urban area.

The developmental period in utero is a critical window for environmental exposure. Epigenetic fetal programming via DNA methylation is a pathway through which metal exposure influences the risk of developing diseases later in life. Genetic damage repair can be modified by alterations in DNA methylation, which, in turn, may modulate gene expression due to metal exposure. We investigated the impact of prenatal metal exposure on global and gene-specific DNA methylation and mRNA expression in 181 umbilical cord blood samples from newborns in Mexico City. Global (LINE1) and promoter methylation of DNA-repair (OGG1 and PARP1) and antioxidant (Nrf2) genes was evaluated by pyrosequencing. Prenatal metal exposure (As, Cu, Hg, Mn, Mo, Pb, Se, and Zn) was determined by ICP-MS analysis of maternal urine samples. Multiple regression analyses revealed that DNA methylation of LINE1, Nrf2, OGG1, and PARP1 was associated with potentially toxic (As, Hg, Mn, Mo, and Pb) and essential (Cu, Se, and Zn) elements, and with their interactions. We also evaluated the association between gene expression (mRNA levels quantified by p-PCR) and DNA methylation. An increase in OGG1 methylation at all sites and at CpG2, CpG3, and CpG4 sites was associated with reduced mRNA levels; likewise, methylation at the CpG5, CpG8, and CpG11 sites of PARP1 was associated with reduced mRNA expression. In contrast, methylation at the PARP1 CpG7 site was positively associated with its mRNA levels. No associations between Nrf2 expression and CpG site methylation were observed. Our data suggest that DNA methylation can be influenced by prenatal metal exposure, which may contribute to alterations in the expression of repair genes, and therefore, result in a lower capacity for DNA damage repair in newborns.

Exposure to diethylhexyl phthalate (DEHP) and monoethylhexyl phthalate (MEHP) promotes the loss of alveolar epithelial phenotype of A549 cells.

Di(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer that is metabolized to mono(2-ethylhexyl) phthalate (MEHP). Inhalation is an important exposure route for both phthalates, and their effects on lungs include inflammation, alteration of postnatal maturation (alveolarization), enlarged airspaces and cell differentiation changes, suggesting that alveolar epithelial cells-2 (AEC) are targets of phthalates. This study evaluated the cell progression, epithelial and mesenchymal markers, including surfactant secretion in A549 cells (AEC) that were exposed to DEHP (1-100 µM) or MEHP (1-50 µM) for 24-72 h. The results showed an increased cell proliferation at all concentrations of each phthalate at 24 and 48 h. Cell migration showed a concentration-dependent increase at 24 and 48 h of exposure to either phthalate and enlarged structures were seen. Decreased levels of both surfactants (SP-B/SP-C) were observed after the exposure to either phthalate at 48 h, and of SP-C positive cells exposed to MEHP, suggesting a loss of the epithelial phenotype. While a decrease in the epithelial marker E-cadherin and an increase in the mesenchymal marker fibronectin were observed following exposure to either phthalate. Our results showed that DEHP and MEHP altered the structure and migration of A549 cells and promoted the loss of the epithelial phenotype.

Spermatozoa nucleus takes up lead during the epididymal maturation altering chromatin condensation.

Lead (Pb) alters sperm chromatin condensation (CC) and the mechanisms are investigated. During spermatogenesis, protamines replace histones and disulfide bonds formation during epididymal maturation condense the chromatin. We evaluated sperm Pb uptake in testis and epididymis and the effects on CC in mice (0.06% Pb(2+)/16 weeks/drinking water). Spermatozoa from caput epididymis (CP) and cauda epididymis-vas deferens (CE-VD) were obtained and CC was measured by SCSA. Lead levels in spermatozoa from CP were lower than those from CE-VD, and correlated with a decreased CC, while Pb in CE-VD spermatozoa correlated with an increased CC. Lead accumulation into the nucleus was observed and Pb binding to nuclear sulfhydryl groups decreased chromatin decondensation in vitro. Our results suggest that spermatozoa take up Pb during testicular development and epididymal transport and alter CC, depending of the timing of Pb incorporation into the sperm nucleus, which finally may interfere with the chromatin decondensation process after fertilization.

Clinical effectiveness of exenatide in diabetic patients waiting for bariatric surgery.

BACKGROUND: Bariatric surgery constitutes the most effective treatment for severely obese type 2 diabetic patients. Exenatide is a glucagon-like peptide 1 receptor agonist that can improve glycemic control and cause weight loss in patients with type 2 diabetes. Clinical experience with exenatide in obese patients with type 2 diabetes waiting for bariatric surgery has not been reported. The aim of the study was to evaluate, in clinical practice, weight and metabolic effects of exenatide (after 3 and 6 months) in patients with type 2 diabetes and obesity waiting for bariatric surgery. METHODS: A total of 100 diabetic adult subjects with a BMI ≥ 35 kg/m(2) were included. Primary endpoints were changes in weight and HbA1c after 6 months of treatment. Secondary endpoints were changes from baseline of a variety of clinical measures (triglycerides levels, blood pressure, and waist circumference). Data were analyzed at 3 and 6 months of follow-up. RESULTS: Treatment for 6 months with exenatide decreased significantly body weight (-12.5 kg) and waist circumference (-13 cm). Twenty percent of patients reduced their BMI under 35 kg/m(2) and significantly improved their metabolic profile (HbA1c <7 %). Significant and maintained decreases in HbA1c of 1 % were observed in the 3 and 6 months cohorts. Triglycerides levels and blood pressure also decreased from baseline to the end of the study. Treatment was discontinued in 19 % of patients mainly due to drug inefficacy (6 %) or adverse events (4 %). CONCLUSIONS: Exenatide twice daily (BID) leads to early, robust, and significant weight loss in a subset of patients with diabetes and severe obesity before bariatric surgery. Clinical trials are needed to confirm the benefits of GLP-1 agonists in type 2 diabetic obese patients or high-risk super-obese patients waiting for bariatric surgery.

COVID 19 y embarazo en Chile: Informe preliminar del estudio multicéntrico GESTACOVID / COVID-19 and pregnancy in Chile: preliminary report of the GESTACOVID multicenter study

INTRODUCCIÓN: En Chile, los efectos maternos y perinatales de la pandemia por SARS-CoV-2 son aún desconocidos. GESTACOVID es un estudio multicéntrico que incluye embarazadas y puérperas hasta el día 42 con COVID-19. El objetivo de este estudio es presentar un informe preliminar, describiendo el impacto de la enfermedad en las embarazadas, factores de riesgo asociados y resultados perinatales. MÉTODOS: Estudio de cohorte descriptivo que incluye 661 pacientes enroladas entre el 7 de marzo y el 6 de julio de 2020, en 23 centros hospitalarios del país. Se analizaron variables demográficas, comorbilidades, características clínicas y del diagnóstico de COVID-19 y resultado materno y perinatal. RESULTADOS: Las pacientes hospitalizadas por COVID-19 tuvieron mayor prevalencia de hipertensión arterial crónica [10% vs 3%; OR=3,1 (1,5-6,79); p=0,003] y de diabetes tipo 1 y 2 [7% vs 2%; OR=3,2 (1,3-7,7); p=0,009] que las pacientes manejadas ambulatoriamente. Un IMC >40 kg/mt2 se asoció con un riesgo dos veces mayor de requerir manejo hospitalizado [OR=2,4 (1,2 - 4,6); p=0,009]. Aproximadamente la mitad de las pacientes (54%) tuvo un parto por cesárea, y un 8% de las interrupciones del embarazo fueron por COVID-19. Hasta la fecha de esta publicación, 38% de las pacientes continuaban embarazadas. Hubo 21 PCR positivas en 316 neonatos (6,6%), la mayoría (17/21) en pacientes diagnosticadas por cribado universal. CONCLUSIONES: Las embarazadas con COVID-19 y comorbilidades como diabetes, hipertensión crónica y obesidad mórbida deben ser manejadas atentamente y deberán ser objeto de mayor investigación. La tasa de transmisión vertical requiere una mayor evaluación para diferenciar el mecanismo y tipo de infección involucrada.

INTRODUCTION: In Chile, effects of the SARS-CoV-2 infection in pregnant women are unknown. GESTACOVID is a multicenter collaborative study including pregnant women and those in the postpartum period (until 42 days) who have had COVID-19. The purpose of this study is to report our preliminary results describing the clinical impact of COVID-19 in pregnant women, the associated risk factors and perinatal results. METHODS: Descriptive cohort study including 661 patients between April 7th and July 6th, 2020, in 23 hospitals. Demographical, comorbidities, clinical and diagnostic characteristics of COVID-19 disease and maternal and perinatal outcomes were analyzed. RESULTS: Pregnant women with COVID-19 admitted to the hospital were more likely to have chronic hypertension [10% vs 3%; OR=3.1 (1.5-6.79); p=0,003] and diabetes type 1 and 2 [7% vs 2%; OR=3.2 (1.3-7.7); p=0.009] than those with outpatient management. A body mass index of >40 kg/mt2 was associated with two-fold higher risk of hospitalization [OR=2.4 (1.2-4.6); p=0.009]. Almost half of patients (54%) were delivered by cesarean section, and 8% of the medically indicated deliveries were due to COVID-19. So far, 38% of the patients are still pregnant. Among 316 newborns, there were 21 positive PCR tests (6.6%), mostly from asymptomatic mothers undergoing universal screening. CONCLUSIONS: Pregnant women with COVID-19 and comorbidities such as diabetes, chronic hypertension and morbid obesity need a close follow up and should be a matter for further research. Vertical transmission of COVID-19 should be thoroughly studied to define the mechanisms and type of infection involved.

Cardiac involvement in acromegaly: specific myocardiopathy or consequence of systemic hypertension?

To evaluate the relative contributions of past or present GH hypersecretion and of hypertension to the cardiac abnormalities present in acromegaly, we have studied the serum GH and insulin-like growth factor I concentrations, systolic and diastolic blood pressures, and morphological and functional cardiac indexes as measured by echocardiography-Doppler, in 39 patients with active or cured acromegaly, 16 hypertensive controls, and 17 normotensive controls. Hypertension was present in 42.8% of patients with active acromegaly and in 28.0% of patients in which acromegaly was cured. Hypertension was independently related to an increase in indexes of cardiac morphology (left ventricular mass, left ventricular posterior wall thickness, interventricular septum thickness, relative wall thickness with respect to the diastolic diameter of the left ventricle, and left atrial end-systolic diameter), systolic function (stroke volume, fractional shortening, and end-systolic stress), and diastolic function (isovolumic relaxation time and maximal late diastolic flow velocity) and to a reduction in the early to late maximal diastolic flow velocity ratio. Acromegaly was related to an increase in left ventricular mass, stroke volume, cardiac output, and isovolumic relaxation time, which were independent from the presence of hypertension. End-systolic stress was reduced by acromegaly. In the five patients in which active acromegaly was successfully treated, left ventricular mass and left ventricular posterior wall thickness were reduced 1 yr later. In conclusion, the asymptomatic morphological and functional cardiac abnormalities present in acromegalic patients are independently related to acromegaly and hypertension, pointing to the existence to a specific acromegalic myocardiopathy that might be aggravated by the coexistence of hypertension.