Maternal vaccination against COVID-19 and neonatal outcomes during Omicron: INTERCOVID-2022 study.

BACKGROUND: In early 2023, when Omicron was the variant of concern, we showed that vaccinating pregnant women decreased the risk for severe COVID-19-related complications and maternal morbidity and mortality. OBJECTIVE: This study aimed to analyze the impact of COVID-19 during pregnancy on newborns and the effects of maternal COVID-19 vaccination on neonatal outcomes when Omicron was the variant of concern. STUDY DESIGN: INTERCOVID-2022 was a large, prospective, observational study, conducted in 40 hospitals across 18 countries, from November 27, 2021 (the day after the World Health Organization declared Omicron the variant of concern) to June 30, 2022, to assess the effect of COVID-19 in pregnancy on maternal and neonatal outcomes and to assess vaccine effectiveness. Women diagnosed with laboratory-confirmed COVID-19 during pregnancy were compared with 2 nondiagnosed, unmatched women recruited concomitantly and consecutively during pregnancy or at delivery. Mother-newborn dyads were followed until hospital discharge. The primary outcomes were a neonatal positive test for COVID-19, severe neonatal morbidity index, severe perinatal morbidity and mortality index, preterm birth, neonatal death, referral to neonatal intensive care unit, and diseases during the neonatal period. Vaccine effectiveness was estimated with adjustment for maternal risk profile. RESULTS: We enrolled 4707 neonates born to 1577 (33.5%) mothers diagnosed with COVID-19 and 3130 (66.5%) nondiagnosed mothers. Among the diagnosed mothers, 642 (40.7%) were not vaccinated, 147 (9.3%) were partially vaccinated, 551 (34.9%) were completely vaccinated, and 237 (15.0%) also had a booster vaccine. Neonates of booster-vaccinated mothers had less than half (relative risk, 0.46; 95% confidence interval, 0.23-0.91) the risk of being diagnosed with COVID-19 when compared with those of unvaccinated mothers; they also had the lowest rates of preterm birth, medically indicated preterm birth, respiratory distress syndrome, and number of days in the neonatal intensive care unit. Newborns of unvaccinated mothers had double the risk for neonatal death (relative risk, 2.06; 95% confidence interval, 1.06-4.00) when compared with those of nondiagnosed mothers. Vaccination was not associated with any congenital malformations. Although all vaccines provided protection against neonatal test positivity, newborns of booster-vaccinated mothers had the highest vaccine effectiveness (64%; 95% confidence interval, 10%-86%). Vaccine effectiveness was not as high for messenger RNA vaccines only. Vaccine effectiveness against moderate or severe neonatal outcomes was much lower, namely 13% in the booster-vaccinated group (all vaccines) and 25% and 28% in the completely and booster-vaccinated groups, respectively (messenger RNA vaccines only). Vaccines were fairly effective in protecting neonates when given to pregnant women ≤100 days (14 weeks) before birth; thereafter, the risk increased and was much higher after 200 days (29 weeks). Finally, none of the neonatal practices studied, including skin-to-skin contact and direct breastfeeding, increased the risk for infecting newborns. CONCLUSION: When Omicron was the variant of concern, newborns of unvaccinated mothers had an increased risk for neonatal death. Neonates of vaccinated mothers had a decreased risk for preterm birth and adverse neonatal outcomes. Because the protective effect of COVID-19 vaccination decreases with time, to ensure that newborns are maximally protected against COVID-19, mothers should receive a vaccine or booster dose no more than 14 weeks before the expected date of delivery.

Development of the Placenta and Brain Are Affected by Selective Serotonin Reuptake Inhibitor Exposure During Critical Periods.

Selective serotonin reuptake inhibitors (SSRIs) are usually prescribed to treat major depression and anxiety disorders. Fetal brain development exhibits dependency on serotonin (5-hydroxytryptamine, 5-HT) from maternal, placental, and fetal brain sources. At very early fetal stages, fetal serotonin is provided by maternal and placental sources. However, in later fetal stages, brain sources are indispensable for the appropriate development of neural circuitry and the rise of emergent functions implied in behavior acquisition. Thus, susceptible serotonin-related critical periods are recognized, involving the early maternal and placental 5-HT synthesis and the later endogenous 5-HT synthesis in the fetal brain. Acute and chronic exposure to SSRIs during these critical periods may result in short- and long-term placental and brain dysfunctions affecting intrauterine and postnatal life. Maternal and fetal cells express serotonin receptors which make them susceptible to changes in serotonin levels influenced by SSRIs. SSRIs block the serotonin transporter (SERT), which is required for 5-HT reuptake from the synaptic cleft into the presynaptic neuron. Chronic SSRI administration leads to pre- and postsynaptic 5-HT receptor rearrangement. In this review, we focus on the effects of SSRIs administered during critical periods upon placentation and brain development to be considered in evaluating the risk-safety balance in the clinical use of SSRIs.

Effects of Prenatal Cannabinoids Exposure upon Placenta and Development of Respiratory Neural Circuits.

Cannabis use has risen dangerously during pregnancy in the face of incipient therapeutic use and a growing perception of safety. The main psychoactive compound of the Cannabis sativa plant is the phytocannabinoid delta-9-tetrahydrocannabinol (A-9 THC), and its status as a teratogen is controversial. THC and its endogenous analogues, anandamide (AEA) and 2-AG, exert their actions through specific receptors (eCBr) that activate intracellular signaling pathways. CB1r and CB2r, also called classic cannabinoid receptors, together with their endogenous ligands and the enzymes that synthesize and degrade them, constitute the endocannabinoid system. This system is distributed ubiquitously in various central and peripheral tissues. Although the endocannabinoid system's most studied role is controlling the release of neurotransmitters in the central nervous system, the study of long-term exposure to cannabinoids on fetal development is not well known and is vital for understanding environmental or pathological embryo-fetal or postnatal conditions. Prenatal exposure to cannabinoids in animal models has induced changes in placental and embryo-fetal organs. Particularly, cannabinoids could influence both neural and nonneural tissues and induce embryo-fetal pathological conditions in critical processes such as neural respiratory control. This review aims at the acute and chronic effects of prenatal exposure to cannabinoids on placental function and the embryo-fetal neurodevelopment of the respiratory pattern. The information provided here will serve as a theoretical framework to critically evaluate the teratogen effects of the consumption of cannabis during pregnancy.

Pregnancy outcomes and vaccine effectiveness during the period of omicron as the variant of concern, INTERCOVID-2022: a multinational, observational study.

BACKGROUND: In 2021, we showed an increased risk associated with COVID-19 in pregnancy. Since then, the SARS-CoV-2 virus has undergone genetic mutations. We aimed to examine the effects on maternal and perinatal outcomes of COVID-19 during pregnancy, and evaluate vaccine effectiveness, when omicron (B.1.1.529) was the variant of concern. METHODS: INTERCOVID-2022 is a large, prospective, observational study, involving 41 hospitals across 18 countries. Each woman with real-time PCR or rapid test, laboratory-confirmed COVID-19 in pregnancy was compared with two unmatched women without a COVID-19 diagnosis who were recruited concomitantly and consecutively in pregnancy or at delivery. Mother and neonate dyads were followed until hospital discharge. Primary outcomes were maternal morbidity and mortality index (MMMI), severe neonatal morbidity index (SNMI), and severe perinatal morbidity and mortality index (SPMMI). Vaccine effectiveness was estimated, adjusted by maternal risk profile. FINDINGS: We enrolled 4618 pregnant women from Nov 27, 2021 (the day after WHO declared omicron a variant of concern), to June 30, 2022: 1545 (33%) women had a COVID-19 diagnosis (median gestation 36·7 weeks [IQR 29·0-38·9]) and 3073 (67%) women, with similar demographic characteristics, did not have a COVID-19 diagnosis. Overall, women with a diagnosis had an increased risk for MMMI (relative risk [RR] 1·16 [95% CI 1·03-1·31]) and SPMMI (RR 1·21 [95% CI 1·00-1·46]). Women with a diagnosis, compared with those without a diagnosis, also had increased risks of SNMI (RR 1·23 [95% CI 0·88-1·71]), although the lower bounds of the 95% CI crossed unity. Unvaccinated women with a COVID-19 diagnosis had a greater risk of MMMI (RR 1·36 [95% CI 1·12-1·65]). Severe COVID-19 symptoms in the total sample increased the risk of severe maternal complications (RR 2·51 [95% CI 1·84-3·43]), perinatal complications (RR 1·84 [95% CI 1·02-3·34]), and referral, intensive care unit (ICU) admission, or death (RR 11·83 [95% CI 6·67-20·97]). Severe COVID-19 symptoms in unvaccinated women increased the risk of MMMI (RR 2·88 [95% CI 2·02-4·12]) and referral, ICU admission, or death (RR 20·82 [95% CI 10·44-41·54]). 2886 (63%) of 4618 total participants had at least a single dose of any vaccine, and 2476 (54%) of 4618 had either complete or booster doses. Vaccine effectiveness (all vaccines combined) for severe complications of COVID-19 for all women with a complete regimen was 48% (95% CI 22-65) and 76% (47-89) after a booster dose. For women with a COVID-19 diagnosis, vaccine effectiveness of all vaccines combined for women with a complete regimen was 74% (95% CI 48-87) and 91% (65-98) after a booster dose. INTERPRETATION: COVID-19 in pregnancy, during the first 6 months of omicron as the variant of concern, was associated with increased risk of severe maternal morbidity and mortality, especially among symptomatic and unvaccinated women. Women with complete or boosted vaccine doses had reduced risk for severe symptoms, complications, and death. Vaccination coverage among pregnant women remains a priority. FUNDING: None.

Characterization of Alzheimer's disease-like neuropathology in Duchenne's muscular dystrophy using the DBA/2J mdx mouse model.

Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disorder caused by a mutation in the dystrophin gene. In addition to muscle pathology, some patients with DMD will exhibit cognitive impairments with severity being linked to age and type of genetic mutation. Likewise, some studies have shown that mdx mice display impairments in spatial memory compared with wild-type (WT) controls, while others have not observed any such effect. Most studies have utilized the traditional C57BL/10 (C57) mdx mouse, which exhibits a mild disease phenotype. Recently, the DBA/2J (D2) mdx mouse has emerged as a more severe and perhaps clinically relevant DMD model; however, studies examining cognitive function in these mice are limited. Thus, in this study we examined cognitive function in age-matched C57 and D2 mdx mice along with their respective WT controls. Our findings show that 8- to 12-week-old C57 mdx mice did not display any differences in exploration time when challenged with a novel object recognition test. Conversely, age-matched D2 mdx mice spent less time exploring objects in total as a well as less time exploring the novel object, suggestive of impaired recognition memory. Biochemical analyses of the D2 mdx brain revealed higher soluble amyloid precursor protein ß (APPß) and APP in the prefrontal cortex of mdx mice compared with WT, and lower soluble APPα in the hippocampus, suggestive of a shift towards amyloidogenesis and a similar pathogenesis to Alzheimer's disease. Furthermore, our study demonstrates the utility of the D2 mdx model in studying cognitive impairment.

Post-transplant lymphoproliferative disorders in a cohort of adult patients with a liver transplant from a reference hospital in Bogotá, Colombia / Trastornos linfoproliferativos en una cohorte de pacientes adultos con trasplante hepático atendidos en un hospital de referencia en Bogotá, Colombia.

Introduction: The post-transplant lymphoproliferative disorders (PTLD) are characterized by an uncontrolled pathological lymphoid proliferation as a consequence of transplant immunosuppression therapy. Objective: To characterize the clinical and pathological characteristics of PTLD in a cohort of adult patients with liver transplant during a 15 year period at the Hospital Universitario Fundación Santa Fe de Bogota. Materials and methods: We conducted an observational retrospective study by searching for the PTLD cases diagnosed during the study period in the databases of the Liver Transplantation Unit and the Pathology Department. We collected the epidemiological, clinical, and pathological information and performed the corresponding statistics analyses. Results: During the research period, 572 patients were transplanted; the incidence of PTDL was 2.44%; 79% of them were man and the average age at the time of diagnosis was 62.5 years; 71% of the cases were diagnosed during the first year after the transplant and the same percentage EBV-seropositive patients. The most frequent pathological phenotype was monomorphic and the majority of tumors was detected in the hepatic hilum. The one-year survival was 50%. Conclusion: The high proportion of early cases and the high frequency of Epstein-Barr virus seropositivity both in donors and receptors drewour attention. More studies are necessary to have a better understanding of this condition in Colombia. This is the first PTLD clinical and pathological analysis in liver-transplant patients from Colombia to date.

Introducción. Los trastornos linfoproliferativos después de un trasplante se caracterizan por la proliferación descontrolada de linfocitos como consecuencia del tratamiento inmunosupresor posterior a este. Objetivo. Caracterizar clínica y patológicamente los casos de trastornos linfoproliferativos después de trasplante (Post-Transplant Lymphoproliferative Disorders, PTLD) en una cohorte de pacientes adultos con trasplante de hígado atendidos a lo largo de 15 años en el Hospital Universitario Fundación Santa Fe de Bogotá. Materiales y métodos. Se hizo un estudio observacional retrospectivo a partir de la revisión de las bases de datos de la Unidad de Trasplante Hepático y del Departamento de Patología del Hospital en busca de los casos de PTLD diagnosticados durante el periodo de estudio. Se recolectó la información epidemiológica, clínica y patológica, y se adelantaron los análisis estadísticos. Resultados. Durante el periodo de estudio, hubo 572 pacientes con trasplante de hígado, la incidencia de trastornos linfoproliferativos fue de 2,44 %, el 79 % en hombres, y la edad promedio en el momento del diagnóstico fue de 62,5 años. El 71 % de los casos se presentó durante los primeros 12 meses después del trasplante y el mismo porcentaje fue seropositivo para el virus de Epstein-Barr (EBV). El fenotipo patológico más frecuente fue el monomorfo y la mayoría de los tumores se detectaron en el hilio hepático. La supervivencia al año fue del 50 %. Conclusiones. Llamó la atención el alto porcentaje de casos de presentación temprana, así como la gran frecuencia de seropositividad para el EBV tanto en los donantes como en los receptores. Deben adelantarse estudios más detallados para una mejor comprensión de esta enfermedad en el país. Este es el primer análisis clínico y patológico de PTLD en pacientes con trasplante de hígado adelantado en Colombia hasta la fecha.

Trastornos linfoproliferativos en una cohorte de pacientes adultos con trasplante hepático atendidos en un hospital de referencia en Bogotá, Colombia / Post-transplant lymphoproliferative disorders in a cohort of adult patients with a liver transplant from a reference hospital in Bogotá, Colombia

Introducción. Los trastornos linfoproliferativos después de un trasplante se caracterizan por la proliferación descontrolada de linfocitos como consecuencia del tratamiento inmunosupresor posterior a este. Objetivo. Caracterizar clínica y patológicamente los casos de trastornos linfoproliferativos después de trasplante (Post-Transplant Lymphoproliferative Disorders, PTLD) en una cohorte de pacientes adultos con trasplante de hígado atendidos a lo largo de 15 años en el Hospital Universitario Fundación Santa Fe de Bogotá. Materiales y métodos. Se hizo un estudio observacional retrospectivo a partir de la revisión de las bases de datos de la Unidad de Trasplante Hepático y del Departamento de Patología del Hospital en busca de los casos de PTLD diagnosticados durante el periodo de estudio. Se recolectó la información epidemiológica, clínica y patológica, y se adelantaron los análisis estadísticos. Resultados. Durante el periodo de estudio, hubo 572 pacientes con trasplante de hígado, la incidencia de trastornos linfoproliferativos fue de 2,44 %, el 79 % en hombres, y la edad promedio en el momento del diagnóstico fue de 62,5 años. El 71 % de los casos se presentó durante los primeros 12 meses después del trasplante y el mismo porcentaje fue seropositivo para el virus de Epstein-Barr (EBV). El fenotipo patológico más frecuente fue el monomorfo y la mayoría de los tumores se detectaron en el hilio hepático. La supervivencia al año fue del 50 %. Conclusiones. Llamó la atención el alto porcentaje de casos de presentación temprana, así como la gran frecuencia de seropositividad para el EBV tanto en los donantes como en los receptores. Deben adelantarse estudios más detallados para una mejor comprensión de esta enfermedad en el país. Este es el primer análisis clínico y patológico de PTLD en pacientes con trasplante de hígado adelantado en Colombia hasta la fecha.

Introduction: The post-transplant lymphoproliferative disorders (PTLD) are characterized by an uncontrolled pathological lymphoid proliferation as a consequence of transplant immunosuppression therapy. Objective: To characterize the clinical and pathological characteristics of PTLD in a cohort of adult patients with liver transplant during a 15 year period at the Hospital Universitario Fundación Santa Fe de Bogota. Materials and methods: We conducted an observational retrospective study by searching for the PTLD cases diagnosed during the study period in the databases of the Liver Transplantation Unit and the Pathology Department. We collected the epidemiological, clinical, and pathological information and performed the corresponding statistics analyses. Results: During the research period, 572 patients were transplanted; the incidence of PTDL was 2.44%; 79% of them were man and the average age at the time of diagnosis was 62.5 years; 71% of the cases were diagnosed during the first year after the transplant and the same percentage EBV-seropositive patients. The most frequent pathological phenotype was monomorphic and the majority of tumors was detected in the hepatic hilum. The one-year survival was 50%. Conclusion: The high proportion of early cases and the high frequency of Epstein-Barr virus seropositivity both in donors and receptors drewour attention. More studies are necessary to have a better understanding of this condition in Colombia. This is the first PTLD clinical and pathological analysis in liver-transplant patients from Colombia to date.

Coarse-Grained Parameters for Divalent Cations within the SIRAH Force Field.

Although molecular dynamics simulations allow for the study of interactions among virtually all biomolecular entities, metal ions still pose significant challenges in achieving an accurate structural and dynamical description of many biological assemblies, particularly to coarse-grained (CG) models. Although the reduced computational cost of CG methods often makes them the technique of choice for the study of large biomolecular systems, the parameterization of metal ions is still very crude or not available for the vast majority of CG force fields. Here, we show that incorporating statistical data retrieved from the Protein Data Bank (PDB) to set specific Lennard-Jones interactions can produce structurally accurate CG molecular dynamics simulations using the SIRAH force field. We provide a set of interaction parameters for calcium, magnesium, and zinc ions, which cover more than 80% of the metal-bound structures reported in the PDB. Simulations performed on several proteins and DNA systems show that it is possible to preclude the use of topological constraints by modifying specific Lennard-Jones interactions.

Análisis interdisciplinar con perspectiva de género del alcoholismo en mujeres / Interdisciplinary Analysis with a Gender Perspective on Alcoholism in Women

Introducción: El alcoholismo, entendido en el marco del consumo con dependencia, es una problemática que afecta tanto a hombres como mujeres, sin embargo, con una tendencia al alza en estas últimas. Esto reviste una complejidad diferente al momento de ser abordado, asociada a la dimensión social, el género y el clandestinaje. Objetivo: Comprender las maneras en que opera la dimensión cultural y, en específico, el género, en las trayectorias de vida de mujeres alcohólicas. Métodos: Desde un enfoque cualitativo y transversal, la investigación propone el método etnosociológico sobre relatos de vida, basado en estudios de caso. Resultados: La experiencia del consumo de alcohol está marcada por: I- Consumo inicial en la niñez, que facilita el posterior acceso en una etapa adolescente, etapa asociada al consumo reiterado y vinculado a la aceptación social en términos de expectativas de género. II- Consumo adulto, periodo más problemático desde la perspectiva de la dependencia, clandestinaje y experiencias de violencia asociadas. III- Rehabilitación, proceso indefinido cuyo inicio se asocia a la experiencia de género. Todas las etapas del alcoholismo, en las historias de vida analizadas, tienen relación con el género, lo que se expresa principalmente en: el estigma; la vulnerabilidad; la violencia y el consumo clandestino. Conclusiones: los procesos de rehabilitación de alcoholismo en mujeres requieren de una perspectiva interdisciplinaria que integre el enfoque de género(AU)

Introduction: Alcoholism, understood in the s of consumption with dependence, is a concern affecting both men and women, although with is an upward tendency among the latter ones. This is approached with a different complexity, in association with the social dimension, the gender perspective, and concealment. Objective: To analyze the ways in which the cultural dimension affects several aspects, specifically gender, in the life paths of alcoholic women. Methods: A research with a qualitative and cross-sectional approach was carried out. The ethno-sociological method of life stories was used, based on case studies. Results: The experience of alcohol consumption is marked by 1) initial consumption in childhood, which facilitates subsequent access in a teenage stage, a stage associated with repeated consumption and linked to social acceptance in terms of gender expectations; 2) adult consumption, the most problematic period from the perspective of dependency, concealment, and associated experiences of violence; and 3) rehabilitation, an indefinite process whose beginning is associated with the gender experience. All stages of alcoholism, in the life stories analyzed, are related to gender, which is expressed mainly through stigma, vulnerability, violence, and concealed consumption. Conclusions: Alcoholism rehabilitation processes in women require an interdisciplinary perspective integrating the gender approach(AU)

Design, facile synthesis, and evaluation of novel spiro- and pyrazolo[1,5-c]quinazolines as cholinesterase inhibitors: Molecular docking and MM/GBSA studies.

Given the wide spectrum of biological uses of pyrazolo[1,5-c]quinazoline and spiro-quinazoline derivatives as anticancer, anti-inflammatory analgesic agents, and their therapeutic applications in neurodegenerative disorders, it is compulsory to find easy, efficient, and simple methods to obtain and chemically diversify these families of compounds, thereby improving their biological applications. In this paper, we report the design and eco-friendly two-step synthesis of novel, fused spiro-pyrazolo[1,5-c]quinazoline derivatives as cholinesterase inhibitors. In addition, we studied their protein-ligand interactions via molecular docking and MM/GBSA calculations for a further rational design of more potent inhibitors. In first step, 2-(1H-pyrazol-5-yl)anilines were obtained through microwave (MW) assisted solvent-free/catalyst-free conditions and the second step involved the synthesis of the spiro-pyrazolo[1,5-c]quinazolines by a cyclocondensation reaction between 2-(1H-pyrazol-5-yl)anilines and cyclic ketones, or acetophenones, using stirring at room temperature. The compounds were obtained in high purity, good yields (50-97%), and at varying reaction times. The spiro-compounds were evaluated as acetylcholinesterase and butyrylcholinesterase inhibitors (AChEIs/BuChEIs) respectively, and the most potent compound exhibited a moderate AChE inhibitory activity (5f: IC50 = 84 µM). Molecular docking studies indicated that the binding mode of the compound 5f share common characteristics with the galantamine/donepezil-AChE complexes. Moreover, free binding energy (ΔG) calculations showed a good agreement with the experimental biological activity values. Our theoretical results indicated that halogen bond interactions could be involved with differential potency of these compounds and provide a new starting point to design novel pyrazolo[1,5-c]quinazolines as new anti-Alzheimer agents.

Variables inespecíficas en psicoterapia: [revisión] / Inespecific variables in psychoterapy: [revision]

Este artículo presenta una sistematización teórica de las variables inespecíficas que se han estudiado intervienen en el proceso psicoterapéutico.Se realiza una revisión de la investigación de proceso en psicoterapia y la influencia de los factores comunes en el cambio terapéutico, para finalizar con una descripción de los principales hallazgos respecto a las variables inespecíficas reportadas en la literatura: del consultante, del terapeuta y de la relación.

This paper presents a theoretical systematization of the non specific variables, that have been studied to intervene in the psychotherapy process. The article presents a review of the psychotherapy process research and its influence of the common factors in psychotherapeutic change. It finishes with a description to the principal findings about non specifics variables to the literature reports: to the patient, to the therapist and the therapeutic relationship.