Redox Regulation of LAT Enhances T Cell-Mediated Inflammation.

The positional cloning of single nucleotide polymorphisms (SNPs) of the neutrophil cytosolic factor 1 (Ncf1) gene, advocating that a low oxidative burst drives autoimmune disease, demands an understanding of the underlying molecular causes. A cellular target could be T cells, which have been shown to be regulated by reactive oxygen species (ROS). However, the pathways by which ROS mediate T cell signaling remain unclear. The adaptor molecule linker for activation of T cells (LAT) is essential for coupling T cell receptor-mediated antigen recognition to downstream responses, and it contains several cysteine residues that have previously been suggested to be involved in redox regulation. To address the possibility that ROS regulate T cell-dependent inflammation through LAT, we established a mouse strain with cysteine-to-serine mutations at positions 120 and 172 (LATSS). We found that redox regulation of LAT through C120 and C172 mediate its localization and phosphorylation. LATSS mice had reduced numbers of double-positive thymocytes and naïve peripheral T cells. Importantly, redox insensitivity of LAT enhanced T cell-dependent autoimmune inflammation in collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis (RA). This effect was reversed on an NCF1-mutated (NCF1m1j), ROS-deficient, background. Overall, our data show that LAT is redox-regulated, acts to repress T cell activation, and is targeted by ROS induced by NCF1 in antigen-presenting cells (APCs).

R programming environment in wildlife: Are Veterinary Sciences at the same level than other research areas?

The computing environment has revolutionized the management and analysis of data in sciences during the last decades. This study aimed to evaluate the use of R software in research articles addressing the study of wildlife worldwide, particularly focusing on the research area "Veterinary Sciences". For this purpose, a systematic review mainly performed in the Web of Science database was conducted. Out of a total of 509 articles reviewed, our results show an increasing trend of the number of publications using the R software over time, as well as a wide geographical distribution at a global scale, particularly in North America, Europe, Australia and China. Most publications were categorized in research areas related to "Biological Sciences", while a minority of them was included in "Veterinary Sciences" (5.9%; 30/509). About the species groups assessed, many articles evaluated a single species group (96.5%), being mammals (50.7%) and birds (14.8%) the most studied ones. The present study showed a high variety of R-packages used in the publications reviewed, all of them related to data analysis, the study of genetic/phylogenetic information and graphical representation. Interestingly, the common use of packages between different research areas is indicative of the high interest of using R software in scientific articles. Our study points the R software as an open-source programming language that allows to support research addressing the study of wildlife, becoming a key software for many research areas, including "Veterinary Sciences". However, an in-depth methodological description about the use of R software in publications to improve the tracking, reproducibility and transparency is encouraged.

Manejo materno de recién nacidos atendidos en el Centro de Salud Tulcán No. 1. Ecuador, 2021-2022

Fundamento: la correcta atención materna en etapa neonatal es un factor elemental para el estado de salud del niño. Objetivo: describir el manejo materno de recién nacidos atendidos en el Centro de Salud Tulcán No. 1. Métodos: estudio observacional, descriptivo, transversal sobre madres de recién nacidos que asistieron al Centro de Salud Tulcán N°1 en el periodo de septiembre de 2021 a febrero de 2022. La población estudiada fue de 30 madres. Se analizaron las variables: identificación de signos de alarmas, elementos referidos a la alimentación, cuidados y características del cordón umbilical, higiene en el manejo del recién nacido y momento de asistencia al primer control neonatal. Para la recolección de la información se empleó una encuesta. Resultados: el 90 % de las madres identificó la presencia de signos de alarma en su hijo (el 33,33 % no puedo alimentarse y/o respirar); el 50 % de los recién nacidos recibieron lactancia materna exclusiva. El 26,67 % de las madres refirió que el estómago de su bebé se pone duro después de la lactancia, y el 26,67 % que su hijo experimentó vómitos después de la alimentación complementaria. El 46,67 % realizó la cura con alcohol como cuidado al cordón umbilical y el 26,67 % presentó una coloración roja del mismo. El 33,33 % refirió lavarse las manos después de cambiar el pañal y el 36,67 % realizó la higiene de los genitales del neonato con cada cambio de pañal. El 16,67 % asistió a la primera consulta de control neonatal en tiempo. Conclusiones: aún existen insuficiencias en el manejo materno del neonato para poder disminuir los factores de riesgo que generan complicaciones.

Foundation: correct maternal care in the neonatal stage is an elementary factor for the child's health state. Objective: to describe the maternal management of newborns treated at the Tulcán Health Center No. 1. Methods observational, descriptive, cross-sectional study on mothers of newborns who attended the Tulcán Health Center N°1 from September 2021 to February 2022. The population studied was 30 mothers. The analyzed variables were: identification of warning signs, elements related to feeding, care and characteristics of the umbilical cord, hygiene in handling the newborn and time of attendance at the first neonatal check-up. A survey was used to collect the information. Results: 90% of the mothers identified the presence of warning signs in their child (33.33% could not feed and/or breathe); 50% of newborns were exclusively breastfed. 26.67% of mothers reported that their baby´s; stomach becomes hard after breastfeeding, and 26.67% reported that their child experienced vomiting after complementary feeding. 46.67% performed the cure with alcohol as care for the umbilical cord and 26.67% presented a red color to it. 33.33% reported washing their hands after changing the diaper and 36.67% cleaned the newborn's genitals with each diaper change. 16.67% attended the first neonatal check-up consultation on time. Conclusions: there are still inadequacies in the maternal management of the newborn to reduce the risk factors that generate complications.

Exploring the diversity of tick-borne pathogens: The case of bacteria (Anaplasma, Rickettsia, Coxiella and Borrelia) protozoa (Babesia and Theileria) and viruses (Orthonairovirus, tick-borne encephalitis virus and louping ill virus) in the European continent.

Ticks are the main vectors for the transmission of bacterial, protist and viral pathogens in Europe affecting wildlife and domestic animals. However, some of them are zoonotic and can cause serious, sometimes fatal, problems in human health. A systematic review in PubMed/MEDLINE database was conducted to determine the spatial distribution and host and tick species ranges of a selection of tick-borne bacteria (Anaplasma spp., Borrelia spp., Coxiella spp., and Rickettsia spp.), protists (Babesia spp. and Theileria spp.), and viruses (Orthonairovirus, and flaviviruses tick-borne encephalitis virus and louping ill virus) on the European continent in a five-year period (November 2017 - November 2022). Only studies using PCR methods were selected, retrieving a total of 429 articles. Overall, up to 85 species of the selected tick-borne pathogens were reported from 36 European countries, and Anaplasma spp. was described in 37% (159/429) of the articles, followed by Babesia spp. (34%, 148/429), Borrelia spp. (34%, 147/429), Rickettsia spp. (33%, 142/429), Theileria spp. (11%, 47/429), tick-borne flaviviruses (9%, 37/429), Orthonairovirus (7%, 28/429) and Coxiella spp. (5%, 20/429). Host and tick ranges included 97 and 50 species, respectively. The highest tick-borne pathogen diversity was detected in domestic animals, and 12 species were shared between humans, wildlife, and domestic hosts, highlighting the following zoonotic species: Anaplasma phagocytophilum, Babesia divergens, Babesia microti, Borrelia afzelii, Borrelia burgdorferi s.s., Borrelia garinii, Borrelia miyamotoi, Crimean-Congo hemorrhagic fever virus, Coxiella burnetii, Rickettsia monacensis and tick-borne encephalitis virus. These results contribute to the implementation of effective interventions for the surveillance and control of tick-borne diseases.

Effect of high-volume insecticide spraying on sand fly vectors in household gardens in Spain.

This study investigated the efficacy of high-volume spraying with the adulticide α-cypermethrin alone and in combination with the larvicide diflubenzuron on the density of sand flies in gardens of three detached households in periurban areas in southeast Spain. Treatments were applied four times between June and August 2016, and four nearby sites, two households and two non-urbanized sites, were untreated controls. The number of sand flies collected between May and October 2016 using sticky interception and light attraction traps, was 4446 specimens. Species identified morphologically included Sergentomyia minuta (n = 2101; 48%), Phlebotomus perniciosus (n = 1922; 44%), Phlebotomus papatasi (n = 173; 4%), Phlebotomus sergenti (n = 161; 4%) and Phlebotomus ariasi (n = 36; 1%). Sand flies were detected in both treated and untreated sites. The proportion of positive sticky traps and the median (range) density of sand flies in positive traps were 61% traps and 7 (2-172) sand flies/m2 /day in untreated sites, and 43% traps and 4 (1-56) sand flies/m2 /day in treated sites (p < 0.05). Similarly, for light traps, it was 96% traps and 30 (3-168) flies/trap/day, and 83% traps and 3 (1-12) sand flies/trap/day, respectively (p < 0.05). However, sand fly density followed a comparable seasonal pattern in untreated and treated sites and did not consistently decrease following insecticide applications. These results were confirmed with mixed negative binomial modelling of sand fly density adjusted for time since application, month, environmental setting and site. The limited efficacy of the treatments, added to their cost, the impact of insecticides on non-target organisms and human health, and the risk of development of insecticide resistance, should dissuade similar outdoor applications to control sand fly vector populations in residential areas.

[Impact of vaccination against SARS-CoV-2 on the incidence of infection in school settings]. / Impacto de la vacunación contra SARS-CoV-2 en la incidencia de infección en ámbito escolar.

Background: The SARS-CoV-2 pandemic affected the school-aged population because of the disease itself and due to the measures applied for prevention and control of the infection. The aim of the study was to evaluate the effect of population-based vaccination against COVID-19 on the incidence of infection in school settings. Material and Methods: A retrospective descriptive study of COVID-19 cases and school outbreaks was carried out at the province level. Students, teachers and staff from different educational stages of the schools were included. The outcome measure was the incidence according to educational stage, case profile and clinic during the first of the academic year 2020/2021 versus the same period 2021/2022. Results: The total incidence of SARS-CoV-2 in classrooms was 2,470 cases per 100,000 population in the first trimester of the academic year 2020/2021 and 2,720 cases per 100,000 population in the same period 2021/2022. The number of reported school outbreaks was 7 times higher in this second period; and the risk of infection in classrooms over 12 years of age (students and teachers) was reduced by 43.1% (vaccinated in high percentage). Conclusions: This study shows a reduction in transmission of SARS-CoV-2 infection in students of higher educational stages (secondary and high school) during the first of the academic year 2021/2022 (group with high vaccination coverage at the beginning of the period) compared to the previous school year (without vaccination).

Sex differences in long QT syndrome.

Long QT Syndrome (LQTS) is a rare, inherited channelopathy characterized by cardiac repolarization dysfunction, leading to a prolonged rate-corrected QT interval in patients who are at risk for malignant ventricular tachyarrhythmias, syncope, and even sudden cardiac death. A complex genetic origin, variable expressivity as well as incomplete penetrance make the diagnosis a clinical challenge. In the last 10 years, there has been a continuous improvement in diagnostic and personalized treatment options. Therefore, several factors such as sex, age diagnosis, QTc interval, and genetic background may contribute to risk stratification of patients, but it still currently remains as a main challenge in LQTS. It is widely accepted that sex is a risk factor itself for some arrhythmias. Female sex has been suggested as a risk factor in the development of malignant arrhythmias associated with LQTS. The existing differences between the sexes are only manifested after puberty, being the hormones the main inducers of arrhythmias. Despite the increased risk in females, no more than 10% of the available publications on LQTS include sex-related data concerning the risk of malignant arrhythmias in females. Therein, the relevance of our review data update concerning women and LQTS.

Reevaluation of ambiguous genetic variants in sudden unexplained deaths of a young cohort.

Sudden death cases in the young population remain without a conclusive cause of decease in almost 40% of cases. In these situations, cardiac arrhythmia of genetic origin is suspected as the most plausible cause of death. Molecular autopsy may reveal a genetic defect in up to 20% of families. Most than 80% of rare variants remain classified with an ambiguous role, impeding a useful clinical translation. Our aim was to update rare variants originally classified as of unknown significance to clarify their role. Our cohort included fifty-one post-mortem samples of young cases who died suddenly and without a definite cause of death. Five years ago, molecular autopsy identified at least one rare genetic alteration classified then as ambiguous following the American College of Medical Genetics and Genomics' recommendations. We have reclassified the same rare variants including novel data. About 10% of ambiguous variants change to benign/likely benign mainly because of improved population frequencies. Excluding cases who died before one year of age, almost 21% of rare ambiguous variants change to benign/likely benign. This fact makes it important to discard these rare variants as a cause of sudden unexplained death, avoiding anxiety in relatives' carriers. Twenty-five percent of the remaining variants show a tendency to suspicious deleterious role, highlighting clinical follow-up of carriers. Periodical reclassification of rare variants originally classified as ambiguous is crucial, at least updating frequencies every 5 years. This action aids to increase accuracy to enable and conclude a cause of death as well as translation into the clinic.

Predictive factors for flea occurrence in red foxes (Vulpes vulpes) from semi-arid Mediterranean environments.

The role of red fox as host for a wide range of parasites, particularly fleas and other arthropods causing vector-borne diseases, in combination with its capability to adapt to anthropized environments, makes this wild canid an epidemiologically remarkable species at the wildlife-domestic-human interface, especially in the present time of rise of emerging and re-emerging diseases. This study evaluated the prevalence and parasite intensity of fleas in 88 foxes from Murcia Region (Southeastern Spain) and determined the geographic distribution of areas with the highest potential risk of flea presence. Pulex irritans, Ctenocephalides felis, Spilopsyllus cuniculi and Nosopsyllus fasciatus were identified. The overall prevalence was 76.13%. This is the first time that N. fasciatus has been reported in foxes from Murcia Region. The predictive model established a certain pattern to determine the areas with the highest risk of acquiring fleas. Positive correlation of daily potential evapotranspiration (ET0 ) in winter and the opposite effect occurring for ET0 in summer were obtained, as well as positive correlations for mean daily temperature (Tmean ) in summer and mean precipitation (Pmean ) in winter and summer. The model was also found positively correlated in the forest habitat ecotone areas and the anthropized areas.

Torsión uterina causada por miomatosis: reporte de un caso / Uterine torsion caused by myomatosis: A case report

Resumen ANTECEDENTES: La torsión uterina es una rotación del útero sobre su eje mayor de más de 45°; por lo general sucede en torno del istmo uterino. Los leiomiomas son el factor predisponente más frecuente en úteros no grávidos. OBJETIVO: Reportar el caso de una paciente con torsión uterina cervical y miomatosis de grandes elementos. CASO CLÍNICO: Paciente de 42 años, nuligesta, con antecedente de miomatosis uterina de grandes elementos de 27 x 27 cm. Los síntomas se iniciaron con síndrome doloroso abdominal intenso, tipo cólico, localizado en el hipogastrio y la fosa iliaca. En la exploración física el abdomen se percibió doloroso a la palpación superficial y profunda, con una tumoración cercana a la cicatriz umbilical (25 cm), móvil y dolorosa. En la laparotomía exploradora se encontró líquido peritoneal hemorrágico y se observó una torsión uterina (una vuelta) cerca del cuello del útero, además de un mioma subseroso en la cara posterior, de 27 x 27 cm. El útero, los anexos y las salpinges se advirtieron con datos francos de daño vascular, con áreas de isquemia. Por lo anterior se decidieron la histerectomía total abdominal y la salpingooforectomia bilateral. El informe histopatológico reportó: útero con cambio isquémico extenso panmural, sin evidencia de neoplasia maligna. CONCLUSIONES: El dolor abdominal es el síntoma más común de la torsión uterina que puede variar de leve a agudo. El diagnóstico preoperatorio rápido y preciso de torsión uterina es decisivo y se justifica la intervención quirúrgica de urgencia.

Abstract BACKGROUND: Uterine torsion is a rare entity that is defined as a rotation of the uterus on its major axis of more than 45°, generally occurring at the level of the uterine isthmus. Leiomyomas are the most frequent predisposing factor in non-gravid uterus. OBJECTIVE: Report of a case of a gynecological patient with uterine torsion at the cervical level in a uterus with uterine myomatosis of large elements. CLINICAL CASE: A 42-year-old patient, nulliparous, with a history of uterine myomatosis with large elements of 27 x 27 cm. The symptoms began with intense abdominal pain syndrome, colic type, located in the hypogastrium and the iliac fossa. On physical examination, the abdomen was perceived as painful on superficial and deep palpation, with a mobile and painful tumor close to the umbilical scar (25 cm). In the exploratory laparotomy, hemorrhagic peritoneal fluid was found and a uterine torsion (one turn) was observed near the cervix, as well as a subserous myoma on the posterior face, measuring 27 x 27 cm. The uterus, the annexes and the salpinges were noted with frank data of vascular damage, with areas of ischemia. Therefore, total abdominal hysterectomy and bilateral salpingo-oophorectomy were decided. The histopathological report reported: uterus with extensive panmural ischemic change, without evidence of malignancy. CONCLUSIONS: In uterine torsion, abdominal pain is the most common symptom and can range from mild to severe abdominal symptoms. Therefore, a prompt and accurate preoperative diagnosis of uterine torsion is crucial and urgent surgical intervention is warranted.

Ruptura uterina asociada con útero didelfo y placenta acreta. Reporte de caso / Uterine rupture associated with uterus didelphus and placenta accreta. A case report

Resumen ANTECEDENTES: Las malformaciones müllerianas son consecuencia de una alteración en la formación de los conductos de Müller durante el desarrollo del feto. El momento en que sucede la alteración determina el tipo de malformación. La clasificación actual es la de la American Society for Reproductive Medicine ASMR que se asocia con múltiples complicaciones obstétricas, entre las más graves está la ruptura uterina. CASO CLÍNICO: Paciente primigesta de 23 años, con 39.1 semanas de embarazo, sin antecedentes personales patológicos para el padecimiento actual, sin control prenatal, con dolor abdominal intenso generalizado y disminución de los movimientos fetales desde 12 horas previas a su valoración. Al ingreso de la paciente al hospital su feto se encontró muerto; hemoglobina de 7.9 g/dL, tensión arterial de 96-53 mmHg, taquicárdica, con datos clínicos de irritación peritoneal. En la laparotomía exploradora el feto se encontró muerto, en la cavidad abdominal. Hemoperitoneo de 1300 mL, útero didelfo, con ruptura uterina hacia el fondo. Datos de acretismo placentario. Por lo anterior, se procedió a la histerectomía obstétrica, con sangrado de 2000 cc. Fue necesaria la reanimación y la permanencia de 24 horas en la unidad de cuidados intensivos. La TAC abdomino-pélvica se reportó sin alteraciones renales, con una tumoración adherida cerca del peritoneo parietal sugerente de riñón ectópico. El puerperio trascurrió sin contratiempos por lo que fue dada de alta del hospital. CONCLUSIÓN: En el embarazo, las malformaciones müllerianas son causa de complicaciones obstétricas graves, entre ellas la ruptura uterina. El diagnóstico oportuno es decisivo para la prevención de complicaciones y el control prenatal.

Abstract BACKGROUND: Müllerian malformations are the consequence of an alteration in the formation of the Müllerian ducts during fetal development. The time at which the alteration occurs determines the type of malformation. The current classification is that of the American Society for Reproductive Medicine ASMR, which is associated with multiple obstetric complications, among the most serious of which is uterine rupture. CLINICAL CASE: A 23-year-old primigravid patient, 39.1 weeks pregnant, with no personal pathological history for the current condition, without prenatal control, with severe generalized abdominal pain and decreased fetal movements for 12 hours prior to her evaluation. On the patient admission to the hospital her fetus was found dead; hemoglobin 7.9 g/dL, blood pressure 96-53 mmHg, tachycardic, with clinical data of peritoneal irritation. At exploratory laparotomy the fetus was found dead, in abdominal cavity. Hemoperitoneum of 1300 mL, didelphic uterus, with uterine rupture towards the fundus. Data of placental accretism. Therefore, obstetric hysterectomy was performed, with bleeding of 2000 cc. Resuscitation and a 24-hour stay in the intensive care unit was necessary. The abdomino-pelvic CT scan showed no renal alterations, with an adherent tumor near the parietal peritoneum suggestive of ectopic kidney. The puerperium was uneventful, and she was discharged from the hospital. CONCLUSION: In pregnancy, Müllerian malformations are a cause of serious obstetric complications, including uterine rupture. Timely diagnosis is decisive for the prevention of complications and prenatal management.

Cuidados paliativos al final de la vida: visión comparativa en dos décadas / Palliative care at the end of life: comparative vision in two decades

RESUMEN Introducción: las enfermedades neoplásicas, cardiovasculares y procesos degenerativos predominan en estos tiempos, provocando la aparición del "enfermo crónico", cuya curación se considera muy lejana o inalcanzable. Esto propicia que la medicina paliativa esté experimentando un gran auge, por lo que se realizó una investigación sobre los cuidados paliativos en Matanzas, Cuba. La visión de estudios anteriores sobre el tema puede sustentar elementos de criterio sobre necesidades al respecto en la atención sanitaria. Objetivo: comparar el comportamiento de los cuidados paliativos en tres períodos de tiempo a través de investigaciones realizadas. Materiales y métodos: se realizó una revisión sistemática de tres estudios epidemiológicos observacionales descriptivos -contenidos en tres tesis de terminación de especialidad en Medicina Interna-, efectuados en la provincia de Matanzas en tres períodos de tiempo diferentes (2000-2001, 2009-2010 y 2017-2018), con el objetivo de realizar una comparación del comportamiento de los cuidados paliativos en pacientes en estado terminal y/o avanzado de su enfermedad. Resultados: aunque la mayoría de lo estudiado fueron neoplasias malignas, hubo presencia de otras enfermedades como cardiopatías, diabetes mellitus, enfermedad pulmonar obstructiva crónica, hepatopatías crónicas, enfermedad cerebrovascular, demencias e insuficiencia renal crónica. Fue valorado el seguimiento de los pacientes por el equipo de salud, así como la evidencia de necesidades de recursos insatisfechas y lo que ello genera en los cuidadores. Conclusiones: hay necesidades materiales que interfieren en la calidad de vida de los enfermos. Los cuidadores necesitan la atención por parte del equipo de salud. Es necesario incentivar la investigación y los conocimientos sobre los cuidados paliativos.

ABSTRACT Introduction: neoplastic and cardiovascular diseases and degenerative processes predominate in these times, causing the appearance of the "chronic patient", whose cure is considered very distant or unattainable. This favors a great boom of the palliative medicine, which is why an investigation was carried out on palliative care in Matanzas, Cuba. The vision of previous studies on the topic con support elements of criteria on health care needs in this regard. Objective: to compare the behavior of palliative care in three time periods through researches carried out. Materials and methods: a systematic review of three descriptive observational epidemiological studies-contained in three specialty completion theses in Internal Medicine-carried out in the province of Matanzas in three different time periods (2000-2001, 2009-2010 and 2017-2018), with the aim of making a comparison of the behavior of palliative care patients in patients in terminal and/or advances stages of their diseases. Results: although most of the studied were malignant neoplasms, there was the presence of other diseases as heart disease, diabetes mellitus, chronic obstructive pulmonary disease, chronic liver disease, cerebrovascular disease, dementia and chronic kidney failure. The follow-up of the patients was assessed by the health team, as well as the evidence of unsatisfied resources needs and what this generates in caregivers. Conclusions: there are material needs that interfere in the quality of life of the sick people. Caregivers need care from the health team. It is necessary to encourage research and knowledge about palliative care.

Structural Heart Alterations in Brugada Syndrome: Is it Really a Channelopathy? A Systematic Review.

Brugada syndrome (BrS) is classified as an inherited cardiac channelopathy attributed to dysfunctional ion channels and/or associated proteins in cardiomyocytes rather than to structural heart alterations. However, hearts of some BrS patients exhibit slight histologic abnormalities, suggesting that BrS could be a phenotypic variant of arrhythmogenic cardiomyopathy. We performed a systematic review of the literature following Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA) criteria. Our comprehensive analysis of structural findings did not reveal enough definitive evidence for reclassification of BrS as a cardiomyopathy. The collection and comprehensive analysis of new cases with a definitive BrS diagnosis are needed to clarify whether some of these structural features may have key roles in the pathophysiological pathways associated with malignant arrhythmogenic episodes.

Analytical Methods for Determination of BPA Released from Dental Resin Composites and Related Materials: A Systematic Review.

Knowing the impacts of bisphenol A (BPA) on human health, this systematic review aimed to gather the analytical methods for the quantification of BPA release of BPA in dental materials in in vitro and in vivo (biological fluids) studies. A brief critical discussion of the impacts of BPA on human health and the possible association with BPA in dental materials was also presented. The research was carried out by three independent researchers, (according to PRISMA guidelines) in PUBMED and SCOPUS databases, by searching for specific keywords and articles published between January 2011 and February 2022. Seventeen articles met the eligibility criteria and were included in this systematic review: 10 in vitro and 7 in vivo. In in vitro studies, the highest amounts of BPA released were from flowable to conventional resins, followed by resin-modified glass ionomer. In contrast, the smallest amount was released from "BPA-free" composites and CAD-CAM blocks. Regarding in vivo studies, a higher concentration of BPA were found in saliva than urine or blood. The best analytical method for trace quantifying BPA is LC-MS/MS (Liquid Chromatography with Tandem Mass Spectrometry) due to its selectivity, low quantification limits, and the unequivocal identification. However, further studies are required to develop faster and more sensitive methods, in order to obtain more reliable results.

Redox regulation of PTPN22 affects the severity of T-cell-dependent autoimmune inflammation.

Chronic autoimmune diseases are associated with mutations in PTPN22, a modifier of T cell receptor (TCR) signaling. As with all protein tyrosine phosphatases, the activity of PTPN22 is redox regulated, but if or how such regulation can modulate inflammatory pathways in vivo is not known. To determine this, we created a mouse with a cysteine-to-serine mutation at position 129 in PTPN22 (C129S), a residue proposed to alter the redox regulatory properties of PTPN22 by forming a disulfide with the catalytic C227 residue. The C129S mutant mouse showed a stronger T-cell-dependent inflammatory response and development of T-cell-dependent autoimmune arthritis due to enhanced TCR signaling and activation of T cells, an effect neutralized by a mutation in Ncf1, a component of the NOX2 complex. Activity assays with purified proteins suggest that the functional results can be explained by an increased sensitivity to oxidation of the C129S mutated PTPN22 protein. We also observed that the disulfide of native PTPN22 can be directly reduced by the thioredoxin system, while the C129S mutant lacking this disulfide was less amenable to reductive reactivation. In conclusion, we show that PTPN22 functionally interacts with Ncf1 and is regulated by oxidation via the noncatalytic C129 residue and oxidation-prone PTPN22 leads to increased severity in the development of T-cell-dependent autoimmunity.

Brugada Syndrome in Women: What Do We Know After 30 Years?

Brugada syndrome (BrS) was initially described in 1992 by Josep and Pedro Brugada as an arrhythmogenic disease characterized by ST segment elevation in the right precordial leads and increased risk of sudden cardiac death (SCD). Alterations in the SCN5A gene are responsible for approximately 30% of cases of BrS, following an autosomal dominant pattern of inheritance. However, despite its autosomal transmission, sex-related differences are widely accepted. BrS is more prevalent in males than in females (8-10 times), with males having a 5.5-fold higher risk of SCD. There are also differences in clinical presentation, with females being more frequently asymptomatic and older than males at the time of diagnosis. Some factors have been identified that could explain these differences, among which testosterone seems to play an important role. However, only 30% of the available publications on the syndrome include sex-related information. Therefore, current findings on BrS are based on studies conducted mainly in male population, despite the wide acceptance of gender differences. The inclusion of complete clinical and demographic information in future publications would allow a better understanding of the phenotypic variability of BrS in different age and sex groups helping to improve the diagnosis, management and risk management of SCD.

Discerning the Ambiguous Role of Missense TTN Variants in Inherited Arrhythmogenic Syndromes.

The titin gene (TTN) is associated with several diseases, including inherited arrhythmias. Most of these diagnoses are attributed to rare TTN variants encoding truncated forms, but missense variants represent a diagnostic challenge for clinical genetics. The proper interpretation of genetic data is critical for translation into the clinical setting. Notably, many TTN variants were classified before 2015, when the American College of Medical Genetics and Genomics (ACMG) published recommendations to accurately classify genetic variants. Our aim was to perform an exhaustive reanalysis of rare missense TTN variants that were classified before 2015, and that have ambiguous roles in inherited arrhythmogenic syndromes. Rare missense TTN variants classified before 2015 were updated following the ACMG recommendations and according to all the currently available data. Our cohort included 193 individuals definitively diagnosed with an inherited arrhythmogenic syndrome before 2015. Our analysis resulted in the reclassification of 36.8% of the missense variants from unknown to benign/likely benign. Of all the remaining variants, currently classified as of unknown significance, 38.3% showed a potential, but not confirmed, deleterious role. Most of these rare missense TTN variants with a suspected deleterious role were identified in patients diagnosed with hypertrophic cardiomyopathy. More than 35% of the rare missense TTN variants previously classified as ambiguous were reclassified as not deleterious, mainly because of improved population frequencies. Despite being inconclusive, almost 40% of the variants showed a potentially deleterious role in inherited arrhythmogenic syndromes. Our results highlight the importance of the periodical reclassification of rare missense TTN variants to improve genetic diagnoses and help increase the accuracy of personalized medicine.

Clinical Genetics of Inherited Arrhythmogenic Disease in the Pediatric Population.

Sudden death is a rare event in the pediatric population but with a social shock due to its presentation as the first symptom in previously healthy children. Comprehensive autopsy in pediatric cases identify an inconclusive cause in 40-50% of cases. In such cases, a diagnosis of sudden arrhythmic death syndrome is suggested as the main potential cause of death. Molecular autopsy identifies nearly 30% of cases under 16 years of age carrying a pathogenic/potentially pathogenic alteration in genes associated with any inherited arrhythmogenic disease. In the last few years, despite the increasing rate of post-mortem genetic diagnosis, many families still remain without a conclusive genetic cause of the unexpected death. Current challenges in genetic diagnosis are the establishment of a correct genotype-phenotype association between genes and inherited arrhythmogenic disease, as well as the classification of variants of uncertain significance. In this review, we provide an update on the state of the art in the genetic diagnosis of inherited arrhythmogenic disease in the pediatric population. We focus on emerging publications on gene curation for genotype-phenotype associations, cases of genetic overlap and advances in the classification of variants of uncertain significance. Our goal is to facilitate the translation of genetic diagnosis to the clinical area, helping risk stratification, treatment and the genetic counselling of families.

Trends in the Utilization of Lipid-Lowering Medications in Australia: An Analysis of National Pharmacy Claims Data.

Lipid-lowering medications comprise standard of care in the prevention of cardiovascular disease. This study examined the trends in the utilization of statin and non-statin medications in the Australian general population between 2013 and 2019. Pharmacoepidemiological analyses were performed using pharmacy dispensing data from Australian Pharmaceutical Benefits Scheme. One-year prevalence and incidence of statin and non-statin prescribing patterns were reported, and relative variations in prescribing examined via Poisson regression modelling. The one-year prevalence of statins' prescriptions decreased between 2013-2019 by 5.5% (from 25.0%-19.5%). Females were less likely than males to be prescribed statins (rate ratio [RR]=0.90, 95% confidence interval [CI] 0.89-0.91). The one-year prevalence of ezetimibe alone, and in combination with statins, increased consistently from 2013-2019 from 1.5%-3.6% (P<0.01) and 0.1%-1.1% (P<0.01), respectively. The prevalence was higher among those aged 61-80 years (RR=1.20, 95%CI 1.10-1.21) and those aged older than 80 years (RR=1.34, 95%CI 1.22-1.47), when compared to people aged <60 years. The incidence of ezetimibe prescriptions was highest in people aged 61-80 years (RR=1.36, 95%CI 1.31-1.41) compared to those aged <60 years. The one-year prevalence of proprotein convertase subtilisin/kexin type 9 inhibitor prescriptions was highest among those aged 46-60 years (RR=1.24, 95%CI 0.97-4.97) compared to people aged <46 and >60 years. Females were less likely than males to be prescribed a proprotein convertase subtilisin/kexin type 9 inhibitor (RR=0.87, 95%CI 0.75-0.98). Statins remain the most prevalent lipid-lowering medication prescribed in Australia. The prescribing of non-statin medications remains low, but is increasing.

Colecistitis aguda durante el segundo trimestre del embarazo: reporte de un caso / Acute cholecystitis during the second trimester of pregnancy: A case report

Resumen ANTECEDENTES: La colecistitis aguda es la segunda causa más frecuente de urgencia quirúrgica no obstétrica, con una incidencia de 1 caso por cada 1600 a 10,000 embarazos. OBJETIVO: Reportar el caso de una paciente con colecistitis aguda durante el segundo trimestre del embarazo tratada mediante cirugía laparoscópica. CASO CLÍNICO: Paciente de 34 años, con 16.5 semanas de embarazo. Acudió a consulta debido a un dolor abdominal de tipo cólico en el hipocondrio derecho. A la exploración física se encontraron: abdomen blando, depresible, dolor a la palpación en el flanco e hipocondrio derechos, signo de Murphy negativo, sin datos de irritación peritoneal; no se palparon plastrones; el útero se encontraba arriba de la sínfisis del pubis. El ultrasonido abdominal mostró la vesícula debidamente delimitada, con bordes regulares y definidos, con pared delgada y múltiples cálculos en su interior. No se evidenció leucocitosis. Los reportes de la laparoscopia fueron: vesícula con paredes a tensión, el conducto cístico corto, dilatado, con un cálculo retenido. No se informaron complicaciones. La paciente fue dada de alta a las 48 horas del posoperatorio. Continuó en control prenatal y finalizó el embarazo por cesárea. El desenlace neonatal fue satisfactorio. CONCLUSIONES: La colecistitis es una de las principales alteraciones durante el embarazo. Postergar la cirugía supone consecuencias para la madre y el feto, por lo que debe establecerse el diagnóstico y tratamiento oportunos.

Abstract BACKGROUND: Bile duct pathologies, specifically acute cholecystitis, is the second most common cause of non-obstetric surgical emergency, with an incidence of 1 in 1,600 to 10,000 pregnancies. OBJECTIVE: Report of a case of a patient with acute cholecystitis during the second trimester of pregnancy treated by laparoscopic surgery. CLINICAL CASE: 34-year-old female, pregnancy 3, childbirth 2; with pregnancy of 16.5 weeks. She presented colicky abdominal pain located in the right upper quadrant. Physical examination revealed abdomen with normoaudible peristalsis, soft, depressible, pain on medium and deep palpation in the right hypochondrium, murphy sign (-), no evidence of peritoneal irritation, no plastrons palpated, uterus above symphysis of the pubis. Abdominal ultrasound reports a well-defined vesicle with regular and well-defined borders, with a thin wall, with the presence of multiple stones in its interior. There was no presence of leukocytosis. Laparoscopic surgical management was decided, during which a gallbladder with tension walls, a short, dilated cystic duct, with an impacted stone was found. No complications were reported. She continued her prenatal care in our hospital unit and the pregnancy was resolved by cesarean section. Neonatal outcomes were optimal. CONCLUSIONS: Cholecystitis is one of the main non-obstetric surgical pathologies that occur in pregnancy, it is important to consider that the fact of postponing surgery could have consequences for both the mother and the fetus, so the timely diagnosis and management of this type of pathology must be carried out.