CPAMD8 loss-of-function underlies non-dominant congenital glaucoma with variable anterior segment dysgenesis and abnormal extracellular matrix

Abnormal development of the ocular anterior segment may lead to a spectrum of clinical phenotypes ranging from primary congenital glaucoma (PCG) to variable anterior segment dysgenesis (ASD). The main objective of this study was to identify the genetic alterations underlying recessive congenital glaucoma with ASD (CG-ASD). Next-generation DNA sequencing identified rare biallelic CPAMD8 variants in four patients with CG-ASD and in one case with PCG. CPAMD8 is a gene of unknown function and recently associated with ASD. Bioinformatic and in vitro functional evaluation of the variants using quantitative reverse transcription PCR and minigene analysis supported a loss-of-function pathogenic mechanism. Optical and electron microscopy of the trabeculectomy specimen from one of the CG-ASD cases revealed an abnormal anterior chamber angle, with altered extracellular matrix, and apoptotic trabecular meshwork cells. The CPAMD8 protein was immunodetected in adult human ocular fluids and anterior segment tissues involved in glaucoma and ASD (i.e., aqueous humor, non-pigmented ciliary epithelium, and iris muscles), as well as in periocular mesenchyme-like cells of zebrafish embryos. CRISPR/Cas9 disruption of this gene in F0 zebrafish embryos (96 hpf) resulted in varying degrees of gross developmental abnormalities, including microphthalmia, pharyngeal maldevelopment, and pericardial and periocular edemas. Optical and electron microscopy examination of these embryos showed iridocorneal angle hypoplasia (characterized by altered iris stroma cells, reduced anterior chamber, and collagen disorganized corneal stroma extracellular matrix), recapitulating some patients’ features. Our data support the notion that CPAMD8 loss-of-function underlies a spectrum of recessive CG-ASD phenotypes associated with extracellular matrix disorganization and provide new insights into the normal and disease roles of this gene

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

El desempleo en Colombia: tasa natural, desempleo cíclico y estructural y la duración del desempleo, (1976-1998)

Este estudio, desagrega la tasa observada de desempleo en Colombia (19.5%) en sus componente natural (11.5%, de los cuales 6.5% se deben a factores estructurales y 5% al llamado desempleo friccional), y cíclico (8%), y analiza la duración del desempleo. Teniendo en cuenta que la tasa natural de desempleo (aquella con lo cual la economía se mantiene en equilibrio, es decir que no existen presiones inflacionarias ante políticas que estimulen la demanda de bienes y servicios), es del 11, 5% existe un espacio suficiente para aplicar políticas de demanda que reduzcan el desempleo a corto plazo

Efecto del consumo de jugo de tomate de árbol (Cyphomandra betacea) sobre el perfil lipídico y las concentraciones de glucosa en adultos con hiperlipidemia, Ecuador

En este trabajo se evaluó el efecto del consumo del jugo de tomate de árbol (Cyphomandra betacea) sobre parámetros nutricionales y bioquímicos en 54 voluntarios (44 mujeres y 10 hombres) con edades 45±8 años de Ecuador. Al inicio se les realizó una evaluación nutricional y bioquímica, luego se les invitó a consumir el jugo (100g de fruto en 150 ml de agua) diariamente durante 6 semanas. Finalizado este tiempo, se procedió a realizar la evaluación nutricional y bioquímica nuevamente. La evaluación nutricional determinó 67% de obesidad abdominal. Disminuyendo a 53% después del consumo del jugo de tomate de árbol. El 87% de los voluntarios antes del tratamiento, mostraron hipercolesterolemia; 40,7% y 46,3% tenían los triglicéridos y el LDL elevados y 18,5% valores de glucosa entre 98-130mg/dL. Valores que disminuyeron significativamente en este grupo después de la toma del jugo En general, tanto en voluntarios con y sin sobrepeso se observó disminución significativa de colesterol total, LDL y glucosa; sin cambios significativos en los valores de HDL. El consumo del jugo no afectó la actividad de las enzimas alanina-aminotransferasa ni aspartato-aminotransferasa, tampoco las concentraciones de creatinina, urea y ácido úrico; ni la presión arterial, demostrando que no afecta la función hepática ni renal. Estos resultados indican que el consumo del jugo de tomate de árbol, durante seis semanas, parece ejercer un efecto hipolipemiante y moduladora en el metabolismo de la glucosa y colocan a C betacea como uno de los frutos andinos con alto potencial nutraceutico. Sin embargo, estos aspectos deben ser investigados con más detalles.In this work the effect of consumption of tree tomato juice (Cyphomandra betacea) was evaluated on nutritional and biochemical parameters in 54 volunteers (44 women and 10 men) aged 45 ± 8 years-Ecuador. A nutritional and biochemical evaluation was performed in volunteers; then they were invited to drink tree tomato juice (100g of fruit in 150 ml of water) daily for 6 weeks. Finished these 6 weeks, volunteers were nutritional and biochemical evaluated again. 67% abdominal obesity was found, decreasing at 53% after drinking the established dosage of juice. 87% of the volunteers before treatment, showed hypercholesterolemia, 40.7% and 46.3% had hypertriglyceridemia and elevated LDL, respectively and 18.5% glucose concentrations between 98-130 mg/dL. These values decrease significantly in this group after drinking tomato juice. In general, Total Cholesterol, LDL and glucose concentrations decrease significantly after drinking tree tomato juice in all the voluntaries with or without overweight. There is no change in HDL concentrations. The consumption of tree tomato juice did not affect the activity of alanine aminotransferase or aspartate aminotransferase enzymes either creatinine, urea and uric acid concentrations, neither blood pressure suggesting that does not affect renal or liver function. These results indicate that consumption of tree tomato juice for six weeks appears to have a lipid-lowering and modulating effect on glucose metabolism, suggesting C betacea as one of the high Andean fruits nutraceutical potential. However, this issue should be investigated in more detail

A first insight into the genetic diversity of Mycobacterium Tuberculosis in Veracruz, Mexico

Objective/Background: Tuberculosis (TB) remains one of the most important infectious diseases. Although Mexico is one of the Latin American countries with the largest contribution to these statistics, there are few reports that describe the genotypic characteristics of TB. The aim of this study was to use the MIRU-VNTR-24 loci to analyze the genetic diversity of M. tuberculosis circulating in the state of Veracruz, Mexico. Methods: Here, we analyze by MIRU-VNTR-24 loci 80 clinical isolates from individuals with confirmed TB from Veracruz México, also clinical and epidemiological variables were recovered and analyzed. Results: Of the individuals included in the analyses 65% were from men with an average age of 42 (± 17) years, 17% and 6% were drug and multi-drug resistant. 88% of the isolates were included in 20 clusters, of which 52% were classified into twelve orphan clusters and the remaining 37% were distributed among eight lineages: LAM (10%), EAI (9%), Haarlem (8%), H37Rv (4%), S (4%) and TUR (2%). Conclusion: An important diversity of lineages and unknown genotypes was identified; however, more studies are necessary in order to understand the characteristics of the genotypes displayed in the region. There is no doubt regarding the need for a molecular epidemiological surveillance system that can help to evaluate the dynamics of genotypes circulating in the country and support strategies for the prevention and management of populations affected by TB

Efecto del consumo de jugo de tomate de árbol (Cyphomandra betacea) sobre el perfil lipídico y las concentraciones de glucosa en adultos con hiperlipidemia, Ecuador

En este trabajo se evaluó el efecto del consumo del jugo de tomate de árbol (Cyphomandra betacea) sobre parámetros nutricionales y bioquímicos en 54 voluntarios (44 mujeres y 10 hombres) con edades 45±8 años de Ecuador. Al inicio se les realizó una evaluación nutricional y bioquímica, luego se les invitó a consumir el jugo (100g de fruto en 150 ml de agua) diariamente durante 6 semanas. Finalizado este tiempo, se procedió a realizar la evaluación nutricional y bioquímica nuevamente. La evaluación nutricional determinó 67% de obesidad abdominal. Disminuyendo a 53% después del consumo del jugo de tomate de árbol. El 87% de los voluntarios antes del tratamiento, mostraron hipercolesterolemia; 40,7% y 46,3% tenían los triglicéridos y el LDL elevados y 18,5% valores de glucosa entre 98-130mg/dL. Valores que disminuyeron significativamente en este grupo después de la toma del jugo En general, tanto en voluntarios con y sin sobrepeso se observó disminución significativa de colesterol total, LDL y glucosa; sin cambios significativos en los valores de HDL. El consumo del jugo no afectó la actividad de las enzimas alanina-aminotransferasa ni aspartato-aminotransferasa, tampoco las concentraciones de creatinina, urea y ácido úrico; ni la presión arterial, demostrando que no afecta la función hepática ni renal. Estos resultados indican que el consumo del jugo de tomate de árbol, durante seis semanas, parece ejercer un efecto hipolipemiante y moduladora en el metabolismo de la glucosa y colocan a C betacea como uno de los frutos andinos con alto potencial nutraceutico. Sin embargo, estos aspectos deben ser investigados con más detalles

Zika virus infection in pregnant travellers and impact on childhood neurodevelopment in the first two years of life: A prospective observational study.

The emergence of Zika virus (ZIKV) represents a threat with consequences on maternal and children's health. We aimed to assess the clinical and epidemiological characteristics of pregnant women returning from ZIKV affected areas, and the effects of maternal ZIKV infection on birth outcomes and children's health. This was a hospital-based prospective observational study conducted at the Hospital Clínic of Barcelona and Hospital Sant Joan de Déu, Barcelona, Spain, from January 2016 to February 2020. One hundred and ninety-five pregnant women who had travelled to ZIKV affected areas during pregnancy were recruited. Four women (2.1%) had a confirmed ZIKV infection, 40 women (20.5%) a probable infection, and 151 (77.4%) were negative for ZIKV. Among the ZIKV confirmed cases, a pregnant woman suffered a miscarriage, highly plausible to be associated with ZIKV infection. Brain cysts and microcalcifications were detected in 7% of fetuses or infants from women with confirmed or probable ZIKV infection. Neurodevelopmental delay in the language function was found in 33.3% out of the 21 children evaluated. These findings contribute to the understanding of ZIKV prevalence estimates, and the impact of maternal ZIKV infection on pregnancy outcomes and children's health. Results highlight the importance of long-term surveillance in pregnant travellers and their children.This work was supported by the Government of Spain [grant number PI16/0123, ISCIII-AES Proyectos de Investigación en Salud, 2016]; a predoctoral fellowship from “la Caixa” Foundation (ID 100010434) [fellowship LCF/BQ/ES17/11600006]; the Ministry of Science, Innovation and Universities, Government of Spain through a Ramon y Cajal Grant [RYC-2013-14,512]; RICET, a Tropical Disease Cooperative Research Network in Spain [RD12/0018/0010] cofounded by ISCIII and the Fondo Europeo de Desarrollo Regional (FEDER); the Departament d’Universitats I Recerca de la Generalitat de Catalunya, Spain, AGAUR [grant 2017SGR924]; and ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya.S

Structural characterization and biological implications of sulfated N-glycans in a serine protease from the neotropical moth Hylesia metabus (Cramer [1775]) (Lepidoptera: Saturniidae).

International audienceContact with the urticating setae from the abdomen of adult females of the neo-tropical moth Hylesia metabus gives rise to an urticating dermatitis, characterized by intense pruritus, generalized malaise and occasionally ocular lesions (lepidopterism). The setae contain a pro-inflammatory glycosylated protease homologous to other S1A serine proteases of insects. Deglycosylation with PNGase F in the presence of a buffer prepared with 40% H2 (18)O allowed the assignment of an N-glycosylation site. Five main paucimannosidic N-glycans were identified, three of which were exclusively α(1-6)-fucosylated at the proximal GlcNAc. A considerable portion of these N-glycans are anionic species sulfated on either the 4- or the 6-position of the α(1-6)-mannose residue of the core. The application of chemically and enzymatically modified variants of the toxin in an animal model in guinea pigs showed that the pro-inflammatory and immunological reactions, e.g. disseminated fibrin deposition and activation of neutrophils, are due to the presence of sulfate-linked groups and not on disulfide bonds, as demonstrated by the reduction and S-alkylation of the toxin. On the other hand, the hemorrhagic vascular lesions observed are attributed to the proteolytic activity of the toxin. Thus, N-glycan sulfation may constitute a defense mechanism against predators

Prevalence of SARS-CoV-2 infection in Baja California, Mexico: Findings from a community-based survey in February 2021 in the Mexico-United States border.

Between March 2020 and February 2021, the state of Baja California, Mexico, which borders the United States, registered 46,118 confirmed cases of COVID-19 with a mortality rate of 238.2 deaths per 100,000 residents. Given limited access to testing, the population prevalence of SARS-CoV-2 infection is unknown. The objective of this study is to estimate the seroprevalence and real time polymerase chain reaction (RT-PCR) prevalence of SARS-CoV-2 infection in the three most populous cities of Baja California prior to scale-up of a national COVID-19 vaccination campaign. Probabilistic three-stage clustered sampling was used to conduct a population-based household survey of residents five years and older in the three cities. RT-PCR testing was performed on nasopharyngeal swabs and SARS-CoV-2 seropositivity was determined by IgG antibody testing using fingerstick blood samples. An interviewer-administered questionnaire assessed participants' knowledge, attitudes, and preventive practices regarding COVID-19. In total, 1,126 individuals (unweighted sample) were surveyed across the three cities. Overall prevalence of SARS-CoV-2 infection by RT-PCR was 7.8% (95% CI 5.5-11.0) and IgG seroprevalence was 21.1% (95% CI 17.4-25.2). There was no association between border crossing in the past 6 months and SARS-CoV-2 prevalence (unadjusted OR 0.40, 95%CI 0.12-1.30). While face mask use and frequent hand washing were common among participants, quarantine or social isolation at home to prevent infection was not. Regarding vaccination willingness, 30.4% (95% CI 24.4-3 7.1) of participants said they were very unlikely to get vaccinated. Given the high prevalence of active SARS-CoV-2 infection in Baja California at the end of the first year of the pandemic, combined with its low seroprevalence and the considerable proportion of vaccine hesitancy, this important area along the Mexico-United States border faces major challenges in terms of health literacy and vaccine uptake, which need to be further explored, along with its implications for border restrictions in future epidemics