Exome Sequencing has a high diagnostic rate in sporadic congenital hypopituitarism and reveals novel candidate genes.

CONTEXT: The pituitary gland is key for childhood growth, puberty, and metabolism. Pituitary dysfunction is associated with a spectrum of phenotypes, from mild to severe. Congenital Hypopituitarism (CH) is the most commonly reported pediatric endocrine dysfunction with an incidence of 1:4000, yet low rates of genetic diagnosis have been reported. OBJECTIVE: We aimed to unveil the genetic etiology of CH in a large cohort of patients from Argentina. METHODS: We performed whole exome sequencing of 137 unrelated cases of CH, the largest cohort examined with this method to date. RESULTS: Of the 137 cases, 19.1% and 16% carried pathogenic or likely pathogenic variants in known and new genes, respectively, while 28.2% carried variants of uncertain significance. This high yield was achieved through the integration of broad gene panels (genes described in animal models and/or other disorders), an unbiased candidate gene screen with a new bioinformatics pipeline (including genes high loss of function intolerance), and analysis of copy number variants. Three novel findings emerged. First, the most prevalent affected gene encodes the cell adhesion factor ROBO1. Affected children had a spectrum of phenotypes, consistent with a role beyond pituitary stalk interruption syndrome. Second, we found that CHD7 mutations also produce a phenotypic spectrum, not always associated with full CHARGE syndrome. Third, we add new evidence of pathogenicity in the genes PIBF1 and TBC1D32, and report 13 novel candidate genes associated with CH (e.g. PTPN6, ARID5B). CONCLUSION: Overall, these results provide an unprecedented insight into the diverse genetic etiology of hypopituitarism.

Chilean consensus by expert panel using the Delphi technique for primary and secondary prevention of gastric cancer. / Estrategias para la prevención primaria y secundaria del cáncer gástrico: consenso chileno de panel de expertos con técnica Delfi.

INTRODUCTION: Gastric cancer (GC) is the first cause of cancer-related death in Chile and 6th in Latin America and the Caribbean (LAC). Helicobacter pylori (H. pylori) is the main gastric carcinogen, and its treatment reduces GC incidence and mortality. Esophageal-gastro-duodenoscopy (EGD) allows for the detection of premalignant conditions and early-stage GC. Mass screening programs for H. pylori infection and screening for premalignant conditions and early-stage GC are not currently implemented in LAC. The aim of this study is to establish recommendations for primary and secondary prevention of GC in asymptomatic standard-risk populations in Chile. METHODS: Two on-line synchronous workshops and a seminar were conducted with Chilean experts. A Delphi panel consensus was conducted over 2 rounds to achieve>80% agreement on proposed primary and secondary prevention strategies for the population stratified by age groups. RESULTS: 10, 12, and 12 experts participated in two workshops and a seminar, respectively. In the Delphi panel, 25 out of 37 experts (77.14%) and 28 out of 52 experts (53.85%) responded. For the population aged 16-34, there was no consensus on non-invasive testing and treatment for H. pylori, and the use of EGD was excluded. For the 35-44 age group, non-invasive testing and treatment for H. pylori is recommended, followed by subsequent test-of-cure using non-invasive tests (stool antigen test or urea breath test). In the ≥45 age group, a combined strategy is recommended, involving H. pylori testing and treatment plus non-invasive biomarkers (H. pylori IgG serology and serum pepsinogens I and II); subsequently, a selected group of subjects will undergo EGD with gastric biopsies (Sydney Protocol), which will be used to stratify surveillance according to the classification Operative Link for Gastritis Assessment (OLGA); every 3 years for OLGA III-IV and every 5 years for OLGA I-II. CONCLUSION: A "test-and-treat" strategy for H. pylori infection based on non-invasive studies (primary prevention) is proposed in the 35-44 age group, and a combined strategy (serology and EGD) is recommended for the ≥45 age group (primary and secondary prevention). These strategies are potentially applicable to other countries in LAC.

The Effect of Developmental Pleiotropy on the Evolution of Insect Immune Genes.

The pressure to survive ever-changing pathogen exposure explains the frequent observation that immune genes are among the fastest evolving in the genomes of many taxa, but an intriguing proportion of immune genes also appear to be under purifying selection. Though variance in evolutionary signatures of immune genes is often attributed to differences in gene-specific interactions with microbes, this explanation neglects the possibility that immune genes participate in other biological processes that could pleiotropically constrain adaptive selection. In this study, we analyzed available transcriptomic and genomic data from Drosophila melanogaster and related species to test the hypothesis that there is substantial pleiotropic overlap in the developmental and immunological functions of genes involved in immune signaling and that pleiotropy would be associated with stronger signatures of evolutionary constraint. Our results suggest that pleiotropic immune genes do evolve more slowly than those having no known developmental functions and that signatures of constraint are particularly strong for pleiotropic immune genes that are broadly expressed across life stages. These results support the general yet untested hypothesis that pleiotropy can constrain immune system evolution, raising new fundamental questions about the benefits of maintaining pleiotropy in systems that need to rapidly adapt to changing pathogen pressures.

Seroprevalencia de anticuerpos anti SARS-CoV-2 en médicos de un hospital pediátrico / Seroprevalence of SARS-CoV-2 antibodies among physicians from a children's hospital

Introducción. En pocos meses, la enfermedad por coronavirus 2019 (COVID-19) se transformó en una pandemia, alcanzando millones de casos y centenas de miles de muertos. Por la enorme capacidad de contagio, el personal de salud se encuentra más expuesto a contraerla. Sin embargo, aún hay muy poca información al respecto, particularmente, entre pediatras.Objetivo. Evaluar la seroprevalencia de anticuerpos anti SARS-CoV-2 en médicos de un hospital pediátrico, a 3 meses del primer caso en la Argentina. Explorar si algunas características demográficas, profesionales y epidemiológicas son factores de riesgo para presentar seropositividad para SARS-CoV-2.Métodos. Estudio transversal, con médicos seleccionados aleatoriamente de la nómina de un hospital pediátrico. En todos, se pesquisaron anticuerpos anti SARS-CoV-2por quimioluminiscencia (inmunoglobulinas G/M -IgG/IgM-) y se recogieron antecedentes epidemiológicos (edad, lugar de residencia, categoría profesional, contacto con enfermos), para explorar asociación entre los predictores y seropositividad.Resultados. Se incluyeron 116 médicos, con una edad promedio de 45,6 ± 13,3 años. El 62,9 % eran médicos de planta, y el resto, residentes. El 42,2 % prestaban servicios en áreas dedicadas a la asistencia directa de pacientes con COVID-19.Cuatro (el 3,5 %) refirieron contacto con enfermos sin la debida protección, y 6 (el 5,2 %), viaje previo a zonas de riesgo. Solo se identificaron anticuerpos anti-SARS-CoV-2 (IgG) en un profesional. Debido a ello, no se pudo evaluar asociación entre los potenciales predictores y la presencia de anticuerpos anti-SARS-CoV-2.Conclusión. Se encontró que solo el 0,9 % de los médicos de un hospital pediátrico presentaban anticuerpos anti-SARS-CoV-2.

Introduction. In just a few months, coronavirus disease 2019 (COVID-19) has become a pandemic, causing millions of cases and hundreds of thousands of deaths. Due to its high infectiousness, the health care staff is even more exposed. Nevertheless, there is still very limited information about it, especially among pediatricians.Objective. To assess the seroprevalence of SARS-CoV-2 antibodies among physicians from a children's hospital 3 months after the first case in Argentina. To explore if certain demographic, occupational, and epidemiological characteristics are risk factors for SARS-CoV-2 seropositivity.Methods. Cross-sectional study of physicians randomly selected from the list of workers of a children's hospital. All of them were screened for SARS-CoV-2 antibodies by chemiluminescence (immunoglobulins G/M [IgG/IgM]) and their epidemiological history was collected (age, place of residence, professional category, contact with infected people) in order to explore the association between predictors and seropositivity.Results. A total of 116 physicians were included; their average age was 45.6 ± 13.3 years. Of them, 62.9 % were staff physicians, and the rest, residents; 42.2 % worked in areas designated for direct care of COVID-19 patients. Four (3.5 %) referred contact with infected people without the appropriate protection, and 6 (5.2 %), having traveled to risk areas. SARS-CoV-2 antibodies (IgG) were only detected in one of the professionals. Because of this, it was impossible to assess the association between potential predictors and the presence of SARS-CoV-2 antibodies.Conclusion. It was observed that only 0.9 % of the physicians from a children's hospital had SARS-CoV-2 antibodies

Seroprevalence of SARS-CoV-2 antibodies among physicians from a children's hospital. / Seroprevalencia de anticuerpos anti SARS-CoV-2 en médicos de un hospital pediátrico.

INTRODUCTION: In just a few months, coronavirus disease 2019 (COVID-19) has become a pandemic, causing millions of cases and hundreds of thousands of deaths. Due to its high infectiousness, the health care staff is even more exposed. Nevertheless, there is still very limited information about it, especially among pediatricians. OBJECTIVE: To assess the seroprevalence of SARSCoV- 2 antibodies among physicians from a children's hospital 3 months after the first case in Argentina. To explore if certain demographic, occupational, and epidemiological characteristics are risk factors for SARS-CoV-2 seropositivity. METHODS: Cross-sectional study of physicians randomly selected from the list of workers of a children's hospital. All of them were screened for SARS-CoV-2 antibodies by chemiluminescence (immunoglobulins G/M [IgG/IgM]) and their epidemiological history was collected (age, place of residence, professional category, contact with infected people) in order to explore the association between predictors and seropositivity. RESULTS: A total of 116 physicians were included; their average age was 45.6 ± 13.3 years. Of them, 62.9 % were staff physicians, and the rest, residents; 42.2 % worked in areas designated for direct care of COVID-19 patients. Four (3.5 %) referred contact with infected people without the appropriate protection, and 6 (5.2 %), having traveled to risk areas. SARS-CoV-2 antibodies (IgG) were only detected in one of the professionals. Because of this, it was impossible to assess the association between potential predictors and the presence of SARS-CoV-2 antibodies. CONCLUSION: It was observed that only 0.9 % of the physicians from a children's hospital had SARS-CoV-2 antibodies.

Introducción. En pocos meses, la enfermedad por coronavirus 2019 (COVID-19) se transformó en una pandemia, alcanzando millones de casos y centenas de miles de muertos. Por la enorme capacidad de contagio, el personal de salud se encuentra más expuesto a contraerla. Sin embargo, aún hay muy poca información al respecto, particularmente, entre pediatras. Objetivo. Evaluar la seroprevalencia de anticuerpos anti SARS-CoV-2 en médicos de un hospital pediátrico, a 3 meses del primer caso en la Argentina. Explorar si algunas características demográficas, profesionales y epidemiológicas son factores de riesgo para presentar seropositividad para SARS-CoV-2. Métodos. Estudio transversal, con médicos seleccionados aleatoriamente de la nómina de un hospital pediátrico. En todos, se pesquisaron anticuerpos anti SARS-CoV-2 por quimioluminiscencia (inmunoglobulinas G/M -IgG/IgM-) y se recogieron antecedentes epidemiológicos (edad, lugar de residencia, categoría profesional, contacto con enfermos), para explorar asociación entre los predictores y seropositividad. Resultados. Se incluyeron 116 médicos, con una edad promedio de 45,6 ± 13,3 años. El 62,9 % eran médicos de planta, y el resto, residentes. El 42,2 % prestaban servicios en áreas dedicadas a la asistencia directa de pacientes con COVID-19. Cuatro (el 3,5 %) refirieron contacto con enfermos sin la debida protección, y 6 (el 5,2 %), viaje previo a zonas de riesgo. Solo se identificaron anticuerpos anti-SARS-CoV-2 (IgG) en un profesional. Debido a ello, no se pudo evaluar asociación entre los potenciales predictores y la presencia de anticuerpos anti-SARS-CoV-2. Conclusión. Se encontró que solo el 0,9 % de los médicos de un hospital pediátrico presentaban anticuerpos anti-SARS-CoV-2.

Development and reliability of the Prospective Memory Assessment for Children & Youth (PROMACY): A preliminary study in a nonclinical sample.

Prospective memory (PM), "remembering to remember," has been linked to important functional outcomes in adults. Studies of PM in children and adolescents would benefit from the development and validation of developmentally appropriate clinical measures with known psychometric properties. The Prospective Memory Assessment for Children & Youth (PROMACY), a performance-based measure of PM, was developed for the Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol, Memory and Executive Functioning Substudy, and includes Summary, Time-, and Event-based scores derived from eight trials with an ongoing word search task. Fifty-four healthy perinatally HIV-exposed, uninfected children and youth, mean age 13 years, 54% female, 76% Black/non-Hispanic, and 61% impoverished were included in this psychometric analysis. PROMACY Summary Scores demonstrated low, but broadly acceptable internal consistency as measured by Cronbach's alpha and Spearman-Brown. Better PROMACY performance was associated with older age, but no other demographic factors. Generally medium-sized correlations were observed between the PROMACY Summary Score and standard clinical measures of retrospective memory, working memory, executive functions, and IQ. Findings from this preliminary psychometric study of nonclinical children and youth provide cautious support for the internal consistency and construct validity of PROMACY's Summary Score that awaits replication and extension in larger samples of healthy children, youth and clinical populations.

Successful pregnancy in a CKD patient on a low-protein, supplemented diet: an opportunity to reflect on CKD and pregnancy in Mexico, an emerging country.

Pregnancy is probably the most important challenge in young women with chronic kidney disease (CKD). The challenge is greater in developing countries, in which access to dialysis is uneven, and prenatal care for CKD patients is not uniformly available. This case report summarizes some of the challenges faced by pregnant CKD women in a developing country. A 35-year-old woman, affected by an undiagnosed kidney disease, experienced preeclampsia at 24 years of age, and started dialysis in emergency at age 31 in the context of severe preeclampsia in her second pregnancy. Following slow recovery of kidney function, after 18 months of dialysis she started a moderately restricted, supplemented, low-protein diet, which allowed her to discontinue dialysis. A few months after dialysis discontinuation, she started a new pregnancy in the presence of severely reduced kidney function (serum creatinine 4.6 mg/dl at the last pre-pregnancy control). Interestingly, she discontinued nephrology and nutritional follow-up, mainly because she was worried that she would be discouraged from continuing the pregnancy, but also because she continued to feel well. She self-managed her diet in pregnancy and delivered a healthy baby, with normal intrauterine growth, at term; while the last laboratory data confirmed the presence of severe kidney function impairment, she is still dialysis-free at the time of the present report. Her story, with its happy ending, underlines the importance of dedicated programs for CKD pregnancies in developing countries and confirms the safety of moderately protein-restricted diets in pregnancy.

Learning and Memory in Children and Adolescents With Perinatal HIV Infection and Perinatal HIV Exposure.

BACKGROUND: Learning and memory in youth with perinatally acquired HIV (PHIV) are poorly understood, despite their importance for academic, healthcare and daily functioning. METHODS: PHIV (n = 173) and perinatally HIV-exposed but uninfected (PHEU, n = 85) participants (aged 9-19 years) in a substudy of the Pediatric HIV/AIDS Cohort Study completed age-standardized tests of verbal and visual learning and delayed memory. Linear regression models implemented via generalized estimating equations were used to compare memory measures in PHEU participants versus PHIV youth with and without Centers for Disease Control and Prevention class C diagnosis (PHIV-C, n = 45 and PHIV-non-C, n = 128, respectively), adjusting for sociodemographic covariates. RESULTS: Participants (mean age = 14.10 years) were 54% female, 75% Black and 18% Hispanic. Although unadjusted analyses showed significantly lower visual recognition memory and verbal delayed recall for PHIV-C compared with PHEU participants and lower verbal learning for PHIV-C and non-C groups compared with PHEU, differences persisted only for visual recognition memory after adjusting for sociodemographic covariates. For PHIV youth, current CD4% <25 was associated with poorer verbal learning, and older age at peak viral load was associated with poorer verbal delayed recall and design memory. CONCLUSIONS: Youth with PHIV, particularly those with Centers for Disease Control and Prevention class C diagnosis, showed poorer performance on some measures of learning and memory compared with PHEU. Although group differences in verbal memory were largely attributable to sociodemographic characteristics, associations of class C diagnosis with poorer visual recognition memory and of current CD4% with poorer verbal learning suggest subtle effects of HIV on learning and memory in youth with PHIV.

A robust method for estimating landfill methane emissions.

Because municipal solid waste (MSW) landfills emit significant amounts of methane, a potent greenhouse gas, there is considerable interest in quantifying surficial methane emissions from landfills. The authors present a method to estimate methane emissions, using ambient air volatile organic compound (VOC) measurements taken above the surface of the landfill. Using a hand-held monitor, hundreds of VOC concentrations can be taken easily in a day, and simple meteorological data can be recorded at the same time. The standard Gaussian dispersion equations are inverted and solved by matrix methods to determine the methane emission rates at hundreds of point locations throughout a MSW landfill. These point emission rates are then summed to give the total landfill emission rate. This method is tested on a central Florida MSW landfill using data from 3 different days, taken 6 and 12 months apart. A sensitivity study is conducted, and the emission estimates are most sensitive to the input meteorological parameters of wind speed and stability class. Because of the many measurements that are used, the results are robust. When the emission estimates were used as inputs into a dispersion model, a reasonable scatterplot fit of the individual concentration measurement data resulted.

Abnormal lipid concentrations in cystic fibrosis.

BACKGROUND: Concentrations of cholesterol and triacylglycerol are commonly believed to be low in persons with cystic fibrosis and thus not of concern. OBJECTIVE: The goal was to determine whether concentrations of cholesterol and triacylglycerol are related to glucose tolerance or nutritional status in patients with cystic fibrosis. DESIGN: Fasting lipid profiles were measured in 192 patients ( +/- SD age: 21 +/- 11 y) in conjunction with an oral-glucose-tolerance test. RESULTS: Cystic fibrosis patients in all age groups had higher triacylglycerol (1.51 +/- 0.95 mmol/L) and lower cholesterol (3.57 +/- 0.96 mmol/L) concentrations than US population means. Thirty patients (16%) had hypertriglyceridemia (3.22 +/- 1.22 mmol/L), and 8 patients (4%) had elevated cholesterol (6.05 +/- 1.32 mmol/L). In most cases, hypertriglyceridemia was isolated; only 3 subjects had elevation of both cholesterol and triacylglycerol. Lipid concentrations were not related to body mass index, weight, glucose tolerance, the areas under the curve for glucose or insulin, or glycated hemoglobin. Lipid concentrations also did not correlate with cystic fibrosis genotype, use of systemic steroids, blood pressure, liver enzymes, C-reactive protein, or pulmonary function. CONCLUSIONS: Isolated hypertriglyceridemia appears to be common in cystic fibrosis, whereas cholesterol concentrations are generally low. Hypertriglyceridemia may be related to chronic low-grade inflammation or to a dietary macronutrient imbalance with excessive simple carbohydrate absorption relative to fat absorption. Whether it is associated with a risk of cardiovascular disease in this population is uncertain, but the clinical significance of triacylglycerol elevation may become important as survival improves.

Histotropismo y patogenicidad de Trypanosoma cruzi en ratón albino (NHI) aislado de triatominos en Nuevo León, México / Histotropism and pathogenicity of Trypanosoma cruzi in albinus mouse (NHI) isolated from triatomines in Nuevo Leon, Mexico

La cepa neolonesa de Trypanosoma cruzi se obtuvo de las deyecciones de los triatominos (Triatoma gerstaeckeri) capturados en General Terán y Dr. Coss, Nuevo León. La cepa fue reproducida en pases sucesivos ratón triatoma y viceversa. Posteriormente, los nidos de amastigotes se localizaron en fibras musculares y cardíacas del ratón albino Mus musculus NHI, mediante observaciones al microscopio de luz y al microscopio electrónico de transmisión, clasificándola como una cepa miotrópica, estableciéndose en menor grado en hígado, riñón y bazo. Los principales cambios patológicos observados fueron la inflamación intersticial, disrupción de fibras musculares, miocarditis, alteración mitocondrial y vacuolización citoplásmica