A C126R de novo Mutation in CYBB Leads to X-linked Chronic Granulomatous Disease With Recurrent Pneumonia and BCGitis

Chronic granulomatous disease (CGD) is an innate immune deficiency of phagocytic cells caused by mutations that affect components of the NADPH oxidase system, with resulting impairment in reactive oxygen species production. Patients with CGD are susceptible to recurrent infections and hyperinflammatory responses. Mutations in CYBB lead to the X-linked form of CGD and are responsible for ~ 70% of cases. In this study, we report the case of a 2.5-year-old male patient with recurrent pneumonia and Bacillus Calmette-Guérin infection (BCGitis). As his first clinical manifestation, he presented with bullous impetigo at 18 days of age, which was followed by recurrent pneumonia and regional BCGitis. Genetic analysis revealed a de novo mutation in exon 5 of the CYBB gene: a single-nucleotide substitution, c.376T > C, leading to a C126R change

Tendência genética para peso adulto, escores visuais e características de crescimento em bovinos de corte da raça Nelore

Mature weight (MW) of cows is related to the costs of their production. Usually, cows with moderate MW are more efficient in challenging environments, such as those available in the production systems in Brazil. In the present study, the selection index comprises the following traits: conformation, finishing precocity, musculature at weaning (WC, WP, WM) yearling (YC, YP and YM), scrotal circumference at yearling (SC), days to gain 160kg from birth to weaning (D160) and 240kg after weaning (D240). This are related to birth weight gain at weaning (WG) and from weaning to yearling (YG). The mature (MW) and birth weight (BW) traits were not considered in the selection index. The aim of this study was to estimate the values for the genetic trends (GT) of some important selection (MW) and economic traits (BW). A bi-character analysis of MW and other characteristics was performed to estimate the (co)variance components and genetic parameters. The GT results obtained for MW were null (0.0065% or 0.02718kg per year) in the period 1990-2007. The GT values were determined for BW (-0.0650% or -0.02017kg), WG (0.0758% or 0.0865kg), YG (0.1051% or 0.11377kg), and MW (0.0393% or 0.11276kg) per year. The visual score values (in score units) were also determined for GTat weaning [WC (0.2310%; 0.00707), WP (0.3624%; 0.3623%),aWM (0.01149; 0.01087)] yearling [YC (0.3256%; 0.00990), YP (0.4795%; 0.01496),YM (0.5041%; 0.01457)] per year. Index-based selection was effective to promote genetic progress in WG, WC, WP, WM, YG, YC, YP, and YM characteristics keeping BW and MW constant.O peso adulto das vacas (PV) está relacionado com os custos de produção. Em geral, vacas com PV moderados são mais eficientes em ambientes desafiadores, como aqueles disponíveis nos sistemas de produção no Brasil. No presente estudo, o índice de seleção compreende as seguintes características: conformação, precocidade e musculatura nas fases da desmama (CD, PD e MD) e sobreano (CS, PS e MS), circunferência escrotal no sobreano (CE), dias para ganhar 160kg do nascimento até a desmama (D160) e 240kg pós-desmama (D240), que estão relacionadas com os ganhos de peso do nascimento à desmama (GD) e, da desmama ao sobreano (GS). As características PV e PN não foram consideradas no índice de seleção. O objetivo deste estudo foi estimar os valores das tendências genéticas (TG) das importantes características de seleção (PV) e econômicas (PN). Para estimar os componentes de (co)variâncias e os dados genéticos, foram realizadas análises bi-caracter de PV com as demais características. Os resultados de TG obtidos para PV foram nulos (0,0065% ou 0,02718kg por ano) no período de 1990 á 2007. Os valores de TG foram estimados para PN (-0,0650% ou -0,02017kg), GD (0,0758% ou 0,0865kg), GS (0,1051% ou 0,11377kg) e PF (0,0393% ou 0,11276kg) por ano. Os valores dos escores visuais (em unidades de escore) foram determinados para TG à desmama [CD (0,2310%; 0,00707), PD (0,3624%; 0,3623%) e MD (0,01149; 0,01087)] e sobreano [CS (0,3256%; 0,00990), PS (0,4795%; 0,01496) e MS (0,5041%; 0,01457)] ao ano. A seleção baseada no índice foi efetiva para promover o progresso genético nas características de GD, CD, PD, MD, GS, CS, PS e mantendo PN e PV constantes

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Screening of Single Nucleotides Polymorphism (SNPs) in the gene Heat Shock Protein-70.2 (HSP-70.2) in adolescents with and whitout varicocele

Objetivo: O presente estudo teve por finalidade verificar a presenca de polimorfismos no gene Heat Shock Protein-70.2 (HSP-70.2) em adolescentes com e sem varicocele. Metodos: Foi pesquisada a mutacao do gene HSP-70-2 em 30 adolescentes, sendo 20 com varicocele (grupo de estudo) e 10 sem varicocele (grupo controle), atraves do polimorfismo conformacional de fita simples (SSCP) do DNA amplificado pela tecnica de PCR (reacao em cadeia da polimerase) nas seis regioes do exon; para os pacientes com alteracao do padrao de corrida eletroforetica (banda anormal no SSCP) foram analisados o sequenciamento do DNA e comparadas com as sequencias do gene HSP-70.2 publicadas no banco de dados do GeneBank. Resultados: Nao houve diferenca estatisticamente significante quanto as caracteristicas seminais e as dosagens hormonais entre os grupos de estudo e controle, exceto pelo menor nivel se rico de LH nos pacientes com varicocele, ainda que ambos os grupos estivessem dentro dos limites de normalidade. Tambem nao foi possivel identificar polimorfismos no gene HSP-70.2 em todas as amostras analisadas. Conclusoes: Nao ha correlacao de polimorfismos no gene HSP-70.2 em adolescentes com varicocele. A ausencia de variacao genica ou SNPs em adolescentes com ou sem varicocele indica o alto grau de conservacao deste gene e confirma o papel fundamental na espermatogenese e na resposta ao estresseBV UNIFESP: Teses e dissertaçõe