Bonobo personality traits are heritable and associated with vasopressin receptor gene 1a variation

Despite being closely related, bonobos and chimpanzees show remarkable behavioral differences, the proximate origins of which remain unknown. This study examined the link between behavioral variation and variation in the vasopressin 1a receptor gene (Avpr1a) in bonobos. Chimpanzees are polymorphic for a ~360 bp deletion (DupB), which includes a microsatellite (RS3) in the 5′ promoter region of Avpr1a. In chimpanzees, the DupB deletion has been linked to lower sociability, lower social sensitivity, and higher anxiety. Chimpanzees and bonobos differ on these traits, leading some to believe that the absence of the DupB deletion in bonobos may be partly responsible for these differences, and to the prediction that similar associations between Avpr1a genotypes and personality traits should be present in bonobos. We identified bonobo personality dimensions using behavioral measures (Sociability(B), Boldness(B), Openness(B), Activity(B)) and trait ratings (Assertiveness(R), Conscientiousness(R), Openness(R), Agreeableness(R), Attentiveness(R), Extraversion(R)). In the present study we found that all 10 dimensions have nonzero heritabilities, indicating there is a genetic basis to personality, and that bonobos homozygous for shorter RS3 alleles were lower in Attentiveness(R) and higher in Openness(B). These results suggest that variations in Avpr1a genotypes explain both within and between species differences in personality traits of bonobos and chimpanzees

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

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 middle-income 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 low-income 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 low-income, 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

“UTILIZAÇÃO DA FARMACOCINÉTICA INDIVIDUAL POR PACIENTES COM HEMOFILIA A GRAVE E SUA REPERCUSSÃO NA FREQUÊNCIA, NOS TIPOS DE SANGRAMENTOS E NAS ATIVIDADES DE VIDA DIÁRIAS”

Introdução: A hemofilia é definida como uma condição genética hereditária, em que há um defeito no gene localizado no cromossomo X, que determina como o corpo faz os fatores de coagulação VIII, IX ou XI. A hemofilia é dividida em tipos: hemofilia A, sendo o tipo mais comum, em que a proteína afetada é o fator VIII; e a hemofilia B, em que o fator IX é diminuído. A gravidade dos sangramentos depende da quantidade de fator presente no plasma do paciente. Em razão disso, estão sendo realizados avanços no tratamento da hemofilia que consistem na reposição do fator VIII de coagulação, por meio dos concentrados de fator plasmático e engenharia genética para profilaxia dos sangramentos. Juntamente, o aplicativo MYPKFIT foi desenvolvido recentemente envolvendo a farmacocinética de cada paciente e, com isso, institui o tratamento para avaliação pré e pós fator e melhoria da qualidade de vida do paciente. Objetivos: Avaliar a utilização que os pacientes fazem do MYPKFIT e a monitorização da frequência de sangramentos com o uso do aplicativo. Metodologia: Os pacientes foram avaliados através de questionários que buscavam tais informações: identificar a gravidade da hemofilia A, saber o início da entrada do paciente no aplicativo, o que faz no dia a dia, pôr em questão se existem limitações por conta da hemofilia e mudanças na vida após o aplicativo, contendo critérios de inclusão e exclusão. Resultados: Obtivemosos dados de 40 pacientes quanto ao uso do aplicativo e de seus sangramentos. Todos apresentam hemofilia A grave, são homens, majoritariamente naturais e procedentes de Sorocaba, se encontram na faixa etária dos 21 aos 48 anos e têm parentes com o mesmo diagnóstico.Todos referiram ter apresentado sangramentos recentes, predominantemente em joelhos e cotovelos ‒ dentre eles, cerca de 25% relataram sangramentos graves, 75% de forma mais leve e 70% sofrem de sequelas como artrose nos joelhos e ombros e dificuldade para dobrar as articulações. Aproximadamente 57,5% dos pacientes fazem uso do MYPKFIT e relataram ter os auxiliado na organização de sua rotina e na prevenção de eventos hemorrágicos. De acordo com as respostas, objetivamos suas informações farmacocinéticas: 41,1% foram os pacientes que apresentaram menores níveis de fatores após 24h infusão e que, concomitantemente a isso, referiram ter maior frequência de sangramentos. Conclusão: Observamos que os pacientes que utilizam o aplicativo fazem bom uso, são mais organizados em relação à rotina e são mais tranquilos para realizarem atividades físicas por saberem quando estão vulneráveis aos sangramentos - resultando em uma melhor qualidade de vida. Além disso, pôde-se comprovar que, nos pacientes os quais apresentaram menor nível de fator VIII no tempo 24h após administração, os sangramentos foram mais recorrentes, fato este que comprova que o nível do fator sérico é inversamente proporcional à probabilidade de sangramento