GHEP-ISFG collaborative exercise on mixture profiles of autosomal STRs (GHEP-MIX01, GHEP-MIX02 and GHEP-MIX03): results and evaluation

One of the main objectives of the Spanish and Portuguese-Speaking Group of the International Society for Forensic Genetics (GHEP-ISFG) is to promote and contribute to the development and dissemination of scientific knowledge in the area of forensic genetics. Due to this fact, GHEP-ISFG holds different working commissions that are set up to develop activities in scientific aspects of general interest. One of them, the Mixture Commission of GHEP-ISFG, has organized annually, since 2009, a collaborative exercise on analysis and interpretation of autosomal short tandem repeat (STR) mixture profiles. Until now, three exercises have been organized (GHEP-MIX01, GHEP-MIX02 and GHEP-MIX03), with 32, 24 and 17 participant laboratories respectively. The exercise aims to give a general vision by addressing, through the proposal of mock cases, aspects related to the edition of mixture profiles and the statistical treatment. The main conclusions obtained from these exercises may be summarized as follows. Firstly, the data show an increased tendency of the laboratories toward validation of DNA mixture profiles analysis following international recommendations (ISO/IEC 17025:2005). Secondly, the majority of discrepancies are mainly encountered in stutters positions (53.4%, 96.0% and 74.9%, respectively for the three editions). On the other hand, the results submitted reveal the importance of performing duplicate analysis by using different kits in order to reduce errors as much as possible. Regarding the statistical aspect (GHEP-MIX02 and 03), all participants employed the likelihood ratio (LR) parameter to evaluate the statistical compatibility and the formulas employed were quite similar. When the hypotheses to evaluate the LR value were locked by the coordinators (GHEP-MIX02) the results revealed a minor number of discrepancies that were mainly due to clerical reasons. However, the GHEP-MIX03 exercise allowed the participants to freely come up with their own hypotheses to calculate the LR value. In this situation the laboratories reported several options to explain the mock cases proposed and therefore significant differences between the final LR values were obtained. Complete information concerning the background of the criminal case is a critical aspect in order to select the adequate hypotheses to calculate the LR value. Although this should be a task for the judicial court to decide, it is important for the expert to account for the different possibilities and scenarios, and also offer this expertise to the judge. In addition, continuing education in the analysis and interpretation of mixture DNA profiles may also be a priority for the vast majority of forensic laboratories.Fil: Sala, Adriana Andrea. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Servicio de Huellas Digitales Genéticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Crespillo, M.. Instituto Nacional de Toxicología y Ciencias Forenses; EspañaFil: Barrio, P. A.. Instituto Nacional de Toxicología y Ciencias Forenses; EspañaFil: Luque, J. A.. Instituto Nacional de Toxicología y Ciencias Forenses; EspañaFil: Alves, Cíntia. Universidad de Porto; PortugalFil: Aler, M.. Servicio de Laboratorio. Sección de Genética Forense y Criminalística; EspañaFil: Alessandrini, F.. Università Politecnica delle Marche. Department of Biomedical Sciences and Public Health; ItaliaFil: Andrade, L.. Instituto Nacional de Medicina Legal e Ciências Forenses, Delegação do Centro. Serviço de Genética e Biologia Forenses; PortugalFil: Barretto, R. M.. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Bofarull, A.. Instituto Nacional de Toxicología y Ciencias Forenses; EspañaFil: Costa, S.. Instituto Nacional de Medicina Legal y Ciencias Forenses; PortugalFil: García, M. A.. Servicio de Criminalística de la Guardia Civil. Laboratorio Central de Criminalística. Departamento de Biología; EspañaFil: García, O.. Basque Country Police. Forensic Genetics Section. Forensic Science Unit; EspañaFil: Gaviria, A.. Cruz Roja Ecuatoriana. Laboratorio de Genética Molecular; EcuadorFil: Gladys, A.. Corte Suprema de Justicia de la Nación; ArgentinaFil: Gorostiza, A.. Grupo Zeltia. Genomica S. A. U.. Laboratorio de Identificación Genética; EspañaFil: Hernández, A.. Instituto Nacional de Toxicología y Ciencias Forenses; EspañaFil: Herrera, M.. Laboratorio Genda S. A.; ArgentinaFil: Hombreiro, L.. Jefatura Superior de Policía de Galicia. Brigada de Policía Científica. Laboratorio Territorial de Biología – ADN; EspañaFil: Ibarra, A. A.. Universidad de Antioquia; ColombiaFil: Jiménez, M. J.. Policia de la Generalitat – Mossos d’Esquadra. Divisió de Policia Científica. Àrea Central de Criminalística. Unitat Central de Laboratori Biològic; EspañaFil: Luque, G. M.. Instituto Nacional de Toxicología y Ciencias Forenses; EspañaFil: Madero, P.. Centro de Análisis Genéticos; EspañaFil: Martínez Jarreta, B.. Universidad de Zaragoza; EspañaFil: Masciovecchio, M. Verónica. IACA Laboratorios; ArgentinaFil: Modesti, Nidia Maria. Provincia de Córdoba. Poder Judicial; ArgentinaFil: Moreno, F.. Servicio Médico Legal. Unidad de Genética Forense; ChileFil: Pagano, S.. Dirección Nacional de Policía Técnica. Laboratorio de Análisis de ADN para el CODIS; UruguayFil: Pedrosa, S.. Navarra de Servicios y Tecnologías S. A. U.; EspañaFil: Plaza, G.. Neodiagnostica S. L.; EspañaFil: Prat, E.. Comisaría General de Policía Científica. Laboratorio de ADN; EspañaFil: Puente, J.. Laboratorio de Genética Clínica S. L.; EspañaFil: Rendo, F.. Universidad del País Vasco; EspañaFil: Ribeiro, T.. Instituto Nacional de Medicina Legal e Ciências Forenses, Delegação Sul. Serviço de Genética e Biologia Forenses; PortugalFil: Santamaría, E.. Instituto Nacional de Toxicología y Ciencias Forenses; EspañaFil: Saragoni, V. G.. Servicio Médico Legal. Departamento de Laboratorios. Unidad de Genética Forense; ChileFil: Whittle, M. R.. Genomic Engenharia Molecular; Brasi

History Shaped the Geographic Distribution of Genomic Admixture on the Island of Puerto Rico

Contemporary genetic variation among Latin Americans human groups reflects population migrations shaped by complex historical, social and economic factors. Consequently, admixture patterns may vary by geographic regions ranging from countries to neighborhoods. We examined the geographic variation of admixture across the island of Puerto Rico and the degree to which it could be explained by historic and social events. We analyzed a census-based sample of 642 Puerto Rican individuals that were genotyped for 93 ancestry informative markers (AIMs) to estimate African, European and Native American ancestry. Socioeconomic status (SES) data and geographic location were obtained for each individual. There was significant geographic variation of ancestry across the island. In particular, African ancestry demonstrated a decreasing East to West gradient that was partially explained by historical factors linked to the colonial sugar plantation system. SES also demonstrated a parallel decreasing cline from East to West. However, at a local level, SES and African ancestry were negatively correlated. European ancestry was strongly negatively correlated with African ancestry and therefore showed patterns complementary to African ancestry. By contrast, Native American ancestry showed little variation across the island and across individuals and appears to have played little social role historically. The observed geographic distributions of SES and genetic variation relate to historical social events and mating patterns, and have substantial implications for the design of studies in the recently admixed Puerto Rican population. More generally, our results demonstrate the importance of incorporating social and geographic data with genetics when studying contemporary admixed populations

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

Global variations in diabetes mellitus based on fasting glucose and haemogloblin A1c

Fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c) are both used to diagnose diabetes, but may identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening had elevated FPG, HbA1c, or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardised proportion of diabetes that was previously undiagnosed, and detected in survey screening, ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the agestandardised proportion who had elevated levels of both FPG and HbA1c was 29-39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global gap in diabetes diagnosis and surveillance.peer-reviewe

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

Meningoencephalitis by Naegleria fowleri: epidemiological study in Anzoategui state, Venezuela Meningoencefalite por Naegleria fowleri: estudo epidemiológico no Estado de Anzoategui, Venezuela

A case of primary amoebic meningoencephalitis produced by Naegleria fowleri was diagnosed in the Independencia county of Anzoategui State, Venezuela. This case motivated the realization of the present epidemiological study with the aim of identifying free-living amoebae in this area. Representative water samples were taken and physicochemical and microbiologic analyses were carried out. Trophozoites and cysts of Naegleria spp, were detected in 44.4% (n=4). An excellent concordance was found among the observations of free-living amoebae in smears and those of monoxenic cultures in non nourishing agar with Klebsiella pneumoniae (Kappa=1; p= 0.003). A variable load of aerobic mesophils was obtained. Moulds and yeast averages presented 3.0 CFU/ml (SD&plusmn; 2.0) and 102.9 CFU/ml (SD&plusmn; 32.2), respectively. One hundred per cent of the samples presented a most probable number of total and fecal coliforms of 240,000 NMP/100mL. Naegleria spp was present in waters of the Independence county of Anzoategui state, which constitutes a risk for people that use these sources.<br>Um caso de meningoencefalite amebiana primária, causada por Naegleria fowleri, foi diagnosticada no município de Independência no Estado de Anzoategui, Venezuela. Este caso motivou a realização deste estudo epidemiológico com o objetivo de identificar amebas de vida livre nessa área. Foram colhidas amostras representativas de água e realizadas análises fisicoquímicas e microbiológicas. Trofozoítos e cistos de Naegleria spp foram detectados em 44,4% (n=4). Verificou-se excelente concordância entre a observação das amebas de vida livre em esfregaços e aquelas de culturas monoxênicas em ágar não nutriente com Klebsiella pneumoniae (Kappa=1; p=0,003). Obteve-se uma carga variável de microrganismos mesófilos aeróbicos. As médias de mofos e leveduras foram de 3,0 CFU/ml (SD+2,0) e 102,9 CFU/ml(SD+32,2), respectivamente. Cem por cento das amostras apresentaram um número maior provável de coliformes totais e fecais de 240.000 NMP/100ml. Naegleria spp estava presente nas águas do município de Independência no Estado de Anzoategui, o que constitui um risco para a população que usa essas fontes

Respostas morfofisiológicas de plantas de açacu (Hura crepitans L.) provenientes de várzeas do rio Amazonas: efeito da anoxia do solo

Neste trabalho foram avaliadas as respostas morfofisiológicas de plantas de açacu (Hura crepitans) sob a anoxia do solo com diferentes idades (90 e 120 dias) e períodos de inundação (0, 10, 20 e 30 dias). O estudo identificou que as plantas desenvolveram mecanismos adaptativos (estruturas morfológicas como lenticelas hipertróficas e raízes adventícias) e apresentaram comportamento fisiológico que lhes propiciaram tolerância à anoxia. As respostas das plantas ao excesso de água no solo incluíram inibição do crescimento vegetativo, clorose e senescência foliar. O estresse hídrico por anoxia comprometeu a viabilidade das plantas de 90 dias de idade, enquanto as plantas de açacu de 120 dias de idade mostraram-se tolerantes ao alagamento