Neonatal mortality risk of large-for-gestational-age and macrosomic live births in 15 countries, including 115.6 million nationwide linked records, 2000-2020.

OBJECTIVE: We aimed to compare the prevalence and neonatal mortality associated with large for gestational age (LGA) and macrosomia among 115.6 million live births in 15 countries, between 2000 and 2020. DESIGN: Population-based, multi-country study. SETTING: National healthcare systems. POPULATION: Liveborn infants. METHODS: We used individual-level data identified for the Vulnerable Newborn Measurement Collaboration. We calculated the prevalence and relative risk (RR) of neonatal mortality among live births born at term + LGA (>90th centile, and also >95th and >97th centiles when the data were available) versus term + appropriate for gestational age (AGA, 10th-90th centiles) and macrosomic (≥4000, ≥4500 and ≥5000 g, regardless of gestational age) versus 2500-3999 g. INTERGROWTH 21st served as the reference population. MAIN OUTCOME MEASURES: Prevalence and neonatal mortality risks. RESULTS: Large for gestational age was common (median prevalence 18.2%; interquartile range, IQR, 13.5%-22.0%), and overall was associated with a lower neonatal mortality risk compared with AGA (RR 0.83, 95% CI 0.77-0.89). Around one in ten babies were ≥4000 g (median prevalence 9.6% (IQR 6.4%-13.3%), with 1.2% (IQR 0.7%-2.0%) ≥4500 g and with 0.2% (IQR 0.1%-0.2%) ≥5000 g). Overall, macrosomia of ≥4000 g was not associated with increased neonatal mortality risk (RR 0.80, 95% CI 0.69-0.94); however, a higher risk was observed for birthweights of ≥4500 g (RR 1.52, 95% CI 1.10-2.11) and ≥5000 g (RR 4.54, 95% CI 2.58-7.99), compared with birthweights of 2500-3999 g, with the highest risk observed in the first 7 days of life. CONCLUSIONS: In this population, birthweight of ≥4500 g was the most useful marker for early mortality risk in big babies and could be used to guide clinical management decisions.

A transdiagnostic dimensional approach towards a neuropsychological assessment for addiction: an international Delphi consensus study.

BACKGROUND: The US National Institutes of Mental Health Research Domain Criteria (RDoC) seek to stimulate research into biologically validated neuropsychological dimensions across mental illness symptoms and diagnoses. The RDoC framework comprises 39 functional constructs designed to be revised and refined, with the overall goal of improving diagnostic validity and treatments. This study aimed to reach a consensus among experts in the addiction field on the 'primary' RDoC constructs most relevant to substance and behavioural addictions. METHODS: Forty-four addiction experts were recruited from Australia, Asia, Europe and the Americas. The Delphi technique was used to determine a consensus as to the degree of importance of each construct in understanding the essential dimensions underpinning addictive behaviours. Expert opinions were canvassed online over three rounds (97% completion rate), with each consecutive round offering feedback for experts to review their opinions. RESULTS: Seven constructs were endorsed by ≥ 80% of experts as 'primary' to the understanding of addictive behaviour: five from the Positive Valence System (reward valuation, expectancy, action selection, reward learning, habit); one from the Cognitive Control System (response selection/inhibition); and one expert-initiated construct (compulsivity). These constructs were rated to be related differentially to stages of the addiction cycle, with some linked more closely to addiction onset and others more to chronicity. Experts agreed that these neuropsychological dimensions apply across a range of addictions. CONCLUSIONS: The study offers a novel and neuropsychologically informed theoretical framework, as well as a cogent step forward to test transdiagnostic concepts in addiction research, with direct implications for assessment, diagnosis, staging of disorder, and treatment.

Lost crops of the Incas: Origins of domestication of the Andean pulse crop tarwi, Lupinus mutabilis.

PREMISE OF THE STUDY: The Andean highlands are a hotspot of domestication, yet our understanding of the origins of early Andean agriculture remains fragmentary. Key questions of where, when, how many times, and from what progenitors many Andean crops were domesticated remain unanswered. The Andean lupine crop tarwi (Lupinus mutabilis) is a regionally important pulse crop with exceptionally high seed protein and oil content and is the focus of modern breeding efforts, but its origins remain obscure. METHODS: A large genome-wide DNA polymorphism data set was generated using nextRADseq to infer relationships among more than 200 accessions of Andean Lupinus species, including 24 accessions of L. mutabilis and close relatives. Phylogenetic and demographic analyses were used to identify the likely progenitor of tarwi and elucidate the area and timing of domestication in combination with archaeological evidence. KEY RESULTS: We infer that tarwi was domesticated once in northern Peru, most likely in the Cajamarca region within, or adjacent to the extant distribution of L. piurensis, which is the most likely wild progenitor. Demographic analyses suggest that tarwi split from L. piurensis around 2600 BP and suffered a classical domestication bottleneck. The earliest unequivocal archaeological evidence of domesticated tarwi seeds is from the Mantaro Valley, central Peru ca. 1800 BP. CONCLUSIONS: A single origin of tarwi from L. piurensis in northern Peru provides a robust working hypothesis for the domestication of this regionally important crop and is one of the first clear-cut examples of a crop originating in the highlands of northern Peru.

Global conservation priorities for crop wild relatives.

The wild relatives of domesticated crops possess genetic diversity useful for developing more productive, nutritious and resilient crop varieties. However, their conservation status and availability for utilization are a concern, and have not been quantified globally. Here, we model the global distribution of 1,076 taxa related to 81 crops, using occurrence information collected from biodiversity, herbarium and gene bank databases. We compare the potential geographic and ecological diversity encompassed in these distributions with that currently accessible in gene banks, as a means to estimate the comprehensiveness of the conservation of genetic diversity. Our results indicate that the diversity of crop wild relatives is poorly represented in gene banks. For 313 (29.1% of total) taxa associated with 63 crops, no germplasm accessions exist, and a further 257 (23.9%) are represented by fewer than ten accessions. Over 70% of taxa are identified as high priority for further collecting in order to improve their representation in gene banks, and over 95% are insufficiently represented in regard to the full range of geographic and ecological variation in their native distributions. The most critical collecting gaps occur in the Mediterranean and the Near East, western and southern Europe, Southeast and East Asia, and South America. We conclude that a systematic effort is needed to improve the conservation and availability of crop wild relatives for use in plant breeding.

Meta-analysis of lipid-traits in Hispanics identifies novel loci, population-specific effects, and tissue-specific enrichment of eQTLs.

We performed genome-wide meta-analysis of lipid traits on three samples of Mexican and Mexican American ancestry comprising 4,383 individuals, and followed up significant and highly suggestive associations in three additional Hispanic samples comprising 7,876 individuals. Genome-wide significant signals were observed in or near CELSR2, ZNF259/APOA5, KANK2/DOCK6 and NCAN/MAU2 for total cholesterol, LPL, ABCA1, ZNF259/APOA5, LIPC and CETP for HDL cholesterol, CELSR2, APOB and NCAN/MAU2 for LDL cholesterol, and GCKR, TRIB1, ZNF259/APOA5 and NCAN/MAU2 for triglycerides. Linkage disequilibrium and conditional analyses indicate that signals observed at ABCA1 and LIPC for HDL cholesterol and NCAN/MAU2 for triglycerides are independent of previously reported lead SNP associations. Analyses of lead SNPs from the European Global Lipids Genetics Consortium (GLGC) dataset in our Hispanic samples show remarkable concordance of direction of effects as well as strong correlation in effect sizes. A meta-analysis of the European GLGC and our Hispanic datasets identified five novel regions reaching genome-wide significance: two for total cholesterol (FN1 and SAMM50), two for HDL cholesterol (LOC100996634 and COPB1) and one for LDL cholesterol (LINC00324/CTC1/PFAS). The top meta-analysis signals were found to be enriched for SNPs associated with gene expression in a tissue-specific fashion, suggesting an enrichment of tissue-specific function in lipid-associated loci.

Producción de nanopartículas de PLGA por el método de emulsión y evaporación para encapsular N-Acetilcisteína (NAC) / PLGA nanoparticles production by emulsion and evaporation to encapsulate N-acetylcysteine (NAC) / Produção de nanopartículas de PLGA pelo método de emulsão e evaporação para encapsular N-Acetilcisteína (NAC)

Se fabricaron nanopartículas de copolímero de ácido láctico y glicólico (PLGA) de tamaños inferiores a 200 nm que atraparan y transportaran N acetilcisteína (NAC) en futuras aplicaciones como sistema de liberación de fármacos. Para esto se eligió el método de emulsión sencilla con evaporación, empleándose acetato de etilo como solvente, Pluronic F127® como tensoactivo, ultrasonido como medio para generar la emulsión y agua. Se estudió el efecto de parámetros entre la fase orgánica y acuosa, amplitud y tiempo de sonicación. Se encontraron nanopartículas de 114 nm, estables coloidalmente y que atraparon un 15% de NAC. Las condiciones encontradas fueron: relación de fase orgánica a acuosa de 1 a 5, amplitud del 60% y 60 s como tiempo de ultrasonido.

Lactic and glycolic acid (PLGA) copolymer nanoparticles of less than 200 nm were produced to trap and transport N acetylcysteine (NAC) to be used in future applications, in the field of drug delivery systems. To do this, we selected the simple emulsion and evaporation method, using ethyl acetate as a solvent, Pluronic F127® as a surfactant, water and used ultrasound to generate the emulsion. The effect of the parameters during the organic to the aqueous phase was assessed as well as the amplitude and sonication. We found nanoparticles of 114 nm that trapped colloidally stable 15% NAC; the ratio of organic to the aqueous phase was 1 to 5, the amplitude 60% and the ultrasound period was 60 s.

Fabricaram-se nanopartículas e copolímero de ácido láctico e glicólico (PLGA) de tamanhos inferiores a 200 nm que capturaram e transportaram N acetilcisteína (NAC) em futuras aplicações como sistema de libertação de fármacos. Para isto se selecionou o método de emulsão simples com evaporação, empregando-se acetato de etilo como solvente, Pluronic F127® como tensioativos, ultrasons como meio para produzir a emulsão de água. Estudou-se o efeito de parâmetros entre a fase orgânica e aquosa, amplitude e tempo de sonicação. Encontraram-se nanoparticulas de 114nm, estáveis coloidamente e que capturaram cerca de 15% de NAC. As condições encontradas foram: relação da fase orgânica a aquosa de 1 a 5, amplitude de 60% e 60s como tempo de ultrasons.

Determinants of infant growth in four age windows: a twin study.

OBJECTIVE: To identify determinants of growth during infancy. STUDY DESIGN: The sample included 424 twin pairs from the East Flanders Prospective Twin Survey. Multilevel regression analysis was performed and intrapair growth correlations were calculated. The main outcome measure was growth, measured in g/kg/d (0-1 month) or in change in weight z-score (0-6, 6-12 and 12-24 months). RESULTS: Growth during infancy was associated with birth weight and gestational age. One z-score increase in birth weight resulted in -1.77 g/kg/d less growth from 0-1 month (P < .0001). The effect size decreased with age until -0.02 (P = .70) z-scores less growth from 12 to 24 months. Corresponding numbers for one z-score increase in gestational age decreased from 0.78 (P = .001) to 0.06 (P = .40). From 12 to 24 months, paternal height had a significant positive effect. The difference in growth similarity within the twin pair between monozygotic and dizygotic twins increased from non-significant from 0 to 1 month (P = .49) to a monozygotic:dizygotic ratio approximating 2:1 from 12 to 24 months (P = .002). CONCLUSION: From 0 to 1 month, environmental factors are most important for growth, whereas genetic factors become more important over time. This is a first step in identifying age windows for future counseling and interventions on the effects of accelerated growth.

Morphological and cytochemical characterization of spores and gills of Lepista sordida (Fungi: Basidiomycota) / Caracterização morfológica e citoquímica dos esporos e lamelas de Lepista sordida (Fungi: Basidiomycota)

Some ultrastructural and cytochemical aspects of Lepista sordida are described. Basidiospores with verruculose and irregular ornamentations were observed through scanning electron microscopy. Confocal microscopy indicated that most of them exhibited a single large lipid body, no acidic vesicles and nucleus localized in the cell periphery.

Este trabalho descreve aspectos ultraestruturais e citoquímicos de Lepista sordida. Basidiósporos recobertos com ornamentações verruculosas e irregulares foram observados através de microscopia eletrônica de varredura. Através de microscopia confocal verificou-se que a maioria apresentava um grande corpo lipídico, ausência de vesículas ácidas e núcleo localizado na periferia.

Morphological and cytochemical characterization of spores and gills of Lepista sordida (Fungi: Basidiomycota).

Some ultrastructural and cytochemical aspects of Lepista sordida are described. Basidiospores with verruculose and irregular ornamentations were observed through scanning electron microscopy. Confocal microscopy indicated that most of them exhibited a single large lipid body, no acidic vesicles and nucleus localized in the cell periphery.

Phagocytosis, endosomal/lysosomal system and other cellularaspects of macrophage activation by Canova medication.

Canova is a homeopathic medication with immunomodulatory properties, recommended for diseases where the immune system is depressed. Our research aims to study the activation of mice peritoneal macrophages when submitted to in vivo and in vitro Canova treatment. Morphological parameters and acid phosphatase activity were analyzed using light and transmission electron microscopy. Differential interference contrast microscopy, including serial time acquisition in living cells, was also performed. The results demonstrated a greater spreading ability in Canova treated macrophages, a higher phagocytic activity of non-infective microorganisms (Saccharomyces cerevisiae and Tripanosoma cruzi epimastigotes) and a tendency to lower the phagocytic activity of the infective microorganisms T. cruzi trypomastigotes and Leishmania amazonensis, when compared with control cells. Acid phosphatase activity was analyzed and showed that Canova treatment stimulates an increase of the endosomal/lysosomal system. Treated macrophages that do or do not interact with yeast present a higher number of acid phosphatase marked vesicles compared to control cells. In contrast, the activity of tartrate resistant acid phosphatase (TRAP), is lower in Canova treated macrophages. The net results demonstrate that Canova medication is an effective stimulator of macrophage activity.

Recombination resulting in virulence shift in avian influenza outbreak, Chile.

Influenza A viruses occur worldwide in wild birds and are occasionally associated with outbreaks in commercial chickens and turkeys. However, avian influenza viruses have not been isolated from wild birds or poultry in South America. A recent outbreak in chickens of H7N3 low pathogenic avian influenza (LPAI) occurred in Chile. One month later, after a sudden increase in deaths, H7N3 highly pathogenic avian influenza (HPAI) virus was isolated. Sequence analysis of all eight genes of the LPAI virus and the HPAI viruses showed minor differences between the viruses except at the hemagglutinin (HA) cleavage site. The LPAI virus had a cleavage site similar to other low pathogenic H7 viruses, but the HPAI isolates had a 30-nucleotide insert. The insertion likely occurred by recombination between the HA and nucleoprotein genes of the LPAI virus, resulting in a virulence shift. Sequence comparison of all eight gene segments showed the Chilean viruses were also distinct from all other avian influenza viruses and represent a distinct South American clade.

Statistical analyses of structural magnetic resonance imaging of the head of the caudate nucleus in Colombian children with attention-deficit hyperactivity disorder.

Magnetic resonance imaging (MRI) studies of the caudate nucleus have reported reversal asymmetry and alterations of its size, suggesting a striate cortical disorder related to attention-deficit hyperactivity disorder (ADHD). The objective was to evaluate whether alterations of the asymmetry and size of the caudate nucleus head exist in a sample of well-controlled 7- to 11-year-old Colombian children, with different types of ADHD. Two groups of cases-ADHD of the combined type and ADHD of the inattentive type-and one control group, were selected. Multiple methods for assessing ADHD (rating scales, psychologic.interview, neurologic history and examination, and neuropsychologic evaluation) were used to confirm the diagnoses. Participants with a history of language disorder, learning disabilities, depression, and other major neurologic and psychiatric conditions were excluded. Finally all groups had 15 children, matched by sex (7 male, 8 female), age, socioeconomic status, and grade. Height, weight, head circumference, and encephalic index were statistically controlled. Three T1-weighted volumetric (three-dimensional) MRI slides of the caudate nucleus head were obtained with a 1.5-Tesla Gyroscan apparatus. The control group had a significantly higher Wechsler Full-Scale IQ than the groups with ADHD of the combined type and ADHD of the inattentive type (P < .001). Volumes from the left caudate nucleus head were significantly larger than volumes from the right in all groups (P < .001). There were no group differences when volumes were compared between groups. All of the groups had left caudate nucleus head volumes significantly higher than right, although there were no between-group differences. The results in relation to previous studies are discussed.

Molecular approaches to malaria and Babesisosis diagnosis

The development of additional methods for detecting and identifuing Babesia and Plasmodium infections may be useful in disease monitoring, management and control efforts. To preliminarily evaluate sunthetic peptide-based serodiagnosis, a hydrophilic sequence (DDESEFDKEK)was selected from published BabR gene of B. bovis. Immunization of rabbits and cattle with the hemocyanin-conjugated peptide elicited antibody responses that specifically detected both P. falciparum and B. bovis antigens by immunofluorescence and Western blots. Using a dot-ELISA with this peptide, antisera from immunized and naturally-infected cattle, and immunized rodents, were specifically detected. Reactivity was weak and correlated with peptide immunization or infection. DNA-based detection using repetitive DNA was species-specific in dot-blot formats for B. bovis DNA, and in both dot-blot and in situ formats for P. falciparum; a streamlined enzymelinked synthetic DNA assay for P. falciparum detected 30 parasites/mm(cúbicos) from patient blood using either colorimetric (2-15 h color development) or chemiluminescent detection (0.5-6-min. exposures). Serodiagnostic and DNA hybridization methods may be complementary in the respective detection of both chronic and acute infections. However, recent improvements in the polymerase chain reaction (PCR) make feasible a more sensitive and uniform approach to the diagnosis of these and other infectious disease complexes, with appropriate primers and processing methods. An analysis of ribosomal DNA genes of Plasmodium and Toxoplasma identified Apicomplexa-conserved sequence regions. Specific and distinctive PCR profiles were obtained for primers spanning the internal transcribed spacer locus for each of several Plasmodium and Babesia species