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.

Neonatal mortality risk for vulnerable newborn types in 15 countries using 125.5 million nationwide birth outcome records, 2000-2020.

OBJECTIVE: To compare neonatal mortality associated with six novel vulnerable newborn types in 125.5 million live births across 15 countries, 2000-2020. DESIGN: Population-based, multi-country study. SETTING: National data systems in 15 middle- and high-income countries. METHODS: We used individual-level data sets identified for the Vulnerable Newborn Measurement Collaboration. We examined the contribution to neonatal mortality of six newborn types combining gestational age (preterm [PT] versus term [T]) and size-for-gestational age (small [SGA], <10th centile, appropriate [AGA], 10th-90th centile or large [LGA], >90th centile) according to INTERGROWTH-21st newborn standards. Newborn babies with PT or SGA were defined as small and T + LGA was considered as large. We calculated risk ratios (RRs) and population attributable risks (PAR%) for the six newborn types. MAIN OUTCOME MEASURES: Mortality of six newborn types. RESULTS: Of 125.5 million live births analysed, risk ratios were highest among PT + SGA (median 67.2, interquartile range [IQR] 45.6-73.9), PT + AGA (median 34.3, IQR 23.9-37.5) and PT + LGA (median 28.3, IQR 18.4-32.3). At the population level, PT + AGA was the greatest contributor to newborn mortality (median PAR% 53.7, IQR 44.5-54.9). Mortality risk was highest among newborns born before 28 weeks (median RR 279.5, IQR 234.2-388.5) compared with babies born between 37 and 42 completed weeks or with a birthweight less than 1000 g (median RR 282.8, IQR 194.7-342.8) compared with those between 2500 g and 4000 g as a reference group. CONCLUSION: Preterm newborn types were the most vulnerable, and associated with the highest mortality, particularly with co-existence of preterm and SGA. As PT + AGA is more prevalent, it is responsible for the greatest burden of neonatal deaths at population level.

Vulnerable newborn types: Analysis of population-based registries for 165 million births in 23 countries, 2000-2021.

OBJECTIVE: To examine the prevalence of novel newborn types among 165 million live births in 23 countries from 2000 to 2021. DESIGN: Population-based, multi-country analysis. SETTING: National data systems in 23 middle- and high-income countries. POPULATION: Liveborn infants. METHODS: Country teams with high-quality data were invited to be part of the Vulnerable Newborn Measurement Collaboration. We classified live births by six newborn types based on gestational age information (preterm <37 weeks versus term ≥37 weeks) and size for gestational age defined as small (SGA, <10th centile), appropriate (10th-90th centiles), or large (LGA, >90th centile) for gestational age, according to INTERGROWTH-21st standards. We considered small newborn types of any combination of preterm or SGA, and term + LGA was considered large. Time trends were analysed using 3-year moving averages for small and large types. MAIN OUTCOME MEASURES: Prevalence of six newborn types. RESULTS: We analysed 165 017 419 live births and the median prevalence of small types was 11.7% - highest in Malaysia (26%) and Qatar (15.7%). Overall, 18.1% of newborns were large (term + LGA) and was highest in Estonia 28.8% and Denmark 25.9%. Time trends of small and large infants were relatively stable in most countries. CONCLUSIONS: The distribution of newborn types varies across the 23 middle- and high-income countries. Small newborn types were highest in west Asian countries and large types were highest in Europe. To better understand the global patterns of these novel newborn types, more information is needed, especially from low- and middle-income countries.

One hundred citation classics in benign anorectal disease: a bibliometric analysis of seven decades (1950-2019) / Cem clássicos de citações em doença anorretal benigna: uma análise bibliométrica de sete décadas (1950-2019)

ABSTRACT Background & aim Bibliometric analysis is used to explore the historical development in a particular field. The aim is to identify and analyse most cited papers in benign anorectal disease in the last 7 decades (1950-2018). Method Thomson Reuters Web of Science database was used to find the top 100 cited articles in benign anorectal conditions. Papers were independently extracted by two investigators. The top 100 cited articles were identified and ranked according to number of citations. The articles were then sorted by author, journal, institution, country and publication date. The study subject was divided into 5 groups. Results The most frequently cited article received 1307 citations whereas the least cited received 154 citations. The earliest recorded article was published in 1960 and the most recent was from 2010. More than half of the articles addressed faecal incontinence and sphincter related literature (n = 54). The articles were published in 29 different journals. A majority (69%) of manuscripts originated from the USA (n = 35; 9221 citations) and UK (n = 34; 7796 citations). The origin of these top 100 classic papers was from 53 different institutions. St. Mark's Hospital in the UK had the highest number of articles (n = 21), followed by Cleveland clinic (n = 5) and University of Minnesota (n = 5). Conclusion The most highly cited manuscripts in benign anorectal disease cover a wide range of topics. Faecal incontinence and sphincter related articles had the highest number of citations. This review serves as a reference for researchers to find the influential papers in this field.

RESUMO Justificativa e objetivo A análise bibliométrica é usada para explorar o desenvolvimento histórico em um campo específico. O objetivo é identificar e analisar os artigos mais citados em doença anorretal benigna nas últimas 7 décadas (1950-2018). Método A base de dados Thomson Reuters Web of Science foi usada para encontrar os 100 artigos mais citados em doenças anorretais benignas. Os artigos foram extraídos de forma independente por dois pesquisadores. Os 100 artigos mais citados foram identificados e classificados de acordo com o número de citações. Os artigos foram classificados por autor, revista médica, instituição, país e data de publicação. Os sujeitos do estudo foram divididos em cinco grupos. Resultados O artigo mais citado recebeu 1.307 citações, enquanto o menos citado recebeu 154 citações. O artigo mais antigo foi publicado em 1960 e o mais recente a partir de 2010. Mais da metade dos artigos abordou a incontinência fecal e a literatura relacionada ao esfíncter (n = 54). Os artigos foram publicados em 29 revistas diferentes. A maioria (69%) dos manuscritos é originária dos EUA (n = 35; 9.221 citações) e do Reino Unido (n = 34; 7.796 citações). Os 100 artigos clássicos mais citados são originários de 53 instituições diferentes. O St. Mark's Hospital, no Reino Unido, teve o maior número de artigos (n = 21), seguido pela Clínica de Cleveland (n = 5) e pela Universidade de Minnesota (n = 5). Conclusão Os manuscritos mais citados em doença anorretal benigna abrangem uma grande variedade de tópicos. Os artigos relacionados à incontinência fecal e ao esfíncter tiveram o maior número de citações. Esta revisão serve de referência para os pesquisadores encontrarem os artigos influentes nesse campo.

Ameliorative effect of propolis against hepatorenal alterations induced by methotrexate: morphohistopathological study / Efecto protector del propóleo en las alteraciones hepatorrenales inducidas por el metotrexato: estudio morfohistopatológico

Methotrexate (MTX) is widely used in the treatment of some forms of cancer but having severe side effects. The present work aimed to investigate the protective role of propolis treatment against alterations induced by MTX on the hepatic and renal tissues. Rabbits were exposed to MTX (0.25 mg/kg), with or without propolis (50 mg/kg) while hepatic and renal biopsies were examined for histological and histochemical abnormalities. Methotrexate induced hydropic degeneration, pyknosis, sinusoidal dilatation and bile duct hyperplasia in the liver together with renal tubular degeneration, glomerular shrinkage and hyaline droplet precipitation. While propolis partially ameliorated some of the morphometric and biochemical alterations, none of the hepatic alterations induced by MTX was protected by propolis treatment. Nevertheless glomerular shrinkage and renal tubule degeneration were partially protected in animals received both MTX plus propolis. It is concluded that propolis treatment has little or no ameliorative effect in protecting the hepatic and renal tissues from MTX toxicity.

El metotrexato (MTX) es ampliamente utilizado en el tratamiento de algunas formas de cáncer, pero tiene efectos secundarios graves. El presente trabajo tuvo como objetivo investigar el papel protector del tratamiento con própoleo frente a las alteraciones inducidas por el MTX en los tejidos hepático y renal. Se expusieron conejos a MTX (0,25 mg / kg), en grupos con y sin propóleo (50 mg / kg), y se realizaron biopsias hepáticas y renales, que fueron examinadas buscando anomalías histológicas e histoquímicas. El metotrexato indujo la degeneración hidrópica, picnosis, dilatación sinusoidal e hiperplasia del conducto biliar en el hígado, junto con la degeneración tubular renal, la contracción glomerular y la precipitación hialina. Mientras que el propóleo parcialmente mejoró algunas de las alteraciones morfométricas y bioquímicas, ninguna de las alteraciones hepáticas inducidas por MTX fue protegido por el tratamiento con propóleo. Sin embargo, la contracción glomerular y la degeneración de los túbulos renales fueron parcialmente protegidos en animales que recibieron MTX más propóleo. Se concluye que el tratamiento con propóleo tiene poco o ningún efecto mejorador en la protección de los tejidos hepáticos y renales sometidos a la toxicidad de MTX.

PARK2 polymorphisms predict disease progression in patients infected with hepatitis C virus.

 Background. The protein encoded by PARK2 gene is a component of the ubiquitin-proteasome system that mediates targeting of proteins for the degradation pathway. Genetic variations at PARK2 gene were linked to various diseases including leprosy, typhoid and cancer. The present study investigated the association of single nucleotide polymorphisms (SNPs) in the PARK2 gene with the development of hepatitis C virus (HCV) infection and its progression to severe liver diseases. MATERIAL AND METHODS: A total of 800 subjects, including 400 normal healthy subjects and 400 HCV-infected patients, were analyzed in this study. The patients were classified as chronic HCV patients (group I), patients with cirrhosis (group II) and patients with hepatocellular carcinoma (HCC) in the context of cirrhosis (group III). DNA was extracted and was genotyped for the SNPs rs10945859, rs2803085, rs2276201 and rs1931223. RESULTS: Among these SNPs, CT genotype of rs10945859 was found to have a significant association towards the clinical progression of chronic HCV infection to cirrhosis alone (OR = 1.850; 95% C. I. 1.115-3.069; p = 0.016) or cirrhosis and HCC (OR = 1.768; 95% C. I. 1.090-2.867; p value = 0.020). CONCLUSION: SNP rs10945859 in the PARK2 gene could prove useful in predicting the clinical outcome in HCV-infected patients.

In vitro differentiation of sperm from male germline stem cell.

In this study, we developed a model of sperm in vitro differentiation to study the mechanism of spermatogenesis. We isolated newborn male germ cells for in vitro differentiation. We found that after 4-5 weeks of culture, sperm-like cells were occasionally observed in cell co-culture and the feed-layer. After 1-2 weeks of culture followed by 4-5 weeks of co-culture, sperm-like cells were observed.

Behavior of calf Sertoli cells and fibroblast cells transfected with the human HNP-1 gene.

Human neutrophil peptide-1 (HNP-1) is an important defense molecule in neutrophils and Sertoli cells and plays an important role in the blood-testis barrier. In this study, we investigated the behavior of Sertoli cells transfected with the HNP-1 gene and compared the ability of Sertoli cells and fibroblast cells to resist transfection. Total RNA was isolated from human blood. The DNA coding sequence of HNP-1 was amplified by reverse transcription-polymerase chain reaction (RT-PCR) and the eukaryotic expression vector pEGFP-N3-HNP-1 was identified by PCR, endonuclease digestion, and sequencing. Bovine Sertoli cells and fibroblast cells were transfected with pEGFP-N3-HNP-1 using Liposome reagent. The transfection efficiency and the behavior of the transfected cells were evaluated at 24, 48 and 72 h as well as at other times after transfection. The plasmid pEGFP-N3-HNP-1 was successfully constructed. The cells achieved maximum transfection efficiency at 48 h. Two weeks after transfection, the cells began to stop dividing. The ability of Sertoli cells to resist transfection was higher compared to fibroblast cells. The ability of the 2 cell types to resist transfection was higher with plasmid pEGFP-N3-HNP-1 than with the plasmid pEGFP-N3. The injury to Sertoli cells caused by transfection with the HNP-1 gene was less pronounced than in fibroblast cells, which may be closely correlated with the physiological function of Sertoli cells.

The tomato wilt fungus Fusarium oxysporum f. sp. lycopersici shares common ancestors with nonpathogenic F. oxysporum isolated from wild tomatoes in the Peruvian Andes.

Fusarium oxysporum is an ascomycetous fungus that is well-known as a soilborne plant pathogen. In addition, a large population of nonpathogenic F. oxysporum (NPF) inhabits various environmental niches, including the phytosphere. To obtain an insight into the origin of plant pathogenic F. oxysporum, we focused on the tomato (Solanum lycopersicum) and its pathogenic F. oxysporum f. sp. lycopersici (FOL). We collected F. oxysporum from wild and transition Solanum spp. and modern cultivars of tomato in Chile, Ecuador, Peru, Mexico, Afghanistan, Italy, and Japan, evaluated the fungal isolates for pathogenicity, VCG, mating type, and distribution of SIX genes related to the pathogenicity of FOL, and constructed phylogenies based on ribosomal DNA intergenic spacer sequences. All F. oxysporum isolates sampled were genetically more diverse than FOL. They were not pathogenic to the tomato and did not carry SIX genes. Certain NPF isolates including those from wild Solanum spp. in Peru were grouped in FOL clades, whereas most of the NPF isolates were not. Our results suggested that the population of NPF isolates in FOL clades gave rise to FOL by gaining pathogenicity.

Microbial and chemical transformation studies of the bioactive marine sesquiterpenes (S)-(+)-curcuphenol and -curcudiol isolated from a deep reef collection of the Jamaican sponge Didiscus oxeata.

Microbial and chemical transformation studies of the marine sesquiterpene phenols (S)-(+)-curcuphenol (1) and (S)-(+)-curcudiol (2), isolated from the Jamaican sponge Didiscus oxeata, were accomplished. Preparative-scale fermentation of 1 with Kluyveromyces marxianus var. lactis (ATCC 2628) has resulted in the isolation of six new metabolites: (S)-(+)-15-hydroxycurcuphenol (3), (S)-(+)-12-hydroxycurcuphenol (4), (S)-(+)-12,15-dihydroxycurcuphenol (5), (S)-(+)-15-hydroxycurcuphenol-12-al (6), (S)-(+)-12-carboxy-10,11-dihydrocurcuphenol (7), and (S)-(+)-12-hydroxy-10,11-dihydrocurcuphenol (8). Fourteen-days incubation of 1 with Aspergillus alliaceus (NRRL 315) afforded the new compounds (S)-(+)-10beta-hydroxycurcudiol (9), (S)-(+)-curcudiol-10-one (10), and (S)-(+)-4-[1-(2-hydroxy-4-methyl)phenyl)]pentanoic acid (11). Rhizopus arrhizus (ATCC 11145) and Rhodotorula glutinus (ATCC 15125) afforded (S)-curcuphenol-1alpha-D-glucopyranoside (12) and (S)-curcudiol-1alpha-D-glucopyranoside (13) when incubated for 6 and 8 days with 1 and 2, respectively. The absolute configuration of C(10) and C(11) of metabolites 7-9 was established by optical rotation computations. Reaction of 1 with NaNO(2) and HCl afforded (S)-(+)-4-nitrocurcuphenol (14) and (S)-(+)-2-nitrocurcuphenol (15) in a 2:1 ratio. Acylation of 1 and 2 with isonicotinoyl chloride afforded the expected esters (S)-(+)-curcuphenol-1-O-isonicotinate (16) and (S)-(+)-curcudiol-1-O-isonicotinate (17), respectively. Curcuphenol (1) shows potent antimicrobial activity against Candida albicans, Cryptococcus neoformans, methicillin-resistant Staphylococcus aureus, and S. aureus with MIC and MFC/MBC ranges of 7.5-25 and 12.5-50 microg/mL, respectively. Compounds 1 and 3 also display in vitro antimalarial activity against Palsmodium falciparium (D6 clone) with MIC values of 3600 and 3800 ng/mL, respectively (selectivity index >1.3). Both compounds were also active against P. falciparium (W2 clone) with MIC values of 1800 (S.I. >2.6) and 2900 (S.I. >1.6) ng/mL, respectively. Compound 14 shows anti-hepatitis B virus activity with an EC(50) of 61 microg/mL.