Anti-Helicobacter pylori activity and immunostimulatory effect of extracts from Byrsonima crassa Nied. (Malpighiaceae)

<p>Abstract</p> <p>Background</p> <p>Several <it>in vitro </it>studies have looked at the effect of medicinal plant extracts against <it>Helicobacter pylori </it>(<it>H. pylori</it>). Regardless of the popular use of <it>Byrsonima crassa </it>(<it>B. crassa</it>) as antiemetic, diuretic, febrifuge, to treat diarrhea, gastritis and ulcers, there is no data on its effects against <it>H. pylori</it>. In this study, we evaluated the anti-<it>H. pylori </it>of <it>B. crassa </it>leaves extracts and its effects on reactive oxygen/nitrogen intermediates induction by murine peritoneal macrophages.</p> <p>Methods</p> <p>The minimal inhibitory concentration (MIC) was determined by broth microdilution method and the production of hydrogen peroxide (H₂O₂) and nitric oxide (NO) by the horseradish peroxidase-dependent oxidation of phenol red and Griess reaction, respectively.</p> <p>Results</p> <p>The methanolic (MeOH) and chloroformic (CHCl₃) extracts inhibit, <it>in vitro</it>, the growth of <it>H. pylori </it>with MIC value of 1024 μg/ml. The MeOH extract induced the production H₂O₂and NO, but CHCl₃extract only NO.</p> <p>Conclusion</p> <p>Based in our results, <it>B. crassa </it>can be considered a source of compounds with anti-<it>H. pylori </it>activity, but its use should be done with caution in treatment of the gastritis and peptic ulcers, since the reactive oxygen/nitrogen intermediates are involved in the pathogenesis of gastric mucosal injury induced by ulcerogenic agents and <it>H. pylori </it>infections.</p

Brazilian network for HIV Drug Resistance Surveillance (HIV-BresNet): a survey of treatment-naive individuals

Introduction: In Brazil, more than 487,450 individuals are currently undergoing antiretroviral treatment. In order to monitor the transmission of drug-resistant strains and HIV subtype distribution in the country, this work aimed to estimate its prevalence and to characterize the nationwide pretreatment drug resistance in individuals recently diagnosed with HIV between 2013 and 2015. Methods: The HIV threshold survey methodology (HIV-THS, WHO) targeting antiretroviral-naive individuals with recent HIV diagnosis was utilized, and subjects were selected from 51 highly populated cities in all five Brazilian macroregions. The HIV pol genotypic test was performed by genomic sequencing. Results: We analysed samples from 1568 antiretroviral-naive individuals recently diagnosed with HIV, and the overall transmitted drug resistance (TDR) prevalence was 9.5% (150 sequences). The regional prevalence of resistance according to Brazilian geographical regions was 9.4% in the northeast, 11.2% in the southeast, 6.8% in the central region, 10.2% in the north and 8.8% in the south. The inhibitor-specific TDR prevalence was 3.6% for nucleoside reverse transcriptase inhibitors (NRTIs), 5.8% for non-nucleoside reverse transcriptase inhibitors (NNRTIs) and 1.6% for protease inhibitors (PIs)1.0% of individuals presented resistance to more than one class of inhibitors. Overall, subtype B was more prevalent in every region except for the southern, where subtype C prevails. Conclusions: To the best of our knowledge, this is the first TDR study conducted in Brazil with nationwide representative sampling. The TDR prevalence revealed a moderate rate in the five Brazilian geographical regions, although some cities presented higher TDR prevalence rates, reaching 14% in Sao Paulo, for example. These results further illustrate the importance of surveillance studies for designing future strategies in primary antiretroviral therapy, aiming to mitigate TDR, as well as for predicting future trends in other regions of the globe where mass antiretroviral (ARV) treatment was implemented.Brazilian Ministry of HealthUniv Fed Rio de Janeiro, Lab Virol Mol, Dept Genet IB, Rio De Janeiro, RJ, BrazilFdn Med Trop Amazonas, Manaus, Amazonas, BrazilLAPI Univ Fed Bahia, Hosp Univ Prof Edgar Santos, Lab Pesquisa, Salvador, BA, BrazilLab Cent Saude Publ Ceara Lacen CE, Fortaleza, Ceara, BrazilLab Cent Saude Publ Dist Fed, Setor Grandes Areas Norte SGAN 601, Brasilia, DF, BrazilUniv Fed Minas Gerais UFMG, Fac Med, Lab Imunol & Biol Mol DIP, Belo Horizonte, MG, BrazilLab Cent Saude Publ Mato Grosso Sul, Campo Grande, MS, BrazilLab Cent Saude Publ Pernambuco, Recife, PE, BrazilLab Municipal Curitiba, Curitiba, PR, BrazilFiocruz MS, Lab AIDS & Imunol Mol, Dept Imunol, Rio De Janeiro, RJ, BrazilUniv Fed Rio de Janeiro, Hosp Univ Clementino Fraga Filho, Lab Carga Viral, Rio de Janeiro, RJ, BrazilInst Biol Exercito, Rio De Janeiro, RJ, BrazilLab Cent Saude Publ Rio Grande Sul, Porto Alegre, RS, BrazilLab Hosp Nossa Senhora Conceicao, Porto Alegre, RS, BrazilLab Cent Saude Publ Santa Catarina, Florianopolis, SC, BrazilUNESP, Lab Biol Mol Hemocentro Botucatu, Fac Med, Botucatu, SP, BrazilUniv Estadual Campinas, Lab Pesquisa AIDS, Hosp Clin, Campinas, SP, BrazilInst Adolfo Lutz Sao Jose do Rio Preto, Lab Biol Mol, Sao Jose Do Rio Preto, SP, BrazilUniv Fed Sao Paulo UNIFESP, Escola Paulista Med, Lab Retrovirol, Sao Paulo, SP, BrazilInst Adolfo Lutz Cent, Lab Retrovirus, Ctr Virol, Nucleo Doencas Sanguineas & Sexuais, Sao Paulo, SP, BrazilMinist Saude, Dept Vigilancia Prevencao & Controle DST AIDS & H, Setor Adm Fed Sul SAFS 02, Secretaria Vigilancia Saude, Brasilia, DF, BrazilUniv Brasilia, Programa Pos Grad Saude Colet, Fac Med, Fac Ciencias Saude, Brasilia, DF, BrazilUniv Sao Paulo, Fac Med, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP, Escola Paulista Med, Lab Retrovirol, Sao Paulo, SP, BrazilBMH: TC 298/12Web of Scienc

A Missense Mutation in PPP1R15B Causes a Syndrome Including Diabetes, Short Stature, and Microcephaly.

Dysregulated endoplasmic reticulum stress and phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) are associated with pancreatic β-cell failure and diabetes. Here, we report the first homozygous mutation in the PPP1R15B gene (also known as constitutive repressor of eIF2α phosphorylation [CReP]) encoding the regulatory subunit of an eIF2α-specific phosphatase in two siblings affected by a novel syndrome of diabetes of youth with short stature, intellectual disability, and microcephaly. The R658C mutation in PPP1R15B affects a conserved amino acid within the domain important for protein phosphatase 1 (PP1) binding. The R658C mutation decreases PP1 binding and eIF2α dephosphorylation and results in β-cell apoptosis. Our findings support the concept that dysregulated eIF2α phosphorylation, whether decreased by mutation of the kinase (EIF2AK3) in Wolcott-Rallison syndrome or increased by mutation of the phosphatase (PPP1R15B), is deleterious to β-cells and other secretory tissues, resulting in diabetes associated with multisystem abnormalities.This work was supported by the European Union 7th Framework Programme (project BetaBat), the Actions de Recherche Concertées de la Communauté Française, and Fonds National de la Recherche Scientifique (FNRS), Belgium, and by grants from the Agence Nationale pour la Recherche (ANR-09-GENO-021), the European Foundation for the Study of Diabetes/JDRF/Novo Nordisk, the Assistance Publique-Hôpitaux de Paris Programme Hospitalier de Recherche Clinique (DIAGENE), the GIS Maladies Rares, and the Wellcome Trust (084812/Z/08/Z). A.T.H. is a Wellcome Trust and National Institute for Health Research senior investigator, and D.R. is a Wellcome Trust Principal Research Fellow. B.A. was supported by an European Molecular Biology Organization Short-Term Fellowship and an FNRS-FRIA fellowship. M.I.-E. is a scientific collaborator of the FNRS. M.D. was supported by a doctoral fellowship from the Ministère de l’Education Nationale, de l’Enseignement Supérieur et de la Recherche, France.This is the author accepted manuscript. The final version is available from the American Diabetes Association via http://dx.doi.org/10.2337/db15-047

Measurement of the Tau Lepton Polarisation at LEP2

A first measurement of the average polarisation P_tau of tau leptons produced in e+e- annihilation at energies significantly above the Z resonance is presented. The polarisation is determined from the kinematic spectra of tau hadronic decays. The measured value P_tau = -0.164 +/- 0.125 is consistent with the Standard Model prediction for the mean LEP energy of 197 GeV.A first measurement of the average polarisation Pτ of tau leptons produced in e + e − annihilation at energies significantly above the Z resonance is presented. The polarisation is determined from the kinematic spectra of tau hadronic decays. The measured value Pτ=−0.164±0.125 is consistent with the Standard Model prediction for the mean LEP energy of 197 GeV.A first measurement of the average polarisation P_tau of tau leptons produced in e+e- annihilation at energies significantly above the Z resonance is presented. The polarisation is determined from the kinematic spectra of tau hadronic decays. The measured value P_tau = -0.164 +/- 0.125 is consistent with the Standard Model prediction for the mean LEP energy of 197 GeV

Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel

Imputing genotypes from reference panels created by whole-genome sequencing (WGS) provides a cost-effective strategy for augmenting the single-nucleotide polymorphism (SNP) content of genome-wide arrays. The UK10K Cohorts project has generated a data set of 3,781 whole genomes sequenced at low depth (average 7x), aiming to exhaustively characterize genetic variation down to 0.1% minor allele frequency in the British population. Here we demonstrate the value of this resource for improving imputation accuracy at rare and low-frequency variants in both a UK and an Italian population. We show that large increases in imputation accuracy can be achieved by re-phasing WGS reference panels after initial genotype calling. We also present a method for combining WGS panels to improve variant coverage and downstream imputation accuracy, which we illustrate by integrating 7,562 WGS haplotypes from the UK10K project with 2,184 haplotypes from the 1000 Genomes Project. Finally, we introduce a novel approximation that maintains speed without sacrificing imputation accuracy for rare variants

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Determination of quantum numbers for several excited charmed mesons observed in B- -> D*(+)pi(-) pi(-) decays

A four-body amplitude analysis of the B − → D * + π − π − decay is performed, where fractions and relative phases of the various resonances contributing to the decay are measured. Several quasi-model-independent analyses are performed aimed at searching for the presence of new states and establishing the quantum numbers of previously observed charmed meson resonances. In particular the resonance parameters and quantum numbers are determined for the D 1 ( 2420 ) , D 1 ( 2430 ) , D 0 ( 2550 ) , D ∗ 1 ( 2600 ) , D 2 ( 2740 ) and D ∗ 3 ( 2750 ) states. The mixing between the D 1 ( 2420 ) and D 1 ( 2430 ) resonances is studied and the mixing parameters are measured. The dataset corresponds to an integrated luminosity of 4.7     fb − 1 , collected in proton-proton collisions at center-of-mass energies of 7, 8 and 13 TeV with the LHCb detector