Public subsidies and the recommendation of child vaccines among primary care physicians : a nationwide cross-sectional study in Japan.

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ケツエキ トウセキ カンジャ ノ チョウキ セイメイ ヨゴ ヨソク インシ トシテノ トウセキゴ ノ ケッショウANP ト BNPノウド ノ ユウヨウセイ : 15ネンカン ノ ヨゴ チョウサ

透析患者52人において心胸比を透析前に,収縮期血圧,血清アルブミン,血漿心房性ナトリウム利尿ペプチド(atrial natriuretic peptide ; ANP),脳性ナトリウム利尿ペプチド(brain natriuretic peptide ; BNP),血漿レニン活性(plasma renin activity ; PRA),血漿ノルアドレナリン(plasma noradrenaline ; PNA)濃度を透析直後に測定した.患者は上記測定の中央値で高低2群に分けてKaplan-Meier (KM)生存曲線を求め,両群の比較をLogrank法で行った.生存期間に及ぼす因子解析は測定値を説明変数,生存期間を目的変数としてCox比例hazard法で行った.いずれもp<0.05を有意と判定した. 15年間で43人が死亡し,うち40人が病死であった. KM生存曲線は高年齢群(p<0.001),高ANP群(p=0.006),高BNP群(p=0.039)で有意に生存期間が短く,心胸比,収縮期血圧,血清アルブミン, PRA, PNAにおいては高低2群間に有意差を認めなかった. Cox比例hazard法による単変量解析では年齢(p<0.001),心胸比(p=0.011), ANP (p=0.003), BNP (p=0.002)が生命予後の有意なリスク因子となり,多変量解析ではp値は年齢<0.001,心胸比0.965, ANP 0.055, BNP 0.041となり,年齢とBNPが生命予後の独立したリスク因子であった.以上より透析患者において透析直後の血漿BNP濃度は長期生命予後の独立したリスク因子であり,血漿ANP濃度もリスク因子としてBNPに次いで重要であることが示された.This study was designed to clarify the clinical significance of post-dialysis plasma vasoactive substances including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), plasma renin activity (PRA) and noradrenaline (PNA) as a survival predictor in chronic hemo-dialysis (HD) patients. Immediately after HD, blood samples were collected for the measurements of serum albumin, ANP, BNP, PRA and PNA in 52 HD patients. During 15-year follow-up period 43 patients died ; 40 of diseases, 2 accident, 1 suicide. Patients were divided into two groups using the median of their age and clinical and laboratory variables. Kaplan-Meier survival analysis revealed that the groups of older age, higher plasma ANP and BNP concentration had significantly lower survival rates as compared with each counterpart (p<0.001, p=0.006, p=0.039, respectively). Univariate and multivariate Cox proportional hazard regression analyses were used to assess the potential association of their age, and clinical and laboratory variables with a survival rate. As a result of Univariate Cox hazard analysis, age, cardiothoracic ratio (CTR), and plasma ANP, and BNP concentrations had significant relationship with overall mortality (p<0.001, p=0.011, p=0.003, and p=0.002, respectively). However, stepwise multivariate analysis revealed that the significant relationship with overall mortality was shown for their age (p<0.001) and BNP (p=0.041). These results demonstrated that the post-dialysis plasma BNP concentration was an independent risk factor for long-term survival and the post-dialysis plasma ANP concentration was also an important risk factor next to the BNP concentration

Genetic polymorphisms in malaria vaccine candidate Plasmodium falciparum reticulocyte-binding protein homologue-5 among populations in Lagos, Nigeria

Abstract Background Vaccines are the most reliable alternative to elicit sterile immunity against malaria but their development has been hindered by polymorphisms and strain-specificity in previously studied antigens. New vaccine candidates are therefore urgently needed. Highly conserved Plasmodium falciparum reticulocyte-binding protein homologue-5 (PfRH5) has been identified as a potential candidate for anti-disease vaccine development. PfRH5 is essential for erythrocyte invasion by merozoites and crucial for parasite survival. However, there is paucity of data on the extent of genetic variations on PfRH5 in field isolates of Plasmodium falciparum. This study described genetic polymorphisms at the high affinity binding polypeptides (HABPs) 36718, 36727, 36728 of PfRH5 in Nigerian isolates of P. falciparum. This study tested the hypothesis that only specific conserved B and T cell epitopes on PfRH5 HABPs are crucial for vaccine development. Methods One hundred and ninety-five microscopically confirmed P. falciparum samples collected in a prospective cross-sectional study of three different populations in Lagos, Nigeria. Genetic diversity and haplotype construct of Pfrh5 gene were determined using bi-directional sequencing approach. Tajima’s D and the ratio of nonsynonymous vs synonymous mutations were utilized to estimate the extent of balancing and directional selection in the pfrh5 gene. Results Sequence analysis revealed three haplotypes of PfRH5 with negative Tajima’s D and dN/dS value of − 1.717 and 0.011 ± 0.020, respectively. A single nucleotide polymorphism, SNP (G → A) at position 608 was observed, which resulted in a change of the amino acid cysteine at position 203 to tyrosine. Haplotype and nucleotide diversities were 0.318 ± 0.016 and 0.0046 ± 0.0001 while inter-population genetic differentiation ranged from 0.007 to 0.037. Five polypeptide variants were identified, the most frequent being KTKYH with a frequency of 51.3%. One B-cell epitope, 151 major histocompatibility complex (MHC) class II T-cell epitopes, four intrinsically unstructured regions (IURs) and six MHC class I T-cell epitopes were observed in the study. Phylogenetic analysis of the sequences showed clustering and evidence of evolutionary relationship with 3D7, PAS-2 and FCB-2 RH5 sequences. Conclusions This study has revealed low level of genetic polymorphisms in PfRH5 antigen with B- and T-cell epitopes in intrinsically unstructured regions along the PfRH5 gene in Lagos, Nigeria. A broader investigation is however required in other parts of the country to support the possible inclusion of PfRH5 in a cross-protective multi-component vaccine

Additional file 7 of Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Additional file 7: Table S5. Lookup of all prioritized lipid genes in the Therapeutic Target Database 2022

Additional file 2 of Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Additional file 2: Table S2. Association results for the multi-ancestry index SNPs with the gene prioritization

Additional file 4 of Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Additional file 4: Table S3. Text mining results for the PoPS+ prioritized genes