Hinesoutzen8064

Phenylketonuria (PKU) is an autosomal recessive amino acid metabolism disorder caused by variants in the gene encoding phenylalanine hydroxylase (PAH; EC1.14.16.1). This study aimed to assess the specific heterogeneity of PAH variants found in Thai population as well as evaluate enzyme activity and expression of novel variants. PAH gene from 13 patients was analyzed by PCR amplification and direct Sanger-sequencing of 13 exons of the coding region. The novel variants were transiently transfected in COS-7 cells for functional verification. Eleven different PAH variants were identified all pathogenic variants were missense variants, of which the most frequent variant was p.R169L, accounting for 24% (6/25) of all identified alleles. Two novel variants p.R169L and p.Y317N and previously reported variants with mutated residues at the same positions (p.R169H and p.Y317H) were expressed in COS-7 cells. These showed mildly impaired residual activity levels (42.3-63.1% of wild type), while the protein levels were well expressed (82.8-110%), except for p.R169L, which showed decreased protein expression of 55.7% compared to the wild type enzyme. All subjects with p.R169L identified in at least one of pathogenic alleles (one case is homozygous) had a metabolic phenotype of mild hyperphenylalaninemia (HPA). Our data has expanded the information on the genetic heterogeneity of Thai patients with PAH deficiency. This finding emphasizes the importance of genotyping in patients with HPA, and in vitro studies can provide additional information for prediction of phenotype.The G-protein coupled estrogen receptor (GPER) mediates short-term non-genomic effects of estrogen in diverse cell types and tissues. According to the NCBI nucleotide database, three variants of GPER are known. They are NM_001505.2 (GPER-v2), NM_001039966.1 (GPER-v3), and NM_001098201.1 (GPER-v4). Investigations on GPER expression are key to understand its physiological and pathological roles. However, most studies on GPER mRNA expression have considered total GPER mRNA expression regardless of the individual variants. The present study is motivated by a novel transcript observed in the UCSC Genome Browser (uc010ksd.1), which is annotated as GPER. The novel variant is similar to the known transcript variants of GPER in terms of the protein-coding sequence and the 3'UTR. However, it has a unique 5'UTR, which distinguishes it from other GPER variants. Using primers specific for uc010ksd.1, we have performed RT-PCR to show that the novel GPER transcript (hereafter referred to as GPER-v5) is expressed in human cancer cell lines, such as MCF-7, SW-620, COLO-205, and HT-29. Preliminary evidences indicate that GPER-v5 is a novel GPER mRNA variant. The expression of GPER-v5 in primary cells and tissues should be investigated before probing into its role and relevance in physiological and pathological conditions.

Patients with type 2 diabetes (T2D) in Japan are prescribed a lower dose of metformin that their counterparts in Western countries due to concerns for the risk of lactic acidosis incidence. Here we report our study on the association between high-dose metformin administration and the incidence of lactic acidosis in Japanese patients with T2D.

A Japanese claims database (April 2008-November 2018) was analyzed. Factors associated with the incidence of lactic acidosis were first identified from the database records by conducting a case-control study, and these were then used as confounding factors in subsequent analyses. The association between high-dose metformin administration (≥ 1000mg/day) and the incidence of lactic acidosis was compared with that between low-dose metformin (< 1000mg/day) or no metformin administration and lactic acidosis incidence by using the following approaches a logistic regression analysis hypothesizing that metformin-associated lactic acidosis is short term; a time-dependent pciation between metformin administration and the incidence of lactic acidosis, but an increase in the incidence rate of lactic acidosis was not observed in those patients receiving high-dose metformin compared to those receiving low-dose metformin.

The results suggest an association between metformin administration and the incidence of lactic acidosis, but an increase in the incidence rate of lactic acidosis was not observed in those patients receiving high-dose metformin compared to those receiving low-dose metformin.This study aims to compare clinical characteristics and severity between adults with respiratory syncytial virus (RSV-p) and influenza-related pneumonia (Flu-p). A total of 127 patients with RSV-p, 693 patients with influenza A-related pneumonia (FluA-p), and 386 patients with influenza B-related pneumonia (FluB-p) were retrospectively reviewed from 2013 through 2019 in five teaching hospitals in China. A multivariate logistic regression model indicated that age ≥ 50 years, cerebrovascular disease, chronic kidney disease, solid malignant tumor, nasal congestion, myalgia, sputum production, respiratory rates ≥ 30 beats/min, lymphocytes less then 0.8×109/L, and blood albumin less then 35 g/L were predictors that differentiated RSV-p from Flu-p. After adjusting for confounders, a multivariate logistic regression analysis confirmed that, relative to RSV-p, FluA-p (OR 2.313, 95% CI 1.377-3.885, p = 0.002) incurred an increased risk for severe outcomes, including invasive ventilation, ICU admission, and 30-day mortality; FluB-p (OR 1.630, 95% CI 0.958-2.741, p = 0.071) was not associated with increased risk. selleck Some clinical variables were useful for discriminating RSV-p from Flu-p. The severity of RSV-p was less than that of FluA-p, but was comparable to FluB-p.

Comparative effectiveness of natalizumab and fingolimod over a follow-up longer than 2 years has been not addressed yet.

To compare the effect on no evidence of disease activity (NEDA-3) in relapsing-remitting multiple sclerosis (RRMS) patients treated with natalizumab or fingolimod for at least 4 years.

We included RRMS patients switched from first-line agents to natalizumab or fingolimod. Patients were propensity score (PS)-matched on a 1-to-1 basis. Percentages of patients reaching NEDA-3 status at 2 and 4 years of follow-up were compared using the chi-square test. The risk of not achieving NEDA-3 at 4 years was explored in matched samples by Cox regression models.

We evaluated 174 PS-matched patients. Patients receiving natalizumab reached a NEDA-3 status at 2 and 4 years more frequently than those exposed to fingolimod (63% vs 44%, p=0.037; 45.7% vs 25.8%, p=0.015, respectively). Patients receiving natalizumab were at a significant lower risk of not achieving the NEDA-3 status at 4 years compared to those exposed to fingolimod (hazard ratio (95% confidence interval) 0.