Predictive Factors for Tracheal Intubation in Patients with Coronavirus Disease 2019 Treated Using a High-flow Nasal Cannula

Background : In Japan, patients with coronavirus disease 2019 (COVID-19)＊ requiring a high-flow nasal cannula (HFNC) are often initially treated in non-specialized facilities and transferred to an intensive care unit if tracheal intubation is required. We aimed to investigate the factors associated with severe respiratory failure requiring tracheal intubation at an early stage in patients with COVID-19 treated using HFNCs. Methods : This retrospective cohort study compared the clinical features of consecutively enrolled patients with polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus-2 infection admitted to two centers in Japan between early February 2020 and late June 2021. Results : A total of 35 patients with COVID-19 treated using HFNCs were included. Treatment success and failure occurred in 25 and 10 patients, respectively. The oxygen saturation (ROX) index (ratio of oxygen saturation [SpO2] to fraction of inspired oxygen [FiO2] and the respiratory rate) 12 h post-HFNC insertion was a useful predictor of HFNC failure (success group, 8.0 ; failure group, 6.5 : P＝0.0005). Moreover, the time from symptom onset to respiratory failure was significantly shorter in the failure group than in the success group (3.0 and 5.0 days, P＝0.004). Conclusions The ROX index and time from symptom onset to respiratory failure were useful predictors of HFNC failure.Article信州医学雑誌 71(6) : 403-409, (2023)journal articl

Analysis of SNPs and Haplotypes in Vitamin D Pathway Genes and Renal Cancer Risk

In the kidney vitamin D is converted to its active form. Since vitamin D exerts its activity through binding to the nuclear vitamin D receptor (VDR), most genetic studies have primarily focused on variation within this gene. Therefore, analysis of genetic variation in VDR and other vitamin D pathway genes may provide insight into the role of vitamin D in renal cell carcinoma (RCC) etiology. RCC cases (N = 777) and controls (N = 1,035) were genotyped to investigate the relationship between RCC risk and variation in eight target genes. Minimum-p-value permutation (Min-P) tests were used to identify genes associated with risk. A three single nucleotide polymorphism (SNP) sliding window was used to identify chromosomal regions with a False Discovery Rate of <10%, where subsequently, haplotype relative risks were computed in Haplostats. Min-P values showed that VDR (p-value = 0.02) and retinoid-X-receptor-alpha (RXRA) (p-value = 0.10) were associated with RCC risk. Within VDR, three haplotypes across two chromosomal regions of interest were identified. The first region, located within intron 2, contained two haplotypes that increased RCC risk by approximately 25%. The second region included a haplotype (rs2239179, rs12717991) across intron 4 that increased risk among participants with the TC (OR = 1.31, 95% CI = 1.09–1.57) haplotype compared to participants with the common haplotype, TT. Across RXRA, one haplotype located 3′ of the coding sequence (rs748964, rs3118523), increased RCC risk 35% among individuals with the variant haplotype compared to those with the most common haplotype. This study comprehensively evaluated genetic variation across eight vitamin D pathway genes in relation to RCC risk. We found increased risk associated with VDR and RXRA. Replication studies are warranted to confirm these findings

A sweet taste receptor-dependent mechanism of glucosensing in hypothalamic tanycytes

Hypothalamic tanycytes are glial-like glucosensitive cells that contact the cerebrospinal fluid of the third ventricle, and send processes into the hypothalamic nuclei that control food intake and body weight. The mechanism of tanycyte glucosensing remains undetermined. While tanycytes express the components associated with the glucosensing of the pancreatic β cell, they respond to nonmetabolisable glucose analogues via an ATP receptor-dependent mechanism. Here, we show that tanycytes in rodents respond to non-nutritive sweeteners known to be ligands of the sweet taste (Tas1r2/Tas1r3) receptor. The initial sweet tastant-evoked response, which requires the presence of extracellular Ca2+, leads to release of ATP and a larger propagating Ca2+ response mediated by P2Y1 receptors. In Tas1r2 null mice the proportion of glucose nonresponsive tanycytes was greatly increased in these mice, but a subset of tanycytes retained an undiminished sensitivity to glucose. Our data demonstrate that the sweet taste receptor mediates glucosensing in about 60% of glucosensitive tanycytes while the remaining 40% of glucosensitive tanycytes use some other, as yet unknown mechanism

Pycnogenol® Induces Browning of White Adipose Tissue through the PKA Signaling Pathway in Apolipoprotein E-Deficient Mice

Beige adipocytes in white adipose tissue (WAT) have received considerable recognition because of their potential protective effect against obesity. Pycnogenol (PYC), extracted from French maritime pine bark, has anti-inflammatory and antioxidant properties and can improve lipid profiles. However, the effect of PYC on obesity has never been explored. In this study, we investigated the effects of PYC on obesity and WAT browning in apolipoprotein E- (ApoE-) deficient mice. The results showed that PYC treatment clearly reversed body weight and the mass of eWAT gain resulting from a high-cholesterol and high-fat diet (HCD), but no difference in food intake. The morphology results showed that the size of the adipocytes in the PYC-treated mice was obviously smaller than that in the HCD-fed mice. Next, we found that PYC upregulated the expression of genes related to lipolysis (ATGL and HSL), while it decreased the mRNA level of PLIN1. PYC significantly increased the expression of UCP1 and other genes related to beige adipogenesis. Additionally, PYC increased the expression of proteins related to the protein kinase A (PKA) signaling pathway. The findings suggested that PYC decreased obesity by promoting lipolysis and WAT browning. Thus, PYC may be a novel therapeutic target for obesity