Photocatalytic activity of TiO2 particulate films prepared by depositing TiO2 particles with various sizes

TiO2 particles of various sizes were prepared by grinding in cyclohexanone, and TiO2 particulate films were obtained by depositing these TiO2 particles with various sizes onto a glass or quartz substrate. The effect of the particle size and thickness on the photocatalytic properties of the films was evaluated via oxidative degradation of gaseous 2-propanol. The initial rate of 2-propanol degradation under UV light irradiation for the films deposited with 30 nm TiO2 particles increased with increasing film thickness up to 600 nm, and reached a saturated value above this film thickness. Photocatalytic activity for the films with thickness below 600nm was larger when smaller TiO2 particles were deposited onto the substrate, due to the increase in the surface area of the particulate films. Furthermore, saturated values of the photocatalytic activity for thick films were smaller for the films deposited with smaller particles, which is mainly attributed to the change in crystal form of the particles during the grinding treatment.     

Polygenic Risk Score of Adolescent Idiopathic Scoliosis for Potential Clinical Use

Adolescent idiopathic scoliosis (AIS) is a common disease causing three-dimensional spinal deformity in as many as 3% of adolescents. Development of a method that can accurately predict the onset and progression of AIS is an immediate need for clinical practice. Because the heritability of AIS is estimated as high as 87.5% in twin studies, prediction of its onset and progression based on genetic data is a promising option. We show the usefulness of polygenic risk score (PRS) for the prediction of onset and progression of AIS. We used AIS genomewide association study (GWAS) data comprising 79,211 subjects in three cohorts and constructed a PRS based on association statistics in a discovery set including 31,999 female subjects. After calibration using a validation data set, we applied the PRS to a test data set. By integrating functional annotations showing heritability enrichment in the selection of variants, the PRS demonstrated an association with AIS susceptibility (p = 3.5 × 10⁻⁴⁰ with area under the receiver-operating characteristic [AUROC] = 0.674, sensitivity = 0.644, and specificity = 0.622). The decile with the highest PRS showed an odds ratio of as high as 3.36 (p = 1.4 × 10⁻¹⁰) to develop AIS compared with the fifth in decile. The addition of a predictive model with only a single clinical parameter (body mass index) improved predictive ability for development of AIS (AUROC = 0.722, net reclassification improvement [NRI] 0.505 ± 0.054, p = 1.6 × 10⁻⁸), potentiating clinical use of the prediction model. Furthermore, we found the Cobb angle (CA), the severity measurement of AIS, to be a polygenic trait that showed a significant genetic correlation with AIS susceptibility (rg = 0.6, p = 3.0 × 10⁻⁴). The AIS PRS demonstrated a significant association with CA. These results indicate a shared polygenic architecture between onset and progression of AIS and the potential usefulness of PRS in clinical settings as a predictor to promote early intervention of AIS and avoid invasive surgery. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Clinical features and impact of p53 status on sporadic mismatch repair deficiency and Lynch syndrome in uterine cancer

The clinical features of sporadic mismatch repair deficiency (MMRd) and Lynch syndrome (LS) in Japanese patients with endometrial cancer (EC) were examined by evaluating the prevalence and prognostic factors of LS and sporadic MMRd in patients with EC. Targeted sequencing of five LS susceptibility genes (MLH1, MSH2, MSH6, PMS2, and EPCAM) was carried out in 443 patients with EC who were pathologically diagnosed with EC at the National Cancer Center Hospital between 2011 and 2018. Pathogenic variants in these genes were detected in 16 patients (3.7%). Immunohistochemistry for MMR proteins was undertaken in 337 of the 433 (77.9%) EC patients, and 91 patients (27.0%) showed absent expression of at least one MMR protein. The 13 cases of LS with MMR protein loss (93.8%) showed a favorable prognosis with a 5-year overall survival (OS) rate of 100%, although there was no statistically significant difference between this group and the sporadic MMRd group (p = 0.27). In the MMRd without LS group, the 5-year OS rate was significantly worse in seven patients with an aberrant p53 expression pattern than in those with p53 WT (53.6% vs. 93.9%, log-rank test; p = 0.0016). These results suggest that p53 abnormalities and pathogenic germline variants in MMR genes could be potential biomarkers for the molecular classification of EC with MMRd.     

A Phase II study of polyclonal anti-TNF-α (AZD9773) in Japanese patients with severe sepsis and/or septic shock

Because tumor necrosis factor-alpha (TNF-α) induces many of the pathophysiological signs and symptoms observed in sepsis, it is a potential therapeutic target for treatment. The primary objective of this study was to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple intravenous (i.v.) infusions of two doses of AZD9773 in Japanese patients with severe sepsis and/or septic shock. In this Phase II, double-blind, placebo-controlled, dose-escalation study (ClinicalTrials.gov Identifier: NCT01144624), Japanese patients were randomized to two successive treatment cohorts (cohort 1, loading/maintenance doses of 250/50 U/kg or placebo; cohort 2, loading/maintenance doses of 500/100 U/kg or placebo) for a 5-day treatment period, then a follow-up period to day 29. Twenty patients were enrolled (AZD9773 cohort 1, n = 7; AZD9773 cohort 2, n = 7; placebo, n = 6), and all completed the study. Most treatment-emergent adverse events (TEAEs) were mild or moderate and none led to discontinuation. The most common TEAEs in the AZD9773 cohorts were pleural effusion (64.3 %) and peripheral edema (28.6 %). Pharmacokinetic data demonstrated an approximately proportional increase in concentration with increasing dose. Treatment with AZD9773 led to a decrease in TNF-α concentrations, which was more discernible in the AZD9773 cohort 2; TNF-α concentrations generally decreased with time in patients receiving placebo. A similar pattern of response was observed with interleukin-6 (IL-6) and IL-8. AZD9773 was generally well tolerated with dose-proportional pharmacokinetics in Japanese patients with severe sepsis/septic shock.     

Association between germline pathogenic variants in cancer‐predisposing genes and lymphoma risk

The application of advanced molecular technology has significantly expanded lymphoma classification, allowing risk stratification and treatment optimization. Limited evidence suggests the presence of a genetic predisposition in lymphoma, indicating the potential for better individualized clinical management based on a novel lymphoma classification. Herein, we examined the impact of germline pathogenic variants in 27 cancer‐predisposing genes with lymphoma risk and explored the clinical characteristics of pathogenic variant carriers. This study included 2,066 lymphoma patients and 38,153 cancer‐free controls from the Japanese population. Following quality control of sequencing data, samples from 1,982 lymphoma patients and 37,592 controls were further analyzed. We identified 309 pathogenic variants among 4,850 variants in the 27 cancer‐predisposing genes. Pathogenic variants in the following four cancer‐predisposing genes were associated with a high risk of lymphoma: ATM (odds ratio [OR], 2.63; 95% confidence interval [CI], 1.25–5.51; p = 1.06 × 10⁻²), BRCA1 (OR, 5.88; 95% CI, 2.65–13.02; p = 1.27 × 10⁻⁵), BRCA2 (OR, 2.94; 95% CI, 1.60–5.42; p = 5.25 × 10⁻⁴), and TP53 (OR, 5.22; 95% CI, 1.43–19.02; p = 1.23 × 10⁻²). The proportion of carriers of these genes was 1.6% of lymphoma patients. Furthermore, pathogenic variants in these genes were especially associated with a higher risk of mantle cell lymphoma (OR, 21.57; 95% CI, 7.59–61.26; p = 8.07 × 10⁻⁹). These results provide novel insights concerning monogenic form into lymphoma classification. Some lymphoma patients may benefit from surveillance and targeted treatment, such as other neoplasms.     

Changes in the heart rate and plasma epinephrine and norepinephrine concentrations of the stallion during copulation

Aim  The physiological indexes of the copulatory behavior of the stallion have not been investigated in detail and may differ from those of other species, such as humans and rats. Methods  In order to understand the breeding capability of various stallions, their behavior during copulation was observed, and heart rate (HR) and the plasma concentrations of norepinephrine (NA) and epinephrine (Ad) were measured sequentially for a total of 13 copulations carried out during 2 days. Results  The mean HR at rest was 35.3 ±0.9 beats per minute (b.p.m.) and it peaked during mounting (162.1 ±5.4 b.p.m.). The HR at ejaculation was 145.7 ±5.1 b.p.m, which was less than the peak. The plasma concentrations of NA and Ad showed similar changes to the HR; immediately after ejaculation they were, respectively, 4.7-fold and 1.9-fold higher than the resting values and there was a difference in the degree of increase of each catecholamine. Conclusions  The present results show that in the stallion the HR peaks at mounting and there is a greater change in the activity of the sympathetic nervous system because of the shortterm, highly intense exercise performed during copulation. It is considered that this, combined with the particular mental stress placed on the stallion during copulation, has the potential to cause sudden cardiac death.     

Early detection of cone photoreceptor cell loss in retinitis pigmentosa using adaptive optics scanning laser ophthalmoscopy

Graefe's Archive for Clinical and Experimental Ophthalmology - The purpose of the study was to investigate the characteristics of the parafoveal cone density changes in patients with retinitis...     

Genetic polymorphism of pleiotrophin is associated with pain experience in Japanese adults: Case-control study

Genetic factors play a role in individual differences in pain experience. Here, we performed a genome-wide association study (GWAS) to identify novel loci regulating pain processing. We conducted a 2-stage GWAS and the candidate single-nucleotide polymorphisms (SNPs) association study on pain experience using an exploratory cohort of patients with cancer pain. The confirmatory cohort comprised of participants from the general population with and without habitual use of analgesic medication. In the exploratory cohort, we evaluated pain intensity using a numerical rating scale, recorded daily opioid dosages, and calculated pain reduction rate. In the confirmatory cohort, pain experience was defined as habitual nonsteroidal anti-inflammatory drug usage. Using linear regression models, we identified candidate SNP in the exploratory samples, and tested the association between phenotype and experienced pain in the confirmatory samples. We found 1 novel SNP (rs11764598)—located on the gene encoding for pleiotrophin on chromosome 7—that passed the genome-wide suggestive significance at 20% false discovery rate (FDR) correction in the exploratory samples of patients with cancer pain (P = 1.31 × 10^-7, FDR = 0.101). We confirmed its significant association with daily analgesic usage in the confirmatory cohort (P = .028), although the minor allele affected pain experience in an opposite manner. We identified a novel genetic variant associated with pain experience. Further studies are required to validate the role of pleiotrophin in pain processing.     

Diabetes and cancer risk: A Mendelian randomization study

Earlier cohort studies using conventional regression models have consistently shown an increased cancer risk among individuals with type 2 diabetes. However, reverse causality and residual confounding due to common risk factors could exist, and it remains unclear whether diabetes per se contributes to cancer development. Mendelian randomization analyses might clarify the true association between diabetes and cancer risk. We conducted a case–cohort study with 10,536 subcohort subjects and 3,541 newly diagnosed cancer cases derived from 32,949 eligible participants aged 40–69 years within the Japan Public Health Center-based Prospective Study. With 29 known type 2 diabetes susceptibility variants, we used an inverse variance-weighted method to estimate hazard ratios for the associations of diabetes with risks of total and site-specific cancers. The hazard ratios of cancer per doubling of the probability of diabetes were 1.03 (95% confidence interval [CI], 0.92–1.15) overall, 1.08 (95% CI: 0.73–1.59) for the pancreas, 0.80 (95% CI: 0.57–1.14) for the liver and 0.90 (95% CI: 0.74–1.10) for the colorectum. Additional analyses, using publicly available large-scale genome-wide association study data on colorectal cancer in Japan, resulted in a narrower CI (hazard ratio: 1.00; 95% CI: 0.93–1.07). In this prospective Mendelian randomization study with a large number of incident cancer cases, we found no strong evidence to support associations between diabetes and overall and site-specific cancer risks. Our findings suggest that there is little evidence to support the genetic role of type 2 diabetes in cancer development in the Japanese population.