Genetic Polymorphism in Alcohol Metabolism and Drinking Behavior are Associated with Gastric Cancer Risk in Men.

Objective In recent years, there has been a growing focus on health risks associated with alcohol consumption. The present study investigated whether or not the genetic variant of aldehyde dehydrogenase 2 (ALDH2) influences the risk of gastric cancer among individuals identified as hazardous drinkers using the Alcohol Use Disorders Identification Test (AUDIT), which provides a comprehensive assessment of hazardous drinking behavior. Patients We enrolled men with hazardous drinking behavior (AUDIT score ≥ 8) who had undergone gastric cancer screening (either endoscopy or a barium X-ray examination of the upper gastrointestinal tract) between April 2013 and March 2020 within 1 year from entry and who had subsequently undergone at least one more gastric cancer screening up to March 2021. Functional single-nucleotide polymorphisms of ALDH2 (rs671) were measured using a direct TaqMan PCR method with unprocessed saliva. Results A total of 246 men were enrolled, comprising 193 individuals with active ALDH2 (ALDH2*1/*1) and 53 with less-active ALDH2 (ALDH2*1/*2). The cumulative incidence of gastric cancer in the less-active group was higher than in the active ALDH2 group (p=0.01, hazard ratio: 4.6, 95% confidence interval: 1.2-16.7). Alcohol consumption was lower in the less-active ALDH2 group than in the active ALDH2 group, although no marked difference was observed in the AUDIT score. Conclusion In individuals with hazardous drinking behavior, a heightened risk of gastric cancer was observed among those with less-active ALDH2 variants, even when their alcohol consumption was comparatively lower than in those with active ALDH2 variants.

Isolation of azole-resistant Aspergillus spp. from food products.

The prevalence of azole-resistant Aspergillus fumigatus is increasing worldwide and is speculated to be related to the use of azole pesticides. Aspergillus spp., the causative agent of aspergillosis, could be brought into domestic dwellings through food. However, studies on azole-resistant Aspergillus spp. in food products are limited. Therefore, we aimed to isolate Aspergillus spp. from processed foods and commercial agricultural products and performed drug susceptibility tests for azoles. Among 692 food samples, we isolated 99 strains of Aspergillus spp. from 50 food samples, including vegetables (22.9%), citrus fruits (26.3%), cereals (25.5%), and processed foods (1.8%). The isolates belonged to 18 species across eight sections: Aspergillus, Candidi, Clavati, Flavi, Fumigati, Nidulantes, Nigri, and Terrei. The most frequently isolated section was Fumigati with 39 strains, followed by Nigri with 28 strains. Aspergillus fumigatus and A. welwitschiae were the predominant species. Ten A. fumigatus and four cryptic strains, four A. niger cryptic strains, two A. flavus, and four A. terreus strains exceeded epidemiological cutoff values for azoles. Aspergillus tubingensis, A. pseudoviridinutans, A. lentulus, A. terreus, and N. hiratsukae showed low susceptibility to multi-azoles. Foods containing agricultural products were found to be contaminated with Aspergillus spp., with 65.3% of isolates having minimal inhibitory concentrations below epidemiological cutoff values. Additionally, some samples harbored azole-resistant strains of Aspergillus spp. Our study serves as a basis for elucidating the relationship between food, environment, and clinically important Aspergillus spp.

[A case of acute bilateral blindness presumably caused by reversible cerebral vasoconstriction syndrome after traumatic brain injury].

A 62-year-old man was admitted to our hospital for acute bilateral blindness two days after a head injury. Hemorrhagic cerebellar infarction was found on the initial MRI, and peripheral arteries were poorly visualized on MRA. On the follow-up MRA nine days later, peripheral arteries were clearly depicted. These imaging findings suggested reversible cerebral vasoconstriction syndrome (RCVS). We started steroid pulse therapy for suspected optic neuritis with no clear response. The initial fundoscopic examination revealed no abnormalities in the optic disc, but optic nerve atrophy developed one month later. Based on the course of events, we diagnosed the patient with posterior ischemic optic neuropathy triggered by RCVS.

Seven Epithemia taxa (Bacillariophyta) from Lake Akan (Japan) and their salinity tolerances.

The ecologies (salinity tolerance) of many diatoms are largely unknown, despite their potential to contribute to more detailed paleoenvironmental reconstructions. This study therefore aimed to investigate the relationship between diatom species and salinity. We cultured seven cosmopolitan benthic diatom species obtained from Lake Akan, a freshwater inland lake in Japan: Epithemiaadnata, E.frickei, E.gibba, E.operculata, E.sorex, E. sp. and E.turgida. Each species was cultured at eleven salinities between 0‰ and 50‰. Epithemiaadnata, E.frickei and E.sorex had the highest growth rate at a salinity of 3‰, with no further increase observed above 25‰. However, E.gibba had the highest growth rate at a salinity of 5‰, with no increase at salinities ≥ 30‰. These results suggest that E.adnata, E.frickei, E.gibba, and E.sorex grow in freshwater to brackish-water environments. Epithemiaoperculata and E. sp. proliferated at all salinities, indicating that they can adapt to hypersaline environments. However, E.turgida did not survive in salinities >10‰, making it the species with the narrowest salinity tolerance range. These results provide new knowledge that improves the understanding of the ecology of these species in modern environments and offer insights into paleoenvironmental reconstructions through diatom analysis.

Utility of nerve ultrasound in the management of primary neurolymphomatosis: Case report and review of the literature.

Introduction: Primary neurolymphomatosis (NL) is a critical differential diagnosis of asymmetric multiple mononeuropathy and radiculoplexopathy. Its diagnosis is often challenging due to the lack of typical clinical signs of systemic lymphoma. We report a case of primary NL where nerve ultrasound (NUS) played an important role in the diagnosis and follow-up of the disease. Case presentation: A 52-year-old man developed asymmetric painful multiple mononeuropathy in the right upper limb with cranial nerve involvement. After being referred to our department, the patient underwent NUS, which revealed marked enlargement and increased vascularity in the right upper limb nerves, brachial plexus, and cervical nerve roots. Furthermore, an epineural hypoechoic mass, a characteristic finding of NL, was seen in the right median nerve. These NUS findings prompted us to perform 18F-fluorodeoxyglucose positron emission tomography/computed tomography and a subsequent biopsy on the right axillary lymph node, confirming NL. Notably, the NUS abnormalities dramatically subsided, demonstrating the effectiveness of chemotherapy. Discussion: The diagnostic utility of NUS for NL has been documented by many recent reports. Additionally, NUS can work as a quick follow-up tool for NL, as seen in our case.

Transmission of COVID-19 in Nightlife, Household, and Health Care Settings in Tokyo, Japan, in 2020.

Importance: There have been few studies on the heterogeneous interconnection of COVID-19 outbreaks occurring in different social settings using robust, surveillance epidemiological data. Objectives: To describe the characteristics of COVID-19 transmission within different social settings and to evaluate settings associated with onward transmission to other settings. Design, Setting, and Participants: This is a case series study of laboratory-confirmed COVID-19 cases in Tokyo between January 23 and December 5, 2020, when vaccination was not yet implemented. Using epidemiological investigation data collected by public health centers, epidemiological links were identified and classified into 7 transmission settings: imported, nightlife, dining, workplace, household, health care, and other. Main Outcomes and Measures: The number of cases per setting and the likelihood of generating onward transmissions were compared between different transmission settings. Results: Of the 44 054 confirmed COVID-19 cases in this study, 25 241 (57.3%) were among male patients, and the median (IQR) age of patients was 36 (26-52) years. Transmission settings were identified in 13 122 cases, including 6768 household, 2733 health care, and 1174 nightlife cases. More than 6600 transmission settings were detected, and nightlife (72 of 380 [18.9%]; P < .001) and health care (119 [36.2%]; P < .001) settings were more likely to involve 5 or more cases than dining, workplace, household, and other settings. Nightlife cases appeared in the earlier phase of the epidemic, while household and health care cases appeared later. After adjustment for transmission setting, sex, age group, presence of symptoms, and wave, household and health care cases were less likely to generate onward transmission compared with nightlife cases (household: adjusted odds ratio, 0.03; 95% CI, 0.02-0.05; health care: adjusted odds ratio, 0.57; 95% CI, 0.41-0.79). Household settings were associated with intergenerational transmission, while nonhousehold settings mainly comprised transmission between the same age group. Among 30 932 cases without identified transmission settings, cases with a history of visiting nightlife establishments were more likely to generate onward transmission to nonhousehold settings (adjusted odds ratio, 5.30 [95% CI, 4.64-6.05]; P < .001) than those without such history. Conclusions and Relevance: In this case series study, COVID-19 cases identified in nightlife settings were associated with a higher likelihood of spreading COVID-19 than household and health care cases. Surveillance and interventions targeting nightlife settings should be prioritized to disrupt COVID-19 transmission, especially in the early stage of an epidemic.

Influence of Bisphenol A and 17ß-Trenbolone Exposure in Oryzias Congeners.

Japanese medaka is specified as a model fish in the test guidelines of the Organisation for Economic Co-operation and Development. Recently, populations of Japanese medaka in Japan were divided into two species, the northern Oryzias sakaizumii and the southern O. latipes. Previously, we reported that induction concentrations for sex reversal by exposure to 17α-methyltestosterone differed significantly between these two species, indicating that they respond differently to endocrine-disrupting chemica. In the present study, we examined the effects of exposure to two more endocrine-disrupting chemicals (bisphenol A and 17ß-trenbolone) in O. sakaizumii, and compared the results with those previously reported for O. latipes. Exposure to both bisphenol A and 17ß-trenbolone induced testis-ova formation or sex reversal in O. sakaizumii. Exposure to 17ß-trenbolone also increased expression of gonadal soma-derived factor (gsdf). Least-observed-effect concentrations for gonadal sex differentiation and gsdf expression were lower for O. latipes than for O. sakaizumii after exposure to bisphenol A, and were lower for O. sakaizumii than for O. latipes after exposure to 17ß-trenbolone. These results demonstrate that O. sakaizumii and O. latipes respond differently to androgenic and estrogenic endocrine-disrupting chemicals. Environ Toxicol Chem 2023;42:673-678. © 2022 SETAC.

Adverse effects of thyroid-hormone-disrupting chemicals 6-propyl-2-thiouracil and tetrabromobisphenol A on Japanese medaka (Oryzias latipes).

Thyroid-hormone-disrupting chemicals are increasingly attracting attention because of their potential harmful effects on animal health, including on fishes. Here, we investigated the effects of exposure to the thyroid-hormone-disrupting chemicals 6-propyl-2-thiouracil (PTU) and tetrabromobisphenol A (TBBPA) on swim bladder inflation, eye development, growth, swimming performance, and the expression of thyroid-related genes in Japanese medaka (Oryzias latipes). PTU exposure resulted in reductions in eye size, growth, and swim bladder inflation, and these effects led to poorer swimming performance. These phenotypic effects were accompanied by increased expression of the thyroid-stimulating hormone subunit beta (tshß) paralog tshß-like, but there were no significant changes in expression for tshß, deiodinase 1 (dio1), deiodinase 2 (dio2), and thyroid hormone receptor alpha (trα) and beta (trß). For PTU exposure, we identified the key event (swim bladder inflation reduction) and an adverse outcome (swimming performance reduction). No significant effects from TBBPA exposure were seen on swim bladder inflation, eye development, growth, or swimming performance. However, expression of tshß-like and tshß (significantly enhanced) and trα and trß (significantly reduced) were affected by TBBPA exposure albeit not in dose-dependent manners. There were no effects of TBBPA on the expression of dio1 and dio2. We thus show that the two thyroid-hormone-disrupting chemicals PTU and TBBPA differ in their effect profiles with comparable effects on the studied phenotypes and thyroid-related gene expression to those reported in zebrafish.

[Management of Food Hygiene and Safety by Hazard Analysis and Critical Control Point (HACCAP)].

Advances in food production technology and newer distribution systems have made it easier to obtain fresh ingredients from both within and outside of Japan. Although convenient, mass distribution of food over wide areas involves the risk of expanding the health damage caused by foods. Comprehensive management from production to consumption, using systems, such as hazard analysis and critical control point (HACCP), is required to ensure the safety of foods. Improved inspection methods are also required to detect the effects of environmental changes on food. In this paper, we demonstrate the use of "Methods of Analysis in Health Science 2020" for food hygiene and safety management.

Development of Drone-Mounted Multiple Sensing System with Advanced Mobility for In Situ Atmospheric Measurement: A Case Study Focusing on PM2.5 Local Distribution.

This study was conducted using a drone with advanced mobility to develop a unified sensor and communication system as a new platform for in situ atmospheric measurements. As a major cause of air pollution, particulate matter (PM) has been attracting attention globally. We developed a small, lightweight, simple, and cost-effective multi-sensor system for multiple measurements of atmospheric phenomena and related environmental information. For in situ local area measurements, we used a long-range wireless communication module with real-time monitoring and visualizing software applications. Moreover, we developed four prototype brackets with optimal assignment of sensors, devices, and a camera for mounting on a drone as a unified system platform. Results of calibration experiments, when compared to data from two upper-grade PM2.5 sensors, demonstrated that our sensor system followed the overall tendencies and changes. We obtained original datasets after conducting flight measurement experiments at three sites with differing surrounding environments. The experimentally obtained prediction results matched regional PM2.5 trends obtained using long short-term memory (LSTM) networks trained using the respective datasets.

Cooperativity of the Activated CH/π Interaction Probed through CH Stretching Vibrations in Phenol-(Acetylene)n (∼16 ≤ n ≤ ∼30) and (Acetylene)n+ (10 ≤ n ≤ 70) Clusters.

The acidity of acetylene CH is stronger than that of alkane CH, and the attractive interaction between an acetylene CH with π-electrons, which shows a clear hydrogen bond property, is called activated CH/π interaction. In this study, cooperative enhancement of the activated CH/π interaction has been probed through the cluster size dependence of the red shift of the acetylene CH stretching vibrational band in neutral phenol-(acetylene)n (∼16 ≤ n ≤ ∼30) and (acetylene)n+ (10 ≤ n ≤ 70). In both the clusters, the characteristic asymmetric (red-shaded) shape of the CH stretch band has been observed. This band shape means that the magnitude of the activated CH/π interaction is enhanced by its cooperativity in the interior moiety of the cluster. The red-shifted component of the band extends with increasing cluster size, and the edge of this component seems to reach to the CH stretch band position of crystalline acetylene at the size of n = 20-30, indicating that dozens of molecules need to interact each other to maximize cooperativity in the activated CH/π interaction of acetylene. On the other hand, the peak position of the band does not converge to that of crystalline acetylene in the observed size range. The present result suggests that the spectral convergence of acetylene clusters to the bulk may occur in the cluster size range of hundreds or larger.

Determining C5, C6 and C7 myotomes through comparative analyses of clinical, MRI and EMG findings in cervical radiculopathy.

OBJECTIVE: There are many myotome charts in the literature, but few studies have presented actual data to support their identification. We aimed to determine C5/C6/C7 myotomes based on clinical and EMG data of patients with cervical spondylotic radiculopathy (CSR) having a single-root lesion confirmed by MRI. METHODS: Medical Research Council (MRC) scores and EMG findings were retrospectively reviewed for patients enrolled from our EMG database. RESULTS: Enrolled were 25 patients (10 C5, 6 C6, and 9 C7 CSR). In C5 CSR, weakness or denervation potentials in EMG, or both, were observed in the deltoid (Del) and infraspinatus (Isp) muscles for all patients, and in the biceps brachii (BB) and brachioradialis (BR) muscles for 9/10 and 8/9 patients, respectively. In C6 CSR, weakness of the wrist extensor and/or denervation of the extensor carpi radialis longus (ECRL)/extensor carpi radialis brevis (ECRB), and those of the pronator teres (PT) were observed for all patients. Weakness was not observed for any other muscle in C6 CSR. Denervation potentials of ECRL were found in 5/8 and 3/5 patients with C5 and C6 CSR, respectively, whereas those of ECRB were found in 1/5, 6/6, and 2/5 patients with C5, C6 and C7 CSR, respectively. In C7 CSR, weakness/denervation of the triceps brachii (TB) and denervation potentials of the flexor carpi radialis (FCR) were observed for all patients. Denervation potentials in PT and weakness/denervation of the extensor digitorum (ED) were observed in 2/9 and 4/9 patients, respectively. CONCLUSION: Suggested dominant myotomes are: C5 for the Del, Isp, BB, and BR, C5/6 for the ECRL, C6 > C7 for the ECRB and PT, and C7 for the TB and FCR. SIGNIFICANCE: The current study identified dominant myotomes that differ from the existing literature.

Male-Dominant Hepatitis A Outbreak Observed among Non-HIV-Infected Persons in the Northern Part of Tokyo, Japan.

Recently, we experienced an outbreak of acute hepatitis A virus (HAV) infection between 2018 and 2020. Herein, we describe this male-dominant HAV infection outbreak observed among non-human immunodeficiency virus (HIV)-infected persons in the northern part of Tokyo, Japan. Clinical information was collected from patient interviews and from medical record descriptions. In the present study, 21 patients were retrospectively analyzed. A total of 90.4 and 33.3% of patients were males, and men who have sex with men (MSM), respectively. The total bilirubin levels and platelet counts tended to be lower in the MSM group than in the non-MSM group. C-reactive protein (CRP) levels tended to be higher in acute liver failure (ALF) patients than in non-ALF patients. Prolonged cholestasis was observed in one patient (4.8%). We also found that 18 HAV isolates belonged to HAV subgenotype IA/subgroup 13 (S13), which clustered with the HAV isolate (KX151459) that was derived from an outbreak of HAV infection among MSM in Taiwan in 2015. Our results suggest that the application of antivirals against HAV, as well as HAV vaccines, would be useful for the treatment and prevention of severe HAV infection.

The effect of daily calf stroking frequency during the postnatal period on the establishment of the human-calf relationship.

OBJECTIVE: Stroking calves during the postnatal period could effectively improve humancalf relationships. The objective of this study is to examine how daily calf stroking frequency during the postnatal period affects the establishment of human-calf relationships. METHODS: Six calves were stroked by a trainer for 6 minutes once daily for 5 days after birth (D1). Six calves were stroked by a trainer for 3 minutes twice daily for 5 days after birth (D2). A further four calves were stared at but not stroked as the control group. The overall stroking or staring duration was the same for all groups, at 6 min/d and 30 min over 5 days. The tests for reactions to the stationary trainer in an unfamiliar environment and avoidance distance measurements for an approaching trainer were conducted at 1 month and 3 months after the treatment. RESULTS: Calves in both stroking groups approached significantly closer to the stationary trainer, vocalized less, and looked at the trainer shorter than the control group at 1 month. However, at 3 months, there was no significant difference between the D1 and the control group, whereas the D2 approached significantly closer to the trainer and vocalized less, and looked at the trainer for a shorter time than the control group. For the avoidance distance, the trainer could approach closer to both stroking groups than the control at 1 month, however, there was no difference among groups at 3 months. CONCLUSION: Our results suggested that the difference in the calf stroking procedure affected the established human-calf relationships, even though the total stroking duration was the same for all stroked calves. It is likely to be more effective to stroke more frequently than intensively when the aim is to establish better human-calf relationships within limited labor time.

Influence of triphenyltin on morphologic abnormalities and the thyroid hormone system in early-stage zebrafish (Danio rerio).

In the present study, we assessed the negative effects of triphenyltin (TPT) on zebrafish (Danio rerio) by exposing embryos and early-stage larvae to various concentrations of TPT from 2 h after fertilization (haf) until 30 days after hatching (dah). Whether test groups were fed or fasted during ecotoxicity studies using fish models has varied historically, and whether this experimental condition influences test results is unknown. Here, we confirmed that the lethal concentration of TPT to embryo and early-stage larvae (i.e., 3 dah or younger) showed in fed (lowest observed effect concentration (LOEC); 6.34 µg/L) and fasted (LOEC; 6.84 µg/L) groups. In addition, 84% and 100% of the larvae in the 2.95 and 6.64 µg/L exposure groups, respectively, had uninflated swim bladders; all affected larvae died within 9 dah. This finding suggests that morphologic abnormalities in early larval zebrafish are useful as endpoints for predicting the lethality of chemical substances after hatching. We then assessed the expression of several genes in the thyroid hormone pathway, which regulates swim bladder development in many fish species, including zebrafish. Larvae exposed to 6.64 µg/L TPT showed significant increases in the mRNA expression levels of thyroid hormone receptor α (trα) and trß but not of thyroid stimulating hormone ß subunit. These findings suggest that TPT disrupts the thyroid system in zebrafish.

CH7233163 Overcomes Osimertinib-Resistant EGFR-Del19/T790M/C797S Mutation.

Osimertinib is the only EGFR-tyrosine kinase inhibitor (TKI) capable of overcoming EGFR-T790M-mutated NSCLC, but osimertinib-resistant EGFR triple mutations (Del19/T790M/C797S or L858R/T790M/C797S) have been reported. Although allosteric EGFR TKIs (e.g., EAI-045) that potentially overcome L858R/T790M/C797S have been identified, there are no effective inhibitors against Del19/T790M/C797S. In this study, we identified CH7233163 as having the potential to overcome EGFR-Del19/T790M/C797S. CH7233163 showed potent antitumor activities against tumor with EGFR-Del19/T790M/C797S in vitro and in vivo In addition to EGFR-Del19/T790M/C797S, the characterization assays showed that CH7233163 more selectively inhibits various types of EGFR mutants (e.g., L858R/T790M/C797S, L858R/T790M, Del19/T790M, Del19, and L858R) over wild type. Furthermore, crystal structure analysis suggested that CH7233163 is a noncovalent ATP-competitive inhibitor for EGFR-Del19/T790M/C797S that utilizes multiple interactions with the EGFR's αC-helix-in conformation to achieve potent inhibitory activity and mutant selectivity. Therefore, we conclude that CH7233163 is a potentially effective therapy for osimertinib-resistant patients, especially in cases of EGFR-Del19/T790M/C797S.