Association Between Gender and Payments Received From Pharmaceutical Companies Among Medical Professors and Associate Professors in Japan.

Introduction While prior research showed gender gaps in industry payments for medical professionals in the United States, there are limited data in Japan. So, this study seeks to investigate the potential gender gap in the receipt of pharmaceutical companies (PFCs) across all medical fields in Japan. Based on the results of previous studies, we developed a hypothesis that male doctors get more PFC than female doctors. Materials and methods Data from 92 pharmaceutical companies in Japan, covering 2016 to 2019, were analyzed. The analysis was conducted on professors and associate professors at all national and public medical universities in Japan, with gender as a factor variable and payments as an outcome variable, and variables that may have influenced the factor or outcome variables in previous studies, such as specialization, university type, region, rank and years since graduation, as control variables. Payments were converted to US dollars using the December 31, 2021, rate of 115 yen to the dollar for comparison purposes. Results Out of 1,825 subjects, 1,755 were males and 70 females. Males consistently received higher median payments from pharmaceutical companies (PFCs) than females across categories. In particular, among physicians specializing in internal medicine, the median PFC for men was $25 compared to $8 for women. For physicians affiliated with former imperial universities (the seven former imperial universities founded before World War II), the median PFC for men was $32 compared to $5 for women. Multivariate analysis confirmed significantly higher total benefits for males from 2016 to 2019, with the gender gap widening during this period (incidence rate ratio (IRR) for 2016: 0.51, IRR for 2019: 0.44). Conclusions Japanese male professors and associate professors received significantly higher PFCs than their female counterparts, and this gender gap expanded from 2016 to 2019, highlighting persistent gender inequality in the medical field in Japan, similar to trends observed in the United States.

Immunoglobulin G4-related Autoimmune Pancreatitis and Hypopituitarism Following Immune Checkpoint Inhibitor Therapy: A Case Report.

A 70-year-old man underwent nephrectomy for renal cell carcinoma followed by 3 cycles of pembrolizumab as adjuvant chemotherapy. Three months later, he complained of appetite loss. He was diagnosed with secondary adrenal insufficiency and pancreatic tumor. Amylase and immunoglobulin G (IgG) 4 levels were normal. The differential diagnosis poses challenges in distinguishing pancreatic cancer, renal cell carcinoma metastasis, and autoimmune pancreatitis, necessitating tumor resection surgery. A histological examination revealed IgG4-related sclerosing pancreatitis. Postoperatively, there was no recurrence of pancreatitis. It is essential to consider the potential development of IgG4-related diseases after the administration of immune checkpoint inhibitors.

Intestinal Morphology and Glucose Transporter Gene Expression under a Chronic Intake of High Sucrose.

Sucrose is a disaccharide that is degraded into fructose and glucose in the small intestine. High-sucrose and high-fructose diets have been reported, using two-dimensional imaging, to alter the intestinal morphology and the expression of genes associated with sugar transport, such as sodium glucose co-transporter 1 (SGLT1), glucose transporter 2 (GLUT2), and glucose transporter 5 (GLUT5). However, it remains unclear how high-fructose and high-sucrose diets affect the expression of sugar transporters and the intestinal morphology in the whole intestine. We investigate the influence of a chronic high-sucrose diet on the expression of the genes associated with sugar transport as well as its effects on the intestinal morphology using 3D imaging. High sucrose was found to increase GLUT2 and GLUT5 mRNA levels without significant changes in the intestinal morphology using 3D imaging. On the other hand, the delay in sucrose absorption by an α-glucosidase inhibitor significantly improved the intestinal morphology and the expression levels of SGLT1, GLUT2, and GLUT5 mRNA in the distal small intestine to levels similar to those in the proximal small intestine, thereby improving glycemic control after both glucose and sucrose loading. These results reveal the effects of chronic high-sugar exposure on glucose absorption and changes in the intestinal morphology.

Rethinking the Utility of the Audio-Only Encounter: A Case of Herpes Zoster Co-Infection in Asymptomatic SARS-CoV-2.

Background: Telemedicine with video communication has become commonly applied during and after the COVID-19 pandemic. While audio-only encounters are not allowed in Japan after August 2023. The Centers for Medicaid and Medicare Services (CMS) in the United States revised the telehealth policy to make the video visit standard. We present here a case with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and diagnosed her with the Herpes zoster at audio-only encounters followed by an in-person clinic visit. Case Presentation: A 31-year-old woman called our hospital for a complaint of right chest discomfort and a tingling sensation. The SARS-CoV-2 infection was confirmed on her with the polymerase chain reaction (PCR) test 4 days before the symptom onset. A telephone encounter was made for her since the video communication failed to be prepared. The attending physician made a diagnosis of herpes zoster based on her verbal explanation of symptoms and localized skin lesions. An anti-viral medication with amenamevir was given. The photos of skin lesions were sent 3 days after the audio visit, which was consistent with herpes zoster. The patient visited our outpatient clinic and was confirmed for herpes zoster serologically with positive antibodies of both varicella-zoster IgM and IgG. Conclusions: The audio-only visit could help diagnose herpes zoster if the follow-up examinations are performed adequately. Audio-only encounters preserve the flexibility of telemedicine when video communication cannot be prepared promptly.

Prevalence of iron-deficient but non-anemic university athletes in Japan: an observational cohort study.

BACKGROUND: Iron deficiency (ID) and iron deficiency anemia (IDA) are long-standing health problems in athletes, affecting both performance and health. ID prevalence in young athletes remains high and a matter of concern. ID and IDA can lead to fatigue, reduced endurance, and decreased oxygen transport, potentially compromising athletic performance. We hypothesized that ID would still be a major health concern in university athletes across sports clubs in Japan. PURPOSE: The study aimed to investigate the prevalence of ID and IDA in athletes participating in Kendo, badminton, baseball, and handball at the University of Tsukuba (Tsukuba, Ibaraki Prefecture, Japan). The study also examined the correlation between hypoferritinemia and other variables, such as previous use of iron supplements, body mass index (BMI), energy intake, and years of athletics. METHODS: Between January and December 2019, 126 university athletes, consisting of 79 males and 47 females, underwent physical measurements and blood tests. The blood test included complete blood count, levels of serum ferritin, serum iron, and total iron-binding capacity. The anemia was defined in accordance with the WHO criteria. Daily energy and iron intake were estimated with the food frequency questionnaire in Japanese (FFQg). Thirty-four female athletes responded to a survey about their menstruation and low-dose estrogen-progestin (LEP) usage. RESULTS: While none of the athletes had anemia, 22 (47%) female athletes exhibited serum ferritin levels of 30 ng/mL or less, defining them as hypoferritinemia. The multivariate logistic regression model revealed that a shorter duration of the athletic experience (adjusted odd ratio [95% confidence interval]: 0.62 [0.43-0.90]), lower energy intake (0.994 [0.989-0.999]), and higher dietary iron intake (4.40 [1.12-17.26]) were associated with hypoferritinemia. Seventeen (50%) female athletes reported a decline in subjective performance during menstruation, albeit two took LEP regularly. CONCLUSIONS: This study reveals that ID is a prevalent health concern among young female athletes across sports clubs. It underscores the need for their education on the importance of assessing ID status. Limitation includes the nature of single-site and observational study, the absence of hepcidin measurement, and an unspecified amount of exercise. Comprehensive investigations are needed to elucidate the causes and optimal treatments for ID in young athletes.

Enhancement of Inhibitory Activity by Combining Allosteric Inhibitors Putatively Binding to Different Allosteric Sites on Cathepsin K.

BACKGROUND: Cathepsin K, which is involved in bone resorption, is a good target for treating osteoporosis, but no clinically approved medicine has been developed. Recently, allosteric inhibitors with high specificity and few side effects have been attracting attention for use in new medicines. METHODS: Cathepsin K inhibitors were isolated from the methanol extract of Chamaecrista nomame (Leguminosae) using cathepsin K inhibition activity-assisted multi-step chromatography. Standard kinetic analysis was employed to examine the mechanism of cathepsin K inhibition when an isolated inhibitor and its derivative were used. The allosteric binding of these cathepsin K inhibitors was supported by a docking study using AutoDock vina. Combinations of allosteric cathepsin K inhibitors expected to bind to different allosteric sites were examined by means of cathepsin K inhibition assay. RESULTS: Two types of cathepsin K inhibitors were identified in the methanol extract of Chamaecrista nomame. One type consisted of cassiaoccidentalin B and torachrysone 8-ß-gentiobioside, and inhibited both cathepsin K and B with similar inhibitory potential, while the other type of inhibitor consisted of pheophytin a, and inhibited cathepsin K but not cathepsin B, suggesting that pheophytin a binds to an allosteric site of cathepsin K. Kinetic analysis of inhibitory activity suggested that pheophytin a and its derivative, pheophorbide b, bind allosterically to cathepsin K. This possibility was supported by a docking study on cathepsin K. The cathepsin K inhibitory activity of pheophytin a and pheophorbide b was enhanced by combining them with the allosteric inhibitors NSC 13345 and NSC94914, which bind to other allosteric sites on cathepsin K. CONCLUSIONS: Different allosteric inhibitors that bind to different sites in combination, as shown in this study, may be useful for designing new allosteric inhibitory drugs with high specificity and few side effects.

Loss of participation among evacuees aged 20-37 years in the disaster cohort study after the Great East Japan Earthquake.

The present study aimed to clarify the characteristics of young evacuees who had missed the Comprehensive Health Check of the Fukushima Health Management Survey (FHMS) after the Great East Japan Earthquake in 2011. The FHMS has been conducted as a prospective cohort study to evaluate the health status of evacuees annually after the great earthquake in 2011. This study focused on the annual participation rate in the Comprehensive Health Check of evacuees aged between 20 and 37 years in 2011 who evacuated due to the Fukushima Daiichi Nuclear Power Plant accident. The characteristics of subjects who did not participate after the second survey year were identified with a multivariate logistic regression model. The participation rate was estimated at 26.6% (9720 among 36,502 residents) and 15.6% (5691 residents) in 2011 and 2012, respectively. The logistic regression model revealed the following characteristics at baseline as independent predictors of non-participation after the second year of the survey: age ≤ 24 years (adjusted odds ratio 2.11, 95% CI 1.84-2.42), 25-29 years of age (1.28, 1.13-1.45), men (1.52, 1.38-1.69), evacuation outside the municipality but within Fukushima prefecture (1.54, 1.40-1.70), evacuation outside the Fukushima prefecture (1.40, 1.21-1.63), anemia (1.23, 1.06-1.43), smoking habit (1.34, 1.21-1.48), and drinking habit (1.20, 1.09-1.32). A medical history of heart disease showed opposite odds ratios, which indicate the association with continuous participation (0.43, 0.26-0.72, respectively). We observed deteriorated participation in the prospective study of the Comprehensive Health Check of the FHMS among evacuees of a younger age group, men, those evacuated outside their municipalities, and those with history of anemia, smoking and drinking habits. Hence, the cohort study may have missed certain population groups with worse health behaviors. Thus, it is necessary to consider various measures to increase the participation rate in the disaster cohort study to understand the long-term health effects of disasters on younger residents in evacuation zones.

Asymptomatic gastric anisakiasis detected in gastric cancer screening: A case report.

Anisakiasis is a parasitic disease caused by Anisakis simplex and has become an emerging zoonosis as preferences for eating raw or undercooked seafood have become more common. Few case reports of asymptomatic anisakiasis have been published to date. A 79-year-old asymptomatic man underwent esophagogastroduodenoscopy (EGD) for gastric cancer screening. The gastroenterologist diagnosed superficial gastritis without any malignant lesions but found an Anisakis larva while reviewing EGD images. The physician performed a second EGD and removed the larva. The patient reported that he ate the flatfish sashimi for dinner on the day before the first EGD. This case indicates the existence of asymptomatic gastric anisakiasis, indicating that anisakiasis incidence may have previously been underestimated.

Effectiveness of the Booster of SARS-CoV-2 Vaccine among Japanese Adolescents: A Cohort Study.

Vaccination is effective in preventing COVID-19-related hospitalization among all age groups, but there is limited evidence on the effectiveness of the booster of the SARS-CoV-2 vaccine among adolescents. We analyzed the data on the status of SARS-CoV-2 infection and their vaccination profiles in adolescents aged 13-18 years in Soma city (Fukushima, Japan) (n = 1835) from 14 May to 15 June 2022. The crude incidence rate and 95% confidence interval were calculated with the negative-binomial regression model after classifying the immunization status. The crude effectiveness of a booster administration to prevent infections was estimated as 86.4% (95% confidence interval: 57.2-95.7) when compared with the primary vaccination alone. The results of this study support that the community-based mass vaccination campaign of a booster dose among adolescents has additional protection from COVID-19 during the period of the B.1.1.529 (omicron) variant wave.

Liquid Enteral Nutrients Alter the Pharmacokinetics of Orally Administered Carbamazepine in Rats.

The interaction between enteral nutrients (ENs) and drugs co-administered through a nasogastric (NG) tube reportedly affects the absorption and resultant plasma concentrations of the respective drugs. However, the gastrointestinal absorption of carbamazepine (CBZ), an antiepileptic drug, co-administered with liquid ENs through an NG tube has not been clarified. In this study, we measured the recovery rate (%) of CBZ (Tegretol® powder) passed through an NG tube when co-administered with distilled water or ENs (F2α®, Racol® NF, Ensure Liquid®, and Renalen® LP) of different compositions, frequently used in Japan. We also measured the plasma CBZ level in 26 rats after oral co-administration of CBZ with liquid ENs. The CBZ recovery rate was close to 100% in rats of all EN groups after passage through the NG tube. Furthermore, CBZ area under the plasma concentration-time curve from time zero to 9 h (AUC0→9h) of the Ensure liquid® group decreased compared with that of control group (P < 0.05) and Renalen® LP group (P < 0.01). However, the AUC0→9h of CBZ remained unchanged when co-administered with Ensure liquid® 2 h after initial CBZ administration. In conclusion, the co-administration of CBZ with Ensure Liquid® caused a reduction in the absorption of CBZ from the gastrointestinal tract, without adsorption on the NG tube. The administration of Ensure Liquid® 2 h after CBZ is a way to prevent a decrease in plasma CBZ concentration. Our findings suggest that carefully monitoring the plasma levels of CBZ is necessary in co-administation with Ensure liquid® to prevent the unintended effects of the interaction between CBZ and liquid EN.

Changes in the proportion of anemia among young women after the Great East Japan Earthquake: the Fukushima health management survey.

This study aimed to evaluate the sequential changes in the proportion of anemia among young women over eight years after the Great East Japan Earthquake in 2011 using a prospective study of the Fukushima Health Management Survey. This study focused on the women aged between 20 and 44 who lived in the evacuation area of the nuclear power plant accident. The yearly age-adjusted proportion of anemia was accessed with data between July 2011 and March 2019. A total of 9,198 women participated in the health checkup in 2011, albeit the participation was decreased to 1,241 in 2018. The age-adjusted proportion of anemia was 16.7% in 2012 and then declined after 2013 (p with Cochran-Armitage trend test = 0.03). The multivariate regression analysis identified < 23 kg/m2 of body mass index (BMI), no history of smoking, and no habitual alcohol use as independent baseline characteristics predictive of temporality anemic condition after the disaster (Adjusted odds ratios [95% confidence interval]; 1.98 [1.43-2.74], 1.85 [1.21-2.83], and 1.42 [1.07-1.90], respectively). Thus, women with low BMI and healthier habits might risk temporarily anemic status after the disaster. Our findings signal the importance of preventing anemia in young women after the disaster.

Portopulmonary hypertension and the risk of high right ventricular systolic pressure in liver transplant candidates.

AIM: Portopulmonary hypertension (PoPH) is a rare and serious complication of liver cirrhosis and portal hypertension that can interfere with liver transplantation (LT). We evaluated the prevalence of PoPH and the clinical features of right ventricular systolic pressure (RVSP), which is equivalent to pulmonary artery systolic pressure, in LT candidates. METHODS: This was a single-center retrospective study. A total of 157 Japanese patients with decompensated liver cirrhosis or portal hypertension (76 men, median age = 52 years [range: 18-68 years]) were enrolled. The relationships between RVSP and clinical parameters, and the prevalence of PoPH in LT candidates, were evaluated. RESULTS: The cardiological parameters were as follows: brain natriuretic peptide (BNP), 39.1 (4.0-780.5) pg/mL; RVSP, 31.2 (16.0-122.4) mmHg; ejection fraction, 58% (28-72%); and mean peak tricuspid regurgitation velocity, 2.3 (1.5-5.3) m/s. The RVSP was significantly higher in females (p = 0.02) and primary biliary cholangitis (PBC) patients (p = 0.01), and was weakly correlated with the BNP level (r = 0.40, p = 0.01). For RVSPs of < 36 and ≥ 36 mmHg, the 5-year survival rates were 36.1% versus 34.1%, and 85.4% versus 85.3%, in non-LT and LT cases, respectively (p = 0.47 and 0.69, respectively). Among six patients with an RVSP ≥ 50 mmHg, three (1.9%) were diagnosed with PoPH and treated with vasodilators. CONCLUSIONS: PoPH was observed in 3 cases (1.9%) in 157 LT candidates. In patients with suspected mild pulmonary hypertension (RVSP, 36 - 50 mmHg), LT was successfully performed.

Profiles of anemia in adolescent students with sports club membership in an outpatient clinic setting: a retrospective study.

BACKGROUND: Anemia is a common health issue among adolescents. Anemic conditions could affect physical performance; however, the actual profiles of anemia in adolescent students in sports clubs have not been well documented. METHODS: We conducted a retrospective chart review of individuals aged 13-22 years who belonged to sports clubs in schools and visited an outpatient clinic between August 1, 2016, and August 31, 2020. The medical and laboratory records, including serum levels of ferritin, folate, vitamin B12, and creatinine kinase at their first visit were assessed. RESULTS: A total of 485 individuals (231 male (48%) and 254 female (52%) patients) were eligible for the study. The most common club activity was track and field (n = 171 (35%)). The overall prevalence of the World Health Organization-defined anemia was 16.5% (95% CI [13.1-20.4]; 9.0% [5.4-13.8] and 23.1% [17.8-29.2] in males and females, respectively) after excluding pre-treated individuals. Hypoferritinemia and elevation of serum creatinine kinase levels were identified as independent contributors to anemia in both sexes (odds ratios: 13.2 (95% CI [4.2-41.1]), p < 0.001 and 14.7 (95% CI [1.8-118.4]), p = 0.012, respectively for males; odds ratios: 6.6 (95% CI [1.3-13.9]), p < 0.001 and 2.7 (95% CI [1.4-5.5]), p = 0.004, respectively for females). DISCUSSION: Anemia is prevalent in both male and female adolescent students in sports clubs. Iron deficiency and excessive training indicated by elevated creatinine kinase levels may contribute to the risk of anemia. Physicians should assess the amount of exercise, and not merely iron storage, in clinical practice.

Young gastric cancer patient with high CA19-9 complicated by Trousseau syndrome.

A 47-year-old Japanese woman presented with epigastric discomfort and anorexia. Upper endoscopy showed type 4 advanced gastric cancer in the gastric antrum with stenosis of the pyloric portion. Abdominopelvic CT revealed peritoneal dissemination, and stage IV advanced gastric cancer was diagnosed. Laparoscopic gastrojejunostomy and enterostomy were performed. Trousseau syndrome occurred 7 days post-surgery. Despite appropriate treatment, the patient developed a pulmonary embolism 13 days later and died 18 days post-surgery. Even in young cancer patients without lifestyle disease complications, it is important to pay attention to Trousseau syndrome as part of cancer management.

Metabolomic investigation of differences in components and taste between hon-mirin and mirin-like-seasoning.

Hon-mirin (HM) is a traditional Japanese brewed seasoning used to confer sweetness and koku. Mirin-like-seasoning (MLS) is a less-expensive alternative to HM because it is not subjected to liquor tax in Japan. In this study, components and taste qualities of HM and MLS were compared by gas chromatography/mass spectrometry (GC/MS)-based metabolomics and a sensory evaluation. GC/MS analyses of foods with high sugar content are limited by contamination of the ion source and difficulty in detecting other compounds. To resolve this issue, solid-phase analytical derivatization (SPAD), in which the extraction and derivatization of analytes can be conducted in a single step, was applied as a novel sample preparation method in this study. The effect of sugar was removed by the specific absorption, derivatization, and elution of ionic compounds, such as amino acids and organic acids, with ion-exchange solid-phases. The SPAD method application enabled the detection of 15 amino acids and 14 organic acids using ion-exchange solid-phases by performing GC/MS analysis twice. These ionic compounds were not detected in mirin using conventional sample preparation. HM samples had a higher amino acid content and a lower sugar content than those of MLS samples. Furthermore, differences in sweetness and koku between HM and MLS were observed in a sensory evaluation. This is the first GC/MS-based metabolomics analysis of mirin using the SPAD method; our results provide insight into the differences between HM and MLS.

Visualization of mandibular movement relative to the maxilla during mastication in mice: integration of kinematic analysis and reconstruction of a three-dimensional model of the maxillofacial structure.

BACKGROUND: Mastication is one of the most fundamental functions for the conservation of human life. To clarify the pathogenetic mechanism of various oral dysfunctions, the demand for devices for evaluating stomatognathic function has been increasing. The aim of the present study was to develop a system to reconstruct and visualize 3-dimensional (3D) mandibular movements relative to the maxilla, including dynamic transition of occlusal contacts between the upper and lower dentitions during mastication in mice. METHODS: First, mandibular movements with six degrees of freedom were measured using a motion capture system comprising two high-speed cameras and four reflective markers. Second, 3D models of maxillofacial structure were reconstructed from micro-computed tomography images. Movement trajectories of anatomical landmark points on the mandible were then reproduced by integrating the kinematic data of mandibular movements with the anatomical data of maxillofacial structures. Lastly, 3D surface images of the upper dentition with the surrounding maxillofacial structures were transferred to each of the motion capture images to reproduce mandibular movements relative to the maxilla. We also performed electromyography (EMG) of masticatory muscles associated with mandibular movements. RESULTS: The developed system could reproduce the 3D movement trajectories of arbitrary points on the mandible, such as incisor, molars and condylar points with high accuracy and could visualize dynamic transitions of occlusal contacts between upper and lower teeth associated with mandibular movements. CONCLUSIONS: The proposed system has potential to elucidate the mechanisms underlying motor coordination of masticatory muscles and to clarify their roles during mastication by taking advantage of the capability to record EMG data synchronously with mandibular movements. Such insights will enhance our understanding of the pathogenesis and diagnosis of oral motor disorders by allowing comparisons between normal mice and genetically modified mice with oral behavioral dysfunctions.

Influence of stereochemistry on the activity of rapadocin, an isoform-specific inhibitor of the nucleoside transporter ENT1.

Rapadocin is a novel rapamycin-inspired polyketide-tetrapeptide hybrid macrocycle that possesses highly potent and isoform-specific inhibitory activity against the human equilibrative nucleoside transporter 1 (hENT1). Rapadocin contains an epimerizable chiral center in phenylglycine and an olefin group, and can thus exist as a mixture of four stereoisomers. Herein, we report the first total synthesis of the four stereoisomers of rapadocin using two different synthetic strategies and the assignment of their structures. The inhibitory activity of each of the four synthetic isomers on both hENT1 and hENT2 was determined. It was found that the stereochemistry of phenylglycine played a more dominant role than the configuration of the olefin in the activity of rapadocin. These findings will guide the future design and development of rapadocin analogs as new modulators of adenosine signaling.