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.

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.

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.

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.

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.

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.

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.

Brassica rapa L. activates macrophages via Toll-like receptors.

Macrophages can initiate innate immune responses against microbes and cancer. The aim of this study was to elucidate the effects of Brassica rapa L. on macrophages. The production of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and interferon-γ induced by the insoluble fraction of B. rapa L. was decreased in macrophage-depleted spleen cells compared with controls. The insoluble fraction of B. rapa L. induced expression of H-2Kb, I-Ab, CD40, and CD86, production of cytokines and nitric oxide, and phagocytic activity in RAW264 cells. After treatment with the insoluble fraction, IL-6 and TNF-α production was significantly decreased by anti-Toll-like receptor (TLR)2 mAb or polymyxin B compared with the control. Furthermore, insoluble fraction-mediated cytokine production was significantly lower in peritoneal macrophages from TLR2-/- and TLR4-/- mice compared with wild-type mice. These results suggest that B. rapa L. is a potentially effective immunomodulator for activating macrophages to prevent infections.

Prevalence of iron deficiency among university kendo practitioners in Japan: an observational cohort study.

BACKGROUND: Iron deficiency is widely recognized as being the cause of anemia in athletes, although iron status in athletes of Kendo, a traditional Japanese martial art based on swordsmanship and practiced as an educational sport, has not been widely investigated. METHODS: We performed a health assessment on anemia and serum ferritin levels, along with nutrient intake evaluation, for Kendo practitioners in a university in Japan. RESULTS: A total of 56 Kendo practitioners (39 male and 17 female) aged between 18 and 23 years participated in the study. No individuals exhibited WHO-defined anemia (less than 13 or 12 g/dL of hemoglobin levels in male or female), while hypoferritinemia (less than 30 ng/mL) was found in seven (41%) females but not in males. Significantly higher body mass index was found in the female athletes with hypoferritinemia compared to females with normo-ferritinemia in sub-analysis (median [interquartile range]; 25.6 [24.2, 26.9] versus 22.6 [21.7, 24.1], respectively. p < 0.05). No significant differences in the intake of iron were registered between males and females (with and without hypoferritinemia) using data from a food-frequency questionnaire survey. CONCLUSION: No apparent anemia was found in adolescent Kendo practitioners, although this study confirmed the presence of hypoferritinemia in several female athletes. Careful follow-up, involving both clinical and nutritional assessment, will be necessary for them to prevent progression into anemia. A future study with larger cohorts in multiple sites is warranted to assess the prevalence of iron deficiency for validation and, if necessary, to devise a strategy for improving the iron status in Kendo athletes.

Iron Deficiency Anaemia: Its Prevalence Among Women of Reproductive Age in Shanghai and Tokyo and Links to Body Mass Index.

In this study, we examined the prevalence of iron deficiency anaemia (IDA) among young women between the ages of 20-44 living in Shanghai, China, and Tokyo, Japan with a particular emphasis on investigating its possible links with body mass index (BMI). Shanghai data were obtained from annual health check-up records conducted between May and September 2016 (n=2,006). Tokyo data were from health examinations of employees working in dispensing pharmacies between July and February 2017 (n=877). Anaemia prevalence was found to be 14.8% and 11.4% in Shanghai and Tokyo, respectively. The proportion of women with a BMI of <18.5 was 9.9% in Shanghai and 25.7% in Tokyo. Anaemia prevalence tends to be high in women with a low BMI. Women with a BMI of <18.5 had the highest prevalence of anaemia (18.2%) in Shanghai. Yet, the prevalence of anaemia was low (9.3%) among Tokyo women with a BMI of <18.5, significantly lower than those with a BMI between 18.5-25.0 (12.5%). IDA is a significant problem among women in both Shanghai and Tokyo, where the 'desire for thinness" is commonplace among young women. The Tokyo participants with a low BMI, however, appear to have managed to avoid developing IDA.

[A case of mucosa-associated lymphoid tissue lymphoma of the bile duct diagnosed using intraductal ultrasonography and transpapillary investigation of the bile duct].

A 78-year-old woman with a chief complaint of mammary tumor was referred to our hospital and was diagnosed with mucosa-associated lymphoid tissue (MALT) lymphoma using needle biopsies. She presented with MALT lymphoma lesions in the stomach, duodenum, and intraperitoneal lymph nodes. Abdominal ultrasonography revealed thickened internal layer of the bile duct. Cholangiocarcinoma, immunoglobulin G4-related sclerosing cholangitis, and MALT lymphoma were suspected. She did not report any abdominal pain, and did not have jaundice. Endoscopic retrograde cholangiopancreatography and intraductal ultrasonography indicated diffuse, irregular wall thickening with the formation of nodule lesions in the extrahepatic bile duct. Transpapillary cytology indicated CD20-positive atypical lymphocytes. MALT lymphoma of the bile duct was diagnosed. CVP with rituximab therapy was performed. After treatment, computed tomography, gastrointestinal endoscopy, endoscopic retrograde cholangiopancreatography, intraductal ultrasonography, and transpapillary cytology revealed that the tumor and the biliary wall thickening had disappeared. It is difficult to diagnose MALT lymphoma of the bile duct. We report a case in which intraductal ultrasound and transpapillary cytology were useful for establishing a diagnosis and evaluating the therapy for MALT lymphoma of the bile duct.

Pathogenic POGZ mutation causes impaired cortical development and reversible autism-like phenotypes.

Pogo transposable element derived with ZNF domain (POGZ) has been identified as one of the most recurrently de novo mutated genes in patients with neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD), intellectual disability and White-Sutton syndrome; however, the neurobiological basis behind these disorders remains unknown. Here, we show that POGZ regulates neuronal development and that ASD-related de novo mutations impair neuronal development in the developing mouse brain and induced pluripotent cell lines from an ASD patient. We also develop the first mouse model heterozygous for a de novo POGZ mutation identified in a patient with ASD, and we identify ASD-like abnormalities in the mice. Importantly, social deficits can be treated by compensatory inhibition of elevated cell excitability in the mice. Our results provide insight into how de novo mutations on high-confidence ASD genes lead to impaired mature cortical network function, which underlies the cellular pathogenesis of NDDs, including ASD.

MicroRNA 16-5p is upregulated in calorie-restricted mice and modulates inflammatory cytokines of macrophages.

Caloric restriction (CR) has long been known to increase median and maximal lifespans and to decrease mortality and morbidity in short-lived animal models, likely by altering fundamental biological processes that regulate aging and longevity. However, the detailed mechanisms of immunomodulation by CR remain unclear. In this study, we established a mouse model for CR and analyzed the changes of immune cells in these mice. The CR mice fed a calorie-restricted diet for 4 weeks had lower body weight and fat mass compared with control mice. The proportions of CD4+, CD8+, and naïve CD4+ T cells in spleen cells from CR mice were higher than those in of control mice. Additionally, the proportion of CD8+ T cells was significantly decreased and the mRNA expression of proinflammatory cytokines in the colon of CR mice was significantly decreased compared with those of control mice. To determine the effect of CR on microRNA (miRNA) expression, serum and tissues were collected from mice and the expression level of miRNA was analyzed by real-time RT-PCR. As a result, the expressions of miR-16-5p, miR-196b-5p, and miR-218-5p in serum from CR mice were higher than those in control mice. The expression of miR-16-5p increased in the spleen, thymus, colon, and stomach of CR mice compared with expression in control mice. Furthermore, RAW264 cells transfected with a miR-16-5p mimic significantly decreased the mRNA expression of IL-1ß, IL-6, and TNF-α under LPS stimulation. These results suggested that miR-16-5p might be a critical factor involving the anti-inflammatory effects of calorie-restricted feeding.

Radiation doses and decontamination effects in Minamisoma city: airborne and individual monitoring after the Fukushima nuclear accident.

After the Fukushima accident, airborne monitoring was implemented to measure airborne radiation. We examined the relationships between airborne and individual radiation monitoring and clarified the use of airborne monitoring to evaluate the effects of decontamination on residents' received doses. We used the air dose rate data from four airborne monitors conducted between 2013 and 2016, and the dose data from four individual monitors (in which a total of 18 392 adults and 3650 children participated), conducted in Minamisoma City during the same period. We examined the Pearson correlation coefficients between the airborne and individual monitoring data and estimated exposure ratios (ERs; ratios of individual dose to air dose rates) among adults and children. We also estimated the effects of decontamination on residents' doses based on airborne monitoring data, adjusting this for timing and dosing through propensity score matching, which were then compared to individual monitoring data. There were significant correlations between airborne and individual monitoring doses among adults and children, and more than 80% of residents showed a good estimation-observation agreement within a factor of two. The median of ERs was 0.304 and 0.250 among adults and children, respectively. There was a significant difference between the two. Effects of decontamination on residents' doses estimated from airborne monitoring were significantly lower than those estimated from individual monitoring. These findings suggest that airborne monitoring can be used to estimate representative radiation doses within residential areas. It may be a useful tool for enhancing communication among stakeholders and supporting individual and policy decisions; however, it is less sensitive for evaluating individual effects of decontamination than individual monitoring. Combined use of airborne and individual monitoring also showed a lower median of ERs in children than in adults and in a Japanese government's model, possibly due to prioritised decontamination for children and differences between their behavioral patterns.

Direct Methylation of Benzene with Methane Catalyzed by Co/MFI Zeolite.

Cobalt-loaded MFI zeolite showed distinct activity for direct methylation of benzene with methane into toluene. High activity was found at around 0.6 of Co/Al molar ratio. Incorporation of carbon from methane into the methyl group of toluene was confirmed with isotope tracer experiments and mass spectroscopy. Ammonia infrared-mass spectroscopy temperature-programmed desorption, transmission electron microscopy, X-ray absorption near edge spectroscopy and extended X-ray absorption fine structure indicated that Lewis acidic divalent (+II of oxidation state) Co species mono-atomically dispersed on the ion exchange site of MFI zeolite was the active species.

[A Case of Arteritis That Developed after Pegfilgrastim Administration during Chemotherapy for Breast Cancer].

A 61-year-old woman presented with metastatic breast cancer in her right lung 4 years and 11 months after the operation for her right breast cancer(HER2 enriched type). Chemotherapy(pertuzumab plus trastuzumab plus docetaxel)were ad- ministered. On day 2 of cycle 2, pegfilgrastim was administered because her neutrophils decreased to 54 cells/mL on day 8 of cycle 1. On day 9 of cycle 2, she developed left neck and chest pain. Moreover, she developed a fever of 39°C on day 14 and visited our hospital. Her WBC and CRP increased to 18,300 cells/mL and 25.48mg/dL, respectively. Computed tomography revealed an increased CT value of the panniculus, around the aorta and left pleural effusion. Ultrasonography of the neck showed a marginal hypoechoic area around the left carotid artery, which corresponded with the pain. Arteritis induced by PFG was suspected. The neck pain and fever almost completely improved 19 days later, and cycle 3 was performed 28 days after cycle 2. To our knowledge, the present case is the second report of arteritis that was suspected to be associated with PFG.

Balancing the risk of the evacuation and sheltering-in-place options: a survival study following Japan's 2011 Fukushima nuclear incident.

OBJECTIVE: The decision to evacuate or shelter-in-place is fundamental to emergency response, especially for a vulnerable population. While an elevated risk of mortality due to a hasty, unplanned evacuation has been well documented, there is little research on and knowledge about the health consequences of sheltering-in-place in disaster contexts. We compared hospital mortality in patients who sheltered-in-place (non-evacuees) after the incident with the baseline preincident mortality and articulated postincident circumstances of the hospital while sheltering-in-place. PARTICIPANTS: We considered all 484 patients admitted to Takano Hospital (located 22 km South of the Fukushima Daiichi nuclear power plant) from 1 January 2008 to 31 December 2016. METHODS: Significant differences in mortality rates between preincident baseline and three postincident groups (evacuees, non-evacuees (our major interest) and new admittees) were tested using the Bayesian survival analysis with Weibull multivariate regression and survival probability using the Kaplan-Meier product limit method. All the analyses were separately performed by the internal and psychiatry department. RESULTS: After adjusting for covariates, non-evacuees in the internal department had a significantly higher mortality risk with an HR of 1.57 (95% credible intervals 1.11 to 2.18) than the baseline preincident. Of them, most deaths occurred within the first 100 days of the incident. No significant increase in mortality risk was identified in evacuees and new admittees postincident in the department, which were adjusted for covariates. In contrast, for the psychiatry department, statistical difference in mortality risk was not identified in any groups. CONCLUSIONS: The mortality risk of sheltering-in-place in a harsh environment might be comparable to those in an unplanned evacuation. If sheltering-in-place with sufficient resources is not guaranteed, evacuation could be a reasonable option, which might save more lives of vulnerable people if performed in a well-planned manner with satisfactory arrangements for appropriate transportation and places to safely evacuate.

Neuroprotective effect of Citrus kawachiensis (Kawachi Bankan) peels, a rich source of naringin, against global cerebral ischemia/reperfusion injury in mice.

Cerebral ischemia/reperfusion is known to induce the generation of reactive oxygen species and inflammatory responses. Numerous studies have demonstrated that naringin (NGIN) has anti-oxidant and anti-inflammatory properties. We previously reported that Citrus kawachiensis contains a large quantity of NGIN in its peel. In the present study, we orally (p.o.) administered dried peel powder of C. kawachiensis to mice of a transient global ischemia model and found in the hippocampus region that it 1) suppressed neuronal cell death, 2) reversed the reduction in the level of phosphorylated calcium-calmodulin-dependent protein kinase II, 3) had the tendency to reverse the reduction in the level of glutathione, and 4) blocked excessive activation of microglia and astrocytes. These results suggested that the dried peel powder of C. kawachiensis had a neuroprotective effect against ischemic brain via anti-oxidative and anti-inflammatory effects. We also showed that these effects of the dried peel powder were more powerful than those obtained with a comparable amount of NGIN alone.

Enhancement of natural killer activity and IFN-γ production in an IL-12-dependent manner by a Brassica rapa L.

Certain food components possess immunomodulatory effects. The aim of this study was to elucidate the mechanism of the immunostimulatory activity of Brassica rapa L. We demonstrated an enhancement of natural killer (NK) activity and interferon (IFN)-γ production in mice that were orally administered an insoluble fraction of B. rapa L. The insoluble fraction of B. rapa L. significantly induced IFN-γ production in mouse spleen cells in an interleukin (IL)-12-dependent manner, and NK1.1+ cells were the main cells responsible for producing IFN-γ. Additionally, the results suggested that the active compounds in the insoluble fraction were recognized by Toll-like receptor (TLR) 2, TLR4, and C-type lectin receptors on dendritic cells, and they activated signaling cascades such as MAPK, NF-κB, and Syk. These findings suggest that B. rapa L. is a potentially promising immuno-improving material, and it might be useful for preventing immunological disorders such as infections and cancers by activating innate immunity.