The complexities of salt taste reception: insights into the role of TMC4 in chloride taste detection.

Although salt is an essential substance vital to life, excessive salt intake could cause various health issues. Therefore, new technologies and strategies should be developed to reduce salt intake without compromising taste. However, the underlying physiological mechanisms of salt taste reception is complex and not completely understood. Sodium chloride is a typical salty substance. It is widely believed that only sodium is important for the generation of salty taste. On the other hand, from a psychophysical perspective, the importance of chloride in salty taste has been indicated. Thus, understanding the mechanisms of both sodium- and chloride-tastes generation is necessary to completely comprehended the fundamentals of salt taste reception. However, the mechanism for detecting chloride taste has remained unclear for many years. Recently, we have identified transmembrane channel-like 4 (TMC4) as the first molecule that mediates the reception of chloride taste. TMC4 functions as a voltage-dependent chloride channel and plays an important role in the reception of the chloride taste by detecting chloride ions. In this mini-review, we first introduce the known reception mechanism of salty taste, and then discuss the roles of TMC4 in the salt taste reception. The finding of TMC4 may serve as a basis for developing new technologies and formulating strategies to reduce salt intake without compromising taste.

Variability in morphology and immunohistochemistry of Crohn's disease-associated small bowel neoplasms: implications of Claudin 18 and Cadherin 17 expression for tumor-targeted immunotherapies.

AIMS: Inflammatory bowel disease-associated colorectal carcinomas are known to have different morphology, immunoprofile, and genetic findings from sporadic colorectal carcinomas; however, little is known for Crohn's disease-associated small bowel neoplasms (CD-SBNs). Cadherin 17 is a useful biomarker of adenocarcinomas with intestinal phenotype and recently reported as an ideal target for chimeric antigen receptor T-cells (CAR-T) therapy for gastrointestinal carcinoma. Claudin 18 is a cell adhesion protein, and Claudin18 isoform 2 (CLDN18.2) is frequently expressed at high levels in gastric-type adenocarcinoma. Zolbetuximab, a targeted monoclonal antibody, has been developed for CLDN18.2-positive gastroesophageal adenocarcinoma. We examined a series of CD-SBNs for both Cadherin 17 and Claudin 18, and also hypothesized that expression of Claudin 18 was associated with gastric phenotype. METHODS AND RESULTS: We performed histological and immunohistochemical examinations on 25 CD-SBNs. Most of adenocarcinomas showed tubular morphology as seen in gastric carcinomas, whereas a subset of dysplasia was morphologically similar to that of the large bowel. Cadherin17 and Claudin 18 expression was identified in 93% and 57% CD-associated adenocarcinomas respectively. In Cadherin 17-positive CD-SBNs, frequent MUC5AC, MUC6, and Claudin18 expression was identified (61%, 57%, and 57%, respectively). Claudin 18-positive CD-SBNs showed significantly more MUC5AC and MUC6 expression than Claudin 18-negative CD-SBNs (P = 0.005, < 0.001 respectively). CONCLUSION: In CD-associated small bowel adenocarcinomas, Cadherin 17 expression was frequently retained and Claudin 18 was frequently co-expressed. Claudin 18 had a positive correlation with the expression of gastric mucins. These results suggest that CD-associated small bowel adenocarcinomas may be candidates for Cadherin 17- and Claudin 18-targeted immunotherapies.

Ki-67 distribution, α-methylacyl-CoA racemase (AMACR) expression and mucin phenotypes are associated with non-polypoid growth in ulcerative colitis-associated neoplasia.

AIMS: Ulcerative colitis-associated neoplasia (UCAN) is characterised by multifocal tumourigenesis. A wide range of metachronous lesions have been reported to occur after endoscopic treatment of UCAN, which suggests the development of sporadic tumours in lesions treated as UCAN. Therefore, we aimed to evaluate differences of immunohistochemistry (IHC) in features and clinicopathological characteristics of intramucosal lesions in patients with ulcerative colitis (UC). METHODS AND RESULTS: We examined 35 intramucosal lesions resected for carcinoma or dysplasia by total colectomy from patients with UC and 71 sporadic adenomas (SAs) endoscopically resected from patients without UC. UC lesions were divided into the conventional UCAN group, defined as p53 mutant pattern and normal expression of ß-catenin, and the non-conventional UCAN group, defined as the rest. Ki-67 distribution, α-methylacyl-CoA racemase (AMACR) expression and mucin phenotypes were compared using IHC, and clinicopathological characteristics were investigated. Conventional and non-conventional UCAN lesions were located in the left colon and rectum. Relative to the SA lesions, UCAN lesions occurred in much younger patients and exhibited more frequent basal distribution of Ki-67 in tumour crypts. Conventional UCAN lesions tended to be non-polyploid and exhibited a higher frequency of normal AMACR expression than SA lesions. UC lesions were heterogeneous-only two of the eight patients with multiple lesions had lesions (both non-conventional UCAN lesions) exhibiting concordant IHC staining features. CONCLUSIONS: The basal pattern of Ki-67 distribution, normal expression of AMACR and a non-intestinal mucin phenotype were determined as characteristic features suggestive of UCAN. Non-polypoid growth was another a key feature of UCAN.

Potential for Drug Repositioning of Midazolam as an Inhibitor of Inflammatory Bone Resorption.

Drug repositioning is a method for exploring new effects of existing drugs, the safety and pharmacokinetics of which have been confirmed in humans. Here, we demonstrate the potential drug repositioning of midazolam (MDZ), which is used for intravenous sedation, as an inhibitor of inflammatory bone resorption. We cultured a mouse macrophage-like cell line with or without MDZ and evaluated its effects on the induction of differentiation of these cells into osteoclasts. For in vivo investigations, we administered lipopolysaccharide (LPS) together with MDZ (LPS+MDZ) to the parietal region of mice and evaluated the results based on the percentage of bone resorption and calvaria volume. Furthermore, we examined the effects of MDZ on the production of reactive oxygen species (ROS) in cells and on its signaling pathway. MDZ inhibited osteoclast differentiation and bone resorption activity. In animal studies, the LPS+MDZ group showed a decreasing trend associated with the rate of bone resorption. In addition, the bone matrix volume in the LPS+MDZ group was slightly higher than in the LPS only group. MDZ inhibited osteoclast differentiation by decreasing ROS production and thereby negatively regulating the p38 mitogen-activated protein kinase pathway. Thus, we propose that MDZ could potentially be used for treating inflammatory bone resorption, for example, in periodontal disease.

Longitudinal and regional association between dietary factors and prevalence of Crohn's disease in Japan.

Although a Western diet has been identified as a risk factor for Crohn's disease (CD), there is still controversy surrounding the specific foods that may contribute to the development of the disease. In this study, we examined the association between food intake and the prevalence of CD in Japan, as Japanese patients with CD are known to have limited genetic involvement. We identified changes in food intake associated with an increase in the number of patients with CD by analyzing the per capita consumption of food types from 1981 to 2014. Additionally, we examined the association between CD prevalence and food intake in each prefecture. Finally, the relationship between food intake and estimated age at CD onset was also investigated. Between 1981 and 2014, we observed Increased consumption of meat, eggs, milk and dairy products, oil, and potatoes and decreased consumption of grains, beans, vegetables, fruit, fish, sugar, and seaweed. The annual incidence of CD increased by 1388% over the same period. We found that meat consumption was significantly associated with CD prevalence (ß = 0.503, p = 0.0003), while a significant negative correlation was observed between CD prevalence and fruit and vegetable consumption (fruit, ß = 0.464, p = 0.0012; vegetables, ß = 0.404, p = 0.0023). Furthermore, we estimated that the peak consumption of more meat and less fruit and vegetables and the peak age of CD onset occurred within the age range of 20-24 years. Our study identified a clear correlation between the consumption of meat, fruits, and vegetables and the prevalence of CD in Japan. Additionally, we found an association between meat, fruit, and vegetable consumption and the age at CD onset.

Mouse TMC4 is involved in the detection of chloride taste of salts.

Licking behavior with various salts in transmembrane channel-like 4 (Tmc4) knockout (KO) mice was observed. In Tmc4 KO mice, a significant decrease in sensitivity to chloride salts, such as NaCl, KCl, and NH4Cl, was observed, while no significant decrease in sensitivity to Na-gluconate was observed. This finding suggests that TMC4 may be involved in the detection of chloride taste.

Unencapsulated thymoma: a case report.

Thymomas, the most common mediastinal tumors, form capsules. Only a few reports have presented small thymomas without capsule formation, so-called microthymomas. Here, we report a case of an unencapsulated thymoma measuring 18 mm. A 42-year-old female presented with an anterior mediastinal tumor. Computed tomography revealed an 18-mm nodule in the anterior mediastinum. Magnetic resonance imaging revealed a solid tumor that was iso-intense on T1-weighted images and hypo-intense on T2-weighted images. Thoracoscopic partial thymectomy was performed. The histopathological diagnosis was a type B1 thymoma. The tumor was localized within the thymic tissue lacked a fibrous capsule and partially invaded the surrounding fat tissue. To our knowledge, this is the first report of an unencapsulated thymoma, except for microthymomas.

Mastication stimuli regulate the heartbeat rate through rhythmic regulation by the hypothalamic-autonomic system; molecular and telemetric studies in weaning-stage rats.

Mastication stimuli have been demonstrated to affect memory function and autonomic nerve activity; however, this process has not been well studied during weaning compared to old age. Previously, we conducted molecular analyses of the thalamus and hippocampus to elucidate the mechanisms underlying this memory-enhancing effect in weaning-stage rats. In this study, we aimed to evaluate the effect of masticatory stimuli on the regulation of heartbeat rate (HR) through the hypothalamic-autonomic system. Three-week-old male rats were administered a powdered diet (P group) or chow-diet (C group) for 10 days. Thereafter, transcriptome analysis was performed. Vasopressin, cocaine-amphetamine-regulated transcript prepropeptide, corticotropin-releasing hormone, and thyrotropin-releasing hormone, which are involved in sympathetic activation of heart rate, were downregulated in the C group. Electrocardiograms were recorded continuously for 12 days under the same condition. Interestingly, rats in the C group had a significantly lower HR than those in the P group on day 11. We checked several parameters representing the autonomic regulation of HR. The C group had higher values for the high-frequency band integration of the HR power spectrum (parasympathetic marker) and root mean square successive difference of R-wave intervals (parasympathetic marker) relative to the P group. Such findings provide a molecular and physiological basis for understanding the regulation of cardiovascular function in response to masticatory stimuli in the autonomic nervous system.

Genetic risk score of cerebral infarction in atrial fibrillation genome-wide association study.

INTRODUCTION: Stroke is a leading cause of death and the primary cause of adult-acquired disability. Patients with cardiogenic embolic stroke also have higher mortality and recurrence rates than patients with other stroke subtypes. Atrial fibrillation (AF) is a major risk factor for cerebral infarction (CI). The large-scale study identified 32 loci in the MEGASTROKE study. However, few studies have attempted to identify novel stroke risk variants in patients with a history of AF. Our overall aim was to identify novel CI risk variants in AF cases and explore whether their associations with the CI risk were affected by the CHADS2 and CHA2DS2-VASc scores. METHODS: We performed association study with CI using 8181 AF cases in previous genome-wide association study (GWAS) and imputation data without controls. We classified AF cases into those with or without past history of CI, and the genetic associations with the CI risk were examined. RESULTS: GWAS identified eight associated loci. The generated genetic risk score (GRS) for the eight loci was significantly associated with CI in patients with AF (1.46 × 10-8 ). We estimated bivariate logistic regression model which contained GRS and CHADS2 score (GRS: p-Value = 7.41 × 10-9 , CHADS2 score: p-Value <2.0 × 10-16 ) or CHA2DS2-VASc scores (GRS: p-Value = 2.52 × 10-10 , CHA2DS2-VASc score: p-Value <2.0 × 10-16 ). CONCLUSION: We identified eight genetic variants that were potentially associated with the risk of CI of AF cases and the significant GRS, whose associations were independent of the CHADS2 or CHA2DS2-VASc score.

Bioinformatics Analysis of the Molecular Networks Associated with the Amelioration of Aberrant Gene Expression by a Tyr-Trp Dipeptide in Brains Treated with the Amyloid-ß Peptide.

Short-chain peptides derived from various protein sources have been shown to exhibit diverse bio-modulatory and health-promoting effects in animal experiments and human trials. We recently reported that the oral administration of the Tyr-Trp (YW) dipeptide to mice markedly enhances noradrenaline metabolism in the brain and ameliorates the working-memory deficits induced by the ß-amyloid 25-35 peptide (Aß25-35). In the current study, we performed multiple bioinformatics analyses of microarray data from Aß25-35/YW-treated brains to determine the mechanism underlying the action of YW in the brain and to infer the molecular mechanisms and networks involved in the protective effect of YW in the brain. We found that YW not only reversed inflammation-related responses but also activated various molecular networks involving a transcriptional regulatory system, which is mediated by the CREB binding protein (CBP), EGR-family proteins, ELK1, and PPAR, and the calcium-signaling pathway, oxidative stress tolerance, and an enzyme involved in de novo l-serine synthesis in brains treated with Aß25-35. This study revealed that YW has a neuroprotective effect against Aß25-35 neuropathy, suggesting that YW is a new functional-food-material peptide.

Correction: Ingestion of taxifolin-rich foods affects brain activity, mental fatigue, and the whole blood transcriptome in healthy young adults: a randomized, double-blind, placebo-controlled, crossover study.

Correction for 'Ingestion of taxifolin-rich foods affects brain activity, mental fatigue, and the whole blood transcriptome in healthy young adults: a randomized, double-blind, placebo-controlled, crossover study' by Fumika Shinozaki et al., Food Funct., 2023, https://doi.org/10.1039/d2fo03151e.

The Effect of a mHealth App (KENPO-app) for Specific Health Guidance on Weight Changes in Adults With Obesity and Hypertension: Pilot Randomized Controlled Trial.

BACKGROUND: Commercial smartphone apps that promote self-monitoring of weight loss are widely available. The development of disease-specific apps has begun, but there is no app for specific health guidance (SHG) to prevent metabolic syndrome, type 2 diabetes, and cardiovascular diseases in middle-aged adults in Japan. OBJECTIVE: This study aimed to determine the efficacy of an SHG mobile health app in facilitating weight loss in Japanese adults with obesity and hypertension. METHODS: In a 12-week, statistician-blinded, randomized parallel controlled trial, 78 overweight and obese men aged 40-69 years were assigned in a 1:1 ratio to either the usual support plus KENPO-app group (intervention group) or the active control group. KENPO-app (release April 10, 2019; OMRON Healthcare Co., Ltd.) was developed by the study team and focus groups and uses behavior change techniques (ie, self-monitoring and goal-setting theory). This app was developed for SHG based on the four specific health checkups and guidance system in Japan: (1) focusing primarily on achieving the target (weight loss of ≥2 kg); (2) assessing healthy eating, exercise habits, smoking habits, relaxation, and self-weighing; (3) providing information on the results of specific health checkups; and (4) starting an intervention period of 6 months with the interim assessment at 3 months. The initial assessment explored the following: personality traits (4 types), health checkup data concerns (10 items), symptom concerns (10 items), and the aim of the intervention (weight loss, improving fitness, symptoms, laboratory data). Chatbot-supported health information on health and health behavior was selected from 392 quizzes based on app data and was provided to participants. The KENPO-app had chatbot-supported feedback and information provision combined with a self-monitoring tool (weight, steps, and blood pressure). Data on active exercise, healthy eating, and healthy lifestyle habits were obtained using a web-based self-administered questionnaire at baseline and 12 weeks. RESULTS: The trial's retention rate was 95% (74/78). The adherence to daily self-weighing, wearing the pedometer, and blood pressure monitoring in the KENPO-app group was significantly higher than those in the active control group. Compared with the active control group, the median body weight and BMI of the intervention group significantly decreased at 3 months (-0.4, IQR -2.0 to 0.6 kg vs -1.1, IQR -2.7 to -0.5 kg; P=.03; -0.1, IQR -0.6 to 0.3 kg vs -0.4, IQR -0.8 to -0.2 kg; P=.02, respectively). The intervention increased the percentage of participants who self-reported taking ≥8000 steps, eating vegetables before rice, eating slowly, and relaxing. Personality traits were associated with the degree of weight loss in the intervention group. CONCLUSIONS: The SHG-specific KENPO-app was feasible and induced modest but significant weight loss in adults with obesity. TRIAL REGISTRATION: University Hospital Medical Information Network Center UMIN000046263; https://tinyurl.com/bderys3b.

Ingestion of taxifolin-rich foods affects brain activity, mental fatigue, and the whole blood transcriptome in healthy young adults: a randomized, double-blind, placebo-controlled, crossover study.

The antioxidant properties of polyphenols, which are found in most plants, have been shown to be useful for maintaining health, including enhancing brain function and alleviating stress. We aimed to investigate the effect of a single intake of taxifolin-containing foods on cognitive task performance and whole blood gene expression in healthy young adults. This study was a randomized, placebo-controlled, double-blind, crossover trial in which healthy young adults were administered a single dose of either a placebo or food containing taxifolin. Cognitive tests (serial 3s, serial 7s, and rapid visual information processing) to examine brain activity and visual analog scale questionnaires to analyze mental fatigue were applied. The set of tests was repeated four times. The findings showed that taxifolin intake improved calculation abilities and reduced mental fatigue. An analysis of whole blood gene expression before and after the test revealed that the expression of foreign substance removal-related genes increased following the ingestion of taxifolin and that most differentially expressed genes were enriched in granulocytes. Taxifolin intake was shown to affect the brain activity of healthy young adults and demonstrated an antifatigue effect, thereby reducing subjective fatigue. A single intake of taxifolin may enhance the removal of foreign substances by strengthening the innate immune system and suppressing the occurrence of injury.

Clinical significance of completion of radium-223 treatment and acute adverse events in patients with metastatic castration-resistant prostate cancer.

Objectives: In the treatment of castration-resistant prostate cancer (CRPC) with bone metastases, radium-223 dichloride (Ra-223) is the only bone-targeted drug that shows survival benefits. Completing six courses of Ra-223 treatment is thought to be associated with better patient survival, but this treatment has a relatively high rate of acute adverse events. Methods: This retrospective study included 85 patients from 12 institutions in Japan to investigate the clinical significance of the completion of Ra-223 treatment and acute adverse events in CRPC patients. Results: Six courses of Ra-223 treatment were completed in 65.9% of the patients. Grade 3 or higher acute adverse events were observed in 27.1% of patients. The prostate specific antigen and alkaline phosphatase declined at 26.9% and 87.9%, respectively. The overall survival rates at 12 and 24 months were 80.7% and 63.2%, respectively. Both completion of six courses of Ra-223 treatment and absence of grade 3 or higher acute adverse events were associated with longer overall survival. In univariate analysis, factors related to the history of treatment (five or more hormone therapy agents and cytotoxic chemotherapy) and hematological parameters (Prostate specific antigen (PSA) doubling time, alkaline phosphatase, hemoglobin, albumin, and serum calcium) were associated with completing six courses of Ra-223 treatment without experiencing grade 3 or higher acute adverse events. Multivariate analysis showed that a history of chemotherapy, PSA doubling time, hemoglobin, and serum calcium showed statistical significance. We built a predictive score by these four factors. Patients with lower scores showed higher rates of treatment success (p<0.001) and longer overall survival (p<0.001) with statistical significance. Conclusions: Accomplishing six courses of Ra-223 treatment without grade 3 or higher acute adverse events was a prognostic factor in patients with mCRPC treated with Ra-223. We built a predictive score of treatment success and need future external validation.

Genes related to cell wall metabolisms are targeted by miRNAs in immature tomato fruits under drought stress.

The metabolism of tomato fruits changes when plants experience drought stress. In this study, we investigated changes in microRNA (miRNA) abundance and detected 32 miRNAs whose expression changes in fruit. The candidate target genes for each miRNA were predicted from the differentially expressed genes identified by transcriptome analysis at the same fruit maturation stage. The predicted targeted genes were related to cell wall metabolisms, response to pathogens, and plant hormones. Among these, we focused on cell wall metabolism-related genes and performed a dual luciferase assay to assess the targeting of their mRNAs by their predicted miRNA. As a result, sly-miR10532 and sly-miR7981e suppress the expression of mRNAs of galacturonosyltransferase-10 like encoding the main enzyme of pectin biosynthesis, while sly-miR171b-5p targets ß-1,3-glucosidase mRNAs involved in glucan degradation. These results will allow the systematic characterization of miRNA and their target genes in the tomato fruit under drought stress conditions.

A Case of Anterior Arytenoid Cartilage Dislocation During Nasal Tracheal Intubation Using an Indirect Video Laryngoscope.

Arytenoid cartilage dislocation can occur as a complication of tracheal intubation and laryngeal trauma, but its occurrence with indirect video laryngoscopy has not been reported. This paper reports anterior arytenoid dislocation occurring after nasotracheal intubation performed under indirect laryngoscopy using a video laryngoscope (McGRATH MAC; Medtronic). The dislocation is presumed to have resulted from the laryngoscope blade being initially inserted too deeply and applying pressure to the posterior aspect of the left cricoarytenoid joint. This patient's anterior arytenoid dislocation was treated conservatively using speech therapy with resolution occurring approximately 40 days postoperatively. On the 74th day after surgery, fibroscopic examination confirmed recovery and healing of the dislocation. However, other types of arytenoid dislocations and laryngeal injuries may require alternative treatment. Early consultation with an otolaryngologist is recommended if arytenoid dislocation is suspected.

Molecular logic of salt taste reception in special reference to transmembrane channel-like 4 (TMC4).

The taste is biologically of intrinsic importance. It almost momentarily perceives environmental stimuli for better survival. In the early 2000s, research into taste reception was greatly developed with discovery of the receptors. However, the mechanism of salt taste reception is not fully elucidated yet and many questions still remain. At present, next-generation sequencing and genome-editing technologies are available which would become pivotal tools to elucidate the remaining issues. Here we review current mechanisms of salt taste reception in particular and characterize the properties of transmembrane channel-like 4 as a novel salt taste-related molecule that we found using these sophisticated tools.

Mastication stimuli enhance the learning ability of weaning-stage rats, altering the hippocampal neuron transcriptome and micromorphology.

Mastication stimuli are known to relieve senile dementia in human and animal studies. However, few studies have focused on its effect on weaning-stage animals and the underlying molecular processes. In this study, 3-week-old male rats were raised on a powdered (P-group) or chow (C-group) diet for 8 days, and their behavior was examined using the Y-maze and novel object recognition tests. In the Y-maze test, the C-group rats showed a larger alternation ratio than the P-group rats. In the novel object recognition test, the C-group rats exhibited a significantly larger discrimination index for novel objects than for familiar objects, but the P-group rats did not. We then compared the hippocampal neuron morphology and transcriptome between the groups. C-group rats exhibited larger dendrite branch numbers in the apical dendrites of pyramidal cells in the cornu ammonis 1 (CA1) region and a larger spine density in the basal dendrites of CA1 neurons than the P-group rats. Using DNA microarray analysis, we identified 621 (P < C) and 96 (P > C) genes that were differentially expressed between the groups. These genes were enriched in functional terms related to dendrite growth and included the Igf2, RhoA, and Rho GEF genes, most of which were upregulated in the C-group. These results suggest that the mastication stimuli during the weaning period can enhance the learning ability of rats by increasing the dendrite branches of hippocampal CA1 neurons and by regulating genes related to dendrite growth.

Mouse Model of Weak Depression Exhibiting Suppressed cAMP Signaling in the Amygdala, Lower Lipid Catabolism in Liver, and Correlated Gut Microbiota.

To establish a mouse model of weak depression, we raised 6-week-old C57BL/6N mice in single (SH) or group housing (GH) conditions for 2 weeks. The SH group showed less social interaction with stranger mice, learning disability in behavioral tests, and lower plasma corticosterone levels. The cecal microbiota of the SH group showed significant segregation from the GH group in the principal coordinate analysis (PCoA). Transcriptome analysis of the amygdala and liver detected multiple differentially expressed genes (DEGs). In the amygdala of SH mice, suppression of the cyclic adenine monophosphate (cAMP) signal was predicted and confirmed by the reduced immunoreactivity of phosphorylated cAMP-responsive element-binding protein. In the liver of SH mice, downregulation of beta-oxidation was predicted. Interestingly, the expression levels of over 100 DEGs showed a significant correlation with the occupancy of two bacterial genera, Lactobacillus (Lactobacillaceae) and Anaerostipes (Lachnospiraceae). These bacteria-correlated DEGs included JunB, the downstream component of cAMP signaling in the amygdala, and carnitine palmitoyltransferase 1A (Cpt1a), a key enzyme of beta-oxidation in the liver. This trans-omical analysis also suggested that nicotinamide adenine dinucleotide (NAD) synthesis in the liver may be linked to the occupancy of Lactobacillus through the regulation of nicotinamide phosphoribosyltransferase (NAMPT) and kynureninase (KYNU) genes. Our results suggested that SH condition along with the presence of correlated bacteria species causes weak depression phenotype in young mice and provides a suitable model to study food ingredient that is able to cure weak depression.

Atypical Splenic Abscesses Due to Clostridioides difficile.

BACKGROUND Splenic abscess is a rare infectious disease that occurs after bloodstream infection and trauma. It has become more common due to an increase in the number of immunocompromised patients. They typically present with round cystic lesions demonstrated by ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI). Clostridioides difficile (formerly Clostridium difficile) is a well-known cause of pseudomembranous colitis, but extraintestinal manifestations are very rare. To the best of our knowledge, only 9 cases of splenic abscess due to C. difficile have been reported in the literature. CASE REPORT A 90-year-old man presented with weight loss, fever, and abdominal pain. Contrast-enhanced CT revealed splenomegaly with irregular hypodense nodules. Image-guided biopsy or drainage was not performed for a technical reason. MRI showed atypical nodules with mixed high and low signals on both T1- and T2-weighted images, which were inconclusive. A laparoscopic splenectomy was performed, which resulted in partial removal due to severe adhesion of the spleen to the surrounding tissues. Cultures of splenic pus yielded C. difficile, Enterococcus faecium, and Bacteroides fragilis. Pathological examination of the spleen showed widespread abscesses with hemorrhage and necrosis, leading to the diagnosis of splenic abscesses. Intravenous administration of vancomycin, clindamycin or metronidazole was ineffective. He died of fatal arrhythmia 5 months after the initial diagnosis of splenic abscess. CONCLUSIONS Splenic abscess can present with atypical imaging findings owing to chronic inflammation, bleeding, and necrosis. Although polymicrobial, this is the tenth reported case of splenic abscess caused by C. difficile.