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1.
Article En | MEDLINE | ID: mdl-38715897

Objectives: Cold snare polypectomy (CSP) is widely performed for small colorectal polyps. However, small colorectal polyps sometimes include high-grade adenomas or carcinomas that require endoscopic resection with electrocautery. This study aimed to evaluate the efficacy and safety of a novel resection technique, hot snare polypectomy with low-power pure-cut current (LPPC-HSP) for small colorectal polyps, compared with CSP and conventional endoscopic mucosal resection (EMR). Methods: Records of patients who underwent CSP, EMR, or LPPC-HSP for nonpedunculated colorectal polyps less than 10 mm between April 2021 and March 2022 were retrospectively evaluated. We analyzed and compared the treatment outcomes of CSP and EMR with those of LPPC-HSP using propensity score matching. Results: After propensity score matching of 396 pairs, an analysis of CSP and LPPC-HSP indicated that LPPC-HSP had a significantly higher R0 resection rate (84% vs. 68%; p < 0.01). Delayed bleeding was observed in only two cases treated with CSP before matching. Perforation was not observed with either treatment. After propensity score matching of 176 pairs, an analysis of EMR and LPPC-HSP indicated that their en bloc and R0 resection rates were not significantly different (99.4% vs. 100%, p = 1.00; 79% vs. 81%, p = 0.79). Delayed bleeding and perforation were not observed with either treatment. Conclusions: The safety of LPPC-HSP was comparable to that of CSP. The treatment outcomes of LPPC-HSP were comparable to those of conventional EMR for small polyps. These results suggest that this technique is a safe and effective treatment for nonpedunculated polyps less than 10 mm.

2.
Schizophr Bull ; 2024 Jun 02.
Article En | MEDLINE | ID: mdl-38825582

BACKGROUND AND HYPOTHESIS: Problematic internet use (PIU) is prevalent among adolescents. Past research suggested cross-sectional associations between PIU and psychotic experiences, but little information is available on the longitudinal association. We hypothesized that PIU in adolescence may be longitudinally associated with psychotic experiences, adjusting for confounders. STUDY DESIGN: We analyzed a random sample of adolescents in the Tokyo Teen Cohort to examine how PIU at ages 10 (2012-2015), 12 (2014-2017), and 16 (2019-2021) was associated with mental health issues at age 16. PIU was evaluated by the modified Compulsive Internet Use Scale, psychotic experiences by the Adolescent Psychotic-like Symptom Screener, and depression by the Short Mood and Feelings Questionnaire. We also examined the mediating role of social withdrawal. STUDY RESULTS: We analyzed 3171 adolescents; 151 reported psychotic experiences and 327 reported depression at age 16. Compared with the lowest tertile PIU group, the highest tertile PIU group at age 12 showed an increased adjusted risk of psychotic experiences (RD 3.3%, 95% CI 2.9%-3.7%; RR 1.65, 95% CI 1.55-1.73) and depression (RD 5.9%, 95% CI 5.5%-6.3%; RR 1.61, 95% CI 1.55-1.68) at age 16. PIU at age 16 showed analogous results, while PIU at age 10 suggested a smaller impact. Social withdrawal mediated 9.4%-29.0% of the association between PIU and psychotic experiences. CONCLUSIONS: PIU is longitudinally associated with psychotic experiences and depression in adolescents. Further longitudinal and intervention studies are warranted to provide robust public health implications and foster a safer digital future.

3.
Front Nutr ; 11: 1349738, 2024.
Article En | MEDLINE | ID: mdl-38706562

Introduction: Macronutrient intake can be one of the most influential factors in cognitive and neural development in adolescents. Adolescence is a specific period of cognitive and neural development, and nutritional effects during this period could be life-long. Therefore, understanding the effects of macronutrient intake on cognitive and neural development in adolescents is crucially important. We thus examined the association across macronutrient intake, intelligence, and neural development using population-based cohort data. Methods: We conducted two studies. In study 1, we included a total of 1,734 participants (boys, 907, age [mean ± standard deviation] 171.9 ± 3.44 months; range 163.0-186.0 months) from the Tokyo TEEN Cohort (TTC) to examine the association between macronutrient intake and intelligence quotient (IQ). In study 2, we included a total of 63 participants (boys, 38, age 174.4 ± 7.7 months; range 160.7-191.6 months) to investigate the effect of nutrition intake on neural development using graph theory analysis for resting-state functional magnetic resonance imaging (rs-fMRI) derived from a subset of the TTC. Results: TTC data revealed that a higher IQ was associated in boys with increased protein intake (ß = 0.068, p = 0.031), and in girls, with reduced carbohydrate intake (ß = -0.076, p = 0.024). Graph theory analysis for rs-fMRI at approximately age 12 has shown that impaired local efficiency in the left inferior frontal gyrus was associated with higher carbohydrate and fat intake ([x, y, z] = [-51, 23, 8], pFDR-corrected = 0.00018 and 0.02290, respectively), whereas increased betweenness centrality in the left middle temporal gyrus was associated with higher carbohydrate, fat, and protein intake ([x, y, z] = [-61, -43, -13], pFDR-corrected = 0.0027, 0.0029, and 0.00075, respectively). Moreover, we identified a significant moderating effect of fat and protein intake on the relationship between change in betweenness centrality over a 2-year measurement gap in the left middle temporal gyrus and intelligence (ß = 12.41, p = 0.0457; ß = 12.12, p = 0.0401, respectively). Conclusion: Our study showed the association between macronutrient intake and neural development related to intelligence in early adolescents. Appropriate nutritional intake would be a key factor for healthy cognitive and neural development.

4.
Article En | MEDLINE | ID: mdl-38740465

BACKGROUND AND AIM: Hot snare excision using electrocautery is widely used for large colorectal polyps (>10 mm); however, adverse events occur due to deep thermal injury. Colorectal polyps measuring 10-14 mm rarely include invasive cancer. Therefore, less invasive therapeutic options for this size category are demanding. We have developed hot snare polypectomy with low-power pure-cut current (LPPC HSP), which is expected to contribute to less deep thermal damage and lower risk of adverse events. This study aimed to evaluate the efficacy and safety of LPPC HSP for 10-14 mm colorectal polyps, compared with conventional endoscopic mucosal resection (EMR). METHODS: In this multicenter, retrospective, observational study, clinical outcomes of EMR and LPPC HSP for 10-14 mm nonpedunculated colorectal polyps between January 2021 and March 2022 were compared using propensity score matching. RESULTS: We identified 203 EMR and 208 LPPC HSP cases. After propensity score matching, the baseline characteristics between the groups were comparable, with 120 pairs. The en bloc and R0 resection rates were not significantly different between EMR and LPPC HSP groups (95.8% vs 97.5%, P = 0.72; 90.0% vs 91.7%, P = 0.82). The rates of delayed bleeding and perforation did not differ between the groups. CONCLUSIONS: Compared with conventional EMR, LPPC HSP showed a similar resection ability without an increase in adverse events. These results suggest that LPPC HSP is a safe and effective treatment for 10-14 mm nonpedunculated colorectal polyps.

5.
Clin J Gastroenterol ; 2024 May 29.
Article En | MEDLINE | ID: mdl-38811510

Sclerosing mesenteritis (SM) is a rare disorder that involves the mesenteric adipose tissue with chronic fibrosing inflammation. Few reports mention the natural history of severe SM cases. Here, we report a severe and relapsing SM case in which a long-term natural history could be followed. The patient had undergone surgery for small bowel stenosis of unknown cause 10 years earlier. He had stopped visiting the hospital at his discretion. He was admitted to the hospital 10 years later due to recurrent symptoms, and a close examination revealed multiple small intestinal strictures; thus, surgery was performed again. The pathological results revealed that the patient had SM, corticosteroid administration dramatically improved his symptoms, and he has maintained remission for a long time.

6.
J Org Chem ; 89(11): 8305-8310, 2024 Jun 07.
Article En | MEDLINE | ID: mdl-38776094

This study analyzes the feasibility of utilizing the catalytic and enantioselective [4 + 2] cycloaddition of sterically demanding heterocycle-incorporated siloxydienes to yield polycyclic skeletons with a tetrasubstituted carbon. A catalyst derived from lanthanide triflimide enabled the reaction. The mechanistic investigations and transformations of the adducts are also discussed. The proposed approach facilitates the synthesis of intricate polysubstituted skeletons, each with multiple contiguous chiral centers, thereby aiding in the production of diverse hydrocarbazoles for drug discovery purposes.

8.
Intern Med ; 2024 Apr 02.
Article En | MEDLINE | ID: mdl-38569907

Cytokeratin (CK) is a specific marker of adenocarcinoma. However, cases of CK7-positive esophageal squamous cell carcinoma (ESCC) have only rarely been reported. We herein report a case of unresectable CK7-positive ESCC with aggressive liver metastasis following nivolumab treatment initiation. Nivolumab treatment was discontinued after one course because of complications. Notably, the liver metastases exhibited accelerated growth. Immunostaining of the necropsy specimens revealed diffuse positivity for forkhead box protein A1 (FOXA1)/CK7, thus indicating a potent poor immune response. The potential correlation between CK7 expression and the immune checkpoint inhibitor response may offer valuable insights into the development of effective therapeutic strategies.

9.
J Alzheimers Dis ; 99(1): 403-415, 2024.
Article En | MEDLINE | ID: mdl-38640160

Background: The emotional impact of the coronavirus disease 2019 (COVID-19) pandemic on people with dementia has been quantified. However, little is known about the impact of change in home-care use owing to the pandemic. Objective: To determine the longitudinal association between dementia, change in home-care use, and depressive symptoms during the pandemic. Methods: We included data of 43,782 home-dwelling older adults from the English Longitudinal Study of Ageing (ELSA), Study of Health, Ageing and Retirement in Europe (SHARE), and National Health and Aging Trends Study (NHATS). This study considered the latest main wave survey prior to the pandemic as the baseline, and the COVID-19 survey as follow-up. In a series of coordinated analyses, multilevel binomial logistic regression model was used to examine the association between baseline dementia, change in home-care use at follow-up, and presence of depressive symptoms. Results: Dementia, using the ELSA, SHARE, and NHATS datasets, was identified in 2.9%, 2.3%, and 6.5% of older adults, and home-care use reduced in 1.7%, 2.8%, and 1.1% of individuals with dementia, respectively. Dementia was significantly associated with the increased risk of depressive symptoms in all three cohorts. However, the interaction between dementia and period (follow-up) was non-significant in SHARE and NHATS. Across all three cohorts, home-care use during the pandemic, regardless of change in amount, was significantly associated with increased depressive symptoms, compared to the non-use of home care. Conclusions: These results highlight the need for tailoring dementia care at home to promote independence and provide sustainable emotional support.


COVID-19 , Dementia , Depression , Home Care Services , Humans , COVID-19/epidemiology , COVID-19/psychology , Female , Dementia/epidemiology , Dementia/psychology , Dementia/therapy , Male , Aged , Depression/epidemiology , Depression/psychology , Longitudinal Studies , Home Care Services/trends , Aged, 80 and over , Europe/epidemiology , Cohort Studies , Middle Aged , SARS-CoV-2 , Independent Living
10.
Org Biomol Chem ; 22(18): 3606-3610, 2024 May 08.
Article En | MEDLINE | ID: mdl-38629974

We have developed a nickel-catalysed regio- and stereoselective hydrocyanation of alkynoates that gives syn-ß-cyanoalkenes. DFT calculations suggest that a favored transition state promotes Cα-H bond formation for determining regio- and stereoselectivity of the products.

11.
Lancet Reg Health West Pac ; 43: 100979, 2024 Feb.
Article En | MEDLINE | ID: mdl-38456092

Background: Psychopathological and behavioral problems in adolescence are highly comorbid, making their developmental trajectories complex and unclear partly due to technical limitations. We aimed to classify these trajectories using deep learning and identify predictors of cluster membership. Methods: We conducted a population-based cohort study on 3171 adolescents from three Tokyo municipalities, with 2344 pairs of adolescents and caregivers participating at all four timepoints (ages 10, 12, 14, and 16) from 2012 to 2021. Adolescent psychopathological and behavioral problems were assessed by using self-report questionnaires. Both adolescents and caregivers assessed depression/anxiety and psychotic-like experiences. Caregivers assessed obsession/compulsion, dissociation, sociality problem, hyperactivity/inattention, conduct problem, somatic symptom, and withdrawal. Adolescents assessed desire for slimness, self-harm, and suicidal ideation. These trajectories were clustered with variational deep embedding with recurrence, and predictors were explored using multinomial logistic regression. Findings: Five clusters were identified: unaffected (60.5%), minimal problems; internalizing (16.2%), persistent or worsening internalizing problems; discrepant (9.9%), subjective problems overlooked by caregivers; externalizing (9.6%), persistent externalizing problems; and severe (3.9%), chronic severe problems across symptoms. Stronger autistic traits and experience of bullying victimization commonly predicted the four "affected" clusters. The discrepant cluster, showing the highest risks for self-harm and suicidal ideation, was predicted by avoiding help-seeking for depression. The severe cluster predictors included maternal smoking during pregnancy, not bullying others, caregiver's psychological distress, and adolescent's dissatisfaction with family. Interpretation: Approximately 40% of adolescents were classified as "affected" clusters. Proactive societal attention is warranted toward adolescents in the discrepant cluster whose suicidality is overlooked and who have difficulty seeking help. Funding: Japan Ministry of Health, Labor and Welfare, Japan Agency for Medical Research and Development, and Japan Science and Technology Agency.

12.
JAMA Netw Open ; 7(2): e2355292, 2024 Feb 05.
Article En | MEDLINE | ID: mdl-38329755

Importance: Few studies have used a large-sample, longitudinal, population-based cohort study to examine whether the COVID-19 pandemic as a global major life event is associated with structural plasticity of the adolescent hippocampus. Objective: To examine whether Japan's first state of emergency (SoE) during the COVID-19 pandemic was associated with alterations in the macrostructures and microstructures of the hippocampus during its development. Design, Setting, and Participants: The population-neuroscience Tokyo TEEN Cohort study is a prospective cohort study with 4 consecutive waves in Tokyo, Japan. Due to the SoE, data collection was suspended between March 27, 2020, and July 30, 2020. Analyzed data, comprising 1149 brain structural scans obtained from 479 participants, of whom 336 participants had undergone 2 or more scans, were collected between October 2013 and November 2021. Data were analyzed from August 2022 to December 2023. Exposures: Japan's first SoE (April 7 to May 25, 2020). Main Outcomes and Measures: Hippocampal volume, 12 hippocampal subfield volumes, and 7 microstructural measures of the hippocampus. Results: A total of 1060 brain scans from 459 participants (214 female participants [47%]) including 246 participants from wave 1 (median [IQR] age, 11.3 [11.1-11.7] years), 358 from wave 2 (median [IQR] age, 13.8 [13.3-14.5] years), 304 from wave 3 (median [IQR] age, 15.9 [15.4-16.5] years), and 152 from wave 4 (median [IQR] age, 17.9 [17.5-18.4] years) were included in the final main analysis. The generalized additive mixed model showed a significant associations of the SoE with the mean hippocampal volume (ß = 102.19; 95% CI, 0.61-203.77; P = .049). The generalized linear mixed models showed the main associations of the SoE with hippocampal subfield volume (granule cell and molecular layer of the dentate gyrus: ß = 18.19; 95% CI, 2.97-33.41; uncorrected P = .02; CA4: ß = 12.75; 95% CI, 0.38-25.12; uncorrected P = .04; hippocampus-amygdala transition area: ß = 5.67; 95% CI, 1.18-10.17; uncorrected P = .01), and fractional anisotropy (ß = 0.03; 95% CI, 0.00-0.06; uncorrected P = .04). Conclusions and Relevance: After the first SoE, a volumetric increase in the hippocampus and trend increase in 3 subfield volumes and microstructural integration of the hippocampus were observed, suggesting that the transient plasticity of the adolescent hippocampus was affected by a major life event along with the typical developmental trajectory.


COVID-19 , Humans , Female , Adolescent , Child , Cohort Studies , Japan/epidemiology , Pandemics , Prospective Studies , Hippocampus/diagnostic imaging
13.
JAMA Netw Open ; 7(1): e2353166, 2024 Jan 02.
Article En | MEDLINE | ID: mdl-38270951

Importance: The suicidal risk of psychopathology in adolescence is suggested to differ based on its longitudinal trajectory, but the comorbidity of these symptom trajectories has not been well examined. This study comprehensively clustered trajectories of multiple psychopathological and behavioral symptoms and examined their associations with suicidal thoughts in adolescence. Objective: To determine which categories and trajectories of psychopathological and behavioral symptoms are associated with suicidal thoughts in adolescence, accounting for comorbid symptoms. Design, Setting, and Participants: This population-based cohort study in Japan used data from the Tokyo Teen Cohort (TTC) study, which was established in 2012 and is currently ongoing. Data from 3 waves of surveys conducted at ages 10, 12, and 16 years from October 2012 to September 2021 were used. Of the adolescents in the cohort, participants with at least 2 evaluations of psychopathological and behavioral symptoms were included. Data were analyzed from December 2022 to March 2023. Exposure: Latent class growth analysis was used to cluster the trajectory of each psychopathological and behavioral symptom. Main Outcomes and Measures: The associations between symptom trajectories and suicidal thoughts at age 16 were examined. Suicidal thoughts were assessed using a self-report questionnaire. Psychopathological and behavioral symptoms were assessed using the 8 subscale scores of the caregiver-report Child Behavior Checklist. Results: This study included 2780 adolescents (1306 female participants [47.0%]). Of the 1920 adolescents with data on suicidal thoughts, 158 (8.2%) had suicidal thoughts. The median (IQR) age was 10.2 (10.0-10.3) years at the first evaluation, 11.9 (11.8-12.1) years at the second evaluation, and 16.3 (16.1-16.5) years at the last evaluation. The clustering pattern of trajectories varied depending on symptom categories. After adjusting for each symptom trajectory and confounders, adolescents with persistent high withdrawn symptoms (odds ratio [OR], 1.88; 95% CI, 1.10-3.21) and those with increasing somatic symptoms (OR, 1.97; 95% CI, 1.16-3.34) had a significantly higher risk of suicidal thoughts than adolescents without these symptoms. There was no interaction between these symptom trajectories and the risk of suicidal thoughts. Conclusions and Relevance: This cohort study found that persistent withdrawn symptoms and increasing somatic symptoms during early to midadolescence were associated with an increased risk of suicidal thoughts in midadolescence, even after accounting for comorbid symptoms and confounders. Attention should be paid to the suicidal risk associated with these symptoms, particularly when they persist or increase in the longitudinal follow-up.


Medically Unexplained Symptoms , Child , Adolescent , Humans , Female , Cohort Studies , Suicidal Ideation , Behavioral Symptoms , Antisocial Personality Disorder
14.
Mol Psychiatry ; 2024 Jan 05.
Article En | MEDLINE | ID: mdl-38182806

Previous studies reported decreased glutamate levels in the anterior cingulate cortex (ACC) in non-treatment-resistant schizophrenia and first-episode psychosis. However, ACC glutamatergic changes in subjects at high-risk for psychosis, and the effects of commonly experienced environmental emotional/social stressors on glutamatergic function in adolescents remain unclear. In this study, adolescents recruited from the general population underwent proton magnetic resonance spectroscopy (MRS) of the pregenual ACC using a 3-Tesla scanner. We explored longitudinal data on the association of combined glutamate-glutamine (Glx) levels, measured by MRS, with subclinical psychotic experiences. Moreover, we investigated associations of bullying victimization, a risk factor for subclinical psychotic experiences, and help-seeking intentions, a coping strategy against stressors including bullying victimization, with Glx levels. Finally, path analyses were conducted to explore multivariate associations. For a contrast analysis, gamma-aminobutyric acid plus macromolecule (GABA+) levels were also analyzed. Negative associations were found between Glx levels and subclinical psychotic experiences at both Times 1 (n = 219, mean age 11.5 y) and 2 (n = 211, mean age 13.6 y), as well as for over-time changes (n = 157, mean interval 2.0 y). Moreover, effects of bullying victimization and bullying victimization × help-seeking intention interaction effects on Glx levels were found (n = 156). Specifically, bullying victimization decreased Glx levels, whereas help-seeking intention increased Glx levels only in bullied adolescents. Finally, associations among bullying victimization, help-seeking intention, Glx levels, and subclinical psychotic experiences were revealed. GABA+ analysis revealed no significant results. This is the first adolescent study to reveal longitudinal trajectories of the association between glutamatergic function and subclinical psychotic experiences and to elucidate the effect of commonly experienced environmental emotional/social stressors on glutamatergic function. Our findings may deepen the understanding of how environmental emotional/social stressors induce impaired glutamatergic neurotransmission that could be the underpinning of liability for psychotic experiences in early adolescence.

15.
Eur Child Adolesc Psychiatry ; 33(2): 561-568, 2024 Feb.
Article En | MEDLINE | ID: mdl-36882639

Previous studies have reported that dissociative symptoms (DIS) are associated with self-harm (SH) in adolescents. However, most of these studies were cross-sectional, which limits the understanding of their theoretical relationship. We aimed to investigate the longitudinal relationship between DIS and SH in the general adolescent population. We used data from the Tokyo Teen Cohort study (N = 3007). DIS and SH were assessed at times 1 and 2 (T1 and T2) (12 years of age and 14 years of age, respectively). DIS were assessed using the parent-report Child Behavior Checklist (CBCL), and severe dissociative symptoms (SDIS) were defined as a score above the top 10th percentile. The experience of SH within 1 year was assessed by a self-report questionnaire. The longitudinal relationship between DIS and SH was examined using regression analyses. Using logistic regression analyses, we further investigated the risk for SH at T2 due to persistent SDIS and vice versa. DIS at T1 tended to predict SH at T2 (odds ratio (OR) 1.11, 95% CI 0.99 to 1.25, p = 0.08), while SH at T1 did not predict DIS at T2 (B = - 0.03, 95% CI - 0.26 to 0.20, p = 0.81). Compared with adolescents without SDIS, those with persistent SDIS had an increased risk of SH at T2 (OR 2.61, 95% CI 1.28 to 5.33, p = 0.01). DIS tended to predict future SH, but SH did not predict future DIS. DIS may be a target to prevent SH in adolescents. Intensive attention should be given to adolescents with SDIS due to their increased risk of SH.


Self-Injurious Behavior , Adolescent , Humans , Cohort Studies , Dissociative Disorders/epidemiology , Dissociative Disorders/diagnosis , Self Report , Self-Injurious Behavior/epidemiology , Surveys and Questionnaires
16.
Psychol Med ; 54(5): 921-930, 2024 Apr.
Article En | MEDLINE | ID: mdl-37721216

BACKGROUND: Little information is available on the association between gender nonconformity during adolescence and subsequent mental health. While the distress related to gender nonconformity may be socially produced rather than attributed to individual-level factors, further research is needed to better understand the role of psychosocial factors in this context. METHOD: We analyzed data from the Tokyo Teen Cohort, obtained through random sampling of adolescents born between 2002 and 2004. We used inverse probability weighting to examine the association of gender nonconformity at ages 12 and 14 as a time-varying variable with subsequent mental health at age 16, while accounting for time-fixed and time-varying confounders. Furthermore, we used a weighting approach to investigate the mediating role of modifiable psychosocial factors in this association, addressing exposure-mediator and mediator-mediator interactions. RESULTS: A total of 3171 participants were analyzed. Persistent gender nonconforming behavior at ages 12 and 14 was associated with subsequent depression (ß = 2.02, 95% confidence interval [CI] 0.85 to 3.19) and psychotic experiences (ß = 0.33, 95% CI 0.14 to 0.52) at age 16. The results remained robust in sensitivity analyses. Approximately 30% of the association between gender nonconformity and depression was consistently mediated by a set of psychosocial factors, namely loneliness, bullying victimization, and relationships with mother, father, and friends. CONCLUSIONS: Persistent gender nonconformity during adolescence is associated with subsequent mental health. Psychosocial factors play a vital mediating role in this association, highlighting the essential need for social intervention and change to reduce stigmatization and ameliorate mental health challenges.


Crime Victims , Mental Health , Humans , Adolescent , Cohort Studies , Gender Identity , Crime Victims/psychology
17.
J Gastroenterol ; 59(2): 109-118, 2024 02.
Article En | MEDLINE | ID: mdl-38097780

BACKGROUND: The association between thiopurine use and testicular reproductive functions remains unclear. In this study, we investigated whether thiopurines affect testicular functions based on the NUDT15 genotypes using Nudt15R138C knock-in mice. METHODS: The male Nudt15R138C knock-in mice (9-12 weeks) were treated with mercaptopurine (MP: 0.5 mg/kg/day) for 4 or 12 weeks. To examine reversibility, some mice were maintained for a further 12 weeks under MP-free condition. RESULTS: After MP treatment for 4 weeks, Nudt15R138C/R138C mice exhibited a significant reduction of testis weight compared to Nudt15+/+ mice and Nudt15+/R138C mice. The epithelial height and diameter of seminiferous tubules were significantly reduced in Nudt15R138C/R138C mice compared to Nudt15+/+ and Nudt15+/R138C mice. Apoptotic cells were significantly increased in Nudt15R138C/R138C mice, and most of apoptotic cells were spermatogonia. There were no significant changes in sperm counts and sperm morphology in MP-treated Nudt15R138C/R138C mice after 4-week MP treatment. On the other hand, after MP treatment for 12 weeks, the Nudt15+/R138C mice, but not Nudt15+/+ mice, exhibited a significant reduction in the testis weight and atrophic changes of seminiferous tubules, but these changes disappeared after 12-week rearing under MP-free condition. Despite a significant increase in abnormal sperm rate, there were no changes in the ability to conceive. No differences in serum levels of follicle-stimulating hormone or testosterone were observed between MP-treated Nudt15+/R138C and Nudt15+/+ mice after 12-week MP treatment. CONCLUSIONS: Thiopurines exert harmful effects on testicular reproductive function according to host NUDT15 genotypes.


Purines , Pyrophosphatases , Semen , Sulfhydryl Compounds , Male , Mice , Animals , Pyrophosphatases/genetics , Mercaptopurine , Spermatogenesis
18.
DEN Open ; 4(1): e326, 2024 Apr.
Article En | MEDLINE | ID: mdl-38155929

A 70-year-old man was diagnosed with early gastric cancer with ulcerative findings. Endoscopic submucosal dissection as an absolute indication was performed, and en bloc resection was achieved. Pathological examination revealed a well-differentiated adenocarcinoma, 3 × 2 mm in size, intramucosal, with an ulcerative scar, no lymphovascular invasion, and a tumor-free margin. We diagnosed it as a curative resection and followed up with annual endoscopy. Sixteen months after endoscopic submucosal dissection, esophagogastroduodenoscopy revealed a singular ulcer scar; however, serum carcinoembryonic antigen level was elevated. Computed tomography scan showed wall thickening of the gastric antrum and an irregular mass on the dorsal side. Additionally, 18F-fluorodeoxyglucose positron emission tomography/coomputed tomography showed 18F-fluorodeoxyglucose uptake in the gastric antrum, irregular mass, and liver. Endoscopic ultrasonography revealed an internally heterogeneous mass in the gastric antrum region extending from the submucosal layer to the muscularis propria layer. Using an endoscopic ultrasonography-guided fine needle biopsy with a 22-gauge needle for the mass, we diagnosed local recurrence with the submucosal tumor-like appearance, lymph node metastasis, and liver metastases. Unfortunately, the patient died of gastric cancer 3 months after the diagnosis. Here, we report a rare case of local recurrence in the submucosal layer, lymph node metastasis, and liver metastases 16 months after curative endoscopic submucosal dissection.

19.
Math Biosci Eng ; 20(12): 21499-21513, 2023 Dec 05.
Article En | MEDLINE | ID: mdl-38124607

Mobility restrictions were widely practiced to reduce contact with others and prevent the spatial spread of COVID-19 infection. Using inter-prefectural mobility and epidemiological data, a statistical model was devised to predict the number of imported cases in each Japanese prefecture. The number of imported cases crossing prefectural borders in 2020 was predicted using inter-prefectural mobility rates based on mobile phone data and prevalence estimates in the origin prefectures. The simplistic model was quantified using surveillance data of cases with an inter-prefectural travel history. Subsequently, simulations were carried out to understand how imported cases vary with the mobility rate and prevalence at the origin. Overall, the predicted number of imported cases qualitatively captured the observed number of imported cases over time. Although Hokkaido and Okinawa are the northernmost and the southernmost prefectures, respectively, they were sensitive to differing prevalence rate in Tokyo and Osaka and the mobility rate. Additionally, other prefectures were sensitive to mobility change, assuming that an increment in the mobility rate was seen in all prefectures. Our findings indicate the need to account for the weight of an inter-prefectural mobility network when implementing countermeasures to restrict human movement. If the mobility rates were maintained lower than the observed rates, then the number of imported cases could have been maintained at substantially lower levels than the observed, thus potentially preventing the unnecessary spatial spread of COVID-19 in late 2020.


COVID-19 , Humans , COVID-19/epidemiology , Japan/epidemiology , Models, Statistical , Travel , Prevalence
20.
Article En | MEDLINE | ID: mdl-37953733

BACKGROUND: Understanding the etiology of psychosis is essential to the development of preventive interventions. The COVID-19 pandemic provides a rare natural experiment that can expand our understanding of the role of social factors in the trajectories and etiology of psychosis across adolescence, particularly in Tokyo where the prevalence of actual COVID-19 infection remained low. We hypothesized that the likelihood of self-reporting psychotic experiences (PEs) would increase following the onset of the COVID-19 pandemic. METHODS: The Tokyo Teen Cohort (TTC) is a prospective cohort study of adolescents in the general population of the Tokyo metropolitan area, followed from age 10 to 16 years. We used multi-level linear regression models to test the associations between the phase of the COVID-19 pandemic and self-reported PEs. RESULTS: Among 1935 adolescents included in the analysis, a rapid increase in PEs occurred at the onset of the COVID-19 pandemic, following approximately 6 years of steady decline across prior waves. This association was more pronounced for boys compared to girls. This increase became more pronounced as the pandemic moved into later phases, defined based on contemporaneous sociopolitical changes in Tokyo (i.e. changes to school closure, social distancing guidelines, and the state of emergency status). CONCLUSIONS: The steady decline in PEs across adolescence was halted and reversed concurrent with the COVID-19 pandemic onset, despite very low rates of COVID-19 infection. This implicates COVID-19 related socioenvironmental factors as contributory etiological factors in the development of PEs in this adolescent cohort.

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