Utility of combining multiple parameters of 123I-IMP SPECT and voxel-based morphometry MRI using a multiparametric scoring system for differentiating dementia with Lewy bodies from Alzheimer's disease.

BACKGROUND: Brain magnetic resonance imaging voxel-based morphometry (VBM) and perfusion single-photon emission computed tomography (SPECT) are useful for differentiating dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). PURPOSE: To determine whether combining multiple parameters of VBM and SPECT using a multiparametric scoring system (MSS) improves diagnostic accuracy in differentiating DLB from AD. MATERIAL AND METHODS: In total, 23 patients with DLB and 57 patients with AD underwent imaging using a voxel-based specific regional analysis system for AD (VSRAD), an easy Z-score imaging system, and a Z-Graph using three-dimensional stereotactic surface projection. The cutoff values were determined using the receiver operating characteristic curve to differentiate DLB from AD for all parameters. Patients were scored 1 (DLB) or 0 (AD) for each statistically significant parameter, according to a threshold. The total score was determined for each case to obtain a cutoff value for the MSS. RESULTS: The mean Z-scores in the medial temporal lobes using the VSRAD were significantly lower in patients with DLB than in those with AD. Each Z-score of the summed Z-scores in all four segmented regions of the occipital lobes using the Z-Graph was significantly higher in patients with DLB than in those with AD. Among the five parameters, the highest accuracy was 80% for the Z-score of the summed Z-scores in the left medial occipital lobe. For the MSS, a cutoff value of four improved the diagnostic accuracy to 82%. CONCLUSION: MSS was more accurate than any single parameter of VBM or SPECT in differentiating DLB from AD.

In vivo imaging of dopamine D1 receptor and activated microglia in attention-deficit/hyperactivity disorder: a positron emission tomography study.

Alterations in the cortical dopamine system and microglial activation have been implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD), one of neurodevelopmental disorders that can be conventionally treated with a dopamine enhancer (methylphenidate) albeit unsatisfactorily. Here, we investigated the contributions of the dopamine D1 receptor (D1R) and activated microglia and their interactions to the clinical severities in ADHD individuals using positron emission tomography (PET). Twenty-four psychotropic-naïve ADHD individuals and 24 age- and sex-matched typically developing (TD) subjects underwent PET measurements with [11C]SCH23390 for the D1R and [11C](R)PK11195 for activated microglia as well as assessments of clinical symptoms and cognitive functions. The ADHD individuals showed decreased D1R in the anterior cingulate cortex (ACC) and increased activated microglia in the dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC) compared with the TD subjects. The decreased D1R in the ACC was associated with severe hyperactivity in the participants with ADHD. Microglial activation in the DLPFC were associated with deficits in processing speed and attentional ability, and that in the OFC was correlated with lower processing speed in the ADHD individuals. Furthermore, positive correlations between the D1R and activated microglia in both the DLPFC and the OFC were found to be significantly specific to the ADHD group and not to the TD group. The current findings suggest that microglial activation and the D1R reduction as well as their aberrant interactions underpin the neurophysiological mechanism of ADHD and indicate these biomolecular changes as a novel therapeutic target.

A loss-of-function variant in SUV39H2 identified in autism-spectrum disorder causes altered H3K9 trimethylation and dysregulation of protocadherin ß-cluster genes in the developing brain.

Recent evidence has documented the potential roles of histone-modifying enzymes in autism-spectrum disorder (ASD). Aberrant histone H3 lysine 9 (H3K9) dimethylation resulting from genetic variants in histone methyltransferases is known for neurodevelopmental and behavioral anomalies. However, a systematic examination of H3K9 methylation dynamics in ASD is lacking. Here we resequenced nine genes for histone methyltransferases and demethylases involved in H3K9 methylation in individuals with ASD and healthy controls using targeted next-generation sequencing. We identified a novel rare variant (A211S) in the SUV39H2, which was predicted to be deleterious. The variant showed strongly reduced histone methyltransferase activity in vitro. In silico analysis showed that the variant destabilizes the hydrophobic core and allosterically affects the enzyme activity. The Suv39h2-KO mice displayed hyperactivity and reduced behavioral flexibility in learning the tasks that required complex behavioral adaptation, which is relevant for ASD. The Suv39h2 deficit evoked an elevated expression of a subset of protocadherin ß (Pcdhb) cluster genes in the embryonic brain, which is attributable to the loss of H3K9 trimethylation (me3) at the gene promoters. Reduced H3K9me3 persisted in the cerebellum of Suv39h2-deficient mice to an adult stage. Congruently, reduced expression of SUV39H1 and SUV39H2 in the postmortem brain samples of ASD individuals was observed, underscoring the role of H3K9me3 deficiency in ASD etiology. The present study provides direct evidence for the role of SUV39H2 in ASD and suggests a molecular cascade of SUV39H2 dysfunction leading to H3K9me3 deficiency followed by an untimely, elevated expression of Pcdhb cluster genes during early neurodevelopment.

Longitudinal association between smartphone ownership and depression among schoolchildren under COVID-19 pandemic.

Under the COVID-19 pandemic, concerns regarding prolonged screen time and mental health effects in children have increased. We examined the association of depression with smartphone ownership in school children at four time points: September 2019, July 2020, December 2020, and March 2021. The analysis revealed an interaction between group and time, indicating that depressive symptoms among smartphone owners were significantly more severe than in the other group. These results were clearer for fourth-year students, pointing that smartphone possession at younger ages may be a risk factor for mental health in the new lifestyle caused by the COVID-19 pandemic.

Interleukin-1ß as a Predictor of Glucocorticoid Response in Ulcerative Colitis.

BACKGROUND/AIM: Currently, there are no established biomarkers to differentiate between glucocorticoid (GC)-resistant and GC-sensitive ulcerative colitis (UC); however, interleukin (IL)-1ß could be one such candidate biomarker. The aim of this study was to investigate whether mucosally expressed IL-1ß could predict the response to GC in patients with UC. METHODS: A total of 27 mucosal tissue samples from 10 patients with GC-resistant UC (GC-resistant group), 9 patients with GC-sensitive UC (GC-sensitive group), and 8 control patients (control group) were analyzed by qRT-PCR for the expression of IL-1ß, GC receptor α (GRα), GRß, and other inflammatory mediators. Rachmilewitz endoscopic index (REI) between the GC-resistant and GC-sensitive groups was matched to avoid any potential influence of inflammation. RESULTS: The REI did not significantly differ between the GC-resistant and GC-sensitive groups. Mucosally expressed IL-1ß levels in the GC-resistant group were significantly higher than those in the GC-sensitive group. However, there were no significant differences in the expression levels of GRα, GRß, and other inflammatory mediators between the 2 groups. We could distinguish between the GC-resistant and GC-sensitive groups with a sensitivity of 90.0% and specificity of 77.8% based on mucosally expressed IL-1ß. CONCLUSIONS: Mucosally expressed IL-1ß can be used as a predictor of GC response in patients with UC.

Atypical Sensory Processing Profiles and Their Associations With Motor Problems In Preschoolers With Developmental Coordination Disorder.

The aims of this study were to identify sensory processing profiles specific to preschoolers with DCD in a community sample and examine the association of sensory processing problems with motor coordination difficulties in these children. Sixty-three 5-year-old children with DCD and without other neurodevelopmental disorders and 106 age-matched typically developing children participated in this study. Sensory processing problems were assessed using the Sensory Profile. Our results demonstrated problems in wide sensory processing patterns (low registration, sensitivity and avoiding) and areas (auditory, vestibular, touch and oral) in children with DCD compared with typically developing children. Additionally, the association of problems in sensory processing patterns (sensitivity and avoiding) and areas (touch and auditory) with motor coordination difficulties were identified in children with DCD alone. Our findings indicate that sensory processing abnormalities may contribute to the pathophysiology of DCD, suggesting the importance of assessing sensory processing functions in children with DCD.

Secondary oxalosis induced by xylitol concurrent with lithium-induced nephrogenic diabetes insipidus: a case report.

BACKGROUND: Xylitol is an approved food additive that is widely used as a sweetener in many manufactured products. It is also used in pharmaceuticals. Secondary oxalosis resulting from high dietary oxalate has been reported. However, reported cases of oxalosis following xylitol infusion are rare. CASE PRESENTATION: A 39-year-old man with a 16-year history of organic psychiatric disorder was hospitalized for a laparoscopic cholecystectomy because of cholecystolithiasis. He had been treated with several antipsychotics and mood stabilizers, including lithium. The patient had polyuria (> 4000 mL/day) and his serum sodium levels ranged from 150 to 160 mmol/L. Urine osmolality was 141 mOsm/L, while serum arginine vasopressin level was 6.4 pg/mL. The patient was diagnosed with nephrogenic diabetes insipidus (NDI), and lithium was gradually discontinued. Postoperative urine volumes increased further to a maximum of 10,000 mL/day, and up to 10,000 mL/day of 5% xylitol was administered. The patient's consciousness level declined and serum creatinine increased to 4.74 mg/dL. This was followed by coma and metabolic acidosis. After continuous venous hemodiafiltration, serum sodium improved to the upper 140 mmol/L range and serum creatinine decreased to 1.25 mg/dL at discharge. However, polyuria and polydipsia of approximately 4000 mL/day persisted. Renal biopsy showed oxalate crystals and decreased expression of aquaporin-2 (AQP2) in the renal tubules. Urinary AQP2 was undetected. The patient was discharged on day 82 after admission. CONCLUSIONS: Our patient was diagnosed with lithium-induced NDI and secondary oxalosis induced by excess xylitol infusion. NDI became apparent perioperatively because of fasting, and an overdose of xylitol infusion led to cerebrorenal oxalosis. Our patient received a maximum xylitol dose of 500 g/day and a total dose of 2925 g. Patients receiving lithium therapy must be closely monitored during the perioperative period, and rehydration therapy using xylitol infusion should be avoided in such cases.

Association between Sleep Disturbances and Emotional/Behavioral Problems in Chinese and Japanese Preschoolers.

Objectives: Sleep disturbances are often associated with emotional/behavioral problems in young children, but whether the association differs among Asian countries remains unknown. This study aimed to investigate the association between sleep disturbances and emotional/behavioral problems in Chinese and Japanese preschoolers and to explore potential differences.Methods: Participants were 1,020 Chinese preschoolers from 10 cities and 438 Japanese preschoolers from 1 city aged 4 to 5 years. Parents filled out the Children's Sleep Habits Questionnaire (CSHQ) and the Strengths and Difficulties Questionnaire (SDQ).Results: Chinese children with sleep disturbances (defined as total CSHQ score >41) demonstrated more peer problems than children without, while there was no such difference in Japanese preschoolers. Domains of sleep disturbances associated with emotional/behavioral problems in Chinese children were sleep disordered breathing and daytime sleepiness, yet in Japanese children were sleep anxiety and night wakings. Children with a higher score of sleep anxiety showed more emotional problems in Japan, but fewer conduct problems in China.Conclusions: Sleep disturbances were associated with emotional/behavioral problems in preschoolers with differences between China and Japan, indicating subcultural differences in preschoolers' sleep within Asian countries.Abbreviations: CSHQ: Children's Sleep Habits Questionnaire; SDQ: Strengths and Difficulties Questionnaire; ANCOVA: analysis of covariance; SD: standard deviation; CI: confidence interval.

The utility of the combined use of 123I-FP-CIT SPECT and neuromelanin MRI in differentiating Parkinson's disease from other parkinsonian syndromes.

BACKGROUND: Neuromelanin magnetic resonance imaging (NmMRI) and 123I-FP-CIT dopamine transporter single photon emission computed tomography (DAT-SPECT) provide specific information that distinguishes Parkinson's disease (PD) from non-degenerative parkinsonian syndrome (NDPS). PURPOSE: To determine whether a multiparametric scoring system (MSS) could improve accuracy compared to each parameter of DAT-SPECT and NmMRI in differentiating PD from NDPS. MATERIAL AND METHODS: A total of 49 patients, including 14 with NDPS, 30 with PD, and five with atypical parkinsonian disorder (APD) underwent both NmMRI and DAT-SPECT and were evaluated. The average (Ave) and the asymmetry index (AI) were calculated in the substantia nigra compacta area (SNc-area), SNc midbrain-tegmentum contrast ratio (SNc-CR), and specific binding ratio (SBR). Cut-off values were determined, using receiver operating characteristic (ROC) analysis, for the differentiation of PD from NDPS on the statistically significant parameters. All cases were scored as either 1 (PD) or 0 (NDPS) for each parameter according to its threshold. These individual scores were totaled for each case, yielding a combined score for each case to obtain a cut-off value for the MSS. RESULTS: The Ave-SNc-area, Ave-SNc-CR, and Ave-SBR in PD were significantly lower than those in NDPS. The AI-SNc-area and AI-SBR in PD were significantly higher than those in NDPS. Of the five parameters, the highest accuracy was 93% for the Ave-SNc-area. For the MSS, a cut-off value of 3 was the accuracy of 96%. Besides, no significant difference was observed between PD and APD on all parameters. CONCLUSION: An MSS has comparable or better accuracy compared to each parameter of DAT-SPECT and NmMRI in distinguishing PD from NDPS.

Coping behaviors and depressive status in individuals with type 2 diabetes mellitus.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is associated with a high prevalence of depression, which is influenced by personality traits and coping style. However, these psychological factors have not been well studied in individuals with T2DM. The association between coping behaviors and the reported levels of depressive symptoms was examined in individuals with T2DM. METHODS: The subjects were 435 T2DM patients (mean age 63.1 ± 12.6 years). Depressive status, personality traits and coping behaviors were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D) and the Brief Scale for Coping Profile (BSCP). Lifestyle factors and glycated hemoglobin A1c (HbA1c) levels in the patients were also included in the analyses. RESULTS: Among the 435 subjects with T2DM, 130 (29.9%) exhibited possible depression, and 68 (15.6%) displayed probable depression. After adjustment for confounders, logistic and multiple regression analyses revealed that certain coping profile scores, such as Changing one's point of view, Emotional expression involving others and Avoidance and suppression, were consistently and significantly associated with the presence and severity of depression. No relationship was found between depression and HbA1c. CONCLUSION: These findings indicate that Maladaptive emotion-focused coping strategies, such as Emotional expression involving others and Avoidance and suppression, are protective factors and that Adaptive emotion-focused coping, such as Changing one's point of view, is a risk factor for depression in T2DM patients. Psychological intervention focusing on the coping profile may reduce depressive symptoms. Additional studies are needed to examine the relationships between psychological factors and depressive symptoms using a longitudinal study design.

Mucosal incision-assisted biopsy versus endoscopic ultrasound-guided fine-needle aspiration with a rapid on-site evaluation for gastric subepithelial lesions: A randomized cross-over study.

OBJECTIVES: This study aimed to compare the diagnostic yield of mucosal incision-assisted biopsy (MIAB) and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) with a rapid on-site evaluation (ROSE) for gastric subepithelial lesions (SEL) suspected of being gastrointestinal stromal tumors (GIST) with an intraluminal growth pattern. METHODS: This was a prospective randomized, cross-over multicenter study. The primary outcome was the diagnostic yield of EUS-FNA and MIAB. The secondary outcomes were the technical success rate, complication rate, procedure time and biopsy frequency. RESULTS: A total of 47 patients were randomized to the MIAB group (n = 23) and EUS-FNA group (n = 24). There was no significant difference in the diagnostic yield of MIAB and EUS-FNA (91.3% vs 70.8%, P = 0.0746). The complication rates of MIAB and EUS-FNA did not differ to a statistically significant extent. The mean procedure time in the MIAB group was significantly longer than that in the EUS-FNA group (34 vs 26 min, P = 0.0011). CONCLUSIONS: The diagnostic yield of MIAB was satisfactorily as high as EUS-FNA with ROSE for gastric SEL with an intraluminal growth pattern.

Chronic inflammatory pain induced GABAergic synaptic plasticity in the adult mouse anterior cingulate cortex.

Background Chronic pain is a persistent unpleasant sensation that produces pathological synaptic plasticity in the central nervous system. Both human imaging study and animal studies consistently demonstrate that the anterior cingulate cortex is a critical cortical area for nociceptive and chronic pain processing. Thus far, the mechanisms of excitatory synaptic transmission and plasticity have been well characterized in the anterior cingulate cortex for various models of chronic pain. By contrast, the potential contribution of inhibitory synaptic transmission in the anterior cingulate cortex, in models of chronic pain, is not fully understood. Methods Chronic inflammation was induced by complete Freund adjuvant into the adult mice left hindpaw. We performed in vitro whole-cell patch-clamp recordings from layer II/III pyramidal neurons in two to three days after the complete Freund adjuvant injection and examined if the model could cause plastic changes, including transient and tonic type A γ-aminobutyric acid (GABAA) receptor-mediated inhibitory synaptic transmission, in the anterior cingulate cortex. We analyzed miniature/spontaneous inhibitory postsynaptic currents, GABAA receptor-mediated tonic currents, and evoked inhibitory postsynaptic currents. Finally, we studied if GABAergic transmission-related proteins in the presynapse and postsynapse of the anterior cingulate cortex were altered. Results The complete Freund adjuvant model reduced the frequency of both miniature and spontaneous inhibitory postsynaptic currents compared with control group. By contrast, the average amplitude of these currents was not changed between two groups. Additionally, the complete Freund adjuvant model did not change GABAA receptor-mediated tonic currents nor the set of evoked inhibitory postsynaptic currents when compared with control group. Importantly, protein expression of vesicular GABA transporter was reduced within the presynpase of the anterior cingulate cortex in complete Freund adjuvant model. In contrast, the complete Freund adjuvant model did not change the protein levels of GABAA receptors subunits such as α1, α5, ß2, γ2, and δ. Conclusion Our results suggest that the induction phase of inflammatory pain involves spontaneous GABAergic plasticity at presynaptic terminals of the anterior cingulate cortex.

Mucosally Expressed Cytokines are Associated with the Esophageal Motility Function.

BACKGROUND AND AIM: Although basic research has shown that certain cytokines affect gastrointestinal motility, the clinical evidence is lacking. The objective of this study was to explore the association between mucosally expressed cytokines and the esophageal motility function in humans. METHODS: We enrolled a total of 57 patients with suspected esophageal motility disorders (EMDs) who underwent high-resolution manometry. RESULTS: The diagnoses of the patients were as follows: normal esophageal motility (n = 25), ineffective esophageal motility (n = 5), esophagogastric junction outflow obstruction (EGJOO; n = 10), distal esophageal spasm (n = 5), achalasia (n = 10), absent contractility (n = 1), and jackhammer esophagus (n = 1). The expression of tumor necrosis factor (TNF)-α in the esophagogastric junction (EGJ) was significantly higher in EGJOO (14.6, 14.0-15.8, n = 10) than in normal esophageal motility (13.3, 12.8-14.1, n = 25); however, there was no difference in the expression of TNF-α between achalasia (13.4, 13.0-14.1, n = 10) and normal esophageal motility (13.3, 12.8-14.1, n = 25). EGJOO was discriminated from achalasia/normal by a linear discriminant analysis (AUC = 0.917). A multivariable regression analysis revealed that interleukin (IL)-13 and IL-23A were predictive of the distal contractile integral, whereas TNF-α and IL-6 were predictive of the basal EGJ pressure. CONCLUSIONS: The esophageal motility was associated with mucosally expressed cytokines in humans; these cytokines could be useful targets for the diagnosis and treatment of EMDs.

Prevalence of pathological and maladaptive Internet use and the association with depression and health-related quality of life in Japanese elementary and junior high school-aged children.

PURPOSE: Pathological Internet use has been predominantly studied in junior high/middle school-aged or older children; data from elementary/primary school-aged children, however, are scarce. The current study aimed to examine the prevalence of problematic Internet use, including pathological and maladaptive Internet use, in elementary and junior high school-aged children and the relationships between problematic Internet use and mental health problems and health-related quality of life. METHODS: The survey was conducted among children who attend national and public elementary and junior high schools in a medium-sized city in Japan; data were received from 3845 elementary school-aged and 4364 junior high school-aged children. RESULTS: Based on the Young's Diagnostic Questionnaire score, the prevalence of pathological and maladaptive Internet use was 3.6% and 9.4% and 7.1% and 15.8% in elementary and junior high school-aged children, respectively. The prevalence of problematic Internet use, including pathological and maladaptive Internet use, consistently increased from the 4th grade to the 8th grade. In addition, the prevalence sharply increased between the 7th grade and the 8th grade. Our study revealed that children with pathological and maladaptive Internet use exhibited more severe depression and decreased health-related quality of life than those with adaptive Internet use. CONCLUSIONS: Our results demonstrated that pathological Internet use is not uncommon even in elementary school-aged children and that those with pathological and maladaptive Internet use have severe mental health problems and decreased health-related quality of life, supporting the importance of providing these children with educational and preventive interventions against problematic Internet use and associated risk factors.

[A case of non-cardiac chest pain caused by esophageal motility disorder observed on esophageal high-resolution manometry].

A 20-year-old man was referred to our hospital with dysphagia and chest pain. Heart disease was denied. No abnormality was observed in upper esophagogastroduodenoscopy and fluoroscopy;furthermore, no gastric acid-related symptoms were observed on combined esophageal multichannel intraluminal impedance and pH monitoring. Esophageal high-resolution manometry (HRM) performed by liquid swallow revealed normal peristalsis;however, HRM performed while the patient was taking solid meals showed abnormal contraction, and the patient simultaneously complained of chest pain. Therefore, we diagnosed this case as non-cardiac chest pain due to esophageal motility disorder.

Endoscopic resection using the Clutch Cutter and a detachable snare for large pedunculated colonic polyps.

Background and study aims Endoscopic snare polypectomy with prophylactic detachable snare of large pedunculated colonic polyps (PCPs) is technically demanding. To facilitate removal of such polyps, we developed endoscopic resection using the Clutch Cutter and a detachable snare (ERCCDS). This study aimed to evaluate the efficacy and safety of the procedure. Patients and methods From April 2010 to July 2015, 14 consecutive patients who had PCPs with head > 10 mm, stalk width > 5 mm, and stalk length > 10 mm were enrolled in this single-center prospective uncontrolled study. They were treated using ERCCDS by a single endoscopist. The efficacy and safety were assessed using a database prospectively formatted from the medical records. Results The Clutch Cutter was able to cut the distal side of the stalk an adequate distance from the detachable snare under good visual control. R0 resections were obtained in all lesions. There were no immediate or delayed complications. Conclusions ERCCDS appears to be a safe, easy, and technically efficient method for large PCPs, although larger studies are needed to compare ERCCDS and standard resection.

Diagnosis and Treatment Strategy of Achalasia Subtypes and Esophagogastric Junction Outflow Obstruction Based on High-Resolution Manometry.

BACKGROUND: Based on Chicago Classification version 3.0, the disorders of esophagogastric junction outflow obstruction (EGJOO) include achalasia (types I, II and III) and EGJOO. Although no curative treatments are currently available for the treatment of the disorders of EGJOO, medical treatments, endoscopic pneumatic dilation (PD), laparoscopic Heller myotomy (LHM), and per-oral endoscopic myotomy (POEM) are usually the sought-after modes of treatment. Since the etiology and pathogenesis might vary depending on the types of EGJOO disorders, treatment strategies should be considered based on those subtypes. SUMMARY: Based on the accumulated evidences, the treatment strategies of our institution are as follows: effects of medical treatments on achalasia are limited. Either PD or LHM/POEM can be considered a first-line in achalasia type I, according to the patient's wish. PD and POEM can be considered first-line in achalasia types II and III, respectively. Conversely, In EGJOO, medical treatments including drugs like acotiamide and/or diltiazem can be tested as a first-line, and PD and POEM will be considered second and third-line treatments, respectively. Key Messages: The classification of subtypes based on high-resolution manometry will help us consider which treatment option can be selected as a first-line treatment depending upon the subtypes of disorders of EGJOO. Acotiamide has the potential to cure patients with EGJOO.

Prevalence of sleep problems in Japanese preschoolers in a medium-sized city: Community-based survey using the Children's Sleep Habits Questionnaire.

Although the mean score of the Children's Sleep Habits Questionnaire (CSHQ) differs between countries, there are no normative data for the CSHQ of Japanese preschoolers based on a community sample. The aims of this study were therefore to present normative data for the CSHQ and determine the prevalence and characteristics of sleep problems in Japanese preschoolers. Parents or the primary caregiver of 482 preschoolers aged 4-5 years completed the CSHQ and the Strength and Difficulties Questionnaire. Approximately 80% of preschoolers scored above the cut-off for sleep disturbance on the CSHQ. In addition, co-sleeping was prevalent in Japanese preschoolers but the habit of co-sleeping contributed little to behavioral and emotional problems. Sleep problems appear to be prevalent in Japanese preschoolers based on the CSHQ, and could be associated with the Japanese sleep habit of co-sleeping.

Enrichment of deleterious variants of mitochondrial DNA polymerase gene (POLG1) in bipolar disorder.

AIM: Rare missense variants, which likely account for a substantial portion of the genetic 'dark matter' for a common complex disease, are challenging because the impacts of variants on disease development are difficult to substantiate. This study aimed to examine the impacts of amino acid substitution variants in the POLG1 found in bipolar disorder, as an example and proof of concept, in three different modalities of assessment: in silico predictions, in vitro biochemical assays, and clinical evaluation. We then tested whether deleterious variants in POLG1 contributed to the genetics of bipolar disorder. METHODS: We searched for variants in the POLG1 gene in 796 Japanese patients with bipolar disorder and 767 controls and comprehensively investigated all 23 identified variants in the three modalities of assessment. POLG1 encodes mitochondrial DNA polymerase and is one of the causative genes for a Mendelian-inheritance mitochondrial disease, which is occasionally accompanied by mood disorders. The healthy control data from the Tohoku Medical Megabank Organization were also employed. RESULTS: Although the frequency of carriers of deleterious variants varied from one method to another, every assessment achieved the same conclusion that deleterious POLG1 variants were significantly enriched in the variants identified in patients with bipolar disorder compared to those in controls. CONCLUSION: Together with mitochondrial dysfunction in bipolar disorder, the present results suggested deleterious POLG1 variants as a credible risk for the multifactorial disease.

Gastric neuroendocrine tumor with hypergastrinemia following type B chronic atrophic gastritis: a case report.

A man in his 60s was referred to our institution for the evaluation of a gastric neuroendocrine tumor (G-NET) located in the fornix and that measured 13mm in size. Blood test results revealed hypergastrinemia (up to 3376pg/ml). Additional tests, including esophagogastroduodenoscopy, computed tomography, and intragastric pH monitoring, indicated that hypergastrinemia was not associated with type A autoimmune gastritis or gastrinoma. The patient was positive for the immunoglobulin G antibody against Helicobacter pylori, suggesting type B chronic atrophic gastritis as the cause for the condition. This report describes a rare case of G-NET with hypergastrinemia following type B chronic atrophic gastritis. Evaluation of similar cases is necessary to determine if H. pylori-associated chronic atrophic gastritis is frequently associated with G-NET.