Anatomical approach to suppression of para-Hisian ventricular arrhythmias with changes in QRS morphology following ablation at the earliest activation site.

BACKGROUND: The anatomical approach for the management of para-Hisian ventricular arrhythmias (VAs) with QRS morphological changes following catheter ablation (CA) has not been well investigated. OBJECTIVES: We aimed to evaluate the electrocardiographic and electrophysiological findings and ablation outcomes of para-Hisian VAs with QRS morphological changes following CA. METHODS: Among 30 patients who underwent CA for para-Hisian VAs at four institutions, 10 (33%) had QRS morphological changes following ablation. All 10 patients underwent an anatomical approach, targeting the site anatomically opposite to the site where the QRS morphology had been changed by ablation. We investigated the safety and efficacy of the anatomical approach. RESULTS: Among the 10 patients evaluated, the approach was switched from the right ventricular septum to the left ventricular septum/aortic root in seven (RL group), whereas three underwent left-to-right switches (LR group). Following CA, the precordial transition zone tended to be earlier in the RL group and later in the LR group. In the RL group, successful VA suppression was achieved despite suboptimal pace map concordance from the left side or a relatively delayed earliest activation time. Of the 10 patients who underwent an anatomical approach, eight had procedural success, and ablation was discontinued in one due to the risk of atrioventricular block. CONCLUSIONS: The anatomical approach showed promising results regarding safety and efficacy. Therefore, it should be considered when QRS morphological changes are observed during or after CA of para-Hisian VAs.

[Decreased family caregiver satisfaction with diabetes treatment of elderly patients is associated with patient depressive symptoms].

OBJECTIVE: To examine the relationship between the dissatisfaction of family caregivers with diabetes treatment and depressive symptoms among the elderly. METHODS: The subjects were diabetic patients of 65 years of age or older and their family caregivers, who were outpatients at Ise Red Cross Hospital. The Japanese version of the Patient Health Questionnaire 9, which consists of nine items, was used to measure depressive symptoms. The Japanese version of the Treatment Satisfaction Scale for Caregivers of Dependent Diabetic Patients (STCD2-J) was used to measure the satisfaction of family caregivers with diabetes treatment. A logistic regression analysis was performed using depressive symptoms as dependent variable, satisfaction of the family caregiver with diabetes treatment as an explanatory variable, and adjustment variables. RESULTS: In total, 272 patients were included in the analysis. Taking the quintiles of STCD2-J scores, the adjusted odds ratios for patient depressive symptoms in Q2 (27-29), Q3 (24-26), Q4 (22-23) and Q5 (14-21) based on Q1 (30-36) (the group with the highest STCD2-J scores) were 2.44 (95% confidence interval (CI), 0.69-8.61; P=0.163), 3.08 (95% CI, 0.93-10.12; P=0.063), 2.69 (95% CI, 0.68-10.65; P=0.156), and 4.54 (95% CI, 1.44-14.32; P=0.010), respectively. CONCLUSION: We found that family caregivers' decreased satisfaction with diabetes treatment was associated with depressive symptoms. It is important to alert primary care physicians about depressive symptoms when they see family caregivers who show decreased satisfaction with diabetes treatment.

Regional random mutagenesis driven by multiple sgRNAs and diverse on-target genome editing events to identify functionally important elements in non-coding regions.

Functional regions that regulate biological phenomena are interspersed throughout eukaryotic genomes. The most definitive approach for identifying such regions is to confirm the phenotype of cells or organisms in which specific regions have been mutated or removed from the genome. This approach is invaluable for the functional analysis of genes with a defined functional element, the protein-coding sequence. By contrast, no functional analysis platforms have been established for the study of cis-elements or microRNA cluster regions consisting of multiple microRNAs with functional overlap. Whole-genome mutagenesis approaches, such as via N-ethyl-N-nitrosourea and gene trapping, have greatly contributed to elucidating the function of coding genes. These methods almost never induce deletions of genomic regions or multiple mutations within a narrow region. In other words, cis-elements and microRNA clusters cannot be effectively targeted in such a manner. Herein, we established a novel region-specific random mutagenesis method named CRISPR- and transposase-based regional mutagenesis (CTRL-mutagenesis). We demonstrate that CTRL-mutagenesis randomly induces diverse mutations within target regions in murine embryonic stem cells. Comparative analysis of mutants harbouring subtly different mutations within the same region would facilitate the further study of cis-element and microRNA clusters.

A Single Atrial Extrastimulation Resetting His Bundle During Supraventricular Tachycardia to Differentiate Atrial Tachycardia.

BACKGROUND: Catheter ablation is the curative treatment for paroxysmal supraventricular tachycardia (SVT). However, atrial tachycardia (AT) diagnosis is often challenging, especially when SVT is terminated by pacing. OBJECTIVES: This study sought to develop a novel method for AT diagnosis. METHODS: A total of 147 SVTs including 28 ATs, 87 atrioventricular nodal re-entrant tachycardias, and 32 orthodromic reciprocating tachycardias were prospectively studied. Single atrial extrastimulation was performed at the proximal coronary sinus from a coupling interval 20 milliseconds shorter than the tachycardia cycle length and gradually decreased until the His bundle (HB) was first reset and further until the SVT was terminated. The response of the SVT during the first HB resetting and the termination pattern were examined. RESULTS: In 27 of 28 ATs, tachycardia was unaffected when HB resetting whereas, in atrioventricular nodal re-entrant tachycardias or orthodromic reciprocating tachycardias (non-AT), tachycardia was simultaneously reset when HB resetting or was terminated with an atrio-Hisian block. When the coupling interval was further shortened for cases in which tachycardia persisted, all 33 SVTs with tachycardia termination with atrio-Hisian block were non-ATs, whereas 5 ATs and 7 non-ATs were terminated with Hisian-atrial block. The sensitivity, specificity, and positive and negative predictive values of the pattern of tachycardia that was unaffected when HB resetting for AT diagnosis were 96%, 100%, 100%, and 99%, respectively. Those of the pattern of tachycardia termination with atrio-Hisian block for non-AT diagnosis were 92%, 100%, 100%, and 42%, respectively. CONCLUSIONS: Single atrial extrastimulation from the proximal coronary sinus during tachycardia was useful and effective for AT diagnosis.

Development of the "Social Participation Barriers in Patients With Diabetes" Questionnaire for Older Patients With Diabetes and Evaluation of its Reliability and Validity.

Objectives: To develop a questionnaire for evaluating the factors hindering social participation in older patients with diabetes (the Social Participation Barriers in Patients with Diabetes [SPBD] questionnaire) and assess its reliability and validity. Materials and Methods: This is a cross-sectional study. This study included outpatients aged ≥60 years having diabetes and undergoing treatment at the Ise Redcross Hospital. A draft questionnaire consisting of 20 questions was developed with reference to previous studies. Logistic regression analysis was conducted, and Cronbach's alpha coefficient was calculated. Exploratory factor analysis was conducted to test construct validity. Pearson's correlation coefficients between SPBD scores and frailty scores, social frailty scores and frequency of outings were calculated. Results: Overall, 353 patients were included in the analysis. After questions without an association in the logistic regression analysis were excluded and results of the exploratory factor analyses were obtained, 10 questions were excluded. As a result, we created a 10-item SPBD questionnaire. Cronbach's alpha coefficient was .87. The SPBD score was significantly associated with frequency of going out, and frailty. Conclusions: We created an SPBD questionnaire to assess barriers to social participation in older adult patients with diabetes. This study indicated the validity and reliability of the questionnaire.

Deletion of Exoc7, but not Exoc3, in male germ cells causes severe spermatogenesis failure with spermatocyte aggregation in mice.

Vesicular trafficking is essential for the transport of intracellularly produced functional molecules to the plasma membrane and extracellular space. The exocyst complex, composed of eight different proteins, is an important functional machinery for "tethering" in vesicular trafficking. Functional studies have been conducted in laboratory mice to identify the mechanisms by which the deletion of each exocyst factor affect various biological phenomena. Interestingly, each exocyst factor-deficient mutant exhibits a different phenotype. This discrepancy may be due to the function of the exocyst factor beyond its role as a component of the exocyst complex. Male germline-specific conditional knockout (cKO) mice of the Exoc1 gene, which encodes one of the exocyst factors EXOC1 (SEC3), exhibit severe spermatogenesis defects; however, whether this abnormality also occurs in mutants lacking other exocyst factors remains unknown. In this study, we found that exocyst factor EXOC3 (SEC6) was not required for spermatogenesis, but depletion of EXOC7 (EXO70) led to severe spermatogenesis defects. In addition to being a component of the exocyst complex, EXOC1 has other functions. Notably, male germ cell-specific Exoc7 cKO and Exoc1 cKO mice exhibited phenotypic similarities, suggesting the importance of the exocyst complex for spermatogenesis. The results of this study will contribute to further understanding of spermatogenesis from the aspect of vesicular trafficking.

Validation of dual atrioventricular nodal physiology in dual atrioventricular nodal non-reentrant tachycardia via adenosine triphosphate injection during atrial pacing: A novel insight into the role of leftward inferior extension.

INTRODUCTION: Dual atrioventricular nodal non-reentrant tachycardia (DAVNNT) is a rare and challenging-to-diagnose arrhythmia, without previous reports associating it with a leftward inferior extension (LIE). METHODS: Diagnosis was made using adenosine triphosphate (ATP) injection during atrial pacing in a suspected DAVNNT patient. RESULTS: Ablation of the rightward inferior extension was unsuccessful in eliminating DAVNNT; however, subsequent ablation of the LIE successfully eradicated the arrhythmia. CONCLUSION: This unique case, marked by the first instance of DAVNNT caused by LIE, diagnosed through ATP injection, underscores the utility of this diagnostic approach and broadens the spectrum of our understanding and management of this condition.

Frequency and Overlap of Cachexia, Malnutrition, and Sarcopenia in Elderly Patients with Diabetes Mellitus: A Study Using AWGC, GLIM, and AWGS2019.

This study aimed to estimate the frequency and overlap of cachexia, malnutrition, and sarcopenia in elderly patients with diabetes mellitus. Patients who were aged at least 65 years, had diabetes mellitus, and were regularly visiting the Ise Red Cross Hospital on an outpatient basis were included. The patients were assessed to determine whether they had cachexia, malnutrition, and sarcopenia according to the Asian Working Group for Cachexia criteria, the Global Leadership Initiative on Malnutrition criteria, and the Asian Working Group for Sarcopenia 2019 criteria. A total of 510 patients (310 men and 200 women) were analyzed in this study. Sarcopenia, cachexia, and malnutrition were found in 84 patients (16.4%), 40 patients (7.8%) (17.8% among patients with chronic diseases), and 110 patients (21.5%), respectively. Among patients with sarcopenia, the frequencies of cachexia and malnutrition were 30% and 71.4%, respectively. Among patients with cachexia, the frequencies of sarcopenia and malnutrition were 65% and 90%, respectively, and among those with malnutrition, the frequencies of sarcopenia and cachexia were 54% and 32.7%, respectively. The overlap among cachexia, malnutrition, and sarcopenia appears to be an important factor to be considered in the treatment of elderly patients with diabetes mellitus.

How to perform effective cryoballooon ablation of the left atrial roof: Considerations after experiencing more than 1000 cases.

INTRODUCTION: Cryoballoon ablation (CBA) of the left atrial (LA) roof in addition to a pulmonary vein isolation has been expected to improve the clinical outcomes post-atrial fibrillation (AF) ablation. We demonstrated the characteristics and efficacy of CBA of the LA roof through our experience with a large volume of procedures. METHODS: Among 1036 AF ablation procedures with CBA of the LA roof, 834 patients who underwent a de novo ablation were analyzed. RESULTS: Complete LA roof line conduction block was obtained in 767 patients (92.0%) solely by CBA (Group A). Compared with the other patients (Group B), the mean nadir balloon temperature during CBA of the LA roof (-44.5 ± 5.6°C for Group A vs. -40.5 ± 7.5°C for Group B, p < .01) and number of cryoballoon applications during the LA roof ablation with a circular mapping catheter located in the left superior pulmonary vein (1.3 ± 0.8 for Group A vs. 1.6 ± 1.0 for Group B, p = .02) were significantly lower in Group A. A multivariate analysis revealed that those were predictors of a complete LA roof conduction block after only CBA. The 1-year Kaplan-Meier atrial arrhythmia free rate estimates were 80.6% for Group A and 59.0% for Group B (p < .01). CONCLUSION: Complete LA roof line conduction block could be obtained with a cryoballoon without touch-up ablation in most cases. The LA roof CBA with a circular mapping catheter located in the right superior pulmonary vein was preferable to obtaining complete LA roof conduction block, which was important with regard to the clinical outcomes.

[A low phase angle is a factor independently associated with falls in elderly diabetic patients].

OBJECTIVE: To examine the relationship between a low phase angle (PA) and falls in elderly diabetic patients. METHODS: The subjects were diabetic patients ≥65 years old who were outpatients at Ise Red Cross Hospital. Patients were asked about their fall history using a self-administered questionnaire. The PA was measured by the multi-frequency bioelectrical impedance method, and the subjects were classified into two groups: the first quartile with the smallest PA (T1 group) and the second and third quartiles (T2/3 groups). A logistic regression analysis with falls as the dependent variable, PA as the explanatory variable, and adjustment variables was used to calculate the odds ratio of the PA for falls. RESULTS: A total of 255 patients were included in the analysis of this study. Of these, 33.3% were in the T1 group, 66.7% were in the T2/3 group, and 28.2% had fallen. The unadjusted and adjusted odds ratios for falls in the PA were 2.92 (95% confidence interval [CI], 1.31-4.07; P=0.004) and 2.34 (95% CI, 1.07-5.09; P=0.031), respectively. CONCLUSION: A low PA was associated with falls in elderly diabetic patients.

[Loneliness is associated with the risk of low nutrition in elderly diabetic patients].

OBJECTIVE: The purpose of this study was to examine the relationship between loneliness and malnutrition in elderly diabetic patients. METHODS: The subjects were diabetic patients ≥65 years old who were outpatients at Ise Red Cross Hospital. The nutritional status was assessed using the Mini Nutritional Assessment Short Form (MNA-SF), and patients were defined as being undernourished if their total score was <11 points. Loneliness was assessed using the Japanese version of the short form of the loneliness scale, a self-administered questionnaire, and a total score of ≥6 was considered to indicate loneliness. A logistic regression analysis was used to calculate the adjusted odds ratio of loneliness to undernutrition, with the dependent variable being undernutrition, the explanatory variable being loneliness, and the adjustment variable being loneliness. RESULTS: A total of 163 patients were included in the analysis of this study. Of these, 25.8% were lonely, and 33.7% were undernourished. The unadjusted and adjusted odds ratios of loneliness to undernutrition were 2.55 (95% confidence interval [CI], 1.24-5.27; P=0.011) and 3.81 (95% CI, 1.27-11.39; P=0.017), respectively. CONCLUSION: Loneliness is associated with a low nutritional status in elderly diabetic patients. It is important to alert diabetic patients with loneliness to their low nutritional status when they are diagnosed.

Loss of CtBP2 may be a mechanistic link between metabolic derangements and progressive impairment of pancreatic ß cell function.

The adaptive increase in insulin secretion in early stages of obesity serves as a safeguard mechanism to maintain glucose homeostasis that cannot be sustained, and the eventual decompensation of ß cells is a key event in the pathogenesis of diabetes. Here we describe a crucial system orchestrated by a transcriptional cofactor CtBP2. In cultured ß cells, insulin gene expression is coactivated by CtBP2. Global genomic mapping of CtBP2 binding sites identifies a key interaction between CtBP2 and NEUROD1 through which CtBP2 decompacts chromatin in the insulin gene promoter. CtBP2 expression is diminished in pancreatic islets in multiple mouse models of obesity, as well as human obesity. Pancreatic ß cell-specific CtBP2-deficient mice manifest glucose intolerance with impaired insulin secretion. Our transcriptome analysis highlights an essential role of CtBP2 in the maintenance of ß cell integrity. This system provides clues to the molecular basis in obesity and may be targetable to develop therapeutic approaches.

["Koshi-heso" (waist-umbilicus) test: A novel screening method for visceral fatty obesity].

OBJECTIVE: To evaluate the screening performance and validity of the "Koshi-heso" (waist-umbilicus) test for visceral fatty obesity in elderly diabetic patients. METHODS: Subjects were diabetic patients ≥65 years old visiting our outpatient clinic. As a "Koshi-heso" test, the distance between the umbilicus and the superior border of the iliac crest (waist) was measured with the patient's own finger. When the index finger reached the umbilicus and there was a gap between the finger and the abdominal wall, the patient was classified as "smaller"; when the index finger reached the umbilicus and there was no gap between the finger and the abdominal wall, the patient was classified as "just fit"; and when the index finger did not reach the umbilicus, the patient was classified as "bigger". Abdominal circumference was used to assess visceral fat obesity, with a cut-off value of ≥85 cm for men and ≥90 cm for women. Visceral fat mass and body fat percentage were evaluated by the multi-frequency bioelectrical impedance method. The sensitivity and specificity of the waist-umbilical test for visceral fat obesity were calculated. Pearson's correlation coefficients between the "Koshi-heso" test and visceral fat mass and body fat percentage were calculated to evaluate the validity of the test. Furthermore, the association between the "Koshi-heso" test and risk factors for vascular disease, microvascular complications and cardiovascular disease was assessed by a logistic analysis. RESULTS: A total of 221 patients were included in the analysis population of the study. The cut-off values of "just fit" in men (sensitivity 0.96, specificity 0.62) and "bigger" in women (sensitivity 0.76, specificity 0.78) were optimal. Furthermore, the "Koshi-heso" test was significantly correlated with abdominal visceral fat mass and body fat percentage as well as with vascular disease risk factors and microvascular complications. CONCLUSION: The "Koshi-heso" test was able to be used as a screening method for visceral fatty obesity in elderly diabetic patients.

[A study of the frequency of cachexia and its associated factors in elderly patients with diabetes mellitus].

OBJECTIVE: To investigate the frequency of cachexia and its associated factors in elderly diabetic patients. METHODS: The subjects were diabetic patients ≥65 years old attending the outpatient diabetes clinic of Ise Red Cross Hospital. Cachexia was evaluated as having three or more of the following: (1) muscle weakness, (2) fatigue, (3) anorexia, (4) decreased lean body mass, and (5) biochemical abnormalities. A logistic regression analysis was used to identify factors associated with cachexia, with the dependent variable as cachexia and explanatory variables as various variables (basic attributes, glucose-related parameters, comorbidities, and treatment). RESULTS: A total of 404 patients (233 males and 171 females) were included in the study. Twenty-two (9.4%) and twenty-two (12.8%) male and female patients, respectively, had cachexia. A logistic regression analysis showed that the HbA1c value (odds ratio [OR], 0.26,95% confidence interval [CI], 0.08-0.81; P=0.021) and cognitive and functional decline (OR, 11.81, 95% CI, 1.81-76.95; P = 0.010) were factors associated with cachexia. In women, type 1 diabetes (OR, 12.39, 95% CI, 2.33-65.87; P=0.003), the HbA1c value (OR, 1.71, 95% CI, 1.07-2.74; P=0.024), and insulin usage (OR, 0.14, 95% CI, 0.02-0.71; P=0.018) were cachexia-related factors. CONCLUSIONS: The frequency of cachexia in elderly diabetic patients and its associated factors were identified. It is important to increase awareness of the risk of cachexia in elderly diabetic patients with poor glycemic control, cognitive and functional decline, type 1 diabetes mellitus, and insulin non-use.

Incidence of sarcopenic obesity in older patients with diabetes and association between sarcopenic obesity and higher-level functional capacity: evaluation based on a consensus statement.

We used a consensus statement to diagnose sarcopenic obesity, evaluated incidence of sarcopenic obesity in older patients with diabetes, and examined whether sarcopenic obesity was associated with their higher-level functional capacity. Outpatients with diabetes (age, ≥65 years) undergoing treatment at Ise Red Cross Hospital were included. The Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC)-a self-administered questionnaire-was used to assess their higher-level functional capacity. Sarcopenic obesity was evaluated based on the consensus statement diagnostic criteria-i.e., presence or absence of decreased skeletal muscle mass was evaluated based on appendicular skeletal muscle mass/body weight and obesity was assessed based on body fat mass percentage. To calculate the adjusted ß coefficient of sarcopenic obesity for higher-level functional capacity, multiple regression analyses were performed using TMIG-IC scores as the dependent variable and four categories (non-sarcopenia/non-obesity was used as a reference) that included sarcopenia and obesity as the predictor and moderator variables. Among the 310 patients included, the sarcopenic obesity incidence was 13.1% and 14.2% in men and women, respectively. When the non-sarcopenia/non-obesity group was used as a reference, the adjusted ß coefficient of sarcopenic obesity for scores of the TMIG-IC was -2.09 (p = 0.014) in men. However, the women showed no relationship between sarcopenic obesity and TMIG-IC scores. In older men with diabetes, sarcopenic obesity was associated with a decline in higher-level functional capacity.

Retrograde fast pathway cryoablation inside the coronary sinus for slow-fast atrioventricular nodal reentrant tachycardia in a patient with persistent left superior vena cava.

INTRODUCTION: Persistent left superior vena cava (PLSVC) is accompanied by enlarged coronary sinus (CS) and deformation of the triangle of Koch. This makes anatomical evaluation of the atrioventricular (AV) nodal pathways difficult. METHODS: We attempted cryoablation of retrograde fast pathway located in the enlarged CS roof of PLSVC for slow-fast AV nodal reentrant tachycardia (AVNRT) induced by inadvertent antegrade fast pathway elimination during ablation of left atrial tachycardia. RESULTS: Slow-fast AVNRT was successfully eliminated without AV block progression. CONCLUSIONS: This is the first case of successful retrograde fast pathway ablation of the CS ostial roof for slow-fast AVNRT with PLSVC.

[Loneliness is associated with a reduced higher-level-function capacity in older diabetic patients].

OBJECTIVE: The present study examined the relationship between loneliness and higher-level functions in elderly diabetic patients. METHODS: The subjects were diabetic patients ≥65 years old who were outpatients at Ise Red Cross Hospital. The Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC), a self-administered questionnaire, was used to assess higher-level functions. To evaluate loneliness, we used a shortened version of the Japanese version of the loneliness scale, a self-administered questionnaire. A multiple regression analysis with TMIG-IC scores as the dependent variable, loneliness as the explanatory variable, and adjustment variables was used to calculate the adjusted partial regression coefficients of loneliness on higher-level functions. RESULTS: One hundred and seventy patients were included in the present analysis. Ninety-one patients (53.5%) had loneliness, and the mean TMIG-IC score was 11.3. The unadjusted and adjusted partial regression coefficients of loneliness on higher-level functions were -1.61 (95% confidence interval [CI], -2.31 to -0.91; < 0.001) and -0.88 (95% CI, -1.52 to -0.23; P=0.008), respectively. CONCLUSION: Loneliness in elderly diabetic patients was found to be associated with lower higher-level functions. It is important to remind patients with diabetes mellitus who have loneliness about the risk of a decline in their higher-level functions.

Regulation of neural stem cell proliferation and survival by protein arginine methyltransferase 1.

Protein arginine methyltransferase 1 (PRMT1), a major type I arginine methyltransferase in mammals, methylates histone and non-histone proteins to regulate various cellular functions, such as transcription, DNA damage response, and signal transduction. PRMT1 is highly expressed in neural stem cells (NSCs) and embryonic brains, suggesting that PRMT1 is essential for early brain development. Although our previous reports have shown that PRMT1 positively regulates oligodendrocyte development, it has not been studied whether PRMT1 regulates NSC proliferation and its survival during development. To examine the role of PRMT1 in NSC activity, we cultured NSCs prepared from embryonic mouse forebrains deficient in PRMT1 specific for NSCs and performed neurosphere assays. We found that the primary neurospheres of PRMT1-deficient NSCs were small and the number of spheres was decreased, compared to those of control NSCs. Primary neurospheres deficient in PRMT1 expressed an increased level of cleaved caspase-3, suggesting that PRMT1 deficiency-induced apoptosis. Furthermore, p53 protein was significantly accumulated in PRMT1-deficient NSCs. In parallel, p53-responsive pro-apoptotic genes including Pmaip1 and Perp were upregulated in PRMT1-deficient NSCs. p53-target p21 mRNA and its protein levels were shown to be upregulated in PRMT1-deficient NSCs. Moreover, the 5-bromo-2'-deoxyuridine (BrdU) incorporation assay showed that the loss of PRMT1 led to cell cycle defects in the embryonic NSCs. In contrast to the above in vitro observations, NSCs normally proliferated and survived in the fetal brains of NSC-specific PRMT1-deficient mice. We also found that Lama1, which encodes the laminin subunit α1, was significantly upregulated in the embryonic brains of PRMT1-deficient mice. These data implicate that extracellular factors provided by neighboring cells in the microenvironment gave a trophic support to NSCs in the PRMT1-deficient brain and recovered NSC activity to maintain brain homeostasis. Our study implies that PRMT1 plays a cell-autonomous role in the survival and proliferation of embryonic NSCs.

Social Isolation of Older Adults With Diabetes.

We aimed to conduct a scoping review of social isolation in elderly patients with diabetes and to clarify current knowledge and gaps and future challenges. A literature search was conducted using Medline, Web of Science, CINAHL, CiNii, and Ichushi, and included studies with an eligibility criterion of a survey of social isolation in elderly patients with diabetes and aged ≥60 years. Social isolation was defined as limited or non-face-to-face contact with family and community. A data extraction form describing characteristics of studies incorporated in the present review was prepared. A total of six studies met eligibility criterion (sample size, 451-3,500). Subjects' age averaged 67 years, and 42% were female. Social isolation ranged from 9% to 49%. Factors related to social isolation included vascular complications,decreased activities of daily living, death, dementia, glycemic fluctuation, disturbance of lifestyle habits, and poor self-management and -rated health. However, research on the cause and mechanism of the relationship and impact of sex-based differences was lacking. In conclusion, additional research is needed on the definition of social isolation in elderly patients with diabetes, the causal relationship with related factors and their mechanisms, and the relationship with other outcomes.