Global cognition and executive functions of older adults with type 1 diabetes mellitus without dementia.

AIMS/INTRODUCTION: This study aimed to characterize the global cognition and executive functions of older adults with type 1 diabetes mellitus in comparison with type 2 diabetes mellitus. MATERIALS AND METHODS: This study included 37 patients with type 1 diabetes mellitus aged ≥65 years and 37 age- and sex-matched patients with type 2 diabetes mellitus. Patients with dementia scoring <24 on the Mini-Mental State Examination were excluded. General cognition, memory, classic, and practical executive function were investigated. RESULTS: Patients with type 1 diabetes mellitus demonstrated lower psychomotor speed scores on Trail Making Tests A and B (P < 0.001, P < 0.013) than those with type 2 diabetes mellitus. The dysexecutive syndrome behavioral assessment revealed similar results in patients with types 1 and 2 diabetes mellitus. The Wechsler Memory Scale-Revised verbal episodic memory and Montreal Cognitive Assessment Japanese version were similar in terms of general cognition, but worse delayed recall subset on the latter was associated with type 2 diabetes mellitus (P = 0.038). A worse Trail Making Test-A performance was associated with type 1 diabetes mellitus and age (P < 0.004, P < 0.029). CONCLUSIONS: Executive function of psychomotor speed was worse in older outpatient adults without dementia with type 1 diabetes mellitus than in those with type 2 diabetes mellitus but with no significant differences in the comprehensive and practical behavioral assessment of dysexecutive syndrome. Patients with type 1 diabetes had more severely impaired executive function, whereas those with type 2 had greater impaired memory than executive function.

Prediction of future insulin-deficiency in glutamic acid decarboxylase autoantibody enzyme-linked immunosorbent assay-positive patients with slowly-progressive type 1 diabetes.

AIMS/INTRODUCTION: This study aimed to identify risk factors that contribute to the progression of slowly-progressive type 1 diabetes by evaluating the positive predictive value (PPV) of factors associated with the progression to an insulin-dependent state. MATERIALS AND METHODS: We selected 60 slowly-progressive type 1 diabetes patients who tested positive for glutamic acid decarboxylase autoantibodies (GADA) at diagnosis from the Japanese Type 1 Diabetes Database Study. GADA levels in these patients were concurrently measured using both radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) techniques. RESULTS: Compared with the non-progressor group (fasting C-peptide [F-CPR] levels maintained ≥0.6 ng/mL), the progressor group showed a younger age at diagnosis, lower body mass index (BMI), lower F-CPR levels and a higher prevalence of insulinoma-associated antigen-2 autoantibodies (IA-2A). The PPV of RIA-GADA increased from 56.3 to 70.0% in the high titer group (≥10 U/mL), and further increased to 76.9, 84.2, 81.0 and 75.0% when combined with specific thresholds for age at diagnosis <47 years, BMI <22.6 kg/m2 , F-CPR <1.41 ng/mL and IA-2A positivity, respectively. In contrast, the PPV of ELISA-GADA (71.8%) remained the same at 73.1% in the high titer group (≥180 U/mL), but increased to 81.8, 82.4 and 79.0% when evaluated in conjunction with age at diagnosis, BMI and F-CPR level, respectively. CONCLUSIONS: Our findings show that, unlike RIA-GADA, ELISA-GADA shows no association between GADA titers and the risk of progression to an insulin-dependent state. The PPV improves when age at diagnosis, BMI and F-CPR levels are considered in combination.

Survey of exposure to stranded dolphins in Japan to investigate an outbreak of suspected infection with highly pathogenic avian influenza (H5N1) clade 2.3.4.4(b) in humans.

Background: A highly pathogenic avian influenza (HPAI) A (H5N1) virus has been detected in domestic and wild animals worldwide. The incidence of HPAI infections in sea mammals has been increasing, as is the number of stranded marine mammals linked to H5N1 viral clade 2.3.4.4(b). In this study, we investigated a stranding event involving dolphins and human-dolphin contact, and investigated the potential risk of animal-to-human H5N1 transmission with a survey of exposure on the Tsurigasaki coast, Japan. Methods: We performed a non-random, convenient-sample-based, survey on Tsurigasaki beach where around 30 melon-headed whales were stranded on April 3, 2023. Face-to-face (n = 25) and telephone (n = 1) interviews among surfers took place on April 7 and 8. A nasal swab for quick antigen testing was taken from those who wished to be tested (n = 13), to detect infections with influenza A virus. Results: Although there was no confirmatory diagnosis of H5N1 in either humans or dolphins (while n = 3 dolphins were autopsied), we found that a large number of surfers had touched the dolphins with their bare hands while attempting to rescue them, and that some surfers were directly exposed to dolphin blood and body fluids in the ocean. Conclusions: The adequate communication of risk is required to minimize the threat of viral transmission at this particular human-animal interface. Administrative and legal responses to cross-species transmission, including guidelines via one health frameworks, a rapid evaluation process of ethical approval, and the systematic involvement of experts in infectious disease, must be urgently formulated.

Evaluating the COVID-19 vaccination program in Japan, 2021 using the counterfactual reproduction number.

Japan implemented its nationwide vaccination program against COVID-19 in 2021, immunizing more than one million people (approximately 1%) a day. However, the direct and indirect impacts of the program at the population level have yet to be fully evaluated. To assess the vaccine effectiveness during the Delta variant (B.1.617.2) epidemic in 2021, we used a renewal process model. A transmission model was fitted to the confirmed cases from 17 February to 30 November 2021. In the absence of vaccination, the cumulative numbers of infections and deaths during the study period were estimated to be 63.3 million (95% confidence interval [CI] 63.2-63.6) and 364,000 (95% CI 363-366), respectively; the actual numbers of infections and deaths were 4.7 million and 10,000, respectively. Were the vaccination implemented 14 days earlier, there could have been 54% and 48% fewer cases and deaths, respectively, than the actual numbers. We demonstrated the very high effectiveness of COVID-19 vaccination in Japan during 2021, which reduced mortality by more than 97% compared with the counterfactual scenario. The timing of expanding vaccination and vaccine recipients could be key to mitigating the disease burden of COVID-19. Rapid and proper decision making based on firm epidemiological input is vital.

Macrophage-mediated extracellular matrix remodeling controls host Staphylococcus aureus susceptibility in the skin.

Hypodermis is the predominant site of Staphylococcus aureus infections that cause cellulitis. Given the importance of macrophages in tissue remodeling, we examined the hypodermal macrophages (HDMs) and their impact on host susceptibility to infection. Bulk and single-cell transcriptomics uncovered HDM subsets with CCR2-dichotomy. HDM homeostasis required the fibroblast-derived growth factor CSF1, ablation of which abrogated HDMs from the hypodermal adventitia. Loss of CCR2- HDMs resulted in accumulation of the extracellular matrix component, hyaluronic acid (HA). HDM-mediated HA clearance required sensing by the HA receptor, LYVE-1. Cell-autonomous IGF1 was required for accessibility of AP-1 transcription factor motifs that controlled LYVE-1 expression. Remarkably, loss of HDMs or IGF1 limited Staphylococcus aureus expansion via HA and conferred protection against cellulitis. Our findings reveal a function for macrophages in the regulation of HA with an impact on infection outcomes, which may be harnessed to limit the establishment of infection in the hypodermal niche.

Nanoprocessing of Self-Suspended Monolayer Graphene and Defect Formation by Femtosecond-Laser Irradiation.

We demonstrate the femtosecond-laser processing of self-suspended monolayer graphene grown by chemical vapor deposition, resulting in multipoint drilling with holes having a diameter of <100 nm. Scanning transmission electron microscopy revealed the formation of many nanopores on the laser-irradiated graphene. Furthermore, atomic-level defects as well as nanopores were found in the graphene membrane by high-resolution transmission electron microscopy, while the overall crystal structure remained intact. Raman spectroscopy showed an increase in the defect density with an increase in the number of laser shots, suggesting that the nanopore formation triggered the creation of the <100 nm holes. The approach presented herein can offer an experimental insight into the simulation of atomic dynamics in graphene under femtosecond-laser irradiation. The thorough examination of the atomic defect formation and secondary effect of surface cleaning observed in this study would help develop engineering methods for graphene and other two-dimensional materials in the future.

Identification of a novel enhancer essential for Satb1 expression in TH2 cells and activated ILC2s.

The genome organizer, special AT-rich binding protein-1 (SATB1), functions to globally regulate gene networks during primary T cell development and plays a pivotal role in lineage specification in CD4+ helper-, CD8+ cytotoxic-, and FOXP3+ regulatory-T cell subsets. However, it remains unclear how Satb1 gene expression is controlled, particularly in effector T cell function. Here, by using a novel reporter mouse strain expressing SATB1-Venus and genome editing, we have identified a cis-regulatory enhancer, essential for maintaining Satb1 expression specifically in TH2 cells. This enhancer is occupied by STAT6 and interacts with Satb1 promoters through chromatin looping in TH2 cells. Reduction of Satb1 expression, by the lack of this enhancer, resulted in elevated IL-5 expression in TH2 cells. In addition, we found that Satb1 is induced in activated group 2 innate lymphoid cells (ILC2s) through this enhancer. Collectively, these results provide novel insights into how Satb1 expression is regulated in TH2 cells and ILC2s during type 2 immune responses.

Comparison of positive rates between glutamic acid decarboxylase antibodies and ElisaRSR™ 3 Screen ICA™ in recently obtained sera from patients who had been previously diagnosed with slowly progressive type 1 diabetes.

AIMS/INTRODUCTION: This study aimed to compare the positivity rates of glutamic acid decarboxylase autoantibodies (GADA) and ElisaRSR™ 3 Screen ICA™ (3 Screen ICA), a newly developed assay for the simultaneous measurement of GADA, insulinoma-associated antigen-2 autoantibodies (IA-2A), and zinc transporter 8 autoantibodies (ZnT8A), in recently obtained sera from patients who had been previously diagnosed with slowly progressive type 1 diabetes (SPIDDM). MATERIALS AND METHODS: We enrolled 53 patients with SPIDDM who were positive for GADA at the diagnosis and 98 non-diabetic individuals, and investigated the diagnostic accuracy of the 3 Screen ICA (cutoff index ≥30 units) compared with that of GADA. In addition, we compared the clinical characteristics of patients with SPIDDM who were negative or positive on 3 Screen ICA. RESULTS: The positivity rates of 3 Screen ICA, GADA, IA-2A, and ZnT8A were 88.7, 86.8, 24.5, and 13.2%, respectively. The respective sensitivity, specificity, and positive and negative predictive values for SPIDDM were 88.7, 100, 100, and 94.2% by 3 Screen ICA and 86.8, 100, 100.0, and 93.3% by GADA. There were no significant differences in age at onset, duration of diabetes, body mass index, glycated hemoglobin and C-peptide levels, and the prevalence of autoimmune thyroiditis between patients with SPIDDM who were positive or negative on 3 Screen ICA. However, the prevalence of insulin users was significantly higher in those who were positive than in those who were negative on 3 Screen ICA. CONCLUSIONS: Similar to GADA, 3 Screen ICA may be a useful diagnostic tool for detecting patients with SPIDDM.

Bi-glandular and persistent enterovirus infection and distinct changes of the pancreas in slowly progressive type 1 diabetes mellitus.

In slowly progressive type 1 diabetes mellitus (SPIDDM), the pancreas shows sustained islet inflammation, pancreatitis, pancreatic acinar cell metaplasia/dysplasia (ADM), and intraepithelial neoplasia (PanIN), a precancerous lesion. The mechanisms underlying these changes remain unclear. The presence of enterovirus (EV) encoded-capsid protein 1 (VP1) and -2A protease (2Apro) and the innate immune responses of the pancreas were studied using immunohistochemistry and in situ hybridization in 12 SPIDDM and 19 non-diabetic control pancreases. VP1, 2Apro, and EV-RNA were detected in islets and the exocrine pancreas in all SPIDDM pancreases. Innate immune receptor, melanoma differentiation-associated gene 5 (MDA5), and interferon (IFN)-beta1 were intensified in the islets of SPIDDM patients with short disease duration. However, expressions of MDA5 and IFN-beta1were suppressed in those with longer disease duration. CD3+ T cell infiltration was observed in the VP1- and insulin-positive islets (insulitis) and exocrine acinar cells. CD11c+ dendritic cells (DCs) in islets were scarce in long-term SPIDDM. This study showed the consistent presence of EV, suggesting an association with inflammatory changes in the endocrine and exocrine pancreas in SPIDDM. Suppressed expressions of MDA5 and IFN-beta1, as well as decreased numbers of DCs in the host cells, may contribute to persistent EV infection and induction of ADM/PanIN lesions, which may potentially provide a scaffold for pancreatic neoplasms.

The DNA integrity number and concentration are useful parameters for successful comprehensive genomic profiling test for cancer using formalin-fixed paraffin embedded tissue.

The acquisition of high-quality biospecimens and the appropriate handling of these materials are indispensable for successful clinical sequencing. We developed a cancer clinical sequencing system targeting 160 cancer genes: PleSSision-Rapid. Through the PleSSision-Rapid system, we have analyzed DNA quality evaluated by DIN (DNA integrity number) with 1329 formalin-fixed paraffin embedded (FFPE) samples including 477 prospectively collected tissues for genomic test (P) and 852 archival samples after routine pathological diagnosis (A1/A2). As a result, the samples with more than DIN 2.1 was 92.0% (439/477) in prospectively collected sample (P), while it was 85.6% (332/388) and 76.7% (356/464) in two types of archival samples (A1/A2). We performed the PleSSision-Rapid sequence using the samples with over DIN 2.1 and DNA concentration >10 ng/µL with which we were able to construct a DNA library, and the probability of sequence success was almost equivalent during all types of specimen processing, at 90.7% (398/439) in (P), 92.5% (307/332) in (A1) and 90.2% (321/356) in (A2), respectively. Our result indicated the clinical benefit to prepare the prospective collection of FFPE materials for indisputable clinical sequence, and that DIN ≥ 2.1 would be a solid parameter for sample preparation of comprehensive genomic profiling tests.

Effects of resistance training on bone mineral density and resting serum hormones in female collegiate distance runners: a randomized controlled pilot trial.

BACKGROUND: Studies report low bone mineral density (BMD) in female distance runners. We aimed to investigate changes in BMD and resting serum hormones, including dehydroepiandrosterone sulfate (DHEA-S) and estradiol (E2), before and after resistance training (RT) interventions in female collegiate distance runners. METHODS: Fourteen female collegiate distance runners (age, 19.8±0.8 years) and 14 age-matched healthy young women as controls (age, 20.5±1.6 years) were included and divided into RT groups and controls (runner with RT, RRT; runner controls, RCON; non-athlete with RT, NRT; non-athlete controls, NCON). The RRT and NRT groups performed squats and deadlifts at 60-85% 1RM load for one session of five sets of five repetitions, twice a week for 16 weeks. BMD of the total body, lumbar spine L2-L4, and femoral neck was measured by dual-energy X-ray absorptiometry scanning. Resting serum cortisol, adrenocorticotropic hormone, testosterone, growth hormone, insulin-like growth factor 1, DHEA-S, progesterone, E2, procollagen type I N-terminal propeptide (P1NP), and N-terminal telopeptide were assayed. RESULTS: The results showed a significant increase in total body BMD in both the RRT and NRT (both P<0.05) groups. P1NP in the RRT group increased significantly after RT, and the increase was higher than in the RCON (P<0.05). Conversely, no significant changes were observed in resting blood hormone levels for all measurements in all groups (all P>0.05). CONCLUSIONS: These findings suggest that 16 weeks of RT in female collegiate distance runners may increase total body BMD.

Bivalent GAD autoantibody ELISA improves clinical utility and risk prediction for adult autoimmune diabetes.

AIM/INTRODUCTION: To investigate the differences in the clinical significance and glutamic acid decarboxylase autoantibody (GADA) affinity between RIA (RIA-GADA) and ELISA (ELISA-GADA) in patients with type 1 diabetes. METHODS: A total of 415 patients with type 1 diabetes were enrolled, including 199 acute-onset type 1 diabetes, 168 slowly progressive type 1 diabetes (SPIDDM), and 48 fulminant type 1 diabetes. GADA affinity was measured by a competitive binding experiment using unlabeled recombinant human GAD65 protein, and the diagnostic performance of both assays and the relationship between GADA affinity and the decline of fasting C-peptide (F-CPR) were examined. RESULTS: While the ELISA-GADA displayed a higher sensitivity than the RIA method in diagnosing type 1 diabetes in acute-onset patients, about 40% of SPIDDM patients with low-titer RIA-GADA were determined as negative by the ELISA method. Patients with type 1 diabetes with RIA-GADA alone had an older age of onset, less diabetic ketoacidosis, a higher BMI, and a higher F-CPR compared with patients positive for both RIA-GADA and ELISA-GADA. Additionally, 36% of RIA-GADA-positive patients had low-affinity GADA (<1010 L/mol), which was significantly higher than in the ELISA-GADA-positive patients (4%, P < 0.0001). Furthermore, over a 3 year monitoring period, F-CPR levels decreased in ELISA-GADA-positive SPIDDM, whereas it was maintained in patients with RIA-GADA alone, regardless of GADA affinity. CONCLUSIONS: These results suggest that bivalent ELISA for GADA is superior to the RIA method in diagnosing type 1 diabetes. Moreover, the diagnostic superiority of the ELISA-GADA made possible the concurrent identification of SPIDDM patients at high-risk of early progression, and allowed for more accurate clinical diagnosis and management.

Comparing the clinical significance and antigen specificity of insulinoma-associated antigen-2 autoantibodies between radioimmunoassay and enzyme-linked immunosorbent assay in Japanese patients with type 1 diabetes.

AIMS/INTRODUCTION: This study aimed to investigate the clinical significance and antigen specificity of autoantibodies to insulinoma-associated antigen-2 (IA-2A) by radioimmunoassay (RIA; IA-2A-RIA) and enzyme-linked immunosorbent assay (ELISA; IA-2A-ELISA) in Japanese patients with type 1 diabetes. MATERIALS AND METHODS: A total of 338 type 1 diabetic patients were enrolled, including 38 fulminant type 1 diabetes, 168 acute-onset type 1 diabetes and 137 slowly-progressive type 1 diabetes (SPIDDM). The concordance, correlation of autoantibody titer, and the relationship between IA-2A and progression to the insulin-deficient state were examined. Also, competitive assay was used to examine the antigen specificity. RESULTS: The prevalence of IA-2A-ELISA was 4-5% lower than that of IA-2A-RIA in both the acute-onset type 1 diabetes and SPIDDM, but the diagnostic sensitivities of both subtypes, when measured in combination with glutamic acid decarboxylase autoantibody, were comparable. The diagnosis of type 1 diabetes using either the RIA or ELISA methods showed substantial agreement with the exponential correlation of autoantibody titers detected by RIA and ELISA. Among the SPIDDM patients, the fasting C-peptide for IA-2A-positive cases by ELISA, but not the RIA method, was significantly lower than in the negative cases (P < 0.05). Furthermore, IA-2A-ELISA proved superior to the RIA method in predicting the progression to insulin deficiency in SPIDDM. Competitive analysis showed that even sera with discrepant results by RIA and ELISA have IA-2-specific autoantibodies. CONCLUSION: These results suggest that IA-2A-ELISA is a reliable marker not only for the diagnosis of type 1 diabetes, but also for the prediction of future insulin dependency; that is, detection of IA-2A-ELISA helps identify a subtype of SPIDDM patients who would likely progress onto insulin-deficient state.

Do media events still unite the host nation's citizens? The case of the Tokyo 2020 Olympic Games.

The Olympic Games are a typical media event and are seen as a festive occasion that monopolizes people's attention through the mass media. The Games and their media coverage have a predetermined schedule that enhances the nation's sense of unity by placing a temporary truce on political conflicts. Governments, especially those of Olympic host countries, tend to take advantage of this effect to garner support for their own policies. However, the effects of such media events may be weakening owing to changes in the media environment and increasing political polarization. Examining the 2020 Tokyo Olympic Games, this case study analyzes a large amount of Twitter data to probe Japanese social media users' attitudes toward the Olympic Games and the relationship of these attitudinal changes with their attitudes toward the political leadership of the prime minister. The results showed that previously negative attitudes toward the Olympic Games improved as people enjoyed the event. However, this positive shift did not appear to be associated with their attitudes toward the prime minister. Users' political predispositions strongly determined their attitudes toward the Olympic Games, indicating that the Olympic Games as a media event had limited implications for support for the administration.

Relationship of muscle power and bone mineral density with the α-actinin-3 R577X polymorphism in Japanese female athletes from different sport types: An observational study.

The aim of this study was to clarify the relationships between muscle power and bone mineral density (BMD) and the α-actinin-3 (ACTN3) R577X polymorphism in Japanese female collegiate athletes participating in sports with various mechanical-load characteristics. This study included 260 female collegiate athletes involved in 10 competitive sports and 26 controls (mean ages, 19.2 ±â€…1.2 and 19.7 ±â€…1.3 years, respectively). The sports were classified into 3 categories (low-impact, multidirectional, and high-impact) based on the exercise load characteristics. Data on sports participation and competition experience were obtained through a questionnaire-type survey. The maximum anaerobic power (MAnP) test was performed to measure muscle power. The total body BMD was measured using dual-energy X-ray absorptiometry. The ACTN3 R577X polymorphism (rs1815739) was analyzed using a TaqMan® assay. The multidirectional sports participants with the RR genotype of the ACTN3 R577X polymorphism had a higher BMD than those with the RX and RX + XX genotypes (P = .018 and P = .003, respectively). The RR genotype was also associated with a higher MAnP than those with the RX + XX genotypes (P = .035). No other variables related to BMD and MAnP were significantly different. Our results suggests that the RR genotype may confer high trainability for BMD and muscle power in Japanese female collegiate athletes participating in multidirectional sport types. However, these associations were not found in the athletes participating in the low- and high-impact sport types.

Sebaceous immunobiology - skin homeostasis, pathophysiology, coordination of innate immunity and inflammatory response and disease associations.

This review presents several aspects of the innovative concept of sebaceous immunobiology, which summarizes the numerous activities of the sebaceous gland including its classical physiological and pathophysiological tasks, namely sebum production and the development of seborrhea and acne. Sebaceous lipids, which represent 90% of the skin surface lipids in adolescents and adults, are markedly involved in the skin barrier function and perifollicular and dermal innate immune processes, leading to inflammatory skin diseases. Innovative experimental techniques using stem cell and sebocyte models have clarified the roles of distinct stem cells in sebaceous gland physiology and sebocyte function control mechanisms. The sebaceous gland represents an integral part of the pilosebaceous unit and its status is connected to hair follicle morphogenesis. Interestingly, professional inflammatory cells contribute to sebocyte differentiation and homeostasis, whereas the regulation of sebaceous gland function by immune cells is antigen-independent. Inflammation is involved in the very earliest differentiation changes of the pilosebaceous unit in acne. Sebocytes behave as potent immune regulators, integrating into the innate immune responses of the skin. Expressing inflammatory mediators, sebocytes also contribute to the polarization of cutaneous T cells towards the Th17 phenotype. In addition, the immune response of the perifollicular infiltrate depends on factors produced by the sebaceous glands, mostly sebaceous lipids. Human sebocytes in vitro express functional pattern recognition receptors, which are likely to interact with bacteria in acne pathogenesis. Sex steroids, peroxisome proliferator-activated receptor ligands, neuropeptides, endocannabinoids and a selective apoptotic process contribute to a complex regulation of sebocyte-induced immunological reaction in numerous acquired and congenital skin diseases, including hair diseases and atopic dermatitis.

A hairy situation for ILC2s.

The overall contribution of type 2 immunity to cutaneous barrier integrity is poorly understood. In this issue of Immunity, Ricardo-Gonzalez et al. demonstrate the mechanisms by which type 2 cytokines and group 2 innate lymphoid cells (ILC2s) regulate Demodex mite colonization and maintain skin homeostasis.

Toward a better understanding of cultural change: Reply to Bao et al. (2022).

Bao et al. (2022) criticize the method, analysis, and conclusion of Hamamura et al. (2021). In this reply, we respond to their three critiques. We trust that this constructive exchange further facilitates our understanding of cultural changes. (PsycInfo Database Record (c) 2022 APA, all rights reserved).