Effect of motivated physicians and elderly patients with hypertension or type 2 diabetes mellitus in prepared communities on health behaviours and outcomes: A population-based PS matched retrospective cohort study during five-year follow-up period.

Effective chronic disease management requires the active participation of patients, communities, and physicians. The objective of this study was to estimate the effectiveness of the Community-based Registration and Management for elderly patients with Hypertension or Type 2 Diabetes mellitus Project (CRMHDP) by using motivated primary care physicians and patients supported by prepared communities, to utilise healthcare and health outcomes in four cities in South Korea. We conducted a propensity score-matched retrospective cohort study using 2010-2011 as the baseline years, alongside a follow-up period until 2015/2016, based on the Korean National Health Insurance database. Both a CRMHDP group (n = 46,865) and a control group (n = 93,730) were applied against healthcare utilisation and difference-in-differences estimations were performed. For the health outcome analysis, the intervention group (n = 27,242) and control group (n = 54,484) were analysed using the Kaplan-Meier method and Cox proportional hazard regression. Results: The difference-in-differences estimation of the average annual clinic visits per person and the average annual days covered were 1.26 (95% confidence interval, 1.13-1.39) and 22.97 (95% CI, 20.91-25.03), respectively, between the intervention and control groups. The adjusted hazard ratio for death in the intervention group, compared to the control group, was 0.90 (95% CI, 0.86-0.93). For stroke and chronic renal failure, the adjusted hazard ratios for the intervention group compared to the control group were 0.94 (95% CI, 0.88-0.99) and 0.80 (95% CI 0.73-0.89), respectively. Our study suggests that for effective chronic disease management both elderly patients and physicians need to be motivated by community support.

How has COVID-19 affected the work environment of delivery workers?: An interpretative phenomenological analysis.

The COVID-19 pandemic has sparked a rapid worldwide increase in the utilization of delivery services. This study delves into the experiences of delivery workers as one of the activley developed industries during the COVID-19 pandemic in South Korea and sheds light on the effects of the pandemic on their working conditions. Through in-depth interviews with 10 Korean delivery workers, data analysis employed the hermeneutic phenomenology research method developed by Van Manen. The findings indicate a substantial rise in income levels and a positive societal perception of delivery labor post-COVID-19. The pandemic also attracted many new workers to the industry due to low entry barriers and work flexibility. However, challenges persisted as delivery workers grappled with an uncertain legal status and sometimes jeopardized their safety to boost earnings in shorter time frames. The pivotal role played by delivery workers in enhancing communal quality of life and connectivity during the pandemic cannot be overlooked. As we step into a post-COVID-19 era, comprehensive efforts are needed to enhance the working environment for delivery workers globally. Notably, clarifying the relationship between delivery workers and companies within the novel digital labor landscape is essential, alongside establishing institutional frameworks to safeguard workers' basic rights, including health and safety provisions.

Contact with the health care system prior to suicide: A nationwide population-based analysis using linkage national death certificates and national health insurance data.

This study aimed to discover the proportion of people dying by suicide who had non-psychiatric medical contact alone or any mental health contact in the year, month, and week prior to suicide. Data on suicide deaths (n = 74,741) of all South Koreans from 2009 to 2013 were linked with National Health Insurance (NHI) data by social security number to identify health care contact during the 12 months prior to suicide. The NHI data includes records on inpatient or outpatient service and type of health care institutes which the decedents have contacted. Among the 74,741 individuals who died by suicide, the proportion of individuals who contacted non-psychiatric health care alone was 60.1%, 46.1%, and 35.5%; and the proportion of those who had any mental health contact was 27.9%, 18.0%, and 7.9% in the year, four weeks, and week before death, respectively. Psychiatric care visits in the year, four weeks and weeks prior to death occurred most frequently in psychiatric local clinics. Non-psychiatric care visits in the year and four weeks prior to death were most common in local clinics at the primary care level, but in the one week before death, non-psychiatric care visits were common in tertiary hospital departments. This study indicates that the majority of suicide cases are not diagnosed and managed preceding death despite high general medical contact rates. It implies that suicide prevention strategy should be applied to non-psychiatric medical settings in countries with high suicide rates like South Korea.

High-Frequency Repetitive Magnetic Stimulation Enhances the Expression of Brain-Derived Neurotrophic Factor Through Activation of Ca2+-Calmodulin-Dependent Protein Kinase II-cAMP-Response Element-Binding Protein Pathway.

Repetitive transcranial magnetic stimulation (rTMS) can be used in various neurological disorders. However, neurobiological mechanism of rTMS is not well known. Therefore, in this study, we examined the global gene expression patterns depending on different frequencies of repetitive magnetic stimulation (rMS) in both undifferentiated and differentiated Neuro-2a cells to generate a comprehensive view of the biological mechanisms. The Neuro-2a cells were randomly divided into three groups-the sham (no active stimulation) group, the low-frequency (0.5 Hz stimulation) group, and high-frequency (10 Hz stimulation) group-and were stimulated 10 min for 3 days. The low- and high-frequency groups of rMS on Neuro-2a cells were characterized by transcriptome array. Differentially expressed genes were analyzed using the Database of Annotation Visualization and Integrated Discovery program, which yielded a Kyoto Encyclopedia of Genes and Genomes pathway. Amphetamine addiction pathway, circadian entrainment pathway, long-term potentiation (LTP) pathway, neurotrophin signaling pathway, prolactin signaling pathway, and cholinergic synapse pathway were significantly enriched in high-frequency group compared with low-frequency group. Among these pathways, LTP pathway is relevant to rMS, thus the genes that were involved in LTP pathway were validated by quantitative real-time polymerase chain reaction and western blotting. The expression of glutamate ionotropic receptor N-methyl d-aspartate 1, calmodulin-dependent protein kinase II (CaMKII) δ, and CaMKIIα was increased, and the expression of CaMKIIγ was decreased in high-frequency group. These genes can activate the calcium (Ca2+)-CaMKII-cAMP-response element-binding protein (CREB) pathway. Furthermore, high-frequency rMS induced phosphorylation of CREB, brain-derived neurotrophic factor (BDNF) transcription via activation of Ca2+-CaMKII-CREB pathway. In conclusion, high-frequency rMS enhances the expression of BDNF by activating Ca2+-CaMKII-CREB pathway in the Neuro-2a cells. These findings may help clarify further therapeutic mechanisms of rTMS.

The Differential Effects of Repetitive Magnetic Stimulation in an In Vitro Neuronal Model of Ischemia/Reperfusion Injury.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive therapy that has been implicated in treatment of serious neurological disorders. However, the neurobiological mechanisms underlying the effects of rTMS remain unclear. Therefore, this study examined the differential effects of repetitive magnetic stimulation (rMS) in an in vitro neuronal model of ischemia/reperfusion (I/R) injury, depending on low and high frequency. Neuro-2a cells were differentiated with retinoic acid and established for in vitro neuronal model of I/R injury under a subsequent 3 h of oxygen and glucose deprivation/reoxygenation (OGD/R) condition. After the I/R injury, the differentiated neuronal cells were stimulated with rMS on day 1 and randomly divided into three groups: OGD/R+sham, OGD/R+low-frequency, and OGD/R+high-frequency groups. High-frequency rMS increases cell proliferation through activation of extracellular signal-regulated kinases and AKT-signaling pathway and inhibits apoptosis in OGD/R-injured cells. Furthermore, high-frequency rMS increases Ca2+-calmodulin-dependent protein kinase II (CaMKII)-cAMP-response element binding protein (CREB) signaling pathway, further leading to alternation of brain-derived neurotrophic factor expression and synaptic plasticity in OGD/R injured cells. These results verified the neurobiological mechanisms of frequency-dependent rMS in I/R injury-treated neuronal cells. These mechanisms will help develop more powerful and credible rTMS stimulation treatment protocols.

Extracellular CADM1 interactions influence insulin secretion by rat and human islet ß-cells and promote clustering of syntaxin-1.

Contact between ß-cells is necessary for their normal function. Identification of the proteins mediating the effects of ß-cell-to-ß-cell contact is a necessary step toward gaining a full understanding of the determinants of ß-cell function and insulin secretion. The secretory machinery of the ß-cells is nearly identical to that of central nervous system (CNS) synapses, and we hypothesize that the transcellular protein interactions that drive maturation of the two secretory machineries upon contact of one cell (or neural process) with another are also highly similar. Two such transcellular interactions, important for both synaptic and ß-cell function, have been identified: EphA/ephrin-A and neuroligin/neurexin. Here, we tested the role of another synaptic cleft protein, CADM1, in insulinoma cells and in rat and human islet ß-cells. We found that CADM1 is a predominant CADM isoform in ß-cells. In INS-1 cells and primary ß-cells, CADM1 constrains insulin secretion, and its expression decreases after prolonged glucose stimulation. Using a coculture model, we found that CADM1 also influences insulin secretion in a transcellular manner. We asked whether extracellular CADM1 interactions exert their influence via the same mechanisms by which they influence neurotransmitter exocytosis. Our results suggest that, as in the CNS, CADM1 interactions drive exocytic site assembly and promote actin network formation. These results support the broader hypothesis that the effects of cell-cell contact on ß-cell maturation and function are mediated by the same extracellular protein interactions that drive the formation of the presynaptic exocytic machinery. These interactions may be therapeutic targets for reversing ß-cell dysfunction in diabetes.

Inhibition of ATP-sensitive K+ channels by taurine through a benzamido-binding site on sulfonylurea receptor 1.

ATP-sensitive potassium (K(ATP)) channels in pancreatic beta-cells comprise sulfonylurea receptor (SUR) 1 and inwardly-rectifying potassium channel (Kir) 6.2 subunits. We have evaluated the effect of intracellular taurine on K(ATP) channel activity in rat pancreatic beta-cells using the patch-clamp technique. The mechanism of taurine action was also examined using recombinant K(ATP) channels. The islets and single beta-cells from male Sprague-Dawley rats were collected by collagenase digestion technique. Single K(ATP) channel currents were recorded by the inside-out mode at a membrane potential of -60mV. Cytosolic free-Ca(2+) concentration ([Ca(2+)](c)) and insulin secretory capacity were measured by the dual-excitation fluorimetry and radioimmunoassay, respectively. The native beta-cell K(ATP) channel was directly inhibited by taurine in a dose-dependent manner. Taurine did not influence ATP-mediated inhibition or MgADP-induced activation of the channel activity. The sensitivity of the K(ATP) channel to glybenclamide, but not gliclazide, was enhanced by taurine. Glybenclamide elicited a greater increase in [Ca(2+)](c) and increased insulin secretion in the beta-cells when pretreated with taurine. Taurine did not inhibit Kir6.2DeltaC36 currents, a truncated form of Kir6.2, expressed in Xenopus oocytes without SUR. These results demonstrate that taurine inhibits the K(ATP) channel activity in the beta-cells, interacting with a benzamido-binding site on SUR1, but not Kir6.2.