Differentiation and homeostasis of effector Treg cells are regulated by inositol polyphosphates modulating Ca2+ influx.

Activated Foxp3+ regulatory T (Treg) cells differentiate into effector Treg (eTreg) cells to maintain peripheral immune homeostasis and tolerance. T cell receptor (TCR)-mediated induction and regulation of store-operated Ca2+ entry (SOCE) is essential for eTreg cell differentiation and function. However, SOCE regulation in Treg cells remains unclear. Here, we show that inositol polyphosphate multikinase (IPMK), which generates inositol tetrakisphosphate and inositol pentakisphosphate, is a pivotal regulator of Treg cell differentiation downstream of TCR signaling. IPMK is highly expressed in TCR-stimulated Treg cells and promotes a TCR-induced Treg cell program. IPMK-deficient Treg cells display aberrant T cell activation and impaired differentiation into RORγt+ Treg cells and tissue-resident Treg cells. Mechanistically, IPMK controls the generation of higher-order inositol phosphates, thereby promoting Ca2+ mobilization and Treg cell effector functions. Our findings identify IPMK as a critical regulator of TCR-mediated Ca2+ influx and highlight the importance of IPMK in Treg cell-mediated immune homeostasis.

Reasons for using e-cigarettes among adults who smoke: comparing the findings from the 2016 and 2020 ITC Korea Surveys.

INTRODUCTION: Dual use of e-cigarettes and cigarettes is a growing usage pattern in adults, but little is known about the motivations underlying this trend. We investigated the reasons for e-cigarette use among adults who smoke, considering variation in sociodemographic subgroups. METHODS: This repeated cross-sectional study analysed adults who smoked at least weekly and vaped at any frequency. Data were from the International Tobacco Control Korea Surveys conducted in 2016 (n=164) and 2020 (n=1088). Fourteen reasons for e-cigarette use were assessed in both waves. Subgroup analyses were performed by age, sex and educational level. RESULTS: The top reasons for e-cigarette use in 2020 were curiosity (62.8%), less harmful than smoking (45.4%) and taste (43.2%). Curiosity was the most cited across age, sex and education subgroups. Significant differences were observed in 2020 compared with 2016, with lower percentages in goal-oriented reasons: helping quit smoking (36.3% vs 48.9%; p=0.017), helping cut down smoking (35.3% vs 52.7%; p=0.001), less harmful to others (39.0% vs 54.6%; p=0.003) and more acceptable (31.6% vs 61.2%; p<0.001). By contrast, non-goal-oriented reasons showed higher percentages in 2020, such as curiosity (62.8% vs 27.9%; p<0.001), taste (43.2% vs 22.1%; p<0.001) and enjoyment (26.8% vs 8.6%; p<0.001). In 2020, a majority of adults who smoked and vaped (53.3%) reported no intention to quit or reduce smoking. CONCLUSIONS: E-cigarette use for curiosity and pleasure predominated among adults who smoked. The reasons for dual use in adults have shifted from goal-oriented to non-goal-oriented.

Public support for tobacco endgame policies in South Korea: Findings from the 2020 International Tobacco Control Korea Survey.

BACKGROUND: Strong public support can increase the likelihood of adopting tobacco control policies. We assessed support for six commercial tobacco endgame policies in South Korea: limiting the nicotine in cigarettes, banning all additives in cigarettes, restricting the number of places where cigarettes are sold, and banning the manufacture and sales of cigarettes (unconditionally, with the provision of cessation support and with alternative tobacco products available). METHODS: Data were obtained from 4740 adults who completed the 2020 International Tobacco Control Korea Survey. Participants were categorised based on their nicotine use: (1) did not use any products, (2) vaped and/or used heated tobacco products (HTPs) but did not smoke cigarettes, (3) smoked cigarettes only and (4) smoked cigarettes and vaped and/or used HTPs. Attitudes towards the policies were classified as supportive, undecided or opposed. Weighted multinomial logistic regression models assessed support levels according to nicotine use. RESULTS: Support was highest for limiting the nicotine content in cigarettes (68.4%; 95% CI 64.6% to 72.3%) and restricting the number of retailers (68.1%; 95% CI 64.5% to 71.7%), and lowest for banning cigarette sales if alternative products are made available (45.0%; 95% CI 40.9% to 49.1%). People who did not use any products were most likely to support endgame policies, except for banning cigarette sales with alternatives available. The proportion of undecided participants exceeded 10% (range 13%-25%) for all policies. CONCLUSION: There is a strong public support for tobacco endgame policies in South Korea. Further research should prioritise the development of strategies to ensure the effective implementation of highly supported policies.

Vision for tobacco endgame in Korea: suggestions for countries with endgame aspirations.

Tobacco endgame is a focal point of discussion at both national and international levels. We aimed to describe efforts related to achieving the tobacco endgame in the Republic of Korea, an exemplar of a country with endgame aspirations, and compare them with the efforts of other nations. We reviewed the tobacco endgame efforts of three nations considered tobacco control leaders: New Zealand (NZ), Australia and Finland. The efforts/attempts of each country were described using an endgame strategy category. The tobacco control leaders had explicit goals to achieve a smoking prevalence of <5% before a target date and had legislation and research centres for tobacco control and/or endgame. NZ is implementing a mixture of conventional and innovative endgame interventions; the others use incremental conventional approaches. In Korea, there has been an attempt to ban the sale and manufacture of combustible cigarettes. The attempt led to the filing of a petition, and a survey of adults showed 70% supported the legislation banning tobacco. The Korean government mentioned a tobacco endgame in a 2019 plan, yet a target and an end date were absent. The 2019 plan in Korea included incremental FCTC strategies. Practices in the leading countries show that legislation and research are key to ending the tobacco epidemic. The MPOWER measures must be strengthened, endgame objectives must be set and bold strategies must be adopted. Key endgame policies include those with evidence of effectiveness, such as retailer reductions.

Manipulating Nanoparticle Aggregates Regulates Receptor-Ligand Binding in Macrophages.

The receptor-ligand interactions in cells are dynamically regulated by modulation of the ligand accessibility. In this study, we utilize size-tunable magnetic nanoparticle aggregates ordered at both nanometer and atomic scales. We flexibly anchor magnetic nanoparticle aggregates of tunable sizes over the cell-adhesive RGD ligand (Arg-Gly-Asp)-active material surface while maintaining the density of dispersed ligands accessible to macrophages at constant. Lowering the accessible ligand dispersity by increasing the aggregate size at constant accessible ligand density facilitates the binding of integrin receptors to the accessible ligands, which promotes the adhesion of macrophages. In high ligand dispersity, distant magnetic manipulation to lift the aggregates (which increases ligand accessibility) stimulates the binding of integrin receptors to the accessible ligands available under the aggregates to augment macrophage adhesion-mediated pro-healing polarization both in vitro and in vivo. In low ligand dispersity, distant control to drop the aggregates (which decreases ligand accessibility) repels integrin receptors away from the aggregates, thereby suppressing integrin receptor-ligand binding and macrophage adhesion, which promotes inflammatory polarization. Here, we present "accessible ligand dispersity" as a novel fundamental parameter that regulates receptor-ligand binding, which can be reversibly manipulated by increasing and decreasing the ligand accessibility. Limitless tuning of nanoparticle aggregate dimensions and morphology can offer further insight into the regulation of receptor-ligand binding in host cells.

Multi-Sensor Data Fusion with a Reconfigurable Module and Its Application to Unmanned Storage Boxes.

We present a multi-sensor data fusion model based on a reconfigurable module (RM) with three fusion layers. In the data layer, raw data are refined with respect to the sensor characteristics and then converted into logical values. In the feature layer, a fusion tree is configured, and the values of the intermediate nodes are calculated by applying predefined logical operations, which are adjustable. In the decision layer, a final decision is made by computing the value of the root according to predetermined equations. In this way, with given threshold values or sensor characteristics for data refinement and logic expressions for feature extraction and decision making, we reconstruct an RM that performs multi-sensor fusion and is adaptable for a dedicated application. We attempted to verify its feasibility by applying the proposed RM to an actual application. Considering the spread of the COVID-19 pandemic, an unmanned storage box was selected as our application target. Four types of sensors were used to determine the state of the door and the status of the existence of an item inside it. We implemented a prototype system that monitored the unmanned storage boxes by configuring the RM according to the proposed method. It was confirmed that a system built with only low-cost sensors can identify the states more reliably through multi-sensor data fusion.

Magnetic Control and Real-Time Monitoring of Stem Cell Differentiation by the Ligand Nanoassembly.

Native extracellular matrix (ECM) exhibits dynamic change in the ligand position. Herein, the ECM-emulating control and real-time monitoring of stem cell differentiation are demonstrated by ligand nanoassembly. The density of gold nanoassembly presenting cell-adhesive Arg-Gly-Asp (RGD) ligand on Fe3 O4 (magnetite) nanoparticle in nanostructures flexibly grafted to material is changed while keeping macroscale ligand density invariant. The ligand nanoassembly on the Fe3 O4 can be magnetically attracted to mediate rising and falling ligand movements via linker stretching and compression, respectively. High ligand nanoassembly density stimulates integrin ligation to activate the mechanosensing-assisted stem cell differentiation, which is monitored via in situ real-time electrochemical sensing. Magnetic control of rising and falling ligand movements hinders and promotes the adhesion-mediated mechanotransduction and differentiation of stem cells, respectively. These rising and falling ligand states yield the difference in the farthest distance (≈34.6 nm) of the RGD from material surface, thereby dynamically mimicking static long and short flexible linkers, which hinder and promote cell adhesion, respectively. Design of cytocompatible ligand nanoassemblies can be made with combinations of dimensions, shapes, and biomimetic ligands for remotely regulating stem cells for offering novel methodologies to advance regenerative therapies.

Prevalence and predictors of heated tobacco product use and its relationship with attempts to quit cigarette smoking among Korean adolescents.

INTRODUCTION: Heated tobacco products (HTPs) have been available in the Korean market since June 2017. In this study, we examined the prevalence and predictors of HTP use among Korean adolescents and the association between HTP and electronic cigarette (EC) use and attempts to quit conventional cigarette (CC) smoking. METHODS: We analysed the data of a representative sample (n=60 040) of 13-18-year-old middle-school and high-school students in Korea who had participated in the 14th Korea Youth Risk Behavior Web-based Survey in 2018. RESULTS: The prevalence of ever HTP use among Korean adolescents was 2.9% (men: 4.4%, women: 1.2%), a year after the introduction of HTPs in the Korean market. Furthermore, 81.3% of the 1568 ever HTP users were triple users of HTPs, ECs and CCs. Multivariate analysis revealed that ever HTP use was greater among men, higher-grade students, current CC and/or EC users and risky alcohol drinkers. Among current CC smokers, ever users of ECs (28%-30%) and ever HTP users and current EC users (48%) were more likely to have attempted to quit CC smoking than those who had never used HTPs and ECs. However, there were fewer HTP and/or EC ever users among ever CC smokers who successfully quit smoking. CONCLUSIONS: Many adolescents, especially CC and EC users, had already used HTPs shortly after the introduction of HTPs in Korea. The use of newer types of tobacco products is associated with lower odds of abstinence from CCs; therefore, it is important to protect adolescents from them.

Foxp3 expression in induced regulatory T cells is stabilized by C/EBP in inflammatory environments.

Proper control of immune responses by Foxp3+ regulatory T cells at inflamed sites is crucial for the prevention of immunopathology. TGF-ß-induced Foxp3+ regulatory T (Treg) cells are generated in inflammatory environments as well as in steady-state conditions. Inflammatory cytokines such as IFN-γ and IL-4 have an antagonistic effect on Treg cell conversion. However, it is not known how naive CD4+ T cells overcome the inhibitory environment in inflamed sites to differentiate into Treg cells. Here, we show that CCAAT/enhancer-binding protein (C/EBP) functions as a safeguard that enhances Treg cell generation by dampening the inhibitory effect of IFN-γ and IL-4 on Foxp3 expression. We find that C/EBPß is induced by retinoic acid and binds to the methyl-CRE sequence in the Foxp3 TSDR to sustain its expression. C/EBPß-transduced iTreg cells show more potent suppressive activity in mouse disease models. We also reveal that C/EBPß-transduced human iTreg cells exhibit more enhanced suppressor function. These results establish C/EBP as a new molecular target for enhancing the formation and stability of Treg cells in inflammatory environments.

Relationship Between Volunteering and Perceived General Health of Individuals with Serious Mental Illness.

Volunteering has been found to be a significant predictor of improved health among the general population. Yet, little is known about the relationship between volunteering and perceived general health among individuals with serious mental illness (SMI). Using data obtained from the 2014 California Health Interview Survey (N = 1127), this study examined the extent to which volunteering is associated with perceived general health of individuals with SMI. Study findings indicate that individuals who engage in volunteering are more likely to report better health status when compared to those who do not engage in volunteering.

Awareness, experience and prevalence of heated tobacco product, IQOS, among young Korean adults.

INTRODUCTION: Philip Morris International introduced 'IQOS' to the Korean market in June 2017. To monitor the use of IQOS among young Korean adults, we identified their awareness, experience and current use of IQOS. METHODS: Three months after the introduction of IQOS in Korea, we conducted an online survey with 228 general young adults, aged 19-24 years. RESULTS: 87 participants (38.1%) were aware of IQOS, 13 (5.7%) were IQOS ever users and 8 (3.5%) were current IQOS users. All the current IQOS users were triple users of conventional cigarettes and electronic cigarettes (e-cigarettes). There were no IQOS-only users and one IQOS ever user was a non-cigarette smoker. Among the eight current IQOS users who smoked 9.1 conventional cigarettes a day on average, four smoked 10-20 HEETS sticks a day. The current IQOS users decided to use IQOS because they believed it was less harmful or to stop smoking. The current conventional cigarette smokers were much more likely to be aware of IQOS (OR 4.496; 95% CI 2.185 to 9.250) and to be IQOS ever users (OR 11.649; 95% CI 1.024 to 132.564). CONCLUSION: Awareness, experience and use of IQOS among young Korean adults were relatively higher than among their Japanese counterparts. Current IQOS users were more likely to smoke conventional cigarettes and/or e-cigarettes, which contradicts the tobacco industry's claims that conventional cigarette smokers will switch to heated tobacco products. Until obtaining robust evidence concerning heated tobacco products, the government should regulate the tobacco industry's marketing tactics and health claims.

Association Between Employment and Mental Health Service Use Among Justice-Involved Individuals.

Using a nationally representative sample of justice-involved persons (N = 1525), the present study examined the extent to which employment status was associated with mental health service use by various service providers. The findings indicate that the rate of mental health service use by general health care providers among the unemployed was higher than that of the employed. Factors associated with mental health service use varied by type of provider. Our findings suggest that employment may be critical for justice-involved people in enhancing their mental health status, which could result in their successful community integration.

Racial-Ethnic Variation in Mental Health Service Utilization Among People with a Major Affective Disorder and a Criminal History.

Using a nationally representative sample, this study examined the extent to which the utilization of various mental health services was associated with racial-ethnic identity among people with major affective disorders who have a criminal history. Approximately 33.7 % of the sample received any type of mental health services in a given year. Multivariate models indicated that married Blacks and Latinos were less likely to use specialty mental health care than their white counterparts. To provide equitable mental health treatment for vulnerable subgroups of this population, mental health professionals should account for the heterogeneity of mental health care in diverse cultural contexts.

Variation in Major Depressive Disorder Onset by Place of Origin Among U.S. Latinos.

Using a nationally representative sample of 2514 U.S. Latinos, this study examined the extent to which major depressive disorder (MDD) onset differs by place of origin and the factors associated with it. The Kaplan-Meier method estimated the survival and hazard functions for MDD onset by place of origin, and Cox proportional hazards models identified its associative factors. Approximately 13% of the sample had experienced MDD in their lifetimes. Cuban respondents showed the highest survival function, while Puerto Ricans showed the lowest. With the entire sample, the smoothed hazard function showed that the risk of MDD onset peaked in the late 20s and early 80s. Puerto Rican respondents showed the highest risk of MDD during their 20s and 30s, whereas Cuban respondents showed a relatively stable pattern over time. The results from the Cox proportional hazards model indicated that age, sex, and marital status were significantly related to MDD onset (p < .05). In addition, the effect of U.S.-born status on MDD onset was greater among Mexican respondents than among Puerto Ricans. Findings from the present study demonstrate that different Latino subgroups experience different and unique patterns of MDD onset over time. Future research should account for the role of immigration status in examining MDD onset.

Racial/Ethnic Differences in Contemporaneous Use of Mental Health and Substance Use Treatment Among Individuals Experiencing Both Mental Illness and Substance Use Disorders.

This study examined whether the well-established racial/ethnic differences in mental health service utilization among individuals with mental illness are reflected in the treatment utilization patterns of individuals experiencing both mental illness and substance use disorders, particularly in regards to the use of contemporaneous mental health and substance abuse treatment. Using pooled data from the National Survey on Drug Use and Health (2009-2013), the patterns of mental health and substance use treatment utilization of 8748 White, Black, or Latino individuals experiencing both mental illness and substance use disorders were analyzed. Multinomial logistic regression was conducted to test the relationships among racial/ethnic groups and the receipt of contemporaneous treatment, mental health treatment alone, and substance use treatment alone as compared with no treatment utilization. Results indicated that Black and Latino respondents were less likely to receive contemporaneous treatment than Whites respondents. Also, significantly associated with outcomes were several interactions between race/ethnicity and predisposing, need and enabling factors known to be associated with service utilization. The findings suggest that an underlying mechanism of racial/ethnic differences among individuals with co-occurring mental illness and substance use disorders in the treatment utilization may differ by the specific types of treatment and between Blacks and Latinos. Therefore, efforts to reduce these disparities should consider specialty in each treatment settings and heterogeneity within diverse racial/ethnic groups.

Discrimination and mental health among Latinos: variation by place of origin.

The US Latino population experiences high rates of discrimination, which may contribute to psychiatric disorders. Yet, little is known about the distinctions in this relationship for Latino subgroups. Using data from the National Latino and Asian American study, we examined the association between discrimination and mental health for 2503 Latinos. Logistic regression analyses were used to examine variation in the relationship by place of origin (Cuba, Puerto Rico, Mexico, or Other). Results suggest that perceived discrimination increased the probability of having a psychiatric disorder. The effect of discrimination on having a psychiatric disorder was greater for Mexicans than Puerto Ricans. The findings of this study suggest that variation exists in the relationship between discrimination and mental health by origin. Implications for practice include increasing awareness of place of origin, in addition to discrimination, as a risk factor for mental illness. Future research should examine this relationship longitudinally and consider immigration status.

Psychiatric disorders after terrorist bombings among rescue workers and bombing survivors in Nairobi and rescue workers in Oklahoma City.

BACKGROUND: To examine the prevalence of psychopathology in 52 male rescue workers responding to the 1998 U.S. Embassy bombing in Nairobi, Kenya, comparing them with 176 male rescue workers responding to the 1995 Oklahoma City, Oklahoma, bombing and with 105 directly exposed male civilian survivors of the Nairobi bombing. METHODS: The Diagnostic Interview Schedule/Disaster Supplement assessed pre-disaster and post-disaster psychiatric disorders and variables related to demographics, exposure, disaster perceptions, and coping in all 3 disaster subgroups. RESULTS: The most prevalent post-disaster disorders were posttraumatic stress disorder (PTSD) (22%) and major depressive disorder (MDD) (27%) among Nairobi rescue workers, which were more than 2 and 4 times higher, respectively, than among Oklahoma City rescue workers. Alcohol use disorder was the most prevalent pre- and post-disaster disorder among Oklahoma City rescue workers. Nairobi rescue workers had a prevalence of PTSD and MDD not significantly different from Nairobi civilian survivors. CONCLUSIONS: Nairobi rescue workers were more symptomatic than Oklahoma City rescue workers and were as symptomatic as Nairobi civilian survivors. The vulnerability of Nairobi rescue workers to psychological sequelae may be a reflection of their volunteer, rather than professional, status. These findings contribute to understanding rescue worker mental health, especially among volunteer rescue workers, with potential implications for the importance of professional status of rescue workers in conferring protection from adverse mental health outcomes.

Effects of Nativity, Length of Residence, and County-Level Foreign-Born Density on Mental Health Among Older Adults in the U.S.

Using the 2004-2007 Medical Expenditure Panel Survey data that are linked to county-level data from the Area Health Resources Files, this study examined whether the healthy immigrant effect applies to mental health of foreign-born older adults. Additionally, testing a protective ethnic density effect on older foreign-born individuals' mental health, this study examined how the percentage of foreign-born population in the county affected the relationship between older adults' immigration status (U.S.-nativity and length of residence in the U.S.) and their mental health status. The sample included 29,011 individuals (level-1) from 920 counties (level-2) across 50 states and D.C. Using the Mental Component Summary of the Short-Form 12, the Kessler Index (K-6), and the Patient Health Questionnaire (PHQ-2), U.S.-born individuals (n = 24,225), earlier immigrants (≥15 years in the U.S.; n = 3866), and recent immigrants (<15 years in the U.S.; n = 920) were compared. The results indicate that recent immigrants showed worse mental health on all three measures compared with U.S.-born individuals and on the K-6 and PHQ-2 compared with earlier immigrants. Higher county-level foreign-born densities were associated with worse mental health status of individuals. However, the significant interactions found in the full conditional multilevel models indicated that the high foreign-born density functioned as a risk factor for worse mental health only among recent immigrants but not among the U.S.-born. In conclusion, the results revealed the vulnerability of older recent immigrants, especially those living in the counties with high foreign-born densities.

Effects of comorbid health conditions on healthcare expenditures among people with severe mental illness.

BACKGROUND AND AIMS: Little is known about the incremental cost burden associated with treating comorbid health conditions among people with severe mental illness (SMI). This study compares the extent to which each individual medical condition increases healthcare expenditures between people with SMI and people without mental illness. METHODS: Data were obtained from the 2011 Medical Expenditure Panel Survey (MEPS; N = 17 764). Mental illness and physical health conditions were identified through ICD-9 codes. Guided by the Andersen's behavioral model of health services utilization, generalized linear models were conducted. RESULTS: Total healthcare expenditures among individuals with SMI were approximately 3.3 times greater than expenditures by individuals without mental illness ($11 399 vs. $3449, respectively). Each additional physical health condition increased the total healthcare expenditure by 17.4% for individuals with SMI compared to the 44.8% increase for individuals without mental illness. CONCLUSIONS: The cost effect of having additional health conditions on the total healthcare expenditures among individuals with SMI is smaller than those individuals without mental illness. Whether this is due to limited access to healthcare for the medical problems or better coordination between medical and mental health providers, which reduces duplicated medical procedures or visits, requires future investigation.