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1.
BJPsych Open ; 10(3): e89, 2024 Apr 19.
Article En | MEDLINE | ID: mdl-38639211

BACKGROUND: It is well-known that socioeconomic status is associated with mental illness at both the individual and population levels, but there is a less clear understanding of whether socioeconomic development is related to poor mental health at the country level. AIMS: We aimed to investigate sociodemographic disparities in burden of mental disorders, substance use disorders and self-harm by age group. METHOD: Estimates of age-specific disability-adjusted life years (DALY) rates for mental disorders, substance use disorders and self-harm from 1990 to 2019 for 204 countries were obtained. The sociodemographic index (SDI) was used to assess sociodemographic development. Associations between burden of mental health and sociodemographic development in 1990 and 2019 were investigated, and sociodemographic inequalities in burden of mental health from 1990 to 2019 by age were estimated using the concentration index. RESULTS: Differential trends in sociodemographic disparities in diseases across age groups were observed. For mental disorders, particularly depressive disorder and substance use disorders, DALY rates in high SDI countries were higher and increased more than those in countries with other SDI levels among individuals aged 10-24 and 25-49 years. By contrast, DALY rates for those over 50 years were lower in high SDI countries than in countries with other SDI levels between 1990 and 2019. A higher DALY rate among younger individuals accompanied a higher SDI at the country level. However, increased sociodemographic development was associated with decreased disease burden for adults aged ≥70 years. CONCLUSIONS: Strategies for improving mental health and strengthening mental health system should consider a broader sociocultural context.

2.
Clin Orthop Surg ; 16(2): 313-321, 2024 Apr.
Article En | MEDLINE | ID: mdl-38562625

Background: Although several techniques for the treatment of ulnar impaction syndrome (UIS) have been introduced, there have still been reports on various complications such as delayed union, nonunion, refracture, wrist pain, plate irritation, and chronic regional pain syndrome. This study aimed to compare the differences in radiological and clinical outcomes of patients in which intramedullary bone grafting was performed in addition to plate stabilization with those without additional bone grafting during ulnar shortening osteotomies (USOs). Methods: Between November 2014 and June 2021, 53 wrists of 50 patients with idiopathic UIS were retrospectively reviewed. Patients were divided into 2 groups according to whether intramedullary bone grafting was performed. Among the 53 wrists, USO with an intramedullary bone graft was performed in 21 wrists and USO without an intramedullary bone graft was performed in 32 wrists. Demographic data and factors potentially associated with bone union time were analyzed. Results: There was no significant difference between the 2 groups when comparing postoperative radioulnar distance, postoperative ulnar variance, amount of ulnar shortening, and postoperative Disabilities of the Arm, Shoulder and Hand score. Compared to the without-intramedullary bone graft group, bone union time of the osteotomy site was significantly shortened, from 8.8 ± 3.0 weeks to 6.7 ± 1.3 weeks in the with-intramedullary bone graft group. Moreover, there were no cases of nonunion or plate-induced symptoms. Both in univariable and multivariable analyses, intramedullary bone grafting was associated with shorter bone union time. Conclusions: USO with an intramedullary bone graft for idiopathic UIS has favorable radiological and clinical outcomes. The advantage of this technique is the significant shortening of bone union time.


Joint Diseases , Wrist Joint , Humans , Retrospective Studies , Wrist Joint/diagnostic imaging , Wrist Joint/surgery , Bone Transplantation , Treatment Outcome , Ulna/diagnostic imaging , Ulna/surgery , Joint Diseases/surgery , Osteotomy/methods
3.
BMC Public Health ; 24(1): 576, 2024 Feb 22.
Article En | MEDLINE | ID: mdl-38388412

OBJECTIVES: This study aimed to examine changes in life expectancy (LE), health-adjusted life expectancy (HALE), unhealthy years of life, and disease burden of older people in industrialised countries and associations with health systems. METHODS: We used estimates of LE and HALE, unhealthy years of life, years of life loss (YLL), years lived with disability (YLD) for individuals aged 70 years and over in 33 industrialised countries from 1990 to 2019 from the Global Burden of Disease Study 2019. A linear regression analysis was conducted to examine the association of health outcomes with the Healthcare Access and Quality (HAQ) index. RESULTS: LE and HALE increased with improved HAQ index from 1990 to 2019. However, the number of unhealthy years of life increased. An increased HAQ index was associated with decreases in YLL. However, changes in YLD were relatively small and were not correlated with HAQ index. CONCLUSIONS: The healthcare system needs to more address the increased morbidity burden among older people. It should be designed to handle to healthcare needs of the ageing population.


Global Burden of Disease , Global Health , Humans , Aged , Aged, 80 and over , Life Expectancy , Morbidity , Aging , Quality-Adjusted Life Years
4.
J Korean Med Sci ; 39(4): e39, 2024 Jan 29.
Article En | MEDLINE | ID: mdl-38288540

As extensive as the concept of and the resources required for 'Health for Korean Unification' are, and due to the limited access to information on the state of health and medical care in North Korea, discussion on 'Health for Korean Unification' has tended to be intermittent and lacked concrete action plans. In this article, we specifically distinguished areas of cooperation and selected five executable agenda that meet the goals of international development cooperation: 1) Health security; 2) Easing the burden of major diseases; 3) Resilient healthcare system; 4) R&D cooperation; 5) Sustainable cooperation system. Then we provided corresponding strategic priorities and operative directions, in consideration of future military and political sanctions against North Korea. The strategies we outline are sustainable, preemptive for problems that might affect lives of South and North Korean citizens, and satisfy the unmet needs of the North Korean health system. Throughout the process, we utilized a special platform, the 'Korean Peninsula Healthcare Cooperation Platform,' designed to enable continual communication across sectors engaged in public health and medical care. By doing so, we take the first step to actually carry out the 'Health for Korean Unification,' which tended to have remained on the discussion agenda.


Delivery of Health Care , Public Health , Humans , Democratic People's Republic of Korea , Communication , Republic of Korea
5.
Korean J Gastroenterol ; 82(3): 140-144, 2023 09 25.
Article En | MEDLINE | ID: mdl-37743813

Colonic interposition is the main procedure used in esophageal reconstruction. We report a rare case of simultaneous treatment of an anastomotic site stricture and a neoplasm in the interpositioned colon. A 69-year-old female visited our outpatient clinic with symptoms of progressive dysphagia for 1 year. At the age of 30 years, the patient underwent esophagectomy with retrosternal colonic interposition because of severe esophageal burns after chemical ingestion. Upper gastrointestinal endoscopy revealed stricture at the anastomosis site and a 10-mm flat elevated high-grade dysplasia in the interpositioned colon. First, through-the-scope balloon dilatation was performed for strictures. However, stenosis was observed during the second upper gastrointestinal endoscopy session. Therefore, a second session of through-the-scope balloon dilatation was performed, and simultaneously, endoscopic submucosal dissection was also successfully performed. After 2 months of follow-up, stenosis persisted; consequently, balloon dilatation was performed. No recurrence of neoplasm was confirmed endoscopically. Through-the-scope balloon dilatation of the stricture site and simultaneous endoscopic submucosal dissection of the neoplasm in the interpositioned colon were successfully performed.


Colonic Neoplasms , Endoscopic Mucosal Resection , Female , Humans , Adult , Aged , Esophagectomy/adverse effects , Constriction, Pathologic , Colonic Neoplasms/diagnosis , Colonic Neoplasms/surgery , Endoscopic Mucosal Resection/adverse effects
6.
Exp Mol Med ; 55(8): 1720-1733, 2023 08.
Article En | MEDLINE | ID: mdl-37524868

Autophagy functions in cellular quality control and metabolic regulation. Dysregulation of autophagy is one of the major pathogenic factors contributing to the progression of nonalcoholic fatty liver disease (NAFLD). Autophagy is involved in the breakdown of intracellular lipids and the maintenance of healthy mitochondria in NAFLD. However, the mechanisms underlying autophagy dysregulation in NAFLD remain unclear. Here, we demonstrate that the hepatic expression level of Thrap3 was significantly increased in NAFLD conditions. Liver-specific Thrap3 knockout improved lipid accumulation and metabolic properties in a high-fat diet (HFD)-induced NAFLD model. Furthermore, Thrap3 deficiency enhanced autophagy and mitochondrial function. Interestingly, Thrap3 knockout increased the cytosolic translocation of AMPK from the nucleus and enhanced its activation through physical interaction. The translocation of AMPK was regulated by direct binding with AMPK and the C-terminal domain of Thrap3. Our results indicate a role for Thrap3 in NAFLD progression and suggest that Thrap3 is a potential target for NAFLD treatment.


Non-alcoholic Fatty Liver Disease , Animals , Mice , AMP-Activated Protein Kinases/metabolism , Autophagy/genetics , Diet, High-Fat/adverse effects , Lipid Metabolism , Liver/metabolism , Mice, Inbred C57BL , Mitochondria/metabolism , Non-alcoholic Fatty Liver Disease/metabolism , Transcription Factors/metabolism , Humans , Hep G2 Cells
7.
PLoS One ; 18(7): e0289257, 2023.
Article En | MEDLINE | ID: mdl-37486919

[This corrects the article DOI: 10.1371/journal.pone.0277335.].

8.
Glob Public Health ; 18(1): 2229892, 2023 01.
Article En | MEDLINE | ID: mdl-37438859

Even with a reduced burden of malaria in sub-Saharan Africa (SSA), differences remain in the rate of change among countries and sub-regions. We used data from the Global Burden of Disease Study 2019 to establish the relationship between Development Assistance for Health (DAH) and governance and trends in malaria burden in SSA. The trend was estimated using the Joinpoint regression program and the Institute of Health Metrics and Evaluation's DAH database, and World Bank Governance Indicators to analyze the DAH and governance respectively from 2000 to 2017 and used two-way fixed effects to establish their association with the trend in the period. The findings showed decreases in SSA's age-standardised rates for disability-adjusted life years (ASDR) (-47% (95% uncertainty interval (UI) -69% to -14%)), deaths (-38% (95% UI -65% to -3%)), incidence (-35% (95% UI -44% to -25%)), and prevalence (-34% (95% UI -43% to -24%)). Decreases in ASDR were associated with increases in DAH (ß -134.18, standard error (SE) 27.26) and governance scores (ß -246.19, SE 39.13). The association between reductions in malaria burden and increases in DAH and in governance scores shows the need for accelerated funding of malaria programs and advocacy for better disease governance in malaria-endemic countries.Abbreviations: APC: Annual percentage change; ASDR: Age-standardised disability-adjusted life-year rate; ASIR: Age-standardised incidence rate; ASIR: Age-standardised incidence rate; ASMR: Age-standardised mortality rate; CSSA: Central sub-Saharan Africa; DAH: Development Assistance for Health; DALYs: Disability-adjusted life years; ESSA: Eastern sub-Saharan Africa; GBD: Global burden of disease; GHDx Global Health Data Exchange; IHME: Institute of Health Metrics and Evaluation; SDGs: Sustainable Development Goals; SSA: Sub-Saharan Africa; SSSA: Southern sub-Saharan Africa; UNSD: United Nations Statistics Division; USD: United States dollars; WGI: World Bank Governance Indicators; WHO: World Health Organization; WSSA: Western sub-Saharan Africa.


Cost of Illness , Malaria , Africa South of the Sahara/epidemiology , Malaria/epidemiology , Global Burden of Disease , Disability-Adjusted Life Years
9.
Healthcare (Basel) ; 11(11)2023 Jun 02.
Article En | MEDLINE | ID: mdl-37297769

To investigate the trend of healthcare needs among elders in low-income countries (LICs) and how changes in healthcare access and quality (HAQ) have correlated with these changes from 1990 to 2019, this study used estimates from the global burden of disease (GBD) 2019 study, including prevalence, years of life lost (YLLs), years lived with disability (YLDs), life expectancy (LE), health-adjusted life expectancy (HALE) and the HAQ index for years 1990 and 2019. We found increases in numbers of YLLs, YLDs, and prevalent cases due to NCDs, and the rate of increase was higher for all indicators of non-communicable diseases (NCDs) when compared with communicable, maternal, neonatal and nutritional diseases among elders. We also observed increases in LE and HALE among all countries. However, this was also challenged by increases in unhealthy life years (ULYs) and their constant percentage of LE. The HAQ index of LICs was also found to be low, although it had increased during the period. A reduction in the burden of acute diseases explains the increase in LE, but increases in ULYs and the NCD burden were also observed. LICs need to improve their HAQ to counter the growing threat of longer but less healthy lives.

10.
SSM Popul Health ; 23: 101445, 2023 Sep.
Article En | MEDLINE | ID: mdl-37334332

Background: Life expectancy gaps between North and South Korea have increased but contributions to these gaps remain poorly understood. Using data from the Global Burden of Disease Study (GBD) 2019, we examined how much death from specific diseases contributed to these gaps in different age groups over three decades. Methods: Data for death numbers and population by sex and 5-year age groups in both North and South Korea from 1990 to 2019 were extracted from the GBD 2019 to calculate life expectancy. Joinpoint regression analysis was conducted to investigate changes in life expectancy in North and South Korea. We used decomposition analysis to partition differences in life expectancy within and between the two Koreas into changes in age- and cause-specific death contributions. Results: Life expectancy increased in two Koreas from 1990 to 2019, but North Korea experienced a marked decline in life expectancy during the mid-1990s. The life expectancy gaps between the two Koreas were greatest in 1999, with a difference of 13.3 years for males and 14.9 years for females. The main contributors to these gaps were higher under-5 mortality from nutritional deficiencies for males (4.62 years) and females (4.57 years) in North Korea, accounting for about 30% of the total gap in life expectancy. After 1999, the life expectancy gaps reduced but persisted with differences of about ten years by 2019. Notably, chronic diseases contributed to about 8 out of 10 years of life expectancy gap between the two Koreas in 2019. Differential cardiovascular disease mortality in the older groups was the main contributor to the life expectancy gap. Conclusions: The contributors to this gap have shifted from nutritional deficiencies in children younger than five years to cardiovascular disease among elderly people. Efforts for strengthening social and healthcare systems are needed to curb this large gap.

11.
PLoS One ; 18(6): e0280779, 2023.
Article En | MEDLINE | ID: mdl-37343005

Risk perception research, targeting the general public, necessitates the study of the multi-faceted aspects of perceived risk through a holistic approach. This study aimed to investigate the association between the two dimensions of risk perception of COVID-19, i.e., risk as a feeling and analysis, trust in the current government, political ideologies, and socio-demographic factors in South Korea. This study used a year-long repeated cross-sectional design, in which a national sample (n = 23,018) participated in 23 consecutive telephone surveys from February 2020 to February 2021. Most factors differed in the magnitude and direction of their relationships with the two dimensions of risk perception. However, trust in the current government, alone, delineated an association in the same direction for both dimensions, i.e., those with a lower level of trust exhibited higher levels of cognitive and affective risk perception. Although these results did not change significantly during the one-year observation period, they are related to the political interpretation of risk. This study revealed that affective and cognitive risk perceptions addressed different dimensions of risk perception. These findings could help governments and health authorities better understand the nature and mechanisms of public risk perception when implementing countermeasures and policies in response to the COVID-19 pandemic and other public health emergencies.


COVID-19 , Humans , COVID-19/epidemiology , Cross-Sectional Studies , Trust/psychology , Pandemics , Government , Surveys and Questionnaires , Republic of Korea/epidemiology , Demography
13.
Soc Sci Med ; 326: 115926, 2023 06.
Article En | MEDLINE | ID: mdl-37121069

OBJECTIVE: Suicide ideation is the first stage of suicide behavior, and the long-term course of suicide ideation is highly variable. The aim of this study is to identify trajectories of suicide ideation over an 8-year period and explore the association of socioeconomic status (SES) with suicide ideation trajectories. METHODS: We included 10,017 participants from Waves 7-15 of the Korea Welfare Panel Study; these have data on suicidal ideation (2012-2020). Trajectories analysis was conducted to identify distinct trajectories of suicidal ideation. Multinomial logistic regression was used to examine associations of SES with suicidal ideation trajectories. The interaction effects between current SES and prospective economic condition on trajectories were examined using a synergy index (SI). RESULTS: We identified three suicide ideation trajectory groups: low-stable, moderate-decreasing, and high-persistent. Individuals in both moderate-decreasing and high-persistent trajectories had poorer current SES and prospective economic conditions than low-stable trajectories. Interestingly, those reporting poorer prospective economic conditions had a greater risk of being in a high-persistent trajectory than being in a moderate-decreasing trajectory. Further, individuals with poorer current SES and prospective economic conditions were more likely to be in the high-persistent trajectory. CONCLUSIONS: Our findings demonstrated three distinct trajectories of suicide ideation which provide useful information for specific preventive interventions that could be developed. Moreover, poor prospective economic condition is a significant predictor of the high-persistent suicide ideation trajectory. Supporting economic difficulties and helping make goals and plans to strengthen positive thinking would help attenuate suicidal ideation and prevent suicidal behavior.


Suicidal Ideation , Humans , Follow-Up Studies , Prospective Studies , Logistic Models , Socioeconomic Factors , Risk Factors
15.
Psychol Med ; 53(10): 4811-4819, 2023 07.
Article En | MEDLINE | ID: mdl-36803587

BACKGROUND: Attention deficit-hyperactivity disorder (ADHD) is related to depressive disorder, and adolescents with both present poor outcomes. However, evidence for the safety of concomitantly using a methylphenidate (MPH) and a selective serotonin reuptake inhibitor (SSRI) among adolescent ADHD patients is limited, a literature gap aimed to address through this investigation. METHODS: We conducted a new-user cohort study using a nationwide claims database in South Korea. We identified a study population as adolescents who were diagnosed both ADHD and depressive disorder. MPH-only users were compared with patients who prescribed both a SSRI and a MPH. Fluoxetine and escitalopram users were also compared to find a preferable treatment option. Thirteen outcomes including neuropsychiatric, gastrointestinal, and other events were assessed, taking respiratory tract infection as a negative control outcome. We matched the study groups using a propensity score and used the Cox proportional hazard model to calculate the hazard ratio. Subgroup and sensitivity analyses were conducted in various epidemiologic settings. RESULTS: The risks of all the outcomes between the MPH-only and SSRI groups were not significantly different. Regarding SSRI ingredients, the risk of tic disorder was significantly lower in the fluoxetine group than the escitalopram group [HR 0.43 (0.25-0.71)]. However, there was no significant difference in other outcomes between the fluoxetine and escitalopram groups. CONCLUSION: The concomitant use of MPHs and SSRIs showed generally safe profiles in adolescent ADHD patients with depression. Most of the differences between fluoxetine and escitalopram, except those concerning tic disorder, were not significant.


Attention Deficit Disorder with Hyperactivity , Central Nervous System Stimulants , Methylphenidate , Tic Disorders , Humans , Adolescent , Attention Deficit Disorder with Hyperactivity/drug therapy , Attention Deficit Disorder with Hyperactivity/epidemiology , Attention Deficit Disorder with Hyperactivity/psychology , Selective Serotonin Reuptake Inhibitors/adverse effects , Depression/drug therapy , Depression/epidemiology , Cohort Studies , Escitalopram , Fluoxetine/adverse effects , Methylphenidate/adverse effects , Central Nervous System Stimulants/adverse effects
16.
Psychiatry Investig ; 20(1): 35-42, 2023 Jan.
Article En | MEDLINE | ID: mdl-36721884

OBJECTIVE: Financial hardship influences depression risk, however, the pathway of the effect of financial hardship on depression and the role of self-esteem remain unclear. This study examined whether changes in financial hardship affected depression, and whether self-esteem mediated by this relationship. METHODS: Data from 99,588 observations of 15,331 individuals were extracted from 10 waves of the Korean Welfare Panel Study. The association between changes in financial hardship and depression was investigated using a generalized estimation equation, and the extent to which these associations were mediated by self-esteem was assessed. RESULTS: The results indicated that changes in financial hardship were associated with depression, with varying magnitude. Experiencing severe financial hardship over two consecutive years (odds ratio [OR]: 3.87, 95% confidence interval [CI]=3.09-4.85) or increased financial hardship over the previous year strongly influenced depression (e.g., OR: 3.88, 95% CI=3.09-4.86 for low financial hardship at t-1 year and high at t year). Self-esteem plays a mediating role in the relationship between changes in financial hardship and depression, where persistent financial hardship is associated with low self-esteem, leading to depression. CONCLUSION: These findings highlighted the importance of monitoring and intervention for financial hardship and psychological problems to help manage depression.

17.
PLoS One ; 17(11): e0277335, 2022.
Article En | MEDLINE | ID: mdl-36374924

BACKGROUND: Evidence for the trends and patterns of disease burden in North Korea is limited, and in-depth analysis based on several health outcomes for a better understanding remains challenging. Therefore, we aimed to investigate the trends and patterns of disease burden in North Korea between 1990 and 2019. METHODS: We used data from the Global Burden of Diseases (GBD) 2019 study to analyze the North Korean disease burden in comparison with four groups: global, South Korea, low-sociodemographic index (SDI) countries, Central and Eastern Europe, and Central Asia (former socialist countries). We also examined changes in the disease burden between 1990 and 2019 by disease category and age group. FINDINGS: In 2019, in North Korea, death rates and disability-adjusted life years (DALYs) rates were reduced by 22.2% and 30.7%, respectively, compared to 1990. The rates showed similar trends and patterns to that in former socialist countries. However, these reductions were lower than those of the global rates and rates in low-SDI countries and South Korea. Death rates and DALY rates for under five years dramatically decreased by more than 78%, similar to the trend in South Korea. In contrast, the decline in the death rates and DALY rates of adults was less than those worldwide and in low-SDI countries and South Korea. The burden of diseases among those aged ≥30 years increased largely due to the persistently high burden of non-communicable diseases (NCDs). Cardiovascular diseases, neoplasms, and chronic respiratory diseases were the leading causes of the disease burden in both 1990 and 2019. INTERPRETATION: North Korea's disease burden patterns and trends show clear improvements over the past 30 years but suggest that the current challenges of NCDs in the country are very serious. NCDs should be no longer neglected and should be prioritized in public health agendas in North Korea.


Global Burden of Disease , Noncommunicable Diseases , Adult , Humans , Quality-Adjusted Life Years , Democratic People's Republic of Korea , Global Health , Cost of Illness
18.
SSM Popul Health ; 19: 101246, 2022 Sep.
Article En | MEDLINE | ID: mdl-36238816

Background: Suicide in the working-age population is an important public health issue. This group is heterogeneous regarding marital status, education level, and employment status, which are generally important socioeconomic factors for suicide, and has a wide age range. This study aims to explore the individual and combined effect of these socioeconomic factors on suicide in different age groups among the working-age population. Methods: This study utilized a population-based case-control design for the working-age population in South Korea. Suicide cases were identified in Korean Governmental Death Registry from 2008 to 2017, and eight controls from Korea Community Health Survey were matched to each case by gender, age group, and year of suicide. Conditional logistic regression models estimated the relationship between marital status and socioeconomic status (SES) including educational attainment and employment status and suicide and examined the combined effect of the SES indicators and marital status on suicide. Results: Low education, single status, and unemployment or economically inactive status were associated with suicide, but their magnitude varied across SES indicators. The association between SES and suicide was more pronounced in younger adults. The suicide risk was highest among divorced women aged 25-34 years (OR = 7.93; 95% CI: 7.21-8.72). Individuals experiencing two social adversities among SES or marital status had a significantly increased suicide risk. Those who are divorced and unemployed or economically inactive have the highest suicide risk, specifically among men aged 24-35 years (OR = 17.53; 95% CI: 14.96-20.55). Conclusions: Marital status, education attainment, and employment status have a separate and combined impact on suicide among the working-age population. Specifically, the divorced and unemployed or economically inactive status amplified suicide risk, predominantly among young adults. Monitoring and intervention for those young adults should be considered for suicide prevention.

19.
Child Adolesc Psychiatry Ment Health ; 16(1): 80, 2022 Oct 11.
Article En | MEDLINE | ID: mdl-36221129

BACKGROUND: Methylphenidate (MPH) is the most frequently prescribed medication for the treatment of attention deficit hyperactivity disorder (ADHD). However, the safety of its long-term use remain unclear. In particular, real-world evidence of long-term MPH treatment regarding the risk of depression, conduct disorders, and psychotic disorders in children and adolescents is needed. This study aimed to compare the risks of depression, conduct disorder, and psychotic disorder between long- and short-term MPH treatments in children and adolescents. METHODS: This population-based cohort study used a nationwide claims database of all patients with ADHD in South Korea. Patients aged less than 18 years who were prescribed MPH were included in the study. Long- and short-term MPH were defined as > 1 year, and < 1 year, respectively. Overall, the risk of developing depressive disorder, conduct disorder and oppositional defiant disorder (ODD), and psychotic disorder were investigated. A 1:2 propensity score matching was used to balance the cohorts, and the Cox proportional hazards model was used to evaluate the safety of MPH. RESULTS: We identified 1309 long-term and 2199 short-term MPH users. Long-term MPH use was associated with a significantly lower risk of depressive (hazard ratio [HR], 0.70 [95% confidence interval [CI] 0.55-0.88]) and conduct disorders and ODD (HR, 0.52 [95% CI 0.38-0.73]) than short-term MPH use. Psychotic disorder was not significantly associated with long-term MPH use (hazard ratio [HR], 0.83 [95% confidence interval [CI] 0.52-1.32]). CONCLUSIONS: Our findings suggest that long-term MPH use may be associated with a decreased risk of depression, conduct disorders and ODD. Moreover, the long-term use of MPH does not increase the risk of psychotic disorders. Long-term MPH administration may be considered as a favourable treatment strategy for children and adolescents with ADHD regarding depressive, conduct, and psychotic disorders.

20.
Elife ; 102021 12 29.
Article En | MEDLINE | ID: mdl-34964438

Background: Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation and imbalances in lipid metabolism in the liver. Although nuclear receptors (NRs) play a crucial role in hepatic lipid metabolism, the underlying mechanisms of NR regulation in NAFLD remain largely unclear. Methods: Using network analysis and RNA-seq to determine the correlation between NRs and microRNA in human NAFLD patients, we revealed that MIR20B specifically targets PPARA. MIR20B mimic and anti-MIR20B were administered to human HepG2 and Huh-7 cells and mouse primary hepatocytes as well as high-fat diet (HFD)- or methionine-deficient diet (MCD)-fed mice to verify the specific function of MIR20B in NAFLD. We tested the inhibition of the therapeutic effect of a PPARα agonist, fenofibrate, by Mir20b and the synergic effect of combination of fenofibrate with anti-Mir20b in NAFLD mouse model. Results: We revealed that MIR20B specifically targets PPARA through miRNA regulatory network analysis of nuclear receptor genes in NAFLD. The expression of MIR20B was upregulated in free fatty acid (FA)-treated hepatocytes and the livers of both obesity-induced mice and NAFLD patients. Overexpression of MIR20B significantly increased hepatic lipid accumulation and triglyceride levels. Furthermore, MIR20B significantly reduced FA oxidation and mitochondrial biogenesis by targeting PPARA. In Mir20b-introduced mice, the effect of fenofibrate to ameliorate hepatic steatosis was significantly suppressed. Finally, inhibition of Mir20b significantly increased FA oxidation and uptake, resulting in improved insulin sensitivity and a decrease in NAFLD progression. Moreover, combination of fenofibrate and anti-Mir20b exhibited the synergic effect on improvement of NAFLD in MCD-fed mice. Conclusions: Taken together, our results demonstrate that the novel MIR20B targets PPARA, plays a significant role in hepatic lipid metabolism, and present an opportunity for the development of novel therapeutics for NAFLD. Funding: This research was funded by Korea Mouse Phenotyping Project (2016M3A9D5A01952411), the National Research Foundation of Korea (NRF) grant funded by the Korea government (2020R1F1A1061267, 2018R1A5A1024340, NRF-2021R1I1A2041463, 2020R1I1A1A01074940, 2016M3C9A394589324), and the Future-leading Project Research Fund (1.210034.01) of UNIST.


Fenofibrate/pharmacology , Hypolipidemic Agents/pharmacology , Lipid Metabolism , MicroRNAs/genetics , Non-alcoholic Fatty Liver Disease/genetics , PPAR alpha/genetics , Animals , Female , Humans , Male , Mice , MicroRNAs/metabolism , Non-alcoholic Fatty Liver Disease/physiopathology , PPAR alpha/metabolism
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