Differential trends and patterns of sociodemographic disparities in burden of mental disorders, substance use disorder and self-harm across age groups: ecological study in 204 countries using the Global Burden of Disease Study 2019.

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.

Living longer but in poor health: healthcare system responses to ageing populations in industrialised countries based on the Findings from the Global Burden of Disease Study 2019.

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.

Glucose-mediated mitochondrial reprogramming by cholesterol export at TM4SF5-enriched mitochondria-lysosome contact sites.

BACKGROUND: Transmembrane 4 L six family member 5 (TM4SF5) translocates subcellularly and functions metabolically, although it is unclear how intracellular TM4SF5 translocation is linked to metabolic contexts. It is thus of interests to understand how the traffic dynamics of TM4SF5 to subcellular endosomal membranes are correlated to regulatory roles of metabolisms. METHODS: Here, we explored the metabolic significance of TM4SF5 localization at mitochondria-lysosome contact sites (MLCSs), using in vitro cells and in vivo animal systems, via approaches by immunofluorescence, proximity labelling based proteomics analysis, organelle reconstitution etc. RESULTS: Upon extracellular glucose repletion following depletion, TM4SF5 became enriched at MLCSs via an interaction between mitochondrial FK506-binding protein 8 (FKBP8) and lysosomal TM4SF5. Proximity labeling showed molecular clustering of phospho-dynamic-related protein I (DRP1) and certain mitophagy receptors at TM4SF5-enriched MLCSs, leading to mitochondrial fission and autophagy. TM4SF5 bound NPC intracellular cholesterol transporter 1 (NPC1) and free cholesterol, and mediated export of lysosomal cholesterol to mitochondria, leading to impaired oxidative phosphorylation but intact tricarboxylic acid (TCA) cycle and ß-oxidation. In mouse models, hepatocyte Tm4sf5 promoted mitophagy and cholesterol transport to mitochondria, both with positive relations to liver malignancy. CONCLUSIONS: Our findings suggested that TM4SF5-enriched MLCSs regulate glucose catabolism by facilitating cholesterol export for mitochondrial reprogramming, presumably while hepatocellular carcinogenesis, recapitulating aspects for hepatocellular carcinoma metabolism with mitochondrial reprogramming to support biomolecule synthesis in addition to glycolytic energetics.

TM4SF5-mediated abnormal food-intake behavior and apelin expression facilitate non-alcoholic fatty liver disease features.

Transmembrane 4 L six family member 5 (TM4SF5) engages in non-alcoholic steatohepatitis (NASH), although its mechanistic roles are unclear. Genetically engineered Tm4sf5 mice fed ad libitum normal chow or high-fat diet for either an entire day or a daytime-feeding (DF) pattern were analyzed for metabolic parameters. Compared to wild-type and Tm4sf5-/- knockout mice, hepatocyte-specific TM4SF5-overexpressing Alb-TGTm4sf5-Flag (TG) mice showed abnormal food-intake behavior during the mouse-inactive daytime, increased apelin expression, increased food intake, and higher levels of NASH features. DF or exogenous apelin injection of TG mice caused severe hepatic pathology. TM4SF5-mediated abnormal food intake was correlated with peroxisomal ß-oxidation, mTOR activation, and autophagy inhibition, with triggering NASH phenotypes. Non-alcoholic fatty liver disease (NAFLD) patients' samples revealed a correlation between serum apelin and NAFLD activity score. Altogether, these observations suggest that hepatic TM4SF5 may cause abnormal food-intake behaviors to trigger steatohepatitic features via the regulation of peroxisomal ß-oxidation, mTOR, and autophagy.

The burden of malaria in sub-Saharan Africa and its association with development assistance for health and governance: An exploration of the GBD 2019 study.

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.

Correction: Trends and patterns of North Korea's disease burden from 1990 to 2019: Results from Global Burden of Disease study 2019.

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

Changes in contributions of age- and cause-specific mortality to the widening life expectancy gap between North and South Korea, 1990-2019: An analysis of the Global Burden of Disease Study 2019.

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.

The Trend of Healthcare Needs among Elders and Its Association with Healthcare Access and Quality in Low-Income Countries: An Exploration of the Global Burden of Disease Study 2019.

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.

Long-term trajectories of suicide ideation and its socioeconomic predictors: A longitudinal 8-year follow-up study.

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.

Financial Hardship, Depression, and Self-Esteem: Temporal Analysis Using a Korean Panel Study.

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.

Trends and patterns of North Korea's disease burden from 1990 to 2019: Results from Global Burden of Disease study 2019.

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.

Single and combined effects of marital status, education attainment, and employment status on suicide among working-age population: A case-control study in South Korea.

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.

Systemic TM4SF5 overexpression in ApcMin/+ mice promotes hepatic portal hypertension associated with fibrosis.

Mutation of the gene for adenomatous polyposis coli (APC), as seen in ApcMin/+ mice, leads to intestinal adenomas and carcinomas via stabilization of ß-catenin. Transmembrane 4 L six family member 5 (TM4SF5) is involved in the development of non-alcoholic fatty liver disease, fibrosis, and cancer. However, the functional linkage between TM4SF5 and APC or ß-catenin has not been investigated for pathological outcomes. After interbreeding ApcMin/+ with TM4SF5-overexpressing transgenic (TgTM4SF5) mice, we explored pathological outcomes in the intestines and livers of the offspring. The intestines of 26-week-old dual-transgenic mice (ApcMin/+:TgTM4SF5) had intramucosal adenocarcinomas beyond the single-crypt adenomas in ApcMin/+ mice. Additional TM4SF5 overexpression increased the stabilization of ß-catenin via reduced glycogen synthase kinase 3ß (GSK3ß) phosphorylation on Ser9. Additionally, the livers of the dualtransgenic mice showed distinct sinusoidal dilatation and features of hepatic portal hypertension associated with fibrosis, more than did the relatively normal livers in ApcMin/+ mice. Interestingly, TM4SF5 overexpression in the liver was positively linked to increased GSK3ß phosphorylation (opposite to that seen in the colon), ß-catenin level, and extracellular matrix (ECM) protein expression, indicating fibrotic phenotypes. Consistent with these results, 78-week-old TgTM4SF5 mice similarly had sinusoidal dilatation, immune cell infiltration, and fibrosis. Altogether, systemic overexpression of TM4SF5 aggravates pathological abnormalities in both the colon and the liver. [BMB Reports 2022; 55(12): 609-614].

Clinical Characteristics Associated with Physical Violence in the Elderly: A Retrospective Multicenter Analysis.

BACKGROUND: Elder abuse is predicted to increase with the rapid population ageing in many countries. Violent injury is influenced by individual factors as well as interpersonal and social relationships, with different manifestations based on changes in the socioeconomic position of older adults. We comparatively investigated the clinical and injury characteristics of physical violence in the elderly with those in another age group. METHODS: We included elderly patients (age ≥65 years) who visited six emergency departments (ED) with violence-induced injuries in 2017. The control group comprised patients aged 45-64 years, selected by 1:2 matching based on hospital and sex. Data were extracted from the National Emergency Department Information System and electronic medical records. Both groups were compared for injury mechanism, injury location, activity during injury, diagnosis, and clinical outcomes. RESULTS: Among the 316,944 patients who presented to the 6 ED, 89,178 (28.1%) had traumatic injuries, and 1.6% and 4.5% of injuries were sustained due to violence in the ≥65 and 45-64 year age groups, respectively. There were no significant intergroup differences in the perpetrator (P=0.27), body parts affected (P=0.63), and diagnosis (P=0.23), whereas the older adult group had a significantly higher proportion of traumatic injury by fall (P=0.01), at road and traffic facilities (P=0.01), during work (P=0.01), and multiple injuries (P<0.01). CONCLUSION: The increase in non-regular workers in the elderly after retirement may have increased the risk of traumatic workplace injuries. As workplace injuries may be a new risk factor for physical violence in the elderly, institutional workplace injury prevention policy is needed.

Prioritising Risk Factors for Prescription Drug Overdose among Older Adults in South Korea: A Multi-Method Study.

Older adults are vulnerable to drug overdose. We used a multi-method approach to prioritise risk factors for prescription drug overdose among older adults. The study was conducted in two stages. First, risk factors for drug overdose were classified according to importance and changeability through literature review, determined through 2-phase expert surveys. Second, prescription drug overdose cases during 2011-2015 were selected from a national cohort; the prevalence of 'more important' or 'more changeable' factors determined in stage one was investigated. Scores were assigned according to the Basic Priority Rating Scale formula, reflecting the problem size and seriousness and intervention effectiveness. In the first stage, polypharmacy, old-old age, female sex, chronic disease, psychiatric disease, and low socioeconomic status (SES) were selected as risk factors. In the second stage, 93.9% of cases enrolled had chronic medical disease; 78.3% were using multiple drugs. Low SES was more prevalent than other risk factors. As per the scoring formula, chronic medical disease, polypharmacy, psychiatric disease, low SES, female sex, and old-old age were the most important risk factors in order of priority. Patients with chronic medical disease and those using multiple medications should be prioritised in overdose prevention interventions among older adults.

Instructor-led distance learning for training students in cardiopulmonary resuscitation: A randomized controlled study.

STUDY HYPOTHESIS: Cardiopulmonary resuscitation (CPR) training can increase the likelihood of patient survival and better neurological outcomes. However, conventional learning (CL) has cost, time, and space constraints. This study aimed to evaluate whether laypersons who completed instructor-led distance learning (DL) acquired a level of CPR skill comparable to that achieved via CL training. METHODS: This randomized controlled study recruited students from 28 Korean high schools who were randomized to complete instructor-led DL or CL training. The CL training involved classroom-based face-to-face training, whereas the instructor-led DL training was provided online using a videoconferencing system. RESULTS: The study enrolled 62 students who were randomized to the CL group (31 participants) or the DL group (31 participants). Relative to the CL group, the DL group achieved remarkably similar results in terms of most CPR variables. In addition, the DL group had a significant improvement in the mean compression depth (before: 46 mm [interquartile range: 37-52 mm] vs. after: 49 mm [interquartile range: 46-54 mm], p<0.001). CONCLUSIONS: Instructor-led DL can be a suitable alternative to CL for providing CPR training to laypersons. In settings like the current COVID-19 pandemic, where face-to-face CL is not practical, DL may be a useful tool for delivering CPR training.

Effects of positive dispatcher encouragement on the maintenance of bystander cardiopulmonary resuscitation quality.

BACKGROUND: Implementation of dispatcher-assisted cardiopulmonary resuscitation (DACPR) has increased the likelihood of bystander CPR upon cardiac arrest. However, the quality of CPR has been found to be very low. In this study, we aimed to compare CPR quality between the current DACPR practices and the interventional instruction of adding verbal encouragement from the dispatcher. METHODS: In this randomized controlled trial, we recruited adult (age ≥18) laypersons who were non-health care providers and had never received any previous verified CPR training. They were randomly selected to perform DACPR using metronome sounds (mDACPR) as per the standard protocol, or DACPR with metronome sounds along with human encouragement (mheDACPR). The ratio of accurate compression rate, depth, and complete release for each CPR phase was examined. RESULTS: Sixty nine records (34, mDACPR; 35, mheDACPR) were taken. The median proportion of accurate chest compression rate was initially 29.5% with mDACPR, and significantly increased to 71% after 2 minutes of CPR administration (P = .046). However, the median ratio of accurate chest compression depth was 61.5% in the first phase, and significantly decreased to 0% in the last phase (P < .001). In contrast, for the mheDACPR group, a high accurate compression rate was maintained throughout the 2 minutes of CPR administration (91%, 100%, 100%, 100%). CONCLUSION: To maintain the quality of CPR administered by bystanders, continuous feedback and repeated human encouragement should be provided during DACPR. Active dispatcher intervention reduces the time required to reach an appropriate CPR rate and allows for the maintenance of accurate compression rates.

NMR investigation on the DNA binding and B-Z transition pathway of the Zα domain of human ADAR1.

Human ADAR1, which has two left-handed Z-DNA binding domains, preferentially binds Z-DNA rather than B-DNA with a high binding affinity. Z-DNA can be induced in long genomic DNA by Z-DNA binding proteins through the formation of two B-Z junctions with the extrusion of one base pair from each junction. We performed NMR experiments on complexes of Zα(ADAR1) with three DNA duplexes at a variety of protein-to-DNA molar ratios. This study confirmed that the Zα(ADAR1) first binds to an 8-bp CG-rich DNA segment via a unique conformation during B-Z transition and the neighboring AT-rich region becomes destabilized. We also found that, when DNA duplexes have only 6-bp CG-rich segment, the interaction with Zα(ADAR1) did not affect the thermal stabilities of the 6-bp CG-rich segment as well as the neighboring two A·T base pairs. These results indicate that four Zα(ADAR1) proteins interact with the 8-bp DNA sequence containing a 6-bp CG-repeat segment as well as a dinucleotide step, even though the dinucleotid step contains A∙T base pairs. Thus this study suggests that the length of the CG-rich region is more important than the specific DNA sequence for determining which base-pair is extruded from the B-Z junction structure. This study also found that the Zα(ADAR1) in complex with a 11-bp DNA duplex exhibits a Z-DNA-bound conformation distinct from that of free Zα(ADAR1) and the initial contact conformations of Zα(ADAR1) complexed with 13-bp DNA duplexes.