Familial risk of seropositive rheumatoid arthritis and interaction with smoking: a population-based cohort study.

OBJECTIVES: We evaluated the familial risk of seropositive rheumatoid arthritis (RA) and examined interactions between family history and smoking. METHODS: Using the National Health Insurance and Health Screening Program databases, which include information on familial relationships and lifestyle factors, we identified 5 524 403 individuals with first-degree relatives (FDRs) from 2002-2018. We calculated familial risk using hazard ratios (HRs) with 95% CIs which compare the risk of individuals with and without affected FDRs. Interactions between smoking and family history were assessed on an additive scale using the relative excess risk due to interaction (RERI). RESULTS: Individuals with affected FDR had 4.52-fold (95% CI 3.98, 5.12) increased risk of disease compared with those with unaffected FDR. Familial risk adjusted for lifestyle factors decreased slightly (HR 4.49), suggesting that a genetic contribution is the predominant driver in the familial aggregation of RA. Smoking was associated with an increased risk of disease that was more pronounced among heavy (HR 1.92 95% CI 1.70, 2.18) compared with moderate (HR 1.15 95% CI 1.04, 1.28) smoking. In the interaction analysis, the risk associated with the combined effect of smoking and family history was higher than the sum of their individual effects, though statistically non-significant (RERI 1.30 95% CI ‒0.92, 3.51). Heavy smokers with a positive family history showed a prominent interaction (RERI 4.13 95% CI ‒0.88, 9.13) which exceeded moderate smokers (RERI 0.61 95% CI ‒1.90, 3.13), suggesting a dose-response interaction pattern. CONCLUSION: Our findings indicate the possibility of an interaction between RA-associated genes and smoking.

Familial Risk of Renal Cell Cancer and Interaction with Obesity and Hyperglycemia: A Population-Based Study.

PURPOSE: We quantified the familial risk of renal cell cancer (RCC) among first-degree relatives (FDRs) on a population level, and examined interactions between family history and body mass index or blood glucose. MATERIALS AND METHODS: Using the National Health Insurance database, which covers the entire Korean population, and the National Health Screening Program, we constructed a cohort of 5,524,403 individuals with blood-related FDRs and their lifestyle factors from 2002 to 2018. We calculated familial risk using incidence risk ratios (IRRs) with 95% confidence intervals, which compares the risk of individuals with and without FDR. The combined effect and interaction of a given risk factor and family history of RCC were measured by the relative excess risk due to interaction. RESULTS: Individuals with affected FDRs showed a 2.29-fold (95% CI 1.68-3.13) increased risk of disease. Familial risk adjusted for lifestyle factors showed minimal attenuation (IRR 2.25; 95% CI: 1.65-3.08), suggesting that genetic predisposition is the main contributor in the familial aggregation of RCC. Individuals with both a positive family history and overweight/obesity (IRR 3.71, 95% CI 2.50-4.92) or hyperglycemia (IRR 4.52, 95% CI 2.59-6.45) had a significantly higher risk that exceeded the sum of their individual risks, suggesting an interaction that was statistically significant (relative excess risk due to interaction 95% CI: 0.91, -0.21-2.12; 2.21, 0.28-4.14). CONCLUSIONS: Our findings suggest an interaction between genetic and environmental factors, namely obesity and hyperglycemia. Individuals with both factors should be considered a high-risk group and advised to undergo genetic counseling.

Familial Risk of Inflammatory Bowel Disease: A Population-Based Cohort Study in South Korea.

BACKGROUND & AIMS: Despite the rapid increase in inflammatory bowel disease (IBD), population-level familial risk estimates of IBDs still are lacking in Asian-Pacific countries. We aimed to quantify the familial risk of incident IBD among first-degree relatives (FDRs) of individuals with IBD according to age, sex, and familial relationship. METHODS: Using the South Korea National Health Insurance database (2002-2017), which has complete population coverage and confirmed accuracy of both FDR information and IBD diagnoses, we constructed a cohort of 21,940,795 study subjects comprising 12 million distinct families. We calculated incidence risk ratios of ulcerative colitis (UC) or Crohn's disease (CD) in individuals of affected FDRs compared with individuals without affected FDRs. RESULTS: Of 45,717 individuals with UC and 17,848 individuals with CD, 3.8% and 3.1% represented familial cases, respectively. Overall, there was a 10.2-fold (95% CI, 9.39-11.1) and a 22.1-fold (95% CI, 20.5-24.5) significantly higher adjusted risk of UC and CD among FDRs of individuals with vs without IBD. Familial risk was highest among twins, followed by nontwin siblings, and then offspring of affected parents. Familial risk generally was higher within generations (sibling-sibling) vs between generations (parent-offspring). Familial risk also increased with the increasing number of affected FDRs. CONCLUSIONS: According to this population-based analysis, there is a substantially increased risk of IBD among FDRs of affected individuals, with the highest risk among siblings and for CD. These findings might help with an earlier diagnosis and appropriate therapeutic intervention in FDRs of individuals with IBD. Dedicated studies are needed to evaluate the contributions of shared early-in-life environmental exposures and genetic factors.

Familial risk of Behçet's disease among first-degree relatives: a population-based aggregation study in Korea.

OBJECTIVE: Previous studies have indicated that Behçet's disease (BD) has a genetic component, however population-level familial risk estimates are unavailable. We quantified the familial incidence and risk of BD in first-degree relatives (FDR) according to age, sex and type of family relationship. METHODS: Using the Korean National Health Insurance database, which has full population coverage and confirmed FDR information, we constructed a cohort of 21 940 795 individuals comprising 12 million families, which were followed for a familial occurrence of BD from 2002 to 2017. Age- and sex-adjusted incidence risk ratios for BD were calculated in individuals with affected FDR compared with those without affected FDR. RESULTS: Among the total study population, 53 687 individuals had affected FDR, of whom 284 familial cases developed BD with an incidence of 3.57/104 person-years. The familial risk (incidence) for BD was increased to 13.1-fold (2.71/104 person-years) in individuals with an affected father, 13.9-fold (3.11/104 person-years) with affected mother, 15.2-fold (4.9/104 person-years) with an affected sibling and the highest risk was 165-fold (46/104 person-years) with an affected twin. Familial risks showed age dependence, being higher in younger age groups. The sex-specific familial risk was similar in males and females. CONCLUSION: This study provides quantified estimates of familial incidence and risk in FDR of BD patients in an entire population. Familial risks were higher within generation (sibling-sibling) vs between generations (parent-offspring). This implicates complex interactions between genetic factors and shared childhood environmental exposures in the pathogenesis of BD.

Incidence, mortality, and cardiovascular diseases in pituitary adenoma in Korea: a nationwide population-based study.

PURPOSE: Few nationally representative studies have evaluated the epidemiology of PA (pituitary adenoma). This South Korean study evaluated the incidence of different PA subtypes, cardiovascular disease (CVD), and related mortality. METHODS: This population-based study evaluated 31,898 patients with PA during 2005-2015. The incidence of PA, mortality, and CVD occurrence in PA cases were evaluated during a median follow-up of 5.3 years (range: 0-10 years). Cox regression analysis was used to evaluate the associations between CVD and mortality. RESULTS: The annual incidences (per 100,000 population) were 3.5 for non-functioning pituitary adenoma (NFPA), 1.6 for prolactinoma (PRL), 0.5 for growth hormone-secreting pituitary adenoma (GH), and 0.2 for adrenocorticotropic or thyroid-stimulating hormone-secreting pituitary adenoma (ACTH + TSH). The standardized mortality ratios were 1.9 for ACTH + TSH, 1.7 for NFPA with hypopituitarism, 1.4 for NFPA without hypopituitarism, 1.3 for GH, and 1.1 for PRL. During 2005-2015, the overall incidence of CVD among PA patients was 6.6% (2106 cases), and the standardized incidence ratios were 4.1 for hemorrhagic stroke, 3.0 for ischemic stroke, and 1.7 for acute myocardial infarction. The standardized incidence ratios for stroke were significantly higher in the ACTH + TSH and NFPA groups, which also had higher risks of CVD-related mortality, relative to the PRL and GH groups. CONCLUSION: South Korea had a relatively high incidence of NFPA. The incidence of stroke was highest for ACTH + TSH and NFPA, which was directly related to mortality during long-term follow-up. Patients with these types of PA should receive stroke prevention measures to reduce their risk of mortality.

Familial Risk for Moyamoya Disease Among First-Degree Relatives, Based on a Population-Based Aggregation Study in Korea.

BACKGROUND AND PURPOSE: Genetic factors have been known to play a role in the etiology of moyamoya disease (MMD); however, population-level studies quantifying familial risk estimates are unavailable. We aimed to quantify familial incidence and risk for MMD in first-degree relatives (FDR) in the general population of Korea. METHODS: By using the Korean National Health Insurance database which has complete population coverage and confirmed FDR information, we constructed a cohort of 21 940 795 study subjects constituting 12 million families with blood-related FDR and followed them for a familial occurrence of MMD from 2002 to 2017. Incidence risk ratios were calculated as MMD incidence in individuals with affected FDR compared with those without affected FDR, according to age, sex, and family relationships. RESULTS: Among total study subjects, there were 22 459 individuals with affected FDR, of whom 712 familial cases developed MMD with an incidence of 21.8/104 person-years. Overall, the familial risk for MMD was 132-fold higher in individuals with versus without affected FDR. Familial risk (incidence risk ratio; incidence/104 person-years) increased with the degree of genetic relatedness, being highest in individuals with an affected twin (1254.1; 230.0), followed by a sibling (212.4; 35.6), then mother (87.7; 14.4) and father (62.5; 10.4). Remarkably, there was no disease concordance between spouses. The risks were age-dependent and were particularly high in younger age groups. Familial risks were similar in males and females, and the risk of disease transmission was higher in same-sex parent-offspring and sibling pairs. CONCLUSIONS: Our study indicates that genetic predisposition is the predominant driver in MMD pathogenesis, with minimal contribution of environmental factors. These results could be utilized to direct future genetic studies and clinical risk counseling.

Incidence, prevalence, and survival of moyamoya disease in Korea: a nationwide, population-based study.

BACKGROUND AND PURPOSE: There is a scarcity of information on the epidemiology and natural course of moyamoya disease. The aim of this study was to investigate the nationwide epidemiological features of moyamoya disease in Korea, including incidence, prevalence, and survival. METHODS: We used the data from nationwide, population-based Health Insurance Review and Assessment Service claims database and Rare Intractable Disease registration program, which includes physician-certified diagnoses based on uniform criteria for moyamoya disease from 2007 to 2011. Age-specific incidence and prevalence were calculated, and survival was examined using Kaplan-Meier method. RESULTS: The total number of patients with moyamoya disease was 8154 in 2011, with a female-to-male ratio of 1.8. The incidence from 2007 to 2011 was 1.7 to 2.3/10(5), and the prevalence in 2011 was 16.1/10(5). In total, 66.3% of patients aged 0 to 14 years underwent surgery, whereas only 21.5% in the older than 15 years age group underwent surgery. The 1- and 5-year survival rates of adult patients were 96.9% and 92.9%, respectively, and of child patients were 99.6% and 99.3%, respectively. CONCLUSIONS: The prevalence and incidence presented in this study are higher than those in previous studies. This study demonstrates that the burden of moyamoya disease in Korea is substantial.

A population-based approach indicates an overall higher patient mortality with peritoneal dialysis compared to hemodialysis in Korea.

To date, only a few large-scale studies have measured the effect of dialysis modality on mortality in Asian populations. Here, we sought to compare survival between incident hemodialysis (HD) and peritoneal dialysis (PD) patients using the Korean Health Insurance Review & Assessment Service database. This enabled us to perform a population-based complete survey that included 32,280 incident dialysis patients and followed them for a median of 26.5 months. To reduce biases due to nonrandomization, we first matched 7049 patient pairs with similar propensity scores. Using the log-rank test, we found the mortality rate in PD patients was significantly higher than that in HD patients. Subsequent subgroup analyses indicated that in older patients (55 years and older), with the exception of the subgroup of patients with no comorbidities and the subgroup of patients with malignancy, PD was consistently associated with a higher mortality rate. In younger patients (under 55 years), regardless of the covariates, the survival rate of PD patients was comparable to that of HD patients. Thus, while the overall mortality rate was higher in incident PD patients, mortality rates of some incident PD and HD patients were comparable in Korea.

Familial Risk of Gout and Interaction With Obesity and Alcohol Consumption: A Population-Based Cohort Study in Korea.

OBJECTIVE: Population-based studies of the familial aggregation of gout are scarce, and gene/environment interactions are not well studied. This study was undertaken to evaluate the familial aggregation of gout as well as assess interactions between family history and obesity or alcohol consumption on the development of gout. METHODS: Using the Korean National Health Insurance database, which includes information regarding familial relationships and risk factor data, we identified 5,524,403 individuals from 2002 to 2018. Familial risk was calculated using hazard ratios (HRs) with 95% confidence intervals (95% CIs) to compare the risk in individuals with and those without affected first-degree relatives. Interactions between family history and obesity/alcohol consumption were assessed on an additive scale using the relative excess risk due to interaction (RERI). RESULTS: Individuals with a gout-affected first-degree relative had a 2.42-fold (95% CI 2.39, 2.46) increased risk of disease compared to those with unaffected first-degree relatives. Having both a family history of gout and being either overweight or having moderate alcohol consumption was associated with a markedly increased risk of disease, with HRs of 4.39 (95% CI 4.29, 4.49) and 2.28 (95% CI 2.22, 2.35), respectively, which exceeded the sum of their individual risks but was only statistically significant in overweight individuals (RERI 0.96 [95% CI 0.85, 1.06]). Obese individuals (RERI 1.88 [95% CI 1.61, 2.16]) and heavy drinkers (RERI 0.36 [95% CI 0.20, 0.52]) had a more prominent interaction compared to overweight individuals and moderate drinkers, suggesting a dose-response interaction pattern. CONCLUSION: Our findings indicate the possibility of an interaction between gout-associated genetic factors and obesity/alcohol consumption.

Familial Risk of Graves Disease Among First-Degree Relatives and Interaction With Smoking: A Population-Based Study.

CONTEXT: Population-based studies on the familial aggregation of Graves disease (GD) are scarce and gene-environment interactions are not well-studied. OBJECTIVE: We evaluated the familial aggregation of GD and assessed interactions between family history and smoking. METHODS: Using the National Health Insurance database, which includes information on familial relationships and lifestyle risk factors, we identified 5 524 403 individuals with first-degree relatives (FDRs). Familial risk was calculated using hazard ratios (HRs), comparing the risk of individuals with and without affected FDRs. Interactions between smoking and family history were assessed on an additive scale using relative excess risk due to interaction (RERI). RESULTS: The HR among individuals with affected FDRs was 3.39 (95% CI, 3.30-3.48) compared with those without affected FDR, and among individuals with affected twin, brother, sister, father, and mother, the HRs were 36.53 (23.85-53.54), 5.26 (4.89-5.66), 4.12 (3.88-4.38), 3.34 (3.16-3.54), and 2.63 (2.53-2.74), respectively. Individuals with both a positive family history and smoking had an increased risk of disease (HR 4.68) with statistically significant interaction (RERI 0.94; 95% CI, 0.74-1.19). Heavy smokers with a positive family history showed a nearly 6-fold increased risk, which was higher than moderate smoking, suggesting a dose-response interaction pattern. Current smoking also showed a statistically significant interaction with family history (RERI 0.52; 95% CI, 0.22-0.82), while this was not observed for former smoking. CONCLUSION: A gene-environment interaction can be suggested between smoking and GD-associated genetic factors, which diminishes after smoking cessation. Smokers with a positive family history should be considered a high-risk group and smoking cessation should be advised.

Familial Risk and Interaction With Smoking and Alcohol Consumption in Bladder Cancer: A Population-Based Cohort Study.

Background: Although genetic factors are known to play a role in the pathogenesis of bladder cancer, population-level familial risk estimates are scarce. We aimed to quantify the familial risk of bladder cancer and analyze interactions between family history and smoking or alcohol consumption. Methods: Using the National Health Insurance database, we constructed a cohort of 5,524,403 study subjects with first-degree relatives (FDRs) and their lifestyle risk factors from 2002 to 2019. Familial risk was calculated using hazard ratios (HRs) with 95% confidence intervals (CIs) that compare the risk of individuals with and without affected FDRs. Interactions between family history and smoking or alcohol intake were assessed on an additive scale using the relative excess risk due to interaction (RERI). Results: Offspring with an affected parent had a 2.09-fold (95% CI: 1.41 - 3.08) increased risk of disease compared to those with unaffected parents. Familial risks of those with affected father and mother were 2.26 (95% CI: 1.51 - 3.39) and 1.10 (95% CI: 0.27 - 4.41), respectively. When adjusted for lifestyle factors, HR reduced slightly to 2.04 (95% CI: 1.38 - 3.01), suggesting that a genetic predisposition is the main driver in the familial aggregation. Smokers with a positive family history had a markedly increased risk of disease (HR: 3.60, 95% CI: 2.27 - 5.71), which exceeded the sum of their individual risks, with statistically significant interaction (RERI: 0.72, 95% CI: 0.31 - 1.13). For alcohol consumption, drinkers with a positive family history also had an increased risk of disease, although the interaction was not statistically significant (RERI: 0.05, 95% CI: -3.39 - 3.48). Conclusion: Smokers and alcohol consumers with a positive family history of bladder cancer should be considered a high-risk group and be advised to undergo genetic counseling.

Familial Risk of Hashimoto's Thyroiditis Among First-Degree Relatives: A Population-Based Study in Korea.

Background: Few small-scale studies have reported a genetic and familial predisposition in Hashimoto's thyroiditis (HT), however, quantified familial risk estimates from population-level data are unavailable. We aimed to estimate the incidence and familial risk of HT among first-degree relatives (FDR) according to age, sex, and family relationships. Methods: We conducted a population-based study in the general population of Korea from 2002 to 2017. Using the nationwide health insurance database, which has full population coverage and family relationship information, a cohort of 22 million individuals with blood-related FDR comprising 12 million families were followed up for a familial occurrence of HT. Age- and sex-adjusted incidence risk ratios (IRRs) were calculated in individuals with an affected FDR compared with those without an affected FDR. Results: Among 21,940,795 individuals, 234,912 had an HT-affected FDR, of whom 2425 familial cases developed HT with an incidence of 7.12/10,000 person-years. The familial risk for HT was 6.5-fold (95% confidence interval [CI]: 6.24-6.78) higher in individuals with versus without affected FDR. According to relationship, familial risks were IRR 102.71, IRR 7.80, IRR 5.54, and IRR 5.52 with an affected twin, sibling, mother, and father, respectively, and the corresponding incidence (/10,000 person-years) was 115.57, 10.66, 5.73, and 5.91. Same-sex twins had three times higher risk of developing HT than opposite-sex twins (IRR 121.01 vs. 21.46). The sex-specific familial risk was higher in males than females. The risks demonstrated age dependence, being higher in younger age groups. Conclusions: This study represents the largest population-based study of familial HT risk in Asia. We demonstrated elevated familial risk of incident HT among FDR, but with lower magnitude as those observed in previous studies. Familial risk increased with the degree of genetic relatedness among FDR indicating a prominent role of genetic factors in the familial aggregation of HT. Elevated risks in the younger age groups should motivate clinicians to screen people with a family history, especially those <30 years.

Familial Risk and Its Interaction With Body Mass Index and Physical Activity in Anterior Cruciate Ligament Injury Among First-Degree Relatives: A Population-Based Cohort Study.

BACKGROUND: Genetic and behavioral risk factors have been suggested to play a role in anterior cruciate ligament (ACL) injury. However, population-based familial risk estimates are unavailable. PURPOSE: To quantify familial risk of ACL injury among first-degree relatives (FDRs) after controlling for certain behavioral risk factors. To estimate the combined effect of family history and body mass index (BMI) or physical activity on the risk of ACL injury. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Using nationwide data from the Korean National Health Insurance and National Health Screening Program databases on kinship, lifestyle habits, and anthropometrics, 5,184,603 individuals with blood-related FDRs were identified from 2002 to 2018. Familial risk of ACL injury, as represented as incidence risk ratios (IRRs) with 95% CIs, was analyzed using Cox proportional hazards models among individuals with versus without affected FDRs. Analyses were adjusted for age, sex, and behavioral risk factors. Interaction testing between familial history and BMI or physical activity was performed on an additive scale. RESULTS: The risk of ACL injury was 1.79-fold higher (IRR, 1.79; 95% CI, 1.73-1.85) among individuals with versus without affected FDRs, and the incidence was 12.61 per 10,000 person-years. The IRR (95% CI) was highest with affected twins at 4.49 (3.01-6.69), followed by siblings at 2.31 (2.19-2.44), the father at 1.58 (1.49-1.68), and the mother at 1.52 (1.44-1.61). High BMI and high level of physical activity were significantly associated with the risk of ACL injury. Individuals with positive family history and either high BMI or physical activity had a 2.59- and 2.45-fold increased risk of injury as compared with the general population, respectively, and the combined risks exceeded the sum of their independent risks. CONCLUSION: Familial factors are risk factors for ACL injury with an additional contribution of 2 behavioral factors: BMI and physical activity level. A significant interaction was observed between family history of ACL injury and high BMI/level of physical activity.

Syndecan-2 regulates the migratory potential of melanoma cells.

Syndecan-2, a transmembrane heparan sulfate proteoglycan, is a critical mediator in the tumorigenesis of colon carcinoma cells. We explored the function of syndecan-2 in melanoma, one of the most invasive types of cancers, and found that the expression of this protein was elevated in tissue samples from both nevus and malignant human melanomas but not in melanocytes of the normal human skin tissues. Similarly, elevated syndecan-2 expression was observed in various melanoma cell lines. Overexpression of syndecan-2 enhanced migration and invasion of melanoma cells, whereas the opposite was observed when syndecan-2 levels were knocked down using small inhibitory RNAs. Syndecan-2 expression was enhanced by fibroblast growth factor-2, which is known to stimulate melanoma cell migration; however, alpha-melanocyte-stimulating hormone decreased syndecan-2 expression and melanoma cell migration and invasion in a melanin synthesis-independent manner. Furthermore, syndecan-2 overexpression rescued the migration defects induced by alpha-melanocyte-stimulating hormone treatment. Together, these data strongly suggest that syndecan-2 plays a crucial role in the migratory potential of melanoma cells.

Incidence, Long-Term Visual Outcomes, and Mortality in Retinopathy of Prematurity in Korea: A Nationwide Population-Based Study.

Purpose: To evaluate the incidence, visual prognosis, and mortality in retinopathy of prematurity (ROP) in Korea. Methods: We used the National Health Insurance and the Korean Disability Registry database, which covers the entire newborn population in 2006 to 2014 and includes information on all newborns diagnosed with ROP until 2016. Using these databases, we evaluated the incidence, rate of visual impairment (VI), and mortality in patients with ROP according to the birth weight categories and treatment modalities. Results: The ROP incidence per 1000 newborns was 1.99, which broke down into 317.14 in the very low birth weight (VLBW) less than 1500 g population, 25.45 in the 1500 to 2499 g population, and 0.29 in the 2500 g or greater population. When assessed at age 10, the VI rate was 2.2 per 100 person-years, which was highest at 4.5 per 100 person-years in the VLBW population compared with the population in other birth weight categories. Among treated cases, the proportion of VI in patients undergoing laser photocoagulation or cryotherapy was 1.6% (42/2595), which was lower than the 2.9% (2/68) of patients treated with anti-vascular endothelial growth factor injection, and 32.2% (82/255) of patients undergoing vitrectomy or scleral buckling. The mortality rate was 4.8 per 1000 person-years, which was highest in the VLBW population, but similar across treatment modalities. Conclusions: The ROP incidence in Korea was approximately 1 in 500 among all newborns, and 1 in 3 in the VLBW population. As the first nationwide population-based study of long-term visual prognosis in ROP, we report the higher VI rate in ROP than previously determined in other studies. Differences in visual outcomes and comparable mortality risks between treatment modalities require further verification.

Progressive degeneration of dopamine neurons in 6-hydroxydopamine rat model of Parkinson's disease does not involve activation of caspase-9 and caspase-3.

6-Hydroxydopamine (6-OHDA), a neurotoxin that causes the death of dopamine (DA) neurons, is commonly used to produce experimental models of Parkinson's disease (PD) in rodents. In the rat model of PD first described by Sauer and Oertel, DA neurons progressively die over several weeks following a striatal injection of 6-OHDA. It is generally assumed that DA neurons die through apoptosis after exposure to 6-OHDA, but data supporting activation of a caspase enzymatic cascade are lacking. In this study, we sought to determine if caspases involved in the intrinsic apoptotic cascade play a role in the initial stages of 6-OHDA-induced death of DA neurons in the progressively lesioned rat model of PD. We found that injection of 6-OHDA into adult rat striatum did not activate caspase-9 or caspase-3 or increase levels of caspase-dependent cleavage products in the substantia nigra at various survival times up to 7 days after the lesion, even though this paradigm produced DA neuronal loss. These data suggest that in the adult rat brain DA neurons whose terminals are challenged with 6-OHDA do not die through a classical caspase-dependent apoptotic mechanism.

Structural and Functional Alterations at Pre-Epileptic Stage Are Closely Associated with Epileptogenesis in Pilocarpine-induced Epilepsy Model.

Pilocarpine-induced rat epilepsy model is an established animal model that mimics medial temporal lobe epilepsy in humans. The purpose of this study was to investigate neuroimaging abnormalities in various stages of epileptogenesis and to correlate them with seizure severity in pilocarpine-induced rat epilepsy model. Fifty male Sprague-Dawley rats were subject to continuous video and electroencephalographic monitoring after inducing status epilepticus (SE) and seizure severity was estimated by frequency and total durations of class 3 to 5 spontaneous recurrent seizures (SRS) by modified Racine's classification. The 7.0 Tesla magnetic resonance imaging (MRI) with high resolution flurodeoxyglucose positron emission tomography (FDG-PET) was performed at 3 hours, 1, 3, 7 days and 4 weeks after the initial insult. The initial SRS was observed 9.7±1.3 days after the pilocarpine injection. MRI revealed an abnormal T2 signal change with swelling in both hippocampi and amygdala in acute (day 1 after injection) and latent phases (days 3 and 7), in association with PET hypometabolism in these areas. Interestingly, the mean frequency of class 3 to 5 SRS was positively correlated with abnormal T2 signals in hippocampal area at 3 days. SRS duration became longer with more decreased glucose metabolism in both hippocampi and amygdala at 7 days after pilocarpine injection. This study indicates that development and severity of SRS at chronic phase could be closely related with structural and functional changes in hippocampus during the latent period, a pre-epileptic stage.

Incidence, mortality, and causes of death in physician-diagnosed primary Sjögren's syndrome in Korea: A nationwide, population-based study.

OBJECTIVES: The objective of this study was to investigate the epidemiological features of primary Sjögren's syndrome (pSS) in Korea at a national level, including the incidence, mortality, and causes of death. METHODS: We used a national, population-based registry database called the Rare Intractable Disease Registration Program from the Health Insurance Review and Assessment Service to obtain pSS patient data for the period between 2010 and 2014. pSS was diagnosed by a physician based on uniform criteria. We also used data from Statistics Korea to confirm the mortality and causes of death. RESULTS: Between 2010 and 2014, the total number of patients newly diagnosed with pSS was 5891, resulting in an annual incidence of 2.34 per 100,000 individuals. The female-to-male ratio was 14.5:1. A total of 114 pSS patients died during the study period. The overall survival rate of pSS patients was 99.0%, and the 1-year, 2-year, and 5-year survival rates were 98.7%, 98.1%, and 97.1%, respectively, and the standardized mortality ratio (SMR) was 1.47 (2.14 for males and 1.35 for females). The most common causes of death were respiratory disease (n = 25; 21.9%) followed by circulatory diseases (n = 21; 18.4%), musculoskeletal connective tissue diseases (n = 21; 18.4%), and cancer (n=19; 16.7%). CONCLUSIONS: The national incidence of pSS in Korea presented in this study was lower in comparison with reports from other countries. However, the mortality rate was significantly higher than the corresponding values in the age- and gender-matched general population. The higher mortality in pSS patients is attributable to respiratory diseases and lung cancer.

Prevalence, Age at Diagnosis, Mortality, and Cause of Death in Retinitis Pigmentosa in Korea-A Nationwide Population-based Study.

PURPOSE: To determine the prevalence and mortality of retinitis pigmentosa (RP) patients in Korea. DESIGN: Population-based retrospective cohort study. METHODS: We used data covering the 2011-2014 period from the Rare Intractable Disease (RID) registry and Health Insurance Review and Assessment (HIRA) service, which include information on all patients diagnosed with RP based on predefined diagnostic criteria. Using the HIRA-RID database, we evaluated the prevalence and age at diagnosis of RP patients across the entire Korean population. We further linked the data from Statistics Korea to the HIRA-RID database to confirm mortality and causes of death. RESULTS: The prevalence in the total population across all ages was 11.09 per 105 people, and the prevalence in those over the age of 40 was 16.16 per 105 people. The age at diagnosis ranged from 0 to 95 and, on average, was 44.8. The standardized mortality ratio (SMR) was 1.56 for all ages, peaking at 2.61 in men aged 40-59, which was attributed to 6.6-fold higher suicide rates than the same age group in the general male population. CONCLUSIONS: This is the first nationwide epidemiologic study of RP patients covering the entire population of all ages. The results suggest that the prevalence of RP in Korea is about 1 in 9000 for all ages and 1 in 6000 for those over 40 years of age. The higher mortality of RP patients than that of the general population is attributable to a high suicide rate in male RP patients of working ages, which necessitates a careful attention to their mental health.