Abnormal aggregation of α-synuclein is a key element in the pathogenesis of several neurodegenerative diseases, including Parkinson’s disease (PD), dementia with Lewy bodies, and multiple system atrophy. α-synuclein aggregation spreads through various brain regions during the course of disease progression, a propagation that is thought to be mediated by the secretion and subsequent uptake of extracellular α-synuclein aggregates between neuronal cells. Thus, aggregated forms of this protein have emerged as promising targets for disease-modifying therapy for PD and related diseases. Here, we generated and characterized conformation-specific antibodies that preferentially recognize aggregated forms of α-synuclein. These antibodies promoted phagocytosis of extracellular α-synuclein aggregates by microglial cells and interfered with cell-to-cell propagation of α-synuclein. In an α-synuclein transgenic model, passive immunization with aggregate-specific antibodies significantly ameliorated pathological phenotypes, reducing α-synuclein aggregation, gliosis, inflammation, and neuronal loss. These results suggest that conformation-specific antibodies targeting α-synuclein aggregates are promising therapeutic agents for PD and related synucleinopathies.

BACKGROUND: Cardiovascular risk remains increased despite optimal low density lipoprotein cholesterol (LDL-C) level induced by intensive statin therapy. Therefore, recent guidelines recommend non-high density lipoprotein cholesterol (non-HDL-C) as a secondary target for preventing cardiovascular events. The aim of this study was to assess the efficacy and tolerability of omega-3 fatty acids (OM3-FAs) in combination with atorvastatin compared to atorvastatin alone in patients with mixed dyslipidemia. METHODS: This randomized, double-blind, placebo-controlled, parallel-group, and phase III multicenter study included adults with fasting triglyceride (TG) levels ≥200 and <500 mg/dL and LDL-C levels <110 mg/dL. Eligible subjects were randomized to ATOMEGA (OM3-FAs 4,000 mg plus atorvastatin calcium 20 mg) or atorvastatin 20 mg plus placebo groups. The primary efficacy endpoints were the percent changes in TG and non-HDL-C levels from baseline at the end of treatment. RESULTS: After 8 weeks of treatment, the percent changes from baseline in TG (−29.8% vs. 3.6%, P<0.001) and non-HDL-C (−10.1% vs. 4.9%, P<0.001) levels were significantly greater in the ATOMEGA group (n=97) than in the atorvastatin group (n=103). Moreover, the proportion of total subjects reaching TG target of <200 mg/dL in the ATOMEGA group was significantly higher than that in the atorvastatin group (62.9% vs. 22.3%, P<0.001). The incidence of adverse events did not differ between the two groups. CONCLUSION The addition of OM3-FAs to atorvastatin improved TG and non-HDL-C levels to a significant extent compared to atorvastatin alone in subjects with residual hypertriglyceridemia.

OBJECTIVE: To investigate the correlation between mechanography and clinical parameters in older people at 3 and 6 months after hip fracture surgery.METHODS: A longitudinal follow-up study was conducted in university hospitals with 38 patients at 3 months and 29 patients at 6 months after hip fracture surgery. Subjects 65 years and older completed measurements on the Berg Balance Scale (BBS), Functional Ambulation Category (FAC), walking ability by Koval, Korean version of the fatigue, resistance, ambulation, illnesses, and loss of weight (K-FRAIL) scale, and hand grip strength. The Romberg test with center of foot pressure (COP), chair rise test (CRT), and maximal power (W/kg) were conducted using the Leonardo Mechanograph.RESULTS: COP area and pathway length were correlated with BBS at 3 and 6 months. Change in BBS was correlated with change in COP area, but not with change in COP length. COP area and pathway length were correlated with K-FRAIL at 3 months after hip fracture surgery. The same COP variables showed correlations with FAC and walking ability by Koval at 6 months after surgery. Maximal power during CRT had correlation with chair rise time but not with other clinical parameters.CONCLUSION: The study revealed correlations between mechanography and clinical parameters in older people at 3 and 6 months after hip fracture surgery. Both the clinical assessment and objective test with mechanography may be required for the quantitative and sensitive measurement of postural balance and lower limb muscle power.
Dependent Ambulation ; Fatigue ; Follow-Up Studies ; Foot ; Hand ; Hand Strength ; Hip Fractures ; Hip ; Hospitals, University ; Humans ; Lower Extremity ; Muscle Strength ; Postural Balance ; Walking

BACKGROUND: To estimate and compare the trends of all-cause and cause-specific mortality rates for subjects with and without diabetes in South Korea, from 2003 to 2013. METHODS: Using a population-based cohort (2003 to 2013), we evaluated annual mortality rates in adults (≥30 years) with and without diabetes. The number of subjects in this analysis ranged from 585,795 in 2003 to 670,020 in 2013. RESULTS: Age- and sex-adjusted all-cause mortality rates decreased consistently in both groups from 2003 to 2013 (from 14.4 to 9.3/1,000 persons in subjects with diabetes and from 7.9 to 4.4/1,000 persons in those without diabetes). The difference in mortality rates between groups also decreased (6.61 per 1,000 persons in 2003 to 4.98 per 1,000 persons in 2013). The slope associated with the mortality rate exhibited a steeper decrease in subjects with diabetes than those without diabetes (regression coefficients of time: −0.50 and −0.33, respectively; P=0.004). In subjects with diabetes, the mortality rate from cardiovascular disease decreased by 53.5% (from 2.73 to 1.27 per 1,000 persons, P for trend < 0.001). Notably, the decrease in mortality from ischemic stroke (79.2%, from 1.20 to 0.25 per 1,000 persowns) was more profound than that from ischemic heart disease (28.3%, from 0.60 to 0.43 per 1,000 persons). CONCLUSION: All-cause and cardiovascular mortality rates decreased substantially from 2003 to 2013, and the decline in ischemic stroke mortality mainly contributed to the decreased cardiovascular mortality in Korean people with diabetes.
Adult* ; Cardiovascular Diseases ; Cohort Studies ; Diabetes Mellitus* ; Humans ; Korea* ; Mortality* ; Myocardial Ischemia ; Stroke

OBJECTIVE: To investigate if walking is independently associated with low back pain (LBP) in the general population. METHODS: This cross-sectional study used public data from the Fourth and Fifth Korean National Health and Nutrition Examination Survey. Subjects included 5,982 community-dwelling adults aged ≥50 years. Presence of current LBP was defined as LBP for 1 month or more in the past 3 months. Walking was measured as total walking duration for the past week and subjects were divided into four quartiles. Independent effect of walking on LBP was determined using odds ratios (OR) adjusted for age, sex, osteoporosis, depression or anxiety, and radiographic lumbar spondylosis. RESULTS: Prevalence of LBP was 26.4% in this population. Older people and women had higher prevalence of current LBP. Prevalence of obesity and osteoporosis was higher in subjects with current LBP and quality of life was poorer in subjects with current LBP. Adjusted logistic regression model revealed that older age (OR, 1.655; p=0.018), female sex (OR, 2.578; p<0.001), radiographic lumbar spondylosis (OR, 2.728; p<0.001), depression or anxiety (OR, 5.409; p<0.001), and presence of osteoporosis (OR, 1.467; p=0.002) were positively associated with current LBP. Walking decreased prevalence of current LBP proportionally (2nd quartile OR, 0.795; 3rd quartile OR, 0.770; and 4th quartile OR, 0.686 compared with the 1st quartile of walking). CONCLUSION: Walking was negatively associated with LBP. Further studies are needed to reveal causal relationship of this phenomenon.
Adult ; Anxiety ; Cross-Sectional Studies* ; Depression ; Female ; Humans ; Logistic Models ; Low Back Pain* ; Nutrition Surveys ; Obesity ; Odds Ratio ; Osteoporosis ; Prevalence ; Quality of Life ; Spondylosis ; Walking*

Well-established standards and specifications for medical devices not only provide clarity and consistency in licensing processes but also secure device safety and effectiveness. This study reviewed regulatory standards and specifications for veterinary medical devices in Korea based on data obtained through analyses of those medical devices. General standards for electromechanical, electromagnetic, and biological safety and individual standards for 76 electric and 70 general medical device products have been established by the Korean Ministry of Food and Drug Safety. However, the first standards and specifications for veterinary medical devices were established in March 2000 for two products (disposable needle and syringe). Similar to the large number of standards for medical devices, there have been general standards for safety and individual standards for 72 veterinary medical devices (27 electric medical devices, 12 non-electric medical devices, 10 medical supplies, and 23 other types) established since 2014. These new standards considered, among other aspects, the devices' applications, usage characteristics, and industrial environment. To date, the establishment of standards and specifications for veterinary medical devices remains limited. This study suggests that improvements should be made to the regulation of general and individual standards associated with various veterinary medical instruments, supplies, and in vitro diagnostic medical reagents.
Equipment and Supplies ; Equipment Safety ; In Vitro Techniques ; Indicators and Reagents ; Korea* ; Licensure ; Magnets ; Needles

BACKGROUND/AIMS: Abnormal visceral sensitivity and disordered motility are common in patients with diabetes mellitus. The purpose of the present study was to investigate whether visceral sensation and bowel motility were altered in a rat model of type 2 diabetes mellitus accompanied by weight loss. METHODS: A type 2 diabetic rat model in adulthood was developed by administrating streptozotocin (STZ; 90 mg/kg, i.p.) to neonatal rats. Eight weeks after STZ administration, rats with blood glucose level of 200 mg/dL or higher were selected and used as diabetic group (n = 35) in this study. Abdominal withdrawal reflex and arterial pulse rate were measured to examine visceral nociception induced by colorectal distension (0.1-1.0 mL). The amplitude, frequency, and area under the curve (AUC) of spontaneous phasic contractions of colonic circular muscles were recorded in vitro to examine colonic motility. RESULTS: STZ-treated diabetic rats gained significantly less weight for 8 weeks than control (P < 0.01). Forty-eight percent of the diabetic rats showed enhanced visceral nociceptive response to colorectal distension. Diabetic rats did not differ from control rats in colorectal compliance. However, the frequency and AUC, not the amplitude, of colonic spontaneous contraction in vitro was significantly decreased in diabetic rats compared to control rats (P < 0.01 in frequency and P < 0.05 in AUC). CONCLUSIONS: These results demonstrate visceral hypersensitivity and colonic dysmotility in a rat model of type 2 diabetes mellitus accompanied by weight loss.
Animals ; Area Under Curve ; Blood Glucose ; Colon* ; Compliance ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Heart Rate ; Humans ; Hypersensitivity* ; Models, Animal ; Muscles ; Nociception ; Rats* ; Reflex ; Sensation ; Streptozocin ; Weight Loss

BACKGROUND: A systematic literature review of interspinous dynamic stabilization, including DIAM, Wallis, Coflex, and X-STOP, was conducted to assess its safety and efficacy. METHODS: The search was done in Korean and English, by using eight domestic databases which included KoreaMed and international databases, such as Ovid Medline, Embase, and the Cochrane Library. A total of 306 articles were identified, but the animal studies, preclinical studies, and studies that reported the same results were excluded. As a result, a total of 286 articles were excluded and the remaining 20 were included in the final assessment. Two assessors independently extracted data from these articles using predetermined selection criteria. Qualities of the articles included were assessed using Scottish Intercollegiate Guidelines Network (SIGN). RESULTS: The complication rate of interspinous dynamic stabilization has been reported to be 0% to 32.3% in 3- to 41-month follow-up studies. The complication rate of combined interspinous dynamic stabilization and decompression treatment (32.3%) was greater than that of decompression alone (6.5%), but no complication that significantly affected treatment results was found. Interspinous dynamic stabilization produced slightly better clinical outcomes than conservative treatments for spinal stenosis. Good outcomes were also obtained in single-group studies. No significant difference in treatment outcomes was found, and the studies compared interspinous dynamic stabilization with decompression or fusion alone. CONCLUSIONS: No particular problem was found regarding the safety of the technique. Its clinical outcomes were similar to those of conventional techniques, and no additional clinical advantage could be attributed to interspinous dynamic stabilization. However, few studies have been conducted on the long-term efficacy of interspinous dynamic stabilization. Thus, the authors suggest further clinical studies be conducted to validate the theoretical advantages and clinical efficacy of this technique.
Decompression, Surgical ; Humans ; Postoperative Complications ; *Spinal Fusion/adverse effects/methods ; Spinal Stenosis/physiopathology/surgery

Sarcopenia has been defined as the considerable loss of skeletal muscle mass and strength that results in frailty in the elderly. Because muscle tissue plays diverse important roles in human, sarcopenia presents many negative health-related consequences including impaired energy homeostasis, falls and cardiovascular disease, and subsequently higher mortality. It is becoming evident that sarcopenia has a negative impact on the healthy life of the elderly. The European Working Group on Sarcopenia, the International Working Group on Sarcopenia and the Asian Working Group on Sarcopenia have released position statement regarding sarcopenia, and more recently the Foundation for the National Institutes of Health Sarcopenia Project has provided a new guideline for assessment of sarcopenia. At this time, there have been several data delineating the status of sarcopenia in Korea. This review focuses on largescale cohorts that assessed sarcopenia and highlights the controversies surrounding the clinical definition and prevalence of sarcopenia in Korea.
Aged ; Asian Continental Ancestry Group ; Cardiovascular Diseases ; Cohort Studies ; Homeostasis ; Humans ; Korea ; Mortality ; Muscle, Skeletal ; National Institutes of Health (U.S.) ; Prevalence* ; Sarcopenia*

BACKGROUND: Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist has a wide-ranging influence on multiple components of metabolic syndrome. The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is a useful animal model of metabolic syndrome. To determine genes related to metabolic syndrome, we examined overlapping genes that are simultaneously decreased by PPAR-gamma agonists and increased in OLETF rats using microarrays in two different models. METHODS: In the first microarray analysis, PPAR-gamma agonist-treated db/db mice were compared to standard diet-fed db/db mice. In the second microarray analysis, OLETF rats were compared to Long-Evans Tokushima Otsuka (LETO) rats (control of OLETF rats). RESULTS: Among the overlapping genes, in the present study, we validated that lipocalin-2 expression was significantly decreased in the visceral adipose tissue of PPAR-gamma agonist-treated db/db mice compared to standard diet-fed db/db mice and increased in OLETF rats compared to LETO rats using real time reverse transcription polymerase chain reaction. Furthermore, we showed for the first time that lipocalin-2 expression was significantly increased in the visceral adipose tissues of obese humans compared with nonobese humans. In addition, the expression level of lipocalin-2 in human visceral adipose tissue had a significant positive correlation with body mass index, serum interleukin-6, adipocyte fatty acid binding protein levels, and white blood cell count. CONCLUSION: Lipocalin-2 was confirmed to be a significant adipokine affected by PPAR-gamma agonist and obesity in the present study. Also, for the first time in human visceral adipose tissue, it was determined that the expression of lipocalin-2 from obese humans was significantly increased and correlated with circulating inflammatory markers.
Adipocytes ; Adipokines ; Animals ; Body Mass Index ; Carrier Proteins ; Genes, Overlapping ; Humans ; Interleukin-6 ; Intra-Abdominal Fat ; Leukocyte Count ; Mice ; Microarray Analysis ; Models, Animal ; Obesity ; Peroxisomes ; Polymerase Chain Reaction ; PPAR gamma ; Rats ; Rats, Inbred OLETF ; Reverse Transcription ; Transcriptome*