Background: The purpose of this study was to evaluate the effect of patellar facet angle on pre- and postoperative patellofemoral alignment and the progress of arthritis of the patellofemoral joint in posterior-stabilized total knee arthroplasty (PS TKA) without patellar resurfacing. Methods: Patients who had a PS TKA for a varus osteoarthritic knee who were followed up for more than 2 years were included in this study. The radiologic and clinical outcomes were compared between 72 knees (group A) whose patellar facet angle was greater than 126° (> 126°) and 32 knees (group B) whose patellar facet angle was smaller than or equal to 126° (≤ 126°). For the radiologic assessment, the Kellgren-Lawrence grade, mechanical femorotibial angle, Insall-Salvati ratio, patellar tilt angle, patellar displacement and the osteosclerosis of the patellar ridge were evaluated. The range of motion (ROM) and patient-reported outcomes (the Knee Society knee score, the Knee Society function score, the Feller patellar score, and the Kujala patellofemoral score) were used for the clinical assessment. Results: The preoperative patellar tilt angle was 9.8° (standard deviation [SD] 5.5) and 14.6° (SD 4.1) in group A and group B, respectively, a significant difference (p < 0.001). Other preoperative radiologic parameters and preoperative patient-reported outcomes and ROM showed no significant difference between the two groups (all parameters (p> 0.05). At the last-follow-up, 22 knees (30.6%) showed progression of osteosclerosis of the patellar ridge in group A and 13 knees (40.6%) showed progression of osteosclerosis in group B (p = 0.371). The postoperative radiologic and clinical outcomes showed no significant difference between the two groups (all parameters,p > 0.05). Conclusions Although a narrow patellar facet angle was related to an increase of lateral tilting of the patella, it showed no impact on the preoperative clinical assessment. The radiologic and clinical outcomes evaluated after the PS TKA showed no statistical difference according to the patellar shape. Although the patellar shape evaluated by the patellar facet angle can partially affect the preoperative patellofemoral alignment, this study result indicated insignificant clinical relevance of the patellar shape in the PS TKA.

To date, researchers have developed various animal models of Alzheimer’s disease (AD) to investigate its mechanisms and to identify potential therapeutic treatments. A widely recognized model that mimics the pathology of human sporadic AD involves intracerebroventricular (ICV) injection with streptozotocin (STZ). However, ICV injections are an invasive approach, which creates limitations in generalizing the results. In this study, we produced a rodent model of AD using STZ (3 mg/kg) injection via the cisterna magna (CM) once every week for 4 weeks, and analyzed at 4 weeks and 16 weeks after final injection. In the CM-STZ rodent model of AD, we observed increase in extracellular amyloid-beta (Aβ) deposition and decrease and abnormal morphology of post-synaptic protein, PSD95 in 16 weeks STZ-injected group. The model developed using our less-invasive method induced features of AD-like pathology, including significantly increased extracellular amyloid-beta deposition, and decreased synaptic protein in the hippocampus. These findings supporting the success of this alternative approach, and thus, we suggest this is a promising, less invasive model for use in future AD research.

Ischemic stroke results from arterial occlusion and can cause irreversible brain injury. A non-human primate (NHP) model of ischemic stroke was previously developed to investigate its pathophysiology and for efficacy testing of therapeutic candidates; however, fine motor impairment remains to be well-characterized. We evaluated hand motor function in a cynomolgus monkey model of ischemic stroke. Endovascular transient middle cerebral artery occlusion (MCAO) with an angiographic microcatheter induced cerebral infarction. In vivo magnetic resonance imaging mapped and measured the ischemia-induced infarct lesion. In vivo diffusion tensor imaging (DTI) of the stroke lesion to assess the neuroplastic changes and fiber tractography demonstrated three-dimensional patterns in the corticospinal tract 12 weeks after MCAO. The hand dexterity task (HDT) was used to evaluate fine motor movement of upper extremity digits. The HDT was modified for a home cage-based training system, instead of conventional chair restraint training. The lesion was localized in the middle cerebral artery territory, including the sensorimotor cortex. Maximum infarct volume was exhibited over the first week after MCAO, which progressively inhibited ischemic core expansion, manifested by enhanced functional recovery of the affected hand over 12 weeks after MCAO. The total performance time decreased with increasing success rate for both hands on the HDT. Compensatory strategies and retrieval failure improved in the chronic phase after stroke. Our findings demonstrate the recovery of fine motor skill after stroke, and outline the behavioral characteristics and features of functional disorder of NHP stroke model, providing a basis for assessing hand motor function after stroke.

ymptoms of Parkinson’s disease (PD) caused by loss of dopaminergic neurons are accompanied by movement disorders, including tremors, rigidity, bradykinesia, and akinesia. Non-human primate (NHP) models with PD play an essential role in the analysis of PD pathophysiology and behavior symptoms. As impairments of hand dexterity function can affect activities of daily living in patients with PD, research on hand dexterity function in NHP models with chronic PD is essential. Traditional rating scales previously used in the evaluation of animal spontaneous behavior were insufficient due to factors related to subjectivity and passivity. Thus, experimentally designed applications for an appropriate apparatus are necessary. In this study, we aimed to longitudinally assess hand dexterity function using hand dexterity task (HDT) in NHP-PD models. To validate this assessment, we analyzed the alteration in Parkinsonian tremor signs and the functionality of presynaptic dopaminergic neuron using positron emission tomography imaging of dopamine transporters in these models. In addition, a significant inverse correlation between HDT and DAT level was identified, but no local bias was found. The correlation with intention tremor signs was lower than the resting tremor. In conclusion, the evaluation of HDT may reflect behavioral symptoms of NHP-PD models. Furthermore, HDT was effectively used to experimentally distinguish intention tremors from other tremors.

Mitochondria continuously fuse and divide to maintain homeostasis. An impairment in the balance between the fusion and fission processes can trigger mitochondrial dysfunction. Accumulating evidence suggests that mitochondrial dysfunction is related to neurodegenerative diseases such as Parkinson's disease (PD), with excessive mitochondrial fission in dopaminergic neurons being one of the pathological mechanisms of PD. Here, we investigated the balance between mitochondrial fusion and fission in the substantia nigra of a non-human primate model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD. We found that MPTP induced shorter and abnormally distributed mitochondria. This phenomenon was accompanied by the activation of dynamin-related protein 1 (Drp1), a mitochondrial fission protein, through increased phosphorylation at S616. Thereafter, we assessed for activation of the components of the cyclin-dependent kinase 5 (CDK5) and extracellular signal-regulated kinase (ERK) signaling cascades, which are known regulators of Drp1(S616) phosphorylation. MPTP induced an increase in p25 and p35, which are required for CDK5 activation. Together, these findings suggest that the phosphorylation of Drp1(S616) by CDK5 is involved in mitochondrial fission in the substantia nigra of a non-human primate model of MPTP-induced PD.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; Cyclin-Dependent Kinase 5 ; Cyclin-Dependent Kinases ; Dopaminergic Neurons ; Homeostasis ; Mitochondria ; Mitochondrial Dynamics ; Neurodegenerative Diseases ; Parkinson Disease ; Phosphorylation ; Phosphotransferases ; Primates ; Substantia Nigra

The function of microglia/macrophages after ischemic stroke is poorly understood. This study examines the role of microglia/macrophages in the focal infarct area after transient middle cerebral artery occlusion (MCAO) in rhesus monkeys. We measured infarct volume and neurological function by magnetic resonance imaging (MRI) and non-human primate stroke scale (NHPSS), respectively, to assess temporal changes following MCAO. Activated phagocytic microglia/macrophages were examined by immunohistochemistry in post-mortem brains (n=6 MCAO, n=2 controls) at 3 and 24 hours (acute stage), 2 and 4 weeks (subacute stage), and 4, and 20 months (chronic stage) following MCAO. We found that the infarct volume progressively decreased between 1 and 4 weeks following MCAO, in parallel with the neurological recovery. Greater presence of cluster of differentiation 68 (CD68)-expressing microglia/macrophages was detected in the infarct lesion in the subacute and chronic stage, compared to the acute stage. Surprisingly, 98~99% of transforming growth factor beta (TGFβ) was found colocalized with CD68-expressing cells. CD68-expressing microglia/macrophages, rather than CD206⁺ cells, may exert anti-inflammatory effects by secreting TGFβ after the subacute stage of ischemic stroke. CD68⁺ microglia/macrophages can therefore be used as a potential therapeutic target.
Brain ; Haplorhini ; Immunohistochemistry ; Infarction, Middle Cerebral Artery ; Inflammation ; Macaca mulatta ; Magnetic Resonance Imaging ; Microglia ; Middle Cerebral Artery ; Primates ; Stroke ; Transforming Growth Factor beta

BACKGROUND/OBJECTIVES: Complications of diabetes, such as cardiovascular disease, are associated with increased mortality among type 2 diabetes mellitus patients. Homocysteine has been recently identified as a predictor of cardiovascular disease-related complications in diabetes. We investigated whether or not supplementation with folic acid tablets can lower homocysteine levels and improve parameters related with vascular complications. SUBJECTS/METHODS: We conducted a non-randomized 8-week trial involving postmenopausal diabetic women (n = 25) supplemented with 800 µg of folic acid (400 µg twice a day) daily. Subjects' serum levels of folate, homocysteine, and vitamin B₁₂ were measured, along with vascular function and brachial-ankle pulse wave velocity. RESULTS: Folic acid supplementation significantly increased serum folate levels (P < 0.0001), reduced homocysteine levels (P < 0.0001), and increased vitamin B₁₂ levels (P = 0.0063). There were significant decreases in low-density lipoprotein cholesterol levels as well as the ratios of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol and total cholesterol to high-density lipoprotein cholesterol. Brachial-ankle pulse wave velocities were not altered by supplementation. Changes in serum vitamin B₁₂ after folic acid supplementation were negatively correlated with changes in brachial-ankle pulse wave velocity. CONCLUSIONS: In this study on postmenopausal Korean women with type 2 diabetes mellitus, folic acid supplementation reduced serum homocysteine levels, increased serum folate and vitamin B₁₂ levels, and lowered lipid parameters.
Cardiovascular Diseases ; Cholesterol ; Cholesterol, LDL ; Diabetes Mellitus, Type 2* ; Female ; Folic Acid* ; Homocysteine* ; Humans ; Lipoproteins ; Mortality ; Pulse Wave Analysis ; Tablets ; Vitamin B 12 ; Vitamins

BACKGROUND/OBJECTIVES: This study was aimed at examining the association between dietary flavanones intake and lipid profiles according to the presence of metabolic syndrome (MetS) in Korean women with type 2 diabetes mellitus (T2DM). SUBJECTS/METHODS: A cross-sectional analysis was performed among 502 female T2DM patients (non-MetS group; n = 129, MetS group; n = 373) who were recruited from the Huh's Diabetes Clinic in Seoul, Korea between 2005 and 2011. The dietary intake was assessed by a validated semi-quantitative food frequency questionnaire (FFQ) and the data was analyzed using the Computer Aided Nutritional Analysis program (CAN-Pro) version 4.0 software. The intake of flavanones was estimated on the basis of the flavonoid database. RESULTS: In the multiple linear regression analysis after adjustment for confounding factors, daily flavanones intake was negatively associated with CVD risk factors such as total cholesterol, LDL-cholesterol, and apoB and apoB/apoA1 ratio only in the MetS group but not in the non-MetS group. Multiple logistic regression analysis revealed that the odds ratio for a higher apoB/apoA1 ratio above the median (> or = 0.74) was significantly low in the 4th quartile compared to that in the 1st quartile of dietary flavanones intake [OR: 0.477, 95% CI: 0.255-0.894, P for trend = 0.0377] in the MetS group. CONCLUSIONS: Dietary flavanones intake was inversely associated with the apoB/apoA1 ratio, suggesting a potential protective effect of flavanones against CVD in T2DM women with MetS.
Apolipoproteins ; Apolipoproteins B ; Cholesterol ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2* ; Female ; Flavanones* ; Humans ; Korea ; Linear Models ; Logistic Models ; Odds Ratio ; Risk Factors ; Seoul

BACKGROUND: This study examined the osteoinductive activity of demineralized dentin matrix (DDM) from human and polydeoxyribonucleotide (PDRN) for nude mice. METHODS: Twenty healthy nude mice, weighing about 15~20 g, were used for the study. DDM from human and PDRN were prepared and implanted subcutaneously into the dorsal portion of the nude mice. The nude mice were sacrificed at 1, 2, and 4 weeks after grafting and evaluated histologically by hematoxylin-eosin and Masson's trichrome staining. The specimens were also evaluated via a histomorphometric study. RESULTS: The DDM and PDRN induced new bone, osteoblasts, and fibroblasts in soft tissues. The histological findings showed bone-forming cells like osteoblasts and fibroblasts at 1, 2, and 4 weeks. New bone formation was observed in the histomorphometric study. In particular, the ratio of new bone formation was the highest at 2 weeks compared with the first week and fourth week. CONCLUSIONS: In this study, we showed that the PDRN used in this experimental model was able to induce bone regeneration when combined to the DDM.
Animals ; Bone Regeneration ; Dentin* ; Fibroblasts ; Humans ; Mice ; Mice, Nude ; Models, Theoretical ; Osteoblasts ; Osteogenesis ; Transplants

BACKGROUND/OBJECTIVES: This study was performed to investigate the association between the dietary intake of fish and shellfish, and omega-3 polyunsaturated fatty acids (PUFAs) and cardiovascular disease (CVD) risk factors in the middle-aged Korean female patients with Type 2 diabetes (T2D). SUBJECTS/METHODS: A cross-sectional analysis was performed with 356 female patients (means age: 55.5 years), who were recruited from the Huh's Diabetes Clinic in Seoul, Korea between 2005 and 2011. The dietary intake was assessed by a validated semi-quantitative food frequency questionnaire and analyzed using the Computer Aided Nutritional Analysis program (CAN-Pro) version 4.0 software. RESULTS: In a multiple regression analysis after the adjustment for confounding factors such as age, BMI, duration of diagnosed T2D, alcohol consumption, fiber intake, sodium intake, and total energy intake, fish and shellfish intake of the subjects was negatively associated with triglyceride and pulse wave velocity (PWV). Omega-3 PUFAs intake was negatively associated with triglyceride, systolic blood pressures, diastolic blood pressures, and PWV. The multiple logistic regression analysis with the covariates showed a significant inverse relationship between the omega-3 PUFAs consumption and prevalence of hypertriglyceridemia [OR (95% CI) for greater than the median compared to less than the median: 0.395 (0.207-0.753)]. CONCLUSIONS: These results suggest that the consumption of fish and shellfish, good sources of omega-3 PUFAs, may reduce the risk factors for CVD in the middle-aged female patients with T2D.
Alcohol Drinking ; Cardiovascular Diseases ; Cross-Sectional Studies ; Energy Intake ; Fatty Acids, Unsaturated ; Female* ; Humans ; Hypertriglyceridemia ; Korea ; Logistic Models ; Prevalence ; Pulse Wave Analysis ; Risk Factors* ; Seoul ; Shellfish* ; Sodium ; Triglycerides