Objective: Cognitive reserve has emerged as a concept to explain the variable expression of clinical symptoms in the pathology of Alzheimer’s disease (AD). The association between years of education, a proxy of cognitive reserve, and resting-state functional connectivity (rFC), a representative intermediate phenotype, has not been explored in the preclinical phase, considering risk factors for AD. We aimed to evaluate whether the relationship between years of education and rFC in cognitively preserved older adults differs depending on amyloid-beta deposition and APOE ε4 carrier status as effect modifiers. Methods: A total of 121 participants underwent functional magnetic resonance imaging, [ 18F] flutemetamol positron emission tomography-computed tomography, APOE genotyping, and a neuropsychological battery. Potential interactions between years of education and AD risk factors for rFC of AD-vulnerable neural networks were assessed with wholebrain voxel-wise analysis. Results: We found a significant education years-by-APOE ε4 carrier status interaction for the rFC from the seed region of the central executive (CEN) and dorsal attention networks. Moreover, there was a significant interaction of rFC between right superior occipital gyrus and the CEN seed region by APOE ε4 carrier status for memory performances and overall cognitive function. Conclusion In preclinical APOE ε4 carriers, higher years of education were associated with higher rFC of the AD vulnerable network, but this contributed to lower cognitive function. These results contribute to a deeper understanding of the impact of cognitive reserve on sensitive functional intermediate phenotypic markers in the preclinical phase of AD.

Purpose: Neuroinflammation is considered an important pathway associated with several diseases that result in cognitive decline. 18F-THK5351 positron emission tomography (PET) signals might indicate the presence of neuroinflammation, as well as Alzheimer’s disease-type tau aggregates. β-amyloid (Aβ)-negative (Aβ–) amnestic mild cognitive impairment (aMCI) may be associated with non-Alzheimer’s disease pathophysiology. Accordingly, we investigated associations between 18F-THK5351 PET positivity and cognitive decline among Aβ– aMCI patients. Materials and Methods: The present study included 25 amyloid PET negative aMCI patients who underwent a minimum of two follow-up neuropsychological evaluations, including clinical dementia rating-sum of boxes (CDR-SOB). The patients were classified into two groups: 18F-THK5351-positive and -negative groups. The present study used a linear mixed effects model to estimate the effects of 18F-THK5351 PET positivity on cognitive prognosis among Aβ– aMCI patients. Results: Among the 25 Aβ– aMCI patients, 10 (40.0%) were 18F-THK5351 positive. The patients in the 18F-THK5351-positive group were older than those in the 18F-THK5351-negative group (77.4±2.2 years vs. 70.0±5.5 years; p<0.001). There was no difference between the two groups with regard to the proportion of apolipoprotein E ε4 carriers. Interestingly, however, the CDR-SOB scores of the 18F-THK5351-positive group deteriorated at a faster rate than those of the 18F-THK5351-negative group (B=0.003, p=0.033). Conclusion The results of the present study suggest that increased 18F-THK5351 uptake might be a useful predictor of poor prognosis among Aβ– aMCI patients, which might be associated with increased neuroinflammation (ClinicalTrials.gov NCT02656498).

BACKGROUND: Over the past 10 years, monopolar radiofrequency (MRF) technology has been widely used by dermatologists as a valuable modality to effectively tighten and rejuvenate photoaged skin. It also has the benefit of a short recovery time. OBJECTIVE: Using an objective parameter, this study aimed to assess the efficacy and safety of MRF, which is the basic modality of radiofrequency technologies, for treatment of periorbital wrinkles in Korean patients. METHODS: We enrolled 70 middle-aged female patients with periorbital wrinkles for this study. Each patient underwent triple sessions of MRF treatment in the periorbital region, separated by 2-week intervals. Clinical photographs were obtained, and the areas of wrinkles were measured using a Robo Skin Analyzer CS50 (Inforward Inc., Japan) at baseline and 4 weeks after the final treatment session. RESULTS: Significant reduction in the mean area of periorbital wrinkles was detected at 1-month follow-up (80.64±28.96 mm2) compared to baseline (95.08±31.93 mm2). The improvement ratio of the wrinkle area was 15.19%. Pain during procedure seemed to be tolerable without any local anesthesia for all patients. Transient mild erythema was the only side effect reported during the study. CONCLUSION: In conclusion, MRF could still be an attractive modality for Korean patients with periorbital wrinkles if the treatment is conducted repeatedly with sufficient energy and proper intervals.
Anesthesia, Local ; Erythema ; Female ; Follow-Up Studies ; Humans ; Skin

BACKGROUND/AIMS: The objective of this study was to determine the efficacy and safety of add-on therapy with certolizumab pegol (CZP) in active rheumatoid arthritis (RA) patients of a single ethnicity. METHODS: In this 24-week, phase 3, randomized, double-blind, placebo-controlled trial, eligible patients (n = 127) were randomized 2:1 to subcutaneous CZP + methotrexate (MTX; 400 mg at week 0, 2, and 4 followed by 200 mg every 2 weeks) or placebo + MTX. RESULTS: At week 24, the American College of Rheumatology criteria for 20% (ACR20) response rate was significantly greater with CZP + MTX than with placebo (66.7% vs. 27.5%, p < 0.001). Differences in ACR20 response rates for CZP vs. placebo were significant from week 1 (p < 0.05) and remained significant through week 24. The CZP group reported significant improvement in physical function and disability compared to the placebo group (p < 0.001) at week 24, as assessed by Korean Health Assessment Questionnaire-Disability Index (KHAQ-DI). Post hoc analysis indicated that the proportion of patients who had ACR70 responses, Disease Activity Score 28 (DAS28) low disease activity, and DAS28 remission at week 24 was greater in CZP + MTX-treated patients who achieved a decrease in DAS28 ≥ 1.2 (43.8%) at week 4 than in nonresponders. Among 18 (22.2%) and 14 patients (35.0%) in CZP and placebo groups who had latent tuberculosis (TB), none developed active TB. Most adverse events were mild or moderate. CONCLUSIONS: CZP treatment combined with MTX in active RA patients with moderate to severe disease activity and an inadequate response to MTX resulted in rapid onset of efficacy, which is associated with better clinical outcome at week 24 and has an acceptable safety profile, especially in an intermediate TB-burden population.
Arthritis, Rheumatoid* ; Certolizumab Pegol ; Humans ; Latent Tuberculosis ; Methotrexate* ; Rheumatology

BACKGROUND: Recurrence of glenohumeral dislocation after arthroscopic Bankart repair can be associated with a large osseous defect in the posterosuperior part of the humeral head. Our hypothesis is that remplissage is more effective to prevent recurrence of glenohumeral instability without a severe motion deficit. METHODS: Engaging Hill-Sachs lesions were observed in 48 of 737 patients (6.5%). Twenty-four patients underwent arthroscopic Bankart repair combined with remplissage (group I) and the other 24 patients underwent arthroscopic Bankart repair alone (group II). Clinical outcomes were prospectively evaluated by assessing the range of motion. Complications, recurrence rates, and functional results were assessed utilizing the American Shoulder and Elbow Surgeons (ASES) score, Rowe score, and the Korean Shoulder Score for Instability (KSSI) score. Capsulotenodesis healing after remplissage was evaluated with magnetic resonance imaging. RESULTS: The average ASES, Rowe, and KSSI scores were statistically significantly higher in group I than group II. The frequency of recurrence was statistically significantly higher in group II. The average loss in external rotation measured with the arm positioned at the side of the trunk was greater in group II and that in abduction was also higher in group II. CONCLUSIONS: Compared to single arthroscopic Bankart repair, the remplissage procedure combined with arthroscopic Bankart repair was more effective to prevent the recurrence of anterior shoulder instability without significant impact on shoulder mobility in patients who had huge Hill-Sachs lesions.
Arm ; Elbow ; Humans ; Humeral Head ; Joint Instability ; Magnetic Resonance Imaging ; Prospective Studies ; Range of Motion, Articular ; Recurrence ; Shoulder Dislocation ; Shoulder* ; Surgeons

BACKGROUND: The use of dipeptidyl peptidase-4 (DPP-4) inhibitors is increasing among renal transplant patients with diabetes. However, the glucose-lowering efficacies of various DPP-4 inhibitors and their effects on blood cyclosporine levels have not been fully investigated. We compared the glucose-lowering efficacies of DPP 4 inhibitors and evaluate their effects on the blood levels of cyclosporine in renal transplant recipients with diabetes. METHODS: Sixty-five renal allograft recipients who received treatment with DPP-4 inhibitors (vildagliptin, sitagliptin, or linagliptin) following kidney transplant were enrolled. The glucose-lowering efficacies of the DPP-4 inhibitors were compared according to the changes in the hemoglobin A1c (HbA1c) levels after 3 months of treatment. Changes in the trough levels of the cyclosporine were also assessed 2 months after treatment with each DPP-4 inhibitor. RESULTS: HbA1c significantly decreased in the linagliptin group in comparison with other DPP-4 inhibitors (vildagliptin –0.38%±1.03%, sitagliptin –0.53%±0.95%, and linagliptin –1.40±1.34; P=0.016). Cyclosporine trough levels were significantly increased in the sitagliptin group compared with vildagliptin group (30.62±81.70 ng/mL vs. –24.22±53.54 ng/mL, P=0.036). Cyclosporine trough levels were minimally changed in patients with linagliptin. CONCLUSION: Linagliptin demonstrates superior glucose-lowering efficacy and minimal effect on cyclosporine trough levels in comparison with other DPP-4 inhibitors in kidney transplant patients with diabetes.
Allografts ; Cyclosporine* ; Diabetes Mellitus ; Dipeptidyl-Peptidase IV Inhibitors ; Humans ; Hyperglycemia* ; Kidney ; Kidney Transplantation ; Pilot Projects* ; Transplantation

OBJECTIVES: The posttraumatic stress disorder (PTSD) checklist (PCL) is currently the most popular self-report scale employed in screening PTSD. This study was conducted 1) to test the reliability and validity of PCL in veterans of the Vietnam War and 2) to compare the results when using a conventional paper survey and mobile app survey. METHODS: Participants included 186 Korean veterans of the Vietnam War. Mini Mental Status Examination, PTSD module of Structured Clinical Interview for DSM-IV (SCID), and Life Event Checklist were administered. PCL was administered in either written format or mobile app. Diagnostic validity of the PCL was compared using the PTSD module of SCID. Other psychometric properties of PCL were also calculated. RESULTS: PCL results using different methods, paper and mobile app, showed no significant difference in each item and total score. Cronbach's coefficient of PCL was 0.95, optimal cut-off 49.5, sensitivity 91.7%, and specificity 93.5%. CONCLUSION: PCL showed excellent internal reliability, sensitivity, specificity, and validity. There was no statistically significant difference between survey methods. These results suggest that PCL is a reliable self-report scale in veterans. In addition, PCL with mobile app can be helpful in screening PTSD.
Aged* ; Checklist* ; Surveys and Questionnaires ; Diagnostic and Statistical Manual of Mental Disorders ; Humans ; Mass Screening ; Mobile Applications* ; Psychometrics ; Reproducibility of Results ; Sensitivity and Specificity ; Stress Disorders, Post-Traumatic* ; Veterans* ; Vietnam*

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of oral antihyperglycemic drugs; inhibition of the cotransporter allows for increased renal glucose excretion that consequently leads to reduced plasma glucose level. We report a rare case of a 73-year-old woman with type 2 diabetes mellitus who developed severe ketoacidosis caused by an SGLT2 inhibitor. At admission, severe ketoacidosis with arterial PH 6.99 was observed, though her serum glucose level of 232 mg/dL was not excessively high. It is necessary to pay attention to patients with type 2 diabetes being treated with an SGLT2 inhibitor, as anorexia, diarrhea, dehydration, and weight loss can develop in conjunction with a high fat/protein diet.
Aged ; Anorexia ; Blood Glucose ; Dehydration ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Diabetic Ketoacidosis* ; Diarrhea ; Diet ; Female ; Glucose ; Humans ; Hydrogen-Ion Concentration ; Ketosis ; Weight Loss

Bisphosphonates are the mainstay of osteoporosis treatment. Despite the fact that bisphosphonates have a relatively good safety record and are tolerated well by the majority of patients, serious adverse events have been associated with their use. A 41-year-old man had been diagnosed with osteoporosis and had taken etidronate 200 mg/day daily for 2 years due to the judgmental error. He was referred for the management of refractory bone pain and generalized muscle ache. Serum calcium, phosphate, 25-hydroxy-vitamin D (25(OH)D), and immunoreactive parathyroid hormone (iPTH) were within normal range. Plain X-ray showed multiple fractures. Whole body bone scan confirmed multiple sites of increased bone uptakes. Tetracycline-labeled bone biopsy showed typical findings of osteomalacia. He was diagnosed with iatrogenic, etidronate-induced osteomalacia. The patient received daily parathyroid hormone (PTH) injection for 18 months. PTH effectively reverses impaired bone mineralization caused by etidronate misuse. Currently, he is doing well without bone pain. Bone mineral density significantly increased, and the increased bone uptake was almost normalized after 18 months. This case seems to suggest that human PTH (1-34) therapy, possibly in association with calcium and vitamin D, is associated with important clinical improvements in patients with impaired bone mineralization due to the side effect of bisphosphonate.
Adult ; Biopsy ; Bone Density ; Calcification, Physiologic ; Calcium ; Diphosphonates ; Etidronic Acid ; Humans ; Judgment ; Muscles ; Osteomalacia ; Osteoporosis ; Parathyroid Hormone ; Reference Values ; Vitamin D

PURPOSE: Primary aldosteronism (PA) is characterized by hypertension (HTN), hypokalemia, suppressed plasma renin activity, and inappropriate aldosterone secretion. The purpose of this study was to analyze postoperative results on blood pressure (BP), and to determine the factors associated with resolution of HTN after adrenalectomy for PA. METHODS: One hundred eight patients (66 females and 42 males) with a mean age of 46 years underwent adrenalectomy for PA between January 1, 1996 and September 30, 2009. Their clinical characteristics and biochemical parameters were reviewed retrospectively. RESULTS: All patients had HTN preoperatively and 20 patients (18.1%) had uncontrolled HTN. Hypokalemia was evident in 89.1% of patients, cardiovascular events in 4.5% and cerebrovascular events in 8.2%. There was a significant decrease in both systolic BP and diastolic BP postoperatively, as compared with that before operation. Median systolic BP decreased from 150 mmHg to 125 mmHg at the last follow-up (P<0.01), and median diastolic BP decreased from 93.5 mmHg to 81.5 mmHg (P<0.01). Sixty two (57.4%) patients were cured of HTN and did not require any hypertensive agent, and 38 (35.1%) patients had an improvement in BP control, whereas 9 (8.3%) patients had no change in BP. Univariate analysis showed that duration of HTN and more than two HTN treatment agents were independent factors predicting sustained hypertension after surgery. CONCLUSION: The duration of HTN and the severity of HTN are factors influencing persistence of HTN after operation for a PA.
Adrenalectomy* ; Adrenocortical Adenoma ; Aldosterone ; Blood Pressure ; Female ; Follow-Up Studies ; Humans ; Hyperaldosteronism* ; Hypertension ; Hypokalemia ; Plasma ; Renin ; Retrospective Studies