Vertebral fracture is associated with myocardial infarction in incident hemodialysis patients: a Korean nationwide population-based study.

Chronic kidney disease (CKD)-mineral and bone disorder suggests that fragile bone and vascular disorder might be connected closely in CKD patients. In this study, fracture event was significantly associated with myocardial infarction (MI) in end-stage renal disease patients on hemodialysis (HD), especially for vertebral fractures. INTRODUCTION: CKD-mineral and bone disorder is characterized by biochemical abnormalities, bone disorders, and vascular calcification. We aimed to verify the association between fracture and MI in CKD patients. METHODS: Records for incident CKD stage 3 to 5 patients and patients who initiated HD between July 2014 and June 2018 were retrieved from the Korean Health Insurance Review & Assessment Service Database. Fractures were defined using diagnostic codes and were classified into vertebral, femoral, and other site fractures. MI was defined using a combination of MI diagnostic codes and related procedure codes. Multiple logistic regressions and 1:1 propensity score matching analysis were conducted. RESULTS: A total of 38,935 patients (HD, 11,379; pre-dialysis CKD, 27,556) were included in this study. A total of 5,057 (13.0%) patients experienced fracture, and 1,431 (3.7%) patients had MI. Multiple logistic regression analysis showed that fracture was significantly associated with MI in the HD group (odds ratio (OR) 1.34, P = 0.024), but not in the pre-dialysis CKD group (OR 1.04, P = 0.701). After propensity score matching for age, gender, and diabetes mellitus between patients with and without fracture, fracture still significantly correlated with MI in HD patients (OR 1.47, P = 0.034) but not in patients with pre-dialysis CKD (OR 1.04, P = 0.751). Subgroup analysis by fracture site found that vertebral fracture was associated with MI in HD patients (OR 2.11, P = 0.024), but femoral or other site fractures were not. CONCLUSION: In HD patients, fracture was significantly associated with MI, especially for vertebral fractures patients.

The change of bone mineral density and bone metabolism after gastrectomy for gastric cancer: a meta-analysis.

Bone mineral density (BMD) is significantly decreased after gastrectomy in patients with gastric cancer. Calcium malabsorption, secondary hyperparathyroidism, and dominant bone resorption appear to contribute to bone loss in these patients. Patients should undergo early surveillance and nutritional or pharmacologic intensive interventions for bone health. PURPOSE: Survivorship care, including bone health, has become an important issue in gastric cancer. We performed a meta-analysis of the available observational studies to determine whether and how osteoporosis risk is increased after gastrectomy in patients with gastric cancer. METHODS: A total of 1204 patients (802 men) from 19 cohort studies were included. We evaluated the prevalence of osteoporosis in postgastrectomy patients, comparing the incidence according to the type of gastrectomy and sex. Additionally, we evaluated changes in bone mineral density (BMD) and bone metabolism-related markers pre- to postoperatively and between patients who underwent gastrectomy and matched controls. Proportion meta-analysis was performed and pooled odds ratios (ORs) were calculated. RESULTS: The pooled incidence estimate was 36% [95% confidence interval (CI), 32-40]. The incidence of osteoporosis was significantly higher in women than in men (OR = 1.90, p < 0.001) but was similar between partial and total gastrectomy groups (OR = 0.983, p = 0.939). BMD was significantly decreased, and calcium, phosphorous, and parathyroid hormone levels were significantly increased in patients after gastrectomy compared to those before gastrectomy. BMD and calcium and 25OH-vitamin D levels were significantly decreased, and parathyroid hormone and 1,25OH-vitamin D levels were significantly increased in the gastrectomy group compared to that in the control group. CONCLUSION: We found that BMD is significantly decreased after gastrectomy in patients with gastric cancer. Vitamin D deficiency and secondary hyperparathyroidism are suggested to be common mechanism underlying BMD impairment. After resection, patients should undergo long-term nutritional and bone health surveillance, in addition to their oncological follow-up.

Development of Novel Continuous and Interval Exercise Programs by Applying the FITT-VP Principle in Dogs.

Although proper exercise training induces positive physiological effects, improper exercise can lead to injury, fatigue, and poor performance. The frequency, intensity, time/duration, type, volume, and progression (FITT-VP) are the essential components of exercise training to maintain or improve physical fitness and health. The purpose of this study was to develop specific exercise programs by applying the FITT-VP principle and to examine the effects on heart rate (HR) and hematological and biochemical parameters in dogs. The healthy male Beagles (n = 4) included in this study performed continuous and interval exercises, comprising 12 protocols. The HR monitoring elicited an affirmative response to activities but varied depending on the protocols. The hematologic parameters (e.g., red blood cell count, white blood cell count, hemoglobin, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration) were within the reference ranges both before and after exercise. The creatine kinase level significantly increased, and the cholesterol level decreased after exercises. In conclusion, the continuous and interval exercise program elicits an appropriate HR reaction, has no adverse effects on the serum parameters, and provides valuable insight for healthcare in dogs.

0.5% 5-Fluorouracil/10% Salicylic Acid for the Treatment of Distal Actinic Keratoses Under Daily Practice Conditions

Background: Actinic keratosis (AKs) are sun-induced skin lesions that are at risk to progress to invasive squamous cell carcinoma (SCC). Treatments have shown to be effective on face or balding scalp area but limited data support their efficacy on distal extremities. Objective: To describe the efficacy of 0.5% 5-fluorouracil/10% salicylic acid (5FU/AS) in the treatment of distally-located AKs in daily clinical practice. Additional objectives were to review tolerance and adherence to this treatment. Methods: Retrospective review of 23 patients with distal grade II to III AKs who were treated with 5FU/AS under daily practice conditions. Primary endpoint included local skin response according to percentage on AKs reduction at week 20 (8 weeks after ending the treatment). Results: 75% (30/40) treatment areas showed a percentage reduction in AKs from to 75% to 100% at week 20. Complete response (100% clearance) was recorded in more than half of the cases (53%, 21/40). Good, partial, and low responses were respectively observed in 22% (9/40), 20% (8/40), and 5% (2/40) of patients. Most adverse events were graded as low, and adherence to treatment was considered correct in 25 patients (63%). In addition, a correct adherence to treatment was significantly related to a better response (P=0.001). Conclusion: Findings indicate that topical 5FU/AS is an effective treatment for multiple distal AKs, with a proper safety profile. J Drugs Dermatol. 2019;18(3):285-288.

The association between muscle mass deficits and arterial stiffness in middle-aged men.

BACKGROUND AND AIMS: Early diagnosis of arteriosclerosis is fundamental for the prevention of cardiovascular morbidity and mortality. The current study was performed to identify major predictors of arteriosclerosis and to assess the association between arterial stiffness as measured by cardio-ankle vascular index (CAVI) and muscle mass deficit (MMD) estimated by bioelectrical impedance analysis (BIA) in middle-aged men. METHODS AND RESULTS: Data were gathered from 3356 middle-aged men who visited a health promotion center. CAVI was measured as an index of arterial stiffness. Body composition analysis was performed using BIA. MMD was positively associated with CAVI in the regression model. The odds ratios for high-CAVI (≥9.0) rose with MMD grade in a dose-dependent manner after adjusting for age, lifestyle factors and current medication use. The estimated mean CAVI rose as MMD grade increased (P for trend >0.001). CONCLUSIONS: MMD estimated from BIA was positively associated with arterial stiffness in middle-aged men. These findings show a close interaction between low muscle mass and cardiovascular risk.

Successful tracheostomy decannulation after complete or sensory incomplete cervical spinal cord injury.

STUDY DESIGN: Retrospective study. OBJECTIVES: To report the successful tracheostomy decannulation/extubation in cervical spinal cord injury (C-SCI) patients. SETTING: Tertiary university hospital, pulmonary rehabilitation center. METHODS: Complete or sensory incomplete C-SCI patients who had received invasive acute phase respiratory management, and succeeded in decannulation/extubation became candidates of this study. Retrospective review was conducted on the transitions of the respiratory status. RESULTS: Sixty-two patients (M: 55, F: 7) were identified. Traumatic etiologies accounted for 93.5%, and mean onset age was 47.6±15.8 years. Sixty patients (96.8%) had undergone tracheostomy and the other two received endotracheal intubation during acute phase. All patients succeeded in decannulation/extubation after employing mechanically assisted coughing and noninvasive mechanical ventilation (NIV). Mean time since tracheostomy to decannulation was 7.0±14.5 months. Of the 60 tracheostomized patients, 12 succeeded in decannulation without applying long-term NIV, 31 switched to continuous NIV after decannulation. Fifteen patients totally weaned off from ventilators after NIV. Two patients who once succeeded in decannulation were re-tracheostomized. For the 31 patients with continuous NIV, mean hours of daily need for ventilatory support had reduced from 15.3±8.0 to 5.7±5.7 h at final follow-ups. CONCLUSION: Complete or sensory incomplete C-SCI patients, even with high neurological level can be successfully decannulated through NIV and aggressive use of mechanically assisted coughing. Undesirable tracheostomy can be avoided by employing the noninvasive respiratory management.

Costs of illness and quality of life in patients with systemic lupus erythematosus in South Korea.

OBJECTIVE: To assess the costs of illness, health-related quality of life (HRQOL) and their associated factors in patients with systemic lupus erythematosus (SLE) in South Korea. METHOD: Two hundred and one patients with SLE were enrolled at the Rheumatology clinic of Seoul National University Hospital. Direct, indirect and total costs and HRQOL were measured using hospital electronic data and face-to-face interview. Socio-demographic and clinical factors associated with cost of illness and HRQOL were analyzed using multiple regression and multivariate logistic regression. RESULTS: The average total cost of illness was estimated to be KRW 9.82 million (US $ 8993) per year, of which 41.6% was accounted for by direct costs and 58.4% by indirect costs. In multivariate regression, patients with renal involvement and those with depression incurred an average increment in annual total costs of 37.6% (p = 0.050) and 49.1% (p = 0.024), respectively, and an average increment in annual direct costs of 26.4% (p = 0.050) and 43.3% (p = 0.002), respectively, compared with patients without renal involvement and depression, respectively. In addition, disease damage was positively associated with an average increment in annual total and direct costs (55.3%, p = 0.006; 33.3%, p = 0.013, respectively), and the occurrence of indirect costs (OR 2.21, 1.09-4.88). There was no significant difference in HRQOL between patients with and without renal involvement (0.655 vs. 0.693, p = 0.203) CONCLUSION: Renal involvement, depression, and disease damage were major factors associated with higher total and medical costs for patients with SLE in South Korea. Effective treatment of renal disorders and depression may reduce the high economic burden of SLE.

Analgesic efficacy of caudal dexamethasone combined with ropivacaine in children undergoing orchiopexy.

BACKGROUND: Epidural administration of dexamethasone might reduce postoperative pain in adults. We evaluated whether a caudal block of 0.1 mg kg(-1) dexamethasone combined with ropivacaine improves analgesic efficacy in children undergoing day-case orchiopexy. METHODS: This randomized, double-blind study included 80 children aged 6 months to 5 yr who underwent day-case, unilateral orchiopexy. Patients received either 1.5 ml kg(-1) of 0.15% ropivacaine (Group C) or 1.5 ml kg(-1) of 0.15% ropivacaine in which dexamethasone of 0.1 mg kg(-1) was mixed (Group D) for caudal analgesia. Postoperative pain scores, rescue analgesic consumption, and side-effects were evaluated 48 h after operation. RESULTS: Postoperative pain scores at 6 and 24 h post-surgery were significantly lower in Group D than in Group C. Furthermore, the number of subjects who remained pain free up to 48 h after operation was significantly greater in Group D [19 of 38 (50%)] than in Group C [four of 37 (10.8%); P<0.001]. The number of subjects who received oral analgesic was significantly lower in Group D [11 of 38 (28.9%)] than in Group C [20 of 37 (54.1%); P=0.027]. Time to first oral analgesic administration after surgery was also significantly longer in Group D than in Group C (P=0.014). Adverse events after surgery including vomiting, fever, wound infection, and wound dehiscence were comparable between the two groups. CONCLUSIONS: The addition of dexamethasone 0.1 mg kg(-1) to ropivacaine for caudal block can significantly improve analgesic efficacy in children undergoing orchiopexy. Clinical trial registration NCT01604915.

Fabrication of GaAs/Al0.3Ga0.7As multiple quantum well nanostructures on (100) si substrate using a 1-nm InAs relief layer.

Nanometer scale thin InAs layer has been incorporated between Si (100) substrate and GaAs/Al0.3Ga0.7As multiple quantum well (MQW) nanostructure in order to reduce the defects generation during the growth of GaAs buffer layer on Si substrate. Observations based on atomic force microscopy (AFM) and transmission electron microscopy (TEM) suggest that initiation and propagation of defect at the Si/GaAs interface could be suppressed by incorporating thin (1 nm in thickness) InAs layer. Consequently, the microstructure and resulting optical properties improved as compared to the MQW structure formed directly on Si substrate without the InAs layer. It was also observed that there exists some limit to the desirable thickness of the InAs layer since the MQW structure having thicker InAs layer (4 nm-thick) showed deteriorated properties.

Advances in the diagnosis of drug eruptions.

Drug eruptions affecting the skin or mucosas (toxicoderma) are the most common adverse effects of drugs and represent one of the more common diagnostic challenges for the dermatologist. A better understanding of the pathogenic mechanisms of drug reactions, pharmacogenetics, and pharmacoepidemiology will help us to resolve the main dilemmas and to anticipate and even prevent such reactions. Many drug eruptions are due to T cell-mediated hypersensitivity reactions that can involve activation of different proinflammatory mechanisms, which would explain the varied manifestations. Some aspects defy the classical understanding of antigen processing and presentation. New immunological hypotheses, such as the «p-i concept¼, have been introduced to complement the hapten theory and, at least in part, help to explain why drug reactions tend to affect the skin and why certain viral infections increase the risk of drug eruptions. In this paper we analyze these pathogenic concepts and the role of HLA genes in the susceptibility to certain severe adverse drug reactions, and also examine other advances in the diagnosis of drug eruptions. We briefly discuss a number of recently described reactions to new drugs.

Rebamipide attenuates pain severity and cartilage degeneration in a rat model of osteoarthritis by downregulating oxidative damage and catabolic activity in chondrocytes.

OBJECTIVE: The objectives were to investigate the in vivo effects of treatment with rebamipide on pain severity and cartilage degeneration in an experimental model of rat osteoarthritis (OA) and to explore its mode of action. MATERIALS AND METHODS: OA was induced in rats by intra-articular injection of monosodium iodoacetate (MIA). Oral administration of rebamipide was initiated on the day of MIA injection, 3 or 7 days after. Limb nociception was assessed by measuring the paw withdrawal latency and threshold. We analyzed the samples macroscopically and histomorphologically, and used immunohistochemistry to investigate the expression of matrix metalloproteinase-13 (MMP-13), interleukin-1ß (IL-1ß), hypoxia-inducible factor-2α (HIF-2α), inducible nitric oxide synthase (iNOS), and nitrotyrosine in knee joints. Real-time quantitative reverse transcription-polymerase chain reaction was used to quantify the mRNA for catabolic and anticatabolic factors in human OA chondrocytes. RESULTS: Rebamipide showed an antinociceptive property and attenuated cartilage degeneration. Rebamipide reduced the expression of MMP-13, IL-1ß, HIF-2α, iNOS, and nitrotyrosine in OA cartilage in a dose-dependent manner. Nitrotyrosine expression in the subchondral bone region was decreased in the rebamipide-treated joints. mRNA expression of MMP-1, -3, and -13, and ADAMTS5 was attenuated in IL-1ß-stimulated human OA chondrocytes. By contrast, rebamipide induced the mRNA expression of tissue inhibitor of metalloproteinase-1 and -3. CONCLUSION: The results show the inhibitory effects of rebamipide on pain production and cartilage degeneration in experimentally induced OA. The suppression of oxidative damage and the restoration of extracellular matrix homeostasis of articular chondrocyte suggest that rebamipide is a potential therapeutic strategy for OA.

Upregulation of stromal cell-derived factor by IL-17 and IL-18 via a phosphatidylinositol 3-kinase-dependent pathway.

Th17 cells that produce interleukin (IL)-17 play a key role in the pathogenesis of autoimmune inflammation. Among the various cytokines that are involved in the IL-17 pathway, members of the IL-1ß family, including IL-18, have recently gained attention. In this study, we stimulated synovial fibroblasts with a combination of IL-17 and IL-18 and quantified their stromal cell-derived factor-1 (SDF-1) production by enzyme-linked immunosorbent assay and their transcript levels by reverse transcription-polymerase chain reaction. Both IL-17 and IL-18 significantly increased the level of SDF-1, not only individually but also synergistically (P< 0.05). The synergism was effectively suppressed by anti-IL-17 and -IL-18 antibodies, and a PI3K inhibitor. To the best of our knowledge, this is the first report of PI3K-dependent synergism between IL-18 and IL-17, and this work adds a novel perspective of the role of IL-18 in immune regulation. The individual effects of these two cytokines, and their interactions, suggest an interrelationship between the IL-1 family and IL-17.

Species-specific challenges in dog cloning.

Somatic cell nuclear transfer (SCNT) is now an established procedure used in cloning of several species. SCNT in dogs involves multiple steps including the removal of the nuclear material, injection of a donor cell, fusion, activation of the reconstructed oocytes and finally transfer to a synchronized female recipient. There are therefore many factors that contribute to cloning efficiency. By performing a retrospective analysis of 2005-2012 published papers regarding dog cloning, we define the optimum procedure and summarize the specific feature for dog cloning.

Lessons learned from cloning dogs.

The aim of this article is to review dog cloning research and to suggest its applications based on a discussion about the normality of cloned dogs. Somatic cell nuclear transfer was successfully used for production of viable cloned puppies despite limited understanding of in vitro dog embryo production. Cloned dogs have similar growth characteristics to those born from natural fertilization, with no evidence of serious adverse effects. The offspring of cloned dogs also have similar growth performance and health to those of naturally bred puppies. Therefore, cloning in domestic dogs can be applied as an assisted reproductive technique to conserve endangered species, to treat sterile canids or aged dogs, to improve reproductive performance of valuable individuals and to generate disease model animals.

Reduced pre-pregnancy proteinuria is associated with improving postnatal maternal renal outcomes in IgA nephropathy women.

AIMS: In patients with immunoglobulin A (IgA) nephropathy, postnatal renal outcomes vary depending on kidney function and proteinuria. However, whether a decrease in proteinuria prior to conception improves postnatal maternal renal outcomes is unknown. METHODS: This was a single-center retrospective study. A total of 52 pregnant women with biopsy-proven IgA nephropathy were enrolled in the study between January 2004 and December 2009. We collected data on proteinuria, which had been measured 1 year prior to conception, at conception, during pregnancy, and postnatally. The study outcomes included changes in estimated glomerular filtration rate (eGFR) and proteinuria. RESULTS: The median serum creatinine, eGFR, and proteinuria levels at conception were 0.8 (0.5 - 2.6) mg/dl, 91.2 (24.1 - 157.0) ml/min, 0.7 (0.0 - 3.5) g/g, respectively. Compared with values measured at conception, serum creatinine (0.8 - 1.0 mg/dl, p < 0.01) and proteinuria (0.7 - 1.5 g/g, p < 0.01) increased significantly postnatally, while eGFR decreased (91.2 - 77.8 ml/min, p < 0.01). In a multiple linear regression analysis, proteinuria at conception were independently associated with a faster decline in postnatal maternal eGFR (ß = 4.50, p < 0.05). In addition, a less decline in maternal eGFR was observed in patients with a reduction in proteinuria (> 30%) prior to pregnancy, compared with those with a less reduction (≤ 30%). As for newborn outcomes, preterm delivery, caesarean section, low birth weight < 2,500 g, and need for neonatal intensive care were 15.4%, 46.2%, 25.0% and 7.7%, respectively. CONCLUSIONS: This study showed that in women with IgA nephropathy, proteinuria was significantly associated with the deterioration of postnatal maternal renal outcomes. Our study also suggests that a strategy for reducing proteinuria prior to pregnancy is required to preserve kidney function after delivery.

Differentiating blood samples from scrapie infected and non-infected hamsters by detecting disease-associated prion proteins using Multimer Detection System.

This communication describes the application of a modified sandwich enzyme-linked immunosorbent assay (ELISA), termed Multimer Detection System (MDS) for the detection of disease-associated multimeric forms of the prion protein (PrPd) in hamster blood. PrPd was detected in plasma of prion-affected hamsters while MDS revealed no PrPd in identically-treated plasma of healthy animals. This is the first report of a single ELISA- based immune detection of PrPd from blood samples.

Effects of activin A on the in vitro development and mRNA expression of bovine embryos cultured in chemically-defined two-step culture medium.

The purpose of the present study was to evaluate the effects of activin A on the developmental competence of in vitro fertilized (IVF) bovine embryos derived from a two-step defined culture system (C1/C2 medium) during the early or later stages of embryo development. To evaluate the effects of activin A on transcriptional levels, we analysed genes related to blastocyst hatching and implantation and to activin signalling pathway in IVF embryos. Cumulus-oocyte complexes were matured for 22 h and fertilized in vitro. Presumptive zygotes were cultured in the presence or absence of activin A during early (0-120 h, C1) or later (120-192 h, C2) stages. Although the developmental competence of embryos cultured with activin A in C1 medium was not significantly different from their corresponding controls, development to blastocysts (22.4% vs 34.7%; p < 0.05) and the blastocyst hatching rate (9.3% vs 22.4%; p < 0.05) in C2 medium supplemented with 100 ng/ml activin A were significantly higher than in the control group. To evaluate the effect of activin A on transcription, the relative expression levels of genes related to blastocyst hatching and implantation (Na/K-ATPase, E-cad and Glut-1) as well as activin signalling pathway (ActRII, ActRIIB and Smad2) were analysed. Compared to control medium, gene expression of Na/K-ATPase, E-cad, Glut-1, ActRII and ActRIIB was increased in medium supplemented with activin A. In conclusion, this study suggests that activin A, during the later stage of in vitro bovine embryo development, can enhance in vitro development of embryos by increasing hatching rates and affecting expression levels of genes related to hatching and implantation in defined culture medium.