OBJECTIVES/GOALS: Vitamin D [25(OH)D], known to have anti-inflammatory and anti-fibrotic effects in other tissues, may also impact adipose tissue. We designed parallel studies in humans and rodents to define the effects of vitamin D on adipose tissue inflammation and fibrosis, and on systemic insulin resistance. METHODS/STUDY POPULATION: We performed a randomized, double-blinded placebo-controlled trial to examine the effects of repleting vitamin D at to two levels (to >30 ng/ml and to > 50 ng/ml) in 25(OH)D-deficient (<20 ng/ml), insulin resistant, overweight-to-obese humans (n = 19). A comprehensive study of whole-body insulin action was undertaken with euglycemic stepped hyperinsulinemic clamp studies, both before (1st visit) and after administration of vitamin D or placebo (2nd visit and 3rd visit). Adipose tissue fibrosis and inflammation were quantified by ‘real-time’ rt-PCR and immunofluorescence. To determine whether vitamin D’s effects are mediated through adipocytes, we performed hyperinsulinemic clamp studies and adipose tissue analysis in an adipocyte-specific vitamin D receptor knockout (VDR KO) mouse model. RESULTS/ANTICIPATED RESULTS: 25(OH)D repletion (to >30 ng/ml) was associated with reductions in adipose tissue expression of inflammatory (0.6-0.7-fold decreased expression of TNF-α, IL-6, iNOS and PAI-1) and pro-fibrotic (0.4-0.8-fold decreased expression of TGF-β1, HiF1α, Collagen I, V, VI and MMP7) factors, decreased collagen VI immunofluorescence (p = 0.02) and improved hepatic insulin sensitivity in humans, with suppression of endogenous glucose production (EGP) (1.28 ± 0.20 vs 0.88 ± 0.18 mg/kg/min, p = 0.03). Compared to wild type (WT), VDR KO mice exhibited increased adipose tissue expression of several pro-inflammatory (Tnf-α, iNos, Pai-1, Mcp-1 and F4/80; 4-10 fold) and pro-fibrotic genes (Tgf-β1, Collagen VI, and Tsp1; 2-4 fold), in concert with hepatic insulin resistance (EGP 10 ± 3 vs 3 ± 2 mg/kg/min in WT, p = 0.021). DISCUSSION/SIGNIFICANCE OF IMPACT: Collectively, these complementary human and rodent studies establish a beneficial role of vitamin D to improve hepatic insulin resistance, likely by restraining adipose tissue inflammation and fibrosis. Thus, normalizing 25(OH)D levels could have metabolic benefits in targeted individuals. CONFLICT OF INTEREST DESCRIPTION: N/A

Objectives: Rotator cuff tear is the leading cause of the decline in quality of life for older adults, but comparative evidence on treatment effectiveness is lacking. This study systematically reviewed the effects of various rotator cuff tear treatments through a Bayesian meta-analysis of the related randomized clinical trials (RCTs).

Methods: We searched nine electronic databases for RCTs evaluating rotator cuff tear treatments from their inception through June 2017. A systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the National Institute for Health and Care Excellence-Decision Support Unit guidelines (Supplementary Table 1). Outcomes included functional improvement, pain one year after surgical treatment, and tendon structural integrity. The Bayesian network meta-analysis was applied for functional improvement and pain, based on an assumption of consistency and similarity. Tendon integrity was reported descriptively.

Results: Fifteen RCTs were selected. Patients undergoing physiotherapy after open surgery showed statistically significant functional improvements compared with those undergoing physiotherapy only (mean differences, 9.1 [credible interval, 0.9–17.4]). Open surgery with physiotherapy was associated with a decrease in pain 1 year after treatment compared with when physiotherapy was combined with arthroscopic rotator cuff surgery, mini open surgery, platelet-rich plasma therapy, or physiotherapy alone (absolute value of mean difference 1.2 to 1.4). The tendon integrity results were inconsistent.

Conclusions: Some surgical treatments were associated with significant improvement in function and pain, but evidence regarding their comparative effectiveness is still lacking. A well-designed RCT discussing functional and structural treatment outcomes is needed in future.

Ambidexterity organization, which is defined as the ability of an organization to simultaneously pursues exploration and exploitation, has received attention by researchers who have examined its beneficial effect on organizational performance and success. This study attempted to examine the positive effect of ambidextrous organization culture (AOC), which is regarded as the core characteristic of ambidextrous organizations by using a multilevel model. Specifically, this study examined the effects of AOC on members’ job performance and the mediating role of psychological capital in the relationship between AOC and job performance. The results indicated that AOC had a significantly positive relationship with job performance even after controlling various organizational and individual variables. Moreover, we found that psychological capital fully mediated the relationship between AOC and members’ job performance. This study provides theoretical contributions by empirically examining the positive effect and mechanism of AOC. Furthermore, this study offers practical implications in how practitioners can manage their organizational culture, by helping shape the direction of organizational culture management.

Many transgenic domestic animals have been developed to produce therapeutic proteins in the mammary gland, and this approach is one of the most important methods for agricultural and biomedical applications. However, expression and secretion of a protein varies because transgenes are integrated at random sites in the genome. In addition, distal enhancers are very important for transcriptional gene regulation and tissue-specific gene expression. Development of a vector system regulated accurately in the genome is needed to improve production of therapeutic proteins. The objective of this study was to develop a knock-in system for expression of human fibroblast growth factor 2 (FGF2) in the bovine β-casein gene locus. The F2A sequence was fused to the human FGF2 gene and inserted into exon 3 of the β-casein gene. We detected expression of human FGF2 mRNA in the HC11 mouse mammary epithelial cells by RT-PCR and human FGF2 protein in the culture media using western blot analysis when the knock-in vector was introduced. We transfected the knock-in vector into bovine ear fibroblasts and produced knock-in fibroblasts using the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system. Moreover, the CRISPR/Cas9 system was more efficient than conventional methods. In addition, we produced knock-in blastocysts by somatic cell nuclear transfer using the knock-in fibroblasts. Our knock-in fibroblasts may help to create cloned embryos for development of transgenic dairy cattle expressing human FGF2 protein in the mammary gland via the expression system of the bovine β-casein gene.

During the past decade, carbapenemase-producing Enterobacteriaceae (CPE) has emerged and spread across the world.1 The major carbapenemase enzymes currently being reported are KPC, NDM-1, VIM, IMP, and OXA.2 Because carbapenemase can be effectively transmitted via mobile genetic elements, and current therapeutic options for CPE infections are extremely limited, CPE may be one of the most serious contemporary threats to public health. However, very little is known about the characteristics of CPE carriage during hospitalization. The aims of this study were to investigate the clearance rate of CPE carriage and determine the number of consecutive negative cultures required to confirm CPE clearance. We also examined CPE transmission among hospitalized patients.

Infect. Control Hosp. Epidemiol. 2015;36(11):1361–1362

Background: Low education and illiteracy are associated with an increased risk of dementia. This study aimed to develop a neuropsychological test battery applicable to both illiterate and literate elderly and to assess its reliability and validity for a diagnosis of dementia.

Methods: We developed the Literacy Independent Cognitive Assessment (LICA), which consists of 13 subtests assessing memory, language, visuoconstruction, executive function, attention and calculation. We investigated its reliability and validity on 152 patients with dementia, 66 with mild cognitive impairment and 639 normal controls.

Results: The subtests were found to be applicable to most of the illiterate normal controls (97.3%) and were found to have high inter-rater reliabilities (r = 0.85–1.00, p < 0.001) and moderate to high test-retest reliabilities (r = 0.50–0.86, p < 0.001). The LICA performed well in discriminating participants across Clinical Dementia Rating stages and showed excellent internal consistency and good concurrent validity with the Korean Mini-mental State Examination in both literate and illiterate participants. The area under the curve of the receiver operating characteristic was 0.985 in each of the two literacy groups. Sensitivity and specificity of the LICA to make a diagnosis of dementia was 91.9% and 91.8% at the cutoff point of 186.0 in the literate subjects and 96.2% and 91.1% at the cutoff point of 154.5 in the illiterate subjects. The battery was factored into two separate factors consisting of verbal memory tests and tests for other cognitive domains.

Conclusion: The LICA is a valid and reliable instrument for a diagnosis of dementia in both illiterate and literate elderly.

This study aimed to investigate whether aquaporin 3 (Aqp3) mRNAs are expressed in immature oocytes and altered during in vitro maturation process. Five- to 6-week-old female ICR mice were primed by gonadotropin for 24 and 48 h. Immature oocytes obtained 48 h after priming were also matured in vitro for 17 to 18 h. In vivo matured oocytes were obtained after 48 h priming followed by hCG injection. Total RNAs were extracted from 80 to 150 oocytes in each experimental group, and the levels of Aqp3 mRNA were quantified by real-time reverse transcriptase polymerase chain reaction. The experiments were repeated twice using different oocytes. The Aqp3 mRNA was expressed in immature oocytes, as well as in in vitro and in vivo matured oocytes. The expression level was higher in immature oocytes obtained 48 h after priming (17.2 ± 8.6, mean ± SD) than those with no priming (5.7 ± 0.8) or obtained 24 h after priming (2.5 ± 0.8). The expression of Aqp3 mRNA decreased after in vitro maturation (1.2 ± 0.5), which was similar to in vivo matured oocytes (1.0 ± 0.0). Our work demonstrated that Aqp3 mRNA expression increased during the development of immature oocyte but decreased after completion of in vitro maturation. The results indicate that AQP3 is certainly needed for the acquisition of immature oocytes’ full growing potential within antral follicles.

Human complement regulatory protein hCD46 may reduce the hyperacute rejection (HAR) in pig-to-human xenotransplantation. In this study, an hCD46 gene was introduced into porcine embryonic germ (EG) cells. Treatment of human serum did not affect the survival of hCD46-transgenic EG cells, whereas the treatment significantly reduced the survival of non-transgenic EG cells (p < 0.01). The transgenic EG cells presumably capable of alleviating HAR were transferred into enucleated oocytes. Among 235 reconstituted oocytes, 35 (14.9%) developed to the blastocyst stage. Analysis of individual embryos indicated that 80.0% (28/35) of embryos contained the transgene hCD46. The result of the present study demonstrates resistance of hCD46-transgenic EG cells against HAR, and the usefulness of the transgenic approach may be predicted by this cytolytic assessment prior to actual production of transgenic pigs. Subsequently performed EG cell nuclear transfer gave rise to hCD46-transgenic embryos. Further study on the transfer of these embryos to recipients may produce hCD46-transgenic pigs.

We deposited various nano structured ZnO thin films with plasma treatment on an alumina substrate and fabricate ZnO sensors for acetone detection. The ZnO sensors with various nano structures and the plasma treatment were deposited by radio frequency (RF) magnetron sputtering method with RuO2 micro heater and Ru electrode. In order to control a work function intentionally, the various deposition conditions and the plasma treatment were used. Sensitivities of the ZnO sensor were measured in acetone vapor and air at 250 degree C. In conclusion, we suggested that the sensitivity of ZnO sensors for acetone strongly depends on the work function of the as-deposited or plasma treated nano structured ZnO thin films.

Bonding process using indium-silver alloy which can withstand high temperature was investigated at relatively low temperature. We used a thermal evaporator and vacuum coater for making indium-silver contact. From the result of experiment, we observed that indium and silver films which have good quality are formed. From phase diagram of In-Ag alloy, we can find that melting point of these compounds increases with the silver content, i.e. eutectic (144° C) <AgIn2 (166° C) < (300° C) < (670° C) < (695° C). And these compounds are determined by the composition ratio of the source metal. Now we confirmed the thermal characteristics of Indium-Silver alloy is controlled by silver. Consequently we have developed Ag/In/Ag multi-layer composite which has higher melting point than that of normal contact. The melting point of Ag/In/Ag multi-layer is about 700° C. The joint cross-sections are studied using SEM(scanning electron microscopy) and EDX(Energy Dispersive X-rays). From these data, we observed that the composition and microstructure of Ag/In/Ag multi-layer were reliable and this bonding procedure is a better technique compared to the conventional structure of quantum well LED and GaN/Si LED structure was made by using sapphire for substrate and might be good for high temperature electronic devices in the future.