Efficacy of a Pharmacist Team Clinical Medication Review in Older Adults: A Prospective and Retrospective Observational Study.

Polypharmacy in older adults causes problems such as increased adverse drug reactions, overdose or duplication, and poor medication adherence. We have established a "medication review team" organized by pharmacists. This prospective and retrospective observational study evaluated the effectiveness of the pharmacist-led team-based approach for reducing polypharmacy as compared to the individual pharmacist approach. Data on the individual pharmacist approach were collected retrospectively, but prospectively for the pharmacist-led team approach. The study included patients who were admitted to the nephrology, orthopedic surgery, and psychiatry wards. Characteristics for patient included in each study group were adjusted using the propensity score method. The pharmacist-led team approach had a significantly higher medication change rate compared to that of the individual pharmacist approach (odds ratio (OR), 2.28; 95% confidence interval (CI), 1.21 to 4.46; p = 0.009). The rate of patients with two or more medication discontinuations and the rate of patients with intervention by young clinical pharmacist were also significantly higher in the pharmacist-led team approach (OR, 2.19; 95% CI, 1.06 to 4.74; p = 0.03 and OR, 5.67; 95% CI, 1.22 to 53.15; p = 0.02, respectively). The rate of patients with discontinuation of potentially inappropriate medications was not significantly different between the two groups (OR, 2.07; 95% CI, 0.86 to 5.33; p = 0.11). Our results suggest that it is possible to improve the quality of medication review by conducting team conferences even with only pharmacists.

Classification of Breast Masses on Ultrasound Shear Wave Elastography using Convolutional Neural Networks.

We aimed to use deep learning with convolutional neural networks (CNNs) to discriminate images of benign and malignant breast masses on ultrasound shear wave elastography (SWE). We retrospectively gathered 158 images of benign masses and 146 images of malignant masses as training data for SWE. A deep learning model was constructed using several CNN architectures (Xception, InceptionV3, InceptionResNetV2, DenseNet121, DenseNet169, and NASNetMobile) with 50, 100, and 200 epochs. We analyzed SWE images of 38 benign masses and 35 malignant masses as test data. Two radiologists interpreted these test data through a consensus reading using a 5-point visual color assessment (SWEc) and the mean elasticity value (in kPa) (SWEe). Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated. The best CNN model (which was DenseNet169 with 100 epochs), SWEc, and SWEe had a sensitivity of 0.857, 0.829, and 0.914 and a specificity of 0.789, 0.737, and 0.763 respectively. The CNNs exhibited a mean AUC of 0.870 (range, 0.844-0.898), and SWEc and SWEe had an AUC of 0.821 and 0.855. The CNNs had an equal or better diagnostic performance compared with radiologist readings. DenseNet169 with 100 epochs, Xception with 50 epochs, and Xception with 100 epochs had a better diagnostic performance compared with SWEc (P = 0.018-0.037). Deep learning with CNNs exhibited equal or higher AUC compared with radiologists when discriminating benign from malignant breast masses on ultrasound SWE.

Oligosaccharide modification by N-acetylglucosaminyltransferase-V in macrophages are involved in pathogenesis of bleomycin-induced scleroderma.

Oligosaccharide modification by N-acetylglucosaminyltransferase-V (GnT-V), which catalyses the formation of ß1,6 GlcNAc (N-acetylglucosamine) branches on N-glycans, is associated with various pathologies, such as cancer metastasis, multiple sclerosis and liver fibrosis. In this study, we demonstrated the involvement of GnT-V in the pathophysiology of scleroderma. High expression of GnT-V was observed in infiltrating cells in skin section samples from systemic and localized patients with scleroderma. Most of the infiltrating cells were T cells and macrophages, most of which were CD163(+) M2 macrophages. To determine the role of GnT-V in scleroderma, we next investigated skin sclerosis in GnT-V knockout (MGAT5(-/-) ) mice. Expression of GnT-V was also elevated in bleomycin (BLM)-injected sclerotic skin, and MGAT5(-/-) mice were resistant to BLM-induced skin sclerosis with reduced collagen type 1 α1 content, suggesting the biological significance of GnT-V in skin sclerosis. Furthermore, the number of CD163(+) M2 macrophages and CD3-positive T cells in BLM-induced skin sclerosis was significantly fewer in MGAT5(-/-) mice. In bone marrow-derived macrophages (BMDMs), IL-4-induced expressions of Fizz1 and Ym1 were significantly reduced in MGAT5(-/-) mice-derived BMDMs. Taken together, these results suggest the induction of GnT-V in skin sclerosis progression is possibly dependent on increased numbers of M2 macrophages in the skin, which are important for tissue fibrosis and remodelling.

Upregulation of N-acetylglucosaminyltransferase-V by heparin-binding EGF-like growth factor induces keratinocyte proliferation and epidermal hyperplasia.

Oligosaccharide modification by N-acetylglucosaminyltransferase-V (GnT-V), a glycosyltransferase encoded by the Mgat5 gene that catalyses the formation of ß1,6 GlcNAc (N-acetylglucosamine) branches on N-glycans, is thought to be associated with cancer growth and metastasis. Overexpression of GnT-V in cancer cells enhances the signalling of growth factors such as epidermal growth factor (EGF) and transforming growth factor-ß by increasing galectin-3 binding to polylactosamine structures on receptor N-glycans. We previously demonstrated that transgenic mice overexpressing GnT-V fail to develop spontaneous tumors in any organs, but phenotypes reminiscent of epithelial-to-mesenchymal transition were observed in their skin. However, the biological function of GnT-V in normal skin remained unknown. In this study, we examined the role of GnT-V in keratinocyte proliferation using GnT-V-deficient mice. Proliferation of human keratinocytes was suppressed by treatment with GnT-V siRNA. Mgat5(-/-) mouse keratinocytes also showed impaired cell proliferation through the reduction in EGF receptors on the cell surface. Although the skin of Mgat5(-/-) mice appeared normal, epidermal hyperplasia and proliferation of keratinocytes induced by the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA) were downregulated in these mutants. Moreover, a dramatic increase in GnT-V expression was observed by treatment with TPA or heparin-binding EGF-like growth factor (HB-EGF) in normal human epidermal keratinocytes. This increase was inhibited by an EGF receptor inhibitor. These results indicate that a high expression of GnT-V in keratinocytes contributes to HB-EGF-mediated epidermal hyperproliferation by inhibiting endocytosis of EGF receptors bearing ß1,6 GlcNAc on their N-glycans. Our findings demonstrate a novel role for GnT-V in epidermal homoeostasis, particularly in hyperproliferative conditions.

11ß-Hydroxysteroid dehydrogenase-1 is a novel regulator of skin homeostasis and a candidate target for promoting tissue repair.

11ß-Hydroxysteroid dehydrogenase 1 (11ß-HSD1) catalyzes the interconversion of cortisone and cortisol within the endoplasmic reticulum. 11ß-HSD1 is expressed widely, most notably in the liver, adipose tissue, and central nervous system. It has been studied intensely over the last 10 years because its activity is reported to be increased in visceral adipose tissue of obese people. Epidermal keratinocytes and dermal fibroblasts also express 11ß-HSD1. However, the function of the enzymatic activity 11ß-HSD1 in skin is not known. We found that 11ß-HSD1 was expressed in human and murine epidermis, and this expression increased as keratinocytes differentiate. The expression of 11ß-HSD1 by normal human epidermal keratinocytes (NHEKs) was increased by starvation or calcium-induced differentiation in vitro. A selective inhibitor of 11ß-HSD1 promoted proliferation of NHEKs and normal human dermal fibroblasts, but did not alter the differentiation of NHEKs. Topical application of selective 11ß-HSD1 inhibitor to the dorsal skin of hairless mice caused proliferation of keratinocytes. Taken together, these data suggest that 11ß-HSD1 is involved in tissue remodeling of the skin. This hypothesis was further supported by the observation that topical application of the selective 11ß-HSD1 inhibitor enhanced cutaneous wound healing in C57BL/6 mice and ob/ob mice. Collectively, we conclude that 11ß-HSD1 is negatively regulating the proliferation of keratinocytes and fibroblasts, and cutaneous wound healing. Hence, 11ß-HSD1 might maintain skin homeostasis by regulating the proliferation of keratinocytes and dermal fibroblasts. Thus 11ß-HSD1 is a novel candidate target for the design of skin disease treatments.

Enhanced epithelial-mesenchymal transition-like phenotype in N-acetylglucosaminyltransferase V transgenic mouse skin promotes wound healing.

N-Acetylglucosaminyltransferase V (GnT-V) catalyzes the ß1,6 branching of N-acetylglucosamine on N-glycans. GnT-V expression is elevated during malignant transformation in various types of cancer. However, the mechanism by which GnT-V promotes cancer progression is unclear. To characterize the biological significance of GnT-V, we established GnT-V transgenic (Tg) mice, in which GnT-V is regulated by a ß-actin promoter. No spontaneous cancer was detected in any organs of the GnT-V Tg mice. However, GnT-V expression was up-regulated in GnT-V Tg mouse skin, and cultured keratinocytes derived from these mice showed enhanced migration, which was associated with changes in E-cadherin localization and epithelial-mesenchymal transition (EMT). Further, EMT-associated factors snail, twist, and N-cadherin were up-regulated, and cutaneous wound healing was accelerated in vivo. We further investigated the detailed mechanisms of EMT by assessing EGF signaling and found up-regulated EGF receptor signaling in GnT-V Tg mouse keratinocytes. These findings indicate that GnT-V overexpression promotes EMT and keratinocyte migration in part through enhanced EGF receptor signaling.