Notes

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Epstein-Barr virus (EBV) was discovered as the first human tumor virus more than 50 years ago. EBV infects more than 90% of the human population worldwide and is associated with numerous hematologic malignancies and epithelial malignancies. Dihydroartemisinin ic50 EBV establishes latent infection in B cells, which is the typical program seen in lymphomagenesis. Understanding EBV-mediated transcription regulatory networks is one of the current challenges that will uncover new insights into the mechanism of viral-mediated lymphomagenesis. Here, we describe the regulatory profiles of several cellular factors (E2F6, E2F1, Rb, HDAC1, and HDAC2) together with EBV latent nuclear antigens using next-generation sequencing (NGS) analysis. Our results show that the E2F-Rb-HDAC complex exhibits similar distributions in genomic regions of EBV-positive cells and is associated with oncogenic super-enhancers involving long-range regulatory regions. link2 Furthermore, EBV latent antigens cooperatively hijack this complex to bind at KLFs gene loci and facis multisubunit repressor complex in EBV-positive cells. This provides potential therapeutic targets for the treatment of EBV-associated cancers.Zika virus (ZIKV) can establish infection in immune privileged sites such as the testes, eye, and placenta. Whether ZIKV infection of white blood cells is required for dissemination of the virus to immune privileged sites has not been definitively shown. To assess whether initial ZIKV replication in myeloid cell populations is critical for dissemination during acute infection, recombinant ZIKVs were generated that could not replicate in these specific cells. ZIKV was cell restricted by insertion of a complementary sequence to a myeloid-specific microRNA in the 3' untranslated region. Following inoculation of a highly sensitive immunodeficient mouse model, crucial immune parameters, such as quantification of leukocyte cell subsets, cytokine and chemokine secretion, and viremia, were assessed. Decreased neutrophil numbers in the spleen were observed during acute infection with myeloid-restricted ZIKV that precluded the generation of viremia and viral dissemination to peripheral organs. Mice inoculated with a nos inhibited in myeloid cells by harnessing the RNA interference pathway. Severely immunodeficient mice inoculated with myeloid-restricted ZIKV did not demonstrate clinical signs of disease and survived infection. Furthermore, viral dissemination to peripheral organs was not observed in these mice. Lastly, we identified Ly6Cmid/hi murine monocytes as the major myeloid cell population that disseminates ZIKV.
Feedback is an effective pedagogical tool in clinical teaching and learning, but the actual perception by learners of clinical feedback is often described as unsatisfactory. Unlike assessment feedback or teaching sessions, which often happen within protected time and space, clinical feedback is influenced by numerous clinical factors. Little is known about clinical teachers' motivations to provide feedback in busy clinical settings. We aimed to investigate the motivations behind feedback being given in emergency departments (EDs).

A qualitative analysis of semi-structured interview data was conducted between August 2015 and June 2016. Eighteen attending physicians were purposively sampled from three teaching hospital EDs in Taiwan. Data were thematically analysed, both inductively (from the data) and deductively (using self-determination theory (SDT)). Themes were mapped to the different motivation types identified by the SDT.

Despite working in busy clinical settings, Taiwanese ED clinical teachers repused to develop interventions to enable clinical feedback to be provided in a sustained manner.Extraintestinal manifestations (EIMs) are frequently observed in IBDs and contribute considerably to morbidity and mortality. They have long been considered a difficult to treat entity due to limited therapy options, but the increasing use of anti-tumour necrosis factors has dramatically changed the therapeutic approach to EIM in recent years. Newly emerging therapies such as JAK inhibitors and anti-interleukin 12/23 will further shape the available armamentarium. Clinicians dealing with EIMs in everyday IBD practice may be puzzled by the numerous available biological agents and small molecules, their efficacy for EIMs and their potential off-label indications. Current guidelines on EIMs in IBD do not include treatment algorithms to help practitioners in the treatment decision-making process. Herein, we summarise knowledge on emerging biological treatment options and small molecules for EIMs, highlight current research gaps, provide therapeutic algorithms for EIM management and shed light on future strategies in the context of IBD-related EIMs.
The International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria for gestational diabetes mellitus (GDM) increased the morbidity significantly, but the cost and effectiveness of its application are still unclear. This study aimed to analyze the impact of the IADPSG criteria for diagnosing GDM in China on the perinatal outcomes, and medical expenditure of GDM women versus those with normal glucose tolerance (NGT).

We conducted a retrospective cohort study involving 7794 women admitted at the First Affiliated Hospital of Jinan University (Guangzhou, China), from November 1, 2010 to October 31, 2017. The perinatal outcomes and medical expenditure were retrieved from the electronic medical records in the hospital. Propensity score matching (PSM, in a 11 ratio) algorithm was used to minimize confounding effects on the difference in the two cohorts.

PSM minimized the difference of baseline characteristics between women with and without GDM. Of 7794 pregnant women, half (n=3897) were all oPSG guidelines with the 2-hour, 75 g oral glucose tolerance test can improve short-term maternal and neonatal outcomes.
The pathophysiology of microvascular disease is poorly understood, partly due to the lack of tools to directly image microvessels in vivo.

In this study, we deployed a novel optical coherence tomography (OCT) technique during local skin heating to assess microvascular structure and function in diabetics with (DFU group, n=13) and without (DNU group, n=10) foot ulceration, and healthy controls (CON group, n=13). OCT images were obtained from the dorsal foot, at baseline (33°C) and 30 min following skin heating.

At baseline, microvascular density was higher in DFU compared with CON (21.9%±11.5% vs 14.3%±5.6%, p=0.048). Local heating induced significant increases in diameter, speed, flow rate and density in all groups (all p<0.001), with smaller changes in diameter for the DFU group (94.3±13.4 µm), compared with CON group (115.5±11.7 µm, p<0.001) and DNU group (106.7±12.1 µm, p=0.014). link3 Heating-induced flow rate was lower in the DFU group (584.3±217.0 pL/s) compared with the CON group (908.8±228.2 pL/s, p<0.001) and DNU group (768.8±198.4 pL/s, p=0.014), with changes in density also lower in the DFU group than CON group (44.7%±15.0% vs 56.5%±9.1%, p=0.005).

This proof of principle study indicates that it is feasible to directly visualize and quantify microvascular function in people with diabetes; and distinguish microvascular disease severity between patients.
This proof of principle study indicates that it is feasible to directly visualize and quantify microvascular function in people with diabetes; and distinguish microvascular disease severity between patients.
Non-alcoholic fatty liver disease is reportedly associated with type 2 diabetes and progressive liver fibrosis, as evaluated by transient elastography, and has been linked with micro- and macroangiopathy in people with type 2 diabetes. The purpose of this cross-sectional study was to investigate the association between serum mac-2 binding protein glycosylation isomer (M2BPGi) levels and diabetic complications in people with type 2 diabetes.

Serum M2BPGi levels were measured in terms of cut-off index (C.O.I.) units. Urinary albumin excretion (UAE) was calculated and nephropathy was graded as normoalbuminuria, microalbuminuria, or macroalbuminuria. Retinopathy was divided into three groups no-diabetic retinopathy (NoDR), non-proliferative-diabetic retinopathy (NPDR), or proliferative-diabetic retinopathy (PDR) .

The mean age for the 363 studied subjects (212 males) was 66.4±10.6 years, the median serum M2BPGi level was 0.77 (0.57-1.04) C.O.I., and the median UAE was 22 (9-82.1) mg/g creatinine. M2BPGi levs and diabetic microangiopathy and macroangiopathy in people with type 2 diabetes. The results also show that liver fibrosis, evaluated by M2BPGi, is independently associated with an increased risk of albuminuria.The aims of this systematic review were to assess the clinical relevance and quality of previously published animal models of ischemic ulceration and examine the available evidence for interventions improving ulcer healing in these models. Publicly available databases were searched for original studies investigating the effect of limb ischemia on wound healing in animal models. The quality of studies was assessed using two tools based on the Animal research Reporting of In Vivo Experiments (ARRIVE) guidelines and the clinical relevance of the models. A total of 640 wounds (ischemic=314; non-ischemic=326) were assessed in 252 animals (92 mice, 140 rats, 20 rabbits) from 7 studies. Meta-analyses showed that wound healing was consistently delayed by ischemia at all time-points examined (day-7 standard median difference (SMD) 5.36, 95% CI 3.67 to 7.05; day-14 SMD 4.50, 95% CI 2.90 to 6.10 and day-21 SMD 2.53, 95% CI 1.25 to 3.80). No significant difference in wound healing was observed between 32 diabetic and 32 non-diabetic animals with ischemic wounds. Many studies lacked methods to reduce bias, such as outcome assessors blinded to group allocation and sample size calculations and clinically relevant model characteristics, such as use of older animals and a peripheral location of the wound. Five different interventions were reported to improve wound healing in these models. The impaired wound healing associated with limb ischemia can be modeled in a variety of different animals. Improvements in study design could increase clinical relevance, reduce bias and aid the discovery of translatable therapies.
Angiosarcomas constitute approximately 2% to 3% of all soft tissue sarcomas, are characterised by an aggressive clinical behaviour and poor outcome. Optimal management of localised angiosarcomas consists of complete surgical resection with or without radiation. However, due to the infiltrating nature of this disease, complete resection is often not possible. Despite optimal management, the outcome of patients with localised disease remains poor. The role of (neo)adjuvant chemotherapy in angiosarcomas remains undefined. The aim of this study is to document the outcome of patients treated with (neo)adjuvant chemotherapy and assess the feasibility of performing a prospective trial by evaluating the number of patients treated at sarcoma referral centres.

A retrospective search within participating EORTC (European Organisation for Research and Treatment of Cancer) sites for patients treated with (neo)adjuvant chemotherapy was made. Patients treated between January 2007 and January 2016 were included.

A total of 15 institutions participated and 86 patients were evaluable, 43 were treated with neoadjuvant, 27 with adjuvant chemotherapy and 16 with both.
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