Plasma membrane profiling defines an expanded class of cell surface proteins selectively targeted for degradation by HCMV US2 in cooperation with UL141.

Human cytomegalovirus (HCMV) US2, US3, US6 and US11 act in concert to prevent immune recognition of virally infected cells by CD8+ T-lymphocytes through downregulation of MHC class I molecules (MHC-I). Here we show that US2 function goes far beyond MHC-I degradation. A systematic proteomic study using Plasma Membrane Profiling revealed US2 was unique in downregulating additional cellular targets, including: five distinct integrin α-chains, CD112, the interleukin-12 receptor, PTPRJ and thrombomodulin. US2 recruited the cellular E3 ligase TRC8 to direct the proteasomal degradation of all its targets, reminiscent of its degradation of MHC-I. Whereas integrin α-chains were selectively degraded, their integrin β1 binding partner accumulated in the ER. Consequently integrin signaling, cell adhesion and migration were strongly suppressed. US2 was necessary and sufficient for degradation of the majority of its substrates, but remarkably, the HCMV NK cell evasion function UL141 requisitioned US2 to enhance downregulation of the NK cell ligand CD112. UL141 retained CD112 in the ER from where US2 promoted its TRC8-dependent retrotranslocation and degradation. These findings redefine US2 as a multifunctional degradation hub which, through recruitment of the cellular E3 ligase TRC8, modulates diverse immune pathways involved in antigen presentation, NK cell activation, migration and coagulation; and highlight US2's impact on HCMV pathogenesis.This study was financially supported by grant 101-2917-I-564-035 from the Taiwan National Science Council to JLH; by a Wellcome Trust Fellowship (093966/Z/10/Z) to MPW; an MRC Project Grant and Wellcome Trust Programme Grant (G1000236, WT090323MA) to GWW and PT, European Regional Development Fund and the State Budget of Czech Republic (RECAMO, CZ.1.05/ 2.1.00/03.0101) to ER; a Wellcome Trust Principal Research Fellowship (084957/Z/08/Z) to PJL; and a Medical Research Council (MRC) grant (MC_UU_12014/3) to GSW and AJD. This study was additionally supported by the Cambridge Biomedical Research Centre, UK.This is the final published version. It first appeared at http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004811

Risk Factors for Recurrent Hypoglycemia in Hospitalized Diabetic Patients Admitted for Severe Hypoglycemia

Purpose: Severe hypoglycemia can result in neural damage, impaired cognitive function, coma, seizures, or death. The decision to admit diabetic patients after initial treatment in the emergency department remains unclear. Our purpose is to identify risk factors for developing recurrent hypoglycemia in diabetic patients admitted for severe hypoglycemia. Materials and Methods: We reviewed the records of 233 subjects (92 males, 141 females; mean age, 74.1 ± 9.8 years) with type 2 diabetes treated at a tertiary care teaching hospital and hospitalized for severe hypoglycemia. Results: Seventy-four (31.8%) patients were categorized with recurrent hypoglycemia and 159 (68.2%) with non-recurrent. Multivariate logistic regression analysis revealed that patients with loss of a recent meal, coronary artery disease, infection, and poor renal function (lower estimated glomerular filtration rate) were at risk for recurrent hypoglycemia. The use of calcium-channel blockers appeared to be a protective factor for the development of recurrent hypoglycemia. Conclusion: There may be a subset of patients with severe hypoglycemia and certain risk factors for recurrent hypoglycemia that should be admitted

A Compact Nano-TiO2 Underlayer forEfficient Dye-Sensitized Solar Cell

A compact nano-TiO2 underlayer is formed on atitanium (Ti) foil through a two-step H2O2 + NaOH soakingpretreatment. This underlayer effectively suppresses thecharge recombination reaction on the photoanode side, whichis attributed to efficient electron transfer due to good adhesionbetween Ti and nano-TiO2. It also enhances the electricalcontact with screen-printed TiO2 mesoporous film due to surfacenanostructure. Both fill factor and short-circuit current densityare improved, and accordingly the power conversion efficiencyof dye-sensitized solar cell is enhanced by 22%

STRESS FRACTURE OF THE ULNA IN A BREAK-DANCER

Break dancing is a popular activity in teenagers and is associated with severe trauma to bones and tissues. We report the first known case of a break dancer with an ulnar stress fracture. Such injuries occur in a variety of sports due to substantial stress on the ulna and repetitive excessive rotation of the forearm. In this study we describe a patient who experienced an ulnar stress fracture during break dancing training. The diagnosis was established by history and physical examination. Initial radiographic findings were negative. However, radiographs taken 3 months after initial presented revealed callus formation over the ulnar shaft. This suggested that readjustment is required in break dancing training protocols. It is important to increase awareness of this injury among physicians to expedite the diagnosis and to prevent the possibility of conversion to an overt fracture in the futur

Comparison of clinical parameters and environmental noise levels between regular surgery and piezosurgery for extraction of impacted third molars

Impacted third molars can be extracted by regular surgery or piezosurgery. The aim of this study was to compare clinical parameters and device-produced noise levels between regular surgery and piezosurgery for the extraction of impacted third molars. Methods: Twenty patients (18 women and 2 men, 17–29 years of age) with bilateral symmetrical impacted mandibular or maxillary third molars of the same level were included in this randomized crossover clinical trial. The 40 impacted third molars were divided into a control group (n = 20), in which the third molar was extracted by regular surgery using a high-speed handpiece and an elevator, and an experimental group (n = 20), in which the third molar was extracted by piezosurgery using a high-speed handpiece and a piezotome. The clinical parameters were evaluated by a self-reported questionnaire. The noise levels produced by the high-speed handpiece and piezotome were measured and compared between the experimental and control groups. Results: Patients in the experimental group had a better feeling about tooth extraction and force delivery during extraction and less facial swelling than patients in the control group. However, there were no significant differences in noise-related disturbance, extraction period, degree of facial swelling, pain score, pain duration, any noise levels produced by the devices under different circumstances during tooth extraction between the control and experimental groups. Conclusion: The piezosurgery device produced noise levels similar to or lower than those of the high-speed drilling device. However, piezosurgery provides advantages of increased patient comfort during extraction of impacted third molars

AI Models for Predicting Readmission of Pneumonia Patients within 30 Days after Discharge

A model with capability for precisely predicting readmission is a target being pursued worldwide. The objective of this study is to design predictive models using artificial intelligence methods and data retrieved from the National Health Insurance Research Database of Taiwan for identifying high-risk pneumonia patients with 30-day all-cause readmissions. An integrated genetic algorithm (GA) and support vector machine (SVM), namely IGS, were used to design predictive models optimized with three objective functions. In IGS, GA was used for selecting salient features and optimal SVM parameters, while SVM was used for constructing the models. For comparison, logistic regression (LR) and deep neural network (DNN) were also applied for model construction. The IGS model with AUC used as the objective function achieved an accuracy, sensitivity, specificity, and area under ROC curve (AUC) of 70.11%, 73.46%, 69.26%, and 0.7758, respectively, outperforming the models designed with LR (65.77%, 78.44%, 62.54%, and 0.7689, respectively) and DNN (61.50%, 79.34%, 56.95%, and 0.7547, respectively), as well as previously reported models constructed using thedata of electronic health records with an AUC of 0.71–0.74. It can be used for automatically detecting pneumonia patients with a risk of all-cause readmissions within 30 days after discharge so as to administer suitable interventions to reduce readmission and healthcare costs

Screening and characterization of myositis‐related autoantibodies in COVID‐19 patients

Abstract An efficient host immune response against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2, COVID‐19) appears to be crucial for controlling and resolving this viral infection. However, many studies have reported autoimmune characteristics in severe COVID‐19 patients. Moreover, clinical observations have revealed that COVID‐19‐associated acute distress respiratory syndrome shares many features in common with inflammatory myopathy including interstitial lung disease (ILD), most particularly rapidly progressive (RP)‐ILD. This study explored this phenomenon by seeking to identify and characterize myositis‐specific and related autoantibodies in 25 COVID‐19 patients with mild or severe symptoms. Line blot analysis with the EUROLINE Myopathies Ag kit identified 9 (36%) patients with COVID‐19 with one or more autoantibodies against several myositis‐related antigens (Jo‐1, Ku, Mi‐2β, PL‐7, PL‐12, PM‐Scl 75, PM‐Scl 100, Ro‐52, and SRP); no anti‐MDA5 antibodies were detected. As the presence of antibodies identified by line blots was unrelated to disease severity, we further characterized the autoantibodies by radioimmunoassay, in which [35S]methionine‐labeled K562 cellular antigens were precipitated and visualized by gel electrophoresis. This result was confirmed by an immunoprecipitation assay and immunoblotting; 2 patients exhibited anti‐Ku70 and anti‐Ku80 antibodies. Our data suggest that it is necessary to use more than one method to characterize and evaluate autoantibodies in people recovered from COVID‐19, in order to avoid misinterpreting those autoantibodies as diagnostic markers for autoimmune diseases