Buckling Analysis of CNTRC Curved Sandwich Nanobeams in Thermal Environment

none6siThis paper presents a mathematical continuum model to investigate the static stability buckling of cross-ply single-walled (SW) carbon nanotube reinforced composite (CNTRC) curved sandwich nanobeams in thermal environment, based on a novel quasi-3D higher-order shear deformation theory. The study considers possible nano-scale size effects in agreement with a nonlocal strain gradient theory, including a higher-order nonlocal parameter (material scale) and gradient length scale (size scale), to account for size-dependent properties. Several types of reinforcement material distributions are assumed, namely a uniform distribution (UD) as well as X- and O- functionally graded (FG) distributions. The material properties are also assumed to be temperature-dependent in agreement with the Touloukian principle. The problem is solved in closed form by applying the Galerkin method, where a numerical study is performed systematically to validate the proposed model, and check for the effects of several factors on the buckling response of CNTRC curved sandwich nanobeams, including the reinforcement material distributions, boundary conditions, length scale and nonlocal parameters, together with some geometry properties, such as the opening angle and slenderness ratio. The proposed model is verified to be an effective theoretical tool to treat the thermal buckling response of curved CNTRC sandwich nanobeams, ranging from macroscale to nanoscale, whose examples could be of great interest for the design of many nanostructural components in different engineering applications.openAhmed Amine Daikh; Mohammed Sid Ahmed Houari; Behrouz Karami; Mohamed A. Eltaher; Rossana Dimitri; Francesco TornabeneAmine Daikh, Ahmed; Sid Ahmed Houari, Mohammed; Karami, Behrouz; Eltaher, Mohamed A.; Dimitri, Rossana; Tornabene, Francesc

Treatment of lupus nephritis with abatacept: the Abatacept and Cyclophosphamide Combination Efficacy and Safety Study

OBJECTIVE: To assess the efficacy and safety of a 24-week course of abatacept in the treatment of active lupus nephritis and to assess the potential of abatacept to induce clinical tolerance, defined as sustained clinical quiescence of lupus nephritis after discontinuation of immunosuppressive therapy. METHODS: Patients with active lupus nephritis (n = 134) were enrolled in a randomized, double-blind phase II add-on trial in which they received either abatacept or placebo in conjunction with the Euro-Lupus Nephritis Trial regimen of low-dose cyclophosphamide (CYC) followed by azathioprine (AZA). The primary efficacy outcome was the frequency of complete response at week 24. Thereafter, patients who met either complete or partial response criteria continued blinded treatment through week 52. During this phase of the study, subjects in the abatacept treatment group in whom a complete response was achieved at week 24 discontinued immunosuppressive therapy other than prednisone (10 mg/day). RESULTS: There were no statistically significant differences between groups with respect to the primary outcome or any of the secondary outcomes, including measures of safety. A complete response was achieved in 33% of the subjects in the treatment group and in 31% of the subjects in the control group at week 24. Fifty percent of the subjects in the treatment group who met complete response criteria and therefore discontinued immunosuppressive therapy at week 24 maintained their complete response status through week 52. CONCLUSION: The addition of abatacept to a regimen of CYC followed by AZA did not improve the outcome of lupus nephritis at either 24 or 52 weeks. No worrisome safety signals were encountered

Eosinophilic gastroenteritis in a young girl – long term remission under Montelukast

BACKGROUND: Eosinophilic gastrointestinal disorders are an emerging disease entity characterized by eosinophilic infiltration of the intestinal wall. Oral steroids can be still considered as first line treatment. Unfortunately relapses are quite common. Usually long term low-dose prednisone or immunosuppressive therapy is required, which is especially problematic in young patients. Thus a reliable steroid sparing agent with low side effects suitable for long term use is needed. There are strong hints to a similar pathophysiology of eosinophilic gastrointestinal disorders to that of asthma. Indeed leukotriene D4 plays an important role in the recruitment of eosinophils into the intestinal tissue causing damage. This patho-mechanism provides the rationale for the treatment with a leukotriene D4 receptor antagonist. Recently there have been first reports about successful short term use of Montelukast in eosinophilic gastrointestinal disorders. CASE PRESENTATION: We report the case of a 17 year old girl with a long history of severe abdominal complaints leading to several hospitalizations in the past. Mimicking the picture of an intestinal tuberculosis she received an anti mycobacterial treatment without any success. Marked eosinophilia in blood, ascites and tissue samples of the intestinal tract finally lead to the diagnosis eosinophilic gastroenteritis. Tapering off prednisone caused another severe episode of abdominal pain. At that point leukotriene antagonist Montelukast was started at a dose of 10 mg once daily. Steroids could be tapered off completely within six weeks. The patient has been free of symptoms for over two years by now. Routine examinations, blood tests and endoscopy have rendered regular results. So far no side effects were noted. CONCLUSION: Here report about successful long term remission of eosinophilic gastroenteritis under Montelukast. Further randomized control trials are required to asses the full benefits of Montelukast therapy in the whole spectrum of eosinophilic gastrointestinal disorders

Inhibition of glucose metabolism selectively targets autoreactive follicular helper T cells.

Follicular helper T (TFH) cells are expanded in systemic lupus erythematosus, where they are required to produce high affinity autoantibodies. Eliminating TFH cells would, however compromise the production of protective antibodies against viral and bacterial pathogens. Here we show that inhibiting glucose metabolism results in a drastic reduction of the frequency and number of TFH cells in lupus-prone mice. However, this inhibition has little effect on the production of T-cell-dependent antibodies following immunization with an exogenous antigen or on the frequency of virus-specific TFH cells induced by infection with influenza. In contrast, glutaminolysis inhibition reduces both immunization-induced and autoimmune TFH cells and humoral responses. Solute transporter gene signature suggests different glucose and amino acid fluxes between autoimmune TFH cells and exogenous antigen-specific TFH cells. Thus, blocking glucose metabolism may provide an effective therapeutic approach to treat systemic autoimmunity by eliminating autoreactive TFH cells while preserving protective immunity against pathogens

Construction of 3D models of the CYP11B family as a tool to predict ligand binding characteristics

Aldosterone is synthesised by aldosterone synthase (CYP11B2). CYP11B2 has a highly homologous isoform, steroid 11β-hydroxylase (CYP11B1), which is responsible for the biosynthesis of aldosterone precursors and glucocorticoids. To investigate aldosterone biosynthesis and facilitate the search for selective CYP11B2 inhibitors, we constructed three-dimensional models for CYP11B1 and CYP11B2 for both human and rat. The models were constructed based on the crystal structure of Pseudomonas Putida CYP101 and Oryctolagus Cuniculus CYP2C5. Small steric active site differences between the isoforms were found to be the most important determinants for the regioselective steroid synthesis. A possible explanation for these steric differences for the selective synthesis of aldosterone by CYP11B2 is presented. The activities of the known CYP11B inhibitors metyrapone, R-etomidate, R-fadrazole and S-fadrazole were determined using assays of V79MZ cells that express human CYP11B1 and CYP11B2, respectively. By investigating the inhibitors in the human CYP11B models using molecular docking and molecular dynamics simulations we were able to predict a similar trend in potency for the inhibitors as found in the in vitro assays. Importantly, based on the docking and dynamics simulations it is possible to understand the enantioselectivity of the human enzymes for the inhibitor fadrazole, the R-enantiomer being selective for CYP11B2 and the S-enantiomer being selective for CYP11B1

Lyme Disease in Children

Lyme disease is now the most frequently reported vector-borne disease in the United States. The highest incidence is in children aged 5 to 9 years with a male predominance. The most common manifestation, erythema migrans, is sometimes not recognized, leading to risk of complications. Testing for Lyme disease should only be done if there is a consistent clinical syndrome with exposure in a Lyme-endemic area. Most forms of Lyme disease are successfully treated with short courses of oral therapy. Prevention and management of tick bites is important