Camposfiltenborg1972

Pemphigus encompasses a group of chronic autoimmune blistering diseases of the skin and/or mucosa. Rituximab (RTX) has shown promising efficacy for the treatment of pemphigus in the past decade. Considering potential cardiac side effects, this study was conducted to assess the effects of RTX on electrocardiogram (ECG) parameters in pemphigus patients. This observational cross-sectional study was conducted in 80 consecutive patients with pemphigus who were eligible for RTX infusion. The patients' heart rhythm was monitored before, during and after RTX infusion and ECG parameters were compared before and after the infusion. Eighty patients were included in the study. The median age of the patients was 42 years. The mean and maximum heart rate (HR) increased significantly after RTX infusion compared with pre-infusion mean and maximum HR. The mean corrected QT (QTc) interval, premature atrial contraction (PAC), and premature ventricular contraction (PVC) counts increased significantly after RTX infusion (P value 0.009, 0.004 and 0.007 respectively). According to the results of this study, RTX has potential arrhythmogenic side effects including increased mean and maximum HR, QTc interval, PAC and PVC count. However, these findings are minor and should not prevent eligible patients from receiving RTX infusion.

To evaluate the rate of postpartum glycemic screening tests (PGST) in women with gestational diabetes mellitus (GDM), and to investigate risk factors for abnormal PGST results.

We retrospectively analyzed the obstetric data of 1,648 women with GDM who gave birth after 28 completed weeks of gestation between 1 July 2011 and 31 December 2019 at Taipei Chang Gung Memorial Hospital, Taiwan. GDM was diagnosed by the International Association of Diabetes and Pregnancy Study Groups criteria. PGST was carried out at 6-12weeks postpartum with a 75-g, 2-h oral glucose tolerance test, and the results were classified into normal, prediabetes and diabetes mellitus. Multiple logistic regression was used to assess the associations between various risk factors and abnormal PGST results.

In total, 493 (29.9%) women underwent PGST and 162 (32.9%) had abnormal results, including 135 (27.4%) with prediabetes and 27 (5.5%) with diabetes mellitus. Significant risk factors for postpartum diabetes mellitus included insulin therapy during pregnancy (adjusted odds ratio [OR] 10.79, 95% confidence interval [CI] 4.07-28.58), birthweight >4,000g (adjusted OR 10.22, 95% CI 1.74-59.89) and preterm birth <37weeks' gestation (adjusted OR 3.33, 95% CI 1.09-10.22); whereas prepregnancy body mass index >24.9kg/m

(adjusted OR 1.99, 95% CI 1.24-3.21) was the major risk factor for postpartum prediabetes.

Less than one-third of women with GDM underwent PGST, and nearly one-third of these women had abnormal results. Future efforts should focus on reducing the barriers to PGST in women with GDM.

Less than one-third of women with GDM underwent PGST, and nearly one-third of these women had abnormal results. Future efforts should focus on reducing the barriers to PGST in women with GDM.This article presents a personal and critical review of the history of the malate-aspartate shuttle (MAS), starting in 1962 and ending in 2020. The MAS was initially proposed as a route for the oxidation of cytosolic NADH by the mitochondria in Ehrlich ascites cell tumor lacking other routes, and to explain the need for a mitochondrial aspartate aminotransferase (glutamate oxaloacetate transaminase 2 [GOT2]). The MAS was soon adopted in the field as a major pathway for NADH oxidation in mammalian tissues, such as liver and heart, even though the energetics of the MAS remained a mystery. Only in the 1970s, LaNoue and coworkers discovered that the efflux of aspartate from mitochondria, an essential step in the MAS, is dependent on the proton-motive force generated by the respiratory chain for every aspartate effluxed, mitochondria take up one glutamate and one proton. This makes the MAS in practice uni-directional toward oxidation of cytosolic NADH, and explains why the free NADH/NAD ratio is much higher in the mitochondria than in the cytosol. The MAS is still a very active field of research. Most recently, the focus has been on the role of the MAS in tumors, on cells with defects in mitochondria and on inborn errors in the MAS. The year 2019 saw the discovery of two new inborn errors in the MAS, deficiencies in malate dehydrogenase 1 and in aspartate transaminase 2 (GOT2). #link# This illustrates the vitality of ongoing MAS research.Living systems can form and recover complex chemical patterns with precisely sized features in the ranges of tens or hundreds of microns. We show how designed reaction-diffusion processes can likewise produce precise patterns, termed attractor patterns, that reform their precise shape after being perturbed. We use oligonucleotide reaction networks, photolithography, and microfluidic delivery to form precisely controlled attractor patterns and study the responses of these patterns to different localized perturbations. Linear and "hill"-shaped patterns formed and stabilized into shapes and at time scales consistent with reaction-diffusion models. When patterns were perturbed in particular locations with UV light, they reliably reformed their steady-state profiles. Recovery also occurred after repeated perturbations. By designing the far-from-equilibrium dynamics of a chemical system, this study shows how it is possible to design spatial patterns of molecules that are sustained and regenerated by continually evolving towards a specific steady state configuration.Endoplasmic reticulum (ER) stress has been shown to promote chondrocyte apoptosis and osteoarthritis (OA) progression, but the precise mechanisms via which ER stress is modulated in OA remain unclear. Here we report that DEP domain-containing mTOR-interacting protein (DEPTOR) negatively regulated ER stress and OA development independent of mTOR signaling. DEPTOR is ubiquitinated in articular chondrocytes and its expression is markedly reduced along with OA progression. Deletion of DEPTOR in chondrocytes significantly promoted destabilized medial meniscus (DMM) surgery-induced OA development, whereas intra-articular injection of lentivirus-expressing DEPTOR delayed OA progression in mice. Proteomics analysis revealed that DEPTOR interplayed with TRC8, which promoted TRC8 auto-ubiquitination and degraded by the ubiquitin-proteasome system (UPS) in chondrocytes. Loss of DEPTOR led to TRC8 accumulation and excessive ER stress, with subsequent chondrocyte apoptosis and OA progression. Importantly, an inhibitor of ER stress eliminated chondrocyte DEPTOR deletion-exacerbated OA in mice. Together, these findings establish a novel mechanism essential for OA pathogenesis, where decreasing DEPTOR in chondrocytes during OA progression relieves the auto-ubiquitination of TRC8, resulting in TRC8 accumulation, excessive ER stress, and OA progression. link2 Targeting this pathway has promising therapeutic potential for OA treatment. © 2020 American Society for Bone and Mineral Research (ASBMR).The membrane proximal external region (MPER) of HIV-1 gp41 contains epitopes for at least four broadly neutralizing antibodies. Depending on solution conditions and construct design, different structures have been reported for this segment. link3 We show that in aqueous solution the MPER fragment (gp160660-674 ) exists in a monomer-trimer equilibrium with an association constant in the micromolar range. Thermodynamic analysis reveals that the association is exothermic, more favorable in D2 O than H2 O, and increases with ionic strength, indicating hydrophobically driven intermolecular interactions. Circular dichroism, 13 Cα chemical shifts, NOE, and hydrogen exchange rates reveal that MPER undergoes a structural transition from predominately unfolded monomer at low concentrations to an α-helical trimer at high concentrations. This result has implications for antibody recognition of MPER prior to and during the process where gp41 switches from a pre-hairpin intermediate to its post-fusion 6-helical bundle state.Few analyses of antiresorptive (AR) treatment trials relate short-term changes in bone turnover markers (BTMs) to subsequent fracture reduction seeking to estimate the proportion of treatment effect explained (PTE) by BTMs. Pooling such information would be useful to assess new ARs or novel dosing regimens. In the Foundation for the National Institutes of Health (FNIH) Bone Quality project, we analyzed individual-level data from up to 62,000 participants enrolled in 12 bisphosphonate (BP) and four selective estrogen receptor modulator (SERM) placebo-controlled fracture endpoint trials. Using BTM results for two bone formation markers (bone-specific alkaline phosphatase [bone ALP] and pro-collagen I N-propeptide [PINP]) and one bone resorption marker (C-terminal telopeptide of type I collagen [CTX]) and incident fracture outcome data, we estimated the PTE using two different models. Separate analyses were performed for incident morphometric vertebral, nonvertebral, and hip fractures over 1 to 5 years of follow-up. For vertebral fracture, the results showed that changes in all three BTMs at 6 months explained a large proportion of the treatment effect of ARs (57 to >100%), but not for and non-vertebral or hip fracture. We conclude that short-term AR treatment-related changes in bone ALP, PINP, and CTX account for a large proportion of the treatment effect for vertebral fracture. Change in BTMs is a useful surrogate marker to study the anti-fracture efficacy of new AR compounds or novel dosing regiments with approved AR drugs. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.Spondyloepimetaphyseal dysplasias (SEMDs) are a heterogeneous group of disorders with variable growth failure and skeletal impairments affecting the spine and long bone epiphyses and metaphyses. Here we report on four unrelated families with SEMD in which we identified two monoallelic missense variants and one monoallelic splice site variant in RPL13, encoding the ribosomal protein eL13. In two out of four families, we observed autosomal dominant inheritance with incomplete penetrance and variable clinical expressivity; the phenotypes of the mutation-positive subjects ranged from normal height with or without hip dysplasia to severe SEMD with severe short stature and marked skeletal dysplasia. In this website on patient-derived dermal fibroblasts harboring RPL13 missense mutations demonstrated normal eL13 expression, with proper subcellular localization but reduced colocalization with eL28 (p less then  0.001). Cellular functional defects in fibroblasts from mutation-positive subjects indicated a significant increase in the ratio of 60S subunits to 80S ribosomes (p = 0.007) and attenuated global translation (p = 0.017). In line with the human phenotype, our rpl13 mutant zebrafish model, generated by CRISPR-Cas9 editing, showed cartilage deformities at embryonic and juvenile stages. These findings extend the genetic spectrum of RPL13 mutations causing this novel human ribosomopathy with variable skeletal features. Our study underscores for the first time incomplete penetrance and broad phenotypic variability in SEMD-RPL13 type and confirms impaired ribosomal function. Furthermore, the newly generated rpl13 mutant zebrafish model corroborates the role of eL13 in skeletogenesis. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)..