The association between metabolic syndrome and its components with systemic lupus erythematosus: a comprehensive systematic review and meta-analysis of observational studies

Objectives: Based upon inflammatory-related factors in chronic systemic lupus erythematosus (SLE), as well as the long-term prescription of corticosteroids, metabolic syndrome (MetS) prevalence is expected to be higher in SLE patients than among those without SLE. The aim of this study was to systematically analyze: (1) the worldwide prevalence of MetS in patients with SLE using different criteria, (2) the risk of MetS in patients with SLE compared with those without SLE, and (3) the risk of MetS component in patients with SLE compared with healthy controls. Methods: We searched international databases, such as: Web of Science, Medline, PubMed, Scopus, Embase, CABI, CINAHL, DOAJ and Google Scholar. The articles which reported the prevalence of MetS in SLE patients, between 2006 and 2017, were included in the study if they had a: clear study design, study time and location, sound sampling approach and appropriate statistical analyses. Studies without sufficient data to determine the prevalence of MetS were excluded. Also, studies in patients suffering from other clinical diseases were not included. Results: The meta-analyses of the prevalence (40 studies (n = 6085)) and risk (20 studies (n = 2348)) of MetS in SLE patients were conducted separately. The pooled prevalence of MetS among SLE patients was found to be 26 (95 confidence interval (CI): 22-30), but varied from 18 (95 CI: 11-25) to 34 (95 CI: 25-42), depending upon the diagnostic criteria used. The overall pooled odds ratio (OR) of MetS in SLE patients, compared with healthy controls, was (OR = 2.50; 95 CI: 1.86-3.35), but this ranged from (OR = 1.23; 95 CI: 0.61-2.49) to (OR = 10.71; 95 CI: 1.33-86.48), depending upon the criteria used. Also, the risk of high fasting blood sugar (FBS; OR = 1.59; 95 CI: 1.05-2.40), low high-density lipoprotein cholesterol (HDL-C; OR = 1.43; 95 CI: 1.02-2.01), high blood pressure (BP; OR = 2.76; 95 CI: 2.19-3.47), high triglycerides (TG; OR = 2.85; 95 CI: 2.05-3.95) and high waist circumference (WC; OR = 1.37; 95 CI: 0.97-1.94) were all found to be higher in SLE patients compared with healthy controls. Conclusions: The risk of MetS was significantly higher in SLE patients, compared with healthy controls, even after adjusting for publication bias. Among MetS components, high TG and high BP were most strongly associated with SLE. Considering that high TG and high BP are preventable, there is an international need to implement effective interventions to reduce MetS components in SLE patients in order to prevent serious outcomes such as cardiovascular diseases and mortality

A Roadmap for the Production of a GMP-Compatible Cell Bank of Allogeneic Bone Marrow-Derived Clonal Mesenchymal Stromal Cells for Cell Therapy Applications

Background: Allogeneic mesenchymal stromal cells (MSCs) have been used extensively in various clinical trials. Nevertheless, there are concerns about their efficacy, attributed mainly to the heterogeneity of the applied populations. Therefore, producing a consistent population of MSCs is crucial to improve their therapeutic efficacy. This study presents a good manufacturing practice (GMP)-compatible and cost-effective protocol for manufacturing, banking, and lot-release of a homogeneous population of human bone marrow-derived clonal MSCs (cMSCs). Methods: Here, cMSCs were isolated based on the subfractionation culturing method. Afterward, isolated clones that could reproduce up to passage three were stored as the seed stock. To select proliferative clones, we used an innovative, cost-effective screening strategy based on lengthy serial passaging. Finally, the selected clones re-cultured from the seed stock to establish the following four-tired cell banking system: initial, master, working, and end of product cell banks (ICB, MCB, WCB, and EoPCB). Results: Through a rigorous screening strategy, three clones were selected from a total of 21 clones that were stored during the clonal isolation process. The selected clones met the identity, quality, and safety assessments criteria. The validated clones were stored in the four-tiered cell bank system under GMP conditions, and certificates of analysis were provided for the three-individual ready-to-release batches. Finally, a stability study validated the EoPCB, release, and transport process of the frozen final products. Conclusion: Collectively, this study presents a technical and translational overview of a GMP-compatible cMSCs manufacturing technology that could lead to the development of similar products for potential therapeutic applications. Graphical Abstract: [Figure not available: see fulltext.

Metabolic syndrome and its components among rheumatoid arthritis patients: A comprehensive updated systematic review and meta-analysis

Background Estimating the current global prevalence of metabolic syndrome (MetS), and its components, among rheumatoid arthritis (RA) patients is necessary in order to formulate preventative strategies and to ensure there are adequate community resources available for these patients. Furthermore, the association between RA and MetS is controversial and has not previously been comprehensively assessed. Therefore, the present study aimed to: 1) determine the prevalence of MetS, and its components, among RA patients across the world 2) update the odds ratio of MetS in RA patients, compared to healthy controls, using a comprehensive systematic review and meta-analysis. Methods International databases, including: the Web of Science, PubMed, Scopus, Embase, CINAHL and other relevant databases were searched to identify English language articles which reported the prevalence and risk of MetS in RA patients between January 2000 and August 2016. The meta-analysis only included studies which clearly described the time and location of the study, utilised adequate sampling strategies, and appropriate statistical analyses Results The meta-analyses of prevalence (70 studies [n = 12612]) and risk (43 studies [n = 35220]) of MetS in RA patients were undertaken separately. The overall pooled prevalence of MetS was 30.65% (95% CI: 27.87–33.43), but this varied from 14.32% (95% CI: 10.59–18.05) to 37.83% (95% CI: 31.05–44.61), based upon the diagnostic criteria used. The prevalence of MetS also varied slightly between males (31.94%, 95% CI: 24.37–39.51) and females (33.03%, 95% CI: 28.09–37.97), but this was not statistically significant. The overall pooled odds ratio (OR) of MetS in RA patients, compared to healthy controls, was 1.44 (95% CI: 1.20–1.74), but this ranged from 0.70 (95% CI: 0.27–1.76) to 4.09 (95% CI: 2.03–8.25), depending on the criteria used. The mean age and diagnostic criteria of MetS were identified as sources of heterogeneity in the estimated odds ratios between studies (P<0.05) Conclusions According to the high prevalence of MetS in RA patients, and high risk of MetS, measuring metabolic syndrome in RA patients is strongly recommended. Furthermore, as high waist circumference (WC) is the most common metabolic syndrome component, more attention must be paid to nutrition and weight loss among those with R

Deep learning-based quantification of temporalis muscle has prognostic value in patients with glioblastoma

Background Glioblastoma is the commonest malignant brain tumour. Sarcopenia is associated with worse cancer survival, but manually quantifying muscle on imaging is time-consuming. We present a deep learning-based system for quantification of temporalis muscle, a surrogate for skeletal muscle mass, and assess its prognostic value in glioblastoma. Methods A neural network for temporalis segmentation was trained with 366 MRI head images from 132 patients from 4 different glioblastoma data sets and used to quantify muscle cross-sectional area (CSA). Association between temporalis CSA and survival was determined in 96 glioblastoma patients from internal and external data sets. Results The model achieved high segmentation accuracy (Dice coefficient 0.893). Median age was 55 and 58 years and 75.6 and 64.7% were males in the in-house and TCGA-GBM data sets, respectively. CSA was an independently significant predictor for survival in both the in-house and TCGA-GBM data sets (HR 0.464, 95% CI 0.218–0.988, p = 0.046; HR 0.466, 95% CI 0.235–0.925, p = 0.029, respectively). Conclusions Temporalis CSA is a prognostic marker in patients with glioblastoma, rapidly and accurately assessable with deep learning. We are the first to show that a head/neck muscle-derived sarcopenia metric generated using deep learning is associated with oncological outcomes and one of the first to show deep learning-based muscle quantification has prognostic value in cancer

The effect of modern intensive monitoring in obstetrics on infant mortality and the incidence of hypoxia and acidosis

Peer Reviewe

Cycle-based Cluster Variational Method for Direct and Inverse Inference

We elaborate on the idea that loop corrections to belief propagation could be dealt with in a systematic way on pairwise Markov random fields, by using the elements of a cycle basis to define region in a generalized belief propagation setting. The region graph is specified in such a way as to avoid dual loops as much as possible, by discarding redundant Lagrange multipliers, in order to facilitate the convergence, while avoiding instabilities associated to minimal factor graph construction. We end up with a two-level algorithm, where a belief propagation algorithm is run alternatively at the level of each cycle and at the inter-region level. The inverse problem of finding the couplings of a Markov random field from empirical covariances can be addressed region wise. It turns out that this can be done efficiently in particular in the Ising context, where fixed point equations can be derived along with a one-parameter log likelihood function to minimize. Numerical experiments confirm the effectiveness of these considerations both for the direct and inverse MRF inference.Comment: 47 pages, 16 figure

Taking the Measure of the Universe: Precision Astrometry with SIM PlanetQuest

Precision astrometry at microarcsecond accuracy has application to a wide range of astrophysical problems. This paper is a study of the science questions that can be addressed using an instrument that delivers parallaxes at about 4 microarcsec on targets as faint as V = 20, differential accuracy of 0.6 microarcsec on bright targets, and with flexible scheduling. The science topics are drawn primarily from the Team Key Projects, selected in 2000, for the Space Interferometry Mission PlanetQuest (SIM PlanetQuest). We use the capabilities of this mission to illustrate the importance of the next level of astrometric precision in modern astrophysics. SIM PlanetQuest is currently in the detailed design phase, having completed all of the enabling technologies needed for the flight instrument in 2005. It will be the first space-based long baseline Michelson interferometer designed for precision astrometry. SIM will contribute strongly to many astronomical fields including stellar and galactic astrophysics, planetary systems around nearby stars, and the study of quasar and AGN nuclei. SIM will search for planets with masses as small as an Earth orbiting in the `habitable zone' around the nearest stars using differential astrometry, and could discover many dozen if Earth-like planets are common. It will be the most capable instrument for detecting planets around young stars, thereby providing insights into how planetary systems are born and how they evolve with time. SIM will observe significant numbers of very high- and low-mass stars, providing stellar masses to 1%, the accuracy needed to challenge physical models. Using precision proper motion measurements, SIM will probe the galactic mass distribution and the formation and evolution of the Galactic halo. (abridged)Comment: 54 pages, 28 figures, uses emulateapj. Submitted to PAS

Maxadilan Prevents Apoptosis in iPS Cells and Shows No Effects on the Pluripotent State or Karyotype

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a structurally endogenous peptide with many biological roles. Maxadilan, a 61-amino acid vasodilatory peptide, specifically activates the PACAP type I receptor (PAC1). Although PAC1 has been identified in embryonic stem cells, little is known about its presence or effects in human induced pluripotent stem (iPS) cells. In the present study, we investigated the expression of PAC1 in human iPS cells by reverse transcriptase polymerase chain reaction (RT-PCR) and western blot analysis. To study the physiological effects mediated by PAC1, we evaluated the role of maxadilan in preventing apoptotic cell death induced by ultraviolet C (UVC). After exposure to UVC, the iPS cells showed a marked reduction in cell viability and a parallel increase of apoptotic cells, as demonstrated by WST-8 analysis, annexin V/propidium iodide (PI) analysis and the terminal transferase dUTP nick end labeling (TUNEL) assay. The addition of 30 nM of maxadilan dramatically increased iPS cell viability and reduced the percentage of apoptotic cells. The anti-apoptotic effects of maxadilan were correlated to the downregulation of caspase-3 and caspase-9. Concomitantly, immunofluorescence, western blot analysis, real-time quantitative polymerase chain reaction (RT-qPCR) analysis and in vitro differentiation results showed that maxadilan did not affect the pluripotent state of iPS cells. Moreover, karyotype analysis showed that maxadilan did not affect the karyotype of iPS cells. In summary, these results demonstrate that PAC1 is present in iPS cells and that maxadilan effectively protects iPS cells against UVC-induced apoptotic cell death while not affecting the pluripotent state or karyotype

Prescribing the Jacobian in critical spaces

International audienceWe consider the Sobolev space $X=W^{s,p}({\mathbb S}^m ; {\mathbb S}^{k-1})$. We prove the existence of a robust distributional Jacobian $Ju$ for $u\in X$ provided $sp\ge k-1$. This generalizes a result of Bourgain, Brezis and the second author (Comm. Pure Appl. Math. 2005), where the case $m=k$ is considered. In the critical case where $sp=k-1$, we identify the image of the map $X\ni u\mapsto Ju$. This extends a result of Alberti, Baldo and Orlandi (J. Eur. Math. Soc. 2003) for $s=1$ and $p=k-1$. We also present a new, analytical, dipole construction method

Congenital rubella syndrome in Iran

BACKGROUND: Congenital rubella syndrome (CRS) can be prevented with appropriate vaccination programs. The prevalence rates of rubella and CRS in Iran are unknown; therefore, the risk of exposure in pregnant women is not clear. The prevalence of CRS in the pre-vaccine period can be estimated by evaluating the proportion of children in the population with sensorineural hearing loss attributable to rubella. METHODS: This was a case-control study to estimate prevalence of CRS in Tehran (Iran) by evaluating the proportion of children with sensorineural hearing loss attributable to rubella. The study used rubella antibody titer as an indicator, and compared the prevalence of rubella antibody between children with and without sensorineural hearing loss. Using these findings, the proportion of cases of sensorineural hearing loss attributable to rubella was estimated. RESULTS: A total of 225 children aged 1 to 4 years were entered into the study (113 cases and 112 controls). There was a significant difference between cases and controls with regard to rubella antibody seropositivity (19.5% vs. 8.9%, respectively, odds ratio = 2.47, 95% CI = 1.04–5.97). The proportion of sensorineural hearing loss cases attributable to rubella was found to be 12%, corresponding to a CRS prevalence of 0.2/1000. CONCLUSION: The prevalence of CRS was approximately 0.2/1000 before rubella vaccination in Iran, Moreover; the results suggest that implementation of appropriate rubella vaccination programs could potentially prevent about 12% of cases of sensorineural hearing loss in Iranian children. This data could potentially be used as baseline data, which in conjunction with an appropriate method, to establish a surveillance system for rubella vaccination in Iran. An appropriate surveillance system is needed, because the introduction of a rubella vaccine without epidemiological data and an adequate monitoring program could result in the shifting of rubella cases to higher ages, and increasing the incidence of CRS