The mazEF toxin-antitoxin system as a novel antibacterial target in Acinetobacter baumannii

Although analysis of toxin-antitoxin (TA) systems can be instructive, to date, there is no information on the prevalence and identity of TA systems based on a large panel of Acinetobacter baumannii clinical isolates. The aim of the current study was to screen for functional TA systems among clinical isolates of A. baumannii and to identify the systems' locations. For this purpose, we screened 85 A. baumannii isolates collected from different clinical sources for the presence of the mazEF, relBE and higBA TA genes. The results revealed that the genes coding for the mazEF TA system were commonly present in all clinical isolates of A. baumannii. Reverse transcriptase-polymerase chain reaction analysis showed that transcripts were produced in the clinical isolates. Our findings showed that TA genes are prevalent, harboured by chromosomes and transcribed within A. baumannii. Hence, activation of the toxin proteins in the mazEF TA system should be investigated further as an effective antibacterial strategy against this bacterium

A Gradient Weighted Moving Finite-Element Method with Polynomial Approximation of Any Degree

A gradient weighted moving finite element method (GWMFE) based on piecewise polynomial of any degree is developed to solve time-dependent problems in two space dimensions. Numerical experiments are employed to test the accuracy and effciency of the proposed method with nonlinear Burger equation

The Extent, Nature and Contributing Factors of Violence Against Iranian Emergency Medical Technicians

Background: Workplace Violence (WPV) is one of the most complex and dangerous occupational hazards faced by pre-hospital emergency medical technicians (EMTs). Objectives: This study aimed to assess the extent, nature and contributing factors of WPV against EMTs in Urmia, Iran. Materials and Methods: A cross-sectional study was conducted on 120 EMTs from April to October 2014. A questionnaire was used for collecting the data. Descriptive statistics were applied to the data. Results: Most of the participants (79%) experienced WPV during the past six months. Accident scene was the most important place of violence and the patients’ companions were the main perpetrators of violence. Overall, 76% of violence victims reported “lack of awareness of the EMTs’ duties” as the most important contributing factor for WPV. Conclusions: This study highlighted the high frequency of WPV against EMTs. Evidently, the health care systems’ officials would benefit from taking proper actions in this area, particularly by “staff and public education”

Numerics of stochastic parabolic differential equations with stable finite difference schemes

Abstract In the present article, we focus on the numerical approximation of stochastic partial differential equations of Itˆo type with space-time white noise process, in particular, parabolic equations. For each case of additive and multiplicative noise, the numerical solution of stochastic diffusion equations is approximated using two stochastic finite difference schemes and the stability and consistency conditions of the considered methods are analyzed. Numerical results are given to demonstrate the computational efficiency of the stochastic methods

Adapted MMSE and TYM cognitive tests: how much powerful in screening for Alzheimer�s disease in Iranian people

Alzheimer�s disease (AD) is a major global health priority and providing an efficient way for early diagnosis of people developing dementia is important. The Mini-Mental State Examination (MMSE, total score = 30) and Test Your Memory (TYM, total score = 50) are widely used as screening tests for cognitive function. In the present study 174 subjects including healthy people (CON group) and those having Alzheimer�s disease (AD group) were introduced to MMSE and TYM cognitive tests adjusted to Iranian population. Sensitivities and specificities with optimal cut-off scores, area under curve (AUC), positive predictive value (PPV) and negative predictive value (NPV) were measured for both tests. The MMSE scores of the CON and AD groups were 23.77 ± 0.327 and 10.88 ± 0.762, respectively. The TYM scores were 44.32 ± 0.389 and 14.37 ± 1.368 in the CON and AD participants, respectively. Findings in the MMSE test were: AUC = 0.962, optimal cut-off score = 18.5, sensitivity = 0.90 and specificity = 0.96. Values in the TYM test were: AUC = 0.991, optimal cut-off score = 31, sensitivity = 0.90 and specificity = 1. We found no correlation between the cognitive performance and age in the CON group but a positive correlation in the AD patients. On the other hand, t-test analysis indicated that achievement of the test scores are significantly sex dependent, with more scores attained by the females. Taken together, in regard to correct classification rate (CCR); the TYM test seems to be more appropriate for cognitive screening in our study. However, considering an analogous AUC, both tests are comparable and have high sensitivity and specificity for discriminating between people with and without AD. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group

Does severity of Alzheimer's disease contribute to its responsiveness to modifying gut microbiota? A double blind clinical trial

Alzheimer's disease (AD) is associated with cognitive dysfunction. Evidence indicates that gut microbiota is altered in the AD and, hence, modifying the gut flora may affect the disease. In the previous clinical research we evaluated the effect of a probiotic combination on the cognitive abilities of AD patients. Since, in addition to pathological disorders, the AD is associated with changes in oxidant/antioxidant and inflammatory/anti-inflammatory biomarkers, the present work was designed to evaluate responsiveness of the inflammatory and oxidative biomarkers to the probiotic treatment. The control (CON) and probiotic (PRO) AD patients were treated for 12 weeks by the placebo and probiotic supplementation, respectively. The patients were cognitively assessed by Test Your Memory (TYM = 50 scores). Also serum concentrations of nitric oxide (NO), glutathione (GSH), total antioxidant capacity (TAC), malondialdehyde (MDA), 8-hydroxy-2' -deoxyguanosine (8-OHdG) and cytokines (TNF-α, IL-6, and IL-10) were measured. The cognitive test and the serum biomarkers were assessed pre- and post-treatment. According to TYM test 83.5 of the patients showed severe AD. The CON (12.86 ± 8.33) and PRO (-9.35 ± 16.83) groups not differently scored the cognitive test. Not pronounced change percent was found in the serum level of TNF-α (1.67 ± 1.33 vs. -0.15 ± 0.27), IL-6 (0.35 ± 0.17 vs. 2.18 ± 0.15), IL-10 (0.05 ± 0.10 vs. -0.70 ± 0.73), TAC (0.07 ± 0.07 and -0.06 ± 0.03), GSH (0.08 ± 0.05 and 0.04 ± 0.03) NO (0.11 ± 0.06 and 0.05 ± 0.09), MDA (-0.11 ± 0.03 and -0.17 ± 0.03), 8-OHdG (43.25 ± 3.01 and 42.70 ± 3.27) in the CON and PRO groups, respectively. We concluded that the cognitive and biochemical indications in the patients with severe AD are insensitive to the probiotic supplementation. Therefore, in addition to formulation and dosage of probiotic bacteria, severity of disease and time of administration deeply affects results of treatment. © 2018 Agahi, Hamidi, Daneshvar, Hamdieh, Soheili, Alinaghipour, Esmaeili Taba and Salami

Rescaled coordinate descent methods for linear programming

We propose two simple polynomial-time algorithms to find a positive solution to Ax=0Ax=0 . Both algorithms iterate between coordinate descent steps similar to von Neumann’s algorithm, and rescaling steps. In both cases, either the updating step leads to a substantial decrease in the norm, or we can infer that the condition measure is small and rescale in order to improve the geometry. We also show how the algorithms can be extended to find a solution of maximum support for the system Ax=0Ax=0 , x≥0x≥0 . This is an extended abstract. The missing proofs will be provided in the full version

Severe hematopoietic stem cell inflammation compromises chronic granulomatous disease gene therapy

X-linked chronic granulomatous disease (CGD) is associated with defective phagocytosis, life-threatening infections, and inflammatory complications. We performed a clinical trial of lentivirus-based gene therapy in four patients (NCT02757911). Two patients show stable engraftment and clinical benefits, whereas the other two have progressively lost gene-corrected cells. Single-cell transcriptomic analysis reveals a significantly lower frequency of hematopoietic stem cells (HSCs) in CGD patients, especially in the two patients with defective engraftment. These two present a profound change in HSC status, a high interferon score, and elevated myeloid progenitor frequency. We use elastic-net logistic regression to identify a set of 51 interferon genes and transcription factors that predict the failure of HSC engraftment. In one patient, an aberrant HSC state with elevated CEBPβ expression drives HSC exhaustion, as demonstrated by low repopulation in a xenotransplantation model. Targeted treatments to protect HSCs, coupled to targeted gene expression screening, might improve clinical outcomes in CGD

Reduced fronto-striatal volume in attention-deficit/hyperactivity disorder in two cohorts across the lifespan

Attention-Deficit/Hyperactivity Disorder (ADHD) has been associated with altered brain anatomy in neuroimaging studies. However, small and heterogeneous study samples, and the use of region-of-interest and tissue-specific analyses have limited the consistency and replicability of these effects. We used a data-driven multivariate approach to investigate neuroanatomical features associated with ADHD in two independent cohorts: the Dutch NeuroIMAGE cohort (n = 890, 17.2 years) and the Brazilian IMpACT cohort (n = 180, 44.2 years). Using independent component analysis of whole-brain morphometry images, 375 neuroanatomical components were assessed for association with ADHD. In both discovery (corrected-p = 0.0085) and replication (p = 0.032) cohorts, ADHD was associated with reduced volume in frontal lobes, striatum, and their interconnecting white-matter. Current results provide further evidence for the role of the fronto-striatal circuit in ADHD in children, and for the first time show its relevance to ADHD in adults. The fact that the cohorts are from different continents and comprise different age ranges highlights the robustness of the findings