Pathogen burden and cortisol profiles over the day

Hypothalamic-pituitary-adrenocortical (HPA) regulation in adults is influenced by early psychosocial adversity, but the role of infectious disease history is poorly understood. We studied the association between cumulative pathogen burden and cortisol profile over the day in a sample of 317 healthy men and women aged 51-72 years. Cumulative pathogen burden was defined as positive serostatus for Chlamydia pneumoniae, cytomegalovirus (CMV) and herpes simplex virus 1 (HSV-1). Salivary cortisol was sampled repeatedly over the day. The cortisol slope was defined as the decrease across the day and evening. Age, gender, grade of employment, body mass index, smoking status, self-rated health, cardiovascular medication, depressed mood and time of waking were included as covariates. The pathogen burden averaged 1.76 (S.D. = 0.92). The cortisol slope was inversely associated with pathogen burden after controlling for covariates. When individual pathogens were studied, only CMV was associated with flatter cortisol rhythms in isolation. We conclude that pathogen burden is independently associated with flatter cortisol slopes over the day, and may contribute to disturbed neuroendocrine regulation

Investigation of Natural Effective Gamma Dose Rates case study: Ardabil Province in Iran

Gamma rays pose enough energy to form charged particles and adversely affect human health. Since, the external exposure of human beings to natural environmental gamma radiation normally exceeds that from all man-made sources combined, natural background gamma dose rates and corresponding annual effective doses were determined for selected cities of Ardabil province from 2009 to 2010. Outdoor gamma dose rates were measured using an Ion Chamber Survey Meter in 105 locations in selected districts. Average absorbed dose for Ardabil, Sar-Ein, Germy, Neer, Shourabil Recreational Lake, and Kosar were determined as 265, 219, 344, 233, 352, and 358 nSvh-1, respectively. Although dose rates recorded for Germi and Kosar are comparable with some areas with high natural radiation background, however, the dose rates in other districts are well below the levels reported for such locations. Average annual effective dose due to indoor and outdoor gamma radiation for Ardabil province was estimated to be 1.73 (1.35-2.39) mSv, which is on average 2 times higher than the world population weighted average

The effects of thermal-spatial behaviours of land covers on urban heat islands in semi-arid climates

In recent decades, unsustainable urban development stemming from uncontrolled changes in land cover and the accumulation of population and activities have given rise to adverse environmental consequences, such as the formation of urban heat islands (UHIs) and changes in urban microclimates. The formation and intensity of UHIs can be influenced not only by the type of land cover, but also by other factors, such as the spatial patterns of thermal clusters (e.g., dimensions, contiguity, and integration). By emphasising the differences between semi-arid and cold-and-humid climates in terms of the thermal−spatial behaviours of various types of land cover in these climates, this paper aims to assess the behavioural patterns of thermal clusters in Tehran, Iran. To this end, the relationship between the land surface temperature (LST) and the types of land cover is first demonstrated using combined multispectral satellite images taken by Operational Land Imager (OLI), Thermal Infrared Sensor (TIRS) of the Landsat8 and MODIS, and Sentinel satellites to determine LST and land cover. The effects of different behavioural patterns of thermal clusters on the formation of daytime urban heat islands are then analysed through spatial cross-correlation analysis. Lastly, the thermal behaviours of each cluster are separately examined to reveal how their spatial patterns, such as contiguity, affect the intensity and formation of UHI, with the assumption that each point in a contiguous surface may exhibit different thermal behaviours, depending on its distance from the edge or centre. The results of this study show that the daytime UHIs do not occur in the central parts of Tehran, and instead they are created in the surrounding layer, which mostly consists of barren cover. This finding contrasts with previous research conducted regarding cities located in cold-and-humid climates. Our research also finds that the more compact the hot and cool clusters are, the more contiguous they become, which leads to an increase in UHIs. The results suggest that for every 100 pix/km2 increase, the cluster temperature increases by approximately 0.7−1 °C. Additionally, placing cool clusters near or in combination with hot clusters interrupts the effect of the hot clusters, leading to a significant temperature reduction. The paper concludes with recommendations for potential sustainable and context-based solutions to UHI problems in semi-arid climates that relate to the determination of the optimal contiguity distance and land use integration patterns for thermal clusters

Multi-agent methodology for distributed and cooperative supervisory estimation subject to unreliable information

In this work, a novel multi-agent framework for cooperative supervisory estimation of linear time-invariant systems is proposed. This framework is developed based on the notion of subobservers and a discrete-event system (DES) supervisory control and is applicable to large-scale systems. We introduce a group of subobservers where each subobserver is estimating certain states that are conditioned on a given input, output and state information. The cooperation among the subobservers is managed by a DES supervisor. The supervisor makes decisions regarding the selection and configuration of a set of subobservers to successfully estimate all the system states, while the feasibility of the overall integrated cooperative subobservers is verified. When certain anomalies (faults) are present in the system, or the sensors and subobservers become unreliable, the supervisor reconfigures the set of selected subobservers so that the impacts of anomalies on the estimation performance are minimised to the extent that is possible. The application and capabilities of our proposed methodology in a practical industrial process is demonstrated through numerical simulations

NEURAL STEM/PROGENITOR CELL TRANSPLANTATION FOR SPINAL CORD INJURY TREATMENT; A SYSTEMATIC REVIEW AND META-ANALYSIS

—Despite the vast improvements of cell therapy in spinal cord injury treatment, no optimum protocol has been developed for application of neural stem/progenitor cells. In this regard, the present meta-analysis showed that the effi- cacy of the neural stem/progenitor cell (NSPC) transplantation depends mainly on injury model, intervention phase, transplanted cell count, immunosuppressive use, and probably stem cell source. Improved functional recovery post NSPC transplantation was found to be higher in transection and contusion models. Moreover, NSPC transplantation in acute phase of spinal injury was found to have better functional recovery. Higher doses (>3 � 106 cell/kg) were also shown to be optimum for transplantation, but immunosuppressive agent administration negatively affected the motor function recovery. Scaffold use in NSPC transplantation could also effectively raise functional recovery. � 2016 Published by Elsevier Ltd. on behalf of IBR

Rasagiline Effects on Glucose Metabolism, Cognition, and Tau in Alzheimer’s Dementia

Background: A Phase II proof of concept (POC) randomized clinical trial was conducted to evaluate the effects of rasagiline, a monoamine oxidase B (MAO-B) inhibitor approved for Parkinson disease, in mild to moderate Alzheimer\u27s disease (AD). The primary objective was to determine if 1 mg of rasagiline daily for 24 weeks is associated with improved regional brain metabolism (fluorodeoxyglucose–positron emission tomography [FDG-PET]) compared to placebo. Secondary objectives included measurement of effects on tau PET and evaluation of directional consistency of clinical end points. Methods: This was a double-blind, parallel group, placebo-controlled, community-based, three-site trial of 50 participants randomized 1:1 to receive oral rasagiline or placebo (NCT02359552). FDG-PET was analyzed for the presence of an AD-like pattern as an inclusion criterion and as a longitudinal outcome using prespecified regions of interest and voxel-based analyses. Tau PET was evaluated at baseline and longitudinally. Clinical outcomes were analyzed using an intention-to-treat (ITT) model. Results: Fifty patients were randomized and 43 completed treatment. The study met its primary end point, demonstrating favorable change in FDG-PET differences in rasagiline versus placebo in middle frontal (P \u3c 0.025), anterior cingulate (P \u3c 0.041), and striatal (P \u3c 0.023) regions. Clinical measures showed benefit in quality of life (P \u3c 0.04). Digit Span, verbal fluency, and Neuropsychiatric Inventory (NPI) showed non-significant directional favoring of rasagiline; no effects were observed in Alzheimer\u27s Disease Assessment Scale-Cognitive Subscale (ADAS-cog) or activities of daily living. Rasagiline was generally well tolerated with low rates of adverse events and notably fewer neuropsychiatric symptoms in the active treatment group. Discussion: These outcomes illustrate the potential benefits of rasagiline on clinical and neuroimaging measures in patients with mild to moderate AD. Rasagiline appears to affect neuronal activity in frontostriatal pathways, with associated clinical benefit potential warranting a more fully powered trial. This study illustrated the potential benefit of therapeutic repurposing and an experimental medicine proof-of-concept design with biomarkers to characterize patient and detect treatment response

Experimental Verification of a Predicted Intronic MicroRNA in Human NGFR Gene with a Potential Pro-Apoptotic Function

Neurotrophins (NTs) are a family of secreted growth factor proteins primarily involved in the regulation of survival and appropriate development of neural cells, functioning by binding to their specific (TrkA, TtkB, and TrkC) and/or common NGFR receptor. NGFR is the common receptor of NTs, binding with low-affinity to all members of the family. Among different functions assigned to NGFR, it is also involved in apoptosis induction and tumorigenesis processes. Interestingly, some of the functions of NGFR appear to be ligand-independent, suggesting a probable involvement of non-coding RNA residing within the sequence of the gene. Here, we are reporting the existence of a conserved putative microRNA, named Hsa-mir-6165 [EBI accession#: FR873488]. Transfection of a DNA segment corresponding to the pre-mir-6165 sequence in Hela cell line caused the generation of mature exogenous mir-6165 (a ∼200,000 fold overexpression). Furthermore, using specific primers, we succeeded to detect the endogenous expression of mir-6165 in several glioma cell lines and glioma primary tumors known to express NGFR. Similar to the pro-apoptotic role of NGFR in some cell types, overexpression of pre-mir-6165 in U87 cell line resulted in an elevated rate of apoptosis. Moreover, coordinated with the increased level of mir-6165 in the transfected U87 cell line, two of its predicted target genes (Pkd1 and DAGLA) were significantly down-regulated. The latter findings suggest that some of the previously attributed functions of NGFR could be explained indirectly by co-transcription of mir-6165 in the cells