Association of Serum Uric Acid Level with the Severity of Brain Injury and Patient's Outcome in Severe Traumatic Brain Injury

Introduction: The prognostic value of serum Uric Acid (UA) levels in Traumatic Brain Injury (TBI) is unclear. Aim: To investigate the relationship between serum UA levels and prognosis of patients with TBI when in hospital and at six months after discharge. Materials and Methods: All patients attended our emergency department during July 2014 and December 2015 and were consecutively entered into the study and among 890 evaluated candidates based on inclusion criteria we finally investigated the serum UA levels of 725 TBI patients. Computed Tomography (CT) images of the brain were obtained within the first 24 hours of hospitalization. Outcome was assessed using the Glasgow Outcome Scale (GOS) score at discharge and at six months after discharge. Results: Data of 725 patients (42.89 men; mean age: 54.69+/-12.37 years) were analyzed. Mean+/-Standard Deviation (SD) of Glasgow Coma Scale (GCS) scores was 4.65+/-1.76. Serum levels of UA, when in hospital and at six months after discharge, among those who died were lower than those who survived (in hospital: 0.126+/-0.026 vs. 0.243+/-0.942 mmol/l, p = 0.000; 6 months post-discharge: 0.130+/-0.044 vs. 0.286+/-0.069 mmol/l, p<0.001). The mean UA plasma was significantly different between deceased and alive patients according to GOS scores (p<0.001 and p=0.030, respectively). The UA levels showed a significant relationship with GCS scores and severity of brain injury assessed using the Marshall Classification Score (p=0.005). Conclusion: Our results showed a strong relationship between UA levels and patients' outcomes either in hospital or at six months after discharge. Serum UA level could be considered as a valuable marker for evaluating the severity of brain injury and outcomes of TBI

Mortality associated with avian reovirus infection in a free-living magpie (Pica pica) in Great Britain

Avian reoviruses (ARVs) cause a range of disease presentations in domestic, captive and free-living bird species. ARVs have been reported as a cause of significant disease and mortality in free-living corvid species in North America and continental Europe. Until this report, there have been no confirmed cases of ARV-associated disease in British wild birds

Numerical processing in the human parietal cortex during experimental and natural conditions

Human cognition is traditionally studied in experimental conditions wherein confounding complexities of the natural environment are intentionally eliminated. Thus, it remains unknown how a brain region involved in a particular experimental condition is engaged in natural conditions. Here we use electrocorticography to address this uncertainty in three participants implanted with intracranial electrodes and identify activations of neuronal populations within the intraparietal sulcus region during an experimental arithmetic condition. In a subsequent analysis, we report that the same intraparietal sulcus neural populations are activated when participants, engaged in social conversations, refer to objects with numerical content. Our prototype approach provides a means for both exploring human brain dynamics as they unfold in complex social settings and reconstructing natural experiences from recorded brain signals

Some Physiological Effects of Nanofertilizers on Wheat-Aphid Interactions

The increasing use of nanofertilizers in modern agriculture and their impact on crop yield and pest management require further research. In this study, the effects of nano-Fe, -Zn, and -Cu (which are synthesized based on nanochelating technology), and urea (N) fertilizers on the antioxidant activities of wheat plants (cv. Chamran), and the wheat green aphid Schizaphis graminum (Rondani) are investigated. The authors observed the highest levels of phenolics in non-infested nano-Zn-treated plants (26% higher compared with control). The highest H2O2 levels are in the infested and non-infested nano-Zn-treated and infested nano-Fe-treated plants (in infested nano-Zn and nano-Fe treated plants, 18% and non-infested nano-Zn-treated plants, 28% higher compared with control). The highest peroxidase (POX) activity is observed in the infested and non-infested N-treated and non-infested water-treated plants (almost 14%, 37%, and 46% higher than control, respectively). The lowest activity is in the infested plants’ nano-Zn and -Fe treatments (almost 7 and 5 folds lower compared to the control, respectively). The highest and lowest catalase (CAT) activity are in the infested N-treated plants (almost 42% higher than control) and water-treated plants, respectively. The infested nano-Zn, -Fe, -Cu and Hoagland-treated plants showed the highest superoxide dismutase (SOD) activity. Regarding the antioxidant enzyme activities of S. graminum, the highest POX activity is in the nano-Cu treatment (more than two folds higher compared with control); the highest CAT and SOD activities are in the nano-Cu and -Zn treatments. It can be concluded that the application of nanofertilizers caused increasing effects on the wheat plant’s antioxidant system and its resistance to S. graminum

Development of analytical characterization tools for process monitoring of adenovirus-based vaccines (ChAdOx and Ad5)

Product quality understanding is a critical part of viral vector vaccine manufacturing and regulation. Mass spectrometry is a technique that has widely been applied to protein-based therapeutics and could be used as a characterisation tool to monitor viral vector vaccine product quality. The ultimate objective of this Bill and Melinda Gates Foundation funded project is to enable vaccine manufacturing in Low and Middle-income countries (LMIC) through increased scientific understanding of viral vector vaccine manufacturing bottlenecks and therefore de-risking of vaccine development and manufacturing. Please click Download on the upper right corner to see the full abstract

Differential electrophysiological response during rest, self-referential, and non-self-referential tasks in human posteromedial cortex

The electrophysiological basis for higher brain activity during rest and internally directed cognition within the human default mode network (DMN) remains largely unknown. Here we use intracranial recordings in the human posteromedial cortex (PMC), a core node within the DMN, during conditions of cued rest, autobiographical judgments, and arithmetic processing. We found a heterogeneous profile of PMC responses in functional, spatial, and temporal domains. Although the majority of PMC sites showed increased broad gamma band activity (30-180 Hz) during rest, some PMC sites, proximal to the retrosplenial cortex, responded selectively to autobiographical stimuli. However, no site responded to both conditions, even though they were located within the boundaries of the DMN identified with resting-state functional imaging and similarly deactivated during arithmetic processing. These findings, which provide electrophysiological evidence for heterogeneity within the core of the DMN, will have important implications for neuroimaging studies of the DMN

Measurement of Adenovirus-Based Vector Heterogeneity

Adenovirus vectors have become an important class of vaccines with the recent approval of Ebola and COVID-19 products. In-process quality attribute data collected during Adenovirus vector manufacturing has focused on particle concentration and infectivity ratios (based on viral genome: cell-based infectivity), and data suggest only a fraction of viral particles present in the final vaccine product are efficacious. To better understand this product heterogeneity, lab-scale preparations of two Adenovirus viral vectors, (Chimpanzee adenovirus (ChAdOx1) and Human adenovirus Type 5 (Ad5), were studied using transmission electron microscopy (TEM). Different adenovirus morphologies were characterized, and the proportion of empty and full viral particles were quantified. These proportions showed a qualitative correlation with the sample's infectivity values. Liquid chromatography-mass spectrometry (LC-MS) peptide mapping was used to identify key adenovirus proteins involved in viral maturation. Using peptide abundance analysis, a ∼5-fold change in L1 52/55k abundance was observed between low-(empty) and high-density (full) fractions taken from CsCl ultracentrifugation preparations of ChAdOx1 virus. The L1 52/55k viral protein is associated with DNA packaging and is cleaved during viral maturation, so it may be a marker for infective particles. TEM and LC-MS peptide mapping are promising higher-resolution analytical characterization tools to help differentiate between relative proportions of empty, non-infectious, and infectious viral particles as part of Adenovirus vector in-process monitoring, and these results are an encouraging initial step to better differentiate between the different product-related impurities

A primer set for the rapid isolation of scFv fragments against cell surface antigens from immunised rats

Antibody phage display is a powerful platform for discovery of clinically applicable high affinity monoclonal antibodies against a broad range of targets. Libraries generated from immunized animals offer the advantage of in vivo affinity-maturation of V regions prior to library generation. Despite advantages, few studies have described isolation of antibodies from rats using immune phage display. In our study, we describe a novel primer set, covering the full rat heavy chain variable and kappa light chain variable regions repertoire for the generation of an unbiased immune libraries. Since the immune repertoire of rats is poorly understood, we first performed a deep sequencing analysis of the V(D)J regions of VH and VLK genes, demonstrating the high abundance of IGVH2 and IGVH5 families for VH and IGVLK12 and IGVLK22 for VLK. The comparison of gene’s family usage in naïve rats have been used to validate the frequency’s distribution of the primer set, confirming the absence of PCR-based biases. The primers were used to generate and assemble a phage display library from human CD160-vaccinated rats. CD160 represents a valid therapeutic target as it has been shown to be expressed on chronic lymphocytic leukaemia cells and on the surface of newly formed vessels. We utilised a novel phage display panning strategy to isolate a high affinity pool (KD range: 0.399–233 nM) of CD160 targeting monoclonal antibodies. Subsequently, identified binders were tested for function as third generation Chimeric Antigen Receptors (CAR) T cells demonstrating specific cytolytic activity. Our novel primer set coupled with a streamlined strategy for phage display panning enable the rapid isolation and identification of high affinity antibodies from immunised rats. The therapeutic utility of these antibodies was demonstrated in CAR format

A novel antigen capture ELISA for the specific detection of IgG antibodies to elephant endotheliotropic herpes virus

BACKGROUND Elephants are classified as critically endangered animals by the International Union for Conservation of Species (IUCN). Elephant endotheliotropic herpesvirus (EEHV) poses a large threat to breeding programs of captive Asian elephants by causing fatal haemorrhagic disease. EEHV infection is detected by PCR in samples from both clinically ill and asymptomatic elephants with an active infection, whereas latent carriers can be distinguished exclusively via serological assays. To date, identification of latent carriers has been challenging, since there are no serological assays capable of detecting seropositive elephants. RESULTS Here we describe a novel ELISA that specifically detects EEHV antibodies circulating in Asian elephant plasma/serum. Approximately 80 % of PCR positive elephants display EEHV-specific antibodies. Monitoring three Asian elephant herds from European zoos revealed that the serostatus of elephants within a herd varied from non-detectable to high titers. The antibody titers showed typical herpes-like rise-and-fall patterns in time which occur in all seropositive animals in the herd more or less simultaneously. CONCLUSIONS This study shows that the developed ELISA is suitable to detect antibodies specific to EEHV. It allows study of EEHV seroprevalence in Asian elephants. Results confirm that EEHV prevalence among Asian elephants (whether captive-born or wild-caught) is high

MEASURING SPATIAL ACCESSIBILITY TO HEALTHCARE FACILITIES IN ISFAHAN METROPOLITAN AREA IN IRAN

Appropriate spatial accessibility to healthcare facilities is an important component of the efficient delivery of healthcare. This study aims to measure spatial accessibility to healthcare facilities in Isfahan Metropolitan Area, a rapidly growing megacity in Iran. We used two methods of population-weighted fuzzy analytic hierarchy process and the two-step floating catchment area (2SFCA) to measure spatial accessibility to urban healthcare facilities, including hospitals, pharmacies, clinics, and laboratories. The results of these two methods were compared. Not surprisingly, the center of Isfahan has the highest accessibility scores for healthcare facilities, and the peripheral areas of the city have the lowest levels. Despite the existence of higher numbers of healthcare facilities in northern parts of Isfahan, accessibility to healthcare facilities is low because of the large population. Both methods show that healthcare services are not evenly distributed in Isfahan. Some areas with a high population have low accessibility to health facilities. Ideally, these areas would be prioritized for future health infrastructure investment. The methods used here can help urban healthcare policymakers identify spatial inequalities in access to care and thus target the areas in need