Neuroinflammation and Cerebrovascular Disease in Old Age: A Translational Medicine Perspective

The incidence of cerebrovascular disease is highest in the elderly population. However, the pathophysiological mechanisms of brain response to cerebral ischemia in old age are currently poorly understood. Ischemic changes in the commonly used young animal stroke models do not reflect the molecular changes associated with the aged brain. Neuroinflammation and oxidative stress are important pathogenic processes occurring during the acute phase of cerebral ischemia. Free radical generation is also implicated in the aging process, and the combination of these effects in elderly stroke patients could explain the higher risk of morbidity and mortality. A better understanding of stroke pathophysiology in the elderly patient would assist in the development of new therapeutic strategies for this vulnerable age group. With the increasing use of reperfusion therapies, inflammatory pathways and oxidative stress remain attractive therapeutic targets for the development of adjuvant neuroprotective agents. This paper will discuss these molecular aspects of acute stroke and senescence from a bench-to-bedside research perspective

Novel deep learning approach to model and predict the spread of COVID-19

SARS-CoV2, which causes coronavirus disease (COVID-19) is continuing to spread globally, producing new variants and has become a pandemic. People have lost their lives not only due to the virus but also because of the lack of counter measures in place. Given the increasing caseload and uncertainty of spread, there is an urgent need to develop robust artificial intelligence techniques to predict the spread of COVID-19. In this paper, we propose a deep learning technique, called Deep Sequential Prediction Model (DSPM) and machine learning based Non-parametric Regression Model (NRM) to predict the spread of COVID-19. Our proposed models are trained and tested on publicly available novel coronavirus dataset. The proposed models are evaluated by using Mean Absolute Error and compared with the existing methods for the prediction of the spread of COVID-19. Our experimental results demonstrate the superior prediction performance of the proposed models. The proposed DSPM and NRM achieve MAEs of 388.43 (error rate 1.6%) and 142.23 (0.6%), respectively compared to 6508.22 (27%) achieved by baseline SVM, 891.13 (9.2%) by Time-Series Model (TSM), 615.25 (7.4%) by LSTM-based Data-Driven Estimation Method (DDEM) and 929.72 (8.1%) by Maximum-Hasting Estimation Method (MHEM)

COMPARISON OF IRON STORES IN HEALTHY INDIVIDUALS AND PATIENTS WITH ISCHAEMIC HEART DISEASE

ABSTRACT Excess body iron has been linked to atherosclerosis owing to its pro-oxidative properties. However, inconsistent results have emerged from the epidemiological studies linking iron status and the risk of cardiovascular diseases (CVD). Objective of the present study is to compare iron stores of healthy individuals and patients with ischaemic heart disease (IHD). A total of 137 subjects were included in the study, 90 patients of IHD and 47 healthy subjects with no history of IHD as controls. We compared body iron stores of patients and controls. Serum ferritin, serum transferrin receptor (sTfR) and sTfR/ferritin ratio were used as measures of body iron stores. Our results revealed that mean serum ferritin concentration of cases was significantly higher than controls. Moreover, mean sTfR and sTfR/ferritin ratio of controls was significantly higher than the patients. We conclude from our results that IHD patients have higher iron stores than healthy subjects suggesting a possible association between high iron stores and the risk of IHD

A conceptual framework for determinants of customer satisfaction of fixed-line telecom services in Pakistan

With the progression of communication technologies, there has been a decline in people's utilization of fixed-line telephones. It is essential to ascertain the fundamental causes underlying this phenomenon. There are numerous assumptions that service providers tend to favor their interests. Gaining an understanding of the factors that contribute to client satisfaction may require a significant investment of effort. Consequently, this study aims to ascertain the determinants that impact consumers' happiness with their fixed-line telecommunications service. In order to achieve the objectives of the research, a theoretical framework is presented whereby consumer satisfaction is considered the dependent variable. At the same time, responsiveness, perceived value, perceived service quality, and staff attitude are regarded as independent variables. The primary objective of this study is to ascertain the key factors that significantly influence Customer Satisfaction with Fixed-Line Telecom Services in Pakistan

Fabrication and Biological Assessment of Antidiabetic α-Mangostin Loaded Nanosponges: In Vitro, In Vivo, and In Silico Studies

From MDPI via Jisc Publications RouterHistory: accepted 2021-10-29, pub-electronic 2021-11-01Publication status: PublishedFunder: King Saud University; Grant(s): RSP-2021/406Type 2 diabetes mellitus has been a major health issue with increasing morbidity and mortality due to macrovascular and microvascular complications. The urgent need for improved methods to control hyperglycemic complications reiterates the development of innovative preventive and therapeutic treatment strategies. In this perspective, xanthone compounds in the pericarp of the mangosteen fruit, especially α-mangostin (MGN), have been recognized to restore damaged pancreatic β-cells for optimal insulin release. Therefore, taking advantage of the robust use of nanotechnology for targeted drug delivery, we herein report the preparation of MGN loaded nanosponges for anti-diabetic therapeutic applications. The nanosponges were prepared by quasi-emulsion solvent evaporation method. Physico-chemical characterization of formulated nanosponges with satisfactory outcomes was performed with Fourier transform infra-red (FTIR) spectroscopy, differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Zeta potential, hydrodynamic diameter, entrapment efficiency, drug release properties, and stability studies at stress conditions were also tested. Molecular docking analysis revealed significant interactions of α-glucosidase and MGN in a protein-ligand complex. The maximum inhibition by nanosponges against α-glucosidase was observed to be 0.9352 ± 0.0856 µM, 3.11-fold higher than acarbose. In vivo studies were conducted on diabetic rats and plasma glucose levels were estimated by HPLC. Collectively, our findings suggest that MGN-loaded nanosponges may be beneficial in the treatment of diabetes since they prolong the antidiabetic response in plasma and improve patient compliance by slowly releasing MGN and requiring less frequent doses, respectively

Multi-Level Interactions between the Nuclear Receptor TRα1 and the WNT Effectors β-Catenin/Tcf4 in the Intestinal Epithelium

Intestinal homeostasis results from complex cross-regulation of signaling pathways; their alteration induces intestinal tumorigenesis. Previously, we found that the thyroid hormone nuclear receptor TRα1 activates and synergizes with the WNT pathway, inducing crypt cell proliferation and promoting tumorigenesis. Here, we investigated the mechanisms and implications of the cross-regulation between these two pathways in gut tumorigenesis in vivo and in vitro. We analyzed TRα1 and WNT target gene expression in healthy mucosae and tumors from mice overexpressing TRα1 in the intestinal epithelium in a WNT-activated genetic background (vil-TRα1/Apc mice). Interestingly, increased levels of β-catenin/Tcf4 complex in tumors from vil-TRα1/Apc mice blocked TRα1 transcriptional activity. This observation was confirmed in Caco2 cells, in which TRα1 functionality on a luciferase reporter-assay was reduced by the overexpression of β-catenin/Tcf4. Moreover, TRα1 physically interacted with β-catenin/Tcf4 in the nuclei of these cells. Using molecular approaches, we demonstrated that the binding of TRα1 to its DNA target sequences within the tumors was impaired, while it was newly recruited to WNT target genes. In conclusion, our observations strongly suggest that increased β-catenin/Tcf4 levels i) correlated with reduced TRα1 transcriptional activity on its target genes and, ii) were likely responsible for the shift of TRα1 binding on WNT targets. Together, these data suggest a novel mechanism for the tumor-promoting activity of the TRα1 nuclear receptor

2017 update of the WSES guidelines for emergency repair of complicated abdominal wall hernias

Emergency repair of complicated abdominal wall hernias may be associated with worsen outcome and a significant rate of postoperative complications. There is no consensus on management of complicated abdominal hernias. The main matter of debate is about the use of mesh in case of intestinal resection and the type of mesh to be used. Wound infection is the most common complication encountered and represents an immense burden especially in the presence of a mesh. The recurrence rate is an important topic that influences the final outcome. A World Society of Emergency Surgery (WSES) Consensus Conference was held in Bergamo in July 2013 with the aim to define recommendations for emergency repair of abdominal wall hernias in adults. This document represents the executive summary of the consensus conference approved by a WSES expert panel. In 2016, the guidelines have been revised and updated according to the most recent available literature.Peer reviewe

WSES guidelines for emergency repair of complicated abdominal wall hernias

Peer reviewe