Impact of Hypoxia on Astrocyte Induced Pathogenesis

Astrocytes are the most abundant cells of the central nervous system. These cells are of diverse types based on their function and structure. Astrocyte activation is linked mainly with microbial infections, but long-term activation can lead to neurological impairment. Astrocytes play a significant role in neuro-inflammation by activating pro-inflammatory pathways. Activation of interleukins and cytokines causes neuroinflammation resulting in many neurodegenerative disorders such as stroke, growth of tumours, and Alzheimer’s. Inflammation of the brain hinders neural circulation and compromises blood flow by affecting the blood–brain barrier. So the oxygen concentration is lowered, causing brain hypoxia. Hypoxia leads to the activation of nuclear factor kappa B (NFkB) and hypoxia-inducible factors (HIF), which aggravates the inflammatory state of the brain. Hypoxia evoked changes in the blood–brain barrier, further complicating astrocyte-induced pathogenesis

The Prospects for the Therapeutic Implications of Genetically Engineered Probiotics

The interest in the therapeutic use of probiotic microorganisms has been increased during the last decade although the doubts have ascended about the probiotics mainly because their beneficial effects are not fully understood, and, in many cases, their usefulness has not been validated in clinical trials. Consequently, the notion got a considerable interest in those strains having proven probiotic potential to be engineered for improvement in their beneficial features. The process of genetic engineering can also be used for probiotic strains for the reversion of antimicrobial resistance and other modifications for their safer and effective human applications. The lactic acid bacilli are predominantly opposite as they already have gained attention owing to their health-promoting benefits and their safety for human consumption; therefore, their use, especially as a delivery agent of vaccines and drugs, is gaining attention. The tailoring of probiotic strains will not only improve the data regarding the probiotic potential of these strains but also clinch the doubts concerning these probiotics. This article focuses on the approaches of bioengineered probiotics and discusses the potential prospects for their therapeutic applications including immunomodulation, cognitive health, and anticancer therapeutics

Estimating the frequency of inpatient adverse events using a two-step retrospective chart review: A study protocol

Introduction: Adverse events are a major cause of patient harm in the hospitalised setting. Low-income and middle-income countries account for a disproportionate share of the global burden of adverse events. However, patient safety research is still centred around high-income countries and high-resource health systems. The methods and data produced from these efforts are ill-suited to low-income and middle-income systems due to the social and technical differences between these settings. We aim to use our pilot-tested, locally developed methodology to estimate the frequency and characteristics of adverse events in hospitalised patients in a lower-middle-income country to inform patient safety policies and initiatives.Methods and analysis: This multi-centre study will employ a two-step chart review methodology to identify adverse events in a representative sample of patients admitted at five hospitals between 1 January 2019 and 31 December 2019. The first step will include assessing patient files against a list of triggers to detect adverse events and the second step will involve an in-depth review of the events to capture pertinent characteristics. The triggers have been adapted from validated tools used in other studies. The reviewing team will be trained on the use of research tools and operational definitions to ensure that data are collected uniformly. The main outcome of interest is the rate at which adverse events occur in hospitalised patients. Further analysis will look to identify and quantify associations between the main outcome of interest and a variety of variables such as patient age and gender using tests of independence and regression techniques.Ethics and dissemination: This study protocol has been approved by the Ethics Review Committee at Aga Khan University (Reference number: 2023-6324-24566). The findings of this study will be published in a peer-reviewed journal and disseminated to the public through national and international conferences, workshops, websites and social media

Structural plasticity of omicron BA.5 and BA.2.75 for enhanced ACE-dependent entry into cells

The current study investigated the binding variations among the wilt type, Omicron sub-variants BA.2.75 and BA.5, using protein-protein docking, protein structural graphs (P SG), and molecular simulation methods. HADDOCK predicted docking scores and dissociation constant (KD) revealed tighter binding of these sub-variants in contrast to the WT. Further investigation revealed variations in the hub residues, protein sub-networks, and GlobalMetapath in these variants as compared to the WT. A very unusual dynamic for BA.2.75 and BA.5 was observed, and secondary structure transition can also be witnessed in the loops (44-505). The results show that the flexibility of these three loops is increased by the mutations as an allosteric effect and thus enhances the chances of bonding with the nearby residues to connect and form a stable connection. Furthermore, the additional hydrogen bonding contacts steer the robust binding of these variants in contrast to the wild type. The total binding free energy for the wild type was calculated to be -61.38 kcal/mol, while for BA.2.75 and BA.5 variants the T BE was calculated to be -70.42 kcal/mol and 69.78 kcal/mol, respectively. We observed that the binding of BA.2.75 is steered by the electrostatic interactions while the BA.5 additional contacts are due to the vdW (Van der Waal) energy. From these findings, it can be observed the Spike (S) protein is undergoing structural adjustments to bind efficiently to the hACE2 (human angiotensin-converting enzyme 2) receptor and, in turn, increase entry to the host cells. The current study will aid the development of structure-based drugs against these variants

Incorporating patient safety and quality course into the nursing curriculum: An assessment of student gains

Background: Training nursing students on quality and patient safety (PS) is crucial to ensuring safe healthcare practices given the key role nurses play on the healthcare team. The aim of this study was to evaluate the impact of quality and PS course on the knowledge, and system thinking of students at different stages of the undergraduate nursing course.Methods: A 4.5-day quality improvement and PS course was conducted at the Aga Khan University School of Nursing and Midwifery for 146 second- and 139 fourth-year students. Students\u27 knowledge, self-assessment of knowledge and skills, and system thinking were assessed using pretest and posttest.Results: Of the total of 20 points, the course significantly improved students\u27 knowledge by a mean of 4.91 points for second-year students (95% confidence interval [CI], 4.32-5.51) and 3.46 points for fourth-year students (95% CI, 2.90-4.02) between pretest and posttest. For systems thinking, the Systems Thinking Scale scores increased by 0.41 points (95% CI, 0.29-0.52) for second-year students and 0.33 points (95% CI, 0.22-0.44) for fourth-year students out of the total of 5 points. The self-assessment scores significantly increased on postcourse assessment for second (P \u3c 0.05) and fourth-year students (P \u3c 0.001). Positive experience reported by students in the narrative reflections complemented these results.Conclusions: There was a significant increase in nursing students\u27 knowledge, self-efficacy, and system thinking after participating in this short PS course. Replication at a national level may improve safety knowledge and skills among nursing students with subsequent gains in the safety of healthcare delivery in Pakistan