Rapid diagnosis of fungal keratitis in patients with corneal ulcer using Calcofluor White stain

Background: The prevalence of fungal keratitis has risen in recent years significantly. To avoid additional complications, diagnosing and treating fungal keratitis is crucial. This study aims to measure the efficacy of a calcofluor white (CFW) stain for the quick diagnosis of fungal keratitis and to contrast the positive rates, sensitivity, and specificity with a 10% potassium hydroxide (KOH)-based smear and culture technique. Methods:From individuals with clinically suspected corneal ulcers, 30 corneal scrapings had been collected. Data on demographics had been analyzed. Results: Of the 30 patients, 40% were women and 60% were men. There was a 1.5:1 man-to-woman ratio. The age of patients ranged from 29 to 71 years (mean 46.67 ± 10.90). The age presentation of those between the ages of 41 and 50 years was the most frequent (36.7%). The majority of cases were farmers (43.3%). Trauma was the most common predisposing factor (46.6%). Twenty-four (80%) cases were culture positive. Eleven (36.7%) were fungal, 13 (43.3%) were bacterial and 6 (20%) showed no growth. Fusarium was the most common fungal isolate (36.4%), followed by Aspergillus (27.3%). While Staphylococcus aureus was the most common bacterial isolate (46.2%), followed by Pseudomonas (38.4%). The sensitivity of KOH wet mount and CFW stain was 72.7% and 90.9%, respectively. The specificity of both KOH wet mount and CFW stain was 100%. Conclusion:The early diagnosis of fungal keratitis can be made rapidly by direct microscopic examination of fungal elements using CFW stain. When diagnosing fungal keratitis, CFW has higher sensitivity to KOH

On a systematic approach for cracked rotating shaft study: breathing mechanism, dynamics and instability

The EDF LMS model for the mechanics of cracked rotating shaftWe present a systematic approach to deal with the modeling and analysis of the cracked rotating shafts behaviour. We begin by revisiting the problem of modelling the breathing mechanism of the crack. Here we consider an original approach based on the form we give to the energy of the system and then identify the mechanism parameters using 3D computations with unilateral contact conditions on the crack lips. A dimensionless flexibility is identified which makes the application of the approach to similar problems straightforward. The additional flexibility due to the crack is then introduced in a simple and comprehensive dynamical system (2 DOF) to characterize the crack effects on the dynamical response of a rotating shaft. Many results could help in early crack detection

On cracked rotating shaft mechanics: a systematic approach

We present a systematic approach to deal with the modeling and analysis of the cracked rotating shafts behaviour. We begin by revisiting the problem of modelling the breathing mechanism ofthe crack. Here we consider an original approach based on the form we give to the energy of the system and then identify the mechanism parameters using 3D computations with unilateral contact conditions on the crack lips. A dimensionless flexibility is identified which makes the application of the approach to similar problems straightforward. The additional flexibility due to the crack is then introduced in a simple and comprehensive dynamical system (2 DOF) to characterize the crack effects on the dynamical response of a rotating shaft. Many results could help in early crack detection

Cellular players that shape evolving pathology and neurodegeneration following traumatic brain injury

Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide, and has emerged as a critical risk factor for multiple neurodegenerative diseases, particularly Alzheimer’s disease (AD). How the inflammatory cascade resulting from mechanical stress, axonal shearing and the loss of neurons and glia following initial impact in TBI, contributes to the development of AD-like disease is unclear. Neuroinflammation, characterized by blood-brain barrier (BBB) dysfunction and activation of brain-resident microglia and astrocytes, resulting in secretion of inflammatory mediators and subsequent recruitment of peripheral immune cells has been the focus of extensive research in attempts to identify drug-targets towards improving functional outcomes post TBI. While knowledge of intricate cellular interactions that shape lesion pathophysiology is incomplete, a major limitation in the field is the lack of understanding of how distinct cell types differentially alter TBI pathology. The aim of this review is to highlight functional differences between populations of bone marrow derived, infiltrating monocytes/macrophages and brain-resident microglia based on differential expression of the chemokine receptors CCR2 and CX3CR1. This review will focus on how unique subsets of mononuclear phagocytes shape TBI pathophysiology, neurotoxicity and BBB function, in a disease-stage dependent manner. Additionally, this review summarizes the role of multiple microglia and macrophage receptors, namely CCR2, CX3CR1 and Triggering Receptor Expressed on Myeloid Cells-2 (TREM2) in pathological neuroinflammation and neurodegeneration vs. recovery following TBI. TREM2 has been implicated in mediating AD-related pathology, and variants in TREM2 are particularly important due to their correlation with exacerbated neurodegeneration. Finally, this review highlights behavioral outcomes associated with microglial vs. macrophage variances, the need for novel treatment strategies that target unique subpopulations of peripheral macrophages, and the importance of development of therapeutics to modulate inflammatory functions of brain-resident microglia at specific stages of TBI

A comprehensive analysis of genetic risk for metabolic syndrome in the Egyptian population via allele frequency investigation and Missense3D predictions

Abstract Diabetes mellitus (DM) represents a major health problem in Egypt and worldwide, with increasing numbers of patients with prediabetes every year. Numerous factors, such as obesity, hyperlipidemia, and hypertension, which have recently become serious concerns, affect the complex pathophysiology of diabetes. These metabolic syndrome diseases are highly linked to genetic variability that drives certain populations, such as Egypt, to be more susceptible to developing DM. Here we conduct a comprehensive analysis to pinpoint the similarities and uniqueness among the Egyptian genome reference and the 1000-genome subpopulations (Europeans, Ad-Mixed Americans, South Asians, East Asians, and Africans), aiming at defining the potential genetic risk of metabolic syndromes. Selected approaches incorporated the analysis of the allele frequency of the different populations’ variations, supported by genotypes’ principal component analysis. Results show that the Egyptian’s reference metabolic genes were clustered together with the Europeans’, Ad-Mixed Americans’, and South-Asians’. Additionally, 8563 variants were uniquely identified in the Egyptian cohort, from those, two were predicted to cause structural damage, namely, CDKAL1: 6_21065070 (A > T) and PPARG: 3_12351660 (C > T) utilizing the Missense3D database. The former is a protein coding gene associated with Type 2 DM while the latter is a key regulator of adipocyte differentiation and glucose homeostasis. Both variants were detected heterozygous in two different Egyptian individuals from overall 110 sample. This analysis sheds light on the unique genetic traits of the Egyptian population that play a role in the DM high prevalence in Egypt. The proposed analysis pipeline -available through GitHub- could be used to conduct similar analysis for other diseases across populations

From genes to drugs: CYP2C19 and pharmacogenetics in clinical practice

The CYP2C19 gene is frequently included in different pharmacogenomic panels tested in clinical practice, due to its involvement in the metabolism of a myriad of frequently prescribed medications. Accordingly, CYP2C19 genotyping can promote precise therapeutic decisions and avoid the occurrence of significant drug-drug-gene interactions in the clinical setting. A comprehensive examination of the role of the CYP2C19 gene in real-world medical settings is presented in this review. This review summarizes the most recent information on how genetic variants in CYP2C19 affect drug metabolism and therapeutic outcomes. It goes into the wide range of CYP2C19 phenotypes, with different degrees of metabolizing activity, and their implications for customized medication response through a review of the literature. The review also analyzes the clinical significance of CYP2C19 in several medical specialties, including cardiology, psychiatry, and gastro-enterology clinics, and illuminates how it affects pharmacological efficacy, safety, and adverse effects. Finally, CYP2C19-supported clinical decision-making is outlined, highlighting the possibility of improving therapeutic outcomes and achieving more affordable treatment options, a step towards optimizing healthcare provision through precision medicine

Current Status of Baricitinib as a Repurposed Therapy for COVID-19

The emergence of the COVID-19 pandemic has mandated the instant (re)search for potential drug candidates. In response to the unprecedented situation, it was recognized early that repurposing of available drugs in the market could timely save lives, by skipping the lengthy phases of preclinical and initial safety studies. BenevolentAI’s large knowledge graph repository of structured medical information suggested baricitinib, a Janus-associated kinase inhibitor, as a potential repurposed medicine with a dual mechanism; hindering SARS-CoV2 entry and combatting the cytokine storm; the leading cause of mortality in COVID-19. However, the recently-published Adaptive COVID-19 Treatment Trial-2 (ACTT-2) positioned baricitinib only in combination with remdesivir for treatment of a specific category of COVID-19 patients, whereas the drug is not recommended to be used alone except in clinical trials. The increased pace of data output in all life sciences fields has changed our understanding of data processing and manipulation. For the purpose of drug design, development, or repurposing, the integration of different disciplines of life sciences is highly recommended to achieve the ultimate benefit of using new technologies to mine BIG data, however, the final say remains to be concluded after the drug is used in clinical practice. This review demonstrates different bioinformatics, chemical, pharmacological, and clinical aspects of baricitinib to highlight the repurposing journey of the drug and evaluates its placement in the current guidelines for COVID-19 treatment

Effect of Counteracting Lifestyle Barriers through Health Education in Egyptian Type 2 Diabetic Patients

BACKGROUND: Egypt is among the world top 10 countries in diabetes prevalence. It is the first country among the MENA region. Healthy lifestyle education and support help people with diabetes to improve health outcomes. Many physical and psychological barriers can hinder patients from following a healthy lifestyle. AIM: This study aimed to examine the effect of lifestyle modification educational sessions in helping Egyptian patients to overcome main barriers of diabetes self-management through improving nutritional behaviours, physical activity, medication compliance, and blood glucose monitoring. METHODS: A cohort study included 205 patients with type 2 diabetes. Baseline assessment of patients' lifestyle behaviours and barriers using personal diabetes questionnaire of Louisville University, with both anthropometric and blood glucose assessment. Interventional lifestyle health education was provided weekly through multiple integrated techniques, followed by a post-intervention assessment to evaluate the effect of the health education sessions. Statistical analysis was done to identify any statistically significant difference before and after the health education intervention. RESULTS: There was a significant improvement of the post-education mean scores of the studied behaviours when compared with the pre-education scores of the participants’ behaviours (p < 0.001). There was also a significant reduction in the barriers facing patients to diabetes self-management including nutritional barriers (P < 0.001), medication compliance barriers (P < 0.001) with a percent change (43%), physical activity barriers (p < 0.001), and blood glucose monitoring (p < 0.001) with a percent change (44%).There was a statistically significant positive correlation between improvement of medication compliance (P = 0.027), blood glucose monitoring(P = 0.045), and glycated haemoglobin of the study participants CONCLUSION: lifestyle modification education of type 2 diabetic patients can overcome the main barriers of following a healthy lifestyle and improve their anthropometric measures and blood glucose level

Traumatic brain injury in hTau model mice: Enhanced acute macrophage response and altered long-term recovery

TBI induces widespread neuroinflammation and accumulation of microtubule associated protein tau (MAPT) - two key pathological features of tauopathies. This study sought to characterize the microglial/macrophage response to TBI in genomic-based MAPT transgenic mice in a Mapt knockout background (called hTau). Two-month-old hTau and age-matched control male and female mice received a single lateral fluid percussion TBI or sham injury. Separate groups of mice were aged to an acute (3 days post-injury [DPI]) or chronic (135 DPI) post-injury time point. As judged by tissue immunostaining for macrophage markers, microglial/macrophage response to TBI was enhanced at 3 DPI in hTau mice compared to control TBI and sham mice. However, MAPT phosphorylation increased in hTau mice regardless of injury group. Flow cytometric analysis revealed distinct populations of microglia and macrophages within all groups at 135 DPI. Unexpectedly, microglial reactivity was significantly reduced in hTau TBI mice compared to all other groups. Instead, hTau TBI mice showed a persistent macrophage response. In addition, TBI enhanced MAPT pathology in the temporal cortex and hippocampus of hTau TBI mice compared to controls 135 DPI. A battery of behavioral test revealed that TBI in hTau mice resulted in compromised use of spatial search strategies to complete a water maze task despite lack of motor or visual deficits. Collectively, these data indicate that the presence of wild-type human tau alters the microglial/macrophage response to a single TBI, induces delayed, region-specific MAPT pathology, and alters cognitive recovery; however, the causal relationship between these events remains unclear. These results highlight the potential significance of communication between MAPT and microglia/macrophages following TBI and emphasize the role of neuroinflammation in post-injury recovery

Oxytocin promotes functional coupling between paraventricular nucleus and both sympathetic and parasympathetic cardioregulatory nuclei

The neuropeptide oxytocin (OXT) facilitates prosocial behavior and selective sociality. In the context of stress, OXT also can down-regulate hypothalamic–pituitary–adrenal (HPA) axis activity, leading to consideration of OXT as a potential treatment for many socioaffective disorders. However, the mechanisms through which administration of exogenous OXT modulates social behavior in stressful environmental contexts are not fully understood. Here, we investigate the hypothesis that autonomic pathways are components of the mechanisms through which OXT aids the recruitment of social resources in stressful contexts that may elicit mobilized behavioral responses. Female prairie voles (Microtus ochrogaster) underwent a stressor (walking in shallow water) following pretreatment with intraperitoneal OXT (0.25 mg/kg) or OXT antagonist (OXT-A, 20 mg/kg), and were allowed to recover with or without their sibling cagemate. Administration of OXT resulted in elevated OXT concentrations in plasma, but did not dampen the HPA axis response to a stressor. However, OXT, but not OXT-A, pretreatment prevented the functional coupling, usually seen in the absence of OXT, between paraventricular nucleus (PVN) activity as measured by c-Fos immunoreactivity and HPA output (i.e. corticosterone release). Furthermore, OXT pretreatment resulted in functional coupling between PVN activity and brain regions regulating both sympathetic (i.e. rostral ventrolateral medulla) and parasympathetic (i.e. dorsal vagal complex and nucleus ambiguous) branches of the autonomic nervous system. These findings suggest that OXT increases central neural control of autonomic activity, rather than strictly dampening HPA axis activity, and provides a potential mechanism through which OXT may facilitate adaptive and context-dependent behavioral and physiological responses to stressors