Disaster Preparedness among Healthcare Professionals in Lebanon.

Background: Disaster disrupts the normal functioning of a community, causing significant damages and losses. In recent years, Lebanon faced multiple disasters, including one of the largest explosions ever recorded, the Beirut Blast, in August 2020. Limited studies in the literature have examined disaster medicine preparedness among healthcare professionals (HCPs).

Healthcare workers' experiences of workplace violence: a qualitative study in Lebanon.

Background: The COVID-19 pandemic has brought unprecedented challenges to healthcare workers (HCWs) around the world. The healthcare system in Lebanon was already under pressure due to economic instability and political unrest before the pandemic. This study aims to explore the impact of COVID-19 and the economic crisis on HCWs' experiences of workplace violence in Lebanon.

Comparative Analysis of Hypertensive Tubulopathy in Animal Models of Hypertension and Its Relevance to Human Pathology.

Assessment of hypertensive tubulopathy for more than fifty animal models of hypertension in experimental pathology employs criteria that do not correspond to lesional descriptors for tubular lesions in clinical pathology. We provide a critical appraisal of experimental hypertension with the same approach used to estimate hypertensive renal tubulopathy in humans. Four models with different pathogenesis of hypertension were analyzed-chronic angiotensin (Ang) II-infused and renin-overexpressing (TTRhRen) mice, spontaneously hypertensive (SHR), and Goldblatt two-kidney one-clip (2K1C) rats.

Comparative analysis of hypertensive nephrosclerosis in animal models of hypertension and its relevance to human pathology. Glomerulopathy.

Current research on hypertension utilizes more than fifty animal models that rely mainly on stable increases in systolic blood pressure. In experimental hypertension, grading or scoring of glomerulopathy in the majority of studies is based on a wide range of opinion-based histological changes that do not necessarily comply with lesional descriptors for glomerular injury that are well-established in clinical pathology. Here, we provide a critical appraisal of experimental hypertensive glomerulopathy with the same approach used to assess hypertensive glomerulopathy in humans.

TCR-induced FOXP3 expression by CD8 T cells impairs their anti-tumor activity.

Adoptive cell transfer therapy using CD8 T lymphocytes showed promising results eradicating metastatic malignancies. However, several regulatory mechanisms limit its efficacy. We studied the role of the expression of the transcription factor FOXP3 on CD8 T cell function and anti-tumor immunity.

Combined anticoagulant and antiplatelet therapy is associated with an improved outcome in hospitalised patients with COVID-19: a propensity matched cohort study.

Background: COVID-19 is a respiratory disease that results in a prothrombotic state manifesting as thrombotic, microthrombotic and thromboembolic events. As a result, several antithrombotic modalities have been implicated in the treatment of this disease. This study aimed to identify if therapeutic anticoagulation (TAC) or concurrent use of antiplatelet and anticoagulants was associated with an improved outcome in this patient population.

CCR8 marks highly suppressive Treg cells within tumours but is dispensable for their accumulation and suppressive function.

CD4 regulatory T (Treg) cells, dependent upon the transcription factor Foxp3, contribute to tumour immunosuppression but are also required for immune homeostasis. There is interest in developing therapies that selectively target the immunosuppressive function of Treg cells within tumours without disrupting their systemic anti-inflammatory function. High levels of expression of chemokine (C-C motif) receptor 8 (CCR8) discriminate Treg cells within tumours from those found in systemic lymphoid tissues.

BACH2 drives quiescence and maintenance of resting Treg cells to promote homeostasis and cancer immunosuppression.

Regulatory T (Treg) cell populations are composed of functionally quiescent resting Treg (rTreg) cells which differentiate into activated Treg (aTreg) cells upon antigen stimulation. How rTreg cells remain quiescent despite chronic exposure to cognate self- and foreign antigens is unclear. The transcription factor BACH2 is critical for early Treg lineage specification, but its function following lineage commitment is unresolved.

Prostaglandin E2 receptor EP1 (PGE2/EP1) deletion promotes glomerular podocyte and endothelial cell injury in hypertensive TTRhRen mice.

Prostaglandin E2 receptor EP1 (PGE/EP) promotes diabetic renal injury, and EP receptor deletion improves hyperfiltration, albuminuria, and fibrosis. The role of EP receptors in hypertensive kidney disease (HKD) remains controversial. We examined the contribution of EP receptors to HKD.

Hyperfiltration in ubiquitin C-terminal hydrolase L1-deleted mice.

Neuronal ubiquitin C-terminal hydrolase L1 (UCHL1) is a deubiquitinating enzyme that maintains intracellular ubiquitin pools and promotes axonal transport. deletion in mice leads to progressive axonal degeneration, affecting the dorsal root ganglion that harbors axons emanating to the kidney. Innervation is a crucial regulator of renal hemodynamics, though the contribution of neuronal UCHL1 to this is unclear.

Podocyte-derived microparticles promote proximal tubule fibrotic signaling via p38 MAPK and CD36.

Tubulointerstitial fibrosis is a hallmark of advanced diabetic kidney disease that is linked to a decline in renal function, however the pathogenic mechanisms are poorly understood. Microparticles (MPs) are 100-1000 nm vesicles shed from injured cells that are implicated in intercellular signalling. Our lab recently observed the formation of MPs from podocytes and their release into urine of animal models of type 1 and 2 diabetes and in humans with type 1 diabetes.

PGE EP receptor inhibits vasopressin-dependent water reabsorption and sodium transport in mouse collecting duct.

PGE2 regulates glomerular hemodynamics, renin secretion, and tubular transport. This study examined the contribution of PGE2 EP1 receptors to sodium and water homeostasis. Male EP1-/- mice were bred with hypertensive TTRhRen mice (Htn) to evaluate blood pressure and kidney function at 8 weeks of age in four groups: wildtype (WT), EP1-/-, Htn, HtnEP1-/-.

Effect of red dyes on blue light phototoxicity against VSC producing bacteria in an experimental oral biofilm.

Oral malodour is considered to be caused mainly by the production of volatile sulfide compounds (VSC) by anaerobic Gram-negative oral bacteria. Previous study showed that these bacteria were susceptible to blue light (wavelengths of 400-500 nm). In the present study, we tested the effect of blue light in the presence of red dyes on malodour production in an experimental oral biofilm.

Identification of novel regulators of developmental hematopoiesis using Endoglin regulatory elements as molecular probes.

Enhancers are the primary determinants of cell identity, and specific promoter/enhancer combinations of Endoglin (ENG) have been shown to target blood and endothelium in the embryo. Here, we generated a series of embryonic stem cell lines, each targeted with reporter constructs driven by specific promoter/enhancer combinations of ENG, to evaluate their discriminative potential and value as molecular probes of the corresponding transcriptome. The Eng promoter (P) in combination with the -8/+7/+9-kb enhancers, targeted cells in FLK1 mesoderm that were enriched for blast colony forming potential, whereas the P/-8-kb enhancer targeted TIE2+/c-KIT+/CD41- endothelial cells that were enriched for hematopoietic potential.

PDGF-AB and 5-Azacytidine induce conversion of somatic cells into tissue-regenerative multipotent stem cells.

Current approaches in tissue engineering are geared toward generating tissue-specific stem cells. Given the complexity and heterogeneity of tissues, this approach has its limitations. An alternate approach is to induce terminally differentiated cells to dedifferentiate into multipotent proliferative cells with the capacity to regenerate all components of a damaged tissue, a phenomenon used by salamanders to regenerate limbs.

PGE2 receptor EP3 inhibits water reabsorption and contributes to polyuria and kidney injury in a streptozotocin-induced mouse model of diabetes.

Aims/hypothesis: The first clinical manifestation of diabetes is polyuria. The prostaglandin E2 (PGE2) receptor EP3 antagonises arginine vasopressin (AVP)-mediated water reabsorption and its expression is increased in the diabetic kidney. The purpose of this work was to study the contribution of EP3 to diabetic polyuria and renal injury.

PGE2, Kidney Disease, and Cardiovascular Risk: Beyond Hypertension and Diabetes.

An important measure of cardiovascular health is obtained by evaluating the global cardiovascular risk, which comprises a number of factors, including hypertension and type 2 diabetes, the leading causes of illness and death in the world, as well as the metabolic syndrome. Altered immunity, inflammation, and oxidative stress underlie many of the changes associated with cardiovascular disease, diabetes, and the metabolic syndrome, and recent efforts have begun to elucidate the contribution of PGE2 in these events. This review summarizes the role of PGE2 in kidney disease outcomes that accelerate cardiovascular disease, highlights the role of cyclooxygenase-2/microsomal PGE synthase 1/PGE2 signaling in hypertension and diabetes, and outlines the contribution of PGE2 to other aspects of the metabolic syndrome, particularly abdominal adiposity, dyslipidemia, and atherogenesis.

Prostaglandin E2 increases proximal tubule fluid reabsorption, and modulates cultured proximal tubule cell responses via EP1 and EP4 receptors.

Renal prostaglandin (PG) E2 regulates salt and water transport, and affects disease processes via EP1-4 receptors, but its role in the proximal tubule (PT) is unknown. Our study investigates the effects of PGE2 on mouse PT fluid reabsorption, and its role in growth, sodium transporter expression, fibrosis, and oxidative stress in a mouse PT cell line (MCT). To determine which PGE2 EP receptors are expressed in MCT, qPCR for EP1-4 was performed on cells stimulated for 24 h with PGE2 or transforming growth factor beta (TGFβ), a known mediator of PT injury in kidney disease.

Endoglin potentiates nitric oxide synthesis to enhance definitive hematopoiesis.

During embryonic development, hematopoietic cells develop by a process of endothelial-to hematopoietic transition of a specialized population of endothelial cells. These hemogenic endothelium (HE) cells in turn develop from a primitive population of FLK1(+) mesodermal cells. Endoglin (ENG) is an accessory TGF-β receptor that is enriched on the surface of endothelial and hematopoietic stem cells and is also required for the normal development of hemogenic precursors.

Chronic kidney disease: targeting prostaglandin E2 receptors.

Chronic kidney disease is a leading cause of morbidity and mortality in the world. A better understanding of disease mechanisms has been gained in recent years, but the current management strategies are ineffective at preventing disease progression. A widespread focus of research is placed on elucidating the specific processes implicated to find more effective therapeutic options.

PTGER1 deletion attenuates renal injury in diabetic mouse models.

We hypothesized that the EP1 receptor promotes renal damage in diabetic nephropathy. We rendered EP1 (PTGER1, official symbol) knockout mice (EP1(-/-)) diabetic using the streptozotocin and OVE26 models. Albuminuria, mesangial matrix expansion, and glomerular hypertrophy were each blunted in EP1(-/-) streptozotocin and OVE26 cohorts compared with wild-type counterparts.

NADPH oxidases, reactive oxygen species, and the kidney: friend and foe.

Reactive oxygen species (ROS) play an important role in normal cellular physiology. They regulate different biologic processes such as cell defense, hormone synthesis and signaling, activation of G protein-coupled receptors, and ion channels and kinases/phosphatases. ROS are also important regulators of transcription factors and gene expression.

Cyclooxygenase-2 mediates induction of the renal stanniocalcin-1 gene by arginine vasopressin.

In rats and mice, the renal stanniocalcin-1 (STC-1) gene is expressed in most nephron segments, but is differentially induced in response to dehydration. In cortical segments STC-1 mRNA levels are upregulated by the hypertonicity of dehydration, while hypovolemia causes gene induction in the inner medulla (papilla). In both cases induction is mediated by arginine vasopressin (AVP) acting via the V2 receptor (V2R).

Celecoxib modifies glomerular basement membrane, mesangium and podocytes in OVE26 mice, but ibuprofen is more detrimental.

The role of COXs/PGs (cyclo-oxygenases/prostaglandins) in diabetic kidneys remains unclear. NSAIDs (non-steroidal anti-inflammatory drugs) that inhibit COXs/PGs are known for their renal toxicity, and COX-2 inhibitors worsen cardiovascular outcomes in susceptible individuals. Given the renal controversies concerning COX-2 inhibitors, we compared the effect of chronic NSAIDs (non-selective, ibuprofen; COX-2-selective, celecoxib) on diabetic kidneys in OVE26 mice from 8 weeks of age.