Population under Stress: The Coping Mechanisms of Lebanese Adults in Times of Intermingling Crises and Their Relationship with Stress.

The Lebanese population has faced numerous stressors due to multiple crises in the past four years. This study aims to measure the perceived stress of the Lebanese population, identify the coping mechanisms being used, and determine whether they are associated with their stress levels. A cross-sectional study of 205 individuals randomly selected from Beirut was conducted. Frequency distribution, descriptive analysis, and multivariable cumulative logit models were used to determine the associations between coping mechanisms and perceived stress. Our results indicated that 95.4% of our population had moderate to high perceived stress levels. Problem-focused coping was the most adopted mechanism and was associated with a statistically significant lower stress level, whereas avoidant coping was associated with a statistically significant higher stress level. Our study can pave the way for raising awareness on the importance of managing stress with adaptive coping mechanisms.

Social and racial inequalities in diabetes and cancer in the United States.

Background: Cancer and diabetes are among the leading causes of morbidity and mortality worldwide. Several studies have reported diabetes as a risk factor for developing cancer, a relationship that may be explained by associated factors shared with both diseases such as age, sex, body weight, smoking, and alcohol consumption. Social factors referred to as social determinants of health (SDOH) were shown to be associated with the risk of developing cancer and diabetes. Despite that diabetes and social factors were identified as significant determinants of cancer, no studies examined their combined effect on the risk of developing cancer. In this study, we aim at filling this gap in the literature by triangulating the association between diabetes, indices of SDOH, and the risk of developing cancer. Methods: We have conducted a quantitative study using data from the Behavioral Risk Factor Surveillance System (BRFSS), whereby information was collected nationally from residents in the United States (US) with respect to their health-related risk behaviors, chronic health conditions, and the use of preventive services. Data analysis using weighted regressions was conducted on 389,158 study participants. Results: Our findings indicated that diabetes is a risk factor that increases the likelihood of cancer by 13% (OR 1.13; 95%CI: 1.05-1.21). People of White race had higher odds for cancer compared to African Americans (OR 0.44; 95%CI: 0.39-0.49), Asians (OR 0.27; 95%CI: 0.20-0.38), and other races (OR 0.56; 95%CI: 0.46-0.69). The indices of SDOH that were positively associated with having cancer encompassed unemployment (OR 1.78; 95%CI: 1.59-1.99), retirement (OR 1.54; 95%CI: 1.43-1.67), higher income levels with ORs ranging between 1.16-1.38, college education (OR 1.10; 95%CI: 1.02-1.18), college graduates (OR 1.31; 95%CI: 1.21-1.40), and healthcare coverage (OR 1.44; 95%CI: 1.22-1.71). On the other hand, the indices of SDOH that were protective against having cancer were comprised of renting a home (OR 0.86; 95%CI: 0.79-0.93) and never married (OR 0.73; 95%CI: 0.65-0.81). Conclusion: This study offers a novel social dimension for the association between diabetes and cancer that could guide setting strategies for addressing social inequities in disease prevention and access to healthcare.

General Versus Locoregional Anesthesia in TEVAR: An NSQIP Analysis.

BACKGROUND: Thoracic Endovascular Aortic Repair (TEVAR) is a minimally invasive surgery for repairing thoracic aneurysms and dissections. This study aims to compare postoperative outcomes of TEVAR performed under general versus locoregional anesthesia. METHODS: Utilizing the 2008-2019 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database, patients older than the age of 18 years who received TEVAR, were identified using the following current procedural terminology codes: 33,880, 33,881, 33,883, 33,884, or 33,886. Patients who underwent concomitant procedures, those with both thoracoabdominal and abdominal aortic pathologies, and trauma cases were excluded. Standard descriptive statistics, in addition to χ2, Fisher's exact test, and Mann-Whitney U-tests were used to compare patient baseline characteristics and postoperative outcomes between general and locoregional anesthesia groups as appropriate. Univariable and multivariable logistic regression analyses were performed to assess independent predictors of hospital length of stay (LOS) greater than 7 days. RESULTS: Of the 1,028 patients included in the study, 86.5% received general anesthesia, and 13.5% received locoregional anesthesia, such as local anesthesia with monitored anesthesia care or regional anesthesia. No significant differences were found between patients receiving locoregional versus general anesthesia in mortality (3.6% vs. 7.9%, respectively, P = 0.071) and morbidity (18.7% and 24.8%, respectively, P = 0.121) within 30 days post-TEVAR, including any wound, pulmonary, thromboembolic, renal, septic, and cardiac arrest complications. Patients who received general anesthesia had significantly higher median LOS compared to those who received locoregional anesthesia [5 days (interquartile range (IQR): 3-10) versus 4 days (IQR: 2-7), P = 0.002], with 34.3% of the general anesthesia group having an LOS greater than 7 days compared to 21.6% of locoregional anesthesia group, P = 0.003. On multivariable logistic regression analysis, general anesthesia was found to be an independent predictor of prolonged LOS greater than 7 days (odds ratio (OR): 1.72, 95% confidence interval (CI): 1.05-2.81, P = 0.031). CONCLUSIONS: Locoregional anesthesia results in significantly lower postoperative hospital LOS with similar postoperative mortality and morbidity compared to general anesthesia in patients undergoing TEVAR.

Shared parameter and copula models for analysis of semicontinuous longitudinal data with nonrandom dropout and informative censoring.

Analysis of longitudinal semicontinuous data characterized by subjects' attrition triggered by nonrandom dropout is complex and requires accounting for the within-subject correlation, and modeling of the dropout process. While methods that address the within-subject correlation and missing data are available, approaches that incorporate the nonrandom dropout, also referred to informative right censoring, in the modeling step are scarce due to the computational intensity and possible intractable integration needed for its implementation. Appreciating the complexity of this problem and the need for a new methodology that is feasible for implementation, we propose to extend a framework of likelihood-based marginalized two-part models to account for informative right censoring. The censoring process is modeled using two approaches: (1) Poisson censoring for the count of visits before dropout and (2) survival time to dropout. Novel consideration was given to the proposed joint modeling approaches for the semicontinuous and censoring components of the likelihood function which included (1) shared parameter, and (2) Clayton copula. The cross-part and within-part correlations were accounted for through a complex random effect structure that models correlated random intercepts and slopes. Feasibility of implementation, and accuracy of these approaches were investigated using extensive simulation studies and clinical application.

Modulation of Neuro-Inflammatory Signals in Microglia by Plasma Prekallikrein and Neuronal Cell Debris.

Microglia, the resident phagocytes of the central nervous system and one of the key modulators of the innate immune system, have been shown to play a major role in brain insults. Upon activation in response to neuroinflammation, microglia promote the release of inflammatory mediators as well as promote phagocytosis. Plasma prekallikrein (PKall) has been recently implicated as a mediator of neuroinflammation; nevertheless, its role in mediating microglial activation has not been investigated yet. In the current study, we evaluate the mechanisms through which PKall contributes to microglial activation and release of inflammatory cytokines assessing PKall-related receptors and their dynamics. Murine N9-microglial cells were exposed to PKall (2.5 ng/ml), lipopolysaccharide (100 ng/ml), bradykinin (BK, 0.1 µM), and neuronal cell debris (16.5 µg protein/ml). Gene expression of bradykinin 2 receptor (B2KR), protease-activated receptor 2 (PAR-2), along with cytokines and fibrotic mediators were studied. Bioinformatic analysis was conducted to correlate altered protein changes with microglial activation. To assess receptor dynamics, HOE-140 (1 µM) and GB-83 (2 µM) were used to antagonize the B2KR and PAR-2 receptors, respectively. Also, the role of autophagy in modulating microglial response was evaluated. Data from our work indicate that PKall, LPS, BK, and neuronal cell debris resulted in the activation of microglia and enhanced expression/secretion of inflammatory mediators. Elevated increase in inflammatory mediators was attenuated in the presence of HOE-140 and GB-83, implicating the engagement of these receptors in the activation process coupled with an increase in the expression of B2KR and PAR-2. Finally, the inhibition of autophagy significantly enhanced the release of the cytokine IL-6 which were validated via bioinformatics analysis demonstrating the role of PKall in systematic and brain inflammatory processes. Taken together, we demonstrated that PKall can modulate microglial activation via the engagement of PAR-2 and B2KR where PKall acts as a neuromodulator of inflammatory processes.

Exercise-Induced Ventricular Ectopy and Cardiovascular Mortality in Asymptomatic Individuals.

BACKGROUND: The prognosis of exercise-induced premature ventricular contractions (PVCs) in asymptomatic individuals is unclear. OBJECTIVES: This study sought to investigate whether high-grade PVCs during stress testing predict mortality in asymptomatic individuals. METHODS: A cohort of 5,486 asymptomatic individuals who took part in the Lipid Research Clinics prospective cohort had baseline interview, physical examination, blood tests, and underwent Bruce protocol treadmill testing. Adjusted Cox survival models evaluated the association of exercise-induced high-grade PVCs (defined as either frequent (>10 per minute), multifocal, R-on-T type, or ≥2 PVCs in a row) with all-cause and cardiovascular mortality. RESULTS: Mean baseline age was 45.4 ± 10.8 years; 42% were women. During a mean follow-up of 20.2 ± 3.9 years, 840 deaths occurred, including 311 cardiovascular deaths. High-grade PVCs occurred during exercise in 1.8% of individuals, during recovery in 2.4%, and during both in 0.8%. After adjusting for age, sex, diabetes, hypertension, lipids, smoking, body mass index, and family history of premature coronary disease, high-grade PVCs during recovery were associated with cardiovascular mortality (hazard ratio [HR]: 1.82; 95% CI: 1.19-2.79; P = 0.006), which remained significant after further adjusting for exercise duration, heart rate recovery, achieving target heart rate, and ST-segment depression (HR: 1.68; 95% CI: 1.09-2.60; P = 0.020). Results were similar by clinical subgroups. High-grade PVCs occurring during the exercise phase were not associated with increased risk. Recovery PVCs did not improve 20-year cardiovascular mortality risk discrimination beyond clinical variables. CONCLUSIONS: High-grade PVCs occurring during recovery were associated with long-term risk of cardiovascular mortality in asymptomatic individuals, whereas PVCs occurring only during exercise were not associated with increased risk.

The association of cardiovascular mortality with a first-degree family member history of different cardiovascular diseases.

OBJECTIVE: To investigate which history of cardiovascular disease [coronary heart disease (CHD), stroke, or peripheral arterial disease] in a first-degree family member predicts cardiovascular mortality. METHODS: We studied a prospective cohort (the Lipid Research Clinics Prevalence Study) from ten primary care centers across North America. The primary outcome was cardiovascular mortality, assessed using Cox survival models. RESULTS: There were 8,646 participants (mean age: 47.4 ± 12.1 years, 46% women, 52% of participants with hyperlipidemia) who were followed up for a mean duration of 19.4 ± 4.9 years. There were 1,851 deaths (21%), including 852 cardiovascular deaths. A paternal, maternal or sibling history of premature CHD (before 60 years) was present in 26% of participants, of stroke in 27% of participants, and of peripheral arterial disease in 24% of participants. After adjusting for risk factors (age, sex, systolic blood pressure, diastolic blood pressure, body mass index, smoking, fasting glucose, low-density lipoprotein cholesterol and triglycerides), only a paternal history of premature or any CHD, a maternal history of diabetes mellitus or premature or any CHD, and a sibling history of premature CHD, hypertension, or hyperlipidemia were individually predictive of cardiovascular mortality. After adjusting for risk factors and the mentioned familial factors, only paternal and maternal histories of CHD, especially before 60 years, remained predictive of cardiovascular mortality, with a somewhat higher association for a maternal history [adjusted hazard ratio (aHR) = 1.99, 95% CI: 1.36-2.92,P < 0.001 for maternal history of premature CHD; aHR = 1.52, 95% CI: 1.10-2.10, P = 0.011 for paternal history of premature CHD]. Family history of stroke or peripheral arterial disease did not predict cardiovascular mortality. Parental history of premature CHD predicted cardiovascular mortality independently of baseline age (< 60 years and ≥ 60 years), hypertension, or hyperlipidemia and carried more important prognostic value in men rather than women. CONCLUSIONS: In this study, a parental history of CHD, especially before 60 years, best predicted cardiovascular mortality. This finding could help more accurately identify high-risk patients who would benefit from preventive strategies.

Sulfated alginate/polycaprolactone double-emulsion nanoparticles for enhanced delivery of heparin-binding growth factors in wound healing applications.

Diabetic foot ulcers (DFUs) that are not effectively treated could lead to partial or complete lower limb amputations. The lack of connective tissue growth factor (CTGF) and insulin-like growth factor (IGF-I) in DFUs results in limited matrix deposition and poor tissue repair. To enhance growth factor (GF) availability in DFUs, heparin (HN)-mimetic alginate sulfate/polycaprolactone (AlgSulf/PCL) double emulsion nanoparticles (NPs) with high affinity and sustained release of CTGF and IGF-I were synthesized. The NPs size, encapsulation efficiency (EE), cytotoxicity, cellular uptake and wound healing capacity in immortalized primary human adult epidermal cells (HaCaT) were assessed. The sonication time and amplitude used for NPs synthesis enabled the production of particles with a minimum of 236 ± 25 nm diameter. Treatment of HaCaT cells with up to 50 µg mL-1 of NPs showed no cytotoxic effects after 72 h. The highest bovine serum albumin EE (94.6 %, P = 0.028) and lowest burst release were attained with AlgSulf/PCL. Moreover, cells treated with AlgSulf/CTGF (250 ng mL-1) exhibited the most rapid wound closure compared to controls while maintaining fibronectin synthesis. Double-emulsion NPs based on HN-mimetic AlgSulf represent a novel approach which can significantly enhance diabetic wound healing and can be expanded for applications requiring the delivery of other HN-binding GFs.

Plasma Kallikrein as a Modulator of Liver Injury/Remodeling.

The occurrence and persistence of hepatic injury which arises from cell death and inflammation result in liver disease. The processes that lead to liver injury progression and resolution are still not fully delineated. The plasma kallikrein-kinin system (PKKS) has been shown to play diverse functions in coagulation, tissue injury, and inflammation, but its role in liver injury has not been defined yet. In this study, we have characterized the role of the PKKS at various stages of liver injury in mice, as well as the direct effects of plasma kallikrein on human hepatocellular carcinoma cell line (HepG2). Histological, immunohistochemical, and gene expression analyses were utilized to assess cell injury on inflammatory and fibrotic factors. Acute liver injury triggered by carbon tetrachloride (CCl4) injection resulted in significant upregulation of the plasma kallikrein gene (Klkb1) and was highly associated with the high mobility group box 1 gene, the marker of cell death (r = 0.75, p < 0.0005, n = 7). In addition, increased protein expression of plasma kallikrein was observed as clusters around necrotic areas. Plasma kallikrein treatment significantly increased the proliferation of CCl4-induced HepG2 cells and induced a significant increase in the gene expression of the thrombin receptor (protease activated receptor-1), interleukin 1 beta, and lectin-galactose binding soluble 3 (galectin-3) (p < 0.05, n = 4). Temporal variations in the stages of liver fibrosis were associated with an increase in the mRNA levels of bradykinin receptors: beta 1 and 2 genes (p < 0.05; n = 3-10). In conclusion, these findings indicate that plasma kallikrein may play diverse roles in liver injury, inflammation, and fibrosis, and suggest that plasma kallikrein may be a target for intervention in the states of liver injury.

Digital thermography and vascular involvement in ß-thalassemia intermedia.

Beta-thalassemia intermedia (ß-TI) is associated with vascular dysfunction. We used digital thermal monitoring (DTM), a non-invasive tool that evaluates vascular function based on changes in fingertip temperature during and after cuff occlusion on ß-TI patients. Thirty-three patients (18 years and older) were recruited in this study and divided into 3 groups: thalassemia, anemic controls, and healthy controls. Exclusion criteria included factors that are known to be associated with vascular damage. Patients underwent DTM and results were extracted as vascular reactivity index (VRI), a measure of how well the circulatory system responds to stimuli that require adjustments of blood flow. One-way analysis of variance (ANOVA) was used to test the mean difference in VRI between the 3 groups. A multiple linear regression was also carried out with VRI as the outcome of interest and a function of covariates that were thought to be of clinical relevance to VRI. The frequency, mean VRI ± standard error (SE) for the thalassemic group were (N = 16), mean = 2.243 ± 0.111; for anemic controls (N = 9), mean = 2.374 ± 0.162; and for the controls (N = 8), mean = 2.338 ± 0.092. ANOVA test indicated a non-significant difference in mean VRI between the three groups (P value = 0.731). Multiple linear regression couldn't detect any significant association between VRI and any of the predictors including the groups. Our study did not show a significant difference in VRI between the 3 study groups. Prospective studies of larger sample size are warranted to establish DTM as a possible non-invasive tool used to evaluate vascular function in ß-TI patients.

Genomic and Proteomic Study of the Inflammatory Pathway in Patients With Atrial Fibrillation and Cardiometabolic Syndrome.

Atrial fibrillation (AF) and cardiometabolic syndrome (CMS) have been linked to inflammation and fibrosis. However, it is still unknown which inflammatory cytokines contribute to the pathogenesis of AF. Furthermore, cardiometabolic syndrome (CMS) risk factors such as obesity, hypertension, insulin resistance/glucose intolerance are also associated with inflammation and increased level of cytokines and adipokines. We hypothesized that the inflammatory immune response is exacerbated in patients with both AF and CMS compared to either AF or CMS alone. We investigated inflammatory cytokines and fibrotic markers as well as cytokine genetic profiles in patients with lone AF and CMS. CMS, lone AF patients, patients with both lone AF and CMS, and control patients were recruited. Genetic polymorphisms in inflammatory and fibrotic markers were assessed. Serum levels of connective tissue growth factor (CTGF) were tested along with other inflammatory markers including platelet-to-lymphocyte ratio (PLR), monocyte-to-HDL ratio (MHR) in three groups of AF+CMS, AF, and CMS patients. There was a trend in the CTGF levels for statistical significance between the AF and AF+CMS group (P = 0.084). Genotyping showed high percentages of patients in all groups with high secretor genotypes of Interleukin-6 (IL-6) (P = 0.037). Genotyping of IFN-γ and IL-10 at high level showed an increase in expression in the AF + CMS group compared to AF and CMS alone suggesting an imbalance between the inflammatory and anti-inflammatory cytokines which is exacerbated by AF. Serum cytokine inflammatory cytokine levels showed that IL-4, IL-5, IL-10, IL-17F, and IL-22 were significant between the AF, AF+CMS, and CMS patients. Combination of both CMS and AF may be associated with a higher degree of inflammation than what is seen in either CMS or AF alone. Thus, the identification of a biomarker capable of identifying metabolic syndrome associated with disease will help in identification of a therapeutic target in treating this devastating disease.

Vascular Cells Proteome Associated with Bradykinin and Leptin Inflammation and Oxidative Stress Signals.

Among the primary contributors to cardiovascular diseases are inflammation and oxidative imbalance within the vessel walls as well as the fibrosis of rat aortic smooth muscle cell (RASMC). Bradykinin (BK) and leptin are inflammatory modulators that are linked to vascular injury. In this study, we employed tandem LC-MS/MS to identify protein signatures that encompass protein abundance in RASMC treated with BK or leptin followed by systems biology analyses to gain insight into the biological pathways and processes linked to vascular remodeling. In the study, 1837 proteins were identified in control untreated RASMC. BK altered the expression of 72 (4%) and 120 (6.5%) proteins, whereas leptin altered the expression of 189 (10.2%) and 127 (6.5%) proteins after 24 and 48 h, respectively, compared to control RASMC. BK increased the protein abundance of leptin receptor, transforming growth factor-ß. On the other hand, leptin increased the protein abundance of plasminogen activator inhibitor 1 but decreased the protein abundance of cofilin. BK and leptin induced the expression of inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-1ß (IL-1ß) and pathway analysis revealed the activation of mitogen-activated protein kinases (MAPKs) and AKT pathways. The proteome profile in response to BK and leptin revealed mechanistic interplay of multiple processes that modulate inflammation and oxidative stress signals in the vasculature.

Barriers to the use of dental services by children in Lebanon and association with parental perception of oral health care.

BACKGROUND: Oral health is important to general health but use of dental services varies considerably, particularly for children. AIMS: We aimed to determine factors associated with parents' use of dental services for their children in Lebanon, and their perception of dental care relative to medical care. METHODS: A convenience sample of public and private schools in Beirut was selected between January and May 2013. Parents of children in grades 2-6 (aged 7-12 years) were invited to complete a questionnaire covering socioeconomic characteristics and use of dental services. Logistic regression analysis was used to assess the relationship between use of dental services, and parents' socioeconomic characteristics and awareness and perceptions of dental services. RESULTS: The parents of 316 children returned the questionnaire. Most children (72.8%) had been taken to the dentist in the past year, mainly for emergency care. Most parents (78.2%) considered dental care as important as or more important than medical care, and 89.9% were willing to contribute to dental insurance. Use of dental services was significantly associated with: older age of the parent (odds ratio, OR = 1.04; 95% confidence interval, CI: 1.02-1.06); awareness of dental care centres offering affordable treatment (OR = 3.18; 95% CI: 1.52-6.68); and children being in private schools (OR = 2.00, 95% CI: 1.08-3.95). It was negatively associated with > 4 children in the family compared with 1 child (OR = 0.18; 95% CI: 0.04-0.81). CONCLUSION: Barriers to dental care for children were mostly related to economic factors.

Longitudinal Plasma Kallikrein Levels and Their Association With the Risk of Cardiovascular Disease Outcomes in Type 1 Diabetes in DCCT/EDIC.

We determined the relationship between plasma kallikrein and cardiovascular disease (CVD) outcomes as well as major adverse cardiovascular events (MACE) in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) cohort of type 1 diabetes (T1D). Plasma kallikrein levels were measured longitudinally in 693 subjects at DCCT baseline (1983-1989), midpoint (1988-1991), and end (1993) and at EDIC years 4-6 (1997-1999), 8-10 (2001-2003), and 11-13 (2004-2006). Cox proportional hazards regression models assessed the association between plasma kallikrein levels and the risk of CVD. In unadjusted models, higher plasma kallikrein levels were associated with higher risk of any CVD during DCCT/EDIC (hazard ratio [HR] = 1.16 per 20 nmol/L higher levels of plasma kallikrein; P = 0.0177) as well as over the EDIC-only period (HR = 1.22; P = 0.0024). The association between plasma kallikrein levels and the risk of any CVD remained significant during the EDIC follow-up after adjustment for age and mean HbA1c (HR = 1.20; P = 0.0082) and in the fully adjusted model for other CVD risk factors (HR = 1.17; P = 0.0330). For MACE, higher plasma kallikrein levels were associated with higher risk in the unadjusted (HR = 1.25; P = 0.0145), minimally adjusted (HR = 1.23; P = 0.0417, and fully adjusted (HR = 1.27; P = 0.0328) models for EDIC only. These novel findings indicate that plasma kallikrein level associates with the risk of any CVD and MACE in T1D individuals.

Thymoquinone induces apoptosis and DNA damage in 5-Fluorouracil-resistant colorectal cancer stem/progenitor cells.

The high recurrence rates of colorectal cancer have been associated with a small population of cancer stem cells (CSCs) that are resistant to the standard chemotherapeutic drug, 5-fluorouracil (5FU). Thymoquinone (TQ) has shown promising antitumor properties on numerous cancer systems both in vitro and in vivo; however, its effect on colorectal CSCs is poorly established. Here, we investigated TQ's potential to target CSCs in a three-dimensional (3D) sphere-formation assay enriched for a population of colorectal cancer stem/progenitor cells. Our results showed a significant decrease in self-renewal potential of CSC populations enriched from 5FU-sensitive and resistant HCT116 cells at 10-fold lower concentrations when compared to 2D monolayers. TQ decreased the expression levels of colorectal stem cell markers CD44 and Epithelial Cell Adhesion Molecule EpCAM and proliferation marker Ki67 in colonospheres derived from both cell lines and reduced cellular migration and invasion. Further investigation revealed that TQ treatment led to increased TUNEL positivity and a dramatic increase in the amount of the DNA damage marker gamma H2AX particularly in 5FU-resistant colonospheres, suggesting that the diminished sphere forming ability in TQ-treated colonospheres is due to induction of DNA damage and apoptotic cell death. The intraperitoneal injection of TQ in mice inhibited tumor growth of spheres derived from 5FU-sensitive and 5FU-resistant HCT116 cells. Furthermore, TQ induced apoptosis and inhibited NF-κB and MEK signaling in mouse tumors. Altogether, our findings document TQ's effect on colorectal cancer stem-like cells and provide insights into its underlying mechanism of action.

Modulation of proteomic and inflammatory signals by Bradykinin in podocytes.

Podocyte damage is one of the hallmarks of diabetic nephropathy leading to proteinuria and kidney damage. The underlying mechanisms of podocyte injury are not well defined. Bradykinin (BK) was shown to contribute to diabetic kidney disease. Here, we evaluated the temporal changes in proteome profile and inflammatory signals of podocytes in response to BK (10-7M). Protein profile was evaluated by liquid chromatography mass Spectrometry (LC-MS/MS) analysis. Proteome profile analysis of podocytes treated with BK (10-7M) for 3 and 6 h, revealed 61 proteins that were differentially altered compared to unstimulated control podocytes. Pathway enrichment analysis suggested inhibition of cell death pathways, engagement of cytoskeletal elements and activation of inflammatory pathways. One of the inflammatory proteins that was identified to be induced by BK treatment is Prostaglandin (PG) H Synthase-2 (Cyclooxygenase-2, COX-2). In addition, BK significantly induced the production and release of PGE2 and this effect was inhibited by both COX-2 and MEK Kinase inhibitors, demonstrating that the production of PGE2 by BK is mediated via COX-2 and MAPK-dependent mechanisms. These findings provide a global understanding of the effector modulated proteome in response to BK and also reveal BK as an important modulator of inflammation and a potential player in podocyte injury.

Knowledge and attitudes towards E-cigarette use in Lebanon and their associated factors.

BACKGROUND: Despite the misconceptions regarding E-cigarettes (ECs), only a few studies have been conducted in the Middle East that focused on this topic. This study assesses the knowledge of and attitudes towards ECs in Lebanon, determines how these two measures are associated, and identifies the variables that explain each of these measures. METHODS: A cross sectional study was conducted on a convenience sample of Lebanese pedestrians aged between 18 and 64 inclusive. A structured self-administered questionnaire comprising of knowledge and attitude scales, and questions on demographical, health and smoking characteristics was used. RESULTS: Scores for attitudes and knowledge of ECs were summed and dichotomized using a 75% cutoff, above which the participant was considered to have a positive attitude and good knowledge. Among the 352 participants (56.6% males, 43.3% females, mean age 30.3, 46.2% smokers), 63.3% exhibited a lower level of EC knowledge. More than 50% erroneously thought that ECs are not associated with lung and bladder cancer or impair lung and heart function. 65% falsely thought that it is harmless and not addictive. As for attitude, 43.3, 53.9, and 44.3% thought that it is socially acceptable, helps in smoking cessation, and is a good replacement for cigarettes and an enjoyable recreational device respectively. Our results revealed an inverse correlation between attitude and knowledge scores (Spearman's correlation = -.30, p < .001). Predictors of knowledge included health-related occupation (p = .010), regular exercise (p = .016), healthy diet (p = .026), EC use (p = .026), perception that ECs are not harmful (p = .001), and help in smoking cessation (p = .017). Predictors of attitude included EC use (p = .008), sex (p = .010), and knowledge that most ECs are addictive (p = .006), harmful (p = .014), and impair heart and lung function (p = .047). CONCLUSIONS: Our study revealed a gap in EC knowledge, especially among participants who displayed a positive attitude towards ECs. Hence, measures should be undertaken to regulate its use by instituting more stringent laws and holding nationwide awareness campaigns.

A Likelihood Based Approach for Joint Modeling of Longitudinal Trajectories and Informative Censoring Process.

We propose a joint modeling likelihood-based approach for studies with repeated measures and informative right censoring. Joint modeling of longitudinal and survival data are common approaches but could result in biased estimates if proportionality of hazards is violated. To overcome this issue, and given that the exact time of dropout is typically unknown, we modeled the censoring time as the number of follow-up visits and extended it to be dependent on selected covariates. Longitudinal trajectories for each subject were modeled to provide insight into disease progression and incorporated with the number follow-up visits in one likelihood function.

Awareness of Colorectal Cancer and Attitudes Towards Its Screening Guidelines in Lebanon.

BACKGROUND: Screening for colorectal cancer (CRC) provides an effective strategy for early detection and prevention of the disease; however, global screening rates are still low. PURPOSE: This study aims at assessing the awareness of CRC risk factors, warning signs, and attitudes towards CRC guidelines and screening modalities, in order to identify the barriers to and correlates of CRC screening in the Lebanese population. METHODS: A self-administered questionnaire was distributed to 371 participants in the largest health care medical center in Lebanon. A validated 12- and 9-item Cancer Awareness Measurement questionnaire was used to assess participants' awareness of CRC risk factors and warning signs. RESULTS: 83% and 67% of participants were not aware of CRC risk factors and warning signs, respectively, 15% have previously undergone CRC screening, 56% were aware of the necessity for screening, and 43% were willing to undergo screening. Factors affecting awareness of the necessity for CRC screening, past screening and willingness to screen included awareness of risk factors and warning signs, undergoing regular physician check-ups, having a family physician as a primary source of knowledge of CRC, and knowing a family member or friend diagnosed with CRC. Barriers to screening were related to participants' evaluation of the screening technique and misconceptions about this disease. CONCLUSION: Serious active measures should be taken by health care sectors, authoritative groups, primary care physicians, and awareness campaigns to fill the gap in awareness of this disease and to alleviate the barriers and misconceptions around it.

Heteromerization fingerprints between bradykinin B2 and thromboxane TP receptors in native cells.

Bradykinin (BK) and thromboxane-A2 (TX-A2) are two vasoactive mediators that modulate vascular tone and inflammation via binding to their cognate "class A" G-protein coupled receptors (GPCRs), BK-B2 receptors (B2R) and TX-prostanoid receptors (TP), respectively. Both BK and TX-A2 lead to ERK1/2-mediated vascular smooth muscle cell (VSMC) proliferation and/or hypertrophy. While each of B2R and TP could form functional dimers with various GPCRs, the likelihood that B2R-TP heteromerization could contribute to their co-regulation has never been investigated. The main objective of this study was to investigate the mode of B2R and TP interaction in VSMC, and its possible impact on downstream signaling. Our findings revealed synergistically activated ERK1/2 following co-stimulation of rat VSMC with a subthreshold dose of BK and effective doses of the TP stable agonist, IBOP, possibly involving biased agonist signaling. Single detection of each of B2R and TP in VSMC, using in-situ proximity ligation assay (PLA), provided evidence of the constitutive expression of nuclear and extranuclear B2R and TP. Moreover, inspection of B2R-TP PLA signals in VSMC revealed agonist-modulated nuclear and extranuclear proximity between B2R and TP, whose quantification varied substantially following single versus dual agonist stimulations. B2R-TP interaction was further verified by the findings of co-immunoprecipitation (co-IP) analysis of VSMC lysates. To our knowledge, this is the first study that provides evidence supporting the existence of B2R-TP heteromerization fingerprints in primary cultured VSMC.