Early Graft Failure After Living-Donor Liver Transplant.

BACKGROUND: Living-donor liver transplantation (LDLT) has been increasing in the USA. While data exist on longer-term patient and graft outcomes, a contemporary analysis of short-term outcomes is needed. AIM: Evaluate short-term (30-day) graft failure rates and identify predictors associated with these outcomes. METHODS: Adult (≥ 18) LDLT recipients from 01/2004 to 12/2021 were analyzed from the United States Scientific Registry of Transplant Recipients. Graft status at 30 days was assessed with graft failure defined as retransplantation or death. Comparison of continuous and categorical variables was performed and a multivariable logistic regression was used to identify risk factors of early graft failure. RESULTS: During the study period, 4544 LDLTs were performed with a graft failure rate of 3.4% (155) at 30 days. Grafts from male donors (aOR: 0.63, CI 0.44-0.89), right lobe grafts (aOR: 0.40, CI 0.27-0.61), recipients aged > 60 years (aOR: 0.52, CI 0.32-0.86), and higher recipient albumin (aOR: 0.73, CI 0.57-0.93) were associated with superior early graft outcomes, whereas Asian recipient race (vs. White; aOR: 3.75, CI 1.98-7.10) and a history of recipient PVT (aOR: 2.7, CI 1.52-4.78) were associated with inferior outcomes. LDLTs performed during the most recent 2016-2021 period (compared to 2004-2009 and 2010-2015) resulted in significantly superior outcomes (aOR: 0.45, p < 0.001). CONCLUSION: Our study demonstrates that while short-term adult LDLT graft failure is uncommon, there are opportunities for optimizing outcomes by prioritizing right lobe donation, improving candidate nutritional status, and careful pre-transplant risk assessment of candidates with known PVT. Notably, a period effect exists whereby increased LDLT experience in the most recent era correlated with improved outcomes.

Outcomes of critically ill COVID-19 patients boarding in the emergency department of a tertiary care center in a developing country: a retrospective cohort study.

BACKGROUND: Boarding of critically ill patients in the emergency department (ED) has long been known to compromise patient care and affect outcomes. During the COVID-19 pandemic, multiple hospitals worldwide experienced overcrowded emergency rooms. Large influx of patients outnumbered hospital beds and required prolonged length of stay (LOS) in the ED. Our aim was to assess the ED LOS effect on mortality and morbidity, in addition to the predictors of in-hospital mortality, intubation, and complications of critically ill COVID-19 ED boarder patients. METHODS: This was a retrospective cohort study, investigating 145 COVID-19-positive adult patients who were critically ill, required intensive care unit (ICU), and boarded in the ED of a tertiary care center in Lebanon. Data on patients who boarded in the emergency from January 1, 2020, till January 31, 2021, was gathered and studied. RESULTS: Overall, 66% of patients died, 60% required intubation, and 88% developed complications. Multiple risk factors were associated with mortality naming age above 65 years, vasopressor use, severe COVID pneumonia findings on CT chest, chemotherapy treatment in the previous year, cardiovascular diseases, chronic kidney diseases, prolonged ED LOS, and low SaO2 < 95% on triage. In addition, our study showed that staying long hours in the ED increased the risk of developing complications. CONCLUSION: To conclude, all efforts need to be drawn to re-establish mitigation strategies and models of critical care delivery in the ED to alleviate the burden of critical boarders during pandemics, thus decreasing morbidity and mortality rates. Lessons from this pandemic should raise concern for complications seen in ED ICU boarders and allow the promotion of health measures optimizing resource allocation in future pandemic crises.

Pharmacometabolomic Approach to Investigate the Response to Metformin in Patients with Type 2 Diabetes: A Cross-Sectional Study.

Metformin constitutes the foundation therapy in type 2 diabetes (T2D). Despite its multiple beneficial effects and widespread use, there is considerable inter-individual variability in response to metformin. Our objective is to identify metabolic signatures associated with poor and good responses to metformin, which may improve our ability to predict outcomes for metformin treatment. In this cross-sectional study, clinical and metabolic data for 119 patients with type 2 diabetes taking metformin were collected from the Qatar Biobank. Patients were empirically dichotomized according to their HbA1C levels into good and poor responders. Differences in the level of metabolites between these two groups were compared using orthogonal partial least square discriminate analysis (OPLS-DA) and linear models. Good responders showed increased levels of sphingomyelins, acylcholines, and glutathione metabolites. On the other hand, poor responders showed increased levels of metabolites resulting from glucose metabolism and gut microbiota metabolites. The results of this study have the potential to increase our knowledge of patient response variability to metformin and carry significant implications for enabling personalized medicine.

Melitracen and flupentixol (deanxit) use disorder in Lebanon.

Introduction: Deanxit is a combination of melitracen and flupentixol, not approved as an antidepressant for sale and use in several countries but still widely available and commonly used among the Lebanese population. The study aimed to assess Deanxit use disorder, assess the source of the medication, and the consumers' awareness of the therapeutic and side effects of Deanxit, among the Lebanese population. Methods: This is a cross-sectional study that included all patients taking Deanxit and visited the Emergency Department between October 2019 and October 2020. All patients who agreed to participate in the research through written consent forms were contacted by telephone and a questionnaire was filled out. Results: A total of 125 patients taking Deanxit were included in the study. According to the DSM-V criteria, 36% (n = 45) had a Deanxit use disorder. Most of the participants were females (n = 99, 79.2%), married (n = 90, 72%), and between the ages of 40-65 years (n = 71, 56.8%). Most patients (n = 41, 91%) had Deanxit prescribed by a physician for anxiety (n = 28, 62%), and obtained it using a prescription (n = 41, 91%). Almost half of all patients (n = 60, 48%) did not have sufficient knowledge of the reason it was prescribed, 54.4% (n = 68) were not sure they are taking the medication appropriately, and 19.2% (n = 23) were satisfied by the overall explanation of the physicians concerning Deanxit use. Conclusion: Deanxit use disorder is underrecognized among Lebanese patients. Most of our patients were prescribed Deanxit by their physicians but reported inadequate knowledge of its side effects and risk of abuse.

Predictors for hospital admission in emergency department patients with benign paroxysmal positional vertigo: A retrospective review.

OBJECTIVE: This study aims to assess the incidence of Emergency Department (ED) visits for benign paroxysmal positional vertigo (BPPV), describe patient characteristics, management practices and predictors of inpatient admission of BPPV patients. METHODS: This was a retrospective chart review of patients presenting with BPPV to a single ED between November 2018 and August 2020. Patients' characteristics, ED management, discharge medications, disposition and unscheduled return visits were determined. RESULTS: In total, 557 patients were included. Average age was 49 years, 54.2% were females and 12.4% required hospital admission. In the ED, 51.1% received intravenous hydration, 33.8% received anti-emetics, 10.1% received benzodiazepines, 31.8% underwent canalith repositioning maneuvers (CRMs) and 56.7% were discharged on acetyl-leucine. Of discharged patients, 2.5% had unscheduled return visits. A higher likelihood of admission was associated with age above 54 years (aOR = 4.86, p<0.001, 95% CI [2.67, 8.86]), home use of proton pump inhibitors (PPIs) (aOR = 2.44, p = 0.03, 95% CI [1.08, 5.53]), use of anti-emetics and benzodiazepines in the ED (aOR = 2.34, p = 0.003, 95% CI [1.34, 4.07]) and (aOR = 2.18, p = 0.04, 95% CI [1.03, 4.64]), respectively. CONCLUSION: While BPPV is a benign diagnosis, a significant number of patients presenting to the ED require admission. Predictors of admission include older age, PPIs use and ED treatment with anti-emetics and benzodiazepines. Although CRMs are the gold standard for management, CRMs usage did not emerge as protective from admission, and our overall usage was low.

The Beirut ammonium nitrate blast: A multicenter study to assess injury characteristics and outcomes.

BACKGROUND: Blasts incidents impose catastrophic aftermaths on populations regarding casualties, sustained injuries, and devastated infrastructure. Lebanon witnessed one of the largest nonnuclear chemical explosions in modern history-the August 2020 Beirut Port blast. This study assesses the mechanisms and characteristics of blast morbidity and mortality and examines severe injury predictors through the Injury Severity Score. METHODS: A retrospective, multicenter cross-sectional study was conducted. Data of trauma patients presenting to five major acute-care hospitals in metropolitan Beirut up to 4 days following the blast were collected in a two-stage process from patient hospital chart review and follow-up phone calls. RESULTS: A total of 791 patients with a mean age of 42 years were included. The mean distance from the blast was 2.4 km (SD, 1.9 km); 3.1% of victims were in the Beirut Port itself. The predominant mechanism of injury was being struck by an object (falling/projectile) (293 [37.0%]), and the most frequent site of injury was the head/face (209 [26.4%]). Injury severity was low for 548 patients (71.2%), moderate for 62 (8.1%), and severe/critical for 27 (3.5%). Twenty-one deaths (2.7%) were recorded. Significant serious injury predictors (Injury Severity Score, >15) were sustaining multiple injuries (odds ratio [OR], 2.62; p = 0.005); a fracture (OR, 5.78; p < 0.001); primary blast injuries, specifically a blast lung (OR, 18.82; p = 0.001), concussion (OR, 7.17; p < 0.001), and eye injury (OR, 8.51; p < 0.001); and secondary blast injuries, particularly penetrating injuries (OR, 9.93; p < 0.001) and traumatic amputations (OR, 13.49; p = 0.01). Twenty-five percent were admitted to the hospital, with 4.6% requiring the intensive care unit. At discharge, 25 patients (3.4%) had recorded neurologic disability. CONCLUSION: Most injuries sustained by the blast victims were minor. Serious injuries were mostly linked to blast overpressure and projectile fragments. Understanding blast injuries characteristics, their severity, and management is vital to informing emergency services, disaster management strategies, hospital preparedness, and, consequently, improving patient outcomes. LEVEL OF EVIDENCE: Prognostic and Epidemiologic; Level III.

Assessing the psychological impact of Beirut Port blast: A cross-sectional study.

Beirut Port blast's magnitude is considered the third after Hiroshima and Nagasaki atomic bombings. This blast occurred in the densely populated section of Beirut, leaving more than six thousand injured patients. The psychological disturbances were assessed in the blast survivors who presented to the Emergency Department (ED) at the American University of Beirut Medical Center (AUBMC). This was a cross-sectional study at the ED of AUBMC. Identified patients were contacted and consented to participate in the study. Post-Traumatic Stress Disorder (PTSD) was selected as an outcome. Depression, PTSD, and concussion were assessed using patient health questionnaire (PHQ)-9, PTSD checklist for DSM-5 (PCL5), and brain injury symptoms (BISx) tools, respectively. The association of patients and injury characteristics with the study outcome was assessed using logistic regression. 145 participants completed the study procedures. The participants' average age was 39.8 ± 15.4 years, and 60% were males. Almost half of the participants showed depression on PHQ, and 2-thirds had PTSD. The participant's age was negatively associated with PTSD, whereas being a female, having depression, and having a concussion were positively associated with PTSD. The results of this study were in line with the previous literature report except for the association between younger age and PTSD, which warrants further investigations to delineate the reasons.

Lead screening in children presenting to three hospitals in Lebanon.

BACKGROUND: Lead damages most body organs and its effects are most profound in children. In a study in Beirut in 2003, before banning the leaded gasoline, 79% of the participants showed blood lead levels (BLLs) higher than 5 µg/dL. The prevalence of lead exposure in Lebanon after the ban on leaded gasoline has not been studied. This study assessed the BLL in Lebanese children aged 1-6 years. METHODS: This cross-sectional study was conducted in three hospitals in Beirut. The children's BLLs were tested, and their caregiver completed a questionnaire to identify subgroups at risk of exposure. Participants were provided with a WHO brochure highlighting the risks of lead. RESULTS: Ninety children with a mean age of 3.5±1.5 years were enrolled in the study and had a mean BLL of 1.1±0.7 µg/dL, with all values being below 5.0 µg/dL, showing a marked decrease in BLL compared with the mean BLL before the ban on leaded gasoline in 2002. Having a father or a mother with a college degree (p=0.01 and p=0.035, respectively) and having a monthly household income greater than $1000 (p=0.021) were associated with significantly lower BLL. Having more rooms at home and residing close to construction sites were associated with a significantly lower BLL (p=0.001 and p=0.026, respectively). Residing in a house aged >40 years and receiving traditional remedies were associated with a significantly higher BLL (p=0.009 and p<0.0001, respectively). CONCLUSION: BLLs have declined among Lebanese children and this could be attributed to multiple factors including the ban of leaded gasoline. It would be beneficial to conduct a larger study with a nationally representative sample to better characterise the BLL.

Psychological impact of COVID-19 on emergency department healthcare workers in a tertiary care center during a national economic crisis.

BACKGROUND: Since the declaration of the novel Corona Virus Disease (COVID-19) as a global pandemic by the World Health Organization, frontline healthcare workers (HCWs) and staff in the Emergency Departments (ED) started experiencing feelings of anxiety and fear from the projected exponential spread and the potential burden on the healthcare system and infrastructure. In Lebanon, major local factors contributing to this fear were the rapid escalation of COVID-19 cases across the country, the lack of preparedness, and the shortage of personal protective equipment, in addition to the evolving economic crisis and financial restrictions. This study aims to investigate the immediate psychological impact of the COVID-19 outbreak on ED staff working in a hospital environment in relation to their household income. METHODS: Self-reported cross-sectional survey was delivered to the frontline staff working at the Department of Emergency Medicine of AUBMC in Beirut, Lebanon. General demographic characteristics, scores of Generalized Anxiety Disorder 7 (GAD-7), scores of Patient Health Questionnaire 9 (PHQ-9), and scores of Burnout Measure-Short (BMS) version were collected. RESULTS: 74 HCWs (49.6%) participated in the study. The mean age for participants was (31.78 ± 9.49). More than half of the participants were nurses and more than 70% reported a monthly salary of less than 2000 USD. The household income was negatively associated with the participants' scores on the GAD-7 and PHQ-9, but not the BMS. Previous mental health diagnosis was positively associated with the PHQ-9 and BMS scores, while seeking mental health care was negatively associated with the PHQ-9 and BMS scores. CONCLUSION: At our tertiary care center in a low-income, low resource country amidst the COVID-19 pandemic, the HCWs reported marked psychological disturbances on different scales. In particular, the financial burden was associated with increased anxiety and clinical depression, but was not associated with burnout.

Pediatric emergency department utilisation during Ramadan: a retrospective cross-sectional study.

OBJECTIVE: To investigate the impact of Ramadan on patient characteristics, diagnoses and metrics in the paediatric emergency department (PED). DESIGN: Retrospective cross-sectional study. SETTING: PED of a tertiary care centre in Lebanon. PATIENTS: All paediatric patients. EXPOSURE: Ramadan (June 2016 and 2017) versus the months before and after Ramadan (non-Ramadan). MAIN OUTCOME MEASURES: Patient and illness characteristics and PED metrics including peak patient load; presentation timings; length of stay; and times to order tests, receive samples and report results. RESULTS: We included 5711 patients with mean age of 6.1±5.3 years and 55.4% males. The number of daily visits was 28.3±6.5 during Ramadan versus 31.5±7.3 during non-Ramadan (p=0.004). The peak time of visits ranged from 18:00 to 22:00 during non-Ramadan versus from 22:00 to 02:00 during Ramadan. During Ramadan, there were significantly more gastrointestinal (GI) and trauma-related complaints (39.0% vs 35.4%, p=0.01 and 2.9% vs 1.8%, p=0.005). The Ramadan group had faster work efficiency measures such as times to order tests (21.1±21.3 vs 24.3±28.1 min, p<0.0001) and to collect samples (50.7±44.5 vs 54.8±42.6 min, p=0.03). CONCLUSIONS: Ramadan changes presentation patterns, with fewer daily visits and a later peak time of visits. Ramadan also affects illness presentation patterns with more GI and trauma cases. Fasting times during Ramadan did not affect staff work efficiency. These findings could help EDs structure their staffing to optimise resource allocation during Ramadan.

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.

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.

Left without being seen in a hybrid point of service collection model emergency department.

OBJECTIVE: This study identifies reasons and predictors of LWBS and examines outcomes of patients in a model that uses "point-of-service" (POS) collection for low acuity patients. METHODS: This was a matched case-control study of all patients who left without being seen from the ED of a tertiary care center in Beirut Lebanon between June 2016 and May 2017. Matching was done for the ESI score, date and time (±2 h). A descriptive analysis and a bivariate analysis were conducted comparing patients who LWBS and those who completed their medical treatment. This was followed by a Logistic regression to identify predictors of LWBS. RESULTS: 133 LWBS cases and 133 matched controls were enrolled in the study. Mean age for LWBS patients was (31.69 ±â€¯15.29). The average reported wait time of LWBS patients was reported as 27.48 min (±25.09). Reasons for LWBS were; non-compensable status (66.9%), financial reasons (12.8%), long waiting times (12.8%), and others (8.3%). The majority of LWBS patients (81.2%) sought medical care after leaving the ED, and 8.3% of the LWBS patients represented to the ED after 48 h. Important predictors of LWBS included male gender, lower than undergraduate education level, waiting room time, non-compensable coverage status and fewer ED visits in the past year. CONCLUSION: In an ED setting with POS collection for low acuity patients, non-compensable coverage status was the strongest predictor for LWBS. Further studies are needed to assess the outcomes of patients who LWBS in this model of care.

Comparison of outcomes in ST-elevation myocardial infarction according to age.

BACKGROUND: Myocardial infarction constitutes a significant cause of morbidity and mortality. Its pathophysiology varies according to age; atherosclerosis is the most common cause in older patients while thrombosis or plaque rupture is behind premature MI. OBJECTIVE: To compare the outcome differences between young (age ≤ 45 years) and older adults (age > 45 years) presenting with STEMI. METHOD: This was a retrospective cohort study of patients presenting with STEMI to the Emergency Department of a tertiary care center, between 2008 and 2018.Cases were patients age ≤ 45 and controls were the older population. Descriptive and bivariate analyses were conducted followed by Logistic regression to identify the outcomes. RESULTS: 107 cases were matched with 214 controls. Majority of patients were males (93% of cases and controls). Younger patients were more likely to be smokers (80% vs. 57%, p < 0.001) and with a family history of MI (56% vs. 37%, p = 0.002). Diabetes, hypertension, dyslipidemia and a previous history of MI were more common among controls, 37%, 60%, 43% and 42% respectively versus 10%, 24%, 36% and 25% in the younger population. Younger patients had a higher prevalence of single-vessel disease compared to older patients (73% vs. 50%, p = 0.001). LAD was the most commonly blocked vessel in both groups (71% vs. 64% respectively). Ejection fraction was within normal range in the majority of controls and cases (63% vs. 56% respectively and 57% vs. 60% respectively). CONCLUSION: Premature MI predominantly affects males and the associated risk factors are smoking and family history of MI. It's characterized by single-vessel disease as compared to older patients.

Characteristics and dispositional determinants of psychiatric emergencies in a University Hospital in Beirut.

Mental health problems are common in Lebanon, and so are psychiatric emergencies. In order to show the characteristics of psychiatric emergencies in Lebanon along with their dispositional determinants, we conducted this retrospective, single-center, chart-review study of patients who presented to the Emergency Department between July 1, 2016 until December 31, 2016 and required an official psychiatrist consultation. Our sample included 195 patients of all age groups. The most common diagnosis was depression (75 patients) followed by anxiety (61 patients). 107 patients (54.8%) required admission for adequate treatment; however only 72 (67.3%) of those were actually admitted, and the rest (32.7%) left the hospital against medical advice. Increased hospital admission was associated with being a female (OR = 3.042), having family history of psychiatric disease (OR = 2.040) and having suicidal ideations (OR = 12.949). In a country that has inadequate health coverage, financial coverage can also be a determining factor in whether or not patients get the admission they need.

Proteome profiling in the aorta and kidney of type 1 diabetic rats.

Diabetes is associated with a number of metabolic and cardiovascular risk factors that contribute to a high rate of microvascular and macrovascular complications. The risk factors and mechanisms that contribute to the development of micro- and macrovascular disease in diabetes are not fully explained. In this study, we employed mass spectrometric analysis using tandem LC-MS/MS to generate a proteomic profile of protein abundance and post-translational modifications (PTM) in the aorta and kidney of diabetic rats. In addition, systems biology analyses were employed to identify key protein markers that can provide insights into molecular pathways and processes that are differentially regulated in the aorta and kidney of type 1 diabetic rats. Our results indicated that 188 (111 downregulated and 77 upregulated) proteins were significantly identified in the aorta of diabetic rats compared to normal controls. A total of 223 (109 downregulated and 114 upregulated) proteins were significantly identified in the kidney of diabetic rats compared to normal controls. When the protein profiles from the kidney and aorta of diabetic and control rats were analyzed by principal component analysis, a distinct separation of the groups was observed. In addition, diabetes resulted in a significant increase in PTM (oxidation, phosphorylation, and acetylation) of proteins in the kidney and aorta and this effect was partially reversed by insulin treatment. Ingenuity pathway analysis performed on the list of differentially expressed proteins depicted mitochondrial dysfunction, oxidative phosphorylation and acute phase response signaling to be among the altered canonical pathways by diabetes in both tissues. The findings of the present study provide a global proteomics view of markers that highlight the mechanisms and putative processes that modulate renal and vascular injury in diabetes.

Multitargeted Flavonoid Inhibition of the Pathogenic Bacterium Staphylococcus aureus: A Proteomic Characterization.

Growth inhibition of the pathogen Staphylococcus aureus with currently available antibiotics is problematic in part due to bacterial biofilm protection. Although recently characterized natural products, including 3',4',5-trihydroxy-6,7-dimethoxy-flavone [1], 3',4',5,6,7-pentahydroxy-flavone [2], and 5-hydroxy-4',7-dimethoxy-flavone [3], exhibit both antibiotic and biofilm inhibitory activities, the mode of action of such hydroxylated flavonoids with respect to S. aureus inhibition is yet to be characterized. Enzymatic digestion and high-resolution MS analysis of differentially expressed proteins from S. aureus with and without exposure to antibiotic flavonoids (1-3) allowed for the characterization of global protein alterations induced by metabolite treatment. A total of 56, 92, and 110 proteins were differentially expressed with bacterial exposure to 1, 2, or 3, respectively. The connectivity of the identified proteins was characterized using a search tool for the retrieval of interacting genes/proteins (STRING) with multitargeted S. aureus inhibition of energy metabolism and biosynthesis by the assayed flavonoids. Identifying the mode of action of natural products as antibacterial agents is expected to provide insight into the potential use of flavonoids alone or in combination with known therapeutic agents to effectively control S. aureus infection.

Cigarette Smoking-Induced Cardiac Hypertrophy, Vascular Inflammation and Injury Are Attenuated by Antioxidant Supplementation in an Animal Model.

Background: Cardiovascular diseases are the leading causes of morbidity and mortality worldwide. Cigarette smoking remains a global health epidemic with associated detrimental effects on the cardiovascular system. In this work, we investigated the effects of cigarette smoke exposure on cardiovascular system in an animal model. The study then evaluated the effects of antioxidants (AO), represented by pomegranate juice, on cigarette smoke induced cardiovascular injury. This study aims at evaluating the effect of pomegranate juice supplementation on the cardiovascular system of an experimental rat model of smoke exposure. Methods: Adult rats were divided into four different groups: Control, Cigarette smoking (CS), AO, and CS + AO. Cigarette smoke exposure was for 4 weeks (5 days of exposure/week) and AO group received pomegranate juice while other groups received placebo. Assessment of cardiovascular injury was documented by assessing different parameters of cardiovascular injury mediators including: (1) cardiac hypertrophy, (2) oxidative stress, (3) expression of inflammatory markers, (4) expression of Bradykinin receptor 1 (Bdkrb1), Bradykinin receptor 2 (Bdkrb2), and (5) altered expression of fibrotic/atherogenic markers [(Fibronectin (Fn1) and leptin receptor (ObR))]. Results: Data from this work demonstrated that cigarette smoke exposure induced cardiac hypertrophy, which was reduced upon administration of pomegranate in CS + AO group. Cigarette smoke exposure was associated with elevation in oxidative stress, significant increase in the expression of IL-1ß, TNFα, Fn1, and ObR in rat's aorta. In addition, an increase in aortic calcification was observed after 1 month of cigarette smoke exposure. Furthermore, cigarette smoke induced a significant up regulation in Bdkrb1 expression level. Finally, pomegranate supplementation exhibited cardiovascular protection assessed by the above findings and partly contributed to ameliorating cardiac hypertrophy in cigarette smoke exposed animals. Conclusion: Findings from this work showed that cigarette smoking exposure is associated with significant cardiovascular pathology such as cardiac hypertrophy, inflammation, pro-fibrotic, and atherogenic markers and aortic calcification in an animal model as assessed 1 month post exposure. Antioxidant supplementation prevented cardiac hypertrophy and attenuated indicators of atherosclerosis markers associated with cigarette smoke exposure.

Characterization of the Kallikrein-Kinin System Post Chemical Neuronal Injury: An In Vitro Biochemical and Neuroproteomics Assessment.

Traumatic Brain Injury (TBI) is the result of a mechanical impact on the brain provoking mild, moderate or severe symptoms. It is acknowledged that TBI leads to apoptotic and necrotic cell death; however, the exact mechanism by which brain trauma leads to neural injury is not fully elucidated. Some studies have highlighted the pivotal role of the Kallikrein-Kinin System (KKS) in brain trauma but the results are still controversial and inconclusive. In this study, we investigated both the expression and the role of Bradykinin 1 and 2 receptors (B1R and B2R), in mediating neuronal injury under chemical neurotoxicity paradigm in PC12 cell lines. The neuronal cell line PC12 was treated with the apoptotic drug Staurosporine (STS) to induce cell death. Intracellular calcium release was evaluated by Fluo 4-AM staining and showed that inhibition of the B2R prevented calcium release following STS treatment. Differential analyses utilizing immunofluorescence, Western blot and Real-time Polymerase Chain Reaction revealed an upregulation of both bradykinin receptors occurring at 3h and 12h post-STS treatment, but with a higher induction of B2R compared to B1R. This implies that STS-mediated apoptosis in PC12 cells is mainly conducted through B2R and partly via B1R. Finally, a neuroproteomics approach was conducted to find relevant proteins associated to STS and KKS in PC12 cells. Neuroproteomics results confirmed the presence of an inflammatory response leading to cell death during apoptosis-mediated STS treatment; however, a "survival" capacity was shown following inhibition of B2R coupled with STS treatment. Our data suggest that B2R is a key player in the inflammatory pathway following STS-mediated apoptosis in PC12 cells and its inhibition may represent a potential therapeutic tool in TBI.