Long-Term Variations of Monthly Mean Sea Level and its Relation to Atmospheric Presssure in the Mediterranean Sea

The monthly mean sea level at 19 stations and the monthly mean atmospheric pressure at 15 stations in the Mediterranean Sea are analysed to find the trend of the sea level and to identify the significant oscillations from the power spectral estimates. The results show that from the present data at Marseille, Trieste and Genova it is expected that the sea level tends to increase by 13 cm /100 years, which will affect the water budget of the area. The spectral analysis of the pressure could explain most of the oscillations in the sea level time series at 12, 6 and 4 months’ periods, except in the Adriatic Sea where the steric effect is expected to have an important contribution

MicroRNAs in Cardiac Hypertrophy

Like other organs, the heart undergoes normal adaptive remodeling, such as cardiac hypertrophy, with age. This remodeling, however, is intensified under stress and pathological conditions. Cardiac remodeling could be beneficial for a short period of time, to maintain a normal cardiac output in times of need; however, chronic cardiac hypertrophy may lead to heart failure and death. MicroRNAs (miRNAs) are known to have a role in the regulation of cardiac hypertrophy. This paper reviews recent advances in the field of miRNAs and cardiac hypertrophy, highlighting the latest findings for targeted genes and involved signaling pathways. By targeting pro-hypertrophic genes and signaling pathways, some of these miRNAs alleviate cardiac hypertrophy, while others enhance it. Therefore, miRNAs represent very promising potential pharmacotherapeutic targets for the management and treatment of cardiac hypertrophy. - 2019 by the authors. Licensee MDPI, Basel, Switzerland

7-O-methylpunctatin, a novel homoisoflavonoid, inhibits phenotypic switch of human arteriolar smooth muscle cells

Remodeling of arterioles is a pivotal event in the manifestation of many inflammation-based cardio-vasculopathologies, such as hypertension. During these remodeling events, vascular smooth muscle cells (VSMCs) switch from a contractile to a synthetic phenotype. The latter is characterized by increased proliferation, migration, and invasion. Compounds with anti-inflammatory actions have been successful in attenuating this phenotypic switch. While the vast majority of studies investigating phenotypic modulation were undertaken in VSMCs isolated from large vessels, little is known about the effect of such compounds on phenotypic switch in VSMCs of microvessels (microVSMCs). We have recently characterized a novel homoisoflavonoid that we called 7-O-methylpunctatin (MP). In this study, we show that MP decreased FBS-induced cell proliferation, migration, invasion, and adhesion. MP also attenuated adhesion of THP-1 monocytes to microVSMCs, abolished FBS-induced expression of MMP-2, MMP-9, and NF-?B, as well as reduced activation of ERK1/2 and FAK. Furthermore, MP-treated VSMCs showed an increase in early (myocardin, SM-22?, SM-?) and mid-term (calponin and caldesmon) differentiation markers and a decrease in osteopontin, a protein highly expressed in synthetic VSMCs. MP also reduced transcription of cyclin D1, CDK4 but increased protein levels of p21 and p27. Taken together, these results corroborate an anti-inflammatory action of MP on human microVSMCs. Therefore, by inhibiting the synthetic phenotype of microVSMCs, MP may be a promising modulator for inflammation-induced arteriolar pathophysiology. - 2019 by the authors. Licensee MDPI, Basel, Switzerland.Funding: This work was supported by the American University of Beirut (Grant # MPP 320133 to A.E.), University of Petra (Grant #: 5/4/2019) to A.B., E.B., and A.E., and the National Council for Scientific Research (CNRS) to M.F.Scopu

Unmasking the interplay between mTOR and Nox4: novel insights into the mechanism connecting diabetes and cancer

Cancer was recently annexed to diabetic complications. Furthermore, recent studies suggest that cancer can increase the risk of diabetes. Consequently, diabetes and cancer share many risk factors, but the cellular and molecular pathways correlating diabetes and colon and rectal cancer (CRC) remain far from understood. In this study, we assess the effect of hyperglycemia on cancer cell aggressiveness in human colon epithelial adenocarcinoma cells in vitro and in an experimental animal model of CRC. Our results show that Nox (NADPH oxidase enzyme) 4-induced reactive oxygen species (ROS) production is deregulated in both diabetes and CRC. This is paralleled by inactivation of the AMPK and activation of the mammalian target of rapamycin (mTOR) C1 signaling pathways, resulting in 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) accumulation, induction of DNA damage, and exacerbation of cancer cell aggressiveness, thus contributing to the genomic instability and predisposition to increased tumorigenesis in the diabetic milieu. Pharmacologic activation of AMPK, inhibition of mTORC1, or blockade of Nox4 reduce ROS production, restore the homeostatic signaling of 8-oxoguanine DNA glycosylase/8-oxodG, and lessen the progression of CRC malignancy in a diabetic milieu. Taken together, our results identify the AMPK/mTORC1/Nox4 signaling axis as a molecular switch correlating diabetes and CRC. Modulating this pathway may be a strategic target of therapeutic potential aimed at reversing or slowing the progression of CRC in patients with or without diabetes.-Mroueh, F. M., Noureldein, M., Zeidan, Y. H., Boutary, S., Irani, S. A. M., Eid, S., Haddad, M., Barakat, R., Harb, F., Costantine, J., Kanj, R., Sauleau, E.-A., Ouhtit, A., Azar, S. T., Eid, A. H., Eid, A. A. Unmasking the interplay between mTOR and Nox4: novel insights into the mechanism connecting diabetes and cancer.Scopu

Mobile health apps use among Jordanian outpatients: A descriptive study

Our purpose in this descriptive cross-sectional study was to examine the prevalence of mobile health (mHealth) apps use, factors associated with downloading mHealth apps, and to describe characteristics of mHealth apps use among Jordanian patients in government-sponsored outpatient clinics. A total of 182 (41.6%) of the 438 outpatients who completed questionnaires downloaded mHealth apps. Common reasons for downloading mHealth apps included tracking physical activity, losing weight, learning exercises, as well as monitoring, and controlling diet. More than two thirds of the users (70%) stopped using the apps they downloaded due to loss of interest, lack of anticipated support, too time consuming, or better apps available. The most common personal reasons for never downloading mHealth apps were lack of interest, in good health, and the most common technical reasons included a limited data plan, lack of trust, cost, and complexity of the apps. We also found that gender, age, weight, and educational level influenced the decision whether to download mHealth apps or not. We have shown the potential in mHealth apps use among Jordanian patients is promising, and health care systems must adopt this technology as well as work through population needs and preferences to supply it

Naturally-Occurring Bioactives in Oral Cancer: Preclinical and Clinical Studies, Bottlenecks and Future Directions

Oral cancer (OC) is the eighth most common cancer, particularly prevalent in developing countries. Current treatment includes a multidisciplinary approach, involving chemo, radio, and immunotherapy and surgery, which depends on cancer stage and location. As a result of the side effects of currently available drugs, there has been an increasing interest in the search for naturally-occurring bioactives for treating all types of cancer, including OC. Thus, this comprehensive review aims to give a holistic view on OC incidence and impact, while highlights the preclinical and clinical studies related to the use of medicinal plants for OC prevention and the recent developments in bioactive synthetic analogs towards OC management. Chemoprophylactic therapies connect the use of natural and/or synthetic molecules to suppress, inhibit or revert the transformation of oral epithelial dysplasia (DOK) into oral squamous cell carcinoma (OSCC). Novel searches have underlined the promising role of plant extracts and phytochemical compounds, such as curcumin, green tea extract, resveratrol, isothiocyanates, lycopene or genistein against this malignancy. However, poor bioavailability and lack of in vivo and clinical studies and complex pharmacokinetic profiles limit their huge potential of application. However, recent nanotechnological and related advances have shown to be promising in improving the bioavailability, absorption and efficacy of such compounds.Scopu

Novel therapeutic strategies for spinal osteosarcomas

At the dawn of the third millennium, cancer has become the bane of twenty-first century man, and remains a predominant public health burden, affecting welfare and life expectancy globally. Spinal osteogenic sarcoma, a primary spinal malignant tumor, is a rare and challenging neoplastic disease to treat. After the conventional therapeutic modalities of chemotherapy, radiation and surgery have been exhausted, there is currently no available alternative therapy in managing cases of spinal osteosarcoma. The defining signatures of tumor survival are characterised by cancer cell ability to stonewall immunogenic attrition and apoptosis by various means. Some of these biomarkers, namely immune-checkpoints, have recently been exploited as druggable targets in osteosarcoma and many other different cancers. These promising strides made by the use of reinvigorated immunotherapeutic approaches may lead to significant reduction in spinal osteosarcoma disease burden and corresponding reciprocity in increase of survival rates. In this review, we provide the background to spinal osteosarcoma, and proceed to elaborate on contribution of the complex ecology within tumor microenvironment giving arise to cancerous immune escape, which is currently receiving considerable attention. We follow this section on the tumor microenvironment by a brief history of cancer immunity. Also, we draw on the current knowledge of treatment gained from incidences of osteosarcoma at other locations of the skeleton (long bones of the extremities in close proximity to the metaphyseal growth plates) to make a case for application of immunity-based tools, such as immune-checkpoint inhibitors and vaccines, and draw attention to adverse upshots of immune-checkpoint blockers as well. Finally, we describe the novel biotechnique of CRISPR/Cas9 that will assist in treatment approaches for personalized medication.This work is funded by a grant (MPP 320133) from the American University of Beirut to Dr. Ali H. Eid

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Evaluation of Apoptotic, Antiproliferative, and Antimigratory Activity of Origanum syriacum against Metastatic Colon Cancer Cells

The effect of an ethanolic extract of fresh leaves of Origanum syriacum (OSEE) on the proliferative, apoptotic, and migratory capacities of LoVo and SW620 colon cancer cells was investigated. OSEE showed a concentration-dependent apoptotic and antiproliferative effect on LoVo and SW620 cells at 500 μg mL−1 or higher after 48 h of exposure. Additionally, OSEE inhibited the migration of both LoVo and SW620 cells by decreasing (50–75%) wound-healing capacity at 500 and 1,000 μg mL−1. The results suggest that OSEE may have potential anticarcinogenic activity in metastatic colon cancer cells through the dual effect of inhibiting cell proliferation and migration and induction of apoptosis.Scopu

Combined epidural-general anesthesia (CEGA) in patients undergoing pancreatic surgery: comparison between bupivacaine 0.125% And 0.25%

Assist Prof., Anesthesia Department, Liver Institute, Mounofia University Associat.Prof.,Anaesthesia, King Khaled University Hospital (KKUH), Riyadh Prof. Anesthesia, Head of department of Anesth&ICU (KKUH), King Saud University Assist. Prof., Head of Hepatobiliary Unit, KKUH, Riyadh, KSABackground: Major abdominal surgery results in homodynamic instability mainly due to endogenous prostacyclin release, bleeding, major intercompartemental fluid shift and the hormonal surgical response. This study compared the effects of low thoracic epidural anesthesia with 0.125% and 0.25% bupivacaine on haemodynamic variables, sevoflurane requirements, and stress hormone responses during pancreatic surgery under combined epidural-general anaesthesia (CEGA). Materials and Methods: Forty patients undergoing different pancreatic surgery were randomly allocated into two equal groups to receive 10 ml of either isobaric bupivacaine 0.125% (group I) or 0.25% (group II) by low thoracic epidural with sevoflurane general anaesthesia. Sevoflurane was adjusted to achieve a target bispectral index (BIS) of 40–60. Measurements included the inspired (FISEVO) and the end-tidal sevoflurane concentrations (E'SEVO), blood pressure (BP) and heart rate (HR) before surgery and every 5 min during surgery for 2 h, and stress hormones. Plasma samples for stress response evaluation were taken before and 1 and 2 h after the start of surgery for measurements of epinephrine, and cortisol. Results: During surgery, both groups were similar for HR, BP and BIS, but FISEVO and E'SEVO were significantly higher and more fluctuated with bupivacaine 0.125% than with 0.25%. Moreover, the total amount of propofol used for induction of general anesthesia and the total fentanyl used during anesthesia were significantly low in 0.25% bupivacaine group. Intraoperative requirements of ephedrine were higher in 0.25% bupivacaine group. Intraoperative blood loss and fluid requirements were significantly increase in 0.125% group. Plasma concentrations of epinephrine and cortisol were found to be higher with bupivacaine 0.125% as compared with 0.25%. Conclusion: Combined thoracic epidural-general anesthesia (CEGA) for pancreatic surgery, with 0.25% bupivacaine significantly reduces sevoflurane requirements, blood loss and fluid requirements. In addition, bupivacaine 0.25% suppressed the stress hormone responses better than 0.125% did. However this was on the expenses of more ephedrine requirements