Investigation of community pharmacists' knowledge and attitudes of pharmacogenomics testing: implication for improved pharmacogenomic testing practice.

BACKGROUND: Community pharmacists must be well-equipped to advance pharmacogenomics services. Nevertheless, limited data is available regarding pharmacists' knowledge and attitudes toward pharmacogenomics testing. The present study aimed to evaluate community pharmacists' knowledge and attitudes toward pharmacogenomics testing in the UAE. METHODS: In this cross-sectional study, a validated, online, self-administered survey, was randomly distributed to community pharmacists across the United Arab Emirates (UAE). RESULTS: The participants demonstrated poor knowledge about pharmacogenomic testing (median score < 8). Having 10-29 (Adjusted odds ration [AOR]: 0.038; 95% CI: 0.01-0.146, p = 0.001) and 30-49 (AOR: 0.097; 95% CI: 0.04-0.237, p = 0.001) patients per day was associated with poorer knowledge. Also, receiving 10-29 (AOR: 0.046; 95% CI: 0.005-0.401, p = 0.005), 30-49 (AOR: 0.025; 95% CI: 0.003-0.211, p = 0.001), and > 50 (AOR: 0.049; 95% CI: 0.005-0.458, p = 0.008) prescriptions decreased the odds of having good knowledge. Around half (43.9%) of the participants did not show a positive attitude toward pharmacogenomic testing (median score < 11). Having 30-49 patients per day (AOR: 5.351; 95% CI: 2.414-11.860, p = 0.001) increased the odds of good knowledge while receiving 10-29 (AOR: 0.133; 95% CI: 0.056-0.315, p = 0.001) and 30-49 (AOR: 0.111; 95% CI: 0.049-0.252, p = 0.001) prescriptions a day were associated with decreased odds of positive attitude toward the pharmacogenomics testing. CONCLUSIONS: The findings indicate a lack of knowledge and less-than-ideal attitudes among community pharmacists regarding pharmacogenomics testing. Enhanced efforts focused on educational initiatives and training activities related to pharmacogenomics testing is needed. Additionally, reducing workload can facilitate better knowledge acquisition and help mitigate unfavorable attitudes.

The flavonoid luteolin reduces mutant huntingtin aggregation and cytotoxicity in huntingtin-mutated neuroblastoma cells.

Background: Huntington's disease is an inherited progressive neurodegenerative disorder caused by an expansion of the polyglutamine tract leading to malformation and aggregation of the mutant huntingtin protein in the cell cytoplasm and nucleus of affected brain regions. The development of neuroprotective agents from plants has received considerable research attention. Objective: Our study aims to investigate the neuroprotective effects of luteolin and the mechanisms that underline its potential mediated protection in the mutant htt neuroblastoma cells. Methods: The mutant htt neuroblastoma cells were transfected with 160Q, and the control wild-type neuroblastoma cells were transfected with 20Q htt for 24 h and later treated with luteolin. Cell viability was determined by MTT and PI staining in both groups, while western blotting was used to evaluate caspase 3 protein expression. Aggregation formation was assessed via immunofluorescence microscopy. Also, western blotting was utilized to measure the protein expression of mutant htt aggregated and soluble protein, Nrf2 and HO-1. The impact of Nrf2 on luteolin-treated neuroblastoma cells was assessed using small interfering RNAs. Results: Our study reports that luteolin can protect cultured cells from mutant huntingtin cytotoxicity, evidenced by increased viability and decreased apoptosis. Also, luteolin reduced the accumulation of soluble and insoluble mutant huntingtin aggregates in mutant htt neuroblastoma cells transfected with 160Q compared to the control wild-type. The mutant htt aggregate reduction mediated by luteolin appeared to be independent of the Nrf2 -HO-1 antioxidant pathway. Conclusion: Luteolin presents a new potential therapeutic and protective agent for the treatment and decreasing the cytotoxicity in neurodegenerative diseases such as Huntington's disease.

Assessment of Knowledge and attitude towards Stroke among the UAE population during the COVID-19 pandemic: A cross-sectional study.

Background: Despite significant advancements in healthcare, the burden of stroke continues to rise in the developed world, especially during the COVID-19 pandemic. Association between COVID-19 infection and stroke is well established. Factors identified for the delay in presentation and management include a lack of awareness regarding stroke. We aimed to assess the general public knowledge and attitudes on stroke and stroke risk factors in the United Arab Emirates during the COVID-19 pandemic. Methods: A cross-sectional study was conducted between September 2021 and January 2022 among adults≥ 18 years old. Participants completed a self-administered questionnaire on sociodemographic characteristics and stroke knowledge and attitudes. Knowledge and attitude scores were calculated based on the number of correct responses. Linear regression analysis was performed to determine the factors related to knowledge and attitude towards stroke. Results: Of the 500 respondents, 69.4% were females, 53.4% were aged between 18 and 25, and nearly half were students (48.4%). The mean knowledge score was 13.66 (range 2-24). Hypertension (69%), smoking (63.2%), stress (56.4%) obesity/overweight (54.4%), and heart disease (53.6%) were identified as risk factors. Overall, the knowledge of signs/symptoms was suboptimal. The mean attitude score was 4.41 (range, 1-6); 70.2% would call an ambulance if someone were having a stroke. A monthly income of 11,000-50,000 AED and being a student were associated with positive knowledge. Being a non-health worker and lacking access to electronic media sources were associated with worse attitudes. Conclusion: Overall, we identified poor knowledge and suboptimal attitudes toward stroke. These findings reflect the need for effective public health approaches to improve stroke awareness, knowledge, and attitudes for effective prevention in the community. Presently, this is of utmost necessity, given the increased occurrence of stroke and its severity among COVID-19 patients.

DNA and protein methyltransferases inhibition by adenosine dialdehyde reduces the proliferation and migration of breast and lung cancer cells by downregulating autophagy.

Protein and DNA methylation is involved in various biological functions such as signal transmission, DNA repair, and gene expression. Abnormal regulation of methyltransferases has been linked to multiple types of cancer, but its link to autophagy and carcinogenesis in breast and lung cancer is not fully understood. We utilized UALCAN, a web tool, to investigate breast and lung cancer database from The Cancer Genome Atlas. We found that 17 methyltransferases are upregulated in breast and/or lung cancer. We investigated the effect of methylation inhibition on two breast cancer cell lines (MDA-MB-231 and MCF-7) and two lung cancer cell lines (H292 and A549) by treating them with the indirect methyltransferase inhibitor adenosine dialdehyde (AdOx). We found that the migration ability of all cell lines was decreased, and the growth rate of MDA-MB-231, MCF-7 and H292 was also decreased after AdOx treatment. These results were correlated with an inhibition of the autophagy in MDA-MB-231, MCF-7 and H292 cell lines, since AdOx treatment induced a decreased expression of ATG7, a reduced ratio LC3-II/LC3-I and an increased p62 level. These findings suggest that inhibiting cells' methylation ability could be a potential target for breast and lung cancer treatment.

Epidemiological, Clinical, and Histopathological Features of Salivary Gland Tumors among 150 Sudanese Patients: 10 Years' Experience.

Background and Objectives: Salivary gland tumors (SGTs) are serious challenges to pathologists. Herein, we aimed to assess epidemiological and histopathological characteristics of SGTs among Sudanese patients. Materials and Methods: This retrospective descriptive study was undertaken at The pathology department in Khartoum State between 2008 and 2018. Patient records, histopathological reports, and slides were retrieved; and re-examined by two histopathologists. Diagnoses were reclassified according to the 2017 WHO classification of SGTs. Results: Overall, 150 cases of Sudanese patients with SGT were included (90 [60%] males and 60 [40%] females). Among these, 105 were benign (70%) and 45 were malignant (30%). The parotid glands were the most common site for both benign and malignant tumors (77/150; 51%: 59 benign (76.6%) and 18 malignant [23.4%]). The next common site was the submandibular gland (54 [36%]: 38 benign [70.3%] and 16 malignant [29.7%]), followed by minor salivary glands (19 [12.7%]: 8 benign and 11 malignant [57.9%]). Benign gland entities included pleomorphic adenoma (88/105; 83.7%), oncocytoma (5/105; 4.8%), myoepithelioma (4/105; 3.8%), Whartin tumors (3/105; 2.9%), basal cell adenoma (3/105; 2.9%), and sialolipoma (2/105; 1.9%). Malignant gland entities included adenoid cystic carcinoma (12; 26.7%), mucoepidermoid carcinoma (10; 22,2%), acinic cell carcinoma (6; 13.3%), poorly differentiated carcinoma (4; 8.9%), adenocarcinoma NOS (not otherwise specified) (4; 8.9%), basal cell adenocarcinoma (3; 6.7%), carcinoma ex pleomorphic adenoma (3; 6.7%), polymorphous adenocarcinoma (2; 4.4%), salivary duct carcinoma (1; 2.2%), and epithelial-myoepithelial carcinoma (2.2%). Conclusions: SGTs shared several epidemiological and histopathological features, exhibiting high incidence in the parotid and submandibular glands, lower prevalence in minor glands, and greater male predominance.

Mini review: The clinical avenues of combined hydralazine-nitrate in subjects with heart failure with reduced ejection fraction

Background: Combined hydralazine-nitrate has an avenue in the management of subjects with heart failure with reduced ejection fraction. Exploring the pharmacotherapy in this context will facilitate the clinical utility of the combined therapy. Objective: The main objective of this mini-review was to evaluate the role of combined hydralazine-nitrate in subjects with heart failure with reduced ejection fraction. Methods: We conducted a literature search on Google scholar, MEDLINE, and PubMed to identify the randomized clinical trials on combined hydralazine-nitrate, in subjects with heart failure with reduced ejection fraction. 2760 articles were returned initially out of which 10 trials were conforming to the inclusion criteria. However, three trails were the focus for the current mini-review. Key findings: The current mini-review lends support to the use of combined hydralazine-nitrate in subjects with heart failure with reduced ejection fraction (HFrEF). The combination may offer subjects who have remained symptomatic with HFrEF despite optimum dosing of standard therapy. Black subjects with HFrEF have proved to benefit from combined hydralazine-nitrate. The combination (e.g. small dose of hydralazine 12.5-25 mg twice a day and isosorbide mononitrate 10 mg twice a day) may provide alternative clinical utility in subjects with contraindications (renal artery stenosis, creatinine clearance less than 30 mL/minute, sustained hyperkalemia) to the use of ACEinh, ARBs, and/or ARNI. Subjects with HFrEF on combined hydralazine-nitrate should be assessed and monitored for systolic BP (keep >120 mmHg) and subjects with chronic kidney disease (keep eGFR > 30 mL/min/1.73 m2). Hydralazine-nitrate was inferior to ACEinh (higher all-cause mortality and cardiovascular mortality. Conclusion: The current mini- review provides the key points to support the use of hydralazine-nitrate in subjects with heart failure with reduced ejection fraction. (AU)

Discovery of Lactomodulin, a Unique Microbiome-Derived Peptide That Exhibits Dual Anti-Inflammatory and Antimicrobial Activity against Multidrug-Resistant Pathogens.

The human body is a superorganism that harbors trillions of microbes, most of which inhabit the gut. To colonize our bodies, these microbes have evolved strategies to regulate the immune system and maintain intestinal immune homeostasis by secreting chemical mediators. There is much interest in deciphering these chemicals and furthering their development as novel therapeutics. In this work, we present a combined experimental and computational approach to identifying functional immunomodulatory molecules from the gut microbiome. Based on this approach, we report the discovery of lactomodulin, a unique peptide from Lactobacillus rhamnosus that exhibits dual anti-inflammatory and antibiotic activities and minimal cytotoxicity in human cell lines. Lactomodulin reduces several secreted proinflammatory cytokines, including IL-8, IL-6, IL-1ß, and TNF-α. As an antibiotic, lactomodulin is effective against a range of human pathogens, and is most potent against antibiotic-resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE). The multifunctional activity of lactomodulin affirms that the microbiome encodes evolved functional molecules with promising therapeutic potential.

Randomized Clinical Trials on the Efficacy and Safety of Tocilizumab in Subjects with Rheumatoid Arthritis: A Systematic Review.

BACKGROUND: The current therapy of Rheumatoid Arthritis (RA) is confronted with many challenges such as inadequate response, infection, and treatment failure. AIM AND OBJECTIVE: The main objective was to assess the efficacy and safety of tocilizumab (TCZ) in subjects with RA using the available evidence from published randomized controlled trials. METHODS: The current systematic review was performed on nine randomized controlled trials from 2002 to 2016 for TCZ in subjects with rheumatoid arthritis. The primary outcomes were the clinical improvement in American College Rheumatology 20% (ACR20) or Disease Activity Score remission (DAS28), in addition to other outcomes such as ACR50 and ACR70 in the intention-to-treat population. RESULTS: We have conducted a systematic review on nine randomized controlled trials, with 4129 [100%] enrolled, of which 3248 [78.7%] were on the intention-to-treat. 2147 (66.1%) were treated with TCZ and 1101 (33.9%) have had received placebo or methotrexate or other conventional Disease- Modifying Anti-rheumatic Drugs (cDMARD) or biologic Disease-Modifying Anti-rheumatic Drugs (bDMARDs). In subjects taking TCZ with or without concomitant methotrexate, compared to placebo, subjects treated with TCZ 4 or 8 mg/kg were substantially and statistically significantly more likely than placebo or methotrexate to achieve the ACR20 and/or DAS28. There were no statistically significant differences in serious adverse events such as serious infection; however, subjects on TCZ were more likely to have increased lipid profiles. CONCLUSION: TCZ mono-therapy or in combination with methotrexate is valuable in diminishing rheumatoid arthritis disease activity and improving disability. Treatment with TCZ was associated with a significant surge in cholesterol levels but no serious adverse effects. Randomized clinical trials with safety as the primary outcome are warranted to report these safety issues.

A Systematic Review of Randomized Clinical Trials on the Efficacy and Safety of Pitavastatin.

BACKGROUND: A subpopulation of statin users such as subjects with chronic kidney disease (CKD), Human Immune virus (HIV), acute coronary syndrome (ACS), revascularization, metabolic syndrome, and/or diabetes may particularly benefit from pitavastatin pharmacotherapy. AIM: The current systematic review aimed systematically to evaluate the effect of pitavastatin on primary cardiac events in subjects receiving pitavastatin in comparison to the other four statin members. METHODS: We conducted a systematic review on phases III and IV of randomized controlled trials (RCT-s, 11 trials) for subjects with primary cardiac events who received pitavastatin. Subjects diagnosed with any type of dyslipidemia (population 4804) and received pitavastatin (interventions) versus comparator (comparison) with the primary efficacy endpoint of minimization of LDL-C and non- HDL-C, had an increase in HDL-C and/or reduction in major adverse cardiac events (MACE, cardiovascular death, myocardial infarction (fatal/nonfatal), and stroke (fatal/nonfatal) and/or their composite (outcomes). The secondary safety endpoint was the development of any adverse effects. RESULTS: In the included trials (11), participants (4804) were randomized for pitavastatin or its comparators such as atorvastatin, pravastatin, rosuvastatin, simvastatin and followed up for 12 to 52 weeks. In terms of the primary outcome (reduction in LDL-C), pitavastatin 4 mg was superior to pravastatin 40 mg in three trials, while the 2 mg pitavastatin was comparable to atorvastatin 10 mg in four trials and simvastatin 20 and 40 mg in two 2 trials. However, rosuvastatin 2.5 mg was superior to pitavastatin 2 mg in two trials. Pitavastatin increased HDL-C and reduced non-HDL-C in eleven trials. Regarding the safety profile, pitavastatin has proved to be tolerated and safe. CONCLUSION: The FDA-approved indications for pitavastatin included primary dyslipidemia and mixed dyslipidemia as a supplementary therapy to dietary changes to lower total cholesterol, LDL-C, apolipoprotein B (Apo B), triglycerides (TG), and enhance HDL-C. Pitavastatin might be suitable for subjects with diabetes, ACS (reduced revascularization), metabolic syndrome, CKD, HIV, and subjects with low levels of HDL-C. We highly recommend rational individualization for the selection of statin.

Association between visual impairment and sleep duration in college students: A study conducted in UAE and Lebanon.

Objective: To examine whether self-reported sleep duration and visual impairment were associated among College students. Participants: Students (n = 1002, age 17-35 years) from Lebanon and the United Arab Emirates. Methods: Students were asked to complete a validated questionnaire between October 2018 and May 2019. The questions were related to sociodemographics, lifestyle characteristics, visual impairment status, sleeping pattern, mobile-phone use and chronic conditions. Results: 18.3% of the respondents reported to suffer from visual impairment. Among them, 72.7% were females (p < .001), 65% admitted to frequently use mobile phones before sleeping (p < .001), 54.6% reported to sleep less than 7 h (p = .008) and 71.6% reported to suffer from sleep disturbances (p = .05). Visual impairment was associated with poor sleep quality (p < .001), mobile phone use before sleeping (p < .01) and daily stress (p < .05). Conclusion: Visual impairment in college students is associated with short sleep duration, mobile phone use before sleeping and stress level.

Scoping Review of Six Retrospective Studies: Risk Factors Associated With the Case Fatality Rate of People Infected With Coronavirus (COVID-19).

Background: It would be rational to describe the pattern of the clinical characteristics of the survivors and the nonsurvivors during the critical intensive-infection era of coronavirus disease 2019 (COVID-19). The explicit objective of the current scoping review was to delineate the predictive risk factors associated with case fatality rate (CFR). Methods: Six retrospective studies of subjects infected with COVID-19 published between December 1, 2020, and March 30, 2020, describing nonsurvivors in Wuhan/Hubei, China, were identified. Results: There were 1769 subjects with a mean age of 52 years, and 65.9% were male. The highest comorbidity reported was cardiovascular diseases at 22.2% (393/1769). The overall number of cases admitted to the intensive care unit was 228 (12.9%). The reported overall CFR was 7.7% (136/1769), with the highest at 28.2% (54/191), and the lowest at 1.4% (15/1099). The mean duration of onset until death for nonsurvivors was 15.3 days. Conclusion: We have found that older age, male gender, the longer duration from onset till death (days), development of acute respiratory distress syndrome/shock, preexisting diabetes, and preexisting cardiovascular diseases were the major risk factors associated with high CFR.

Mini-Review on the Efficacy and Safety of Pitavastatin: "The Novel Seventh Statin Gaining Momentum".

Background: Recently, a plethora of events have affected the statin arena such as muscle-induced myalgia, myopathy, myositis, rare rhabdomyolysis, and new-onset diabetes. The latest statin pitavastatin has emerged with descent stamina (optimum efficacy and improved safety). Objective: The objective of the current review is to explore the pros and cons of pitavastatin as a novel second-generation statin in terms of efficacy and safety that delineate its clinical utility. Methods: The review was conducted via EBSCO hosted Medline search (AL Ain University, UAE subscription) for relevant English written literature articles containing "pitavastatin" as the primary search term "pitavastatin and safety;" "pitavastatin and efficacy" and "pitavastatin and safety and randomized clinical trials;" and "pitavastatin and efficacy and randomized clinical trials." Results: The number of articles containing the word "pitavastatin" as the primary search term used was (n = 901). The next retrieves MeSH term was "pitavastatin and safety" (n = 99) and then "pitavastatin and efficacy" (n = 132). Furthermore, narrowing down the search by adding study design terms revealed: "pitavastatin and safety and randomized clinical trials," (n = 10) and "pitavastatin and efficacy and randomized clinical trials" (n = 13). Combining the two main searches (safety and efficacy) has yielded 23 items, of which 15 articles were satisfying the current mini-review criteria. The prominent efficacy of pitavastatin was depicted by the increase in high-dense lipoprotein cholesterol and a decrease in low-dense lipoprotein cholesterol as illustrated by the clinical trials in the results and discussions section. The safety was enlightened with a very low propensity to cause new-onset diabetes and a low tendency for statin-induced muscular adverse events. Conclusion: Pitavastatin might be suitable for patients with the acute coronary syndrome (ACS), metabolic syndrome, and patients with diabetes. We highly recommend rational individualization for the selection of statin, especially in patients with diabetes and/or with ACS.

Metabolic syndrome; Definition, Pathogenesis, Elements, and the Effects of medicinal plants on it's elements.

Introduction: Metabolic syndrome (MetS) is a cluster of metabolic risk factors that include central obesity, hypertension, insulin resistance, and atherogenic dyslipidemia and is strongly associated with a greater risk for developing cardiovascular disease and type 2 diabetes mellitus. Methods: A literature search was conducted using the words metabolic syndrome, definition and pathogenesis in Scopus, and PubMed. The search also extended to cover medicinal plants and their role as a potential treatment of the metabolic syndrome. The search based on studies published in the English language from 1st of January 2000 to 30th of May 2021. The abstracts and the articles were then screened. Articles were scanned and read; further relevant references in the reference lists are also included. Results: Both lifestyle factors and genetic factors are involved in the pathogenesis of the metabolic syndrome. Recently, MetS have gained significant attention due to the high prevalence of obesity worldwide. Diagnosis of patients with MetS is important to improve the outcomes of the disease by employing lifestyle and risk factors modifications. Currently, there is a rising interest in medicinal plants and their extracts because the medicinal plants have minimal side effects. Here we review the history, definitions, pathogenesis, management of metabolic syndrome and summarize the beneficial effects of some medicinal plants and their extracts on MetS. Conclusion: Further research and clinical studies are needed to establish whether medicinal plants can be safely given as potential therapy for metabolic syndrome and whether this can be beneficial in low resources setting countries.

Correction to: Metabolic syndrome; Definition, Pathogenesis, Elements, and the Effects of medicinal plants on it's elements.

[This corrects the article DOI: 10.1007/s40200-021-00965-2.].

Risk factors associated with lower extremity amputation in Sudanese individuals with diabetes: The need for improvement in primary health care system.

BACKGROUND: Lower extremity amputation (LEA) in individuals with diabetes is a serious health issue with a considerable physical and social burden. The aim of this study was to assess the prevalence and risk factors associated with LEA in diabetic foot ulcer (DFU) patients. MATERIALS AND METHODS: This was a cross-sectional health facility-based study that recruited 315 diabetes individuals with foot ulcers from the diabetes center in Khartoum, Sudan. Direct interviewing of subjects was used to obtain data, using a standardized validated questionnaire. Chi-square and logistic regression analysis were used in data analysis. RESULTS: 69.5% of the diabetic participants were aged 50 years old or more, and 71.1% were males. Most of the subjects (48.2%) were diabetics for a duration of >10 years, while more than one third (37.5%) of them were diabetic for 5-10 years. The majority (89.5%) had type 2 DM, while only 10.5% were type 1 DM. Two hundred forty-five patients had a left lower foot ulcer; 55.1% of the patients' ulcers were present in the toes, while 21.6% were in the foot sole. The overall prevalence of lower limb amputation was 17.1%. Individuals with diabetes patients with LEA had a higher incidence of hypertension (P = 0.000), retinopathy (P = 0.000), nephropathy (P = 0.002), ulcer size >2.5 cm (P = 0.000), and neuropathy (P = 0.000) through Chi-square analysis. Furthermore, logistic regression analysis showed that amputation was significantly associated with retinopathy (P = 0.000), size of ulcer (P = 0.000), and neuropathy (P = 0.016). CONCLUSION: The overall prevalence of LEA was 17.1%. The primary risks factors associated with amputation were presence of neuropathy and ulcer size >2.5 cm. Presence of retinopathy predispose diabetic individuals to amputation. Amputation is associated with disability and psychological problems; therefore, there is an urgent need for more improvement in preventative measures and primary health care system in low resource setting country like Sudan in order to decrease diabetes complications, especially patient's education about diabetes management by primary care physicians.

Knowledge, Attitudes, and Practices Concerning Breast Cancer and Self Examination Among Females in UAE.

Breast cancer (BC) is one of the most prevalent cancers and the leading cause of cancer related deaths among women worldwide with a steadily increasing global annual incidence. This study aims is to evaluate the knowledge, attitude, and practice of females in the UAE toward BC and Breast Self-Examination practice in the seven Emirates. This was a face-to-face questionnaire-based study using CAM (Breast Cancer Awareness Measure) conducted over 3 months (from March to June 2019) on a random sample of females across the UAE. Of the 400 females who filled the questionnaire, 112 (28%) did the CBE at least once, and 184 (46%) practice BSE. Only 33% of participants were aware of the incidence of the BC in the UAE and those females were more likely to practice BSE (P < 0.05). In contrast, the majority showed a high awareness level in identifying cancer as a curable (91.5%) and non-transmittable (87%) disease that can be diagnosed at its earlier stages (93%). Only 11% of the participants identified weight reduction as a way to prevent BC. Knowledge of breast cancer sign/symptoms were good, as 41-87% of respondents were able to identify at least a single sign/symptom. The lack of awareness of BC among females in the UAE is of concern as it leads to low practices of screening and early detection, which ultimately will result in increased morbidity, mortality, and treatment costs. Further initiatives should be taken to increase practice, knowledge and awareness on early detection and screening for BC in the UAE community.

Loss of vascular smooth muscle cell autophagy exacerbates angiotensin II-associated aortic remodeling.

OBJECTIVE: The pathophysiologic processes of abdominal aortic aneurysms (AAAs) and atherosclerosis often intersect. Given that anomalies in vascular smooth muscle cell (SMC) autophagy have been noted in models of atherosclerosis, we sought to evaluate the potential role that SMC autophagy may play in the initiation and progression of AAAs. METHODS: Studies were conducted in ATG7flx/flxSM22α-Cretg/+ (SMC ATG7 knockout [SMC-ATG7-KO]) and ATG7WT/WT; SM22α-Cretg/+ (SMC ATG7 wild-type [SMC-ATG7-WT]) littermates that were continuously infused with angiotensin II (Ang II; 1.5 mg/kg/d) for up to 12 weeks. Mortality, morbidity, hemodynamics, and aortic remodeling were documented. RESULTS: During the 12-week observation window, all of the Ang II-treated SMC-ATG-WT mice (n = 6) survived, whereas 10 of the 19 Ang II-treated SMC-ATG-KO mice had died by week 7 (log-rank test, P < .001). Mean arterial pressure (128.07 ± 3.4 mm Hg for Ang II-treated SMC-ATG-KO vs 138.5 ± 5.87 mm Hg for Ang II-treated SMC-ATG-WT mice) and diastolic arterial pressure (109.7 ± 2.55 mm Hg for Ang II-treated SMC-ATG7-KO vs 119.4 ± 2.12 mm Hg for Ang II-treated SMC-ATG7-WT mice) were significantly different between the two groups (P < .01). Cardiac rupture, myocardial infarct, end-organ damage, pleural effusion, and venous distention were noted in Ang II-treated SMC-ATG7-KO but not in Ang II-treated SMC-ATG7-WT mice. Although the suprarenal aortic diameters of the Ang II-treated SMC-ATG7-KO group demonstrated a trending increase (at week 4, 1.26 ± 0.06 mm [n = 14] for Ang II-treated SMC-ATG-KO mice vs 1.09 ± 0.02 mm [n = 5] for Ang II-treated SMC-ATG-WT mice; P < .05), only 2 of the 19 developed abdominal aortic dissections. CONCLUSIONS: Mice with SMC ATG7 deficiency that are chronically infused with Ang II do not tend to develop dissecting AAA but do exhibit adverse aortic remodeling and appreciable cardiac failure-associated mortality.

Fingerprint of long non-coding RNA regulated by cyclic mechanical stretch in human aortic smooth muscle cells: implications for hypertension.

Emerging evidence suggests that long non-coding RNAs (lncRNAs) represent a cellular hub coordinating various cellular processes that are critical in health and disease. Mechanical stress triggers changes in vascular smooth muscle cells (VSMCs) that in turn contribute to pathophysiological changes within the vasculature. We sought to evaluate the role that lncRNAs play in mechanical stretch-induced alterations of human aortic smooth muscle cells (HASMCs). RNA (lncRNA and mRNA) samples isolated from HASMCs that had been subjected to 10 or 20% elongation (1 Hz) for 24 h were profiled with the Arraystar Human LncRNA Microarray V3.0. LncRNA expression was quantified in parallel via qRT-PCR. Of the 30,586 human lncRNAs screened, 580 were differentially expressed (DE, P < 0.05) in stretched HASMCs. Amongst the 26,109 protein-coding transcripts evaluated, 25 of those DE were associated with 25 of the aforementioned DE lncRNAs (P < 0.05). Subsequent Kyoto Encyclopedia of Genes and Genomes analysis revealed that the DE mRNAs were largely associated with the tumor necrosis factor signaling pathway and inflammation. Gene Ontology analysis indicated that the DE mRNAs were associated with cell differentiation, stress response, and response to external stimuli. We describe the first transcriptome profile of stretch-induced changes in HASMCs and provide novel insights into the regulatory switches that may be fundamental in governing aberrant VSMC remodeling.

Endothelial-specific deletion of autophagy-related 7 (ATG7) attenuates arterial thrombosis in mice.

BACKGROUND: Thrombosis persists as a leading cause of morbidity and mortality. Given that endothelial cells (ECs) play a central role in regulating thrombosis, understanding the molecular endothelial cues that regulate susceptibility or resistance to thrombosis have important translational implications. Accordingly, we evaluated the role of endothelial autophagy in the development of thrombosis. METHODS: We generated mice in which the essential autophagy-related 7 (ATG7) gene was conditionally deleted from ECs (EC-ATG7-/- mice). Three in vivo models of thrombosis were used, and mechanistic studies were conducted with cultured human umbilical vein endothelial cells (HUVECs). RESULTS: We silenced ATG7 in HUVECs and observed >60% decreases in tumor necrosis factor (TNF)-α-induced tissue factor (TF) transcript levels, protein expression, and activity. TF mRNA levels in the carotid arteries of EC-ATG7-/- mice subjected to the prothrombotic stimulus FeCl3 were lower than those in the similarly treated wild-type (WT) littermate group. Compared with WT mice, EC-ATG7-/- mice exhibited prolonged time to carotid (2-fold greater) and mesenteric (1.3-fold greater) artery occlusion following FeCl3 injury. The thrombi generated in laser-injured cremasteric arterioles were smaller in EC-ATG7-/- mice compared with WT mice, and took 2.3-fold longer to appear. CONCLUSIONS: Taken together, these results provide definitive evidence that loss of endothelial ATG7 attenuates thrombosis and reduces the expression of TF. Our findings demonstrate that endothelial ATG7, and thus autophagy, is a critical and previously unrecognized target for modulating the susceptibility to thrombosis.

The putative role of autophagy in the pathogenesis of abdominal aortic aneurysms.

Abdominal aortic aneurysms (AAA) are a significant cause of worldwide mortality and morbidity. While the histopathological characteristics of AAA are well documented, the cellular and molecular mechanisms involved in the pathogenesis of AAA are not entirely understood. Autophagy is a highly conserved basal cellular process in eukaryotic cells that involves the turnover of organelles and proteins. It is also activated as an adaptive response to stressful conditions to promote cell survival. While autophagy typically promotes pro-survival processes, it can sometimes lead to cellular demise. Preclinical studies have revealed autophagy to be a protective mechanism in certain vascular diseases with several autophagy-related genes reported to be markedly upregulated in human aneurysmal tissue. The role autophagy plays in the pathogenesis of AAA, however, remains poorly defined. In this review, we discuss the putative role of autophagy in AAA by reviewing several in vitro and in vivo studies that address the functional significance of autophagy in cells that are involved in the pathophysiology of AAA, amongst which are macrophages, smooth muscle and endothelial cells.