Identification of Candidate Long Noncoding RNAs Associated with Left Ventricular Hypertrophy

Purpose

Long noncoding RNAs (lncRNAs) constitute an emerging group of noncoding RNAs, which regulate gene expression. Their role in cardiac disease is poorly known. Here, we investigated the association between lncRNAs and left ventricular hypertrophy.

Methods

Wild‐type and adenosine A2A receptor overexpressing mice (A2A‐Tg) were subjected to transverse aortic constriction (TAC) and expression of lncRNAs in the heart was investigated using genome‐wide microarrays and an analytical pipeline specifically developed for lncRNAs.

Results

Microarray analysis identified two lncRNAs up‐regulated and three down‐regulated in the hearts of A2A‐Tg mice subjected to TAC. Quantitative PCR showed that lncRNAs 2900055J20Rik and Gm14005 were decreased in A2A‐Tg mice (3.5‐ and 1.8‐fold, p < 0.01). We found from public microarray dataset that 2900055J20Rik and Gm14005 were increased in TAC mice compared to sham‐operated animals (1.8‐ and 1.4‐fold, after 28 days, p < 0.01). Interestingly, in this public dataset, cardioprotective drug JQ1 decreased 2900055J20Rik and Gm14005 expression by 2.2‐ and 1.6‐fold (p < 0.01).

Conclusions

First, we have shown that data on lncRNAs can be obtained from gene expression microarrays. Second, expression of lncRNAs 2900055J20Rik and Gm14005 is regulated after TAC and can be modulated by cardioprotective molecules. These observations motivate further investigation of the therapeutic value of lncRNAs in the heart.     

Sigmoid colon endometriotic mass: A rare cause of complete large bowel obstruction

Large bowel obstruction is a rare complication of gastrointestinal endometriosis. A 32-year-old female patient presented to the emergency department with complaints of diffuse abdominal pain and constipation for 10 days with progressive abdominal distention and vomiting. Plain abdominal x-ray showed grossly dilated large bowel up to the sigmoid colon with no gas in the rectum. Abdominal computed tomography revealed hugely dilated large bowel up to the sigmoid colon, with sigmoid soft tissue mass. Flexible sigmoidoscopy showed a non-ulcerating sigmoid mass, with complete obstruction of the sigmoid colon, which impeded the further advancement of the scope. She underwent exploratory laparotomy with provisional diagnosis of complete large bowel obstruction due to sigmoid tumor. Sigmiodectomy with end colostomy was performed. Histopathology revealed endometrial glands with stroma in muscularis properia of the sigmoid colon mass. Endometriosis should be considered in women of reproductive age presenting with symptoms of large bowel obstruction.Endometriosis is the presence of functional endometrial tissue outside the uterus, which affects up to 15% of childbearing age woman.1 It is an uncommon cause of large bowel obstruction.2 If large bowel obstruction occurs, it may be caused by luminal compression from a pelvic organ endometrioma, a fibrotic reaction resulting in stricture and adhesions, or swelling of endometriotic implants in the intestinal wall or a combination of these 3 mechanisms.3 Herein, a rare case of complete large bowel obstruction due to sigmoid colon endometriotic mass is presented in which the treatment was sigmoidectomy with end colostomy. A brief review of the literature pertaining to this condition is also presented. Our objective in presenting this case is to increase the awareness of physicians to the possibility of endometriosis as a differential diagnosis when assessing females of reproductive age who present with manifestations of intestinal obstruction.     

Clinical utility of dabigatran in United Arab Emirates: A pharmacovigilance study

Objectives:

To provide early data regarding clinical utility of dabigatran in Al-Ain, United Arab Emirates (UAE).

Methods:

This was an ethics approved retrospective cross sectional study. We retrieved a total of 76 patients who were using dabigatran from September to December 2014 in the Cardiology Clinic at Al-Ain Hospital, Al-Ain, UAE. The primary analysis was designed to test the frequency of bleeding events (rate) with dabigatran 75, 110, and 150 mg.

Results:

The mean age ± standard deviation of cohort was 67.9 ± 1.5 years (range; 29-98 years), composed of males (52.6%) with mean age of 66.3 ± 1.7 years, and females (47.4%) with mean age of 69.6 ± 1.1 years. The highest age group was those between 61-80 years (60.5%). Most comprised the age strata of ≤75 years (73.7%). The main indication for dabigatran use was atrial fibrillation. The rate of bleeding with dabigatran was 18/76 (23.7%), and melena was the leading cause of bleeding 8/76 (10.7%). The hospitalization rate was 67.1%, dabigatran withdrawal rate was 0.01%, and mortality rate was 6.5%. The cohort had exhibited incidences of minor bleeding with one fatal major bleeding, high co-morbidities, admission, and readmission, which was not directly linked to dabigatran. We did not identify any relation of death due to dabigatran.

Conclusion:

Dabigatran is a suitable alternative to warfarin obviating the need for repetitive international normalized ratio monitoring, however, it may need plasma drug monitoring.Atrial fibrillation (AF) is the most common cardiac arrhythmia that affects 1-1.5% of population worldwide.1 Atrial fibrillation prevalence increases with age, and rises from 0.7% in those between 55-59 years to 17.8% in those ≥85 years. Nearly 85% of patients with AF are aged >65 years old.2 The lifetime risk for the development of AF as demonstrated in the Framingham study was one in 4 for men and women aged ≥40 years,3 which pose certain concerns in countries with aging populations.4,5 In addition to this, hospitalization related to AF is alarmingly increasing.6 The risk of stroke in patients with AF is 5 folds, and systemic thromboembolism is 3 folds.7,8 Banerjee, et al9 has deployed stroke prevention score in patients with AF, however, the predictive value is of less magnitude. The European Society of Cardiology set estimation of stroke risk in patients with AF as per CHA₂DS₂-VASc score to determine the recommendation for initiating an oral anticoagulant,10 whereas in patients with CHA₂DS₂-VASc ≥2, HAS-BLED score can be used to assess the risk of bleeding, and commencement of anticoagulant.11Warfarin (vitamin K antagonist [VKA]) has proven efficacy in reducing the risk of stroke in patients with AF, however, it poses high bleeding incidences, emergency hospitalizations, unpredictable therapeutic effect, and multiple international normalized ratio (INR) tests leading to many limitations in its clinical utility.12 Novel oral anticoagulants (NOACs) are proved as effective anticoagulants in prevention of stroke in patients with AF. Novel oral anticoagulants were preferred in non-valvular AF, and do not require coagulation monitoring, however, strict adherence to approved indication is highly warranted.13 Dabigatran (Pradaxa^®), a competitive inhibitor of thrombin was approved in October 2010 by the United States of America Food and Drug Administration to reduce the risk of stroke, and systemic embolism in patients with non-valvular AF.14 A systematic review incorporated 6 economic reviews from diverse healthcare systems (USA, Canada, and United Kingdom) utilizing different economic models. It has suggested the benefit of dabigatran in patients with high-risk of stroke, high-risk of intra-cerebral hemorrhage, or suboptimal use of warfarin. The review outlined concerns on tolerability of dabigatran, adherence issues, and adverse consequences.15In comparison with warfarin, dabigatran 150 mg has shown low rates of stroke, and systemic embolism (dabigatran p<0.001 for superiority). However, both drugs exhibited comparable rates of major hemorrhage.16-18 Greater fatal, and non fatal bleeding events were reported with dabigatran than warfarin.19,20 A recent (2015) retrospective Medicare data analysis study20 on dabigatran’s safety highlighted that the incidence of bleeding was higher than with warfarin (33% versus 27%), major bleeding (9% versus 6%), and gastrointestinal bleeding (17% versus 10%). Intracranial hemorrhage occurred more often with warfarin than dabigatran (1.8% versus 0.6%).20 It has been documented that risks of major bleeding from dabigatran is high for patients with chronic kidney disease, and in African Americans.20 The Randomized Evaluation of Long-term Anticoagulant Therapy: Dabigatran versus warfarin-RE-LY studies18 have showed similar risk of bleeding with warfarin versus dabigatran in patients with non-valvular AF. This dictated the importance of age sub-group analysis in studies. In real clinical practice, patients from different countries may have more co-morbid conditions than those in the RE-LY study.21 The current available data around bleeding incidences from dabigatran is relevant to populations with diverse characteristics. Revealing the clinical utility of dabigatran in our Emirati population may demonstrate different perspectives. Therefore, we intend to provide early data around the clinical utility of dabigatran in United Arab Emirates (UAE) Emirati population.     

Health care services provided to type 1 and type 2 diabetic patients in Saudi Arabia

Objectives:

To assess health care services provided to type 1 and type 2 diabetic patients and diabetes health care expenditure in the Kingdom of Saudi Arabia (KSA).

Methods:

This study was part of a nationwide, household, population based cross-sectional survey conducted at the University Diabetes Center, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia between January 2007 and December 2009 covering 13 administrative regions of the Kingdom. Using patients’ interview questionnaires, health care services data were collected by trained staff.

Results:

A total of 5,983 diabetic patients were chosen to assess health care services and expenditure. Approximately 92.2% of health services were governmental and the remaining 7.8% were in private services. The mean annual number of visits to physicians was 6.5±3.9 and laboratories was 5.1±3.9. Diabetic patients required one admission every 3 years with a mean admission duration of 13.3±28.3 days. General practitioners managed 85.9% of diabetic cases alone, or shared with internists and/or endocrinologists. Health care expenditure was governmental in 90% of cases, while it was personal in 7.7% or based on insurance payment in 2.3%.

Conclusion:

Health services and its expenditure provided to diabetic citizens in Saudi Arabia are mainly governmental. Empowerment of the role of both the private sector and health insurance system is badly needed, aside from implementing proper management guidelines to deliver good services at different levels.The health care system (HCS) in the Kingdom of Saudi Arabia (KSA) is growing at an annual rate of 2% to meet the increasing demand for health care services caused by increased population growth, and a surge in chronic non-communicable diseases.1 This has resulted in an increase in the total health care budget by more than 2 times; from 30 billion Saudi Riyals (SR) (US$8 billion) in 2008 to approximately SR69 billion (US$18.4 billion US dollars) in the year 2011 with a cumulative allocation of SR113 billion (U$30.13 billion) in 2010 and 2011; which accounted for 3.7% of the estimated country’s gross domestic product (GDP), which is one of the highest among Gulf Cooperation Council (GCC) countries.2 The Saudi health care system, which is ranked 26th among 190 countries by the World Health Organization (WHO),3 has a lower percentage of average expenditure in relation to the country’s GDP than many developed and developing countries.4 The government HCS in KSA is structured to deliver free health care services to Saudi citizens through various public hospitals and primary health care centers (PHCCs) including government health sectors, such as the Ministry of Health (MOH), Military Health Services and University Health Institutions. In addition to this, the private health care sector, through its clinics and hospitals, provided 31.1% of the total health care services in KSA in 2013.5 The real challenge facing the Kingdom’s HSC is the increased demands for hospital beds and medical personnel to meet international standards.6 The population ratio of physician and nurses in the Kingdom is lower than the global ratio being 9.4 physicians and 21 nurses per 10,000 of population versus 13 physicians and 28 nurses globally.7 This explains the current imbalance between the growth in HCS and the real medical needs of Saudi citizens.Diabetes mellitus, being the most prevalent chronic non-communicable disease in the Kingdom, has a significant effect on the country’s HCS and overall economy.8,9 This is proved by the fact that 25.4% of Saudi citizens older than 30 years of age have diabetes, which implies that there are approximately 1.5 million Saudi citizens suffering from this chronic disease.10 This is aside from the fact that more than 70% of known diabetic patients in the Middle Eastern countries have poorly controlled diabetes,11 associated with high rates of chronic complications that place greater pressure on health services and expenditure, where in 2013, it was estimated that the Middle East and North Africa (MENA) region spent US$13.6 billion on diabetes care with the spending per person with diabetes, where the spending in Saudi Arabia was US$934, which is far below other GCC such as United Arab Emirates (US$2,228), Qatar (US$2,199), and Kuwait (US$1,886),12 although we strongly believe that these figures are underestimated.Diabetic patients are currently managed at all health care levels, from primary to secondary and tertiary levels by general practitioners (GPs), internists, and endocrinologists.13 Since diabetes care involves many medical disciplines, such as ophthalmology, cardiology, nephrology and so forth, specialized diabetes clinics, and diabetes centers are needed to function as liaising bodies. Although health care needs for diabetic patients’ management at a global level have witnessed a clear shift to the primary from secondary and tertiary health care levels,14 diabetic patients in the Kingdom are still receiving services at secondary or even tertiary levels. Since there are no studies so far that have looked into the health care services provided to diabetic patients in KSA, the current study, as a part of the Saudi Abnormal Glucose Metabolism and Diabetes Impact (SAUDI-DM) survey,10 has investigated the current status of health care services provided to diabetic patients. This study aimed to assess the medical system providing care to diabetic patients, and methods of payment through a randomly selected cohort of diabetic patients at a country level.     

Radiographic assessment of impacted teeth and associated pathosis prevalence: Pattern of occurrence at different ages in Saudi male in Western Saudi Arabia

Objectives:

To assess the prevalence of both impaction and associated pathosis in a Saudi population in Al-Madinah, Saudi Arabia based on digital panoramic radiographs.

Methods:

This study was carried out from December 2013 to February 2015. Panoramic radiographs of 359 male patients attending the Oral Diagnosis Clinics, Faculty of Dentistry, Taibah University, Al-Madinah, Saudi Arabia were reviewed. All images were evaluated to determine the prevalence and pattern of impacted third molars and canines, and associated pathosis.

Results:

Among 359 panoramic radiographs examined, 124 patients had impacted teeth. The impacted mandibular third molars were the most prevalent impacted teeth, 77.6% had class II pattern of impaction. Among the impacted maxillary canines, 75% were mesioangular and among 66 impacted maxillary third molars, 63.6% had class C. Our study showed that 5.8% of Saudi patients had 3 or more impacted teeth, 13.1% had 2 impacted teeth, and 15.6% had one impacted tooth. Associated pathosis was found in 18.2% among impacted maxillary third molars, and 31.5% among impacted mandibular third molars. The incidence of impaction decreases with age.

Conclusion:

The prevalence and pattern of impacted third molars among Saudis are almost similar to other racial populations. The number of missing wisdom increases with age. Although the percentage of pathosis associated with impaction was considerably low, it is essential to carry you regular oral examinations to preserve asymptomatic impacted teeth in good health.As eruption is a complex process, therefore tooth retardation or failure of eruption may arise, so failure of permanent teeth eruption and subsequent impaction is a common dental anomaly.1 Previous literature reported that teeth impaction is a usual incident and many factors affect its prevalence including aging and eruption time.2 Genetic and environmental factors play a role in developmental disturbances. The incidence of impacted teeth is contradictory in different populations and ethnic groups.3 Complications associated with impaction may range from simple problems to serious life threatening problems. Hyperplastic follicular space, subsequent dentigerous cyst or odontogenic keratocyst are the most common simple problems with impaction.4,5 Serious complications involve malignant transformation of cystic wall into squamous cell carcinoma or mucoepidermoid carcinoma. Consequently, life threatening conditions maybe a chain of simple problem such as impaction, which if solved from the beginning would cost less, and would be simple to solve.6 Panoramic radiography is a simple tomographic technique that introduces the panoramic view of the maxillofacial region.7 Radiographic examinations are either digital imaging or conventional. Digital imaging has many advantages versus conventional, such as reduction of radiation exposure, feasibility of image manipulation and analysis, which improves sensitivity and diminishes errors.8 The United States guidelines state that the panoramic radiograph is one of the screening images for Adolescent with Permanent Dentition and Adult, Dentate or Partially Edentulous.9 During our daily oral examinations, we notice poor patient awareness of oral health and its implications in Saudi Arabia. Additionally, there is no present data on the prevalence of impacted teeth, and associated pathologies in the Saudi population in Al-Madinah, Saudi Arabia. The aim of the present study was to determine the prevalence and pattern of occurrence of impacted teeth at different ages based on digital panoramic radiograph. In addition, to report the radiographic features of associated pathologies in a Saudi male population, in order to correlate between impaction and associated pathosis     

Exploring end of life priorities in Saudi males: usefulness of Q-methodology

Background

Quality end-of-life care depends on understanding patients’ end-of-life choices. Individuals and cultures may hold end-of-life priorities at different hierarchy. Forced ranking rather than independent rating, and by-person factor analysis rather than averaging may reveal otherwise masked typologies.

Methods

We explored Saudi males’ forced-ranked, end-of-life priorities and dis-priorities. Respondents (n?=?120) rank-ordered 47 opinion statements on end-of-life care following a 9-category symmetrical distribution. Statements’ scores were analyzed by averaging analysis and factor analysis (Q-methodology).

Results

Respondents’ mean age was 32.1 years (range, 18–65); 52 % reported average religiosity, 88 and 83 %?≥?very good health and life-quality, respectively, and 100 %?≥?high school education. Averaging analysis revealed that the extreme five end-of-life priorities were to, be at peace with God, be able to say the statement of faith, maintain dignity, resolve conflicts, and have religious death rituals respected, respectively. The extreme five dis-priorities were to, die in the hospital, not receive intensive care if in coma, die at peak of life, be informed about impending death by family/friends rather than doctor, and keep medical status confidential from family/friends, respectively. Q-methodology classified 67 % of respondents into five highly transcendent opinion types. Type-I (rituals-averse, family-caring, monitoring-coping, life-quality-concerned) and Type-V (rituals-apt, family-centered, neutral-coping, life-quantity-concerned) reported the lowest and highest religiosity, respectively. Type-II (rituals-apt, family-dependent, monitoring-coping, life-quantity-concerned) and Type-III (rituals-silent, self/family-neutral, avoidance-coping, life-quality & quantity-concerned) reported the best and worst life-quality, respectively. Type-I respondents were the oldest with the lowest general health, in contrast to Type-IV (rituals-apt, self-centered, monitoring-coping, life-quality/quantity-neutral). Of the extreme 14 priorities/dis-priorities for the five types, 29, 14, 14, 50, and 36 %, respectively, were not among the extreme 20 priorities/dis-priorities identified by averaging analysis for the entire cohort.

Conclusions

1) Transcendence was the extreme end-of-life priority, and dying in the hospital was the extreme dis-priority. 2) Quality of life was conceptualized differently with less emphasize on its physiological aspects. 3) Disclosure of terminal illness to family/close friends was preferred as long it is through the patient. 4) Q-methodology identified five types of constellations of end-of-life priorities and dis-priorities that may be related to respondents’ demographics and are partially masked by averaging analysis.

     

The effect of cannabis on oxidative stress and neurodegeneration induced by intrastriatal rotenone injection in rats

We investigated the effect of cannabis treatment on the development of oxidative stress and nigrostriatal cell injury induced by intrastriatal rotenone injection in rats. Rotenone was injected into the right striatum at a concentration of 5 mM (3 μl/rat). The control rats received the vehicle (DMSO). Subsequently, the effect of Cannabis sativa extract treatment on rotenone toxicity was evaluated. Starting on the second day of rotenone injection, rats were treated with C. sativa extract (5, 10, or 15 mg/kg) (expressed as Δ⁹-tetrahydrocannabinol) subcutaneously (s.c.) once daily for 30 days. Biochemical markers of oxidative stress, malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide, paraoxonase 1 (PON1) activity, catalase activity, as well as tumor necrosis factor alpha (TNF-α), were determined in different brain areas after 30 days of rotenone treatment. Histopathology and immunohistochemical expression of tyrosine hydroxylase (TH), capase 3, and inducible nitric oxide synthase (iNOS) were also performed. Results showed that intrastriatal injection of rotenone resulted in increased brain oxidative stress in the cerebral cortex, striatum, hippocampus, midbrain, and cerebellum. MDA increased by 41.4–70 %, nitric oxide increased by 48.3–77.5 %, while GSH decreased by 25.0–34.2 %. PON1 and catalase activities decreased by 43.0–60.8 % and by 14.2–36 %, respectively, in these areas. Striatal TNF-α increased by 638.9 % of control value after rotenone injection. Rotenone induced motor deficits (decreased rearing activity). Rotenone caused marked nigrostriatal neurodegeneration, decreased TH immunoreactivity, and increased both iNOS and caspase 3 immunoreactivities in the striatum. Cannabis decreased brain oxidative stress and nitric oxide release induced by intrastriatal rotenone in several brain areas. Cannabis also decreased the elevated TNF-α in the striatum. Cannabis did not protect against the immunohistochemical changes in the striatum and substantia nigra or against neuronal degeneration induced by rotenone treatment. Collectively, these results indicated that the administration of cannabis did not protect against nigrostriatal damage caused by intrastriatal rotenone.     

Platelet-albumin-bilirubin score-a predictor of outcome of acute variceal bleeding in patients with cirrhosis

BACKGROUND The albumin-bilirubin(ALBI) score was validated as a prognostic indicator in patients with liver disease and hepatocellular carcinoma. Incorporating platelet count in the platelet-albumin-bilirubin(PALBI) score improved validity in predicting outcome of patients undergoing resection and ablation.AIM To evaluate the PALBI score in predicting outcome of acute variceal bleeding in patients with cirrhosis.METHODS The data of 1517 patients with cirrhosis presenting with variceal bleeding were analyzed. Child Turcotte Pugh(CTP) class, Model of End-stage Liver Disease(MELD), ALBI and PALBI scores were calculated on admission, and were correlated to the outcome of variceal bleeding. Areas under the receivingoperator characteristic curve(AUROC) were calculated for survival and rebleeding.RESULTS Mean age was 52.6 years; 1176 were male(77.5%), 69 CTP-A(4.5%), 434 CTP-B(29.2%), 1014 CTP-C(66.8%); 306 PALBI-1(20.2%), 285 PALBI-2(18.8%), and 926 PALBI-3(61.1%). Three hundred and thirty-two patients died during hospitalization(21.9%). Bleeding-related mortality occurred in 11% of CTP-B,28% of CTP-C, in 21.8% of PALBI-2 and 34.4% of PALBI-3 patients. The AUROC for predicting survival of acute variceal bleeding was 0.668, 0.689, 0.803 and 0.871 for CTP, MELD, ALBI and PALBI scores, respectively. For predicting rebleeding the AUROC was 0.681, 0.74, 0.766 and 0.794 for CTP, MELD, ALBI and PALBI scores, respectively.CONCLUSION PALBI score on admission is a good prognostic indicator for patients with acute variceal bleeding and predicts early mortality and rebleeding.