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Supplementary Table 1 from Tumor Suppressor Activity and Epigenetic Inactivation of Hepatocyte Growth Factor Activator Inhibitor Type 2/SPINT2 in Papillary and Clear Cell Renal Cell Carcinoma

Following treatment with a demethylating agent, 5 of 11 renal cell carcinoma (RCC) cell lines showed increased expression of hepatocyte growth factor (HGF) activator inhibitor type 2 (HAI-2/SPINT2/Bikunin), a Kunitz-type protease inhibitor that regulates HGF activity. As activating mutations in the MET proto-oncogene (the HGF receptor) cause familial RCC, we investigated whether HAI-2/SPINT2 might act as a RCC tumor suppressor gene. We found that transcriptional silencing of HAI-2 in RCC cell lines was associated with promoter region methylation and HAI-2/SPINT2 protein expression was down-regulated in 30% of sporadic RCC. Furthermore, methylation-specific PCR analysis revealed promoter region methylation in 30% (19 of 64) of clear cell RCC and 40% (15 of 38) of papillary RCC, whereas mutation analysis (in 39 RCC cell lines and primary tumors) revealed a missense substitution (P111S) in one RCC cell line. Restoration of HAI-2/SPINT2 expression in a RCC cell line reduced in vitro colony formation, but the P111S mutant had no significant effect. Increased cell motility associated with HAI-2/SPINT2 inactivation was abrogated by treatment with extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) and phospholipase C-γ inhibitors, but not by an inhibitor of atypical protein kinase C. These findings are consistent with frequent epigenetic inactivation of HAI-2/SPINT2, causing loss of RCC tumor suppressor activity and implicate abnormalities of the MET pathway in clear cell and papillary sporadic RCC. This information provides opportunities to develop novel targeted approaches to the treatment of RCC.

Background Cytokine storm is a marker of severity and severe mortality in patients with coronavirus disease 2019 (COVID-19) pneumonia. Immunomodulatory treatments may reduce morbidity and mortality. Objectives To determine whether a 7-day course of methylprednisolone (MP) administered with and without tocilizumab improves outcomes in patients with severe COVID-19 (SARS-CoV-2) pneumonia requiring oxygen therapy, relative to historical controls. Study design and method In this randomized controlled study, patients hospitalized with severe COVID-19 at Rashid Hospital, Dubai, in June 2020 were randomized 1:1 to receive intravenous MP (40 mg twice daily for 7 days) with or without a single dose of intravenous tocilizumab (400 mg). While data from the control arm, consisting of patients administered usual care, were obtained through retrospective review of their electronic medical records. The patients in the three arms were matched by disease severity and inclusion and exclusion criteria. The primary outcomes were day 45 all-cause mortality after randomization, rate of admission to the intensive care unit (ICU), length of ICU stay, days on ventilators, and length of hospital stay. Results In total, 76 patients were recruited, including 23 treated with MP, 26 with MP plus tocilizumab, and 27 historical controls. The rates of admission to the ICU and invasive mechanical ventilation were lowest in patients treated with MP alone, with the rates in this group being significantly lower than the rates in the control group (p = 0.04). Time on a ventilator was lowest in the MP group (1.09 ± 3.68 days) and highest in the control group (7.93 ± 14.86 days). The number of days in the ICU was significantly lower in the MP group than in the control and MP plus tocilizumab groups (p = 0.043). One patient (4.3%) in the MP group and five (18.5%) in the control arm died within 45 days. Survival was highest in patients treated with MP alone, with the addition of tocilizumab not improving survival or any of the other outcomes significantly. Interpretation/conclusion In patients with severe COVID-19 pneumonia on oxygen support, administration of MP daily for 7 days had reduced mortality at 45 days and was associated with significantly lower ICU admission and ventilation rates compared with usual. Adding tocilizumab to MP did not improve any of the studied outcomes significantly.

OBJECTIVES We aimed to evaluate the awareness, knowledge, and perception of middle-aged women regarding menopause and hormone therapy (HT). METHODS This observational study was conducted on pre-, peri-, post-, and surgically menopausal women (n = 591) from January 2020 until June 2020 in Dubai. A structured questionnaire was developed based on previous literature to assess participants' knowledge and awareness of menopause and HT. The questionnaire was implemented by face-to-face interview. Factors associated with the degree of menopausal knowledge were identified. RESULTS Majority (498, 82%) of participant women had fair to poor overall knowledge on menopause, did not know whom HT is used for (404, 48%), and for whom it is contradicted (455, 77%). Knowledge on menopause and HT was highly associated with better attitudes (P

OBJECTIVES: This study was conducted in order to explore and analyze the status of gestational diabetes (GDM) amongst pregnant women in Dubai, United Arab Emirates (UAE); a country with high prevalence of diabetes. We aimed to describe GDM-associated risk factors and clinical outcomes of pregnant women and their neonates. Our objective was to contribute to the broader literature on reproductive health disparities and to inform efforts to improve GDM care at our region. METHODS: Chart review of case records were used to collect data on both maternal and neonatal parameters and outcomes during the specified study period from two main maternity hospitals in Dubai. RESULTS: UAE national women with GDM were more prone to be obese or overweight compared to non-UAE women (p

The size of our pupils changes continuously in response to variations in ambient light levels, a process known as the pupillary light reflex (PLR). The PLR is not a simple reflex as its function is modulated by cognitive brain function and any long-term changes in brain function secondary to injury should cause a change in the parameters of the PLR. We performed a retrospective clinical review of the PLR of our patients using the BrightLamp Reflex iPhone app. The PLR variables of latency, maximum pupil diameter (MaxPD), minimum pupil diameter (MinPD), maximum constriction velocity (MCV), and the 75% recovery time (75% PRT) were associated with significant differences between subjects who had suffered a concussion and those that had not. There were also significant differences in PLR metrics over the life span and between genders and those subjects with and without symptoms. The differences in PLR metrics are modulated not only by concussion history but also by gender and whether or not the person has symptoms associated with a head injury. A concussive injury to the brain is associated with changes in the PLR that persist over the life span, representing biomarkers that might be used in clinical diagnosis, treatment, and decision making.

Although breastfeeding has been the primary source of nutrition for infants, many women do not choose to practise breastfeeding due to lack of knowledge, inability to do so or personal choices. This study aimed at determining the breastfeeding practices and examining the sociodemographic factors associated with optimal breastfeeding among mothers attending child welfare clinic at Dubai Health Authority. A structured questionnaire was designed consisting of sociodemographic data, knowledge, attitude and practice towards breastfeeding. The main reasons for not breastfeeding the baby within 30 min after delivery were having had a caesarean section, followed by separation of the baby from the mother. We found better practice among homemakers, non-United Arab Emirates (UAE) and married women, those with less monthly income, and those with standard delivery. There is a need for better education on optimal breastfeeding, especially in UAE national pregnant women, who have had caesarean sections, or having babies admitted in the intensive care unit.

Background There are major health benefits of physical activity (PA) during pregnancy, yet there is scant data about a woman's knowledge and understanding of these benefits globally. Design and Methods We aimed to evaluate the knowledge, attitude, and practice of pregnant women in the United Arab Emirates concerning exercise. We wanted to investigate why some women exercise while others do not exercise during pregnancy. We used a cross-sectional study using a paper-based questionnaire involving pregnant women at antenatal clinics in the Dubai health Authority. The Modified form of Pregnancy Physical Activity Questionnaire (PPAQ) was adapted in both Arabic and English and used in this study. Results Women aging 25-35 that had a higher educational level, were employed, having 1 or 2 previous pregnancies, and having better knowledge on the benefits of Physical Activity (PA) during pregnancy had better exercise profiles. Conclusions Our results demonstrate that the majority of the women that participated in our study were shown to have low PA during pregnancy. Better education and communication of the benefits of PA during pregnancy are needed to improve exercise among pregnant women in the UAE population. We found that improved education of women specific to PA with involvement of a healthcare provider were associated with an increase in PA during pregnancy.

Background The COVID-19 pandemic has had an immeasurable impact, affecting healthcare systems, the global economy, and society. Exploration of trends within the existing COVID-19 data may guide directions for further study and novel treatment development. As the world faces COVID-19 disease, it is essential to study its epidemiological and clinical characteristics further to better understand and aid in its detection and containment. Methods We aimed to study the clinical characteristics of patients infected with COVID-19 in Dubai, a multi-national Society. Results Our findings demonstrate that during the first wave of the COVID-19 epidemic, age, gender, and country of origin were associated with more severe cases of COVID-19, higher risk for hospitalization and death. Male individuals between 41 and 60 years of age from India had the most significant hospitalization and death predictor (p = .0001). The predictors for COVID-19 related deaths were slightly less than UAE Nationals by individuals from GCC (p = .02) that were followed closely behind by Pilipino (p = .02) and Arabs (p = .001). Conclusion The vulnerability of individuals to infection and in the spectrum of COVID-19 symptoms remains to be understood. There are large variations in disease severity, one component of which may be genetic variability in responding to the virus. Genomics of susceptibility to COVID-19 infection and the wide variation in clinical response to COVID-19 in patients should become active investigation areas.

Introduction: Women in the UAE and Muslim countries are a largely understudied population with significant disparities in knowledge to most basic health concerns and family planning. Our objective was to identify UAE contraceptive knowledge similarities and variances to other world regions, and to inform efforts to improve contraceptive care at Arab world and Muslim countries. Methods: Structured questionnaire consisting of socio-demographic characteristics, knowledge, beliefs and attitudes related to contraception methods. Results: The use of effective contraception methods was associated with higher educational levels of UAE national women who desired to conceive. These women had knowledge of contraception that was associated with an identified impact of their spouse on their choice of contraception. Religion plays an essential role in knowledge on the risk of contraception and safe type of contraceptive methods in the UAE. Statistically significant predictors of having knowledge on different methods of contraception were nationality, P < 0.002; education level, P < 0.03; number of marriages P < 0.002; monthly income, P < 0.04; and the number of children, P < 0.015. Conclusions: Our results demonstrate that higher education and communication of the benefits and risks of different types of contraceptive methods are needed to improve the use of contraception in the UAE population. We recommend additional training in this area for healthcare providers. The involvement of the spouse in the mutual understanding of contraception and its choice coupled with third party insurance coverage may decrease knowledge and utilization gaps further assisting in providing a best contraceptive method.

Objectives: We aimed to determine the awareness, knowledge, and attitude of people residing in Dubai, United Arab Emirates, regarding cardiovascular disease (CVD) risk factors. Our aim was to further identify prospects to increase awareness of modifiable CVD risk factors and influence behavior. Methods: This observational study was conducted in Dubai: a global city in the United Arab Emirates. Participants were selected using simple randomization approach in primary health care centers, and a questionnaire was implemented based on literature review. Results: Out of 1020 individuals approached, 738 agreed to participate in the study (response rate of 72%).The majority of participants surveyed had good knowledge and attitude toward CVD (528, 71.5% and 445, 60% respectively); yet, poor/fair practice related to CVD risk factors (553, 75%). Predictive Margins of Knowledge Scores were significant for age (p

Background: Studies have shown that public awareness of ovarian cancer is weak, and women are often diagnosed at late stages when treatment is difficult. This study aimed to determine the barriers for seeking early medical care and level of knowledge and awareness among women regarding ovarian cancer. Design and methods: A structured questionnaire was designed and adapted from the validated cancer awareness measure. Results: The recognition level of ovarian cancer symptoms among women in this study varied from 12-51%, and the most alarming ones, back pain, eating difficulties, and persistent abdominal pain, were missed by most of the surveyed women. The most recognized ovarian cancer risk factors were never being pregnant, having a history of infertility, and going through menopause, while the least recognized was having personal or family history of breast cancer. Non-UAE nationals women with higher educational levels had better knowledge of ovarian cancer compared to their peers. Conclusions:A change or implementation model is highly recommended in order to improve women’s awareness of ovarian cancer symptoms. Strengthening education among women with regards to risk factors, early symptoms, and the need to seek early medical help should help to increase ovarian cancer awareness and reduce a delay in the diagnosis. Significance for public health In the absence of effective screening, "appropriate clinical suspicion" of the signs and symptoms of the ovarian cancer is currently the best strategy to detect the disease. To reduce the diagnostic interval, several countries have implemented referral guidelines and organizational changes. Most of these guidelines suggest that individuals presenting with symptoms indicative of cancer (alarm symptoms) should be urgently referred to specialized investigative trajectories. However, many studies worldwide have shown that public awareness levels of ovarian cancer are poor, therefore women are often diagnosed at late stages when treatment is difficult. Our findings demonstrate that the overall level of recognition of risk factors and symptoms of ovarian cancer among women in the UAE is indeed low and within a critical level. Thus, strengthening education among women with regards to risk factors, early symptoms, and the need to seek early medical will be helpful in increasing ovarian cancer awareness and reducing the delay in diagnosis.

Objective: To determine the incidence, demographic data, risk factors, indications, outcome and complications of emergency peripartum hysterectomy (EPH) performed in two major tertiary care hospitals in Dubai, and to compare the results with the literature. Materials and Methods: The records of all women who underwent EPH from January 2000 to December 2015 in two major tertiary care hospitals in Dubai were accessed and reviewed. Maternal characteristics, hysterectomy indications, outcomes, and postoperative complications were recorded using descriptive statistics to describe the cohort. Results: There were 79 EPH out of 168.293 deliveries, a rate of 0.47/1000 deliveries. The most common indications for hysterectomy were abnormal placentation (previa and/or accreta) and uterine atony. The majority of hysterectomies were subtotal (70%). The complications were dominated by massive transfusion, urinary tract injuries, one case of maternal death, and one case of neonatal death. Conclusion: The main indication for EPH was abnormal placentation in scarred uterus and uterine atony. The major method of prevention of EPH is to assess women’s risks and to reduce the number of cesarean section deliveries, by limiting the rate of primary cesareans. This is challenging in the United Arab Emirates (UAE) where the culture is for high gravidity and high parity. Recommendations to act to reduce primary and repeated cesareans should be included on the national agenda in UAE.

Background: The Dubai Residency Training Program (DRTP) is a structured postgraduate educational training program started on 1992 to improve healthcare in the United Arab Emirates (UAE) through education and training; align doctors' training in the UAE with internationally recognized standards; deliver educational best practice; and achieve a balance between clinical service delivery and continuing professional development. The aim of this paper is to review the experiences, challenges and outcomes of the DRTP over the last 25 years. Methods: All documentation relating to the DRTP was reviewed and reevaluated. Results: The DRTP has become a very solid foundation; yet, one of the major challenges we are facing is containing the balance between the health service and education. Another challenge is that our capacity for training is limited, in spite of demand, we are not yet able to open all specialties needed in the UAE. Finally, there is a mandate to separate the educational body from service to better govern the education. Conclusions: The time has come, however, for the UAE to have its own medical specialty board. This would further support high quality, comprehensive specialty training to deliver the bespoke workforce required by the Dubai Health Authority. The concept of structured training where the resident knows what, when, and how to learn the required knowledge and skills is already established, and the UAE has the required numbers of highly trained professionals to form the board. Nevertheless, we should neither be complacent nor underestimate the challenges that remain to deliver the UAE specialty board.

Laila Al Shaer,1 Ranjita Sharma,2 Mahera AbdulRahman2 1College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, UAE; 2Dubai Health Authority, Dubai, UAE Background: To ensure an adequate and safe blood supply, it is crucial to select suitable donors according to stringent eligibility criteria. Understanding the reasons for donor deferral can help in planning more efficient recruitment strategies and evaluating donor selection criteria. This study aims to define donor pre-donation deferral rates, causes of deferral, and characteristics of deferred donors in Dubai.Materials and methods: This retrospective study was conducted on all donors who presented for allogeneic blood donation between January 1, 2010, until June 30, 2013, in Dubai Blood Donation Centre, accredited by the American Association of Blood Banks. The donation and deferral data were analyzed to determine the demographic characteristics of accepted and deferred donors, and frequency analyses were also conducted.Results: Among 142,431 individuals presenting during the study period, 114,827 (80.6%) were accepted for donation, and 27,604 (19.4%) were deferred. The overall proportion of deferrals was higher among individuals less than 21 years old (35%, P

Growing demand for human health research in the United Arab Emirates (UAE) has prompted the need to develop a robust research ethics oversight. Examination of the structure, function, and practices of the human research ethics committees (HRECs), followed by evaluation of standards for measuring research output, was conducted. Results indicate that among the HRECs, 90% followed International Council for Harmonization–Good Clinical Practice guidelines, 66.6% have been in operation for more than 5 years, 95% reviewed proposals within 8 weeks, and 56% reviewed for scientific merit apart from ethics. However, systems to recognize accomplishments of researchers, funding transparency, and adverse event reporting were deployed in less than 30% of all HRECs. Research was incorporated into the vision and mission statements of many (65%) organizations. Research publications, collaborations, and recognitions were used to measure research output and report key performance indicators. In spite, resources to generate research output such as dedicated budget (20%), support staff (20%), and continuous training and mentoring program for medical residents (15%) and HREC members (25%) were somehow lacking. HREC structure and operations in the UAE are similar to other regions of the world. Systems to conduct research and report outcomes are defined in the UAE. Regulatory legislation and allocation of resources to support the clinical research enterprise will not only help to meet growing demand for clinical trials but also transform the quality of patient care in the UAE. It is anticipated that the results of this study will benefit investigators, regulators, pharmaceutical sponsors, and the policy makers in the region.

Aims Diabetes is a self-managed condition; knowledge, attitudes, and practices about the condition can influence the overall treatment outcomes and complications of the disease. The aim of this study was to assess the knowledge, attitude, and practice toward diabetes among T2DM patients in the UAE, a highly prevalent country with diabetes. Methods We used the revised Michigan Diabetes Knowledge Scale on T2DM patients. The awareness on diabetes was then assessed based on socio-demographic characteristics, illness perceptions, medication adherence, diabetic self-care, and T2DM complications. Results Overall assessment of T2DM patients on their knowledge, and attitude toward their diabetes were good in the majority of participants (544, 76%; 570, 76% respectively). However, adherence to diabetic self-care practices was fair in the mainstream (437, 57%). The compliance to medication (527, 70%) and eye care practice (475, 63%), were quite high; yet regular checking blood sugar at home 330 (44%) and the foot care practice 336 (45%) were not satisfying. Conclusion Our results demonstrate that the intensive education service being given and time the physician spends with the T2DM patients is highly associated with better practice and outcome of the disease. There is a need for the establishment of better DM education programs in PHC clinics and the development of more campaigns and enlightening programs, both for health care providers and public on T2DM self-care, complications, and nature of the disease. We suggest that new policies be established with a focus on increasing community awareness of diabetes and preventive measures in UAE.

Academic learning is the most important source of stress among young students worldwide and appears to be quite severe in eastern countries. We aimed to examine the relationship between academic stress and depression among adolescents.A cross-sectional study was conducted among adolescents in United Arab Emirates using the Perceived Stress Scale - 14 (PSS-14) and Educational Stress Scale (ESS) for Adolescents (English and Arabic versions).The overall PSS was high in 186 (20%) of the respondents, and moderate in 695 (76%). A multiple regression model of predictors of the PSS showed statistically significant correlations between the total PSS-14 scores and age (p0.0004), gender (p0.0001), and grade (p0.001). A multiple regression model of the PSS-14 questionnaire as predictors of the ESSA revealed that Four variables on PSS-14 were statistically significant predictors of the ESSA: history of depression (p0.0001), content with academic achievement (p0.0001), high academic expectation of parents (p0.003), and a believe capable of meeting parental expectations (p0.0001).Adolescents with severe academic stress need to be identified early. We suggest that an interdisciplinary team in the schools including student advisors and counselors be developed to further address stressors. In addition, students should be taught different stress management techniques such as cognitive behavioral skills to improve their ability to cope with school demands. The identification of stressors may lead to strategies that might address the quality of teaching and mental health evaluation among adolescents.

Objective The objective of the present study was to explore obstetric management in relation to clinical, maternal and child health outcomes by using the Robson classification system. Methods Data was collected from obstetrics registries in tertiary care hospitals in Dubai, United Arab Emirates (UAE). Results The analysis of > 5,400 deliveries (60% of all the deliveries in 2016) in major maternity hospitals in Dubai showed that groups 5, 8 and 9 of Robson’s classification were the largest contributors to the overall cesarean section (CS) rate and accounted for 30% of the total CS rate. The results indicate that labor was spontaneous in 2,221 (45%) of the women and was augmented or induced in almost 1,634 cases (33%). The birth indication rate was of 64% for normal vaginal delivery, of 24% for emergency CS, and of 9% for elective CS. The rate of vaginal birth after cesarean was 261 (6%), the rate of external cephalic version was 28 (0.7%), and the rate of induction was 1,168 (21.4%). The prevalence of the overall Cesarean section was 33%; with majority (53.5%) of it being repeated Cesarean section. Conclusion The CS rate in the United Arab Emirates (UAE) is higher than the global average rate and than the average rate in Asia, which highlights the need for more education of pregnant women and of their physicians in order to promote vaginal birth. A proper planning is needed to reduce the number of CSs in nulliparous women in order to prevent repeated CSs in the future. Monitoring both CS rates and outcomes is essential to ensure that policies, practices, and actions for the optimization of the utilization of CS lead to improved maternal and infant outcomes.

Objectives: The Dubai Residency Training Program (DRTP) commenced in the year 1993; then, a “Residency Research Program (RRP)” has implemented from 2011 to promote research among young physicians. This study was conducted by the Dubai Health Authority to review the RRP to assess its effectiveness in meeting original objectives and generating desired outcomes. Methods: Source documents such as the chronicles of the DRTP, communication between the stakeholders, resident feedback, research director, and program director reports were accessed and retrospectively reviewed. Results: Seven research workshops and ten advanced statistics courses were held. Ten scholarships were provided to the residents for “Introduction to Clinical Research Training” held by Harvard Medical School. Of 370 residents, a total of 156 residents submitted their research proposal, of which 128 residents presented their thesis. Nineteen residents presented their research on international conferences, 12 published their study, and 9 got award locally. Conclusions: Efforts are focused on improving the quality of the research projects, as well as getting residents involved in research that leads eventually to publication. Research is a major component of DRTP; nevertheless, it is challenging for residents to conduct research successfully because of some barriers inherent in residency training. This experience was the first in the United Arab Emirates, and we believe that this paper will contribute to the integrating research in residency programs by the educators and academics in across countries within the region.

Postpartum depression (PPD) is a significant public health problem adversely affecting mothers, their newborns, and other members of the family. Although PPD is common and potentially dangerous, only a minority of the cases are identified in primary health care settings during routine care, and the majority of depressed mothers in the community lies unrecognized and therefore untreated.In this study, a total of 1500 mothers were approached randomly, 808 accepted to participate, and 504 were within the inclusion criteria (women who had a birth of a singleton full-term healthy infant, had an uncomplicated pregnancy, and were within their one week to six months postpartum). The participants completed the Edinburgh Postnatal Depression Scale.A total of 168 women had an EPDS score ≥10, yielding a crude prevalence rate of 33%. The prevalence of suicidal ideation was 14 out of 504 (3%), among which 11 (79%) had EPDS score of ≥10. We fitted multiple linear regression models to evaluate the predictors of variables measured on the EPDS scale. This model was statistically significant p0.0001 in predicting the total EPDS score. Women's employment status, baby's birth weight, stressful life event and marital conflict were statistically significant predictors.The findings of this study are anticipated to entail the government and policy makers in the region to pay more attention to the apparently high prevalence of unrevealed PPD in the community. It is crucial to enhance screening mechanisms for early detection, providing interventions to manage symptoms, and at the same time mandating local guidelines to address the PPD pathology as a high priority for the UAE population.

Background: Moral competencies and ethical practices of medical professionals are among the desired outcomes of academic training. Unfortunately, academic dishonesty and misconduct are reported from medical colleges across the world. This study investigates the level of academic dishonesty/misconduct among multicultural medical students. Objective: The aim of this study is to investigate the level of academic dishonesty/misconduct among multicultural medical students. Design: Validated and customized version of Dundee Polyprofessionalism Inventory-1 detailing lapses of professionalism in undergraduate health professions education was used to determine the perceived prevalence and self-reported lapses of academic integrity in this study. Results: This study shows that the majority (458/554, 83%) of medical students have admitted to acts of academic dishonesty mentioned in the questionnaire. Approximately 42% (231/554) of the students have given proxy for attendance and 71% of them considered this as an offense. Similarly, 12% (66/554) have copied from the record books of others, and 86% (477/554) have considered it unethical. In addition, 5% (28/554) of the students revealed forging a teacher’s signature in their record or logbooks, with 16% (91/554) of them reporting that they have seen others forge signatures. Conclusion: This is the first multi-center, multi-cultural and multi-ethnic study involving a large number of participants that addresses academic professionalism among medical students in the Middle East. Certainly, the paucity of data limits definitive conclusions about the best approach to prevent academic misconduct in the UAE medical schools. Yet, the results of our study are anticipated not only to benefit the UAE but also to find application in the Arab world, with similar medical school programs, values, culture and tradition.

Workforce planning is critical for being able to deliver appropriate health service and thus is relevant to medical education. It is, therefore, important to understand medical students' future specialty choices and the factors that influence them. This study was conducted to identify, explore, and analyze the factors influencing specialty preferences among medical students of the United Arab Emirates (UAE).A multiyear, multicenter survey of medical student career choice was conducted with all five UAE medical schools. The questionnaire consisted of five sections. Chi-squared tests, regression analysis, and stepwise logistic regression were performed.The overall response rate was 46% (956/2079). Factors that students reported to be extremely important when considering their future career preferences were intellectual satisfaction (87%), work-life balance (71%), having the required talent (70%), and having a stable and secure future (69%). The majority of students (60%) preferred internal medicine, surgery, emergency medicine, or family Medicine. The most common reason given for choosing a particular specialty was personal interest (21%), followed by flexibility of working hours (17%).The data show that a variety of factors inspires medical students in the UAE in their choice of a future medical specialty. These factors can be used by health policymakers, university mentors, and directors of residency training programs to motivate students to choose specialties that are scarce in the UAE and therefore better serve the health-care system and the national community.

Compound heterozygosity for Hb D-Punjab [β121(GH4)Glu→Gln, GAA>CAA] /β-thalassemia (β-thal) must be carefully differentiated from homozygous Hb D-Punjab in premarital screening. This is essential when the partner is a carrier of β-thal trait. The case of a baby born affected with β-thal major (β-TM), from a marriage between a mother with β-thal trait and a father with Hb D-Punjab/β-thal, is presented. The father had been misdiagnozed as homozygous Hb D-Punjab during premarital screening, even though the screening program utilized complete blood counts and high performance liquid chromatography (HPLC). The factors that may have contributed to this midsiagnosis are presented and discussed. It is recommended that cases of Hb D-Punjab, or any other hemoglobin (Hb) variant appearing as homozygous, are carefully evaluated if microcytic hypochromic parameters not associated with α-thal are present. In all cases of suspected hemizygosis, molecular analysis should always be performed, and in particular if one partner is a β-thal carrier.

BACKGROUND: United Arab Emirates (UAE) has a heterogeneous population consisting of more than 160 nationalities and 85% of the population being non-UAE. In 2007, Dubai Blood Donation Centre (DBDC), the major local supplier of blood in the UAE, introduced six-minipool nucleic acid test (NAT) for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV), which in 2008 upgraded to individual-donation (ID)-NAT. The aim of this study was to analyze the efficacy of the donor screening program in the UAE and evaluate the impact of NAT on the yield and residual risk of transfusion-transmissible viral infections (TTVIs). STUDY DESIGN AND METHODS: A total of 169,781 blood donations collected at DBDC between 2004 and 2009 were screened for TTVIs. During the period 2008 through 2009, a total of 59,283 donations were tested with both ID-NAT and serologic assays. The incidence, prevalence, and residual risk for each viral agent were estimated and analyzed. RESULTS: The individual prevalences of HBV, HCV, and HIV per 100,000 donation were 234.4, 110, and 4, respectively. Calculated residual risk per million donations for HBV was decreased from 1.41 in pre-NAT period to 0.92 in post-NAT period. These figures were decreased for HCV and HIV from 1.73 and 0.39 to 0 and 0.32, respectively. CONCLUSION: Incidence rates and estimated residual risk indicate that the current risk of TTVIs attributable to blood donation is relatively low in the UAE. The study recommends the parallel use of both serology and ID-NAT TTVIs screening in blood donations and suggests the exclusion of antibody to hepatitis B core antigen–positive donations as this can eliminate the potential infectivity of these units with marginal effects on the blood stock in UAE.

PHENOMENON: Medical residents' satisfaction with the quality of training for medical residency training specialists is one of the core measures of training program success. It will also therefore contribute to the integrity of healthcare in the long run. Yet there is a paucity of research describing medical residents' satisfaction in the Middle East, and there are no published studies that measure the satisfaction of medical residents trained within the United Arab Emirates (UAE). This makes it difficult to develop a quality residency training program that might meet the needs of both physicians and society.The authors designed a questionnaire to assess medical residents' satisfaction with the Dubai residency training program in order to identify insufficiencies in the training, clinical, and educational aspects. The survey was a self-report questionnaire composed of different subscales covering sociodemographic and educational/academic profile of the residents along with their overall satisfaction of their training, curriculum, work environment, peer teamwork, and their personal opinion on their medical career.Respondents showed a substantial level of satisfaction with the residency training. The vast majority of residents (80%, N = 88) believe that their residency program curriculum and rotation was "good," "very good," or "excellent." Areas of dissatisfaction included salary, excessive paperwork during rotations, and harassment. INSIGHTS: This is the first report that studies the satisfaction of medical residents in all specialties in Dubai, UAE. Our findings provide preliminary evidence on the efficiency of different modifications applied to the residency program in UAE. To our knowledge, there has not been any previous study in the Middle East that has analyzed this aspect of medical residents from different specialties. The authors believe that this report can be used as a baseline to monitor the effectiveness of interventions applied in the future toward improving residency training programs in this region.

von Hippel-Lindau (VHL) disease is a dominantly inherited family cancer syndrome characterized by the development of retinal and central nervous system haemangioblastomas, renal cell carcinoma (RCC) and phaeochromocytoma. Specific germline VHL mutations may predispose to haemangioblastomas, RCC and phaeochromocytoma to a varying extent. Although dysregulation of the hypoxia-inducible transcription factor-2 and JunB have been linked to the development of RCC and phaeochromocytoma, respectively, the precise basis for genotype-phenotype correlations in VHL disease have not been defined. To gain insights into the pathogenesis of RCC in VHL disease we compared gene expression microarray profiles in a RCC cell line expressing a Type 1 or Type 2B mutant pVHL (RCC-associated) to those of a Type 2A or 2C mutant (not associated with RCC). We identified 19 differentially expressed novel VHL target genes linked to RCC development. Eight targets were studied in detail by quantitative real-time polymerase chain reaction (three downregulated and five upregulated by wild-type VHL) and for six genes the effect of VHL inactivation was mimicked by hypoxia (but hypoxic-induction of smooth muscle alpha-actin 2 was specific for a RCC cell line). The potential role of four RCC-associated VHL target genes was assessed in vitro. NB thymosin beta (TMSNB) and proteinase-activated receptor 2 (PAR2) (both downregulated by wt pVHL) increased cell growth and motility in a RCC cell line, but aldehyde dehydrogenase (ALDH)1 and ALDH7 had no effect. These findings implicate TMSNB and PAR2 candidate oncogenes in the pathogenesis of VHL-associated RCC.

Following treatment with a demethylating agent, 5 of 11 renal cell carcinoma (RCC) cell lines showed increased expression of hepatocyte growth factor (HGF) activator inhibitor type 2 (HAI-2/SPINT2/Bikunin), a Kunitz-type protease inhibitor that regulates HGF activity. As activating mutations in the MET proto-oncogene (the HGF receptor) cause familial RCC, we investigated whether HAI-2/SPINT2 might act as a RCC tumor suppressor gene. We found that transcriptional silencing of HAI-2 in RCC cell lines was associated with promoter region methylation and HAI-2/SPINT2 protein expression was down-regulated in 30% of sporadic RCC. Furthermore, methylation-specific PCR analysis revealed promoter region methylation in 30% (19 of 64) of clear cell RCC and 40% (15 of 38) of papillary RCC, whereas mutation analysis (in 39 RCC cell lines and primary tumors) revealed a missense substitution (P111S) in one RCC cell line. Restoration of HAI-2/SPINT2 expression in a RCC cell line reduced in vitro colony formation, but the P111S mutant had no significant effect. Increased cell motility associated with HAI-2/SPINT2 inactivation was abrogated by treatment with extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) and phospholipase C-γ inhibitors, but not by an inhibitor of atypical protein kinase C. These findings are consistent with frequent epigenetic inactivation of HAI-2/SPINT2, causing loss of RCC tumor suppressor activity and implicate abnormalities of the MET pathway in clear cell and papillary sporadic RCC. This information provides opportunities to develop novel targeted approaches to the treatment of RCC.

Breast cancer is a major cause of cancer-related mortality in women. There are major discrepancies concerning the usefulness of various antibodies in detecting breast cancer susceptibility gene 1 (BRCA1) protein and its subcellular localization. The aim of the present study was to determine the specificity and sensitivity of immunohistochemistry (IHC) as a screening method for demonstrating BRCA1 expression. BRCA1 gene expression in archival paraffin-embedded breast cancer tissues was studied simultaneously at the protein and mRNA levels, and the two findings were compared. Forty-eight archival paraffin-embedded breast cancer tissues were studied for BRCA1 gene expression at protein level by IHC using four different antibodies against different BRCA1 epitopes and at mRNA level using real-time RT-PCR. BRCA1 mRNA expression was reduced or absent in 79% of the samples, and this finding correlated significantly with loss of BRCA1 protein expression in 83% of breast cancer tissues using one BRCA1 antibody studied (AB-1, against N-terminus epitope). The specificity of this antibody was 91.3%, and its sensitivity was 66.6%. There was no significant correlation between BRCA1 mRNA and protein expression as demonstrated by the remaining three antibodies. Antibody 8F7 had the highest sensitivity of 100%, but its specificity was 30.4% if mRNA levels were considered as the reference standard.

A collaboration among 157 newborn screening programs in 47 countries has lead to the creation of a database of 705,333 discrete analyte concentrations from 11,462 cases affected with 57 metabolic disorders, and from 631 heterozygotes for 12 conditions. This evidence was first applied to establish disease ranges for amino acids and acylcarnitines, and clinically validate 114 cutoff target ranges. Objective: To improve quality and performance with an evidence-based approach, multivariate pattern recognition software has been developed to aid in the interpretation of complex analyte profiles. The software generates tools that convert multiple clinically significant results into a single numerical score based on overlap between normal and disease ranges, penetration within the disease range, differences between specific conditions, and weighted correction factors. Design: Eighty-five on-line tools target either a single condition or the differential diagnosis between two or more conditions. Scores are expressed as a numerical value and as the percentile rank among all cases with the condition chosen as primary target, and are compared to interpretation guidelines. Tools are updated automatically after any new data submission (2009- 2011: 5.2 new cases added per day on average). Main outcome measures: Retrospective evaluation of past cases suggest that these tools could have avoided at least half of 277 false positive outcomes caused by carrier status for fatty acid oxidation disorders, and could have prevented 88% of false negative events caused by cutoff 7 values set inappropriately. In Minnesota, their prospective application has been a major contributing factor to the sustained achievement of a false positive rate below 0.1% and a positive predictive value above 60%. Conclusions: Application of this computational approach to raw data could make cutoff values for single analytes effectively obsolete. This paradigm is not limited to newborn screening and is applicable to the interpretation of diverse multi-analyte profiles utilized in laboratory medicine. Abstract word