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Objectives: We aimed to study the characterizing clinical and biochemical profiles of Diabetic Ketoacidosis (DKA) in children with newly diagnosed Type 1 Diabetes Mellitus (Type 1DM) compared to children with established diagnosis of Type 1DM presenting with DKA admitted to the pediatric intensive care unit of a large university hospital in the eastern region of Saudi Arabia. Methods: We retrospectively reviewed the medical records of 211 patients who were admitted to the pediatric intensive care unit with diabetic ketoacidosis between 2010 and 2019. The diagnosis of diabetic ketoacidosis was based on symptoms of polydipsia, polyurea, weight loss, vomiting, dehydration, abdominal pain, breathing problems, lethargy or coma, biochemical hyperglycemia (blood glucose level of >200 mg/dL), venous pH of Results: The rate of newly diagnosed Type 1 DM with DKA was 41.7%, out of them who got severe and moderate diabetic ketoacidosis were 61.6% and 38.4%, respectively. We observed significantly increased heart and respiratory rates in patients newly diagnosed with diabetic ketoacidosis and in those with severe diabetic ketoacidosis (p Conclusions: We found that the clinical and biochemical profiles of patients with newly diagnosed Type 1 DM children were significantly affected compared to children who were known Type 1DM presenting with DKA.

Abdullah A Yousef,1,2 Bassam H Awary,1 Faisal O AlQurashi,1 Waleed H Albuali,1 Mohammad H Al-Qahtani,1 Syed I Husain,2 Omair Sharif2 1Department of Pediatrics, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 2Vice Deanship for e-learning, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi ArabiaCorrespondence: Faisal O AlQurashiDepartment of Pediatrics, College of Medicine, Imam Abdulrahman Bin Faisal University, P.O Box: 11286, Dammam, 31453, Saudi Arabia, Tel +966555078804, Fax +966138955088, Email Faisal.alqurashi@yahoo.comPurpose: The Objective Structured Clinical Examination (OSCE) is a standard academic assessment tool in the field of medical education. This study presents an innovative method for digitizing OSCE evaluation system for medical students and explores its efficacy compared to the traditional paper-based system, through the analysis of a User Satisfaction Survey.Methods: A cross-sectional, questionnaire-based study involving a User Satisfaction Survey to evaluate assessors’ attitudes toward and acceptance of the Computerized Web-based OSCE Evaluation System (COES) was used. Fifth-year medical students at a College of Medicine were assessed clinically through their 2019 end-of-year OSCE examination by 30 examiners in five different OSCE stations. The traditional paper-based stations were converted into an online electronic version using QuestionPro software. Answers were filled in using smart tablets (iPads). QR codes were used for students’ identification at each station to fully digitize the process and save time. After the completion of the exam, a User Satisfaction Survey was sent electronically to all examiners to evaluate their experiences with the new system.Results: The response rate for the survey was 100% with an internal consistency of 0.83. Almost all the examiners (29, 97%) were satisfied with the application of the COES. Further, 72% of the examiners indicated that the electronic system facilitated the evaluation of the students’ skills, and 84% found using a smart device (iPad) was easier than using a paper form. All examiners expressed their preference for using the electronic system in the future.Conclusion: Users were satisfied with the utilization of the customized COES. This concept of fully digitizing the OSCE assessment process shortened the time needed for both the analysis of results and providing students with feedback. Further observational studies are needed to assess examiners’ behaviors when using this methodology.Keywords: academic performance, clinical competency, clinical skills, medical education, undergraduate, Saudi Arabia

OBJECTIVE: Our objective was to determine the trend and precipitating factors of the severity of diabetic ketoacidosis (DKA) in the population admitted to the Pediatric Intensive Care Unit (PICU) in a large teaching hospital in the Eastern region of Saudi Arabia. METHODS: We conducted a retrospective, analytical study at King Fahad Hospital, Imam Abdulrahman Bin Faisal University, Alkhobar, Saudi Arabia. We retrieved the complete medical records of 2234 children who were admitted to the PICU during the 10-year period of 2010 through 2019. The children included those with polydipsia, polyurea, abdominal pain, vomiting, dehydration, and weight loss, as well as breathing disturbances due to acidosis and CNS issues such as lethargy or coma and elevated blood glucose level, > 200 mg/dL [> 11.1 mmol/L], venous pH 7.3, serum total CO2 15 mmol/L, and blood- hydroxybutyrate concentration 3 mmol/L or moderate or severe ketonuria. RESULTS: Out of 2234 PICU admissions, 211 (9.4%) were diagnosed with DKA. A persistent increase in the rate of DKA ended up at 14.1% in 2019 (p = .005). The incidence of DKA was 88/2234 (3.93%). The severity of DKA was as follows: 130 (61.6%) had severe and 81 (38.4%) had moderate DKA. Excessive sweet intake without adding insulin in 83 (39.3%) patients and unhealthy lifestyles (35.1%) were the best predictors of severe DKA (p = .001). CONCLUSION: Over a 10-year period, the DKA pattern was persistently rising and slightly falling, which ended up at the significantly highest rate of 14.1% in 2019. URTI, pneumonia, unhealthy lifestyle, and excess sweet intake were significant precipitating factors associated with severe DKA.

Objectives: To identify ribosome protein L5 gene variants and the risk of hepatic vein thrombosis in Saudi patients. Methods: A case-control study was conducted during the period of May 2018 to September 2019. Sixty-five patient cases of hepatic vein thrombosis (HVT) were chosen, and 50 healthy individuals of the same ages and both gender were set as a control group. The genotype of the gene RPL5 was determined by PCR please provide abbreviation in full and capillary electrophoresis. Sanger sequencing for genetically screened variants was applied for the RPL5 gene. Results: Alleles A at variant rs182018447 and T allele at variant rs559377519 were strongly corelated (p=0.009 and p=0.037, respectively) with the risk of HVT. The genotype frequencies of the RPL5 gene, the A/A genotypes at rs182018447 and T/T at rs559377519 were associated with HVT (p=0.000 and p=0.004; respectively) and an increase in risk for HVT among these patients. Please rephrase the highlighted text without using the word respectively. Conclusion: Our findings indicate that the 5 genetic novel variants examined in the RPL5 gene were associated with a risk of HVT in all our Saudi cases. Additionally, the A/A at rs182018447 and T/T at rs559377519 genotypes were substantially susceptible to HVT in all these patients.

الملخص: الالتهابات الفيروسية لها تأثير على الفيزيولوجيا المرضية لداء السكري من النوع الأول. هناك القليل من البيانات حول تأثير مرض كوفيد-١٩ على داء السكري من النوع الأول لدى الأطفال وأيضا على الحماض الكيتوني السكري. يمثل هذا العمل الحالة الوحيدة التي تم الإبلاغ عنها لطفل مشخص حديثا بداء السكري من النوع الأول مع الحماض الكيتوني السكري ووجد بالمصادفة أنه مصاب بفيروس كورونا المستجد دون وجود أي أعراض في الجهاز التنفسي. نحن نُبلغ عن فتاة تبلغ من العمر ٧ سنوات قدمت تاريخا من العطاش، والتبول، وفقدان الوزن. وأكدت التحاليل تشخيص داء السكري من النوع الأول مع الحماض الكيتوني السكري. وفقا لبروتوكول مكافحة العدوى، خضعت لفحص فيروس كورونا المستجد المخبري، مما أسفر عن نتيجة إيجابية. خلال إقامتها في المستشفى، لم تظهر عليها أي حمى أو أعراض تنفسية. تم علاج الحماض الكيتوني دون أي مضاعفات. نستنتج أن فيروس كورونا المستجد قد يؤدي إلى ظهور داء السكري من النوع الأول لدى الأطفال وقد يعجل حدوث الحماض الكيتوني في مرضى السكري حتى مع غياب أعراض الجهاز التنفسي. Abstract: Viral infections have a well-known influence on the pathophysiology of type 1 diabetes mellitus (T1DM). There is scant data about the impact of COVID-19 T1DM and diabetic ketoacidosis (DKA) on paediatric patients. This case presents a newly diagnosed paediatric patient with T1DM and DKA who was found to have SARS-CoV-2 without any respiratory symptoms. A 7-year-old girl presented with a history of polydipsia, polyuria, and weight loss. This presentation was complicated by a 2-day history of fatigue and vomiting. Investigations into the patient's condition confirmed T1DM with DKA. Following the infection control protocol, she underwent screening for SARS-CoV-2, which yielded a positive result. During her hospital stay, she did not develop fever or respiratory symptoms. The ketoacidosis was treated without any complications. We conclude that SARS-CoV-2 may trigger the onset of T1DM and may precipitate the occurrence of DKA in paediatric diabetic patients, even in the absence of respiratory symptoms.

Waleed H Albuali, Mohammad H Al-Qahtani, Abdullah A Yousef, Mohammad A Al Ghamdi, Faisal O AlQurashi, Amer A Lardhi Department of Pediatrics, College of Medicine, King Fahad Hospital of the University, Imam Abdulrahman Bin Faisal University, Alkhobar, Saudi ArabiaCorrespondence: Faisal O AlQurashi, Department of Pediatrics, College of Medicine, King Fahad Hospital of the University, Imam Abdulrahman Bin Faisal University, Alkhobar, Saudi Arabia, Tel +966555078804, Fax +966138955088, Email Faisal.alqurashi@yahoo.comPurpose: Myocarditis is the inflammation of the heart muscle and can be caused by a variety of infections, incendiary diseases, and pollutants. It is challenging for an emergency pediatrician to have a sufficiently high degree of suspicion for myocarditis to avoid diagnostic delay given the broad overlap of myocarditis symptoms with other disease processes. The study aimed to evaluate the impact of early presentation and diagnosis on the outcomes of acute myocarditis in children.Patients and Methods: We performed a retrospective analysis of the complete records of 80 pediatric patients diagnosed with acute myocarditis between 2015 and 2019 at a single tertiary center in Saudi Arabia. Patients were two weeks to 14 years of age and were admitted to the pediatric intensive care unit (PICU) for various sequelae of myocarditis. Data from routine clinical and laboratory investigations were collected.Results: The incidence of delayed presentation at the hospital after the onset of symptoms of myocarditis was 42.5%. A total of 22 (27.5%) patients expired during their hospital stay. There was marginally significant association of earlier presentation with in-hospital survival (80.4% vs 61.8%) and delayed presentation with higher proportion of in-hospital mortality (38.2% vs 19.6%, p=0.064). The rate of mechanical ventilator was also marginally significant in delayed presentation (p=0.068). Shock and multisystem organ failure were the significantly associated manifestations of delayed acute myocarditis presentations. Length of stay in PICU was also significant in delayed presentation group. The impact of presenting symptoms, ECG findings, and use of mechanical ventilator was not significantly associated with delayed presentation.Conclusion: An earlier presentation may have a substantial impact on overall prognosis and length of PICU stay and may lead to comparatively lesser frequency of mechanical ventilation use.Keywords: acute myocarditis, emergency pediatric care, early presentation, prognosis

Background: The biomarker procalcitonin (PCT) PCT is good in detecting sepsis in postoperative pediatric trauma patients, especially those with a high suspicion of sepsis, and formu-lating a quick treatment. Its use is still limited to pediatric surgical patients, particularly those in in-tensive care units (ICUs), who are more susceptible to sepsis. The purpose of this study was to see if procalcitonin could be used as a reliable and quick biomarker for sepsis in postoperative pediatric trauma patients and were brought to the PICU. Methods: This retrospective longitudinal study was conducted from January 2017 to December 2019. Postoperative pediatric trauma patients aged > 2 weeks old who were hospitalized at the PICU of King Fahd Hospital of the University due to serious trauma or post-acute surgical events were included. Within 24 hours of admission, PCT levels were measured, and again 48-72 hours later. Results: In our study, 31% of severely ill children developed post-surgical sepsis. When compared to the PRISM III score and 24-hour PCT level, PCT levels at 48-72 hours exhibited the largest area under the curve (AUC). With a sensitivity of 71% and a specificity of 65%, the predictive AUC value was estimated to be 0.71. The AUC of PCT levels at 48-72 hours was 0.72 (95% confidence interval (CI): 0.65-0.79; p < 0.001), indicating high predictive validity using a cutoff point > 0.10, with sensitivity, specificity, and positive and negative predictive values of 68.4%, 63.6%, 45.8%, and 81.8%, respectively. Conclusion: PCT is a sensitive biomarker for detecting sepsis in postoperative pediatric trauma pa-tients, especially those with a high pre-test suspicion for sepsis. In addition, PCT can be used alone or in combination with other clinical findings to help formulate a rapid primary diagnosis of sepsis in this subset of patients.

Purpose Currently, several scoring systems for predicting mortality in severely ill children who require treatment in a pediatric intensive care unit (PICU) have been established. However, despite providing high-quality care, children might develop complications that can cause rapid deterioration in health status and can lead to death. Hence, this study aimed to establish a simple early predictive mortality (SEPM) model with high specificity in identifying severely ill children who would possibly benefit from extensive mechanical ventilation during PICU admission. Patients and methods This is a retrospective longitudinal study that included pediatric patients aged older than two weeks who were on mechanical ventilation and were admitted to the PICU of King Fahd Hospital of the University from January 2015 to December 2019. Results In total, 400 pediatric patients were included in this study. The mortality rate of children on mechanical ventilation was 28.90%, and most deaths were associated with respiratory (n = 124 [31%]), cardiovascular (n = 76 [19%]), and neurological (n = 68 [17%]) causes. The SEPM model was reported to be effective in predicting mortality, with an accuracy, specificity, and sensitivity of 92.5%, 97.31%, and 66.15%, respectively. Moreover, the accuracy, specificity, and sensitivity of the Pediatric Risk of Mortality (PRISM) III score in predicting mortality was 95.25%, 98.51%, and 78.46%, respectively. Conclusion The SEPM model had a high specificity for mortality prediction. In this model, only six clinical predictors were used, which might be easily obtained in the early period of PICU admission. The ability of the SEPM model and the PRISM III score in predicting mortality in severely ill children was comparable. However, the accuracy of the newly established model in other settings should be validated, and a prospective longitudinal study that considers the effect of the treatment on the model's predictive ability must be conducted.

The Emergency Repartment (ER) is one of the most used areas in healthcare institutions. Problems with over utilisation and overcrowding have been reported worldwide. This study aims at examining the characteristics of paediatric ER visits, the rate of hospital admissions and its associated predictors at King Fahd Hospital of the University in the Eastern Province of Saudi Arabia.This is a retrospective, medical record-based study. Variables included gender, age group, nationality, complaints, Triage level, shifts and seasons. Descriptive statistics were reported as frequencies/percentages. P-values were obtained through a Chi-Squared test while unadjusted and adjusted odds ratios were estimated by binary logistic regression, where admission was considered as the outcome.The total number of paediatric patients included was 46,374, and only 2.5% were admitted. Males comprised 55.4% while females comprised 44.6%. The most common age group were toddlers, and 92.4% of the total sample were Saudis. The most common complaint was fever (26.9%) followed by respiratory symptoms (24.9%). Only 7 patients (0.02%) were classified as triage I (Resuscitation), and most were triage IV (Less urgent) (71.0%). Most visits occurred during the winter months. Adjusted ORs showed that neonates had higher odds of admission (OR = 3.85, 95%CI = 2.57-5.76). Moreover, those presenting with haematological conditions showed an OR of 65.49 (95%CI = 47.85-89.64), followed by endocrine conditions showing an OR of 34.89 (95%CI = 23.65-51.47). Triage I had a very high odds of admission (OR = 19.02, 95%CI = 2.70-133.76), whereas triage V was associated with a very low odds of admission (OR = 0.30, 95%CI = 0.23-0.38).A low rate of hospital admission was found in comparison with other rates worldwide. This was mostly attributed to an alarmingly high number of non-urgent ER visits. This further emphasises the problem with improper use of ER services, as these cases should be more appropriately directed towards primary healthcare centres. Further studies to examine the impact of prioritising patients in the ER based on the identified predictors of hospital admission, in addition to the standard triage system, are suggested.

Background The Emergency Room (ER) is one of the most used areas in healthcare institutions. Problems with over utilisation and overcrowding have been reported worldwide. This study aims at examining the characteristics of paediatric ER visits, the rate of hospital admissions and its associated predictors at King Fahd Hospital of the University in the Eastern Province of Saudi Arabia. Methods This is a retrospective, medical record-based study. Variables included gender, age group, nationality, complaints, Triage level, shifts and seasons. Descriptive statistics were reported as frequencies/percentages. P-values were obtained through a Chi-Squared test while unadjusted and adjusted odds ratios were estimated by binary logistic regression, where admission was considered as the outcome. Results The total number of paediatric patients included was 46,374, and only 2.5% were admitted. Males comprised 55.4% while females comprised 44.6%. The most common age group were toddlers, and 92.4% of the total sample were Saudis. The most common complaint was fever (26.9%) followed by respiratory symptoms (24.9%). Only 7 patients (0.02%) were classified as triage I (Resuscitation), and most were triage IV (Less urgent) (71.0%). Most visits occurred during the winter months. Adjusted ORs showed that neonates had higher odds of admission (OR = 3.85, 95%CI = 2.57–5.76). Moreover, those presenting with haematological conditions showed an OR of 65.49 (95%CI = 47.85–89.64), followed by endocrine conditions showing an OR of 34.89 (95%CI = 23.65–51.47). Triage I had a very high odds of admission (OR = 19.02, 95%CI = 2.70–133.76), whereas triage V was associated with a very low odds of admission (OR = 0.30, 95%CI = 0.23–0.38). Conclusions A low rate of hospital admission was found in comparison with other rates worldwide. This was mostly attributed to an alarmingly high number of non-urgent ER visits. This further emphasises the problem with improper use of ER services, as these cases should be more appropriately directed towards primary healthcare centres. Further studies to examine the impact of prioritising patients in the ER based on the identified predictors of hospital admission, in addition to the standard triage system, are suggested.

To identify ribosome protein L5 gene variants and the risk of hepatic vein thrombosis in Saudi patients.A case-control study was conducted during the period of May 2018 to September 2019. Sixty-five patient cases of hepatic vein thrombosis (HVT) were chosen, and 50 healthy individuals of the same ages and both gender were set as a control group. The genotype of the geneAlleles A at variant rs182018447 and T allele at variant rs559377519 were strongly corelated (Our findings indicate that the 5 genetic novel variants examined in the

Background: The Objective Structured Clinical Examination (OSCE) is a standard academic assessment tool in the field of medical education. This study aimed to present an innovative method for digitizing a computerized web-based Objective Structured Clinical Examination (OSCE) evaluation system for medical students and explore its efficacy compared to the traditional paper-based system, through the analysis of a User Satisfaction Survey.Method: A cross-sectional, questionnaire-based study involving a User Satisfaction Survey to test assessors’ attitudes to and acceptance of the new Computerized Web-based OSCE Evaluation System (COES) was used. Fifth-year medical students in the College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia were assessed clinically through their 2019 end-of-year OSCE examination by 30 examiners in five different OSCE stations. The traditional paper-based stations were converted into an online electronic version using QuestionPro software. Answers were filled using smart tablets (iPads). QR codes were used for students’ identification at each station to fully digitize the process and save time. After the completion of the exam, a User Satisfaction Survey was sent electronically to all examiners to evaluate their experiences with the new system.Results: The response rate for the survey was 100% with an internal consistency of 0.83. Almost all the examiners (29, 97%) were satisfied with the application of the new OSCE electronic system. Further, 72% of the examiners indicated that the new electronic system facilitated the evaluation of the students’ skills, and 84% found using a smart device (iPad) was easier than using a paper form. All examiners expressed their preference for using the new electronic system in the future.Conclusion: Users were satisfied with the utilization of the new customized COES. This concept of fully digitizing the OSCE assessment process shortened the time needed for both the analysis of results and providing students with feedback. Further observational studies are needed to assess examiners’ behaviors when using this new methodology.

ObjectiveTo describe the risk factors, clinical profile and outcomes of COVID-19 in the paediatric population.DesignMulticentre, retrospective observational study.SettingFour tertiary hospitals in Saudi Arabia.PatientsWe recruited 390 paediatric patients aged 0–18 years who presented from March to December 2020 and tested positive for COVID-19 on PCR.Main outcome measuresWe retrospectively analysed medical records for sociodemographics, health indicators, clinical presentations, laboratory findings, clinical complications, and outcomes.ResultsThe mean participant age was 5.66±4.90 years, and the mean hospital stay was 2.17±3.48 days. Forty patients, mostly school-aged children (16, 40.00%; p=0.005) and children with comorbidities (25, 62.50%; pConclusionsCOVID-19 complications were limited among our patients. However, dyspnoea, abnormal chest radiographs, lethargy and elevated ferritin and D-dimer were associated with an increased risk of complications. Dyspnoea, leucocytosis, comorbidities and abnormal chest radiographs at presentation increased the risk of ICU admission.

Background/Aims: Lipopolysaccharide (LPS) induces acute lung injury (ALI) through oxidative stress and inflammation. Naringenin exerts antioxidant and anti-inflammatory effects. The possible protective effect of naringenin was investigated against ALI induced by LPS in rats. Methods: Rats received a single injection of LPS (5 mg/kg, i.v.). Naringenin was given for 4 consecutive days, at 2 doses (50 and 100 mg/kg/day, p.o.), starting 3 days before LPS administration. Results: LPS significantly increased wet/dry lung weight ratio, malondialdehyde, nitric oxide (NO), interleukin-6, and myeloperoxidase activity in the lung tissues. Naringenin, particularly the higher dose, significantly ameliorated the LPS-induced changes in the measured parameters. Also, naringenin markedly reduced the histopathological lung tissue injury that resulted from LPS. Naringenin significantly decreased the LPS-induced expression of nuclear factor-κB, inducible NO synthase, tumor necrosis factor-a, caspase-3, and significantly increased heat shock protein 70 expression in the lungs. Conclusion: Naringenin significantly protected against LPS-induced ALI in rats through its anti-inflammatory, antioxidant, antinitrosative, and antiapoptotic effects.

Oxidative/nitrosative stress, inflammation, and apoptosis play a crucial role in the pathogenesis of arsenic-induced testicular injury. Telmisartan, the angiotensin II-receptor antagonist, possesses antioxidant and anti-inflammatory activities. The protective effect of telmisartan against arsenic-induced testicular damage was investigated in rats. Testicular damage was induced by sodium arsenite (10 mg kg–1/day, p.o., for 2 consecutive days). Telmisartan (10 mg kg–1/day, i.p.) was given for 3 consecutive days, starting 1 day before sodium arsenite administration. Telmisartan significantly attenuated the arsenic-induced decrease in the levels of serum testosterone and testicular reduced glutathione, and significantly decreased the elevation of the levels of testicular malondialdehyde, nitric oxide, and arsenic levels, as well as myeloperoxidase activity resulting from sodium arsenite administration. Histopathological and immunohistochemical examination revealed that telmisartan markedly attenuated testicular tissue changes, and decreased the arsenic-induced expression of vascular endothelial growth factor, inducible nitric oxide synthase, tumor necrosis factor-α, cyclooxygenase-2, nuclear factor-κB, and caspase-3. Telmisartan, via its antioxidant and/or anti-inflammatory effects, may represent a potential candidate to protect against the deleterious effects of arsenic on testicular tissue.

The potential protective effect of cannabidiol, the major non-psychotropic Cannabis constituent, was investigated against doxorubicin cardiotoxicity in rats. Cardiotoxicity was induced by six equal doses of doxorubicin (2.5mgkg(-1) i.p., each) given at 48h intervals over two weeks to achieve a total dose of 15mgkg(-1). Cannabidiol treatment (5mgkg(-1)/day, i.p.) was started on the same day of doxorubicin administration and continued for four weeks. Cannabidiol significantly reduced the elevations of serum creatine kinase-MB and troponin T, and cardiac malondialdehyde, tumor necrosis factor-α, nitric oxide and calcium ion levels, and attenuated the decreases in cardiac reduced glutathione, selenium and zinc ions. Histopathological examination showed that cannabidiol ameliorated doxorubicin-induced cardiac injury. Immunohistochemical analysis revealed that cannabidiol significantly reduced the expression of inducible nitric oxide synthase, nuclear factor-κB, Fas ligand and caspase-3, and increased the expression of survivin in cardiac tissue of doxorubicin-treated rats. These results indicate that cannabidiol represents a potential protective agent against doxorubicin cardiac injury.

Sickle cell anemia is common in the Middle East and India where the HbS gene is sometimes associated with the Arab-Indian (AI) β-globin gene (HBB) cluster haplotype. In this haplotype of sickle cell anemia, fetal hemoglobin (HbF) levels are 3-4 fold higher than those found in patients with HbS haplotypes of African origin. Little is known about the genetic elements that modulate HbF in AI haplotype patients. We therefore studied Saudi HbS homozygotes with the AI haplotype (mean HbF 19.2±7.0%, range 3.6 to 39.6%) and employed targeted genotyping of polymorphic sites to explore cis- and trans- acting elements associated with high HbF expression. We also described sequences which appear to be unique to the AI haplotype for which future functional studies are needed to further define their role in HbF modulation. All cases, regardless of HbF concentration, were homozygous for AI haplotype-specific elements cis to HBB. SNPs in BCL11A and HBS1L-MYB that were associated with HbF in other populations explained only 8.8% of the variation in HbF. KLF1 polymorphisms associated previously with high HbF were not present in the 44 patients tested. More than 90% of the HbF variance in sickle cell patients with the AI haplotype remains unexplained by the genetic loci that we studied. The dispersion of HbF levels among AI haplotype patients suggests that other genetic elements modulate the effects of the known cis- and trans-acting regulators. These regulatory elements, which remain to be discovered, might be specific in the Saudi and some other populations where HbF levels are especially high.

Both α- and β-thalassemia (α- and β-thal) are highly prevalent in the population of the Al-Qatif and Al-Ahsa regions in the Eastern Province of Saudi Arabia. This study provides a more precise picture of the α-thal mutations prevalent in 104 transfusion-dependent β-thal patients in the Eastern Province. Detection of α-thal mutations was carried out using the α-globin StripAssay kit. A total of 12 α-thal mutations (21 genotypes) were identified in 33.7% of the chromosomes (46 patients). The heterozygous and homozygous -α(3.7) (α(+)) deletion mutations were the most prevalent in the β-thal patients (21.7%). We identified three α(0) deletions [- -(MED), - -(FIL) and -(α)20.5] that have not been previously reported for the population of Saudi Arabia. The seven point mutations identified in the β-thal patients were: codon 14 [TGG>TAG (α1)], codon 59 [GGC>GAC (α1)] (Hb Adana), polyadenylation signal site (polyA1) [AATAAA>AATAAG (α2)], codon 142 [TAA>TCA (α2)] (Hb Koya Dora), codon 59 [GGC>GAC (α2)] (Hb Adana), initiation codon [ATG>ACG (α2)] and the ααα(anti 3.7) gene triplication. The Hb Koya Dora mutation occurred at the highest frequency (15.38%). Comparison of the clinical phenotype of β-thal patients, with and without an α-thal mutation, showed that patients with β-thal alone had a significantly elevated level of alanine transaminase (ALT) (mean 72.5 IU/L) and aspartate transaminase (AST) (mean 71.8 IU/L) (p

Tremendous changes have taken place in medical curricula in the last two decades; these changes have arguably created some imbalances in the quality of medical graduates around the globe, which may be partly due to the number of resources often demanded by the design of the newer curricula. Therefore, resource-poor countries are often unable to adopt these newer models of training in their entirety and are thus compelled to follow the so- called “Subject-Based Curriculum”. The authors have discussed and prepared some guidelines to provide direction for the adaptation and implementation of Problem-Based Learning Curriculum (PBLC) in countries with different cultures and limited resources. This article addresses the issues and concerns raised by medical educationists on the implementation of PBLC especially in developing countries. These pointers include practical solutions for such common problems as staff, cost, infrastructure and training.

We used a lentiviral vector bearing the viral spike protein to detect neutralizing antibodies against Middle East respiratory syndrome coronavirus (MERS-CoV) in persons from the Eastern Province of Saudi Arabia. None of the 268 samples tested displayed neutralizing activity, which suggests that MERS-CoV infections in humans are infrequent in this province.

The protective effect of naringenin, a flavonoid compound isolated from citrus fruits, was investigated against nephrotoxicity induced by gentamicin (80mgkg(-1)/day, i.p., for eight days) in rats. Naringenin treatment (50mgkg(-1)/day, p.o.) was administered for eight days, starting on the same day of gentamicin administration. Gentamicin caused significant elevations of serum creatinine, and kidney tissue levels of malondialdehyde, nitric oxide, and interleukin-8, and a significant decrease in renal glutathione peroxidase activity. Naringenin treatment significantly ameliorated the changes in the measured biochemical parameters resulted from gentamicin administration. Also, naringenin markedly attenuated the histopathological renal tissue injury observed with gentamicin. Immunohistochemical examinations showed that naringenin significantly reduced the gentamicin-induced expression of kidney injury molecule-1, vascular endothelial growth factor, inducible nitric oxide synthase, and caspase-9, and increased survivin expression in the kidney tissue. It was concluded that naringenin, through its antioxidant and anti-inflammatory effects, may represent a therapeutic option to protect against gentamicin nephrotoxicity.

Asthma is the most common chronic disease of childhood and the leading cause of childhood morbidity. When uncontrolled, asthma can place significant limits on daily life, and is sometimes fatal. The use of magnesium sulphate (MgSO4) is one of numerous treatment options available during acute severe asthma in children. The efficacy of intravenous, or inhaled MgSO4 has been demonstrated, while little is known about the actual clinical use of either intravenous (IV) or inhaled MgSO4.To assess the effectiveness of intravenous (IV) and/or inhaled MgSO4 on hospital admissions and pulmonary function in children with asthma. This systematic review assessed the best available evidence for the use of either intravenous or inhaled MgSO4 in children with acute asthma. Magnesium deficiency is a common electrolyte disorder in children with acute severe asthma. Several authors reported that IV magnesium was effective in the treatment of moderate to acute asthma in children but evidence for nebulised magnesium was insufficient. In addition, it is used in severe, progressed cases to prevent respiratory failure and/or admission to the intensive care unit. It has bronchodilating and anti-inflammatory effects and modulates ion transport and influences intracellular calcium concentration. Intravenous MgSO4 therapy helps in achieving earlier improvement in clinical signs and symptoms of asthma, e.g. respiratory function and significantly reduced hospital admission, in children with acute severe asthma. The role of nebulised MgSO4 in asthmatic children requires further investigation.According to the previous studies, the author recommends the use of intravenous MgSO4 as a safe and effective adjunct to conventional bronchodilator therapy in acute severe asthma in children.

Sickle cell disease (SCD) in Saudi patients from the Eastern Province is associated with the Arab-Indian (AI) HBB (β-globin gene) haplotype. The phenotype of AI SCD in children was described as benign and was attributed to their high fetal haemoglobin (HbF). We conducted a hospital-based study to assess the pattern of SCD complications in adults. A total of 104 patients with average age of 27 years were enrolled. Ninety-six per cent of these patients reported history of painful crisis; 47% had at least one episode of acute chest syndrome, however, only 15% had two or more episodes; symptomatic osteonecrosis was reported in 18%; priapism in 17%; overt stroke in 6%; none had leg ulcers. The majority of patients had persistent splenomegaly and 66% had gallstones. Half of the patients co-inherited α-thalassaemia and about one-third had glucose-6-phosphate dehydrogenase deficiency. Higher HbF correlated with higher rate of splenic sequestration but not with other phenotypes. The phenotype of adult patients with AI SCD is not benign despite their relatively high HbF level. This is probably due to the continued decline in HbF level in adults and the heterocellular and variable distribution of HbF amongst F-cells.

The possible therapeutic effect of cannabidiol, the major non-psychotropic Cannabis constituent, was investigated against acute hepatotoxicity induced by a single oral dose of acetaminophen (500mg/kg) in mice. Cannabidiol (two intraperitoneal injections, 5mg/kg, each) was given 1 hour and 12 hours following acetaminophen administration. Acetaminophen administration caused significant elevations of serum alanine aminotransferase, and hepatic malondialdehyde, and nitric oxide levels, and a significant decrease in hepatic reduced glutathione. Cannabidiol significantly attenuated the deterioration in the measured biochemical parameters resulted from acetaminophen administration. Also, histopathological examination showed that cannabidiol markedly attenuated ameliorated acetaminophen-induced liver tissue damage. These results emphasize that cannabidiol represents a potential therapeutic option to protect against acetaminophen hepartotoxicity which is a common clinical problem., {"references":["W.C. Maddrey, \"Drug induced hepatotoxicity,\" J. Clin. Gastroenterol., vol. 39, pp. 883-889, 2005.","L.P. James, P.R. Mayeux, J.A. Hinson, \"Acetaminophen-induced hepatotoxicity,\" Drug Metab. Dispos., vol. 31, pp. 1499-1506, 2003.","H. Jaeschke, M.R. McGill, C.D. Williams, A. Ramachandran, \"Currentissues with acetaminophenhepatotoxicity—a clinically relevant model to test the efficacy of natural products,\" LifeSci., vol. 88, pp. 737-745, 2011.","P. Mukhopadhyay, M. Rajesh, B. Horvath, S. Batkai, 0. Park, G. Tanashian, R.Y. Gao, V. Patel, D.A. Wink, L. Liaudet, G. Hasko, R. Mechoulam, P. Pacher,\t\"Cannabidiol protects against hepatic \nischemia/reperfusion injury by attenuating inflammatory signaling and response, oxidative/nitrative stress, and cell death,\" Free Radic. Biol. Med., vol. 50, pp. 1368-1381, 2011.","M.R. Pazos, V. Cinquina, A. Gomez, R. Layunta, M. Santos, J. Fernandez-Ruiz, J. Martinez-Orgado, \"Cannabidiol administration after hypoxia-ischemia to newborn rats reduces long-term brain injury and restores neurobehavioral function,\" Neuropharmacology, vol. 63, pp. 776-783, 2012.","T. Iuvone, G. Esposito, D. De Filippis, C. Scuderi, L. Steardo, \"Cannabidiol: a promising drug for neurodegenerative disorders?,\" CNS Neurosci. Ther., vol. 15, pp. 65-75, 2009.","D.R. Blake, P. Robson, M. Ho, R.W. Jubb, C.S. McCabe, \"Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis,\" Rheumatology (Oxford), vol. 45, pp. 50-52, 2006.","M. Rajesh, P. Mukhopadhyay, S. Batkai, V. Patel, K. Saito, S. Matsumoto, Y. Kashiwaya, B. Horvath, B. Mukhopadhyay, L. Becker, G. Hasko, L. Liaudet, D.A. Wink, A. Veves, R. Mechoulam, P. 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Most sickle cell anemia (SCA) patients indigenous to the Eastern Province of Saudi Arabia have their HbS gene on the Arab-Indian (AI) HBB gene cluster haplotype. Their fetal hemoglobin (HbF) levels are near 20% and they have milder disease compared with SCA where the HbS gene is on African origin HBB haplotypes [1–9]. The AI haplotype is characterized by an Xmn1 restriction site at position 2158 50 to HBG2 (rs7482144), a Hinc2 site 50 to HBE (rs3834466) and other polymorphisms [10]. The causal elements that modify HbF might be in linkage disequilibrium with the b globin gene in this Saudi population. We first performed homozygosity mapping using genome-wide single nucleotide polymorphisms (SNPs) in AI HbS homozygotes [11,12] and identified a single large autozygous region including the HBB cluster and surrounding genes. By next generation sequencing, we examined this region in these same individuals and identified several variants that included a SNP in the HBD promoter region at position 268 bp 50 to HBD (CCAAC > TCAAC). We found this SNP only when the HbS gene was on an AI haplotype and not in SCA with other haplotypes. This SNP was functional in reporter assays in K562 cells and is an AI haplotype-specific marker. Table I summarizes the patient characteristics. Using genome-wide SNP data from a limited number of cases, a region of autozygosity was found only in AI HbS homozygotes on chromosome 11 (coordinates 5,196,450– 5,323,071). The region contains HBD, HBG1, HBG2, HBE1, and the Xmn1 50 HBG2 restriction site (rs7482144). By targeted deep sequencing of 400 kb of chromosome 11 (coordinates 5,143,424–5,543,424; average coverage 42x) in 4 AI patients 1,195 variants were found. A homozygous C-T variant 268 bp 50 HBD with high genotyping and mapping quality that was not in dbSNP build 135 or 1,000 Genomes, was present. Resequencing of 15.9 kb of chr11 (coordinates 5,253,531–5,269,435) by Sanger sequencing detected three new SNPs of which one was the 268 C > T SNP. We focused on this SNP because of its location within the Corfu deletion region and its location in the HBD promoter. The C > T SNP in the HBD promoter was found only in individuals with the AI haplotype. Saudi sickle cell trait carriers with the AI haplotype were heterozygous for this SNP; while siblings without HbS did not carry this mutation. Among 25 AI HbS-b thalassemia patients, 16 were heterozygous at this site (C/T) and 9 were homozygous (T/T). All AI HbS-b thalassemia patients who were homozygous T/T were also homozygous for the AI haplotype (Table I). Fifteen African American SCA patients with unusually high HbF, 54 Saudi SCA patients from the Southwestern Province (SW)—mainly Benin but including subjects with the Senegal haplotype—19 SW HbS-b thalassemia patients, 16 SW sickle cell trait cases, and 25 normal Saudi controls did not carry the 268 HBD SNP. This SNP was not found in 1,094 individuals in 1,000 Genomes May 2011 release. It is important to note that hemoglobin electrophoresis results in Table I were performed using different methods, so direct comparison of HbF and HbA2 between different groups will not be accurate. In addition, the effect of coinheritance of a-thalassemia, or presence of iron deficiency anemia on Hb A2 level was not assessed. Finally, HbA2 levels are artifactually high when HbS is present because of the co-elution of minor HbS species. For these reasons, it is not possible to estimate the effects of the 268 C-T SNP on these subjects HbA2 levels. Reduced expression of HBD relative to HBB in normal individuals is partly a result of a degenerate CCAAT box in the HBD promoter (CCAAC). The CCAAC motif is the site of the 268 C > T SNP (TCAAC) [13–15]. When we compared the activity of the wild-type HBD promoter with the promoter containing the 268 C > T SNP the variant promoter was associated with a significant decrease in the expression of a reporter construct suggesting that it could further impair already enfeebled HBD expression (Fig. 1). Although HBG is expressed at high levels in K562 cells, endogenous HBD is also expressed [16]. The expression studies were designed solely to test the hypothesis that the 268 C > T SNP downregulates the expression of the HBD promoter. The literature provides further evidence for a functional role of the 268 C > T SNP. Its presence was associated with d thalassemia in one individual with reduced HbA2 of 2% and a slightly increased HbF of 1.3% [13]. Moreover, mutations at positions 230, 231, 236, 255, 265, 276, and 277 in the HBD promoter were reported in HbVar database (http://globin.cse.psu.edu/) to cause d thalassemia [14,17–19], and HbF levels of 3.3–4.7% have been noted in some hematologically normal individuals with homozygous d thalassemia [19,20]. A mechanism for increased HbF in the presence of less common HBD promoter mutations is unknown. Any role for the 268 C-T SNP as a modifier of HbF in AI haplotype HbS sickle cell disease is unknown. Perhaps HBD promoter SNPs reduce the interaction of the locus control region and the transcription apparatus with this promoter permitting enhanced interactions with HBG promoters [21]. The paradox of the Corfu deletion first suggested the potential of the HBD-HBG1 intergenic area, the site of the 268 C-T SNP, as a silencer of HBG expression [22]. One potential functional area is the polypyrimidine (PYR) binding site about 960 bp upstream of HBD; however, polymorphisms

OBJECTIVES To describe the changes that have occurred in mechanical ventilation in children with acute lung injury in our institution over the last 10-15 yrs and to examine the impact of these changes, in particular of the delivered tidal volume on mortality. DESIGN Retrospective study. SETTING University-affiliated children's hospital. PATIENTS The management of mechanical ventilation between 1988 and 1992 (past group, n = 79) was compared with the management between 2000 and 2004 (recent group, n = 85). INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS The past group patients were ventilated with a significantly higher mean tidal volume (10.2 +/- 1.7 vs. 8.1 +/- 1.4 mL.kg actual body weight, p < .001), lower levels of positive end-expiratory pressure (6.1 +/- 2.7 vs. 7.1 +/- 2.4 cm H2O, p = .007), and higher mean peak inspiratory pressure (31.5 +/- 7.3 vs. 27.8 +/- 4.2 cm H2O, p < .001) than the recent group patients. The recent group had a lower mortality (21% vs. 35%, p = .04) and a greater number of ventilator-free days (16.0 +/- 9.0 vs. 12.6 +/- 9.9 days, p = .03) than the past group. A higher tidal volume was independently associated with increased mortality (odds ratio 1.59; 95% confidence interval 1.20, 2.10, p < .001) and reduction in ventilation-free days (95% confidence interval -1.24, -0.77, p < .001). CONCLUSIONS The changes in the clinical practice of mechanical ventilation in children in our institution reflect those reported for adults. In our experience, mortality among children with acute lung injury was reduced by 40%, and tidal volume was independently associated with reduced mortality and an increase in ventilation-free days.

Human bocavirus (HBoV) is a major etiology of lower respiratory tract infection (LRTI) in young children. We tested 149 patients admitted to King Fahd Hospital of the University with diagnosis of LRTI. Viremia caused by the different studied viruses was detected in 31.5% of the total cases by Real-time Polymerase chain reaction. We report five patients who were positive for HBoV in serum samples. Clinical presentation ranged from mild to severe disease as one of them required admission to intensive care unit. Wheezing was a striking feature in most of our patients, but fever was not a consistent finding.

The administration of drotrecogin alfa (activated) improves outcome in adult patients with severe sepsis. Since the published pediatric experience with this drug is limited, the role of drotrecogin alfa (activated) in children, and especially in newborns is not well established. We describe a 3-day-old neonate with septic shock and multiorgan system failure, including circulatory, respiratory, renal failure, and disseminated intravascular coagulation, refractory to intensive fluid resuscitation and inotrope support. Within hours of drotrecogin alfa (activated) administration, the neonate experienced dramatic improvement in hemodynamic parameters. The infusion was discontinued after 48 hours, without clinical deterioration. Aside from transient thrombocytopenia, no significant side effects were observed. A brain MRI performed on day 18 after discontinuation of treatment was normal. The positive hemodynamic effect and outcome of treatment in this patient, indicates that drotrecogin alfa (activated) may play a similar role in the treatment of sepsis in neonates as already established in adults.

Abstract 1056 Most sickle cell anemia patients (HBB glu6val homozygotes) indigenous to the Eastern Province of Saudi Arabia have a fetal hemoglobin (HbF) level of about 20% that is associated with a mild clinical phenotype. Their HbS gene is on the Saudi-Indian (SI) haplotype characterized by an Xmn1 restriction site at position −158 5' to HBG2 (rs7482144), a Hinc2 site 5' to HBE (rs3834466) and other polymorphisms in the HBB gene-like cluster. However, the functional elements within the HBB gene-like cluster and elsewhere in the genome causing high HbF are yet to be determined. In a previous study we found that Saudi HbS homozygotes with the SI haplotype had a common region of autozygosity that spanned about 126 kb and included the complete HBB cluster. We have sequenced 13.6 kb in the HBD-HBG1 intergenic region (chr11:5255683-5269326, HG19), the region of the Corfu deletion. We found a SNP at position −68 bp 5' to HBD (c.-118 C>T) only in individuals with a SI haplotype. This SNP was not present in dbSNP build 132 or the 1000 Genomes databases. No other mutation in HBD was identified. This same SNP was recently associated with δ thalassemia (Phylipsen et al. Int. J. Lab. Hematol. 2011, 33: 85–91). Homozygotes for the −68 HBD SNP, who were not on hydroxyurea, had a mean HbF of 23%, range 12.1%-33.4% and mean HbA2 of 2.1%, range 1.2%-3%. We did not find the −68 HBD SNP in 15 African Americans with sickle cell anemia selected because of their unusually high HbF (mean HbF 17.2%, range 11%-28.9%). Parents and sickle cell trait carriers from the families of Saudi Eastern Province patients were heterozygous for the −68 HBD mutation (mean HbF 1.6%, range 0–4.2% and mean HbA2 2.7%, range 2.4%-3.2%) and one normal sibling did not carry this mutation (HbF 0 and HbA2 2.9%). Thirty patients with sickle cell disease indigenous to the Southwestern Province of Saudi Arabia, with the HbS gene on an African origin haplotype, (mean HbF 15.5%, range 4.5%-23% and mean HbA2 2.9%, range 2.1%-3.4% in HbS homozygotes) and 13 normal Saudi controls were examined and none carried the −68 HBD mutation. We also sequenced HBD and its promoter in 8 Southwestern Province HbS homozygotes with a Benin haplotype, 4 with HbF 15%, and none had the −68 HBD SNP or any other mutation in HBD. Inverse relationships between percent HbF level and percent HbA2 was seen in 3 groups of HbS homozygotes:1) SI haplotype homozygotes; 2) Benin haplotype homozygotes from the Southwestern Province; 3) African Americans with diverse HbS haplotypes. The increased HbF in sickle cell anemia with δ thalassemia might involve both post-translational and transcriptional mechanisms. Increased HbF levels might in part be due to the preferential post-translational assembly of αγ dimers compared with αδ and αβS dimers. When δ thalassemia reduces available δ-globin chains, this might further favor preferential binding of less positively charged γ-globin subunits to positively charged α-globin compared with more positively charged δ-globin subunits. Perhaps more importantly, at the transcriptional level, the −68 HBD δ+-thalassemia promoter mutation might favor the interactions of transcription complexes with HBG promoters. The stimulus of hemolytic anemia and expanded erythropoiesis might be required before the favorable genetic milieu for increased HbF production can be fully utilized with the achievement of clinically significant increases in HbF that modulates the course of disease. For example, increased HbF levels of only 3.3%-4.7% have been reported in some hematologically normal individuals with homozygous δ0 thalassemia (Ohta et al. Hemoglobin 1980, 4: 417–425). High HbF levels in SI haplotype HbS homozygotes might involve the interactions of one or more HBG regulatory regions linked to the HBB gene-like cluster, like the −68 HBD SNP, perhaps with trans acting elements. Although the −68 HBD δ+-thalassemia mutation is associated with the SI haplotype and high HbF, functional studies are needed to establish causation. Disclosures: No relevant conflicts of interest to declare.