Al-Azhar Assiut Medical Journal

Comparative study of the pattern of tuberculosis in Suez and Damietta Chest Hospitals in the period 2007–2016 Fares Mohammed Oaf, Ezzat Atwa Risk, Abd El Monem El-Shabrawi Metwally, Kamel Abd-Elghafar Elghonemy, Mokhles Abdel Fadil Zineldin, Abdel-Fatah Ahmed Abdel-Khalek Al-Azhar Assiut Medical Journal 2018 16(4):319-326 Background Tuberculosis (TB) is an infectious disease affecting the world population for thousands of years. Aim The aim was to study and compare the pattern of TB in Suez and Damietta Chest Hospitals through the period from 2007 to 2016. Patients and methods This is a retrospective study that was carried out at Damietta and Suez Chest Hospitals and dispensaries and included all cases of TB from January 2007 to December 2016. Data were collected from TB registration units. Direct observed therapies strategy in chest hospitals and dispensaries started since January 1999. Results A total of 1208 (62.3%) cases were men and 732 (37.7%) were women. The highest rate of infection was reported in age group of 20–29 years (45.7%); the lowest affected age group was that greater than 60 years (5.1%). Type of TB was pulmonary in 76.1% and extrapulmonary in 23.9%. The main presenting symptom was cough presented in 50.8%, hemoptysis in 20.3%, chest pain in 14.7%, and fever in 14.2%. The sputum smear was positive in 89.3% and negative in 10.7%; and there was significant increase of positive smear in Damietta when compared with Suez Governorates (92.1 vs. 86.2%, respectively). The most common extrapulmonary lesion was pleural effusion (40.5%); then lymph node (19.4%) and the least was cold abscess (2.6%). Diabetes was reported in 11.5% and prolonged corticosteroid therapy in 6.5%. The condition at discharge was improvement in 85.5%, failure in 6.6%, relapse in 4.8%, and death in 3.1%. Both groups were comparable as regards the studied variables. Conclusion There was progressive decrease of total TB cases in both Damietta and Suez Governorate from 2007 to 2016 and both governorates were comparable.

Magnesium sulfate, dexmedetomidine, and lignocaine in attenuating hypertension during laparoscopic cholecystectomy: a comparative study Ismail M.A Ahmed, Hesham S Abdelraouf Al-Azhar Assiut Medical Journal 2018 16(4):327-332 Background Pneumoperitoneum during laparoscopic surgery is associated with significant hemodynamic changes represented by increasing heart rate, vascular resistance, and blood pressure. This study aimed to compare the safety of each of magnesium sulfate, dexmedetomidine, and lignocaine on hemodynamic responses during pneumoperitoneum. Patients and methods In all, 120 patients were enrolled in the study. They were electively planned for laparoscopic cholecystectomy. Their ages were in the range of 21–60 years. Men were 38.3% and women 61.67%. American Society of Anesthesiologists I: 74.17% and II: 25.83%. The patients were randomly allocated into four groups: each of 30 patients. Group M administered magnesium sulfate preoperatively as loading followed by infusion 50 mg/kg/h, group D received dexmedetomidine preoperatively as loading followed by infusion 0.5 µg/kg/h, group L was given lignocaine preoperatively as loading followed by infusion 1 mg/kg/h, and group C received normal saline. Results A significant difference was noticed as regards heart rate changes and mean arterial blood pressure increase between the groups of magnesium sulfate, dexmedetomidine, lignocaine, and the control group at the time of drug administration, after intubation, throughout pneumoperitoneum at 5 min intervals, postpneumoperitoneum, and in the postoperative period after 10 min (P<0.001). Conclusion Magnesium sulfate and dexmedetomidine infusions have comparable effects. Lignocaine was less effective in the attenuation of the hypertensive response of pneumoperitoneum and reducing the dose requirements of opioids during laparoscopic cholecystectomy.

Immediate and short-term outcome of septoplasty with nasal packing with reference to the effect of arterial blood gases' concentrations Mohamed A Fatahalla, Ashraf A Wahba, Mahmoud M Elsayed Al-Azhar Assiut Medical Journal 2018 16(4):333-342 Objectives To evaluate the outcome of septoplasty and the effect of bilateral anterior nasal packing (NP) on surgical outcome and postoperative (PO) arterial blood gas levels. Patients and methods A total of 90 patients underwent septoplasty: group I included patients who received PO bilateral anterior NP at the end of surgery for 48 h and group II included patients free of NP. Patients were evaluated clinically using the Nasal Obstruction and Septoplasty Effectiveness scale and underwent septoplasty using Cottle’s technique. Arterial blood samples were obtained preoperatively and before NP removal for estimation of arterial blood pH, bicarbonate (HCO3−), partial pressure of O2 (PaO2) and CO2 (PaCO2), and O2 saturation (SaO2) levels. Pain severity was assessed using numeric rating scale at 6 h, D-1, and D-2 PO, and during the first 48 h PO, nasal bleeding in group II was estimated. After NP removal, pack removal-associated pain and amount of bleeding were determined. Results Operations were conducted uneventfully with nonsignificant difference between groups. At 48 h PO, mean PaO2, PaCO2, and SaO2 levels were significantly lower in all patients than preoperative levels, with significantly lower SaO2 and PaCO2 levels in patients of group I than group II. Numeric rating scale pain scores in both groups showed progressive significant decrease till 48 h PO, with significantly lower scores in group II. Removal of NP resulted in pain scored by more than or equal to 4 in 30 patients and induced minimal bleeding, which was significantly lower than bleeding occurred in patients of group II throughout the 48 h PO. All patients enjoyed significant reduction of Nasal Obstruction and Septoplasty Effectiveness score, with nonsignificant difference between both groups. Conclusion NP after septoplasty reduced amount of PO bleeding, but pain associated with NP presence and removal-induced deleterious effect on patients’ satisfaction with deleterious effect on arterial blood O2 and CO2 levels but with nonsignificant effect on arterial blood pH or HCO3 concentration.

Sensory and motor effects of dexmedetomidine as an adjuvant to bupivacaine for brachial plexus block Yousry Kandil Al-Azhar Assiut Medical Journal 2018 16(4):343-348 Background Dexmedetomidine is a highly selective (eight time more selective than clonidine), specific, and potent α2-adrenergic agonist having analgesic, sedative, antihypertensive, and anesthetic sparing effects when used in systemic routes. Patients and methods Forty patients of both sexes, aged between 25 and 70 years; American Society of Anesthesiologists I–II, who were submitted to elective upper limb surgery by supraclavicular brachial plexus block were included in the present study. They were selected during the period from March 2016 to June 2017. The patients were divided randomly by sealed envelopes into two equal groups (n=20). Group I: 20 patients received 30 ml bupivacaine 0.25%. Group II: 20 patients received 30 ml bupivacaine 0.25% plus 100 μg dexmedetomidine. Results The duration was reported in group II 13.13±1.10 and 16.50±1.63 min for the onset of sensory and motor blocks, respectively, and in group I 14.90±1.18 and 18.63±1.12 min for the onset of sensory and motor blocks, respectively. There was significant decrease of median pain score in group II when compared with group I at 4, 8, 12, 16, 20, and 24 h postoperatively. Conclusion Dexmedetomidine had significantly better postoperative analgesic effects, longer duration of sensory and motor blockade, and earlier onset of action. However, it had unwanted side effects in the form of transient bradycardia and hypotension.

Using two scores for the prediction of mortality in pediatric intensive care units Ashraf Abdelkader, Mohamed M Shaaban, Mahmoud Zahran Al-Azhar Assiut Medical Journal 2018 16(4):349-355 Background Pediatric intensive care unit (PICU) has a specific location for the management of seriously ill children. Aim of the work The purpose of the study was to compare two models [Pediatric Risk of Mortality III (PRISM III) and the Pediatric Index of Mortality 3 (PIM3) scores] for the prediction of mortality in PICU in KSA. Patients and methods A prospective, cohort study was conducted and two mortality scores, PRISM III and PIM3, were applied on 68 children admitted to the PICU at As-Salama Hospital, Al Khobar, KSA over a period of 1 year from January till December 2016. Results The mean age was 7.6±5.3 years with more men than women and the mean length of hospital stay was 9.8±7.0 days. The overall expected mortality using the PRISM III score was 6.7% whereas that by PIM3 was 7.4% and the observed mortality was 17.6%. Both tests underpredicted mortality at all probability levels. However, the degree of underprediction was less when the predicted mortality was more than 25%. Both tests showed excellent discrimination with a value of 0.94 (95% confidence interval, 0.86–1.0) with 94.1% sensitivity and 72.0% specificity; and of 0.93 (95% confidence interval, 0.87–0.99) with 82.4% sensitivity and 84.0% specificity, respectively. The Hosmer and Lemeshow goodness-of-fit test showed good calibration for PRISM III score (χ2=4.57, P=0.148) but poor calibration for PIM3 score (χ2=8.66, P=0.01). Conclusion Both PRISM III and PIM3 scores underpredicted mortality at all probability levels. They offered good discrimination; however, the performance of the scoring system in the PICU patients was poor. PRISM III score showed good calibration while PIM3 score showed poor calibration.

Cerebral microembolization in patients with prosthetic valve and anticoagulation assessment using transcranial Doppler ultrasonography Mohamed A Zaki, Mohamed EL Sayed Moussa Al-Azhar Assiut Medical Journal 2018 16(4):356-359 Background Transcranial Doppler detection of microemboli is widely described, and thromboembolism is a major cause of morbidity in patients with prosthetic heart valves. They require lifelong anticoagulation to minimize thrombotic complications. This study was undertaken to assess the clinical relevance of microembolic signals (MESs) and their relation to anticoagulation. Patients and methods Thirty patients with single mitral mechanical prosthetic valve were included. All of them were selected with low intensity of international normalization ratio (INR). After 2-week interval, INR intensities were stabilized to the recommended levels. Transcranial Doppler monitoring for MES detection was done to the same patients, before and after the stabilization of INR intensities. Results Microemboli were detected in 86.7% of patients before and after the INR level adjustment, with mean number of 57.63±13.12 before adjust. The numbers were significantly lowered after the adjustment of INR, as the emboli number became 24.1±9.12. Conclusion Compared with previously thought findings, the study results were different, as there was a significant effect of the anticoagulation on the number of MESs detected in patients with mechanical valve replacement, but without effect in MES incidence, denoting that, there were a variety of MESs rather than thrombotic. Further assessment by MES differentiation to define solid ones will be indicated.

The role of human umbilical cord blood stem cells in modifying the effect of experimentally induced myocardial infarction in male albino rats Mohammed S Tawfeeq, Salah M Ibrahim, Somia H Abd Allah, Randa S Gomaa, Alaa E Salama, Reham M WahidEldin Al-Azhar Assiut Medical Journal 2018 16(4):360-370 Background Ischemic heart diseases are considered as the first cause of death around the world. Mesenchymal stem cells are considered to be a novel therapy that can achieve real success in myocardial infarction (MI). Objective Evaluating the homing capability of human umbilical cord blood stem cells (HUCBSCs) in the injured myocardium and its role in the development of MI in adult male rats. Materials and methods Fifty adult male albino rats were divided into five groups (n=10): control, MI, MI pretreated with HUCBSCs, MI posttreated with HUCBSCs within 24 h, and MI posttreated with HUCBSCs within 1 week. Serum cardiac troponin I and creatine kinase-myoglobin binding levels were evaluated to assess MI induction. Gene expression of human β actin gene was assessed to evaluate HUCBSCs homing and rat caspase-3 gene was assessed to evaluate apoptosis. Myocardial histopathological examination was done to assess fibrosis. Echocardiographic left ventricular dimensions and function and mean arterial blood pressure were assessed. Results β actin gene expression was higher in all HUCBSCs injected groups compared with normal and MI groups. Administration of HUCBSCs decreased caspase-3 gene expression and fibrosis and improved cardiac function and mean arterial blood pressure in all HUCBSCs injected groups compared with the MI group and these effects were more in pretreated group than both posttreated groups. Expression of rat caspase-3 gene, histopathological assessment, and echocardiography results showed more improvement in posttreated within 24 h group than posttreated within 1-week group. Conclusion HUCBSCs have high homing capability in injured myocardium and they could be used as a preventive therapy in case of ischemia to protect the heart from implications of MI. Moreover, it could be an effective therapy especially if administered within 24 h after MI. Further studies are recommended to highlight the preventive role of HUCBSCs and its clinical application especially in cases of unstable angina.

The effect of 'cytochrome P-450 2C9' and 'vitamin K epoxide reductase complex 1' genetic polymorphism upon oral anticoagulation requirements Hossam Y.K Mohammed, Yousry Z Al-Zohairy, Mahmoud Abd El-Latif Hashish Al-Azhar Assiut Medical Journal 2018 16(4):371-376 Background Polymorphisms in the gene encoding the cytochrome P-450 2C9 enzyme (CYP2C9) are known to contribute to variability in sensitivity to Marevan. CYP2C9 is the enzyme primarily responsible for the metabolic clearance of s-enantiomer of Marevan. The vitamin K epoxide reductase complex 1 (VKORC1) is the target of coumarin anticoagulants, and its common genetic variants result in altered sensitivity to Marevan. VKORC1 polymorphisms are associated with a need for lower doses of Marevan during long-term therapy. Aim of work This study aimed to assess the allelic frequencies and to investigate the relationship between ‘CYP2C9’ and ‘VKORC1’ genotype and vitamin K antagonist anticoagulation. Patients and methods This study was conducted on 40 patients. There were 24 females and 16 males, with a male to female ratio of 2 : 3. Their ages ranged from 28 to 72 years. All the studied patients were laboratory investigated with international normalized ratio, complete blood count, and detection of VKORC1 and CYP2C9 by PCR reverse hybridization method using PGX thrombo strip assay (Vienna Lab.). Results Regarding the distribution of patients according to frequency of deep venous thrombosis (DVT) attacks, 16 (40%) patients showed single attack of DVT and 24 (60%) patients showed recurrent attacks. Patients with single attack of DVT comprised 12 (75%) females and four (25%) males, with male to female ratio of 1 : 3. As for the patients with recurrent attacks of DVT, there were 13 (54.2%) female and 11(45.8%) male patients, with a male to female ratio of 1 : 1.2. Conclusion Detection of genetic polymorphisms in CYP2C9 and VKORC1 genes before onset of warfarin therapy greatly influenced response to warfarin and shortened the time required to reach target international normalized ratio, and hence reduced the risk of recurrence of DVT.

Comparative study between cervical polyetheretherketone cages and dynamic cervical implant postanterior cervical discectomy Mostafa G Eldin, Mohammed S Mohammed Al-Azhar Assiut Medical Journal 2018 16(4):377-385 Objective This is a prospective comparative study between polyetheretherketone (PEEK) cages and dynamic cervical implants (DCI) to evaluate the safety, the effectiveness, and the clinical outcome with radiological outcome for patients with single-level degenerated cervical disc disease treated by anterior cervical discectomy. Patients and methods We studied 30 patients with single-level cervical disc disease. Preoperative evaluation included plain cervical radiography including dynamic views. MRI was carried out to confirm the clinical diagnosis. Results Our study showed that the procedures of two groups were safe and easy without major complications and do not show significant differences between DCI and anterior cervical discectomy and fusion (ACDF) with PEEK cages in terms of improvement in clinical symptoms, blood loss, or operation time; however, DCI was associated with better postoperative neck disability index scores and also resulted in better overall cervical range of motion and segmental range of motion at the treated level than ACDF with PEEK cage. ACDF with PEEK cage is still the gold standard technique for treatment of cervical degenerative disc disease. It improves patient activity and provides a stable segment. However, it fails to restore normal cervical biomechanics and does not prevent adjacent segment disease. Conclusion DCI is considered as a new strategy and an intermediate stage between ACDF and total disc replacement.

Infraclavicular brachial plexus block using nalbuphine versus midazolam as adjuvants to bupivacaine in upper limb surgery Mohamed Abdel Gawad Abdel Halim Al-Azhar Assiut Medical Journal 2018 16(4):386-391 Background Brachial plexus block is a regional anesthesia technique for different surgeries in the upper limb. It is useful as a sole regional anesthesia technique or combined with general anesthesia. The adjuvants to local anesthetics may be improving the quality and duration of analgesia of the brachial plexus block. Objective To evaluate the efficacy of nalbuphine and midazolam as adjuvants to bupivacaine in the infraclavicular brachial plexus block. Patients and methods The study was carried out on 70 patients of the American Society of Anesthesiologist, physical status I, II of both sexes, 20–60 years old and scheduled to forearm and hand surgeries. The patients were classified into three equal groups. Group B: using 20 ml of bupivacaine (3 mg/kg) with 1 ml of saline. Group M: using 20 ml of bupivacaine (3 mg/kg) with midazolam 5 mg (1 ml). Group N: using 20 ml of bupivacaine (3 mg/kg) with nalbuphine 1 ml (10 mg). Results The onset time of sensory and motor blocks were significantly shorter in the adjuvant groups N and M compared with group B. There was a significant increase in the duration of postoperative analgesia in group N compared with groups M and B. Conclusion The addition of nalbuphine and midazolam to bupivacaine in the infraclavicular brachial block improves the speed of sensory and motor onset, the quality of anesthesia, and decreases the analgesic requirements during the first 24 h postoperatively without obvious side effects. The addition of nalbuphine to bupivacaine was superior in delaying the postoperative analgesia requirement.

Dental Research and Review

Training module for capacity building to conduct systematic reviews in dentistry Pradnya Kakodkar Journal of Dental Research and Review 2019 6(1):1-2

Novel materials for defluoridation in India: A systematic review Sreekanth Bose, R Yashoda, Manjunath P Puranik Journal of Dental Research and Review 2019 6(1):3-8 Background: Fluorosis is an endemic disease prevalent in 22 states in India affecting 70 million individuals. The process of removal of fluoride ions from water is known as defluoridation. Even though several defluondation techniques have been developed and implemented in India, most of these techniques have many disadvantages. Development of a newer defluoridation technique starts With laboratory experimentation of materials. Objectives: To identify recent advances in laboratory studies in India with regard to the materials used for defluoridation (published from 2010-2017). Methodology: The review was carned out according to the Joanna Briggs Institute (J81) critical appraisal guideline. A three-step search strategy was utilized which yielded twenty articles after the final step. These articles were evaluated to describe, compare and contrast the materials (Chemical, indigenous and herbal) in terms of effectiveness of fluonde removal, critical pH, cost and other factors. Results: Fluoride removal capacity varied around to 100% and optimum pH between 2 to 10 in different studies. Indigenous and herbal materials are cost effective compared to chemicals. But chemicals have better defluoridation capacity. The defluondating properties can be enhanced using certain combinations or pretreatment of these materials (eg-Heat activation). Conclusions: Indigenous and herbal products are suitable for Indian conditions because of the ease of availability and cost-effectiveness. The future research should focus on enhancing the defluoridating properties of locally available materials and field studies regarding the feasibility in real life scenarios.

A clinical trial to evaluate the efficacy of 5% potassium nitrate gel on sensitivity during ultrasonic scaling Nilofar B Attar, Rajesh P Gaikwad, Akshaya B Banodkar, Gulnar D Sethna Journal of Dental Research and Review 2019 6(1):9-12 Context: Ultrasonic scaling is a routinely performed procedure in dental practice. During ultrasonic scaling, sensitivity of teeth is a common occurrence. The sensitivity of teeth causes discomfort and pain to many patients. The potassium nitrate is an antihypersensitivity agent used effectively in dentifrices. Aims: The aim of the study is to evaluate the efficacy of 5% potassium nitrate gel application on the reduction of sensitivity during ultrasonic scaling. Settings and Design: This study is a randomized controlled trial with a split-mouth design. A total of 100 patients were recruited in the study after informed consent. Subjects and Methods: Mandibular anterior teeth were selected as the area for study. About 5% potassium nitrate gel was applied to the left or right side of the teeth. After 5 min, ultrasonic scaling was performed for both test and control sides. Visual analog scale (VAS) and patient satisfaction were recorded for both the groups. Statistical Analysis Used: An unpaired t-test was used to analyze the mean VAS scores with the area treated with or without application of 5% potassium gel during ultrasonic scaling. Chi-square test was used to analyze the satisfaction level with the test and control group. Results: The mean VAS scores and patient satisfaction for the test group were (P < 0.001) statistically significant as compared to the control group. Conclusions: Potassium nitrate gel can be effectively used before ultrasonic scaling to reduce sensitivity.

Comparative evaluation of efficacy of chemomechanical and conventional methods of caries excavation in young permanent molar teeth: In vivo study Harsha S Nalawade, Gauri Shailesh Lele, Hrishikesh S Walimbe Journal of Dental Research and Review 2019 6(1):13-18 Aim: To evaluate and compare the efficacy of chemomechanical method using Carie-Care (Eco Works Pvt. Ltd.) and conventional method (airotor and hand instruments) during excavation of caries in young permanent molar teeth. Methodology: Twelve children in the age group of 6–9 years having moderate occlusal caries in any two first permanent molars according to the ICDAS-3 or 4 category were selected. Caries excavation in Group I was carried out by the conventional method using airotor and hand instruments. In Group II, it was carried out using Carie-Care gel. The findings recorded in the study included pain response during caries excavation using the Wong-Baker Faces Pain Scale (WBFPS), time taken for caries excavation using a stopwatch (Taksun TS-1809), and the need felt for administration of local anesthesia in children for both the methods. Results: Data obtained were subjected to statistical analysis. Intergroup comparison for WBFPS scores and time needed for caries excavation was done using unpaired t-test and the results obtained were statistically highly significant (P < 0.01). Conclusion: It was concluded from the present study that the use of Carie-Care resulted in reduced pain response from the children during caries excavation. Thus, it can be used as an alternative to the conventional method in children with dental phobia to achieve better cooperation and maintain a positive dental attitude for future treatment.

Social trait rating of halitosis sufferers: A Crosssectional study Clement C Azodo Journal of Dental Research and Review 2019 6(1):19-22 Objective: The objective of this study is to determine the social trait rating of halitosis sufferers by others who are Nigerian undergraduates. Materials and Methods: This prospective study was conducted among main (Ugbowo) campus residential undergraduates of University of Benin, Nigeria. The questionnaire that assessed health status, quality of life, intelligence, caring, trustworthiness, attractiveness, sexiness, aggressiveness, happiness, pleasantry, motivation, spirituality, satisfaction with life, and social life activity of halitosis sufferers was the data collection tool. Results: A total of 245 individuals aged between 17 and 35 years comprising 100 males and 145 females were studied. The worst affected traits were attractiveness and sexiness followed by pleasantry, motivation, satisfaction with life, social life activity, and happiness. The least affected traits were intelligent and trustworthiness. Conclusion: It can be concluded that the low rating of halitosis sufferers on pleasantry, motivation, satisfaction with life, and happiness made them less attractive and sexy and cumulated in diminished social life.

Modified access osteotomy for a rare pterygoid plate osteoma: A technical note Subbiah Shanmugam, Gopu Govindasamy, Syed Afroze Hussain, Rajkiran Thanikachalam Journal of Dental Research and Review 2019 6(1):23-25 Osteomas are benign bone tumors which are rarely seen in the maxillofacial region. This is a technical note of modified access osteotomy for a rare pterygoid plate osteoma with good cosmetic and functional results.

Radicular cyst of the anterior maxilla: An insight into the most common inflammatory cyst of the jaws Sushmit Koju, Nitesh Kumar Chaurasia, Vinay Marla, Deepa Niroula, Pratibha Poudel Journal of Dental Research and Review 2019 6(1):26-29 Radicular cyst is believed to be derived from the epithelial cell rests of Malassez. The associated tooth is nonvital, usually asymptomatic, and may result in swelling, tenderness, tooth mobility, or other problems with rare possibility of neoplastic transformation of its epithelial lining. The treatment options include endodontic procedure, extraction of offending tooth, enucleation with primary closure, and marsupialization. The present report describes the case of a radicular cyst of anterior maxillary region in a 31-year-old male patient, with a detailed description of clinical, radiographic, histopathologic features, pathogenesis, and its surgical management.

Problem-solving for the postgraduate students of public health dentistry Pradnya Kakodkar Journal of Dental Research and Review 2019 6(1):30-32

Academic Medicine

What's new in academic medicine? Things we wish were taught during our medical training Harry L Anderson III, David P Bahner, Michael S Firstenberg, Sagar C Galwankar, Manish Garg, Sona M Garg, Donald Jeanmonod, Rebecca Jeanmonod, Lorenzo Paladino, Thomas J Papadimos, Stanislaw P Stawicki International Journal of Academic Medicine 2019 5(1):1-11

Road traffic-related injuries need to develop capacity building to provide comprehensive care Amrita Ghosh, Ranabir Pal, Sagar Galwankar, Swapan Kumar Paul, Debashis Sinha, Shrayan Pal, AK Jaiswal, Luis Rafael Moscote-Salazar, Amit Agrawal International Journal of Academic Medicine 2019 5(1):12-18 Every year around the world, millions die on road generally from preventable causes and are major public health threat in current times with soaring figures of unnecessary and unacceptable burden of morbidity and disability. We attempted an extensive collection of published literature with specific inclusion criteria in PubMed, Cochrane, Web of Science, and WHO Global Health Library including additional search in indexed literature and website-based population survey reports. Ten percent of road accident fatalities worldwide occur in India, and in addition, more than a million are grievously injured every year. Moreover, victims with nonfatal injuries are forced to live with a range of physical and emotional disabilities with a colossal social and economic impact. In addition, the health-care costs allied with these injuries also create an immense threat to the already stretched out curative health-care load particularly in resource-poor settings of the developing third world countries. Notwithstanding such sobering data, road traffic injuries received less than optimal interest from national health planners to provide comprehensive care from primary health-care levels where maximum injuries come as first contact intervention. Injuries are not accidents and they do not occur by chance alone; like morbidity, they follow a classical model of epidemiological triad of agent-host-environment. Hence, by classifying the risk factors for injury as modifiable and nonmodifiable, it is most likely to forecast and prevent by models. There is a great need to validate brain injury biofluid biomarkers in the acute care setting such as in the emergency departments. The following core competencies are addressed in this article: Medical knowledge, Patient care and procedural skills, and Systems-based practice.

Tattoo-associated complications and related topics: A comprehensive review Jameson M Petrochko, Andrew C Krakowski, Colin Donnelly, John B Wilson, Jennifer Bruno Irick, Stanislaw P Stawicki International Journal of Academic Medicine 2019 5(1):19-50 As tattoos become more common, it is likely that practitioners will encounter adverse tattoo reactions with increasing frequency. While some tattoo-related complications (TRCs) may be nonspecific and challenging to diagnose, others present overtly and can be identified quickly by a well-informed practitioner. TRCs occur at both of these extremes, highlighting the need for better awareness and knowledge sharing regarding this heterogeneous group of morbidities. This review is a result of a compilation of the best available clinical evidence across various groupings of TRCs. The authors' intent was to provide the reader with a comprehensive overview of the topic while creating a rich repository of referenced knowledge for future investigations. From the standpoint of frontline health-care providers, effective recognition and management of TRCs require an open-mind, high degree of clinical suspicion, and nonjudgmental approach to a mainstream phenomenon that is still considered by many to be a taboo. The following core competencies are addressed in this article: Medical knowledge, Patient care, and Systems-based practice.

End-tidal carbon dioxide on emergency department arrival predicts trauma patient need for transfusion, vasopressors, and operative hemorrhage control in the first 24 hours Rebecca Jeanmonod, John Tran, Dhanalakshmi Thiyagarajan, Bryan Wilson, Jason Black, Saira Agarwala, Donald Jeanmonod International Journal of Academic Medicine 2019 5(1):51-56 Introduction: Predicting early need for trauma resuscitation is an important goal of trauma systems. Aim/Hypothesis: We sought to compare the predictive value of end-tidal carbon dioxide (EtCO2) compared to hemoglobin, shock index, systolic blood pressure, heart rate, and respiratory rate in determining transfusion requirement, need for operative hemorrhage control, or pressor use in the first 24 h after trauma alert activation. Materials and Methods: A convenience sample of trauma patients at a Level 1 community trauma center were enrolled. EtCO2 was measured via nasal cannula upon arrival, in addition to initial hemoglobin levels and vital signs. Once stable and competent, patients or families were consented. EtCO2 average over three measurements 3 min apart was used as the EtCO2 value. The electronic medical record was reviewed by a trained research associate who was not involved in the care of the patient to determine the need for transfusion, pressor use, or operative hemorrhage control within the first 24 h of hospitalization. Results: Fifty patients were enrolled, with a median age of 52 years. Seven patients required transfusion, pressor use, and/or surgical hemorrhage control. Vital signs between groups were statistically no different. The mean EtCO2 in patients requiring transfusion was 26.8 (19.5–34.1) versus 34.1 (31.8–36.3) in those who did not (P = 0.027). A cutoff value of EtCO2 ≤33 mmHg was 100% sensitive and 62.8% specific, with an area under the curve of 0.889. Conclusion: EtCO2 has a high sensitivity in predicting the need for intervention in trauma patients. Additional research is needed to determine further utility of this value in the triage and treatment of trauma patients. The following core competency statement: Patient care and Systems-based practice.

Simulating a disaster: Preparing responders in India Benjamin Kaufman, Bryan Jarrett, Pia Daniel, Joseph Freedman, Christina Bloem, Bonnie Arquilla International Journal of Academic Medicine 2019 5(1):57-61 Objective: This study evaluates the effectiveness of a novel modality created by our team to teach disaster preparedness consisting of tabletop drills and disaster simulation. Based on the Incident Command System (ICS) framework, our system prepares medical providers to respond independently to country-level disasters. Background: Disaster response remains an important component of emergency preparedness internationally. To this end, the ICS provides a standardized approach to the command, control, and coordination of emergency response. Methods: A 2-day workshop was conducted with medical providers in Bangalore, India, that used serial disaster simulations to improve disaster response using the ICS. Through increasing responsibility and self-directed tabletops, the participants (doctors, medical students, nurses, and police) gained the skills to respond independently to a simulated countrywide disaster. After the exercise, they were asked to grade the usefulness of simulation and lectures. Results: Forty-four providers responded to the questionnaire, all of which (n = 44, 100%) recommended the course. They graded the final disaster drill as most useful (n = 36, 82%) and also graded lectures from topic experts as useful (n = 36, 83%). Based on qualitative written feedback, participants felt drills helped them in communication and leadership. Conclusion: This novel teaching modality, using simulation and tabletop drills, is an effective tool to teach the ICS to medical providers. Participants felt that they benefitted from training and would respond better to future disasters. The following core competencies are addressed in this article: Systems-based practice, Patient care, Interpersonal and communication skills.

The RECOVER initiative: Supply recovery and donation beyond the operating room Peter F Johnston, Pamela Jumbo-Cueva, Varsha Kurup, Aparna Govindan, Somnath Rao, Ziad C Sifri International Journal of Academic Medicine 2019 5(1):62-66 Background: Similar to previous models for recovery and donation of clean and unused operating room (OR) supplies, that would otherwise be discarded, a new program was started at our institution in 2016. Subsequently, the initiative was expanded to units outside the OR. This study aims to explore the output of these other units on top of our current program. We hypothesize that expansion is feasible and productive, with minimal added effort. Materials and Methods: Clean and unused supplies, in original packaging or open box, which would otherwise be discarded were collected in marked bins from the OR, Surgical Intensive Care Unit (SICU), and the trauma bay (TB) of our urban, academic center. Supplies were sorted, weighed, and inventoried weekly by qualified volunteers. Totals were calculated through proprietary inventory software. Results: The program salvaged 9024 individual items of 129 unique types grouped into 7 categories. In total, 1065 kg of supplies worth an estimated $20,550 USD were collected from the three patient care areas over 7 months. Adding the SICU and TB resulted in a 33% increase in recovered weight and 13% increase in value. Twenty-nine new items were added to our inventory. If this program was expanded to recover supplies from the other ICUs in our hospital, we estimate an additional 951 kg worth $9443 USD could be collected. Conclusions: Thousands of clean, unused supplies, weighing over a metric ton, are discarded in our hospital annually. The OR is the largest source of such material; however, expanding beyond the OR generates significant additional yield. Expansion is feasible with minimally added volunteer hours. Supply recovery initiatives undertaken nationwide and may help mitigate the economic and environmental costs associated with excess medical waste generation and produce staggering quantities of supplies for donation. The following core competencies are addressed in this article: Systems-based practice.

Complex necrotizing soft-tissue infections managed with extra-corporeal membrane oxygenation: 10-year follow-up Melissa E Pastoressa, Blake Haxton, Michael S Firstenberg International Journal of Academic Medicine 2019 5(1):67-70 The use of extracorporeal membrane oxygenation (ECMO) was initially used to support patients in acute cardiopulmonary failure, but its utility has expanded to include a broadspectrum of patients with complex medical conditions. As a growing number of cases continue to mount to prove its successes, ECMO has emerged as a versatile treatment modality in a wide range of clinical scenarios. While the literature documents many successes regarding short-term outcomes, long-term data are lacking. We previously reported two separate cases of profound septic shock where ECMO was implemented as rescue therapy and both patients were able to be successfully discharged. We now provide an update to one of those cases to demonstrate long-term meaningful outcomes in a case where ECMO was utilized successfully. The following core competencies are addressed in this article: Medical knowledge, Patient care and procedural skills, and Systems-based practice.

Academic succession planning: A US perspective Thomas J Papadimos International Journal of Academic Medicine 2019 5(1):71-74 Succession planning for the replacement of vacant academic leadership positions is of paramount importance. It permits organized and minimally disruptive changes during times of transition. Interim chairs have become more common because of increasingly high chair turnover rates and the declining tenure of sitting chairs. In the U.S. nearly 66% of new chairs come from the department of the home institution. Therefore, training faculty members within the department who have the desirable attributes required to be strong leaders will be of assistance to an institution during the turbulent times created by transitions. An emphasis should be placed on the importance of the development of interim chairs as leaders. The following core competencies are addressed in this article: Systems-based practice, Interpersonal and communication skills, and Professionalism.

Learning process and how adults learn Ravi Prakash, Neha Sharma, Uma Advani International Journal of Academic Medicine 2019 5(1):75-79 Learning is a process of changing behavior of learner. Teaching–learning process lasts the entire life span of each individual. Adult education is the intentional systematic process of teaching and learning by which person who occupies adult role acquires new value, attitude, knowledge, skill, and discipline. Art and science of helping adults in learning is called andragogy. Adult learners are autonomous, self-directed, reluctant to learn new things, and they focus mainly on immediate implementation of knowledge. The theories to explain adult learning are conditioning theory, theory of connectionism, and cognitive theory. Adult learning knowledge in medical education helps to keep update for recent advances in different fields. To improve teaching–learning, the principles of adult learning should be applied like active involvement of learner by allowing debate and challenge of ideas using audience response system technique. The adult learner should always be motivated and reinforced by positive feedback. Adults are usually goal oriented; so, we should always relate learning to participant's goal. The following core competencies are addressed in this article: Medical knowledge, Practice-based learning and improvement, Professionalism, Systems-based practice.

Eosinophilic esophagitis: Food impaction as a diagnostic prompt Carilyn E Stark, Soroush Merchant, Thomas J Papadimos International Journal of Academic Medicine 2019 5(1):80-81

Ethnopharmacology

Inhibitory effect of ethanol extract of Ampelopsis brevipedunculata rhizomes on atopic dermatitis-like skin inflammation Publication date: 28 June 2019 Source: Journal of Ethnopharmacology, Volume 238 Author(s): Young-Ae Choi, Ju-Hee Yu, Hong Dae Jung, Soyoung Lee, Pil-Hoon Park, Hyun-Shik Lee, Taeg Kyu Kwon, Tae-Yong Shin, Seung Woong Lee, Mun-Chul Rho, Young Hyun Jang, Sang-Hyun Kim Abstract Ethnopharmacological relevance Extracts from various parts of Ampelopsis brevipedunculata has been used as anti-inflammatory agents in Asian folk medicine. Aim of the study: To demonstrate the medicinal effect of the A. brevipedunculata in skin inflammation, specifically atopic dermatitis (AD). Materials and methods The effect of ethanol extract of A. brevipedunculata rhizomes (ABE) on AD was examined using an AD-like skin inflammation model induced by repeated exposure to house dust mite (Dermatophagoides farinae extract, DFE) and 2,4-dinitrochlorobenzene (DNCB). The mechanism study was performed using tumor necrosis factor (TNF)-α and interferon (IFN)-γ-activated human keratinocytes (HaCaT). Serum histamine and immunoglobulin levels were quantified using enzymatic kits, while the gene expression of cytokines and chemokines was analyzed using quantitative real time polymerase chain reaction. The expression of signaling molecules was detected using Western blot. Results Oral administration of ABE alleviated DFE/DNCB-induced ear thickening and clinical symptoms, as well as immune cell infiltration (mast cells and eosinophils) into the dermal layer. Serum Immunoglobulin (Ig) E, DFE-specific IgE, IgG2a, and histamine levels were decreased after the administration of ABE. ABE also inhibited CD4+IFN-γ+ and CD4+IL-4+ lymphocyte polarization in lymph nodes and expression of TNF-α, IFN-γ, IL-4, IL-13, and IL-31 in the ear tissue. In TNF-α/INF-γ-stimulated keratinocytes, ABE inhibited the gene expression of TNF-α, IL-6, IL-1β, and CCL17. In addition, ABE decreased the nuclear localization of signal transducer and activator of transcription 1 and nuclear factor-κB, and the phosphorylation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase. Conclusion Collectively, our data demonstrate the pharmacological role and signaling mechanism of ABE in the regulation of skin allergic inflammation, which supports our suggestion that ABE could be developed as a potential therapeutic agent for the treatment of AD. Graphical abstract

Anti-inflammatory activities of Canarium subulatum Guillaumin methanol extract operate by targeting Src and Syk in the NF-κB pathway Publication date: 28 June 2019 Source: Journal of Ethnopharmacology, Volume 238 Author(s): Eunju Choi, Mi-Yeon Kim, Jae Youl Cho Abstract Ethnopharmacological relevance Canarium subulatum Guillaumin is an herbal medicinal plant native to Southeast Asia. Ethnopharmacological evidence suggests that plants of the genus Canarium cure a variety of inflammatory diseases. Aim of the study The pharmacological mechanisms of C. subulatum Guillaumin remain poorly understood. In this study, we investigate inflammatory mechanisms and target molecules using C. subulatum Guillaumin methanol extract (Cs-ME) in inflammatory reactions managed by macrophages. Materials and methods To identify the anti-inflammatory activities of Cs-ME, lipopolysaccharide (LPS)-stimulated macrophages and a murine HCl/EtOH-induced gastritis model were chosen. The luciferase reporter gene assay, Western blot analysis, overexpression strategy, and the cellular thermal shift assay (CETSA) were employed to investigate the molecular mechanisms and target enzymes of Cs-ME. The active ingredients of this extract were also determined by HPLC. Results Released levels of nitric oxide (NO) and mRNA expression levels of iNOS and IL-6 were downregulated by Cs-ME without exhibiting cytotoxicity. This extract inhibited MyD88-induced promoter activity and the nuclear translocation of nuclear factor (NF)-κB. Moreover, we found that Cs-ME reduced the phosphorylation of NF-κB upstream signaling molecules including IκBα, IKKα/β, Src, and Syk in LPS-stimulated macrophage-like RAW264.7 cells. The results of Western blot and CETSA confirmed that Src and Syk are anti-inflammatory targets of Cs-ME. In addition, orally injected Cs-ME alleviated HCl/EtOH-induced gastric ulcers in mice. HPLC analysis indicated that quercetin, luteolin, and kaempferol are major active components of this extract with anti-inflammatory activity. Conclusions Cs-ME exhibits anti-inflammatory effects in vitro and in vivo by targeting Src and Syk in the NF-κB signaling pathway. Consequently, Cs-ME could be developed as an anti-inflammatory herbal medicine. Graphical abstract

Anti-obesity effect of argel (Solenostemma argel) on obese rats fed a high fat diet Publication date: 28 June 2019 Source: Journal of Ethnopharmacology, Volume 238 Author(s): Riham A. El-shiekh, Dalia A. Al-Mahdy, Samar M. Mouneir, Mohamed S. Hifnawy, Essam A. Abdel-Sattar Abstract Ethnopharmacological relevance Solenostemma argel (Argel) is a desert plant commonly used in Egyptian and Sudanese traditional medicine to suppress appetite, for treatment of diabetes, and as an antispasmodic and anti-inflammatory agent. Previously the anti-diabetic, hypolipidemic and lipase inhibitory activities of Argel were reported in animal studies and in-vitro assays. However, its specific mechanism of action as an anti-obesity agent has not been studied before. Aim of the study Assessment of the possible anti-obesity effect of Solenostemma argel on diet-induced obesity and elucidation of its mechanism of action, as well as, standardization of the active plant extract. Materials and methods The ethanolic extract (EtOH-E) and its fractions (CH2Cl2-F: methylene chloride and BuOH-F: n-butanol) were prepared from the aerial parts of S. argel and studied at two dose levels; 200 and 400 mg kg−1 in a model of high fat diet (HFD) fed rats. The animals (72 Male Wister rats) were assigned into 9 groups: group (i) fed with normal diet and groups (ii-iv) fed with high fat diet (HFD) for 16 weeks and treated with orlistat, EtOH-E, CH2Cl2-F and BuOH-F in the beginning of the 8th week. At the end of the experiment, blood samples were analysed for lipid and liver biomarkers, glucose and insulin levels, as well as, adipokines and inflammatory markers. Liver and adipose tissues were examined histopathologically and their homogenates were used to determine levels of oxidative stress markers and lipogenesis-related genes. Body weight was monitored weekly during the experiment. Results Our data showed that consumption of S. argel significantly controlled weight gain, attenuated liver steatosis, improved the lipid profile, modulated adipokines activities, increased β-oxidation gene expression, as well as, decreased the expression of lipogenesis-related genes and ameliorated inflammatory and lipid peroxidation derangement. The ethanolic extract was also standardized using LC–MS analysis for its content of stemmoside C. Conclusions The current study revealed that S. argel is a promising Egyptian natural drug, rich in pregnane glycosides, and could be considered a new therapeutic candidate targeting obesity. Graphical abstract

Evaluation of the schistosomicidal, antioxidant and anti-inflammatory activities of the ethyl acetate fraction from Ozoroa pulcherrima Schweinf. Roots on Schistosoma mansoni-induced liver pathology in mice and its phytochemical characterization Publication date: 28 June 2019 Source: Journal of Ethnopharmacology, Volume 238 Author(s): Hermine Boukeng Jatsa, Nestor Gipwe Feussom, Ulrich Membe Femoe, Mérimé Christian Kenfack, Emilienne Tienga Nkondo, Joseph Bertin Kadji Fassi, Nadège Distele Simo, Cyriaque Moaboulou, Calvine Noumedem Dongmo, Christelle Dongmo Tsague, Etienne Dongo, Pierre Kamtchouing, Louis-Albert Tchuem Tchuente Abstract Ethnopharmacological relevance Ozoroa pulcherrima Schweinf. (syn.: Heeria pulcherrrima Schweinf.) is a small shrub belonging to the family Anacardiaceae. In Africa, the stem and the leaves are used to treat dystocia, hyperthermia, and conjunctivitis, while the root is used to treat dysmenorrhea and intestinal helminthiasis. Aim of the study The aim of this study was to assess the schistosomicidal, antioxidant and anti-inflammatory effects of the ethyl acetate fraction from O. pulcherrima roots methanolic extract (EAOp) on S. mansoni- induced liver pathology in mice. Additionally, its phytochemical composition was elucidated. Material and methods The phytochemical characterization of EAOp was carried out by High-Performance Liquid Chromatography-Mass spectrometry (HPLC-MS). Total phenolic and flavonoid contents were also quantified in the fraction. S. mansoni-infected mice received daily and per os, for 28 days, EAOp at 200 or 400 mg/kg, starting from the 36th day post-infection. Praziquantel was used as reference drug. Uninfected-untreated, uninfected-treated and infected-untreated mice served as controls. At the 65th day post-infection mice were sacrificed and parasitological burden monitored. Transaminases, total bilirubin, and total proteins levels were determined in the plasma. Malondialdehyde (MDA), nitrites, superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) levels were measured in the liver as biomarkers of the oxidative stress. Liver histology and morphometric analysis of granulomas were also conducted. Results The HPLC-MS analysis data of EAOp revealed the presence of four triterpenes namely oleaterminaloic acid, hydroxyoleanolic acid, moronic acid, and oleanolic acid; a flavonoid dipentoxybenzoic acid and two alkaloids. Its total phenolic content was 76.46 ± 0.01 mg GAE/g and total flavonoid content 6.26 ± 0.31 mg rutin equivalent/g. The reductions of worm burden (48.89 and 75.56%), fecal egg count (77.76 and 69.52%) and egg load in the liver (65.33 and 77.18%) and intestine (78.06 and 84.63%) were significant after EAOp treatment. EAOp at all doses significantly (p < 0.001) reversed the increasing transaminases activities and total bilirubin level induced by the infection. A normalization of total proteins concentration was also recorded. Treatment of S. mansoni-infected mice with EAOp at 200 or 400 mg/kg resulted in a significant reduction (p < 0.001) of MDA concentration by 73.20% and 67.78% respectively. The level of nitrites which was reduced by the infection significantly increased after the treatment. EAOp significantly increased by 4.67 and 5.69-fold the CAT activity and by 126.67% the GSH level. Histologically, a significant reduction of the number (66.39 and 57.82%) and the volume (52.25 and 34.81%) of liver inflammatory granulomas was recorded after EAOp treatment at all doses. Conclusions These results suggest that the liver pathology in S. mansoni infection is improved by EAOp which disclosed good schistosomicidal, antioxidant and anti-inflammatory activities. Its effects on the liver dysfunction and the hepatic oxidative stress were comparable to that of praziquantel. These findings justified the traditional use of O. pulcherrima for the treatment of intestinal helminthiasis. This fraction can be considered as a promising source for schistosomicidal agents. Graphical abstract

Preclinical study of safety of Dendropanax morbifera Leveille leaf extract: General and genetic toxicology Publication date: 28 June 2019 Source: Journal of Ethnopharmacology, Volume 238 Author(s): Jun-Won Yun, Seung-Hyun Kim, Yun-Soon Kim, Eun Jin Choi, Ji-Ran You, Eun-Young Cho, Jung-Hee Yoon, Euna Kwon, Hyoung-Chin Kim, Ja-June Jang, Jin-Sung Park, Jeong-Hwan Che, Byeong-Cheol Kang Abstract Ethnopharmacology relevance Dendropanax morbifera Leveille (DM) has been used in traditional medicines for infectious and skin diseases, and dysmenorrhea. It exhibits a diverse therapeutic potential including anti-cancer, anti-thrombotic, anti-diabetic, anti-oxidant, and anti-inflammatory activities. Aim of the study Despite promising health benefits of DM, knowledge of its potential adverse effects is very limited. The current study focused on the investigation of subchronic toxicity and genotoxicity of extract obtained from DM according to the test guidelines published by the Organization for Economic Cooperation and Development. Materials and methods We conducted a toxicological evaluation of DM extracts using 14-day repeated-dose toxicity study and 13-week repeated-dose toxicity study in Sprague-Dawley rats administered orally at doses of 500, 1000, or 2000 mg/kg/day. The clastogenicity of DM extract was also evaluated by in vitro chromosome aberration assay and in vivo micronucleus assay. Results Assessment of subchronic toxicity of DM extract by oral administration in rats revealed unremarkable treatment-related findings with respect to food/water consumption, body weight, mortality, urinalysis, hematology, serum biochemistry, necropsy, organ weight and histopathology at doses of 500, 1000, and 2000 mg/kg. Accordingly, the level of no-observed-adverse-effect for DM extract in 13-week subchronic toxicity study was considered to be 2000 mg/kg/day in rats. The data observed from in vitro chromosome aberration assay and in vivo micronucleus assay exclude any clastogenicity of DM extract. Conclusion The results suggest that the oral consumption of DM extract has no adverse effects in humans and represents a safe traditional medicine. Graphical abstract

Curcuma longa L. ameliorates asthma control in children and adolescents: A randomized, double-blind, controlled trial Publication date: 28 June 2019 Source: Journal of Ethnopharmacology, Volume 238 Author(s): Gabriel Manarin, Daniela Anderson, Jorgete Maria e Silva, Juliana da Silva Coppede, Persio Roxo-Junior, Ana Maria Soares Pereira, Fabio Carmona Abstract Ethnopharmacological relevance Roots of Curcuma longa L. are used as medicine for millennia. They possess several pharmacological properties, including anti-inflammatory action, and can be suitable for asthma treatment. Aim of the study We aimed to test the hypothesis that, in children and adolescents with persistent asthma, the administration of powdered roots of C. longa for 6 months, in addition to standard treatment, compared to placebo, will result in better disease control. Patients and methods We conducted a randomized, double-blind, placebo-controlled, phase II clinical trial. Patients were randomly assigned to receive 30 mg/kg/day of C. longa for 6 months, or placebo. Data were collected prospectively. All patients were categorized for asthma severity and control according to GINA-2016 and underwent pulmonary function tests. Results Overall, both groups experienced amelioration of their frequency of symptoms and interference with normal activity, but no differences were found between the two treatment groups. However, patients receiving C. longaexperienced less frequent nighttime awakenings, less frequent use of short-acting β-adrenergic agonists, and better disease control after 3 and 6 months. Conclusion The powdered roots of C. longa led to less frequent nighttime awakenings, less frequent use of short-acting β-adrenergic agonists, and better disease control after 3 and 6 months, when compared to placebo. Graphical abstract

Evaluation of the subacute toxicity of Yongdamsagan-tang, a traditional herbal formula, in Crl:CD Sprague Dawley rats Publication date: 28 June 2019 Source: Journal of Ethnopharmacology, Volume 238 Author(s): Eunsook Park, Mee-Young Lee, Chang-Seob Seo, Hyeun-Kyoo Shin, Su-Cheol Han, Hyekyung Ha Abstract Ethnopharmacological relevance Yongdamsagan-tang, a traditional herbal formula, is used widely for the treatment of inflammatory and viral diseases. However, the safety of Yongdamsagan-tang has not been established. Aim of the study To evaluate the subacute toxicity of Yongdamsagan-tang water extract (YSTE) in Crl:CD Sprague Dawley rats. Materials and methods We evaluated the subacute toxicity of YSTE in male and female Crl:CD Sprague Dawley rats (n = 5 per group). Rats were treated with YSTE at doses of 0, 1000, 2000 and 5000 mg/kg administered once a day by oral gavage for 4 weeks. Results There were no significant changes in mortality, body weight, food intake, serum biochemistry, or results of hematology and urinalysis after YSTE administration. However, all rats treated with 5000 mg/kg/day YSTE exhibited excessive salivation and discolored urine. Necropsy findings showed discoloration in the liver of both male (n = 1) and female (n = 3) rats treated with 5000 mg/kg/day YSTE, and an increase in the relative weights of kidney and liver was also found in male rats treated with 5000 mg/kg/day. In addition, decreases in serum creatinine, total bilirubin, alanine transaminase, and alkaline phosphatase were observed in male rats treated with 2000 or 5000 mg/kg/day YSTE. Conclusions Abnormalities in some rats are considered to be independent of YSTE toxicity. Therefore, the results suggest that oral administration of YSTE in rats for 4 weeks is safe at doses of up to 5000 mg/kg/day. Graphical abstract

Huo Xue Tong Luo capsule ameliorates osteonecrosis of femoral head through inhibiting lncRNA-Miat Publication date: 28 June 2019 Source: Journal of Ethnopharmacology, Volume 238 Author(s): Bin Fang, Ying Li, Chen Chen, Qiushi Wei, Jiaqian Zheng, Yamei Liu, Wei He, Dingkun Lin, Gang Li, Yonghui Hou, Liangliang Xu Abstract Ethnopharmacological relevance Traditional Chinese medicine has a long history of treating various bone diseases including osteoporosis and osteonecrosis etc. In clinical treatment, Huo Xue Tong Luo capsule (HXTL capsule) containing Peach kernel, Safflower carthamus, Angelica sinensis, Ligusticum wallichii etc, is one of the mostly used prescriptions for treating osteonecrosis of the femoral head (ONFH) with promising effects. Objectives This study aims to identify the underlying molecular mechanism of how HXTL capsule exerts its function to ameliorate ONFH. Materials and methods All femoral bone tissues were collected during surgeries. Rat bone marrow mesenchymal stem cells (rMSCs) were used. Quantitative real time PCR was used to check the relative expression levels of genes. ChIP assay was performed to evaluate the binding of H3K4me3 and H3K27me3 in Miat promoter. Results We showed that HXTL capsule promoted osteogenesis in rat MSCs as demonstrated by quantitative real time PCR and Alizarin Red S staining. Then we found silencing the endogenous lncRNA-Miat could promote osteogenesis of rMSCs. In addition, the ChIP assay showed that HXTL capsule significantly increased occupancy of H3K27me3 and decreased H3K4me3 in promoter regions of Miat, meaning HXTL capsule inhibited Miat expression through histone modifications. At last, by examining the femoral heads samples obtained from patients with ONFH during total hip arthroplasty surgery, we found the RNA level of hMiat in necrotic tissue was much higher than that of normal tissue. Conclusions Taken together, our study shows that lncRNA-Miat might play an important role in pathogenesis of ONFH, and HXTL capsule can promote osteogenesis to ameliorate ONFH through inhibiting the transcriptional expression of Miat, at least partially. Graphical abstract

Urginea indica attenuated rheumatoid arthritis and inflammatory paw edema in diverse animal models of acute and chronic inflammation Publication date: 28 June 2019 Source: Journal of Ethnopharmacology, Volume 238 Author(s): Ghazala Akhtar, Arham Shabbir Abstract Ethnopharmacological relevance Urginea indica has been used in the traditional system of medicine to treat various inflammatory diseases. Aim of the study Present study investigates the effects of aqueous and ethanolic extracts of U. indica on joint inflammation using different models of acute and chronic inflammation. Materials and methods FCA-induced arthritic rat model, a model of chronic joint inflammation, was used to evaluate the anti-arthritic effects of plant extracts (500 mg/kg, each extract). Macroscopic arthritic scoring, digital water plethysmometery, and histopathological evaluation (H & E staining) were performed to measure the severity of arthritis. Acute inflammatory models like, carrageenan-, histamine- and serotonin-induced paw edema models were used to evaluate effects of U. indica, and supported by xylene-induced ear edema model. Results Both extracts significantly inhibited arthritic development, paw edema, bone erosion, pannus formation, and infiltration of inflammatory cells. Treatment with U. indica extracts resulted in almost normalization of altered counts of white blood cells (WBCs), platelets, and red blood cells (RBCs), along with Hb content. Both extracts were found safe in terms of hepatotoxicity and nephrotoxicity as determined by non-significant difference of alanine aminotransferase (ALT), aspartate transaminase (AST), urea, and creatinine levels among all groups. U. indica significantly attenuated carrageenan-induced paw edema. There are several mechanisms involved in the attenuation of carrageenan-induced paw edema; inhibition of autacoids is one of those important mechanisms. The autacoid inhibition was confirmed by reduction of histamine- and serotonin-induced paw edema found in plant extract treated groups. Suppression of xylene-induced ear edema by plant extract further validated the suggested mechanism of autacoid inhibition. GC-MS analysis showed the presence of isopropyl palmitate in the highest quantity (26.852%). Conclusions This study validated the folkloric uses of U. indica and showed that plant possessed anti-arthritic and anti-inflammatory properties which might be ascribed to inhibition of autacoids. Graphical abstract

Subchronic toxicity and concomitant toxicokinetics of long-term oral administration of total alkaloid extracts from seeds of Peganum harmala Linn: A 28-day study in rats Publication date: 28 June 2019 Source: Journal of Ethnopharmacology, Volume 238 Author(s): Youxu Wang, Hanxue Wang, Liuhong Zhang, Yunpeng Zhang, Yuchen Sheng, Gang Deng, Shuping Li, Ning Cao, Huida Guan, Xuemei Cheng, Changhong Wang Abstract Ethnopharmacological relevance The seeds of Peganum harmala Linn, in which the most abundant active compounds are harmaline and harmine, have been widely used as a traditional medicine in various countries to treat a broad spectrum of diseases including asthma, cough, depression, Parkinson's and Alzheimer's diseases. However, few studies on long-term or subchronic toxicity of seeds of P. harmala were reported after overdose. Aim of the study To investigate the subchronic toxicity and concomitant toxicokinetics of total alkaloid extracts from seeds of P. harmala (TAEP) after oral administration for four weeks in rats. Materials and methods The subchronic toxicity and concomitant toxicokinetics of TAEP were evaluated after 28-day oral administration in rats at daily dose levels of 15, 45, and 150 mg/kg. The signs of toxicity and mortality were monitored and recorded daily. The body weight and average food consumption were measured weekly. The analyses of hematology, biochemistry, urine, relative organ weights and histopathology were conducted at the termination of treatment and recovery phase. For concomitant toxicokinetics study, the plasma toxicokinetic parameters, tissue distribution, and excretion of predominant ingredients harmaline and harmine in TAEP and metabolites harmalol and harmol were tested. Results Following initial repeated exposure to high-dose (150 mg/kg/day) of TAEP excitotoxic reaction, such as tremor, was observed, but tolerated on the fourth day after multiple dosing. The significant alterations in blood glucose and lipid metabolism in liver were observed, but recovered after four weeks of drug withdrawal. The no-observed-adverse-effect level (NOAEL) of TAEP was considered to be 45 mg/kg/day under the present study conditions. There were no significant gender differences in most indexes of subchronic toxicity throughout the experimental period with the exception of food consumption and body weight. In concomitant toxicokinetics study, the alterations of dynamic characteristic for harmaline, harmine and metabolite harmol after multiple oral administration at three doses had been observed. Harmaline, harmine and metabolites harmalol and harmol were widely distributed in organs and there was no accumulation in the tissues examined. The reduction of harmaline and metabolite harmalol in brain after multiple dosing at dose of 150 mg/kg might be closely related to the tremor tolerance. The main excretory pathway for metabolites harmalol and harmol was urinary excretion via kidney. Conclusions The results revealed that TAEP at doses of 15 and 45 mg/kg/day in rats might be safe. Excitotoxic reaction such as tremor occurred initially at dose of 150 mg/kg/day, however, the toxicity was tolerant and reversible. In addition, harmaline and harmine in TAEP had a quick absorption into blood and metabolized to harmalol and harmol, and there was no drug accumulation in the detected tissues. Further studies should be investigated to clarify the mechanisms of tremor tolerance and neurotoxicity of TAEP. Graphical abstract

Kidney Diseases and Transplantation

Burden, access, and disparities in kidney disease Deidra C Crews, Aminu K Bello, Gamal Saadi, for the World Kidney Day Steering Committee  Saudi Journal of Kidney Diseases and Transplantation 2019 30(2):281-290 Kidney disease is a global public health problem, affecting over 750 million persons worldwide. The burden of kidney disease varies substantially across the world, as does its detection and treatment. In many settings, rates of kidney disease and the provision of its care are defined by socio-economic, cultural, and political factors leading to significant disparities. World Kidney Day 2019 offers an opportunity to raise awareness of kidney disease and highlight disparities in its burden and current state of global capacity for prevention and management. Here, we highlight that many countries still lack access to basic diagnostics, a trained nephrology workforce, universal access to primary health care, and renal replacement therapies. We point to the need for strengthening basic infrastructure for kidney care services for early detection and management of acute kidney injury and chronic kidney disease across all countries and advocate for more pragmatic approaches to providing renal replacement therapies. Achieving universal health coverage world-wide by 2030 is one of the World Health Organization’s Sustainable Development Goals. While universal health coverage may not include all elements of kidney care in all countries, understanding what is feasible and important for a country or region with a focus on reducing the burden and consequences of kidney disease would be an important step towards achieving kidney health equity.

Therapeutic plasma exchange for children with kidney disorders: Definitions, prescription, indications, and complications Khalid A Alhasan Saudi Journal of Kidney Diseases and Transplantation 2019 30(2):291-298 Therapeutic plasma exchange (TPE) is a procedure that involves the removal of a large volume of plasma that is replaced with a replacement fluid, which is usually 5% albumin or fresh-frozen plasma. This therapeutic modality presents several technical challenges in children but has become increasingly used in pediatric nephrology. Owing to advances in technology, scientists have gained substantial knowledge of the molecular pathogenesis underlying many pediatric renal diseases, supporting the use of TPE in treating these disorders. This review presents a synopsis of the literature as it relates to the accepted indications for TPE in children, the technical aspects of the procedure, and the associated complications. Increased collaboration between pediatric nephrologists will hopefully allow scientists to obtain more data in children to assess the benefits of TPE in various renal disorders and improve the quality of care provided in children with renal disorders.

Birth weight, gestational age, and blood pressure: Early life management strategy and population health perspective Issa Al Salmi, Faisal A M. Shaheen, Suad Hannawi Saudi Journal of Kidney Diseases and Transplantation 2019 30(2):299-308 The incidence of hypertension (HTN) is rising worldwide with an estimated prevalence of 22%, 7.5 million deaths (12.8%). It is a major risk factor for coronary heart diseases and hemorrhagic strokes. In Oman, the crude prevalence of HTN was 33.1%, whereas the age-adjusted prevalence was 38.3%. Among Gulf Cooperation Countries, 47.2% of the individuals were hypertensive, and women were more likely to have HTN than men. Similarly, the prevalence of low-birth-weight (LBW) is also rising globally with the more prevalent incidence in developing countries reaching almost a rate just lower than 20.0/100 births. In Oman, the prevalence of LBW was 4.2% in 1980, which doubled (8.1%) in 2000 and has shown a slow but steady increase reaching 10.2% in 2013. LBW term is the most commonly used surrogate measure of intrauterine growth retardation and has been related to increased cardiovascular mortality, due to increased risk of cardiovascular risk factors, including blood pressure (BP), diabetes, cholesterol level, and other risk factors. The epidemiologic evidence clearly points to an inverse association between birth weight and many hemodynamic cardiovascular risk markers. Possible mechanisms operating in fetal life that might determine BP include the structural development of resistance arteries, the setting of hormone levels, and nephron endowment. Retarded fetal growth leads to permanently reduced cell numbers in the kidney. Patients with high BP had almost 50% less number of glomeruli compared to that of the normotensive individuals, and subsequent accelerated growth may lead to excessive metabolic demand on this limited cell mass. It is not merely a reduced nephron number that is responsible for HTN, but compensatory maladaptive changes that occur internally when nephrogenesis is compromised. The likelihood of an adverse outcome is greatly amplified in those born with LBW who later develop obesity or an increased ponderal index.

Chyluria in pregnancy: Etiology, diagnosis, and management perspective Bimalesh Purkait, Gaurav Garg, Manmeet Singh, Ashish Sharma, Siddharth Pandey, Satya Narayan Sankhwar Saudi Journal of Kidney Diseases and Transplantation 2019 30(2):309-314 Chyluria is clinically described as passage of milky urine. Chyle is absorbed by intestinal lacteals and is composed of emulsified fats, few proteins, and fibrin in varying proportions. Parasitic chyluria is caused mainly by Wuchereria bancrofti infection. The incidence of chyluria in pregnancy is not uncommon in endemic regions. The literature pertaining tomedical management of chyluria in pregnancy is scant. The antifilarial drugs have potential teratogenic risk and are not recommended in pregnant patients. Hence, there is a management dilemma for managing patients with chyluria during pregnancy. In this review, we have tried to highlight the evidence-based diagnosis and management of chyluria in pregnancy.

Association of hepcidin and anemia in early chronic kidney disease Satyendra Kumar Sonkar, Neeraj Kumar Singh, Gyanendra Kumar Sonkar, Sant Pandey, Vivek Bhosale, Anil Kumar, Kauser Usman Saudi Journal of Kidney Diseases and Transplantation 2019 30(2):315-324 Hepcidin is being extensively studied for anemia and inflammation in chronic kidney disease (CKD) patients. Hepcidin is thought to regulate iron metabolism by iron blockade through various mechanisms. Patients with CKD have early cardiac mortality due to anemia and subclinical inflammation; hence, we studied hepcidin as a biomarker in patients with early stage of CKD in relation to anemia and inflammation. In our cross-sectional study, a total of 80 patients were enrolled of whom, there were 25, 26, and 29 patients in CKD stages 1, 2, and 3, respectively. Patients were divided into normal iron level (39), functional iron deficiency (FID) (18), and absolute iron deficiency (AID) (23) based on transferrin saturation and ferritin. We found significantly high level of hepcidin (P <0.05) and high-sensitivity C-reactive protein (hsCRP) (P <0.05) in FID as compared to AID as well as normal iron level. We also found other inflammatory markers such as albumin, transferrin, and ferritin to be significantly associated with FID. In univariate analysis, hemoglobin (Hb) varied significantly with serum total iron-binding capacity (r = 0.40, P <0.001), log hsCRP (r = -0.32, P <0.01), and log ferritin (r = -0.23, P <0.05); however, Hb was not affected significantly with log hepcidin (r = -0.07, P >0.05). The study indicates that among early CKD patients with FID, there was high level of hepcidin along with other inflammatory parameters, which may be associated with poor cardiovascular disease outcome due to increased inflammation.

Acute cortical necrosis in pregnancy still an important cause for end-stage renal disease in developing countries Anupma Kaul, Hiral Lal, Prabhakar Mishra, Manoj Jain, Narayan Prasad, Mandakini Pradhan, Manas Ranjan Patel, Amit Gupta, Raj Kumar Sharma Saudi Journal of Kidney Diseases and Transplantation 2019 30(2):325-333 Renal cortical necrosis (RCN) is a serious complication of acute kidney injury (AKI) and pregnancy is a clinical state closely associated with it with poor renal outcomes. The incidence is much higher in obstetrical AKI compared to other causes of RCN. Despite better medical care facilities available, this continues to be an important cause of morbidity and mortality in developing countries. This is a retrospective analysis among all pregnant females presenting with AKI from January 1999 to December 2014 at a tertiary care center in the northern part of India. We looked for the incidence of obstetrical-related RCN in our renal biopsies performed in the last 15 years and to evaluate precipitating factors responsible for RCN. RCN constituted 8.3% of pregnancy-related AKI cases in our institution. The overall incidence has been declining which was 9.09% from 1999 to 2008 to 7.8% from 2009 to 2014. The patient’s median age was 29.3 ± 5.2 years. The average time to presentation from the day of delivery was 8.7 ±2.1 days. The mortality was observed in 11.7% of them with sepsis and multiorgan dysfunction present in all of them. The most common etiology for RCN was found to be septic abortion and puerperal sepsis accounting for - 15.3% each. Postpartum hemorrhage was a cause in 9.09% of patients. The most important cause of RCN was postpartum thrombotic microangiopathy which was observed in 48.7% of patients. Kidney biopsy was helpful in diagnosis in 31 patients while computed tomography scan abdomen alone helped in diagnosis in five patients. Patchy cortical necrosis in histology was seen in 35.4% of patients and morbidity in terms of prolonged hospitalization was seen in 22.7% while dialysis dependency in 61.5% of the study population. In conclusion, strategies need to be implemented in reducing the preventable causes for RCN which is not only catastrophic in terms of renal outcomes but also for social and psychological perspectives as well.

Seroconversion following hepatitis B vaccination in children with chronic kidney disease Nivedita Kamath, Anil Vasudevan, Arpana Iyengar Saudi Journal of Kidney Diseases and Transplantation 2019 30(2):334-338 Seroconversion following hepatitis B vaccination is low in children with chronic kidney disease (CKD). This study aimed to assess the seroconversion and persistence of protective immunity following hepatitis B vaccination in children with CKD. This prospective observational study was conducted in a tertiary pediatric nephrology centre to assess the seroconversion and maintenance of antibody titers (>10 mIU/mL) at one year following hepatitis B vaccination (10 μg at 0, 1, and 2 months) in children with CKD Stages II to V. Those who did not seroconvert after the schedule were re-vaccinated, and antibody titers were checked. Categorical data were expressed as proportions and analyzed using the Chi-square test. Pearson’s correlation test was used to determine the correlation of antibody titers with other continuous variables. Seroconversion was observed in 72% (n = 26/36) after vaccination. Only 60% (n = 6/10) had seroconversion after the second course of vaccination. Only 60% of children (n = 12/20) who seroconverted had protective antibody titers at one year. Seroconversion following three doses of hepatitis B vaccine is low in children with CKD. Antibody titers should be monitored periodically as the protective immunity wanes rapidly.

Status of fasting in Ramadan of chronic hemodialysis patients all over Egypt: A multicenter observational study Abir Farouk Megahed, Ghada El-Kannishy, Nagy Sayed-Ahmed Saudi Journal of Kidney Diseases and Transplantation 2019 30(2):339-349 There is a paucity of data concerning safety of fasting in Ramadan in chronic kidney disease patients on hemodialysis (HD). The aim of the present study was to assess the frequency of fasting in Ramadan in HD patients in Egypt and the possible effect of fasting on clinical and biochemical variables. This observational multicentric study was carried out during 2016 when fasting duration was around 16 h.

A study of detection and comparison of immunofluorescence on formalin-fixed paraffin-embedded tissue with fresh frozen renal biopsy specimen Ranjana Solanki, Madan Kumar Solanki, Deepika Hemrajani, Jayesh Saha Saudi Journal of Kidney Diseases and Transplantation 2019 30(2):350-358 Direct immunofluorescence on the fresh frozen tissue is established way of demonstrating of immunoglobulins and complement deposition in renal biopsies. IF studies can be done on paraffin-fixed tissue (IF-P) and give comparable results to those obtained on frozen tissue for most pathogenic immunoglobulins and immunoglobulin fragments; although, the detection of C3c may be more problematic. In our study, we used proteinase-K method for antigen retrieval. We aimed to detect immunoglobulins and complements in formalin-fixed paraffin-embedded (FFPE) tissue sections from renal biopsies and have comparison of IF staining intensity on FFPE sections with conventional IF on fresh frozen tissue. Based on our results, we conclude that IF-P can serve as salvage technique and has significant diagnostic utility.

Postoperative complications in living liver donors: A retrospective study, single-center experience in Saudi Arabia Nouf Abdulaziz Althonaian, Alanoud Saleh Alsaiari, Weaam Ahmed Almanea, Norah Jezaa Alsubaie, Awatif Ali Almuharimi, Alaa Althubaiti, Abdulrahman Rashed Altamimi, Khalid Omer Abdullah, Wael Abdulaziz Ohali Saudi Journal of Kidney Diseases and Transplantation 2019 30(2):359-364 Living donor liver transplantation (LDLT) offers life to patients with end-stage liver disease. The balance between the benefit to the recipient and the risk to the donor plays a central role in justifying LDLT. However, the incidence rates of complications posttransplant differ widely. This study is designed to identify postoperative complications in LDLT in a tertiary care center King Abdulaziz Medical City (KAMC). This was a retrospective cohort study. All donors at KAMC between January 2003 and December 2015 were reviewed through a hospital database and patient charts to determine the postoperative complications based on the modified Clavien classification system. All donors were relatives of the recipients and assessed before the surgery. A total of 101 donors underwent LDLT: 75 were male and 26 were female, with a mean age of 27.7 ± 6.6. The breakdown of specific surgical procedures was as follows: 65 (64.3%) donors underwent right hepatic lobectomy, 31 (30.6%) underwent left lateral hepatectomy, three (2.97%) underwent extended right hepatectomy with the inclusion of the middle hepatic vein, and two (1.98%) underwent left hepatectomy. Postoperative complications were determined in 20 patients (19.8%), but no mortality was observed. Complications were reported in 14 (21.5%) right and six (19.4%) left lateral hepatectomy donors. A total of 12 patients had Grade I complications, six patients had Grade II complications, and Grade III complications were reported in two cases. The most frequent complications were upper limb weakness to brachial plexus neuropathy and mild bile leak. Life-threatening complications in our center have not been reported in LDLT; however, some donors may experience postoperative morbidity, which usually were mild and had a good prognosis.