Cardiology Plus

Bile acid and cholesterol metabolism in atherosclerotic cardiovascular disease and therapy John Y. L. Chiang, Jessica M Ferrell, Yue Wu, Shannon Boehme Cardiology Plus 2020 5(4):159-170 Dysregulation of lipid metabolism is a major factor contributing to atherosclerotic cardiovascular disease (ACVD), which is the number one cause of death in western countries. The liver plays a central role in maintaining whole body cholesterol homeostasis via catabolism of cholesterol to bile acids, as well as biliary cholesterol excretion. The liver synthesizes lipoproteins that transport dietary cholesterol and fats to muscle and adipose tissue, directs reverse cholesterol transport of excess cholesterol from extrahepatic tissues and macrophages to the liver to convert to bile acids, and thus, protects against metabolism-related nonalcoholic fatty liver disease (NAFLD) and ACVD. Liver fibrosis/nonalcoholic steatohepatitis increases the risk and prevalence of cardiovascular disease morbidity and mortality. Bile acids are signaling molecules and metabolic regulators that activate farnesoid X receptor and G protein-coupled bile acid receptor-1 to regulate lipid, glucose, and energy metabolism. The bidirectional regulation of bile acids and the gut microbiota determine the rate of bile acid synthesis, the bile acid pool size, and the composition of the circulating bile acid pool. The liver-intestine-heart axis regulates lipid metabolism, inflammation, and the pathogenesis of metabolic diseases such as ACVD, NAFLD, diabetes, and obesity. This review focuses on the roles of liver-to-intestine, liver-to-heart and intestine-to-heart axes in cholesterol, lipoprotein, and bile acid metabolism; signaling in heart health and ACVD; and drug therapies for atherosclerosis.

Warfarin or non-Vitamin K antagonist oral anticoagulants: Navigating the choice of oral anticoagulant drugs in the COVID-19 pandemic era Heng Cai, Xin Zhou, Qing Yang Cardiology Plus 2020 5(4):171-174 Emerging evidence indicates that thromboembolic complications are a key determinant of inhospital mortality of patients with COVID-19. Prophylactic anticoagulation therapy is an important component of inhospital management of patients with COVID-19. Considering that millions of patients worldwide are prescribed oral anticoagulation therapy, herein, we summarize the pros and cons of non-Vitamin K antagonist oral anticoagulants (NOACs) and warfarin, in terms of pharmacodynamics, and therapeutic efficacy and adverse effect monitoring in the context of the global pandemic of COVID-19. Despite a lack of evidence from high-quality randomized trials, an NOAC, rather than warfarin, would be a scientifically reasonable treatment option for patients with COVID-19 in the outpatient setting.

Chinese expert consensus on percutaneous coronary intervention through distal transradial artery access Chinese Expert Consensus Group for Percutaneous Coronary Intervention through the Distal Transradial Artery Access; Thumb Club Cardiology Plus 2020 5(4):175-185

The impact of hypertension on left ventricular diastolic dysfunction and arterial stiffness in the elderly: A cross-sectional study Miyesaier Abudureyimu, Jing-Min Zhou, Xue-Juan Jin, Xiao-Tong Cui, Kai Hu, Jun-Bo Ge Cardiology Plus 2020 5(4):186-193 Objectives: To study the prevalence of LVDD and arterial stiffness and the association with LVDD and/or arterial stiffness among residents with HTN, as well as determine whether aging was independently correlated with LVDD and arterial stiffness. This was a cross-sectional study, using results from the Shanghai Heart Health study, a national project in China. Methods: Using data from 2086 participants, we explored the associations of HTN and LVDD with or without arterial stiffness using brachial–ankle pulse wave velocity (baPWV). Correlations of LVDD with or without arterial stiffness were analyzed in adjusted multivariable logistic models. Results: The proportion of subjects with LVDD was 37.5%, arterial stiffness was 47.5%, and HTN was 58.4%. LVDD in participants with arterial stiffness occurred in 55.2% and HTN in 65.9%. Pairwise comparisons showed that systolic blood pressure was significantly different and more strongly associated with HTN (68%) (P < 0.01). For subjects with normal diastolic function of normal baPWV or LVDD with increased value of baPWV, logistic multivariate regression showed that aging (odds ratio [OR]: 1.05, 95% confidence interval [CI]: 1.04–1.81) and HTN (OR: 1.45, 95% CI: 1.08–1.93) were independent correlates of LVDD with arterial stiffness. Conclusions: The prevalence of arterial stiffness increases in the early stages of LVDD. HTN and aging were independently related to LVDD with arterial stiffness among community-dwelling residents.

Cardiac anatomy for electrophysiology Siew Yen Ho Cardiology Plus 2020 5(4):194-202 This article presents some of the important structures relevant to electrophysiological intervention and mapping. Notable structures within the neighborhood of the heart are the respective courses of the esophagus and phrenic nerves. The right atrium contains the sinus node, terminal crest, and cavotricuspid isthmus. The landmarks of the triangle of Koch are a guide to the location of the atrioventricular node, while the central fibrous body and the membranous septum is a guide to the location of the atrioventricular conduction bundle. The arrangement of the ventricular outlets and attachments of semilunar valvar leaflets, as well as the location of aortic sinuses relative to the atria and left ventricular summit, are presented.

Left subclavian arterial thrombosis presenting as acute limb ischemia in a COVID-19 patient – An extreme rarity Meenakshi Gajbiye, Akshay Ashok Bafna, Kishore Deore, Swenil Shah, Varun Bafna Cardiology Plus 2020 5(4):203-206 The peak of the coronavirus disease 2019 (COVID-19) crisis has exposed a substantial number of patients presenting with manifestations of venous and arterial thrombosis. Here, described is an extremely rare case of subclavian arterial thrombosis in a COVID-19 patient. Moreover, the patient presented with normal D-dimer, antinuclear antibody, fibrinogen, serum ferritin levels, prothrombin time, and platelet count. To the best of our knowledge, this is the first such case reported till date.

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Kasr Al Ainy Medical Journal

COVID-19 infection: a magnified look at the kidneys Neveen A Soliman Kasr Al Ainy Medical Journal 2020 26(2):33-36 The global health crisis of novel coronavirus 2019 (COVID-19) pandemic has overwhelmed all medical disciplines, including nephrology. This review focuses on how kidneys are affected by COVID-19 infection and discusses some etiologic, pathogenic, and clinical aspects of kidney involvement in COVID-19 infection, including clinical outcome. Special strategies are required to improve clinical outcome and should be regularly updated based on gained knowledge and evidence.

The broad-spectrum antiparasitic ivermectin against COVID-19 Nadia A El Dib, Mona I Ali Kasr Al Ainy Medical Journal 2020 26(2):37-40 Ivermectin, the FDA-approved broad-spectrum antiparasitic drug, has recently shown excellent antiviral effects against many viral infections. This effect was especially important in the current pandemic infection of COVID-19. There are reports that ivermectin inhibited the replication of the virus in vitro in 48 h. Studies have been done on other viral infections and on this virus in vivo and in vitro. The results showed that it affects the viral replication by its effect on the protein transfer between the cytoplasm and nucleus inside the host cells. More information is still needed to approve its use in the treatment and prevention of COVID-19 pandemic, which will necessitate more studies to adjust the dose and mode of administration.

A practical approach to coronavirus disease 2019 pneumonia imaging Youssriah Y Sabri, Sally Emad-Eldin Kasr Al Ainy Medical Journal 2020 26(2):41-54 Coronavirus disease 2019 (COVID-19) was first recognized in China in December 2019 and then was declared as a pandemic by the WHO in March 2020. The most established diagnostic tool is the real-time reverse transcription-PCR, which is highly specific but has a relative low sensitivity. False-negative results and consequently the need to repeat the test and relative delay in conclusive results are a real diagnostic problem. Other laboratory marker tests are more suggestive than diagnostic. All these factors have made computed tomographic (CT) imaging in cases of clinically suspected COVID-19 a routine and an integral part of the algorithm for disease diagnosis in many countries including Egypt. The role of CT is well established in detecting the presence of a lesion, discriminating different types of lesions, and assessing distribution, severity, complications, associated extrapulmonary chest manifestations, and follow-up of cases. The CT picture of COVID-19 is known to reflect atypical pneumonia and/or organizing pneumonia. The presence of ground-glass opacities, consolidation, or crazy paving in bilateral subpleural distribution with predominant lower lobes affection is considered typical for COVID-19. Based on our experience, in the context of the current pandemic, the presence of CT inflammatory changes in a patient with clinical suspicion of COVID-19 should be considering as an alarming sign for the presence of COVID infection as the cause of ground-glass opacities. A negative CT report for COVID-19 should only be considered in cases of normal CT or if CT lesions do not represent inflammatory changes.

Resilience with the crisis: cardiology department experience to cope with the corona virus disease 2019 pandemic Ahmad Samir, Mera A.S Fahim, Ahmed Mohsen, Hossam Mahrous, Kareem Mahmoud, Ahmed Elamragy, Marwa S Meshaal, Hesham Yehia, Waleed Ammar, Karim Said, Yasser Baghdady, Hesham Salah, Magdy Abdelhamid, Mohamed Abdelghany Kasr Al Ainy Medical Journal 2020 26(2):55-59 Rationale During the coronavirus disease (COVID-19) pandemic, there were many challenges facing practices in different medical specialties. Objectives Maintain medical and educational services provided by Cardiology Department at the required standards amid the COVID-19 pandemic. Methods We described our experience in restructuring various strategies and activities and developing adaptive measures to cope with the crisis. Results and Conclusion Multiple considerations and self-adjusting adaptations are mandated in challenging situations like the COVID-19 crisis. Exchanging experiences is needed to improve performance in similar future situations.

Changes in eye care during the covid-19 pandemic from Egyptian patients' point of view Lameece M Mohamed, Ayah Marrie, Kareem B Elessawy Kasr Al Ainy Medical Journal 2020 26(2):60-67 Purpose This study aims to understand the impact of COVID-19 on patients’ view and willingness to seek ophthalmic services in Egypt. The study analyzes if there were changes in their eye care habits and under the conditions they would seek ocular advice. Patients and methods It is a cross-sectional observational study using a questionnaire that was sent online and the answers were received online. The questionnaire included 31 questions. All questions were closed-ended questions, provided with a list of optional answers (single-answer options or multiple-answer options). Results This study included the responses of 448 participants, who answered the questionnaire fully and included their names and email addresses. Of the participants, 262 were women (58.5%) and 186 (41.5%) were men. The largest age group that answered our questionnaire was between the ages of 20 and 40 years (85.3%). The vast majority of the participants (98%) claimed they would not visit an ophthalmologist during the pandemic and would not undergo any elective surgery. Conclusion Age, medical background, educational level, contact with vulnerable groups, and presence of chronic diseases significantly affect the patients’ willingness to seek ophthalmic services. Changes in populations’ information and doctor practice are needed in this pandemic.

HRCT chest in COVID-19 pneumonia: correlation between duration of symptoms and CT severity score Hegazy M.A Rania, Salah E.L Din Adel Lamia Kasr Al Ainy Medical Journal 2020 26(2):68-75 Objective The aim was to find the correlation between duration of symptoms and computed tomography (CT) severity score in patients with novel coronavirus pneumonia. Patients and methods This study was conducted on 108 patients with proven COVID-19 pneumonia. Results A total of 108 patients were enrolled in this study with proven diagnosis of COVID-19 infection with 81 positive swabs (75%) and 27 negative swabs (25%). The 27 patients with negative swabs had typical features of fever, laboratory studies consistent with infection, and CT features of bilateral pneumonic changes. The study included 72 (66.7%) men and 36 (33.3%) women, with mean age of 52.1 (age range: 34–81 years) years. Patients were categorized according to the duration of onset of initial symptoms and the date of CT scans: stage 1 (0–4 days, n=36); stage 2 (5–9 days, n=30); stage 3 (10–14 days, n=15); stage 4 (15–21 days, n=9); stage 5 (22–28 days, n=3); and stage 6 (>28 days, n=15). Each stage average CT chest score of severity and average percentages of both lung opacities were shown. The authors found that CT severity score increases, as the duration of initial symptom increases, up to 9 days, from the onset of symptoms. CT score has a second peak at less than or equal to 20-day duration of symptoms and a third peak at more than 28 days, where a plateau is reached. Although patient’s clinical condition and oxygen saturation may improve, yet CT changes may persist with a high CT severity score for weeks thereafter. Conclusion CT severity score corresponds to the duration of symptoms only in the early stage of disease. In later stages, some patients develop residual lung affection after recovery from acute symptoms, yet lung changes take weeks to resolve, and in some cases, residual chronic changes may persist.

Evaluation of anthelminthic activity of both pomegranate peels and Artemisia herba-Alba extracts in comparison with praziquantel in experimentally infected mice with Hymenolepis nana Azza H Abbas, Fetouh S Hassanin, Neveen M Sarhan, Heba M Abdelgalil Kasr Al Ainy Medical Journal 2020 26(2):76-82 Background Praziquantel (PZQ), is the drug of choice in the treatment of Hymenolepis nana infection, although it has some adverse effects (side effects and toxicity). Natural biological products that have minimal side effects and more safe. Many researchers demonstrated the antimicrobial and antiparasitic therapeutic effect of pomegranate and Artemisia. Objective Our study aims to evaluate the therapeutic effect of pomegranate and Artemisia as an alternative treatment in H. nana infection. Subjects and Methods 32 male albino mice were inoculated with human fecal sediments containing H. nana eggs (about 100 eggs/gm) and were divided into four groups after proven to be infected with H. nana: Group 1; treated with Pomegranate peels extract, Group 2; treated with Artemisia herb-Alba extract, Group 3; treated with PZQ, and finally, Group 4; treated with Pomegranate peels and Artemisia herb-Alba mixture’ extract. Results Both Pomegranate peels and Artemisia herb-Alba extracts presented a significant decrease (P-value = 0.002 and 0.001, respectively) in the number of viable eggs after 7 days of treatment in comparison to the first day. Pomegranate peels and Artemisia herb-Alba extracts ‘results established anthelmintic effect against H. nana. Conclusion Our results showed that both Pomegranate peels and/or Artemisia herb-Alba extracts can be used as alternative, less expensive and more safe therapeutic approach in H. nana infection.

Coronary angiographic profile in Egyptian patients with xanthelasma palpebrarum Noha Hassanin, Sameh Wadie Ghaly Bakhoum, Mahmoud Elsayed Saraya Kasr Al Ainy Medical Journal 2020 26(2):83-89 Background Xanthelasma palpebrarum are yellow plaques that are found near the inner canthus of the eyelid. However, it is still controversial whether such lesions are marker for coronary artery disease. Aim The aim of the study was to investigate the association between xanthelasma and severity of coronary artery disease using coronary angiography. Settings and design A prospective, case–control study was conducted on 86 patients scheduled for coronary angiography to diagnose coronary artery disease. The study population included two groups. Groups A and B were formed of 43 patients each with and without xanthelasma, respectively. Patients and methods The day before diagnostic coronary angiography, all patients were subjected to full medical history taking; clinical examination; laboratory investigations, including lipoprotein (a) [Lp (a)], serum creatinine, and lipid profile; 12-lead electrocardiogram; and transthoracic echocardiography. A written informed consent was taken from all included patients, and approval of the CMREC (Cairo Medical Research Ethics Committee) was obtained. Results Waist circumferences were increased in patients with xanthelasma compared with those without. Low-density lipoprotein and Lp(a) levels were significantly increased in patients with xanthelasma. The severity of coronary artery disease was significantly increased in patients with xanthelasma. Conclusion Hypertension, diabetes, and dyslipidemia were common in patients with xanthelasma palpebrarum. The presence of xanthelasma and Lp(a) were independent predictors of coronary artery disease. The severity of coronary artery disease was significantly increased in patients with xanthelasma.

Trans-knee amputation with posterior myocutaneous flap in patients with advanced peripheral arterial disease Mohamed T Yousuf Kasr Al Ainy Medical Journal 2020 26(2):90-94 Background Critical limb ischemia can result in major amputation when revascularization proved to be impossible. Major amputation is sometimes unavoidable in patients with acute lower limb ischemia with irreversible damage (category III). When compared with the above-knee amputation (AKA), trans-knee amputation (TKA) or knee disarticulation has a durable end weight-bearing stump with a long, powerful, active lever arm for control of the prosthesis with excellent muscle attachments. The round distal stump enhances suspension of the prosthesis. Another advantage is decreased operative blood loss with less bony or muscular disruption, less energy consumption, and resistance to infection by maintaining the cartilage barrier to infection. Purpose Our objective is to evaluate the outcomes of TKA with posterior myocutaneous flap in patients with advanced peripheral arterial disease who are not candidates for below-knee amputation (BKA). Patients and methods his prospective interventional study included 24 patients with advanced peripheral arterial disease in need for amputation and BKA is likely to fail. All patients underwent TKA with posterior myocutaneous flap including gastrocnemius muscle. The indication for amputation was critical limb ischemia owing to unreconstructable peripheral arterial disease in 21 (87.5%) patients in whom revascularization options are unavailable or exhausted and irreversible (category III) acute thrombotic lower limb ischemia in three (12.5%) patients. Results The study was conducted on 24 patients, comprising 15 (62.5%) males and nine (37.5%) females. The mean age of patients was 65.8±10.5 years. Overall, four (16.6%) patients had previous contralateral AKA. Three (12.5%) patients died: two patients died in the early 3 postoperative days and one patient died in the same hospital admission after 35 days. For the remaining 21 patients, healing by primary intention was achieved in 15 (71.4%) patients, by delayed primary intention (tertiary intention) in one (4.8%) patient, and by secondary intention in two (9.6%) patients. Major wound dehiscence occurred in three (14.2%) patients requiring AKA. Conclusion TKA with posterior myocutaneous flap is a safe operative method of amputation in patients with advanced peripheral arterial disease with good healing rates and acceptable functional outcomes. If it is not possible to perform BKA, TKA should be considered before AKA.

Dysphonia as the main presenting symptom of COVID-19: a case report Ahmad M Eltelety, Ahmed A Nassar Kasr Al Ainy Medical Journal 2020 26(2):95-97 The spectrum of illness associated with COVID-19 is wide, ranging from asymptomatic infection to life-threatening respiratory failure. Herein, the authors are presenting a case in which the main symptoms expressed by a patient infected with SARS-CoV-2 were simultaneous gradual change of voice with loss of olfaction but without nasal obstruction.

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Otorhinolaryngology Head and Neck Surgery

Fibrolipoma of the nasopharynx Mohammad H Shaheen, Heba Z Kufiah Saudi Journal of Otorhinolaryngology Head and Neck Surgery 2020 22(2):41-44 Nasopharyngeal fibrolipoma is exceedingly rare. This review article aims to recognize the characteristics of this rare tumor along with a favorable way to diagnose and treat it. We reviewed six cases of nasopharyngeal fibrolipoma. This lesion involves both sexes at any age. It is tremendously rare with only six case reports in the English literature and should be considered in the differential for nasopharyngeal masses. Nasopharyngeal fibrolipoma can be diagnosed by radiological investigations as a hypodense, well-defined nonenhancing lesion on the computed tomography and confirmed histologically, and endoscopic or transoral surgical excision approach is the most accepted management. However, no cases reported recurrence for this lesion.

Sensible awareness for otolaryngologist in managing aerodigestive foreign bodies in time of COVID-19 Muneera Abdulla Al Khalifa, Noor Yousif Abdulkarim Saudi Journal of Otorhinolaryngology Head and Neck Surgery 2020 22(2):45-49 Background: In the time of COVID-19, the world came to a cease, however medical emergencies are ceaseless. Aerodigestive tract foreign bodies are one of the frequent emergencies in otolaryngology. Within the era of COVID-19, otolaryngologists have been documented to be at high risk of infection. Due to high viral load in the respiratory epithelium, the examination and extraction of foreign bodies in the aerodigestive tract places the otolaryngologist at high risk. Objective: The objective was to highlight the appropriate way of handling aerodigestive foreign bodies in the time of COVID-19 pandemic to insure safety of all involved medical staff. Methods: This was a systematic review of related international published guidelines. Results: A simplified flowchart is suggested to help guide the triaging of emergency patients with aerodigestive foreign body in the COVID-19-affected area. Conclusion: COVID-19 is a highly contagious infection that places health-care workers, especially the workers dealing with the aerodigestive tract at high risk. An appropriate management of these cases is essential to protect the health-care workers.

Oral ranulas: A 15-year retrospective clinico-surgical evaluation in a major referral hospital in the Southern Province of the Kingdom of Saudi Arabia John Spencer Daniels, Ibrahim AlBakry, Ramat Oyebunmi Braimah, Mohammed Ismail Samara Saudi Journal of Otorhinolaryngology Head and Neck Surgery 2020 22(2):50-56 Background: A ranula is a mucous extravasation phenomenon involving the sublingual gland. The main objective of the current study was to present a clinic-surgical evaluation of ranula in our center. Materials and Methods: This is a 15-year retrospective analysis of ranulas in the main referral hospital in the Najran Region of the Kingdom of Saudi Arabia. Data collected includes demographics, type of ranula, modality of occurrence, laterality, surgical approach, and type of treatment. Data were stored and analyzed using IBM SPSS Statistics for IOS Version 25(IBM Corp., Armonk, NY, USA). Results were presented as simple frequencies and descriptive statistics. Results: Fifty-five cases of oral ranula were recorded out of a total of 75 ranulas during the study with a prevalence rate of 0.14 cases/1000 persons. There were 27 males and 28 females with a male-to-female ratio of 1:1.03. Their ages ranged from 2 years to 45 years with mean ± standard deviation (22.2 ± 10.7). The age group from 11 to 20 years had the highest frequency with 19 cases, representing 34.5% followed by the age group of 21–30 years with 16 cases, representing 29.1%. Of the total of 55 cases of oral ranula, 53 (96.4%) had the lesions excised together with the sublingual gland through intraoral approach, while only 2 (3.6%) cases were marsupialized. Conclusions: We have reported that oral ranulas represent about 73.3% of the ranulas. Surgical removal of the lesion and the sublingual gland is essential for the prevention of recurrence. Loose intraoral suturing in the floor of the mouth is advised to prevent saliva refilling.

Nasal bone measurements in the middle eastern population based on radiological analysis: A cross-sectional retrospective study Salma Saud Al Sharhan, Maha I Al Somali, Fahad S Al Zahrani, Mona M Ashoor, Sawsan F Almarzouq, Afnan F Almuhanna, Adnan T Samarah Saudi Journal of Otorhinolaryngology Head and Neck Surgery 2020 22(2):57-62 Objectives: Performing septorhinoplasty surgery requires comprehensive knowledge of nasal morphology. The effect of racial differences on nasal bone morphology has gathered increasing interest. However, previous studies have primarily focused on the Western population with a few studies assessing the Middle Eastern participants. We aimed to provide itemized measurements of the nasal bone morphology as the baseline data for the Middle Eastern population. Study Design: This was a retrospective cross-sectional single-center study. Materials and Methods: We included patients who underwent maxillofacial computed tomography between February and August 2019 at King Fahad Hospital of University. The Kolmogorov–Smirnov test was used to check the assumption of data normality. The Mann–Whitney U-test and Student's t-test were used for nonsymmetrical and symmetrical variables, respectively. One-way analysis of variance was used for symmetrical data. Chi-square test was used to compare the categorical variables. Results: We included 276 cases. The mean right and right nasal bone length was significantly larger in men than in women. Moreover, patients with severe nasal septal deviation angle had significantly lower left and right medial bone thickness, as well as the internasal angle. Conclusion: There were significant between-sex differences in the nasal bone morphology. There was no side predilection for deviated nasal septum and nasal bone thickness. However, severe cases of deviated nasal septum presented a lower medial nasal bone thickness, which could be attributed to ethnic variations in the Middle Eastern population.

The efficacy of botulinum toxin injection on adductor spasmodic dysphonia Hatem Ezzeldin, Gamal Youssef Saudi Journal of Otorhinolaryngology Head and Neck Surgery 2020 22(2):63-68 Background: Adductor spasmodic dysphonia (ASD) is a voice disorder characterized by strained, stuttering-like voice (involuntary disruptions of voice). Botulinum toxin (BT) injection of the vocal folds (VFs) is the treatment of choice, however, the doses and method of injection are variable. Objectives: The aim of this study is to assess the effect of BT injection on the voices of the patients having ASD. Patients and Methods: Twelve patients with ASD treated bilaterally with VF BT injection in the office under local anesthesia. Each patient evaluated by laryngoscopic examination, acoustic analysis, and voice handicap index. Results: All patients improved markedly regarding laryngoscopic, acoustic, and self-assessment parameters. Conclusion: BT can be used effectively for the treatment of ASD and improving phonatory (voice) and quality of patients' life.

Accuracy of fine-needle aspiration in diagnosing of well-differentiated thyroid cancer at a tertiary care center Mazin A Merdad, Zahra'a I Alghafli, Sarah M AlSharif, Marwah S AlQathmi, Ghazi M Sindi, Hani Z Marzouki Saudi Journal of Otorhinolaryngology Head and Neck Surgery 2020 22(2):69-72 Background: Thyroid cancer is the third-most common cancer in Saudi females and males. The Bethesda System for Reporting Thyroid Cytopathology provides a diagnostic framework that can be used in surgical decision-making that allows the use of standardized treatment algorithms for each category. The present study aims to assess the accuracy of fine-needle aspiration (FNA) in diagnosing well-differentiated thyroid cancer in comparison to the corresponding final histopathological results. Methodology: This was a retrospective review of 404 patients who underwent FNA cytology, followed by thyroid surgery during 2010–2018. Data were collected from the medical records of these patients. Results: Based on the final histopathological examination results, 63% of the tested nodules were benign and 36% were malignant. The tested thyroid nodules with Bethesda categories II, III, IV, V, and VI were diagnosed as malignant in 8.7% 33.3%, 50%, 60%, and 94.4%, respectively. FNA (Bethesda categories II and VI) for benign and malignant lesions revealed a sensitivity, specificity, positive predictive value (PPV), and negative predictive value of 79.69%, 97.84%, 94.44%, and 91.28%, respectively. Conclusion: FNA is a reliable diagnostic tool for diagnosing thyroid nodules with a high specificity and PPV. The capability of the relatively high overall malignancy rate can be explained by the nature of our institution, being a major regional tertiary and cancer center. The size of the nodule and its location, body mass index, and age had no significant effect on the accuracy of the FNA.

Laryngeal pathology requiring microlaryngoscopy a retrospective descriptive study of a single tertiary center in bahrain Maryam Isa Khalifa, Fatema Mohamed Alasfoor, Tasabeeh Ahmed Qareeballa Yousif, Fatema Sayed Ali Mohamed Alhashimi Saudi Journal of Otorhinolaryngology Head and Neck Surgery 2020 22(2):73-77 Background: Laryngeal pathologies are commonly encountered in otolaryngology practice, and more benign lesions have been described than malignant ones. Microlaryngoscopy and biopsy are used to obtain a definite diagnosis in such cases. Aim: The aim was to study laryngeal pathologies requiring microlaryngoscopy in our tertiary care center during the period of 2014–2018. Study Design: This was a retrospective cohort study. Materials and Methods: Data were retrospectively extracted from the records of patients who had a suspected diagnosis of laryngeal pathology based on history and clinical examination and eventually underwent microlaryngoscopy procedures under general anesthesia. Results: There were 51 participants who underwent 58 microlaryngoscopic examinations. Males accounted for 61% of the participants. The mean age was 45 years. The most frequently presenting complaint was voice change. Benign lesions were more common than malignant ones. The most frequently described lesions were vocal fold polyps. Conclusion: We believe this is the first epidemiologic study to investigate laryngeal pathologies requiring microlaryngoscopy in Bahrain. The study provides insight into our population presenting with laryngeal pathology requiring microlaryngoscopy and could provide a basis for future research.

Incidence and risk factors of inadvertent parathyroidectomy during thyroid surgery: A single-center retrospective study Abdulaziz Rajeh Alanzi, Abdullah Ghafouri, Wael Khalifa, Hassan Hawsawi, Suzan Alzaidi Saudi Journal of Otorhinolaryngology Head and Neck Surgery 2020 22(2):78-81 Context: Thyroidectomy is considered a relatively safe surgery with morbidity of <5% when undertaken by experienced surgeons. Inadvertent parathyroidectomy (IP) means pathology report has found parathyroid tissue in the thyroid specimen, and it was reported to range from 2.9% to 31%. Aims: The aim of this study is to measure the incidence rate and to evaluate the significant relationship between risk factors and IP during thyroid surgery. Settings and Design: A retrospective chart review study was carried out in King Fahad Armed Forces Hospital, Jeddah, between June 2015 and December 2019. Subjects and Methods: All consecutive patients undergoing unilateral or bilateral thyroidectomy were enrolled in this study. Histopathology reports were reviewed to identify the specimens that included parathyroid tissue and underlying thyroid disease, and these were compared to patients with no parathyroidectomy in terms of gender, pathological features, re-operation, Hashimoto thyroiditis, extrathyroidal extension, and central neck dissection. Statistical Analysis Used: Statistical analysis was carried out using the Statistical Package for the Social Sciences. Results: Retrospective analysis of 181 consecutive thyroidectomy cases reveals that 34 (18.7%) patients had IP. Significant risk factors for IP included extra-thyroid extension (P = 0.008), total thyroidectomy (P = 0.017), and Hashimoto thyroiditis (P = 0.021). Other risk factors, including gender, malignancy, central neck dissection, and re-operation, were not statistically significant in this study. Conclusions: IP during thyroid surgery is not uncommon (18.7%). Total thyroidectomy, hashimoto thyroiditis, and extrathyroidal extension of the tumor were found to be significant risk factors. We recommend more meticulous intra-operative identification of parathyroid glands, particularly for patients with these risk factors.

Skeletonizing the facial nerve underwater: A pilot study Eman Hajr, Laila Hajr, Fida Almuhawas, Farid Alzhrani, Abdulrahman Hagr Saudi Journal of Otorhinolaryngology Head and Neck Surgery 2020 22(2):82-85 Objective: Drilling of the facial recess represents an important step in cochlear implant (CI) surgery. It is crucial for the next step of exposing the round window. This study sought to evaluate the efficacy of underwater drilling (UWD) during the opening of the facial recess for CI surgery. Materials and Methods: This was a prospective clinical pilot study performed at a quaternary care center. We included adult and pediatric patients who underwent bilateral simultaneous CI surgeries. Any patients with facial nerve anomalies or previous ear surgery were excluded from the study. Drilling of the facial recess on one side was performed using UWD (case side); on the other side (control side), drilling was performed by minimal water drilling (MWD). Drilling was performed by the same surgeon on both sides. The time differences between the procedures were recorded. Results: A total of 21 patients were included in this study; 66% (14/21) were males, and the mean age was 8.25 years (standard deviation ± 12.00 years) at the time of surgery. UWD was completed, and the results of a normal facial nerve examination were documented postoperatively. The time needed for UWD (12 ± 6.72 min) was slightly shorter than the time needed for MWD (13 ± 6.15 min), but that difference was not significant (P = 0.71). Conclusion: The drilling of facial recess is one of the most stressful steps during CI surgery, we recommend the use of UWD because of its good safety profile and protective measures.

Left thyroid agenesis case study Bayan Osama Besharah, Haddad Hussin Al-Kaf, Sherif Kamel Abdelmonim, Mohammad Ali Al-Essa Saudi Journal of Otorhinolaryngology Head and Neck Surgery 2020 22(2):86-88 Thyroid hemiagenesis is a rare congenital anomaly, more commonly affecting the left lobe of the thyroid. There is only one case reported in Saudi Arabia in Annals Saudi journals 1997, and this will be the second case to be reported in Saudi. Here, we present a 67-year-old woman with the left thyroid lobe agenesis and multinodular goiter in the right thyroid lobe. The condition was discovered during preoperative preparation for tracheostomy, which showed euthyroid (in laboratory measurements) and an enlarged right large thyroid lobe extending up to cervical vertebra 2 and the retrosternal area (in computed tomography images). The patient underwent total thyroidectomy and tracheostomy. Postoperative thyroid scan and histopathology results confirmed the diagnosis. It is a rare anomaly, with most patients asymptomatic. Consequently, cases may not be readily diagnosed.

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Ophthalmology

Social determinants of blindness in Sudan- 2019 Mohanad Kamaleldin Mahmoud Ibrahim Al-Basar International Journal of Ophthalmology 2020 7(1):1-3 Background: The term blindness is used for complete or nearly complete vision loss. The number of people estimated to be visually impaired worldwide is 285 million; 39 million are blind and 246 have low vision. About 90% of the world visually impaired lives in low-income settings. The overall objective of this study was to identify the social determinants of blindness in Sudan, aiming for prevention and control. Methodology: This was an outreached service cross-sectional study conducted among 858 participants selected using multistage cluster sampling and drawn proportionate to size among four cities in Sudan using probability sampling technique. The data were collected using closed-ended administered questionnaires, and data were analyzed using the Statistical Package for the Social Sciences version 21. The analysis included uni-variate for all determinants and bi-variate cross-tabulation using Chi-square test to reveal associations between variables of interest. The study was estimated at 95% confidence level. Results: The overall socioeconomic profile of the study group was low. The mean monthly income of the blind participants was only 1991 sustainable development goal. The majority of the blind participants were unemployed, where they represented >70% and there was a significant association between occupation and blindness (P = 0.000). More than half of the blind participants (58%) were living in rural areas, and the study revealed a significant association between blindness and living are (P = 0.000). Conclusion: The socioeconomic status in terms of income, occupation, and living area and is significantly associated with blindness. A majority of the blind participants are living in rural areas, unemployed, and earn low monthly income.

Tear film assessment in sudanese diabetic patients attending Jabir Abu Eliz Diabetic Center, Khartoum, Sudan Saeeda Mohammed Osman, Mahgoub Saleem Al-Basar International Journal of Ophthalmology 2020 7(1):4-10 Background: Several local and systemic conditions predispose the eye to the development of dry eye disorders due to tear film dysfunction, which is presented in variable degrees of eye irritations and inflammation. Diabetes mellitus (DM) is among the most common risk factors of dry eye disease (DED). It is more common in older females than males. Tear film assessment can be tested with some simple tests such as Schirmer's test (ST), fluorescein strip (FS) (breakup time [BUT]) test, and lissamine green strip (LGS) test. Objective: The aim of this study is to assess the tear film dysfunction in diabetic patients with ST, FS papers, and LGS papers and compare their diagnostic values. Materials and Methods: In a cross-sectional hospital-based study, consecutive 126 diabetic patients were examined at Jabir Abu Eliz Diabetic Center in Khartoum for their tear film dysfunction. All selected patients had simultaneously undergone ST, FS (BUT) test, and LGS test in the same order and equal definite intervals in all patients over a 2-month period (September 1, 2013–November 1, 2013). Clinical and personal information was obtained by direct patients and chart review before complete ophthalmic examinations. Results: The mean age of the study group was 53 ± 12.1 years (30–78 years). Fifty-seven patients (45.2%) were female and 69 (54.8%) were male. In the age group, 11 (8.7%) patients were of type I DM, whereas 115 (91.3%) of type II DM. Forty-four (34.9%) patients had good DM control and 82 (65.1%) had poor DM control. The ST results of the current study demonstrated the presence of 142 patients (56.3%) in the “normal Schirmer's grade,” 49 patients (19.4%) in “mild-to-moderate Schirmer's grade,” and 61 patients (24.2%) in “severe Schirmer's grade.” In the BUT “FS” test, 165 patients (65.5%) gave normal results, whereas 87 patients (34.5%) showed severe tear dysfunction results, with a highly significant difference with P = 0.001. Whereas, in the LGS test, 201 patients (79.8%) were of “normal grade” results and 51 patients (20.2%) were “mild-to-moderate” grade. Conclusion: DED is an important feature of poorly controlled DM, which can be easily detected by performing a variety of simple quick tests such as the ST, fluorescein tear BUT test, and LGS test. There is notable variation among these three tears; therefore, a combination of any two tests is necessary. There is a strong correlation between qualities of the DM control, duration of DM, and severity of DED.

Screening of retinitis pigmentosa among Sudanese students of Al-Neelain University Eye Hospital, Khartoum, Sudan Reem Elrasheed Gadkariem, Mahgoub Saleem, Saeeda Mohammed Osman Al-Basar International Journal of Ophthalmology 2020 7(1):11-15 Background: Retinitis pigmentosa (RP) is a genetic retinal disorder that leads to progressive visual impairment. Early symptoms are night blindness, followed by the loss of peripheral vision and constricted visual fields. The symptoms and signs worsen as time goes. Objectives: The objective of this study was to determine the incidence of RP among Sudanese students of Al-Neelain University College of Optometry and Visual Science from March to May 2017. Materials and Methods: In a cross-sectional observational hospital-based study, which was conducted at Al-Neelain University Eye Hospital, Gabrah, Khartoum, Sudan, in 3-month period, from March to May 2017, by a consecutive sampling technique, 193 Sudanese students from Al-Neelain University College of Optometry and Visual Science were examined for the presence of RP. Data were statistically analyzed using SPSS. Results: Females were 154 (79.8%) and males were 39 (20.2%). Their mean age was 21.76 years ± 2.5 years (range: 16–25 years). One hundred and forty-five (75.1%) students were between 21 and 25 years and 48 (24.9%) students were between 16 and 20 years. The majority (99.5%) reported negative symptoms of night blindness, and few (0.5%) reported definite positive symptoms of night blindness. Only 2 (1.0%) students out of the whole study group disclosed family history of RP. Sixty-one (31.6%) participants revealed consanguinity; 2 (1%) of them were of first-degree and one (0.5%) of second-degree consanguinity. One hundred and forty-three (74.1%) participants were emmetropic while fifty (25.9%) with minor degrees of ammetropia (±0.5–0.75 diopter). Overall, 188 (97.4%) scored 6/6 best-corrected visual acuity. None of the partinsepants students reviled any degree of color defect. Intraocular pressure in all students was within normal limits. No single student revealed fundus appearance of RP in all 193 candidates and even in those with symptoms of night blindness or family history of RP. Conclusion: No single RP case with typical fundus appearance and visual functional loss was reported in 193 male and female Sudanese students of Al-Neelain University College of Optometry and Visual Science.

Rubella virus in association with congenital cataract at makkah eye complex Muhennad H Halees, Mahgoub Saleem, Arwa Abdalla Al-Basar International Journal of Ophthalmology 2020 7(1):16-20 Background: Rubella is a viral disease that causes many systemic and ocular postnatal anomalies known as congenital rubella syndrome (CRS). The most common ocular disorder is congenital cataract. Purpose: The purpose of this study was to determine the prevalence of CRS and its association with congenital cataract and systemic comorbidities. Materials and Methods: In this cross-sectional, hospital-based study, full ophthalmic and systemic examination was carried out on 45 infants (n = 45), aged below 1 year, with congenital cataract, attending the Pediatric Ophthalmology Clinic at Makkah Eye Complex, Khartoum, Sudan, in the period between February 2015 and June 2016. The 45 children were booked for phacoemulsification plus intraocular lens implantation. The children's biodata and maternal and neonatal history were obtained from the mothers and plotted in case investigation forms. Venous blood sample and lens aspirate were studied for rubella IgM, IgG, and polymerase chain reaction beside rubella virus detection in the National Laboratory of Measles and Rubella. Results: Blood and lens aspirate was collected from the study infants, which revealed that 38 infants (84%) were negative for rubella, whereas only seven infants (16%) showed positive result. The majority of the rubella-positive patients (n = 5, 71%) had bilateral cataract and only two infants had unilateral cataracts. Only one rubella-positive case (14.3%) had microphthalmia in one eye. Unfortunately, screening for pigmentary retinopathy was not done postoperatively. Four (57%) out of the seven rubella-positive cases reported systemic CRS. Microcephaly, patent ductus arteriosus, ventricular septal defect, and pulmonary hypertension were reported in one case (14.3%) each. Three mothers (43%) from the rubella-positive group had a history of febrile illness during pregnancy. Conclusion: Congenital cataract and systemic comorbidities are common in infants with congenital rubella.

Diabetic retinopathy-related knowledge level among the omani population Gopi Suresh Vankudre, Galal Ismail, Noof Salim Hamdan Al Maamari Al-Basar International Journal of Ophthalmology 2020 7(1):21-26 Background: An annual report published by the Ministry of Oman stated the diabetes mellitus (DM) prevalence of 15.7% among the patients attending a nutritional clinic. This estimate is higher than the prevalence rate of 12.3% that was reported in the national survey done in 2008. The Omani population having sight-threatening diabetic retinopathy (DR) ranges from 14.5% to 42.2%. Many factors can lead to the burden of DR, such as nonawareness or nonserious approach toward eye care. Materials and Methods: This cross-sectional questionnaire-based study included 232 participants through a convenient sampling technique. It used a semi-structured interview method to secure the participant responses for evaluating their DR-related knowledge. Statistical Analysis Used: The significance of the association for knowledge among the different study variables was analyzed by applying the Chi-square test and Fisher exact test. One-way analysis of variance was used to compare the knowledge level between participants with different sociodemographic backgrounds. Results: 91.4% of the study population with nonmedical background are aware of ocular complication of diabetes. Condition-linked knowledge adequacy was associated with gender (P < 0.013), personal (P < 0.00) or family history (P < 0.017) of diabetes, and area of residence (P < 0.012). Only 0.61% of the general population had excellent knowledge about DR, whereas 58.28% of the study participants had a poor, and 22.09% had very poor knowledge about the condition. Conclusions: Majority of the study participants are aware of ocular complications due to DM. However, variations were observed for the condition-related knowledge level, its prevention, diagnostic treatment, and managerial options in case of visual impairment.

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Biomedical and Biotechnology Research

Understanding the genetics of gastric and esophageal cancer using Drosophila melanogaster as a model organism Preeti Thiyagarajan, Venkatachalam Deepa Parvathi Biomedical and Biotechnology Research Journal (BBRJ) 2020 4(4):269-273 Drosophila melanogaster, a vicious model, has helped in significant discoveries about several conserved mechanisms. The insect intestine had remained unexplored until the identification of adult somatic stem cells which triggered the invention of genetic amenability of this insect organ in powerful and artistic ways. A variety of mechanisms within the fruit flies' intestine are conserved in human gastrointestinal systems and will, therefore, become relevant within the context of human pathologies such as gastrointestinal cancers and obesity. In line with current guidelines, maintaining a high degree of suspicion of hereditary etiology (genetic involvement) helps in disease diagnosis. In this review, genetics of two crucial cancers are discussed. Mutation or transcriptional silencing of the cadherin-1 (CDH1) gene and tumor protein p53 gene is related to familial diffuse gastric cancer (GC) and esophageal adenocarcinoma, respectively. Testing for CDH1 mutations in patients with familial clustering of hereditary diffuse GC has proven consistent. Further studies on the expression and also the alteration within the proteins within the E-CDH pathways and Hippo pathway may function as biomarkers for early detection. Dysregulation of various mechanisms ends up in invasion, proliferation, and metastases. The promise of targeted therapy and personalized medicine in improving the clinical outcome is now closer than it has ever been.

General awareness on hantavirus infection: A brief review Rashed Noor Biomedical and Biotechnology Research Journal (BBRJ) 2020 4(4):274-279 Hantavirus is a negative, stranded RNA virus, largely known to be transmitted to humans, especially working in forestry from the rodents. The human-to-human transmission of this virus is still in obscure; however, upon transmission of this virus from the rodent fluids, its fatality is noticed mainly through the hyperinflammatory syndrome and the cardiopulmonary syndrome. Several reports revealed an alternation of the immune response including the natural killer cells, CD8+ T cells, neutrophils, and several cytokines during the viral pathogenesis. Unlike the other emerging viruses including the currently ongoing novel coronavirus (COVID-19) pandemic, the global mortality rate due to hantavirus infection is so far very low, which, in turn, made the general people all around the world know a very little about this virus. Besides, no effective antiviral therapy including vaccines has yet been developed to combat the viral infection. Lots of comprehensive reports elaborately discussed this virus pointing toward its dreadfulness. The current review discussed the fatal effects of the hantavirus infection in a relatively simplistic way, which can be easily understood by the general community who are still unaware of the risks posed by this relatively uncommon virus.

Genetic makeup and associated virulence posed by the enteropathogenic Escherichia coli and the Enterotoxigenic Escherichia coli pathotypes Syeda Muntaka Maniha, Rashed Noor Biomedical and Biotechnology Research Journal (BBRJ) 2020 4(4):280-284 The enteropathogenic Escherichia coli (EPEC) is known to trigger diarrhea in infants, whereas the enterotoxigenic E. coli (ETEC) accounts for the children's diarrhea and the travelers' diarrhea. Transmission of the pathogenic bacteria usually occurs in a fecal–oral route usually originating from the poultry items. Thus, the study relating these E. coli pathotypes to the required virulence factors would be of great interest for the welfare of mass public health. Although the reports on the food-oriented pathogenic E. coli so far are actually uncountable, the present review especially concentrated on the genetics of virulence factors required for the pathogenesis by EPEC and ETEC based on the information given by the previous literature. The review focused on the expressional regulation of the components required for the EPEC pathophysiological impact on humans. The necessary studies correlating the genome with the expression of the virulence factors have been well discussed.

Does epstein–barr virus participate in the development of breast cancer? A brief and critical review with molecular evidences Muhammad Usman, Yasir Hameed, Mukhtiar Ahmad Biomedical and Biotechnology Research Journal (BBRJ) 2020 4(4):285-292 The oncogenic potential of Epstein–Barr virus (EBV) has been well studied in human breast cancer (BC) so far but still controversies surround its role. In the present study, we aimed to perform a comprehensive and critical review of the results and methodologies used by the previous studies to identify the association between EBV markers with human breast. We also proposed a criterion based on the Bradford hill postulates of causation and EBV prevalence to evaluate the results of previous studies for proving EBV etiological role in breast cancer. A PubMed search engine-based strategy was implemented to retrieve all the relevant studies. In total, 50 original studies were retrieved. Out of which 20 were case–control studies while others were not. The positivity ratios of EBV detection in breast cancer samples varied study wise. Few studies did not identify the EBV markers in breast cancer while others identified it with different detection positivity ratios varying from 2.9% to 75.8%. Similarly, the EBV detection positivity ratios in normal and benign samples also varied between 0%–35% and 0%–75.8%, respectively. In total, 18 out of 20 case–control studies, the positivity ratios of EBV detection were higher or equal in breast samples as compared to controls, while two case–control studies also report the opposite results. However, the odds ratios and confidence intervals were not reported. The results failed to prove EBV as a potential biomarker of breast cancer but rather suggested its role as a cause-effect or at least co-participant.

The role of estrogen in breast cancer Roaa Khadem, Fatimah Chassab Mahdi, Karrar AI-Mosawi, Ali Abdul Hussein S. AL-Janabi Biomedical and Biotechnology Research Journal (BBRJ) 2020 4(4):293-296 Estrogen has a significant effect on the development of breast cancer. Its activities in the human body are mainly performed by binding to cellular estrogen receptor (ER). Breast cancer in relate to the presence of ER can be divided into ER-positive and ER-negative breast cancer. The role of estrogen and its receptors in the development of breast cancer will be discussed in this review.

Influence of De novo mutation in autism Ann Mary Alappat Sanjeev, Bharathi Kathirvel, Kaviya Mohandass, Vijaya Anand Arumugam Biomedical and Biotechnology Research Journal (BBRJ) 2020 4(4):297-301 Autism and autism spectrum disorders (ASD) affects the areas of social awareness and interaction, verbal and nonverbal communication, and behaviors and interests, which are grouped among neurobehavioral disorders. One in 68 children is affected with ASD according to the estimate from the Center for Disease Control and Prevention's autism and developmental disabilities monitoring network and an increasing prevalence observed worldwide. A characteristic heterogeneity in ASD determined genetic variability as a major contributor. Whole-exome sequencing of ASD individuals revealed that discrete de novo mutation (single-nucleotide variation or small indels) also contribute to the overall genetic risk of ASD apart from rare genetic variation affecting single nucleotides of protein-coding DNA or rare genomic copy number variants as assessed through other high-throughput genomic methods. These genes are involved in synaptic transmission and regulated during brain development by acting upstream or downstream of Wingless- related integration site (WNT), bone morphogenetic proteins/transforming growth factor-β, sonic hedgehog, fibroblast growth factor, and retinoic acid signaling pathways. The current review focuses on genes involved in synaptic function, undergoing de novo mutation leading to ASD condition.

FNCas9 editor-linked uniform detection assay: An innovative COVID-19 sleuth Tarun Kumar Suvvari, MD Nawaz, Mani Kruthika Mantha Biomedical and Biotechnology Research Journal (BBRJ) 2020 4(4):302-304 Relying on traditional diagnostic approaches like quantitative polymerase chain reaction is not appropriate for both time and cost in sudden outbreaks and pandemics such as COVID-19. In such cases, diagnostic approaches through rapid sequencing of pathogenic DNA and RNA are important for accelerated clinical prognosis. FNCas9 Editor-Linked Uniform Detection Assay (FELUDA) is one such diagnostic approach toward the pathogenic genome, developed by CSIR-IGIB. FELUDA is a paper strip diagnostic test like pregnancy, based on clustered regularly interspaced short palindromic repeats/Cas technology of gene editing. FELUDA showed 96% sensitivity and 98% specificity across all range of viral loads in clinical samples. Due to its low cost, it can drastically reduce the Indian budget toward the rapid testing and COVID-19 diagnostic kits.

Phytochemical and antioxidant assessments of Dioscorea bulbifera stem tuber Othuke Bensandy Odeghe, Elias Adikwu, Chioma Cynthia Ojiego Biomedical and Biotechnology Research Journal (BBRJ) 2020 4(4):305-311 Background: Dioscorea bulbifera (D. bulbifera) is used in traditional medicine for the treatment of many disease conditions. However, there is a paucity of information on the antioxidant potential of its stem tuber. Methods: The antioxidant activity of the methanolic extract of D. bulbifera stem tuber was evaluated by measuring its ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, superoxide anion radical (O2-) and nitric oxide (NO) radical. It was also analyzed for bioactive secondary metabolites using standard qualitative and quantitative spectrophotometric methods. Results: The extract showed total phenolic content (0.243 ± 0.052 mg) gallic acid equivalent compared to tannins content (0.259 ± 0.034 mg). Low flavonoid contents (0.060 ± 0.025 mg) quercetin equivalent (QE) and high flavonol contents (1.399 ± 0.075 mg) QE were found in the extract. The extract showed a potent concentration-dependent DPPH radical inhibitory potential with maximal inhibition activity (69.39 ± 1.62%) at 5000 μg/mL compared to ascorbic acid with maximal inhibition activity (88.9 ± 2.67%) at the same concentration. The extract produced maximal O2- anion inhibitory activity (52.86 ± 0.68%) at 2500 μg/mL compared to quercetin with maximal inhibitory activity (68.23 ± 0.41%) at the same concentration. The extract exhibited NO activity in a dose-depend fashion when compared to α-tocopherol. Conclusion: These results showed that D. bulbifera stem tuber extract contains bioactive secondary metabolites with potent-free radical scavenging activity, which could be extracted and standardized for use as food, medicine, and in industries.

Detailed analyses about predictive value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in invasive lobular breast cancer Esra Arslan, Tamer Aksoy Biomedical and Biotechnology Research Journal (BBRJ) 2020 4(4):312-317 Backgrounds: Management of invasive lobular breast cancer (ILC) is limited with only using standard uptake value (SUV) max of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography. We aimed detailed predictive, prognostic and clinical value of parameters, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) with survival data. Methods: Forty-nine ILC was included in this study. SUVmax, MTV, and TLG documented in molecular and histopathological subtypes. SUVmax, MTV, and TLG compared with nodal involvement, distant metastasis, estrogen receptor (ER), progesterone receptors (PR) and HER status, Ki-67 and survival data. Results: 61.2% luminal A, 36.7% luminal B and 2.0% TN. 53.1% classic and 46.9% pleomorphic. 93.9% ER + and 81.6% had e-cadherin loss. Mean SUVmax was 8.32 ± 4.73. No statistically significant relationship found between classical and pleomorphic with SUVmax (P = 0.616). FDG uptake found significantly higher with tumor >2 cm (P = 0.039). Luminal B SUVmax significantly higher than luminal A (P = 0.013). PR-, Ki-67 high expression, axillary involvement and luminal B significantly reduced survival time (P = 0.034, 0.019, 0.032, and 0.005, respectively). Statistically significant correlation found between high MTV and TLG, tumor diameter (TD) (P = 0.001 and 0.000, respectively). Conclusions: Loss e-cadherin and pleomorphic types did not affect the prognosis. ILC shows low FDG sensitivity compared other breast cancer types, it found to be significantly associated with prognostic factors; TD, molecular subtype, Ki-67 and metastasis. Although volumetric parameters did not add extrapredictive value to FDG involvement pattern, it was found that method remains in diagnosis, staging, and treatment follow-up of ILC.

Synthesis, characterization, and In vitro antibacterial activity and molecular docking studies of N4, N4'-dibutyl-3,3'-dinitro-[1,1'-Biphenyl]-4,4'-diamine K Muddukrishnaiah, V Vijayakumar, B Samuel Thavamani, VP Shilpa, N Radhakrishnan, Heba S Abbas Biomedical and Biotechnology Research Journal (BBRJ) 2020 4(4):318-322 Background: Resistant growth is recognized as a significant public health hazard to human health worldwide among the most critical bacterial diseases. The evolving multidrug-resistant species are now commonly found in community settings, not just in the hospital area, which means that antibiotic bacteria reservoirs are beyond the hospital. Aim: In this study, we synthesized novel N4, N4'-dibutyl-3,3'-dinitro-[1,1'-biphenyl]-4,4'-diamine from 3,3'-dinitro-[1,1'-biphenyl]-4,4'-diamine and evaluation of its antimicrobial activity against clinical bacteria. Methods: Single-step synthesis of novel N4, N4'-dibutyl-3,3'-dinitro-[1,1'-biphenyl]-4,4'-diamine from 3,3'-dinitro-[1,1'-biphenyl]-4,4'-diamine and well characterized using spectroscopic methods, namely FT-IR, NMR, mass spectrometry, and CHNS. Besides, prepared compound molecular docking investigations, molecular physicochemical, absorption, distribution, metabolism, and excretion (ADME) analysis were also carried out. Results and Discussion: Novel Synthesized N4, N4'-dibutyl-3,3'-diaminobenzidine (DAB) was conducted for antibacterial activity against clinical Klebsiella spp. and Staphylococcus aureus and Pseudomonas spp. by the disc-diffusion method and followed by serial dilution method. N4, N4'-dibutyl-3,3'-DAB showed bacteriostatic action of 500 μg/ml, 1000 μg/ml for Klebsiella spp. and Staphylococcus aureus. The molecular physicochemical investigation exhibited that 1 violation and ADME analysis presented a low gastro intestinal effect. Docking investigations disclosed the capability of synthesized molecule potential to dock with beta-lactamase protein through patch dock methodology. Conclusion: N4, N4'-dibutyl-3,3'-DAB is the novel compound that was found to be attractive for the “drug hunters” as a potential agent for the management of infectious diseases against the human pathogens Klebsiella spp. and Staphylococcus aureus.

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Pharmaceutical Sciences

Preparation and characterization of ethylcellulose microspheres for sustained-release of pregabalin Haya Yasin, Bashar Al-Taani, Mutaz Sheikh Salem Research in Pharmaceutical Sciences 2021 16(1):1-15 Background and purpose: Pregabalin is used in the treatment of epilepsy, chronic pain, and other psychological disorders. Preparation of pregabalin in the sustained-release formulation will enhance patient compliance and reduce the incidence of side effects. The aim of this study was to prepare sustained-release microspheres for pregabalin utilizing ethylcellulose and evaluate the processing factors that influence the fabrication and the performance of the prepared microspheres. Experimental approach: The microspheres were prepared using the water-oil-oil double emulsion solvent evaporation method. Microspheres were characterized for particle size, encapsulation efficiency, and in vitro drug release. The influence of the processing variables on the characteristics of the prepared microspheres was studied. Microspheres solid-state characterization performed using differential scanning calorimetry, Fourier transform infrared spectroscopy and scanning electron microscopy. Findings/Results: The results described in the context of the current work illustrated the suitability of the water-oil-oil system in the preparation of sustained-release microspheres for pregabalin. The optimum formulation was prepared at a drug to polymer ratio of 1:3 w/w, stirring speed of 600 rpm, surfactant concentration of 1.5%, and external phase volume of 150 mL. This formula produced microspheres particle size in the range 600-1000 μm, with 87.6% yield, and 80.14 ± 0.53% encapsulation efficiency. Drug release from the microspheres was found to be diffusion controlled, with a pH-independent behavior. Conclusion and implication The current work presented a successful attempt to fabricate a sustained-release microsphere comprising pregabalin. This will help overcome the frequent dosing problems with conventional pregabalin dosage forms and improve product performance.

Immunomodulatory effects of standardized extract of Curcuma mangga val. on cytokines, antibody and delayed-type hypersensitivity response in Wistar rats Yuandani , Sony Eka Nugraha, Lia Laila, Denny Satria Research in Pharmaceutical Sciences 2021 16(1):16-25 Background and purpose: Recently, we have highlighted the immunomodulatory activity of Curcuma mangga Val. on phagocytosis ability. The current study was conducted to determine the immunomodulatory effects of the standardized extract of C. mangga rhizomes by in vitro and in vivo studies. Experimental approach: The C. mangga extract was standardized according to a guideline for herbal preparation. The extract was investigated for its immunomodulatory effects on gene expression of cytokines, cytokines and antibody production as well as delayed-type hypersensitivity (DTH) response. The gene expression of cytokines on lipopolysaccharide-induced-RAW 264.7 cells was analysed by reverse transcription-polymerase chain reaction (RT-PCR) method. The effect of the extract on DTH response was investigated by the paw edema method, meanwhile the effects of the extract on antibody and cytokine production from normal and cyclophosphamide-induced Salmonella typhimurium infected rats were determined using an enzyme-linked immunosorbent assay (ELISA). Findings/Results: The extract of C. mangga demonstrated an inhibitory effect on gene expression of interleukin-1β (IL-1β), tumor necrosis factor-α, and IL-6 as compared to lipopolysaccharide-induced cells. The extract also depicted inhibitory activity on IL-4 production as compared to the negative control. Whereas, the DTH response and production of immunoglobulin G from both groups after treatment with C. mangga extract were higher than those of negative control (P < 0.05). Conclusion and implications: The results indicated that the C. mangga extract has immunomodulatory effects, emphasizing its potential to be developed as immunotherapeutic agent.

Prodigiosin induced the caspase-dependent apoptosis in human chronic myelogenous leukemia K562 cell Maryam Niakani, Ahmad Majd, Parviz Pakzad, Hassan Malekinejad Research in Pharmaceutical Sciences 2021 16(1):26-34 Background and purpose: Chronic myeloid leukemia (CML) as a myeloproliferative disease is characterized by increased cellularity of bone marrow. Implementing the latest treatment protocols is currently accompanied by serious and life-threatening side effects. There are worldwide attempts to find new effective and potent therapeutic agents with minimal side effects on CML patients. This in vitro study was carried out to discover the potential antiproliferative and apoptotic effects of naturally produced prodigiosin (PDG) on K562 cells as an accepted model of CML. Experimental approach: The anti-proliferative effect of PDG was measured by MTT assay. To highlight the mechanism of cytotoxicity, the apoptotic cell death pathway was investigated by morphological and biochemical assessments. The dual acridine orange/ethidium bromide staining technique and western blotting method were applied to assess the mechanism of the potential apoptotic impact of PDG on K562 cells. Findings/Results: PDG-induced time- and concentration-dependent anti-proliferative effects were revealed with an estimated IC50 value of 54.06 μM. The highest cell viability reduction (60%) was recorded in cells, which were exposed to 100 μM concentration. Further assays demonstrated that in the dual acridine orange/ethidium bromide staining method the cell population in the late apoptosis phase was increased in a concentration-dependent manner, which was confirmed with remarkable DNA fragmentation. Conclusion and implications: We found that the PDG-induced apoptosis in K562 cells is mediated through the caspase-3 activation both in mRNA and protein levels. Our results suggest that PDG could be a potent compound for further pharmacokinetic and pharmacodynamics studies in the in vivo model of CML.

Synthesis, antioxidant activity, and density functional theory study of some novel 4-[(benzo[d]thiazol-2-ylimino)methyl]phenol derivatives: a comparative approach for the explanation of their radical scavenging activities Mohammad hossein Asgarshamsi, Afshin Fassihi, Farshid Hassanzadeh, Lotfollah Saghaei, Ahmad Movahedian Attar, Hossein Mohammad-Beigi Research in Pharmaceutical Sciences 2021 16(1):35-47 Background and purpose: Radicals produced by Fenton and Haber-Weiss reactions play detrimental roles in our body. Some oxidized proteins as toxic configurations are identified in amyloid-β deposits. These deposits mostly occur in conditions, such as Alzheimer’s disease. Here, we report the synthesis, evaluation of the antioxidant activity, and implementation of density functional theory (DFT) calculations of some4- [(benzo[d]thiazol-2-ylimino) methyl]phenol derivatives. The aim of this study was to provide a comparative theoretical-experimental approach to explain the antioxidant activities of the compounds. Experimental approach: Compounds were synthesized by the reaction between para hydroxybenzaldehyde and aminobenzothiazole derivatives. The scavenging activity of the compounds was evaluated. Various electronic and energetic descriptors such as high occupied molecular orbital and low unoccupied molecular orbital energy gaps, bonding dissociation enthalpy of OH bond, ionization potential, electron affinity, hardness, softness, and spin density of the radical and neutral species were calculated. DFT calculations with B3LYP hybrid functional and 6-311++ G** basis set in the polarizable continuum model were utilized to obtain these descriptors. Findings/Results: Ascorbic acid showed the best DPPH scavenging activity. However, 4d and 4c showed promising antioxidant activity. The values of EHOMO for 4c and 4d were closer to zero, thus, they showed the best scavenging activities. The computational results were in accordance with the experimental ones. The energetic descriptors indicated that the sequential proton loss-electron transfer mechanism is preferred over other mechanisms. Conclusion and implication: Antioxidant activity of 4-[(Benzo[d]thiazol-2-ylimino) methyl]phenol derivatives confirmed by experimental and theoretical documents proves them as novel antioxidants against amyloid-β based disease.

The potential neuroprotective roles of olive leaf extract in an epilepsy rat model induced by kainic acid Safoura Khamse, Saeed Mohammadian Haftcheshmeh, Seyed Shahabeddin Sadr, Mehrdad Roghani, Mohammad Kamalinejad, Parvane Mohseni Moghaddam, Ravieh Golchoobian, Fatemeh Ebrahimi Research in Pharmaceutical Sciences 2021 16(1):48-57 Background and purpose: Epilepsy is recognized as a chronic neurologic disease. Increasing evidence has addressed the antioxidant and anti-inflammatory roles of olive leaf extract (OLE) in neurodegenerative diseases. So, the current study aimed to investigate the neuroprotective roles of OLE in epilepsy. Experimental approach: Forty rats were divided into 4 groups including a control group, sham group, kainic acid (KA) group, and KA + OLE group. KA (4 μg/rat) was injected intrahippocampal, and OLE (300 mg/kg) was orally administrated for 4 weeks. Animals were sacrificed, and their hippocampi were isolated. KA- induced seizure activity was recorded. Oxidative stress index was assessed by measuring its indicators including malondialdehyde (MDA), nitrite, nitrate, and glutathione (GSH) as well as the catalase (CAT) activity. The supernatant concentration of tumor necrosis factor-α (TNF-α) and the apoptosis rate in neurons were measured. Findings/Results: Treatment with OLE significantly reduced the seizure score. OLE decreased oxidative stress index by reducing the concentration of MDA, nitrite, and nitrate as well as increasing the level of GSH. OLE had a significant anti-apoptotic effect on neurons. However, CAT activity and the level of TNF-α were not affected. Conclusion and implications: Our findings indicated neuroprotective properties of OLE, which is mainly mediated by its antioxidant and anti-apoptotic effects, therefore, could be considered as a valuable therapeutic supplement for epilepsy.

Interactions and effects of food additive dye Allura red on pepsin structure and protease activity; experimental and computational supports Fatemeh Balaei, Mohabbat Ansari, Negin Farhadian, Sajad Moradi, Mohsen Shahlaei Research in Pharmaceutical Sciences 2021 16(1):58-70 Background and purpose: Today, color additives such as Allura red (AR) are widely used in different kinds of food products. Pepsin is a globular protein that is secreted as a digestive protease from the main cells in the stomach. Because of the important role of pepsin in protein digestion and because of its importance in digestive diseases the study of the interactions of pepsin with chemical food additives is important. Experimental approach: In this study, the interactions between AR and pepsin were investigated by different computational and experimental approaches such as ultraviolet and fluorescence spectroscopy along with computational molecular modeling. Findings/Results: The experimental results of fluorescence indicated that AR can strongly quench the fluorescence of pepsin through a static quenching. Thermodynamic analysis of the binding phenomena suggests that van der Waals forces and hydrogen bonding played a major role in the complex formation. The results of synchronous fluorescence spectra and furrier transformed infra-red (FTIR) experiments showed that there are no significant structural changes in the protein conformation. Also, examined pepsin protease activity revealed that the activity of pepsin was increased upon ligand binding. In agreement with the experimental results, the computational results showed that hydrogen bonding and van der Waals interactions occurred between AR and binding sites. Conclusion and implications: From the pharmaceutical point of view, this interaction can help us to get a deeper understanding of the effect of this synthetic dye on food digestion.

Protective effects of a standardized extract of Iris germanica on pancreas and liver in streptozotocin-induced diabetic rats Mohammad Reza Mahdinezhad, Sara Hooshmand, Mohammad Soukhtanloo, Shirin Taraz Jamshidi, Sajad Ehtiati, Ahmad Ghorbani Research in Pharmaceutical Sciences 2021 16(1):71-78 Background and purpose: Previous studies have shown the antioxidant, anti-inflammatory, immunomodulatory, and hypolipidemic activities of Iris germanica. The aim of the present study was to evaluate the protective effects of hydroalcoholic extract of Iris germanica rhizomes on streptozotocin-induced diabetic rats. Experimental approach: Twenty-four male Wistar rats were randomly assigned into four groups including a normal control group, diabetic control group, diabetic groups treated for 4 weeks with 100 and 200 mg/kg/day of the Iris germanica extract (IGE). Findings/Results: Induction of diabetes significantly decreased the body weight gain and considerably increased the serum levels of glucose, triglyceride, blood urea nitrogen (BUN), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). Diabetes also diminished the antioxidant capacity of the liver (decrease of thiol groups) and significantly degenerated pancreatic islands. The IGE at both doses of 100 and 200 mg/kg significantly reduced the levels of glucose, triglyceride, AST, ALT, and ALP. Moreover, IGE increased the total antioxidant capacity of the liver and ameliorated pancreatic island morphology. The extract had no significant effect on body weight and BUN level. Conclusion and implication: These findings suggest that Iris germanica rhizomes inhibits the progression of hyperglycemia and hypertriglyceridemia and has protective effects against diabetes-induced injury of the liver and pancreas. Therefore, this plant has the potential to be used as a natural product for controlling diabetes.

Chitosan/tripolyphosphate nanoparticles in active and passive microchannels Mona Akbari, Zohreh Rahimi, Masoud Rahimi Research in Pharmaceutical Sciences 2021 16(1):79-93 Background and purpose: In recent years, the interest in chitosan nanoparticles has increased due to their application, especially in drug delivery. The main aim of this work was to find a suitable method for simulating pharmaceutical nanoparticles with computational fluid dynamics (CFD) modeling and use it for understanding the process of nanoparticle formation in different types of microchannels. Experimental approach: Active and passive microchannels were compared to find the advantages and disadvantages of each system. Twenty-eight experiments were done on microchannels to quantify the effect of 4 parameters and their interactions on the size and polydispersity index (PDI) of nanoparticles. CFD was implemented by coupling reactive kinetics and the population balance method to simulate the synthesis of chitosan/tripolyphosphate nanoparticles in the microchannel. Findings/Results: The passive microchannel had the best performance for nanoparticle production. The most uniform microspheres and the narrowest standard deviation (124.3 nm, PDI = 0.112) were achieved using passive microchannel. Compared to the active microchannel, the size and PDI of the nanoparticles were 28.7% and 70.5% higher for active microchannels, and 55.43% and 105.3% higher for simple microchannels, respectively. Experimental results confirmed the validity of CFD modeling. The growth and nucleation rates were determined using the reaction equation of chitosan and tripolyphosphate. Conclusion and implications: CFD modeling by the proposed method can play an important role in the prediction of the size and PDI of chitosan/tripolyphosphate nanoparticles in the same condition and provide a new perspective for studying the production of nanoparticles by numerical methods.

Protective and therapeutic effects of ethanolic extract of Nasturtium officinale (watercress) and vitamin E against bleomycin-induced pulmonary fibrosis in rats Sanaz Ramezani, Iraj Javadi, Esmaeel Panahi Kokhdan, Navid Omidifar, Jafar Nikbakht, Heibatollah Sadeghi, Amir Hossein Doustimotlagh, Nazanin Danaei, Reza Abbasi, Hossein Sadeghi Research in Pharmaceutical Sciences 2021 16(1):94-102 Background and purpose: Pulmonary fibrosis is a chronic disease of the lungs caused by inflammation, species of reactive oxygen, and immune defects. Antioxidant properties of Nasturtium officinale has been reported in some studies. Therefore, the objective of the current study was to evaluate the effect of ethanolic extract of Nasturtium officinale (EENO) on bleomycin (BLM)-induced lung fibrosis in rats. Experimental approach: Forty adult male Wistar rats (180-220 g) were randomly divided into 5 experimental groups. Normal control, BLM control received a single dose of BLM (6 IU/kg) intratracheally only on the first day, EENO + BLM group received EENO (500 mg/kg) one week before intratracheal BLM instillation and two weeks afterward, BLM + EENO group and BML + vitamin E group received EENO (500 mg/kg) and vitamin E (500 mg/kg) half-hour after BLM installation, respectively. The animals were sacrificed on day 22. Change in body weight, lung index, serum level of malondialdehyde (MDA) and nitric oxide (NO) metabolite, lung tissue hydroxyproline content and lung pathology were assessed. Findings/Results: Pre- or post-treatment with EENO attenuated pulmonary fibrosis as evidenced by normalized lung index, improved histological changes and inhibited collagen deposition (hydroxyproline) in the animal lung. EENO also decreased MDA and NO metabolite release in comparison to the BLM control. vitamin E (500 mg/ kg) also significantly inhibited the BLM-induced lung toxicity. Conclusions and implications: EENO can prevent BLM-induced lung fibrosis in rats via antioxidant activities. However, more studies are needed to elicit the exact mechanism of this effect.

Development and characterization of a nano-drug delivery system containing vasaka phospholipid complex to improve bioavailability using quality by design approach Nandhini Sundaresan, Ilango Kaliappan Research in Pharmaceutical Sciences 2021 16(1):103-117 Background and purpose: Vasicine is a potential bronchodilator and can be used for the effective management of asthma and bronchitis. It has low absorption in the gastrointestinal tract due to its poor solubility thereby low bioavailability. The objective of this research was to develop a novel drug delivery system of vasaka extract to improve its bioavailability by enhancing the solubility and absorption of vasicine. Experimental approach: Vasaka-loaded phytosomes were developed and optimized by thin-layer hydration technique using systematic quality by design approach. Box-Behnken design (32 factorial design) using Design-Expert software was employed to optimize phytosome wherein phosphatidylcholine concentration (X1), stirring temperature (X2), and stirring time (X3) were selected as independent variables. Yield (%), particle size (nm), and entrapment efficiency (%) were evaluated as responses. The optimized phytosome was characterized by studying the surface morphology such as FE-SEM and TEM analysis, thermal characteristics by thermal gravimetric analysis and spectral and diffraction studies by FTIR and XRD analysis and studying the dissolution behaviour of phytosome by in vitro release study. Findings/Results: The percentage yield, particle size, and entrapment efficiency values of the phytosomes were found in the range of 30.03-97.03%, 231.0-701.4 nm, and 20.02-95.88% w/w, respectively. The optimized phytosome showed the zeta potential of -23.2 mV exhibited good stability and SEM and TEM analysis revealed the spherical shape and smooth particles with the uniform particle size distribution of phytosomes. The comparative in vitro drug release study of vasaka extract and phytosome revealed the sustained release characteristics of phytosome which reached 68.80% at 8 h compared to vasaka extract reached a maximum of 45.08% at 4 h. Conclusion and implication: The results highlighted the importance of optimization of formulation development using quality by design strategy to achieve consistent quality of pharmaceutical products.

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