In silico drug repositioning of FDA-approved drugs to predict new inhibitors for alpha-synuclein aggregation

One of the hallmarks of Parkinson's disease (PD), a long-term neurodegenerative syndrome, is the accumulation of alpha-synuclein (α-syn) fibrils. Despite numerous studies and efforts, inhibition of α-syn protein aggregation is still a challenge. To overcome this issue, we propose an in silico pharmacophore-based repositioning strategy, to find a pharmaceutical drug that, in addition to their defined role, can be used to prevent aggregation of the α-syn protein. Ligand-based pharmacophore modeling was developed and the best model was selected with validation parameters including 72 % sensitivity, 98 % specificity and goodness score about 0.7. The optimal model has three groups of hydrogen bond donor (HBD), three groups of hydrogen bond acceptor (HBA), and two aromatic rings (AR). The FDA-Approved reports in the ZINC15 database were screened with the pharmacophore model taken from inhibitor compounds. The model identified 22 hits, as promising candidate drugs for Parkinson's therapy. It is noteworthy that among these, 10 drugs have been reported to inhibition of α-syn aggregation or treat/reduce Parkinson's pathogenesis. This model was used to virtual screen ZINC, NCI databases, and natural products from the pomegranate. The results of this screen were filtered for their inability to cross the blood-brain barrier, poor oral bioavailability, etc. Finally, the selected compounds of two ZINC and NCI databases were combined and structurally clustered. Remained compounds were clustered in 28 different clusters, and the 17 compounds were introduced as final candidates

An optimal two-level supply chain model for Small- and Medium-sized Enterprises (SMEs) considering rework for new products and price-dependent demands

With the advent of new technologies, several factors such as globalization of markets, customers' different needs, and increasingly fierce economic competition have encouraged Small- and Medium-sized Enterprises (SMEs) to improve their engagement with suppliers and to involve themselves with cost management practices in order to survive. SMEs clearly need to focus on the interests of the entire supply chain by enacting win-win policies. In this regard, the present study investigated a two-level inventory model featuring a manufacturer and a buyer in the competitive market with the policy of producing new products. The proposed model took into account imperfect and low-quality products and their capacities for rework. In other words, due to the competitive nature of the market, any increase in prices would lead to a decrease in demand. The mathematical model was proposed in two scenarios: one with the possibility of shortage and one without it. The objective function of the mathematical model revolves around maximizing the total profit of the supply chain considering both independent and joint optimization by the supply chain members. A new algorithm was then proposed to solve the mathematical model whose applicability was evaluated by using a numerical example in the analysis software MATLAB as the input. The results were then analyzed and discussed based on a sensitivity analysis approach

The Relationship between Psychological Hardiness and Academic Enthusiasm and Vitality in Students of Arak University of Medical Sciences

Background: Psychological hardiness as a protective factor plays an essential role in how students face academic challenges. Paying attention to academic enthusiasm and vitality due to their strong impact on various aspects of students' academic life is of great importance. Objectives: The aim of this study was to investigate the relationship between psychological hardiness and academic enthusiasm and vitality in students of Arak University of Medical Sciences. Methods: This descriptive-correlational study was conducted in 2017-2018 on 341 students of Arak University of Medical Sciences selected by stratified random sampling based on gender. Data were collected using the Ahvaz Hardiness Inventory (AHI), Academic Enthusiasm Inventory developed by Fredricks et al., and Academic Vitality Scale. Data were analyzed using SPSS software. Results: There was a negative and significant relationship between psychological hardiness and academic enthusiasm (r=-0.17, P=0.002) and vitality (r=-0.38, P=0.001). Also, a positive and significant relationship was observed between academic enthusiasm and academic vitality (r=0.15, P=0.008). There was a significant difference between the mean scores of academic vitality of male and female students. Conclusion: In order to increase the quality of academic life of medical students, it is essential to teach the components of psychological hardiness, academic enthusiasm, and academic vitality to students. Keywords: Psychological Hardiness, Academic Enthusiasm, Academic Vitalit

Clinical results of everolimus-eluting stents and sirolimus-eluting stents in patients undergoing percutaneous coronary intervention

Background: It has been pronounced that everolimus-eluting stent (EES) had lower charge of goal-lesion revascularization and stent thrombosis as compared with sirolimus-eluting stents (SES).The goal of this observation was to compare the efficacy and protection of EES with SES in primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). Methods: In this retrospective study, a total of 404 patients with coronary artery stenosis who underwent angioplasty of one or more coronary arteries were included in the study. Of these, 202 were treated with SES and the others with EES. The data were collected by a questionnaire through which the annual incidence of coronary stent complications including the occurrence of stent thrombosis (confirmed by re-angiography), the occurrence of acute coronary syndrome leading to hospitalization, the occurrence of vascular myocardial infarction related to the stenting vessel, the need for re-angiography and angioplasty and finally the incidence of cardiac mortality were evaluated. Results: This study showed that the odds ratio of EES thrombosis to SES stent in the unadjusted model is 1.01 (0.06-16.34) and in the adjusted model for confounding variables was equal to 0.80 (0.04-13.35) which in both models, these values were not statistically significant. Conclusion: The findings of the present study indicate that there is no statistically significant difference between the outcomes in the two groups treated with SES and EES release stents

Utilisation of waste gas sludge for waste water treatment

This hypothesis driven research investigated the removal of Cu, Fe, Zn and Mn from synthetic metal solutions and real Acid Mine Drainage (AMD) from Wheal Jane mine in West Cornwall UK, employing waste gas sludge (BOS sludge) which is an end waste reside generated from steel production. Batch experiments showed the efficiency and adsorption rates increased with reduction in BOS sludge particle size, lower in initial metal concentration, increase in BOS sludge dosage, an increase in initial pH and increase in agitation speed. Fitting of the Langmuir isotherm model to experimental data gave a good fit with correlation coefficients R$^2$≥0.99 and the selectivity series of BOS sludge was: Cu$^2$$^+$>Fe$^3$$^+$>Zn$^2$$^+$>Mn$^2$$^+$. For single and multiadsorbate systems, a Pseudo second order model was the most appropriate theory to satisfactorily describe experimental data and the rate limiting step for this process was chemisorption. Adsorption was spontaneous and high pH promoted adsorption possibly by precipitation and/or ion exchange processes which had taken place between the exchangeable cations present in BOS and solutions. Results from the treatment of real and synthetic AMD solutions revealed that BOS sludge worked well and hence BOS sludge as a novel low cost material could be used as a sustainable sorbent in AMD treatment technologies

Specific pattern of bone scan as a Result of Unintentional-Intraarterial Injection Into the Ulnar Artery

Background: Bone scintigraphy with 99mTc labeled radiopharmaceuticals is a valuable method in nuclear medicine for assessing the bony structure. In clinical setting, bone scintigraphy is accomplished after the injection of 99mTc labeled diphosphonate complexes into a peripheral vein. Inadvertent intra-arterial injection on the antecubital region may cause a special form of artifacts leading to problems inaccurately interpreting these studies as functional images. Case Presentation: We present a 44-year-old man with history of chest wall pain for bone scintigraphy as part of a work-up for determining the pain source. The patient received an injection of 740MBq 99mTc-methylene diphosphonate (MDP) into a blood vessel at the right forearm. Two hours later, an increased uptake of activity was observed on the right forearm and ulnar half of the wrist-hand in the whole body and spot images. The scan findings were consistent with the anatomical and physiological expectations of the ulnar arterial perfusion range. This case displays that an incidental injection with a 99mTc labeled diphosphonate into the ulnar artery results in a hot ulnar half of the palm and ulnar-sided three digits, because these areas are directly exposed to radiopharmaceutical, therefore more radiopharmaceutical is deposited. Conclusion: It is important for the physician, and especially for the nuclear medicine technician, to know the specific appearance created in the bone scan due to such an event so that they do not make a diagnostic mistake. &#160

Comparing Formation or Non-Formation of Bladder Flap at Cesarean Section on Perioperative and Postoperative Complications: Double-Blind Clinical Trial

Objective: To investigating formation or non-formation of bladder flap at Cesarean section on the complications during and after surgery. Materials and methods: This is a double-blind clinical trial study conducted during February 2014 to May 2015 on 64 pregnant women with gestational age of 36 weeks or more who were delivered by Cesarean section for the first time. They were randomly divided into two groups (intervention group: non-formation of bladder flap; control group: formation of bladder flap). The time to cut out the baby by Cesarean section, total duration of operation, bladder injury, intraoperative bleeding, hematocrit changes expected prior to during and following operation, postoperative pain, macroscopic and microscopic hematuria, postoperative complications and duration of  hospitalization were compared between two groups. The data were analyzed with SPSS version 16 using and statistics tests. p < 0.05 was considered significant. Results: Time to cut out the baby for the intervention group (124.9 ± 40.5 seconds and for control group 155.1 ± 42.9 seconds) and total duration of the operation (intervention group: 27.7 ± 5.2 min and control group: 34 ± 4.73 min) were significantly different (p = 0.000). Number of gauze consumption during operation and postoperative hematocrit drop in the intervention group was significantly lower in the intervention group compared the control group (p = 0.000). The postoperative pain score in the intervention group (4.8 ± 1.1) and in control group (6.3 ± 0.9) were significantly different (p = 0.000). Conclusion: Omission of the bladder flap at Cesarean section leads to short-term benefits such as reducing the time to cut out the fetus, duration of surgery, decreasing postoperative bleeding and lowering pain

اهداف توسعۀ هزارۀ سوم: سلامت مادران بر اساس آموزه‌های دین اسلام

خلفية البحث وأهدافه: أعلنت منظمة الصحة العالمیة أنّ صحة الأمهات هي الهدف الخامس من بین الأهداف التنمویة للألفیة الثالثة. لهذا تسعی هذه الدراسة أن تسلط الضوء علی تعالیم الإسلام ومدی اهتمام الشرع بالأم بوصفها الهدف الخامس للخطط التنمویة للألفیة الثالثة ومدی اهتمام الشرع بسلامتها. منهجية البحث: المنهج الذي اعتمدت علیه الدراسة هو منهج المراجعة، فقد أجری الباحثون مراجعة شاملة للمقالات الفارسیة والإنجلیزیة خلال زیارتهم مواقع المقالات الدولیة المعتبرة مثل موقع ویب آف ساینس وساینس دایرکت، باب مد، جوجل اسکولار والبحث عن مصطلحات مثل,Islamic Health Women, Millenium goals, Maternal Health بصورة منفردة ومزجیة، وأیضاً البحث عن مترادفات هذه المصطلحات في اللغة الفارسیة للعثور علی معلومات في المواقع الفارسیة ذات القیمة العلمیة الکبیرة مثل إس.آي.دي و ایرانداك، ومجیران. إنّ مؤلف البحث لم یشیر إلی أيّ تضارب في المصالح. المعطیات: من بین مجموع التعالیم الإسلامیة المتعلقة بصحة الأمهات یمکن الإشارة إلی الإهتمام بحقوق الإمهات في أبعادها المختلفة الفردیة، والأسریة، والإجتماعیة؛ والإهتمام بأبعاد سلامتها الجسدیة، والنفسیة، والإجتماعیة؛ وتوفیر العنایة الصحیة العادلة، والتحذیر من العنف ضد المرأة، والإهتمام بالمنزلة الإجتماعیة للمرأة، والتعالیم المتعلقة بالحمل الصحي السلیم؛ والتحذیر من الإجهاض غیرالمبرر الذي یهدد سلامة الأمهات، والتحذیر من تناول الأطعمة والعقاقیر غیر الصحیة أثناء فترة الحمل ومعظم هذه التعالیم قریبة إلی حد بعید إلی تعالیم منظمة الصحة العالمیة المتعلقة بصحة الإمهات وسلامتهن الجسدیة والنفسیة. الاستنتاج: نظراً إلی أنّ تعالیم الشریعة الإسلامیة وُضعت علی أساس الفطرة البشریة وغریزة الإنسان، فهي أفضل دلیل وخطة لنیل الحیاة السلیمة. لهذا یمکن أن یأخذ الإنسان هذه التعالیم الشرعیة دلیلاً یستدل به للوصول إلی حیاة سلمیة وصحیة للإمهات ویعتبرها إستراتجیة ناجعة لنیل الأهداف التنمویة للألفیة الثالثة.Background and Objective: The United Nations identified maternal health as the fifth goal of the third millennium development goals. Therefore, the present study has been conducted with the aim of examining the teachings of Islam in relation to the fifth development goal of the third millennium, namely maintaining the health of mothers. Methods: The present study is a review study involving a comprehensive review of Persian and English articles using international databases of Web of Science, Direct Science, PubMed, Google Scholar and using English keywords such as Islamic Health, Women, Millennium goals, Maternal Health performed individually and in combination, as well as the Persian equivalent keywords on Persian databases, including SID, Irandak, and search engines. The authors of the article did not report any conflict of interests. Results: Among the teachings of Islam regarding the protection of mothers' health are paying attention to women's rights in various personal, family and social dimensions, paying attention to the dimensions of women's physical, mental and social health, fair access to health care, avoiding violence against women, paying attention to women's social status, advising on healthy pregnancies, avoiding unjustified abortions threatening women's health, avoiding unhealthy foods during sensitive pregnancies, etc., many of which are similar to the guidelines of the World Health Organization in maintaining maternal health. Conclusion: The teachings of Islam, because they are based on human nature, are the best guide to having a healthy life; therefore, the recommendations of Islam in maintaining the health of mothers can be used as one of the basic strategies to achieve the development goals of the third millennium.سابقه و هدف: سازمان ملل سلامت مادران را پنجمین آرمان اهداف توسعۀ هزارۀ سوم بیان نموده است. ازاین‌رو مطالعۀ حاضر با هدف بررسی آموزه‌های دین اسلام در جهت نایل‌شدن به آرمان پنجم توسعۀ هزارۀ سوم یعنی حفظ سلامت مادران صورت گرفته است. روش کار: مطالعۀ حاضر از نوع مروری است که طی آن مروری جامع بر مقالات فارسی و انگلیسی زبان با استفاده از بانک‌های اطلاعاتی بین‌المللی وب‌ آو ساینس، ساینس دایرکت، پاب‌مد، گوگل اسکولار و با استفاده از کلیدواژه‌های انگلیسی Women ,Islamic Health ,Millenium goals ,Maternal Health به‌صورت تکی و ترکیبی و همچنین معادل کلیدواژه‌های فارسی در بانک‌های اطلاعات فارسی شامل اس.‌آی.‌دی، ایرانداک و مگیران جست‌وجو صورت گرفت. مؤلفان مقاله تضاد منافعی گزارش نکرده‌اند. یافته‌ها: از جمله آموزه‌های دین اسلام دربارۀ حفظ سلامت مادران عبارت است از توجه به حقوق زنان در ابعاد مختلف فردی، خانوادگی و اجتماعی؛ توجه به ابعاد سلامت جسمی، روحی و اجتماعی زنان؛ دسترسی عادلانه به مراقبت‌های سلامتی؛ پرهیز از خشونت علیه زنان؛ توجه به منزلت اجتماعی زنان؛ توصیه به بارداری سالم؛ پرهیز از سقط‌های غیرموجه تهدیدکنندۀ سلامت زنان و پرهیز از غذاهای ناسالم در دوران حساس بارداری که بسیاری از آنها مشابه دستورالعمل‌های سازمان جهانی بهداشت در حفظ سلامت مادران کاربرد عملی دارد. نتیجه‌گیری: آموزه‌های دین اسلام چون بر مبنای فطرت بشر ارائه شده، بهترین راهنما در جهت داشتن زندگی سالم است؛ بنابراین می‌توان از توصیه‌های دین اسلام دربارۀ حفظ سلامت مادران استفاده کرد و به‌عنوان یکی از راهبردهای اساسی برای نایل‌شدن به اهداف توسعۀ هزارۀ سوم به جهانیان عرضه کرد