Molecular docking of alpha-enolase to elucidate the promising candidates against Streptococcus pneumoniae infection.

PURPOSE: To predict potential inhibitors of alpha-enolase to reduce plasminogen binding of Streptococcus pneumoniae (S. pneumoniae) that may lead as an orally active drug. S. pneumoniae remains dominant in causing invasive diseases. Fibrinolytic pathway is a critical factor of S. pneumoniae to invade and progression of disease in the host body. Besides the low mass on the cell surface, alpha-enolase possesses significant plasminogen binding among all exposed proteins. METHODS: In-silico based drug designing approach was implemented for evaluating potential inhibitors against alpha-enolase based on their binding affinities, energy score and pharmacokinetics. Lipinski's rule of five (LRo5) and Egan's (Brain Or IntestinaL EstimateD) BOILED-Egg methods were executed to predict the best ligand for biological systems. RESULTS: Molecular docking analysis revealed, Sodium (1,5-dihydroxy-2-oxopyrrolidin-3-yl)-hydroxy-dioxidophosphanium (SF-2312) as a promising inhibitor that fabricates finest attractive charges and conventional hydrogen bonds with S. pneumoniae alpha-enolase. Moreover, the pharmacokinetics of SF-2312 predict it as a therapeutic inhibitor for clinical trials. Like SF-2312, phosphono-acetohydroxamate (PhAH) also constructed adequate interactions at the active site of alpha-enolase, but it predicted less favourable than SF-2312 based on binding affinity. CONCLUSION: Briefly, SF-2312 and PhAH ligands could inhibit the role of alpha-enolase to restrain plasminogen binding, invasion and progression of S. pneumoniae. As per our investigation and analysis, SF-2312 is the most potent naturally existing inhibitor of S. pneumoniae alpha-enolase in current time.

Thymoquinone: From Nigella sativa to a protective pharmacological compound in managing opioid dependence and amphetamine type stimulant issues.

Opioids, amphetamines, and other types of substances have been widely abused around the world. Opioid dependence and tolerance are two distinct phenomena that have been associated with substance abuse issues. The management of its adverse consequences is becoming more challenging. More and more people are treated in Methadone Maintenance Therapy (MMT) program yet the issues are still unresolved. Researchers are continuing to study the best formulation in treating opioid dependent people starting with modern and alternative drug therapies. Since 2008 , thymoquinone (TQ) has been extensively studied by researchers around the world and has emerged to be a new potential drug candidate in managing substance abuse issues. Thus, the aim of this article is to review the effects that TQ may have on opioid dependent subjects and other abused substances such as amphetamine may have been studied. All of the articles from 2008 until 2019 involving the effects of TQ on substance abuse from Google Scholar®, Scopus®, and Pubmed® databases have been searched and reviewed. The keywords used were thymoquinone, opioid dependence, amphetamine, and Nigella sativa. The research results also have been discussed in this article. Based on the research conducted, TQ was effective in reducing the adverse health consequences associated with substance abuse such as withdrawal symptoms, tolerance, and cell damages. It is concluded that TQ could be a potential drug that can be complemented with the currently available drugs in substance abuse therapies.

Disruption of the cpsE and endA Genes Attenuates Streptococcus pneumoniae Virulence: Towards the Development of a Live Attenuated Vaccine Candidate.

The majority of deaths due to Streptococcus pneumoniae infections are in developing countries. Although polysaccharide-based pneumococcal vaccines are available, newer types of vaccines are needed to increase vaccine affordability, particularly in developing countries, and to provide broader protection across all pneumococcal serotypes. To attenuate pneumococcal virulence with the aim of engineering candidate live attenuated vaccines (LAVs), we constructed knockouts in S. pneumoniae D39 of one of the capsular biosynthetic genes, cpsE that encodes glycosyltransferase, and the endonuclease gene, endA, that had been implicated in the uptake of DNA from the environment as well as bacterial escape from neutrophil-mediated killing. The cpsE gene knockout significantly lowered peak bacterial density, BALB/c mice nasopharyngeal (NP) colonisation but increased biofilm formation when compared to the wild-type D39 strain as well as the endA gene knockout mutant. All constructed mutant strains were able to induce significantly high serum and mucosal antibody response in BALB/c mice. However, the cpsE-endA double mutant strain, designated SPEC, was able to protect mice from high dose mucosal challenge of the D39 wild-type. Furthermore, SPEC showed 23-fold attenuation of virulence compared to the wild-type. Thus, the cpsE-endA double-mutant strain could be a promising candidate for further development of a LAV for S. pneumoniae.

Molecular Modulation of Stress Induced to Abnormal Haematological Indices in Medical Students, Malaysian Perspective.

Medical students in Malaysia and globally were considered among the most exposure groups in the community to stress due to several sources. The most significant and severe sources of stress in medical students is an academic sources, includes a lot of exams/tests, lack of time and facilities for entertainment, stay in a hostel, high parental expectations and vastness of syllabus, in addition to emotional problems and others personal sources. Stress is a very important issue that leads to a worsening of health problems. Stress develops in the body and leads to oxidative stress which in turn leads to a disorder in the whole body. Oxidative stress may lead to abnormal haematological indices elevated white blood cells (WBCs) count. Oxidative stress can lead to massive destruction of red blood cells (RBCs). The brain and the gastrointestinal system (GI) are intimately connected as one system. The brain has a direct impact on the GI tract. A stressful brain can send signals to the gut, just as a troubled intestine can send signals to the brain. Therefore, stress can be the cause of block the breakdown and assimilation of food for energy and nutriment. This malabsorption can then lead to a reciprocal negative effect to the stress and can be another cause of anaemia through malabsorption minerals and vitamins that are to erythropoiesis. So, stress can be one of the leading causes of anaemia among medical students. Stress is a chronic epidemic in the most medical students and can directly affect how well body works. This review article discovers the effect of stress in medical students that can be effect on their studies and further create researcher's interest to generate database that help to reduce stress response and bring about the empowerment of balanced life among Malaysian medical students besides the increasing level of health and academic performance.

Study on personality dimension negative emotionality affecting academic achievement among Malaysian medical students studying in Malaysia and overseas.

Personality dimension negative emotionality is known to be associated with academic achievement. The present study focuses on the influence of negative emotionality (neuroticism) on the medical students' academic achievements. The main objective of this study was to ascertain the negative emotionality scores among the first year Malaysian medical students studying in Malaysia and India, further to find out the association between negative emotionality and their academic achievements. The current study sample includes 60 first year Malaysian medical students from Universiti Sultan Zainal Abidin, Malaysia, and USM-KLE IMP, Belgaum, India. They were selected by convenient sampling technique. The Medico-Psychological questionnaire was used to find out the negative emotionality scores among the students and these scores were compared with academic scores. The data were analyzed using SPSS- 20. Thus, the study result goes with the prediction that there is a significant correlation between academic achievement and negative emotionality. We concluded that negative emotionality has a negative impact on medical student's academic achievement regardless of the fact whether they study in their own country or overseas.

Perceptions of students in different phases of medical education of the educational environment: Universiti Sultan Zainal Abidin.

BACKGROUND: The Dundee Ready Education Environment Measure (DREEM) was planned and designed to quantify the educational environment precisely for medical schools and health-related professional schools. DREEM is now considered a valid and reliable tool, which is globally accepted for measuring the medical educational environment. The educational environment encountered by students has an impact on satisfaction with the course of study, perceived sense of well-being, aspirations, and academic achievement. In addition to being measurable, the educational environment can also be changed, thus enhancing the quality of medical education and the environment, and the medical education process. The objective of this study was to assess the educational environment of the Universiti Sultan Zainal Abidin (UniSZA) undergraduate medical program from the students' perspective. The study expected to explore UniSZA medical students' overall perceptions, perceptions of learning, teachers, atmosphere, academic self-perception, and social self-perception using the DREEM questionnaire. METHODS: A cross-sectional survey was conducted to study the perceptions of the students toward the educational environment of UniSZA as a new medical school, using the DREEM questionnaire. All medical students of UniSZA from Years I-V enrolled in the Bachelor of Medicine and Bachelor of Surgery programs were the target population (n=270). Therefore, the universal sampling technique was used. The data were analyzed using the SPSS 20 software. This study obtained ethical clearance from the Faculty of Medicine and Health Sciences, UniSZA. RESULTS: A total of 195 out of 270 students responded. Respondents included 31% males and 69% females. The overall DREEM scores were significantly higher (P<0.001) for females than males. CONCLUSION: The medical students at UniSZA showed a positive perception of their educational environment. The new medical faculty, established for only a few years, has achieved an above-average, conducive educational environment for students. Most of the students showed a positive perception for the entire five domains tested in the DREEM survey. Females were consistently satisfied with UniSZA's educational environment, and self-perception was high, as compared to male undergraduates.

Breakage of an intramedullary rod after bone union in congenital pseudoarthrosis of the tibia: a report of two cases.

We report 2 patients with congenital pseudoarthrosis of the tibia who underwent intramedullary Rush rod transfixation through the ankle joint following refracture and nonunion of vascularised fibular grafting 6 and 8 months earlier. After 9 and 5 years, both Rush rods were broken at the level of the ankle joints, while the reconstructed area was solidly united. The growth of the distal tibia increased the distance of the tips of the broken rod and hence the ankle joint motion. The broken tips may damage the articular cartilage and result in valgus deformity of the ankle and limb length discrepancy.