The Discovery of Putative Small Molecules via Ligand-based Pharmacophore Modelling Targeting Human Tau Protein for an Effective Treatment of Parkinson’s Disease

@#Introduction: The human tau protein is a key protein involved in various neurodegenerative disease (NDs) including Parkinson’s disease (PD). The protein has high tendency to aggregate into oligomers, subsequently generating insoluble mass in the brain. Symptoms of PD include tremor, bradykinesia, rigidity, and postural instability. Currently drugs for PD treatment are only symptom-targeted while effective therapeutic treatment remains a challenge. The objective of this study is to identify novel promising anti-PD drugs using computational techniques. Method: ligand-based (LB) receptor modelling was conducted using LigandScout, validated and subjected to Glide XP docking, virtual screening, ADMET, and molecular dynamics predictions. Results: The adopted LB modelling generated pharmacophoric features of 5 hydrogen bond donors, 1 aromatic rings, and 7 hydrogen bond acceptors. The validation result indicated GH score of 0.73 and EF of 36.30 as validation protocols, probing it to be an ideal model. Using 3D query of the modelling a total of 192 compounds were retrieved from interbioscreen database containing 70,436 natural compounds. Interestingly, ligands 1, 2, 3, 4 and 5 orderly indicated higher binding affinities to the receptor with Glide XP docking of -7.451, -7.368, -7.101, -6.878, and -6.789 compared to a clinical drug Anle138b with -4.552 kcal/mol respectively. Furthermore, molecular dynamics and pkCSM pharmacokinetics demonstrated ligands 1, 2, & 4 having better stability and low toxicity profiles compared to the reference. Conclusion: In summary, the study pave way for discovery of small molecules that could be recommended as adjuvant /single candidate as ant-PD candidates upon further translational study.

Características de lesões em paratletas da Indonésia antes das Olimpíadas de Tóquio em 2020: um estudo transversal / Injury characteristics of Indonesian paraathletes prior to Tokyo Olympics 2020: a crosssectional study

OBJETIVOS: Esta pesquisa tem como objetivo elucidar as características das lesões em atletas da seleção da Indonésia. MÉTODOS: Os sujeitos deste estudo foram nove atletas (masculino = 5, feminino = 4) com homens em torno da idade de 28 ± 9,13 e mulheres 28 ± 5,66 anos. A abordagem do método é descritiva com uma técnica de estudo transversal usando um questionário sobre histórico de lesões, tipos de lesões, fatores de lesões e gerenciamento de lesões para atletas indonésios que competiram nos Jogos Olímpicos de Tóquio em 2020. A análise de dados é representada em números e porcentagens e o teste exato de Fisher é usado para determinar a relação entre as variáveis. RESULTADOS: Os resultados do estudo relataram que os atletas indonésios sofreram lesões nos membros inferiores (70%), a parte do corpo que frequentemente sofre lesões foi a coxa (28%) e o tipo de lesão que frequentemente sofreu foi entorse / torção. CONCLUSÃO: As características da lesão na categoria sprint (pista) formam um padrão de lesões na coxa, tendão de Aquiles, tornozelo e joelho. Parece não haver correlação entre gênero, frequência de treinamento, proporção de lesões, número de partidas e tipo de aquecimento. A implicação é que o gerenciamento de lesões é necessário antes e durante a competição, considerando a biomecânica, a fisiopatologia e os problemas psicossociais. As estratégias de prevenção de lesões por treinadores e equipes médicas devem levar a uma redução mais significativa de lesões e otimizar a saúde, segurança e bem-estar dos atletas.

BACKGROUND: Sports for people with disabilities and injuries have been the subject of discourse in the professional literature in the fields of traumatology and sports medicine. OBJECTIVE: This research aims to elucidate the injury characteristics of athletes in the Indonesian national team. The subject of this study were nine athletes (male=5, female=4) with males around the age of 28±9.13 and females 28±5.66 years. METHOD: The method approach is descriptive with a crosssectional study technique using a questionnaire about injury history, types of injury, injury factors, and injury management for Indonesian Para Athletics Athletes who have competed in the 2020 Tokyo Olympics. Data analysis is depicted in numbers and percentages and Fisher's exact test is used to determine the relationship between variables. RESULTS: The study results reported that Indonesian athletes suffered injuries of the lower limbs (70%), part of the body that is frequently injured was the thigh (28%) and the type of injury that was often experienced sprain/twist. CONCLUSION: The injury characteristics in the sprint (track) category form a pattern of injuries to the thigh, Achilles tendon, ankle, and knee. There appears to be no correlation between gender, training frequency, injury share, match number, and warm-up type. The implication is that injury management is necessary before and during competition by considering biomechanics, pathophysiology, and psychosocial problems. Injury prevention strategies by coaches and medical teams should lead to more significant injury r

Assessment and Comparison of Microbiological Efficacy of Moxifloxacin plus Vancomycin Combined Therapy with Fortified Vancomycin in Bacterial Conjunctivitis

Background: Bacterial Conjunctivitis or red eye being highly communicable need to be tackle at the earliest. Newer antibiotics may kill bacteria more rapidly. Thus, we aim to assess and compare microbiological efficacy of Moxifloxacin (0.5%) plus Vancomycin (2.5%) combined therapy to Fortified Vancomycin (5%) in relation to organism isolated in positive culture of bacterial conjunctivitis. Methods: The present study was conducted on patients who presented at Ophthalmology OPD, Jawaharlal Nehru Medical College Hospital, Aligarh and Gandhi Eye Hospital, Aligarh. The patients with bilateral conjunctivitis were included in the study. Right eyes were instilled moxifloxacin plus vancomycin combination therapy and Left eyes were instilled fortified vancomycin. Microbiological outcomes were recorded on first visit and on follow up visits during course of treatment. Results: A total of 35 patients were included in the study. At first visit, 14 cases were positive with coagulase negative Staphylococcus (CoNS) being the most common organisms. All the positive smears became negative in first follow-up (3rd day) in both the groups. No significant difference was found in microbiological study outcome between the two-study groups. Conclusions: We conclude that both the drugs, i.e. moxifloxacin (0.5%) plus vancomycin (2.5%) combined therapy and fortified vancomycin (5%) had good efficiency in microbial elimination in cases of bacterial conjunctivitis with equivalent outcome and can be considered as an alternative to other antimicrobial therapy in bacterial conjunctivitis.

[Effect of some plant extracts on growth inhibition of Macrophomina phaseolina]

The study showed that water extracts of plants, such as, Azadirachta indica, Thevetia neirefolia, Citrullus colonynthis, Datura stramonium, Neriutn oleander, Eucalyptus camaldulensis, save effect on growth of the M. phaseolina, the causative factor of charcoal root rot on Sesame Sesnium indicum. The results showed the efficiency of all treatments compared with control. The highest effect was given by T. neirefolia extract as 0.7 cm fungus growth inhibition, while the lowest was given by T. camaldulensis extract as 3.9 cm Water extracts of plants oil of: Azadirachta indica, Thevetia neirefolia, Citrullus colonynthis and Datura stramonium at consentration of 1,5 and 10% were tested. The lowest growth inhibition was given by D. stramonium extract [4.2 cm] and the highest effect was that given by A. indica [2 cm] at concentration of 10%. Extracts of T neirefolia, showed only 77.8% growth inhibition

[Efficacy of some plant powders in protecting Sesame seeds against Macrophomina phaseolina in greenhouse]

The study has showed the effect of some powder plant materials i.e, Azadarichta indica seed, Datura stramonium seed, Nerium oleander leaves, Eucalyptus camaldulensis leaves, control, control against the fungus Macrophomina phaseolina that causes charcoal rot. The powder plant material powder was used as 60, 40, 20g/kg of soil. Sesmum indicum seeds have showed the highest germination rate in the soils treated with A. indica seeds powder. Germination rate for S. indium seesds in the soils treated with A. indica seeds powder reached about 69%, whereas germination rate for control was about 4%. The study has also indicated that the highest percentage of infected S. indicum seeds under the soils treated with Eucalyptus leaves powder was [84.78%], while percentage infected seeds under A. indica treated soils was about 25%. All treatments with different concentrations of plants powder have shown inhibition effects on Macrophomina phaseolina growth. The highest percentage of inhibition was seen under the treatment with A. indica seed powder [73.86%], whereas Eucalyptus leaves treatment powder was about 11.36%