COMPUTATIONAL ANALYSIS OF PHYTOCOMPOUNDS PRESENT IN LEUCAS ASPERA TO TARGET PARKINSON’S DISEASE-CAUSING ALPHA-SYNUCLEIN

Objective: Parkinson’s disorder is the second most prevalent neurodegenerative disorder in the world that manifests in both the motor and non-motor systems. The pathogenesis of the disorder involves alpha-synuclein in a variety of ways, and therefore, this protein can be appraised as a therapeutic target. In the present study, the bioactive phytocompounds from Leucas aspera were examined to establish their inhibitory activity against alpha-synuclein protein. Methods: In this study, ten phytocompounds were selected from L. aspera and their efficacy to counteract Parkinson’s disease (PD)-causing alpha-synuclein was evaluated. The study was done computationally using Indian medicinal plants, phytochemistry, and therapeutics and PubChem to source information and molecular structures of the phytocompounds. Several other tools were used for pharmacological assessment of these compounds under ADME properties and ProTox-II was used for toxicity prediction. Results: Molecular docking using PyRx and BIOVIA revealed that Baicalein and Leucasperones A were the best antagonists for 3Q25 Parkinson’s causing alpha-synuclein. Hence, these compounds can be used as potential candidates to produce drugs which help prevent PD. Conclusion: Since ancient times, plants have been used to cure several maladies. The phytochemical Baicalein and Leucasperones A present in L. aspera, bind to disease causing alpha-synuclein, and help in disease management

Scaling in Small-World Resistor Networks

We study the effective resistance of small-world resistor networks. Utilizing recent analytic results for the propagator of the Edwards-Wilkinson process on small-world networks, we obtain the asymptotic behavior of the disorder-averaged two-point resistance in the large system-size limit. We find that the small-world structure suppresses large network resistances: both the average resistance and its standard deviation approaches a finite value in the large system-size limit for any non-zero density of random links. We also consider a scenario where the link conductance decays as a power of the length of the random links, $l^{-\alpha}$. In this case we find that the average effective system resistance diverges for any non-zero value of $\alpha$.Comment: 15 pages, 6 figure

Psychological morbidity, sources of stress and coping strategies among undergraduate medical students of Nepal

<p>Abstract</p> <p>Background</p> <p>In recent years there has been a growing appreciation of the issues of quality of life and stresses involved medical training as this may affect their learning and academic performance. However, such studies are lacking in medical schools of Nepal. Therefore, we carried out this study to assess the prevalence of psychological morbidity, sources and severity of stress and coping strategies among medical students in our integrated problem-stimulated undergraduate medical curriculum.</p> <p>Methods</p> <p>A cross-sectional, questionnaire-based survey was carried out among the undergraduate medical students of Manipal College of Medical Sciences, Pokhara, Nepal during the time period August, 2005 to December, 2006. The psychological morbidity was assessed using General Health Questionnaire. A 24-item questionnaire was used to assess sources of stress and their severity. Coping strategies adopted was assessed using brief COPE inventory.</p> <p>Results</p> <p>The overall response rate was 75.8% (407 out of 525 students). The overall prevalence of psychological morbidity was 20.9% and was higher among students of basic sciences, Indian nationality and whose parents were medical doctors. By logistic regression analysis, GHQ-caseness was associated with occurrence of academic and health-related stressors. The most common sources of stress were related to academic and psychosocial concerns. The most important and severe sources of stress were staying in hostel, high parental expectations, vastness of syllabus, tests/exams, lack of time and facilities for entertainment. The students generally used active coping strategies and alcohol/drug was a least used coping strategy. The coping strategies commonly used by students in our institution were positive reframing, planning, acceptance, active coping, self-distraction and emotional support. The coping strategies showed variation by GHQ-caseness, year of study, gender and parents' occupation.</p> <p>Conclusion</p> <p>The higher level of psychological morbidity warrants need for interventions like social and psychological support to improve the quality of life for these medical students. Student advisors and counselors may train students about stress management. There is also need to bring about academic changes in quality of teaching and evaluation system. A prospective study is necessary to study the association of psychological morbidity with demographic variables, sources of stress and coping strategies.</p

Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella Typhi identifies inter- and intracontinental transmission events.

The emergence of multidrug-resistant (MDR) typhoid is a major global health threat affecting many countries where the disease is endemic. Here whole-genome sequence analysis of 1,832 Salmonella enterica serovar Typhi (S. Typhi) identifies a single dominant MDR lineage, H58, that has emerged and spread throughout Asia and Africa over the last 30 years. Our analysis identifies numerous transmissions of H58, including multiple transfers from Asia to Africa and an ongoing, unrecognized MDR epidemic within Africa itself. Notably, our analysis indicates that H58 lineages are displacing antibiotic-sensitive isolates, transforming the global population structure of this pathogen. H58 isolates can harbor a complex MDR element residing either on transmissible IncHI1 plasmids or within multiple chromosomal integration sites. We also identify new mutations that define the H58 lineage. This phylogeographical analysis provides a framework to facilitate global management of MDR typhoid and is applicable to similar MDR lineages emerging in other bacterial species

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes