Molecular docking, DFT analysis, and dynamics simulation of natural bioactive compounds targeting ACE2 and TMPRSS2 dual binding sites of spike protein of SARS CoV-2.

The scientific community is continuously working to discover drug candidates against potential targets of SARS-CoV-2, but effective treatment has not been discovered yet. The virus enters the host cell through molecular interaction with its enzymatic receptors i.e., ACE2 and TMPRSS2, which, if, synergistically blocked can lead to the development of novel drug candidates. In this study, 1503 natural bioactive compounds were screened by HTVS, followed by SP and XP docking using Schrodinger Maestro software. Bio-0357 (protozide) and Bio-597 (chrysin) were selected for dynamics simulation based on synergistic binding affinity on S1 (docking score -9.642 and -8.78 kcal/mol) and S2 domains (-5.83 and -5.3 kcal/mol), and the RMSD, RMSF and Rg analyses showed stable interaction. The DFT analysis showed that the adsorption of protozide/chrysin, the band gap of protozide/chrysin-F/G reduced significantly. From SERS, results, it can be concluded that QDs nanocluster will act as a sensor for the detection of drugs. The docking study showed Bio-0357 and Bio-0597 bind to both S1 and S2 domains through stable molecular interactions, which can lead to the discovery of new drug candidates to prevent the entry of SARS-CoV-2. This in-silico study may be helpful to researchers for further in vitro experimental validation and development of new therapy for COVID-19.

A Comparative Study of Yoga with Paroxetine for the Treatment of Premature Ejaculation: A Pilot Study.

CONTEXT: Premature ejaculation (PME) is a common sexual disorder. Drugs used commonly used for its treatment have various side effects and disadvantages. Yoga is being increasingly studied in a variety of medical disorders with positive results. However, its evidence for patients with PME is very limited. AIMS: The aims of this study were to investigate the effect of yoga on ejaculation time in patients with PME and to compare it with paroxetine. SETTINGS AND DESIGN: This was a nonrandomized nonblinded comparative study in a tertiary care center. MATERIALS AND METHODS: Among patients with PME, 40 selected paroxetine and 28 yoga. Intravaginal ejaculation latency time (IELT) was measured in seconds once before and three times after intervention. STATISTICAL ANALYSIS USED: Mean, standard deviation, paired and unpaired t-tests, and repeated measures ANOVA were used for statistical analysis. RESULTS: IELT was significantly increased in both groups - paroxetine (from 29.85 ± 11.9 to 82.19 ± 32.9) and yoga (from 25.88 ± 16.1 to 88697 + 26.9). Although the effect of yoga was slightly delayed in onset, its effect size (η2 = 0.87, P < 0.05) was more than paroxetine (η2 = 0.73, P < 0.05). One-fifth of the patients in the paroxetine group (19.5%) and 8% in the yoga group continued to have the problem of PME at the end of the trial. CONCLUSIONS: Yoga caused improvement in both intravaginal ejaculation latency time and subjective sexual experience with minimal side effect. Therefore, yoga could be an easily accessible economical nonpharmacological treatment option for the patient with PME.

Primary care physician's approach for mental health impact of COVID-19.

As the world struggles to control coronavirus infection with the exhausting capacity of health care systems globally, the role of primary care physician and family physician becomes more important as the first point of contact with the community. Limited availability of mental health services in India requires general practitioners to deal with psychological disorders arising due to infection outbreak and its restrictive control strategies. This article discusses what and how primary physicians can manage the psychological burden of a pandemic, and therefore, reducing the reliance on mental health specialist.

Health anxiety among medical students: A comparison between preclinical and clinical years of training.

OBJECTIVE: It is common among medical students to falsely attribute bodily sensations/symptoms and holds a belief of having a medical illness with varying level of conviction. We studied and compared this condition known as "medical student syndrome", a type of hypochondriasis, between preclinical and clinical years students. METHODOLOGY: This research was a descriptive study where a total of 100 students were approached and were asked to complete a short form of health anxiety inventory (SHAI) which has Cronbach's alpha 0.855. No personal identifiers were included in the study questionnaires. All statistical analyses were performed using the SPSS statistical software package (IBM SPSS Statistics Version 23, SPSS Inc., Chicago, IL, USA). RESULTS: The response rate among participants was 88% (42 from preclinical and 48 from clinical years of training). Health-related anxiety (SHAI main section score ≥ 18) was found in 14.77% of students with a higher proportion in preclinical than clinical, 16.66% and 13.04%, respectively. The difference was not significant between the two groups (χ 2 = 0.429 [1], P = 0.766). Students having medical professional in family had lower rate of health-related anxiety, χ 2 (1, n = 88) = 0.228, P = 0.633. The association between family or personal history of psychiatry or medical illness was not significant with SHAI scores. No relation was noted between current health anxiety (SHAI score) and the number of visits to the doctor per year before entering the medical course (χ = 0.174, P = 0.112). CONCLUSION: Every seventh medical student was found to have health-related anxiety. It was not affected by personal and family history of either psychiatric or medical illness.

Traumatic experiences and dissociation in patients with conversion disorder.

OBJECTIVE: To explore the association between childhood trauma and dissociation in patients of conversion disorder. METHODS: The cross-sectional study was conducted in Lahore, Pakistan, from April to December 2016, and comprised female patients aged 18-40 years diagnosed with conversion disorder at three major public hospitals of the city. Urdu version of symptom checklist for conversion disorder, the dissociative experiences scale and traumatic experiences checklist were used to measure study variables. In this paper, Spearman's Rank Order Correlation SPSS 21 was used for data analysis. RESULTS: Of the 51 subjects, 27(53%) were in the 18-25 year age bracket, Of the total, 36(70%) patients reported emotional neglect, while 30(59%) reported emotional abuse. Also, 14(27%) patients reported physical abuse, while sexual harassment was reported by 33(65%) and sexual abuse by 12(23.5%).A relationship of childhood trauma, emotional abuse and sexual abuse with dissociation was observed (p<0.001 each). CONCLUSIONS: Emotional and sexual abuse were found to be significant predictors of dissociation, but physical abuse was not.

Nusinersen: The First Option Beyond Supportive Care for Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by degeneration of spinal motor neurons and poses significant adverse outcome in affected population. Survival motor neuron 1 (SMN1) protein encoded by SMN1 gene located on 5q13 is critical for survival and functioning of motor neurons. Almost identical gene SMN2, present on the same chromosome, produces a small truncated protein (SMN2) because of skipping of exon 7 from translation due to translation silent C6U substitution in exon 7 of SMN2 pre-mRNA transcript. Only 10% of the SMN2 mRNAs produce full length SMN2 protein by including exon 7 in healthy individuals. A large deletion or sometimes a point mutation in SMN1 gene is responsible for SMA. In this case the number of copies of SMN2 genes in an individual determines the severity of disease (the more the number of copies the less severe the disease). Nusinersen (ISIS 396443) binds to intron splicing silencer-N1 (ISS-N1; a site present ten nucleotides down to the junction of exon 7 and intron 7), modulating the splicing of SMN2 pre-mRNA transcript to increase the inclusion of exon 7, thereby increasing the production of full length SMN2 protein. Major evidence of its efficacy came from a sham controlled phase 3 clinical study ENDEAR. The study was stopped early based on significantly favorable results in interim analysis and all the patients were transitioned to receive nusinersen in an ongoing open-label, phase 3 study, SHINE, which will evaluate the long-term efficacy, safety and tolerability of the drug. Nusinersen is globally the first drug approved (by the US FDA) for treatment of SMA in children and adults.

Psychological problems among women with infertility problem: a comparative study.

OBJECTIVE: To explore the difference between anxiety and depression among infertile and fertile women. METHODS: The study was conducted in 2009 and comprised fertile and infertile women. The sample of infertile women was drawn from the Liaquat National Hospital, Patel Hospital, Infertility Concept and Zainub Hospital, located in urban areas of Karachi, while fertile women were drawn from the general population in urban Karachi. All the subjects had at least 10 years of education and were in the age range of 20-35 years. They two groups were further divided into two sub-groups of working and non-working women. Institute for Personality and Ability Testing Depression and Anxiety scales were used to assess depression and anxiety. SPSS 14.0 was used to analyse the data. RESULT: Of the 120 subjects, the two groups had 60(50%) each. The mean age of fertile women was 27.48±160.75 and that in the infertile group was 27.36±160.75. Depression among fertile women was 21.85±10.98 compared to 32.01±12.49 among the infertile women. Corresponding values for anxiety was 24.45±9.63 and 36.20±12.51. The difference was significant. CONCLUSION: Women with infertility experience a greater psychological impact.