In silico screening of potential plant peptides against the non-structural proteins of dengue virus.

BACKGROUND OBJECTIVES: Peptides isolated from different sources of plants have the advantages of specificity, lower toxicity, and increased therapeutic effects; hence, it is necessary to search for newer antivirals from plant sources for the treatment of dengue viral infections. METHODS: In silico screening of selected plant peptides against the non-structural protein 1, NS3 protease domain (NS2B-NS3Pro) with the cofactor and ATPase/helicase domain (NS3 helicase domain/NS3hel) of dengue virus was performed. The physicochemical characteristics of the peptides were calculated using Protparam tools, and the allergenicity and toxicity profiles were assessed using allergenFP and ToxinPred, respectively. RESULTS: Among the tested compounds, Ginkbilobin demonstrated higher binding energy against three tested nonstructural protein targets. Kalata B8 demonstrated maximum binding energy against NSP-1 and NSP-2, whereas Circulin A acted against the NSP3 protein of dengue virus. INTERPRETATION CONCLUSION: The three compounds identified by in silico screening can be tested in vitro, which could act as potential leads as they are involved in hampering the replication of the dengue virus by interacting with the three prime non-structural proteins.

In silico screening of potential plant peptides against the Non-structural proteins of Dengue virus.

BACKGROUND OBJECTIVES: Peptides isolated from different sources of plants have the advantages of specificity, lower toxicity, and increased therapeutic effects; hence, it is necessary to search for newer antivirals from plant sources for the treatment of dengue viral infections. METHODS: In silico screening of selected plant peptides against the non-structural protein 1, NS3 protease domain (NS2B-NS3Pro) with the cofactor and ATPase/Helicase domain (NS3 helicase domain/NS3hel) of Dengue virus was performed. The physicochemical characteristics of the peptides were calculated using Protparam tools, and the allergenicity and toxicity profiles were assessed using allergenFP and ToxinPred, respectively. RESULTS: Among the tested compounds, Ginkbilobin demonstrated higher binding energy against three tested non-structural protein targets. Kalata ß-8 demonstrated maximum binding energy against NSP-1 and NSP-2, whereas Circulin A acted against the NSP3 protein of the dengue virus. INTERPRETATION CONCLUSION: Hence, the three compounds identified by in silico screening can be tested further for in vitro studies, which could act as potential leads as they are involved in hampering the replication of the dengue virus by interacting with the three prime non-structural proteins.

Too little, too late: ineffective regulation of dietary supplements in the United States.

Millions of people in the United States consume dietary supplements hoping to maintain or improve their health; however, extensive research has failed to demonstrate the efficacy of numerous supplements in disease prevention. In addition, concerns about the safety of routine and high-dose supplementation have been raised. The Food and Drug Administration regulates dietary supplement quality, safety, and labeling, and the Federal Trade Commission monitors advertisements and marketing; still, vast enforcement challenges remain, and optimal governmental oversight has not been achieved. If the composition and quality of ingredients cannot be reliably ensured, the validity of research on dietary supplements is questionable. Moreover, the health of the US public is put at risk.

Does Platelet-Rich Plasma Deserve a Role in Accelerating the Recovery of Reflex Sympathetic Dystrophy Following Distal Radius Fracture?

Introduction: This study was to evaluate the efficacy of multiple platelet-rich plasma injections in reflex sympathetic dystrophy following distal radius fracture after previous various treatments have failed. Materials and methods: This comparative prospective study was designed for 64 patients of reflex sympathetic dystrophy developed following distal radius fracture, from January 2009 to December 2020 were enrolled in this study. This cohort of patient was given either four multiple subcutaneous platelet-rich plasma injections at weekly interval (n = 32) or two injections in a month with 15 days interval (n = 32). The primary outcome measure assessed with patient rated wrist evaluation questionnaire score. The secondary outcome was a visual analogue scale pain score. The final follow up was at 2 years. p ≤ 0.05 is considered statistically. Results: The patient rated wrist evaluation score for usual and specific activities and EQ-VAS for pain level showed statistically significant greater improvement in group A (42 ± 21%) compared to group B (19 ± 24%), (p = 0.37). Patients also had improvement in wrist movements with no statistically significant differences in both groups. The standard difference in means of all three functional scores was almost similar between both groups A and B (standard difference in means = 0.032; 95% CI 0.236-0.830; p = 0.495), considered clinically meaningful. Conclusion: This study results suggest autologous platelet-rich plasma injections seem to be safe, cost effective, efficacious algorithm treatment for reflex sympathetic dystrophy following distal radius fracture patients where previous treatments have failed.

In silico screening of plant peptides against the envelope protein of dengue virus.

Peptide therapeutics are found to be an emerging and attractive class of treatment due to their highly specific and safe nature. Hence twenty plant peptides were subjected to screening by molecular docking against the envelope protein of the dengue virus using Clus Pro, Patch Dock, and HADDOCK servers. Physicochemical parameters, allergenicity, and toxicity profile of the plant peptides were estimated by Protparam analysis, AllergenFP, and ToxinPred web servers. Six potential compounds namely Ginkbilobin, Cycloviolin-D, Circulin-B, Circulin-A, Cycloviolacin-013, and Circulin-C showed the highest binding energy with both nonallergenic and nontoxic properties. They also exhibited desirable half-lives extending to 30 hrs except for Ginkbilobin, which showed the least half-life of 4.4 hours and non-polar activity. The residues of Ala-4 of Ginkbilobin; Arg-30 of Cycloviolin D; Arg-29 of Circulin A and C interacted with the Try 101 of the domain II of Envelope protein, implying the possible inhibition of the insertion process of the trimeric E protein during fusion with the host cells. Thus, the identified plant peptides could serve as potential leads upon further subjection to in vitro studies.

Nontuberculous mycobacteria - clinical and laboratory diagnosis: experiences from a TB endemic country.

AIM: To evaluate the performance of VITEK®MS with DNA sequencing for laboratory diagnosis of non-tuberculous mycobacteria (NTM) species in a resource-limited setting. METHODS: 16SrRNA sequencing and MALDI-TOF mass spectrometry (VITEK®MS) was performed at a tertiary-care hospital in India. MALDI-TOF results were confirmed by 16S rRNA sequencing. In addition, sequencing of the internal transcribed spacer region was performed on slowly growing NTM. RESULTS: Commonest species isolated were M. abscessus, M. intracellulare, M. avium, M. fortuitum and M. simiae. 16S rRNA sequencing and MALDI-TOF results had agreement of 94.5% for rapidly growing and 77.5% for slowly growing NTM. CONCLUSION: There is good correlation between VITEK®MS and sequencing for rapidly growing NTM. For slowly growing species, sequencing would be required in a third isolates.

Prevalence of Risk and Protective Factors Associated with HIV and HCV Infections Among Male High School Students Who Have Sex with Males-Hawai'i, 2013, 2015, and 2017.

Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections are increasing among young adults, and males who have sex with males (MSM) are at high risk for both infections. Limited Hawai'i data exists on the extent to which populations, such as MSM, are engaging in behaviors that place them at increased risk for either infection. This analysis quantified the proportion of Hawai'i public high school students who are MSM and are at risk for HCV and HIV infections. Data from the 2013, 2015, and 2017 Hawai'i Youth Risk Behavior Surveys (YRBS) were combined (n=16,751) to investigate the prevalence of risk factors associated with HIV and HCV infections (eg, sexual risk behaviors, substance use) and protective factors among MSM public high school students. Among sexually experienced male students (n=3,391), 13.1% were classified as MSM and among these, 40.3% identified as heterosexual despite reporting same-sex sexual contact. Multivariate modeling demonstrated that MSM students are significantly more likely than non-MSM students to engage in behaviors that increase their risk for HIV and HCV infections (composite risk variable; adjusted Prevalence Ratio: 1.40, 95% CI 1.15 - 1.70) and are significantly less likely to have protective factors. Evidence-based prevention strategies for reducing HIV and HCV risk behaviors while improving protective factors among sexual minority youth in Hawai'i are necessary and must address sexual behavior along with other dimensions of sexual orientation.

Insights in Public Health: Formative Factors for a Statewide Tobacco Control Advocacy Infrastructure: Insights from Hawai'i.

Hawai'i has comprehensive statewide tobacco control policies and was the first US state to raise the minimum age of sale, purchase, and possession of tobacco products to age 21 ("Tobacco 21") in a policy including not just cigarettes, but also electronic smoking devices and other tobacco products. This insights article provides strategic thinking about tobacco control advocacy planning. Specifically, we identify formative factors critical to building and sustaining our cross-sector, statewide advocacy infrastructure that has been able to address many ongoing challenges of tobacco-use prevention and control over time. This can provide new insights for other large-scale tobacco-control advocacy efforts.

A prospective randomized controlled study: Theophylline on oxidative stress and steroid sensitivity in chronic obstructive pulmonary disease patients.

OBJECTIVE: Oxidative stress is involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Corticosteroid fails to suppress inflammation and oxidative stress due to steroid resistance. Theophylline has an effect on histone deacetylase (HDAC) activity and improves steroid sensitivity in COPD. Given changes in oxidative stress associated with diminished corticosteroid effects, a clinical study in which antioxidants and free radicals are estimated can suggest a correlation between antioxidants, theophylline, and corticosteroid sensitivity. MATERIALS AND METHODS: A randomized controlled study was conducted in 60 participants divided into 4 groups: Group I (controls) - 15 normal healthy volunteers, Group II - COPD patients who received theophylline 300 mg + salbutamol 8 mg, Group III - patients who inhaled budesonide 400 µg + salbutamol 8 mg, and Group IV - theophylline 300 mg + inhaled budesonide 400 µg + salbutamol 8 mg 12 weeks. Blood samples were collected at the time of diagnosis and at 4-week interval for 3 months from all the groups and antioxidant parameters, spirometric % forced expiratory volume in 1 s (FEV1) were measured. RESULTS: The mean difference between groups was analyzed using one-way ANOVA. There was a significant increase in antioxidant enzymes such as catalase, glutathione (GSH) serum transferase, (P < 0.05), reduced GSH, and superoxide dismutase (P < 0.01) and a significant decrease in lipid peroxidation (P < 0.01) at 12 weeks of the study period. Postbronchodilator FEV1 values have also shown a significant increase at 12 weeks (P < 0.01). CONCLUSION: Theophylline increases the expression and activity of HDAC and improves steroid sensitivity thereby decreases oxidative stress. Hence, novel therapeutic strategy is therefore the reversal of this corticosteroid resistance by increasing the expression and activity of HDAC achieved using corticosteroids along with theophylline.

Insights in Public Health: For the Love of Data! The Hawai'i Health Data Warehouse.

Data form the framework around which important public health decisions are made. Public health data are essential for surveillance and evaluating change. In Hawai'i, public health data come from a multitude of sources and agencies. The Hawai'i Health Data Warehouse (HHDW) was created to pull those data into a single location and to present results in a form that is easy for the public to access and utilize. In the years since its creation, HHDW has built a second consumer-focused web site, Hawai'i Health Matters, and is now introducing new functionality on the original site that allows users to define their own enquiry. The newly adopted Indicator-Based Information System (IBIS) uses a web interface to perform real-time data analysis and display results. This gives users the power to examine health data by a wide range of demographic and socioeconomic dimensions, permitting them to pinpoint the data they need.

Late onset paraplegia--a sequela to Pott's disease. A report on imaging, prevention and management.

Late onset paraplegia is a neurological complication that develops after a variable period in a patient with healed tuberculous disease of the vertebrae. In this retrospective analysis clinical features, imaging in diagnosis and treatment of this condition are described among 5 cases seen over a period of 5 years. This complication occurred even after successful treatment of initial spinal lesions with rifampicin-containing regimens. Magnetic resonance imaging was useful in pinpointing the exact pathology; one case had syrinx and two cases had marked internal gibbus with cord atrophy. Of the two cases who accepted surgical treatment, one improved.

In silico screening of plant peptides against the envelope protein of dengue virus

@#Peptide therapeutics are found to be an emerging and attractive class of treatment due to their highly specific and safe nature. Hence twenty plant peptides were subjected to screening by molecular docking against the envelope protein of the dengue virus using Clus Pro, Patch Dock, and HADDOCK servers. Physicochemical parameters, allergenicity, and toxicity profile of the plant peptides were estimated by Protparam analysis, AllergenFP, and ToxinPred web servers. Six potential compounds namely Ginkbilobin, Cycloviolin-D, Circulin-B, Circulin-A, Cycloviolacin-013, and Circulin-C showed the highest binding energy with both nonallergenic and nontoxic properties. They also exhibited desirable half-lives extending to 30 hrs except for Ginkbilobin, which showed the least half-life of 4.4 hours and non-polar activity. The residues of Ala-4 of Ginkbilobin; Arg-30 of Cycloviolin D; Arg-29 of Circulin A and C interacted with the Try 101 of the domain II of Envelope protein, implying the possible inhibition of the insertion process of the trimeric E protein during fusion with the host cells. Thus, the identified plant peptides could serve as potential leads upon further subjection to in vitro studies.

Risk factors for completed suicides: a case-control study from Bangalore, India.

INTRODUCTION: Suicides are a hidden and unrecognized epidemic in the Indian region, affecting predominantly younger age groups. Information on causative risk factors and mechanisms is not available in the country, which is crucial for designing intervention programmes. OBJECTIVES: To identify and quantify risk factors for completed suicides in the city of Bangalore. METHODS: A case-control study was conducted with the families of 269 completed suicides and 269 living controls within the broader population of the city using psychological autopsy methods. RESULTS: The study has shown that several factors in the areas of family, marriage, education, occupation, general health, mental health and absence of protective factors contribute significantly for suicides. The cumulative and repetitive interaction of several factors in a complex manner results in suicides. The significant factors were presence of previous suicidal attempt in self (odds ratio (OR) = 42.62), interpersonal conflicts and marital disharmony with spouse (OR = 27.98), alcoholism in self (OR = 23.38), presence of a mental illness (OR = 11.07), sudden economic bankruptcy (OR = 7.1), domestic violence (OR = 6.82) and unemployment (OR = 6.15). Individuals completing suicides did not have a positive outlook towards life, problem-solving approaches and coping skills. CONCLUSION: The observed findings are at variance with suicidal causation in the West in some areas operating in a different sociocultural and economic environment. The intervention strategies should include prioritized macro and micro level efforts aimed at individual, family and society.

A controlled clinical trial of short-course chemotherapy for tuberculoma of the brain.

OBJECTIVE: The efficacy of a short-course regimen in the treatment of brain tuberculoma and computerised tomography (CT) scan appearance before, during and after antituberculosis treatment was studied in a controlled clinical trial. DESIGN: Patients aged over 5 years with tuberculoma of the brain diagnosed by CT scan were randomly allocated to one of the following 2 regimens: Regimen 1: rifampicin, isoniazid and pyrazinamide daily for an initial 3 months followed by rifampicin and isoniazid twice-weekly for 6 months. Regimen 2: rifampicin, isoniazid and pyrazinamide thrice-weekly for an initial 3 months followed by rifampicin and isoniazid twice-weekly for 6 months. The patients were followed intensively for 2 years from the start of treatment. RESULTS: Of the 108 patients analysed (regimen 1: 56, regimen 2: 52), at the end of treatment clinical status was normal in 91% in regimen 1 and 88% in regimen 2. Of the 91 patients with scan assessments, CT scan lesions disappeared at 24 months in 77% of 47 patients in regimen 1 and 80% of 44 in regimen 2, and in both groups 88% of the patients were clinically normal. None had relapses requiring treatment. CONCLUSIONS: Short-course regimens of 9 months' duration are effective in the treatment of tuberculoma of the brain; clinical recovery was faster than scan clearance.