Rate of Recovery and Symptomatic Efficacy of a Polyherbal AYUSH Formulation in the Treatment of SARS-CoV-2 Disease: A Single-arm Trial.

Background: The COVID-19 pandemic, caused by the human coronavirus, SARS-CoV-2, has led to the death of millions across the globe. The SARS-CoV-2 virus is highly infectious, and mutates rapidly. This creates additional challenges for the development of robust therapeutic solutions. Along with modern healthcare, there is a need to explore natural, plant-based antiviral compounds that can be used in the treatment of COVID-19. Objective: The present feasibility study investigates the efficacy of a 13-ingredient Ayurvedic polyherbal formulation, NOQ19, in the management of COVID-19. Methodology: A single-arm, open-label study design was adopted for this feasibility study. 161 RT-PCR-positive COVID-19 patients were enrolled. The enrolled participants were provided with the Ayurvedic intervention - two tablets of NOQ19 thrice daily along with the standard of care treatment. Follow-up COVID-19 RT-PCR tests were conducted on days 5, 10, and 14 or until the patient tested negative. The time taken to turn RT-PCR negative or become asymptomatic was noted. Setting: The study was conducted at Sri Sri Institute for Advanced Research from April 2021 to June 2021. Participants: A total of 161 COVID-19 patients isolating at home were assessed. Intervention: The NOQ19 preparation is a combination of 13 Ayurvedic herbs. Outcomes Measured: RT-PCR tests, the turnaround time to becoming asymptomatic, and regular symptoms assessment. Results: The analysis demonstrated that 74% of the patients tested negative on the RT-PCR within five days of taking NOQ19. Additionally, 98% of the subjects tested negative on the RT-PCR on day 10 after taking NOQ19 and standard of care treatment (as necessary). None of the participants reported any adverse events or side-effects due to NOQ19 medication. Conclusion: The NOQ19 Ayurvedic polyherbal formulation can be an effective and safe option for the symptomatic management of COVID-19.

An In-vitro evaluation of a polyherbal formulation, against SARS-Cov-2.

Background: In the last two years, COVID-19 pandemic caused by SARS-CoV-2 has created a mass destruction among humanity causing a major health crisis around the world. With the emergence of new strains of the virus, lack of targeted drugs and antimicrobial resistance, there is a dire need to discover specific antiviral with minimum side effects targeted against COVID-19. Objective: The present study evaluates the antiviral efficacy of a novel Ayurvedic polyherbal formulation, NOQ19, composed of a 13 well known herbs, in a cell-based setting. Methodology: Vero E6 (CL1008), the African green monkey kidney epithelial cell, were infected with SARS-CoV-2 virus (isolate USA-WA1/2020) in a 96 well-plate. NOQ19 test material was diluted at different concentration: 0.05 mg/ml, 0.1 mg/ml, 0.2 mg/ml, 0.3 mg/ml, 0.4 mg/ml, 0.5 mg/ml, 0.6 mg/ml, 0.7 mg/ml, 0.8 mg/ml and 0.9 mg/ml. These different concentrations of NOQ19 were added to infected cells respectively and incubated for 3 days in 5% CO2 incubator. Remdesivir was used as a positive control. The cells were finally fixed with formaldehyde, stained with crystal violet and plaques were visualized. The number of plaques were counted to determine the PFU(plaque forming units)/ml. Results: The results of the present study demonstrated an excellent an antiviral efficacy of NOQ19 at 0.9 mg/ml concentration, eliminating 100% virus. The IC50 of the drug was found to be 0.2 mg/ml. Conclusion: There is limited data around pre-clinical efficacy of polyherbal Ayurvedic drugs. Ayurvedic and herbal formations need to be tested in a preclinical setting to support the human data. The results of the present study demonstrated viral load reduction using NOQ19 in Vero E6 cell lines infected with SARS-CoV-2 virus. These result along with other preclinical and clinical trials could further evaluate the efficacy of NOQ19 as a potential therapeutic option in the fighting the COVID-19 challenge.

A vegetative storage protein improves drought tolerance in maize.

Vegetative storage proteins (VSPs) are known to serve as nitrogen reserves in many dicot plants but remain undiscovered in grasses, most widely grown group of crops globally. We identified and characterized a VSP in maize and demonstrated that its overexpression improved drought tolerance. Nitrogen supplementation selectively induced a mesophyll lipoxygenase (ZmLOX6), which was targeted to chloroplasts by a novel N-terminal transit peptide of 62 amino acids. When ectopically expressed under the control of various tissue-specific promoters, it accumulated to a fivefold higher level upon expression in the mesophyll cells than the wild-type plants. Constitutive expression or targeted expression specifically to the bundle sheath cells increased its accumulation by less than twofold. The overexpressed ZmLOX6 was remobilized from the leaves like other major proteins during grain development. Evaluated in the field over locations and years, transgenic hybrids overexpressing ZmLOX6 in the mesophyll cells significantly outyielded nontransgenic sibs under managed drought stress imposed at flowering. Additional storage of nitrogen as a VSP in maize leaves ameliorated the effect of drought on grain yield.

Economic Burden of Hearing Loss for the U.S. Military: A Proposed Framework for Estimation.

The goal of this multiphased research is to develop methods to comprehensively determine the economic impact of hearing impairment and noise-induced hearing injury among active duty U.S. Service Members. Several steps were undertaken to develop a framework and model for economic burden analysis: (1) a literature review identifying studies reporting the cost of health conditions and injuries in the Department of Defense, (2) consultation with a panel of subject matter experts who reviewed these cost items, and (3) discussions with DoD data stewards and review of relevant data dictionaries and databases. A Markov model was developed to represent the cumulative economic effect of events along the career span, such as retraining after hearing impairment and injury, by synthesizing inputs from various sources. The model, as developed and proposed in this study, will be a valuable decision-making tool for the DoD to identify high-risk groups, take proactive measures, and develop focused education, customized equipping, and return-to-duty and reintegration programs, thereby maximizing the retention of skilled, experienced, and mission-ready Service Members.

The prevalence and risk factors of Post-Traumatic Stress Disorder among workers injured in Rana Plaza building collapse in Bangladesh.

OBJECTIVES: Prevalence and risk factors of PTSD among injured garment workers who survived a major factory collapse. METHODS: Survivors receiving treatment or rehabilitation care at one year post event were surveyed, which included Post Traumatic Stress Disorder Checklist Specific version. RESULTS: The respondents consisted of 181 people with a mean age of 27.8 years and a majority had less than high school education (91.2%). Multivariable logistic regression found that the odds of having PTSD was higher among married (OR: 3.2 [95% CI: 1.3-8.0]), those who used to work more than 70 hr/week (OR: 2.4 [1.1-5.3]), workers who used to hold higher job positions (OR: 2.6 [1.2-5.6]) or who had a concussion injury (OR: 3.7 [1.4-9.8]). Among the respondents, 83.4% remained unemployed, and only 57.3% (63 people) reported receiving a quarter or less of what they were promised as compensation. CONCLUSIONS: Probable PTSD was prevalent among surviving workers of the Rana Plaza building collapse in Bangladesh.

A cross-sectional study on the relationship between behavioral variables and economic status in periodontal disease among elderly individuals.

OBJECTIVES: The objectives of this study were to examine the relationship between behavioral variables, such as smoking and level of income on the periodontal disease among older South Indian adults. MATERIALS AND METHODS: Data pertaining to participants aged 55 years and above from the Outpatient Department of MR Ambedkar Dental College and Hospital were used. A total of 209 elderly subjects were selected by convenient sampling and a complete evaluation of their periodontal status was carried out. RESULTS: Our study showed that patients belonging to the lower income group and smokers had more severe disease compared to other groups. They were found to have higher plaque scores, higher calculus scores, deeper pockets and attachment loss compared to the subjects of the other groups. CONCLUSION: Variables, such as smoking, gender and low income are associated with the severity of periodontal disease in older adults.

Comparison of orthopantomography and computed tomography image for assessing the relationship between impacted mandibular third molar and mandibular canal.

BACKGROUND: Permanent mandibular third molar are most commonly impacted teeth. In planning the surgical removal of mandibular third molar, correct diagnosis requires not only their precise spatial location, but also a thorough and accurate assessment of the intimate relationship with adjacent anatomical structures. Various imaging modalities have been used for localizing the mandibular third molar but not satisfactorily. AIM: This prospective study of 30 patients with 42 impacted mandibular third molars was carried out with the aim of finding evidence for justifying the use of computed tomography and orthopantomography as a diagnostic modality, prior to surgical intervention of impacted mandibular third molar. MATERIALS AND METHODS: Subjective evaluation of the CT and OPG images by two observed had shown that there was significant difference between the CT and OPG for radiographic visibility of mandibular canal in relation to third molar. RESULTS: Data analysis was done with Chi-square test (X(2)) and z-test to find the significant difference between the two radiographic modalities OPG and CT in localizing special relationship of impacted mandibular third molar. The comparison of OPG and CT showed z-value >1.5 in darkening of roots (1.98), deflection of root (2.00) interruption of z-value = 0 in narrowing of canal and dark, bifid apexes. Also it showed p-value <0.05 in all the radiographic signs except narrowing of mandibular canal and and dark and bifid apexes. CONCLUSION: The spiral CT image provides a unique opportunity to determine the exact position of impacted mandibular third molar and their relationship to adjacent structure in all three planes. CLINICAL SIGNIFICANCE: Computed tomography is highly instrumental in depicting the relationship of mandibular third molar with inferior alveolar nerve canal before treatment and accurate appraisal of the several aspects can be made regarding prognosis.

N-methylation of the c3' amide of taxanes: synthesis of N-methyltaxol C and N-methylpaclitaxel.

A method has been developed for the methylation of the C3' amide of taxol C and paclitaxel. Taxol C and paclitaxel were sequentially silylated at the 2', 7, and 1-hydroxyl groups with tert-butyldimethylsilyl chloride, triethylsilyl chloride, and dimethylsilyl chloride, respectively. Subsequent reaction with potassium tert-butoxide and methyl iodide provided the corresponding N-methylated taxane derivatives. Removal of the silyl protecting groups furnished N-methyltaxol C and N-methylpaclitaxel.

Reduced risk of toxoplasma encephalitis in HIV-infected patients--a prospective study from Gauteng, South Africa.

Toxoplasma seroprevalence was determined in 307 consecutive HIV-infected medical inpatients at the Helen Joseph Hospital, Johannesburg, South Africa, using an enzyme linked immunosorbent assay to detect immunoglobulin G (IgG) and IgM antibodies. The mean age of patients was 36 years, with a female to male ratio of 1.3 to 1. The mean CD4 count was 109 cells/mL. Toxoplasma antibodies were detected in 25 patients (8%). Twenty-two of these patients were IgG positive and IgM negative, i.e. reactivation toxoplasmosis. Only two patients (0.65%) had clinical manifestations of toxoplasmosis (one toxoplasma encephalitis and one retinitis). The risk for toxoplasma encephalitis (TE) was 0.33%. These results indicate that the toxoplasma seroprevalence and the TE risk in this population is low. The implication from this study is that in HIV-infected populations where the toxoplasma seroprevalence is low, the TE risk will be low and empiric treatment of focal brain lesions with anti-toxoplasma therapy may be inappropriate.

Folate receptor-specific antitumor activity of EC131, a folate-maytansinoid conjugate.

EC131, a new folate receptor (FR)-targeted drug conjugate, was prepared by covalently attaching the vitamin folic acid (FA) to a potent microtubule-inhibiting agent, maytansinoid DM1, via an intramolecular disulfide bond. When tested on cells in culture, EC131 was found to retain high affinity for FR-positive cells and to provide FR-specific cytotoxicity with an IC(50) in the low nanomolar range. The activity of EC131 was completely blocked in the presence of an excess of free FA, and no activity was detected against FR-negative cells. When evaluated against s.c. FR-positive M109 tumors in BALB/c mice, EC131 showed marked antitumor efficacy. Furthermore, this therapeutic effect occurred in the apparent absence of weight loss or noticeable organ tissue degeneration. In contrast, no significant antitumor activity was observed in EC131-treated animals that were codosed with an excess of FA, thus demonstrating the targeted specificity of the in vivo activity. EC131 also showed marked antitumor activity against FR-positive human KB tumors, but not against FR-negative A549 tumors, in nude mice with no evidence of systemic toxicity during or after the therapy. In contrast, therapy with the free maytansinoid drug (in the form of DM1-S-Me) proved not to be effective against the KB model when administered at its maximum tolerated dose (MTD). Taken together, these results indicate that EC131 is a highly potent agent capable of producing therapeutic benefit in murine tumor models at sub-MTD levels.

Design, synthesis, and antiproliferative and CDK2-cyclin a inhibitory activity of novel flavopiridol analogues.

The design and synthesis of a small library of 8-amidoflavone, 8-sulfonamidoflavone, 8-amido-7-hydroxyflavone, and heterocyclic analogues of flavopiridol is reported. The potential activity of these compounds as kinase inhibitors was evaluated by cytotoxicity studies in MCF-7 and ID-8 cancer cell lines and inhibition of CDK2-Cyclin A enzyme activity in vitro. The antiproliferative and CDK2-Cyclin A inhibitory activity of these analogues was significantly lower than the activity of flavopiridol. Molecular docking simulations were carried out and these studies suggested a different binding orientation inside the CDK2 binding pocket for these analogues compared to flavopiridol.