Potent antifungal properties of gallic acid in Sarcochlamys pulcherrima against Candida auris.

Candida auris is a major public health concern due to its high transmission and mortality rates, as well as the emergence of pan-resistant strains. This study aimed to identify an antifungal compound from Sarcochlamys pulcherrima , an ethnomedicinal plant, that can inhibit the growth of C. auris. Methanol and ethyl acetate extracts of the plant were obtained, and high-performance thin-layer chromatography (HPTLC) analysis was conducted to identify the major compounds in the extracts. The major compound detected by HPTLC was subjected to in vitro antifungal activity testing, and its antifungal mechanism was determined. The plant extracts inhibited the growth of both C. auris and Candida albicans. HPTLC analysis revealed the presence of gallic acid in the leaf extract. Furthermore, the in vitro antifungal assay showed that gallic acid inhibited the growth of different C. auris strains. In silico studies indicated that gallic acid can bind to the active sites of carbonic anhydrase (CA) proteins in both C. auris and C. albicans, affecting their catalytic activities. Compounds that target virulent proteins such as CA can aid in the reduction of drug-resistant fungi and the development of novel antifungal compounds with unique modes of action. However, additional in vivo and clinical studies are required to conclusively determine gallic acid's antifungal properties. Gallic acid derivatives may be developed in the future to possess more potent antifungal properties and target various pathogenic fungi.

Mapping of long stretches of highly conserved sequences in over 6 million SARS-CoV-2 genomes.

We identified 11 conserved stretches in over 6.3 million SARS-CoV-2 genomes including all the major variants of concerns. Each conserved stretch is ≥100 nucleotides in length with ≥99.9% conservation at each nucleotide position. Interestingly, six of the eight conserved stretches in ORF1ab overlapped significantly with well-folded experimentally verified RNA secondary structures. Furthermore, two of the conserved stretches were mapped to regions within the S2-subunit that undergo dynamic structural rearrangements during viral fusion. In addition, the conserved stretches were significantly depleted for zinc-finger antiviral protein (ZAP) binding sites, which facilitated the recognition and degradation of viral RNA. These highly conserved stretches in the SARS-CoV-2 genome were poorly conserved at the nucleotide level among closely related ß-coronaviruses, thus representing ideal targets for highly specific and discriminatory diagnostic assays. Our findings highlight the role of structural constraints at both RNA and protein levels that contribute to the sequence conservation of specific genomic regions in SARS-CoV-2.

Media Reporting Relating to COVID-19 Vaccination as a Driver of Vaccine Hesitancy Prior to the Second Wave of the COVID-19 Pandemic in India: A Content Analysis of Newspaper and Digital Media Reports.

Background Over 2,40,000 deaths were attributed to the SARS-CoV-2 Delta (B.1.617.2) variant in India during the second wave of the pandemic from April to June 2021 with most deaths occurring in the unvaccinated population. High levels of coronavirus disease 2019 (COVID-19) vaccine hesitancy contributed to significantly reduced vaccination coverage in the eligible population especially among healthcare workers, comorbid and older people. The existing global evidence suggests misinformation through social media to accentuate, while newspaper and mainstream media reporting to be protective against vaccine hesitancy during the COVID-19 pandemic. Content analysis of regular press coverage of COVID-19 vaccination in India during the period of initial deployment and until the onset of the second wave of the pandemic can provide useful learnings and strengthen preparedness for addressing potential vaccine hesitancy concerns during future pandemics. Therefore, we conducted this inductive content analysis of press coverage related to the COVID-19 vaccine hesitancy in India prior to the second (Delta) wave of the COVID-19 pandemic. Methods We examined news reports related to COVID-19 vaccination in India for the period from 1st January 2021 to 28 February 2021 from a high circulation English language daily (Hindustan Times), Hindi (vernacular) language daily (Dainik Jagran), and English language news reports from selected digital news portals. The inclusion criterion was any news report related to COVID-19 vaccination including editorials and guest opinion pieces that could potentially generate COVID-19-related vaccine hesitancy. The news items were classified depending on their potential to drive vaccine hesitancy by either avoiding reporting of positive information related to COVID-19 vaccines, or attributing directly or indirectly, negative or misleading commentary relating to vaccine safety or efficacy. Reports with possible risk of increasing vaccine hesitancy were further analyzed based on content, source of information, and the extent of fact-checking. Results Most of the published newspaper reports examined in this study echoed official news sources and views from government health agencies promoting COVID-19 vaccine acceptance and dispelling doubts on concerns regarding vaccine safety. There were eight unique newspaper reports after excluding duplicated bilingual entries and four news items from online digital Indian news sources that met our criterion of reports with possible contribution to vaccine hesitancy. The reports possibly contributed to vaccine hesitancy were grouped into two themes: (i) Doubts on the safety and efficacy of local manufactured vaccines: most of these reports focused on the granting of emergency use authorization for Covaxin (BBV152) in 'clinical trial mode' without the completion and publication of Phase-3 efficacy data (ii). Doubts on vaccine requirement considering high seroprevalence and reduced virus transmission.  Conclusions Concerns about the efficacy and safety of Covaxin (BBV152), safety of the Covishield vaccine, and questioning the necessity of immunizing all adults with COVID-19 vaccines were observed in multiple press reports with attempts at politicization of vaccination-related decisions. The press reporting with potential for contributing to significant COVID-19 vaccine hesitancy since launch and until the Delta wave of the pandemic in India has important lessons in future pandemic preparedness.

Acquisition of Pragmatic Skills in Paediatric Cochlear Implant Users.

Pragmatic language skills are one of the most complex language skills. Children with hearing loss face difficulty in social participation and effective communication during mainstreaming. Without mastery of these skills, children may encounter significant challenges with abstract conversational communication and literacy. This study aimed to explore the age and pattern of acquisition of pragmatic skills in hearing-impaired children. Twelve (12) children with Cochlear Implants (CI) in the age range of 5 to 10 years with minimum 1-year post-implantation regular therapy and twelve (12) age-matched normal hearing children participated in the study. All participants were administered the 'Test of Pragmatic Skills' (Shulman, 1986) comprising different domains of pragmatics. Their responses were rated on a six-point rating scale from 0 to 5. A qualitative analysis of various domains revealed that paediatric cochlear implant users used varied pragmatic skills at approximately 3 years on average during the post-implantation period compared to the typically developing children who acquired the skills well below 3 years on average. Pragmatics is very well correlated to the child's cognition; hence, the higher the cognitive age, the earlier the acquisition of pragmatic skills. The results prove that pragmatic skills developed proportionately to their implant age but need to be at par with their cognitive age. Rehabilitation of CI children, thus, should levy heavy focus on varied pragmatic domains, which will facilitate contextually appropriate communication at the earliest possible time during the post-implantation period.

Solvent-free mechanochemical grinding facilitates clean synthesis of N-substituted amines.

Herein, we have optimized a highly efficient and neat mechanochemical grinding procedure for the facile synthesis of N-substituted amines using easily available substituted halides and amines. The developed protocol is applicable for gram scale synthesis as well. Advantageous features of this strategy include mild and neat reaction conditions, a short reaction time at room temperature and isolation of products without column chromatography in excellent yields.

Acoustic, Perceptual, and Laryngoscopic Changes Post Vocal Abuse at a College Fest.

INTRODUCTION: College students use their voices at excessively loud intensities and long durations during college fests. The accumulative effect of vocally abusive behaviors in the presence of high ambient noise, poor vocal hygiene, and other environmental factors contribute significantly towards reducing vocal effectiveness in college students. OBJECTIVE: The present study aimed to study the effect of a vocally demanding situation (college Fest) on perceptual and objective voice features of college students. METHODOLOGY: In this study, a total number of 27 undergraduate female students participated in the age range of 18-27 years. Pre-test-post-test research design was applied. Data analysis consisted of video stroboscopic examination, acoustic analysis using the Multi-dimensional voice program (MDVP), and perceptual evaluation with the GRBAS scale. The data obtained were processed using descriptive statistics and non-parametric tests to determine the difference in each measured parameter pre- and postfest. RESULTS AND DISCUSSION: Incomplete glottis closure, asymmetric vibration of vocal folds, and aperiodicity of vocal folds increased significantly postcollege Fest. GRBAS parameters also showed a change from pre Fest scores on grade (hoarseness) increased by 38%, breathiness in 34%, roughness in 26%, Asthenia in 15%, and strain increased in 38% participants. A P-value estimation revealed significantly higher scores in Jitter percent, Shimmer percent, and relative average perturbation than pre-fest scores. CONCLUSION: The results of the present study indicate a high risk of vocal disorders among college students post Fest. This study suggests a potential unmet need for college students to receive education before cultural events on optimal vocal usage, vocal hygiene, and an appropriate period of vocal rest.

1,3,5-Pyrazoline Derivatives in CNS Disorders: Synthesis, Biological Evaluation and Structural Insights through Molecular Docking.

BACKGROUND: Anxiety and oxidative stress are the common disorders prevailing in the modern age. Many new pyrazoline derivatives have been synthesized and patented, but there is still continuous research in progress to explore antidepressant and antioxidant potential of pyrazoline scaffold. OBJECTIVES: The present work was carried out to synthesize, characterize and evaluate the pharmacological potential of 1,3,5-Pyrazoline derivatives. METHODS: Ten new 1,3,5-Pyrazoline derivatives were synthesized and characterized by IR, 1HNMR and mass spectral techniques. The synthesized pyrazoline derivatives were investigated for their in vivo antidepressant activity by Tail Suspension Test (TST) and in vitro antioxidant activity by FRAP and DPPH assay methods. The docking studies and in silico ADME and toxicity characteristics were also evaluated. RESULTS: Among the synthesized analogues, IVh showed the highest antidepressant activity with a significant reduction in the duration of immobility. The compound IVh emerged as the most potent antioxidant compound due to the presence of an electron releasing hydroxyl group. Docking studies of most potent compounds revealed good interaction points with the MAO-A enzyme. The compounds were found to obey Lipinski's Rule of Five and displayed the least in silico toxicity profile. CONCLUSION: The synthesized compounds were found to possess great potential in decreasing the duration of immobility in Swiss albino mice and scavenging free radicals. These compounds may serve as new leads for further drug exploration.