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Objective: This study aims to identify sensitive respiratory, laryngeal, and self-perceptual measures for assessing vocal fatigue and to determine tasks that effectively elicit the experience of vocal fatigue., Methods: A scoping review was conducted using Cochrane, Medscape, PubMed, and Google Scholar databases. A total of 17 studies met the inclusion criteria and were reviewed in full and summarized. The studies were analyzed to extract relevant data on respiratory, laryngeal, and self-perceptual measures used to assess vocal fatigue, as well as the tasks employed to elicit vocal fatigue., Results: Of the 17 articles, 14 studies involved vocally healthy individuals, while three studies included participants with vocal fatigue. Phonation threshold pressure (PTP) was the most used and most consistent indirect respiratory measure in detecting vocal fatigue; however, only five studies included direct measurements of respiratory patterns and only two included ventilatory data. Laryngeal measures demonstrated inconsistent response to a vocal demand task, except mean fundamental frequency among vocally healthy participants, but not in those with complaints of vocal fatigue. Short-duration vowel tasks were found to be capable of eliciting vocal fatigue similar to prolonged reading tasks., Conclusion: Phonation threshold pressure (PTP) consistently captured vocal fatigue and can serve as an indirect respiratory measure. Measures of respiratory patterning and ventilation require further study. Fundamental frequency shows potential as a laryngeal measure of vocal fatigue in vocally healthy individuals but requires further investigation in those with vocal fatigue. Short-duration tasks elicit vocal fatigue and need to be investigated in future study protocols. These findings highlight the need to develop systematic protocols for ongoing assessment and monitoring of vocal fatigue to enhance both clinical practice and research methodologies., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships that may be considered as potential competing interests: Chaya Guntupalli Nanjundeswaran reports a relationship with National Institutes of Health that includes funding grants. Chaya Guntupalli Nanjundeswaran—editorial board member of Journal of Voice. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Calcium oxalate (CaOx) urolithiasis is a prevalent urinary disorder with significant clinical impact. This study investigates the therapeutic potential of Morin Hydrate (MH), a natural bioflavonoid, in preventing CaOx stone formation. Molecular docking studies revealed that MH binds strongly to glycolate oxidase (GO), suggesting its inhibitory effect on oxalate synthesis. In vitro assays demonstrated that MH effectively inhibits CaOx crystal nucleation, aggregation, and growth, altering crystal morphology to less stable forms. Diuretic activity studies in Wistar rats showed that MH substantially increased urine volume and ion excretion, indicating its moderate diuretic effect. In vivo experiments further supported these findings, with MH treatment improving urinary and serum markers, reducing oxidative stress, and protecting renal tissue, as evidenced by histopathological analysis. Notably, MH administration significantly decreased GO and lactate dehydrogenase activities in urolithiatic rats, indicating a reduction in oxalate production. These results suggest that MH is a promising candidate for the prevention and treatment of CaOx urolithiasis, with the potential for clinical application in reducing the risk and recurrence of kidney stones., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The use of in vitro-in vivo correlation (IVIVC) for extended release oral dosage forms is an important technique that can avoid potential clinical studies. IVIVC has been a topic of discussion over the past two decades since the inception of USFDA guidance. It has been routinely used for biowaivers, establishment of dissolution safe space and clinically relevant dissolution specifications, for supporting site transfers, scale-up and post approval changes. Although conventional or mathematical IVIVC is routinely used, other approach such as mechanistic IVIVC can be of attractive choice as it integrates all the physiological aspects. In the present study, we have performed comparative evaluation of mechanistic and conventional IVIVC for establishment of dissolution safe space using divalproex sodium and tofacitinib extended release formulations as case examples. Conventional IVIVC was established using Phoenix and mechanistic IVIVC was set up using Gastroplus physiologically based biopharmaceutics model (PBBM). Virtual dissolution profiles with varying release rates were constructed around target dissolution profile using Weibull function. After internal and external validation, the virtual dissolution profiles were integrated into mechanistic and conventional IVIVC and safe space was established by absolute error and T/R ratio's methods. The results suggest that mechanistic IVIVC yielded wider safe space as compared to conventional IVIVC. The results suggest that a mechanistic approach of establishing IVIVC may be a flexible approach as it integrates physiological aspects. These findings suggest that mechanistic IVIVC has wider potential as compared to conventional IVIVC to gain wider dissolution safe space and thus can avoid potential clinical studies., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Neurological disorders incidences are increasing drastically due to complex pathophysiology, and the nonavailability of disease-modifying agents. Several attempts have been made to identify new potential chemicals to combat these neurological abnormalities. At present, complete abolishment of neurological diseases is not attainable except for symptomatic relief. However, dietary recommendations to help brain development or improvement have increased over the years. In recent times, cruciferous vegetables and their phytochemicals have been identified from preclinical and clinical investigations as potential neuroprotective agents. The present review highlights the beneficial effects and molecular mechanisms of phytochemicals such as indole-3-carbinol, diindolylmethane, sulforaphane, kaempferol, selenium, lutein, zeaxanthin, and vitamins of cruciferous vegetables against neurological diseases including Parkinson's disease, Alzheimer's disease, stroke, Huntington's disease, autism spectra disorders, anxiety, depression, and pain. Most of these cruciferous phytochemicals protect the brain by eliciting antioxidant, anti-inflammatory, and antiapoptotic properties. Regular dietary intake of cruciferous vegetables may benefit the prevention and treatment of neurological diseases. The present review suggests that there is a lacuna in identifying the clinical efficacy of these phytochemicals. Therefore, high-quality future studies should firmly establish the efficacy of the above-mentioned cruciferous phytochemicals in clinical settings., (© 2024 John Wiley & Sons Ltd.)

Hydroxychloroquine (HCQ) and its derivatives have recently gained tremendous attention as a probable medicinal agent in the COVID-19 outbreak caused by SARS-CoV-2. An efficient agent to act directly in inhibiting the SARS-CoV-2 replication is yet to be achieved. Thus, the goal is to investigate the dynamic nature of HCQ derivatives against SARS-CoV-2 main protease and spike proteins. Molecular docking studies were also performed to understand their binding affinity in silico methods using the vital protein domains and enzymes involved in replicating and multiplying SARS-CoV-2, which were the main protease and spike protein. Molecular Dynamic simulations integrated with MM-PBSA calculations have identified In silico potential inhibitors ZINC05135012 and ZINC59378113 against the main protease with -185.171 ± 16.388, -130.759 ± 15.741 kJ/mol respectively, ZINC16638693 and ZINC59378113 against spike protein -141.425 ± 22.447, -129.149 ± 11.449 kJ/mol. Identified Hit molecules had demonstrated Drug Likeliness features, PASS values and ADMET predictions with no violations. Communicated by Ramaswamy H. Sarma.

Cinnamon has been utilized to remedy a lot of afflictions of humans. Literary works illustrate that it possesses numerous biological activities. Our research study is intended to recognize the phyto-derived antiviral substances from Cinnamon against COVID-19 main protease enzyme and to understand the in silico molecular basis of its activity. In the present study, 48 isolates compounds from Cinnamon retrieved from the PubMed database, are subjected to docking analysis. Docking study was performed using Autodock vina and PyRx software. Afterwards, admetSAR, as well as DruLiTo servers, were used to investigate drug-likeness prophecy. Our study shows that the nine phytochemicals of Cinnamon are very likely against the main protease enzyme of COVID-19. Further MD simulations could identify Tenufolin (TEN) and Pavetannin C1 (PAV) as hit compounds. Utilizing contemporary strategies, these phyto-compounds from a natural origin might establish a reliable medication or support lead identification. Identified hit compounds can be further taken for in vitro and in vivo studies to examine their effectiveness versus COVID-19.

Objectives: This research aimed to evaluate the antiangiogenic activity of isolated flavonoid 4a,5,8,8a-tetrahydro-5-hydroxy-3,7,8-trimethoxy-2-(3,4-dimethoxyphenyl) chromen-4-one (TMF) from Tabebuia chrysantha. STAT3-MMP9 signalling is a signal transduction mechanism that promotes angiogenesis in various cancers., Methods: The tumour xenografting chicken embryo chorioallantoic membrane (CAM) model-based ex vivo assay was used to evaluate the activity of TMF. The Western blot, densitometric analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to evaluate the activity of the MMP9. Zebrafish embryos were used to evaluate embryotoxicity, and in vitro free radical scavenging activity of flavonoid was also elucidated., Key Findings: This research assessed the high level of STAT3, p-ERK, VEGF-R and MMP9 in the tissue extract of the control group, and also, the suppression of angiogenesis in the treatment groups was due to scavenged ROS and RNS, dephosphorylation of STAT3 and ERK, and suppression of MMP9 gene expression., Conclusion: The isolated flavonoid named TMF from T. chrysantha functions as specific regulators of target proteins of angiosarcoma. The STAT3-MMP9 signalling may be used as an effective prognostic marker of angiosarcoma., (© 2020 Royal Pharmaceutical Society.)