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A series of unanticipated adverse events or adverse drug reactions (ADRS) that occur over a short period of time and, if confirmed, call into question the risk/benefit ratio, resulting in a crisis situation. In general, a crisis is a period of trauma, discomfort, and changes that are unavoidable. It is frequently difficult to forecast what triggers a crisis, but crises almost always result in changes—typically for the worse. A crisis has the potential to have a major negative impact on the (organization's) operations or to expose the (organization) to severe environmental, economic, reputational, or legal risk. A low-probability, high-impact circumstance that essential stakeholders regard as endangering the organization's viability and that these individuals subjectively perceive as hazardous.

Now days consumption of herbal medicines has expanded many folds a report of side effects observed with standard drugs. Herbal face wash was produce from fresh herbs or fresh fruits to enhance the skin and improve beauty. In the world, increases the need for utilization of herbal medicines. Acne is a chronic inflammatory situation of skin that give rise to pimples and spots, on the face, shoulders, back, neck, chest, and upper arms. In this work, different aims were produce to development and evaluation of the herbal anti-acne gel containing extract of root of radish (Raphanus sativus L.), turmeric is a antibacterial agent, sandal wood as flavoring agent, lemon juice as a preservative, honey as humectant through to make pure herbal formulation. The plants have been described in literature having good anti-acne, anti-microbial, anti-oxidant, antiseptic, and anti-inflammatory activity. Prepared formulation was evaluated for numerous parameters like colour, appearance, pH, stability studies, biological activities. It was very great attempt to begin the herbal anti acne face wash contain extracts of herbal products.

The goal of this research is to create a herbal shampoo that promotes hair growth and strength without harming or destroying it. The herbs reetha, amla, neem, fenugreek, hibiscus, and shikakai were chosen using a traditional system. Shampoo is used to clean the hair while also conditioning, smoothing, and maintaining hair health, keeping it free of dandruff, filth, grease, and lice. Above all, it is meant to provide safety benefits. Antimicrobial agents can be classed as either bactericidal (killing bacteria) or bacteriostatic (slowing the growth of germs). Antibacterial agents are crucial in the fight against infectious diseases. As a result, we discovered good qualities for herbal shampoo in our study, and we will continue to optimise the benefits of herbal shampoo for human usage as a cosmetic product.

Apoplexy of the Pituitary gland is rarely seen critical disorder marked by acute throbbing of head / altered mental status / visual disturbances /decreased consciousness, due to sudden haemorrhagic changes of the pituitary or infarction of the same. There are numerous factors which precipitate apoplexy of the pituitary, sepsis being one of the least common cause, as is elaborated in this case study. Inspite of having a distinctive presentation, pituitary apoplexy eludes diagnosis and proper management as it is complicated by related co-morbidities. Its occurrence in a postpartum lady is an even rarer incident. This article shows a rare occurrence of apoplexy of macroadenoma in a postpartum woman which was managed conservatively.

An essential role played by cardiotocography (CTG), is promptly detecting non-reassuring foetal status during delivery, as these abnormal changes are a prime reason for women to undergo a caesarean section. But all abnormal changes in cardiotocography does not lead to poor outcome in terms of liquor that was meconium stained or a low APGAR score at birth. As a result, research is the need of the hour, to understand their correlation; hence, showing the benefit of CTG in the precise detection of non-reassuring foetal status is correlated from the intraoperative findings discovered later. This review article aimed to see if there was a link between perioperative findings and foetal consequences in women who had a caesarean section due to foetal condition, which was not reassuring according to cardiotocographic findings.

Transfer RNA remains to be a mysterious molecule of the cell repertoire. With its modified bases and selectivity of codon recognition, it remains to be flexible inside the ribosomal machinery for smooth and hassle-free protein biosynthesis. Structural changes occurring in tRNA due to the presence or absence of wybutosine, with and without Mg2+ ions, have remained a point of interest for structural biologists. Very few studies have come to a conclusion correlating the changes either with the structure and flexibility or with the codon recognition. Considering the above facts, we have implemented molecular modeling methods to address these problems using multiple molecular dynamics (MD) simulations of tRNAPhe along with codons. Our results highlight some of the earlier findings and also shed light on some novel structural and functional aspects. Changes in the stability of tRNAPhe in native or codon-bound states result from the conformations of constituent nucleotides with respect to each other. A smaller change in their conformations leads to structural distortions in the base-pairing geometry and eventually in the ribose-phosphate backbone. MD simulation studies highlight the preference of UUC codons over UUU by tRNAPhe in the presence of wybutosine and Mg2+ ions. This study also suggests that magnesium ions are required by tRNAPhe for proper recognition of UUC/UUU codons during ribosomal interactions with tRNA.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has been responsible for the cause of global pandemic Covid-19 and to date, there is no effective treatment available. The spike ‘S’ protein of SARS-CoV-2 and ACE2 of the host cell are being targeted to design new drugs to control Covid-19. Similarly, a transmembrane serine protease, TMPRSS2 of the host cell plays a significant role in the proteolytic cleavage of viral ‘S’ protein helpful for the priming of ACE2 receptors and viral entry into human cells. However, three-dimensional structural information and the inhibition mechanism of TMPRSS2 is yet to be explored experimentally. Hence, we have used a molecular dynamics (MD) simulated homology model of TMPRSS2 to study the inhibition mechanism of experimentally known inhibitors Camostat mesylate, Nafamostat and Bromhexine hydrochloride (BHH) using molecular modeling techniques. Prior to docking, all three inhibitors were geometry optimized by semi-empirical quantum chemical RM1 method. Molecular docking analysis revealed that Camostat mesylate and its structural analogue Nafamostat interact strongly with residues His296 and Ser441 present in the catalytic triad of TMPRSS2, whereas BHH binds with Ala386 along with other residues. Comparative molecular dynamics simulations revealed the stable behavior of all the docked complexes. MM-PBSA calculations also revealed the stronger binding of Camostat mesylate to TMPRSS2 active site residues as compared to Nafamostat and BHH. Thus, this structural information could be useful to understand the mechanistic approach of TMPRSS2 inhibition, which may be helpful to design new lead compounds to prevent the entry of SARS-Coronavirus 2 in human cells.

The COVID19, a fatal disease by coronavirus (SARS-CoV-2) in late 2019 in China is now pandemic caused severe acute respiratory syndrome. The pandemic of COVID-19 has reached almost all regions of the world including territories with the death toll of more than 35,000. It has been estimated that one out every six-person affected by COVID-19 developed life-threatening conditions. The difficulty is that there are no vaccines or no specific treatment modalities for the management of COVID-19, apart from symptomatic treatments. Efforts for the development of vaccines and other specific treatment modalities are co-ordinated by the World Health Organisation (WHO), with many clinical trials ongoing with modern and traditional medicines. In this regard, various Phyto-actives from the plants are getting analyzed, which has earlier shown to be effective in various viral infections. Therefore, keeping the world scenario and due to the lack of vaccine, we have in silico studied the activity of tetrahydrocurcumin, a major metabolite of curcumin, a household spice, matairesinol, a major compound in wheat bran or flaxseed and vitamin K2-7 against both SARS-CoV's main peptide and COVID-19 Mpro.

The rapid outbreak of SARS-Coronavirus 2 (SARS-CoV-2) caused a serious global public health threat. The spike ‘S’ protein of SARS-CoV-2 and ACE2 of the host cell are being targeted to design and discover new drugs to control Covid-19 disease. Similarly, a transmembrane serine protease, TMPRSS2 of the host cell has been found to play a significant role in proteolytic cleavage of viral spike protein priming to the receptor ACE2 present in human cell. However, three dimensional structure and inhibition mechanism of TMPRSS2 is yet to be explored experimentally. Hence, in the present study we have generated a homology model of TMPRSS2 and studied its binding properties with experimentally studied inhibitors viz. Camostat mesylate, Nafamostat and Bromhexine hydrochloride (BHH) using molecular docking technique. Docking analysis revealed that the Camostat mesylate and its structural analogue Nafamostat interacts strongly with residues His296, Ser441 and Asp435 present in catalytic triad of TMPRSS2. However, BHH interacts with Gln438 and other residues present in the active site pocket of TMPRSS2 through hydrophobic contacts effectively. Thus, these results revealed the inhibition mechanism of TMPRSS2 by known inhibitors Camostat mesylate, Nafamostat and Bromhexine hydrochloride in detail at the molecular level. However, Camostat mesylate shows strong binding as compared to other two inhibitors. This structural information could also be useful to design and discover new inhibitors of TMPRSS2, which may be helpful to prevent the entry to SARS-Coronavirus 2 in human cell.

Objective: To assess the efficacy, tolerability and safety of vitamin K2-7 in patients with peripheral neuropathy (PN). Materials and Methods: This study was conducted in 100 patients with PN suffering from VBD or T2DM. Vitamin K2-7 capsules (200 mcg) were given orally for 8 weeks followed up to the 12th week. Symptoms included tingling and numbness along with weakness, fatigue, and cramps. The intensity of the symptoms of PN was assessed on a Visual Analog Scale (VAS). Results: At baseline, the VAS score was 6–9 for VBD group and 8–10 for T2DM group. After treatment with Vitamin K2-7 by the 12th week, VAS score had reduced to 1–2 in both groups. The decrease was statistically significant (P

Objective To investigate the combinatorial effect of hydroalcoholic extracts of Andrographis paniculata Nees. and Pterocarpus marsupium Roxb. plants prospective to diabetes management. Methods Taking a lead from the scientific literature, in silico studies have also been designed for the screening of anti-diabetic targets against andrographolide and pterostilbene compounds followed by in vivo studies from Andrographis paniculata Nees. and Pterocarpus marsupium Roxb. Furthermore, the diabetes was induced by STZ model and the impact of Andrographis paniculata Nees. and Pterocarpus marsupium Roxb. have been conformed by relative expression studies by qPCR. Results Our results have shown that andrographolide and pterostilbene are SGLT2 inhibitors and selective PPARγ agonists in in silico studies. Later, during in vivo mRNA expression studies confirming the same pattern. The findings of the study has shown to overcome the common knowledge of the only C–glycoside based molecules inhibiting the SGLT2. Conclusions The possible mechanism for PtyroneTM in the management of diabetes could be a selective PPARγ agonist, GLUT4 translocation and SGLT2 inhibition molecule.

Importance: This post-marketing surveillance study was conducted to evaluate real-world information about the efficacy and safety of oral Tinefcon? tablets (Sphaeranthus indicus based) in plaque psoriasis patients. Materials and Methods: Patients aged at least 18 years and older with clinical diagnosis of plaque psoriasis, were enrolled in this open label, non-comparative, multicenter trial. All eligible subjects received four 700 mg Tinefcon? tablets/day for 12 weeks. The primary outcome measure was percent change in Psoriasis Area Severity Index (PASI) score from baseline to week 12. The secondary outcome measures were Physician Global Assessment (PGA), Nail Psoriasis Severity Index (NAPSI), Psoriatic Arthritis Evaluation and Gene Expression Profiling and Immunohistochemistry. Results: After completion of Tinefcon? treatment at 12 weeks, more than half of subjects (52%) achieved PASI 50 response; PASI 75 response was attained in 68 (23%) subjects and PASI 90 response in 22 (7%) subjects. Five subjects with severe psoriasis achieved PASI 90 without receiving any concomitant medication. Reduction in severity as assessed by PGA was observed in more than half of patients with moderate disease. Histopathological evaluation revealed that epidermal thickness was considerably reduced in 66% of subjects. The expression of inflammatory marker S100A9 protein was(meaningfully reduced in 60% patients with non-significant reduction of Keratin 10 protein expression. Gene expression analysis showed increase down regulation of SERPINB4; PI3 and KRT16 genes after a 12-week treatment period in subjects with higher PASI scores. Conclusion: Oral Tinefcon? tablets showed good efficacy and had a favorable safety profile in plaque psoriasis patients.