Respected but stigmatized: Healthcare workers caring for COVID-19 patients.

BACKGROUND: Healthcare workers (HCWs) caring for Corona Virus Disease 2019 (COVID-19) patients are at increased risk of being stigmatized, which compromises their individual mental well-being and the quality of care they deliver. Stigma-reduction interventions may (partly) prevent this. However, there is a lack of in-depth understanding of the experiences and underlying causes of COVID-19 stigma among HCWs, which is needed to design such interventions. We conducted in-depth semi-structured interviews to assess COVID-19 stigma among COVID-19 HCWs in Ireland, Nigeria, The Netherlands, Pakistan, and The Philippines. METHODS: We used a purposive and snowball sampling to recruit a total of 53 HCWs for online interviews (13 in Ireland; 15 in Nigeria; 6 in The Netherlands; 6 in Pakistan; and 13 in The Philippines (2021). After verbatim transcribing interviews, we used a thematic approach for data analysis. RESULTS: In all countries, stigmatization of COVID-19 HCWs is driven by fear of infection and the perception of HCWs being carriers of the disease amplified by them wearing of scrubs and personal protective equipment. There were differences between countries in the way stigma manifested in self- anticipated and experienced stigma like scolding, discrimination, avoidance, (self-) isolation, and exclusion in public, in the community, at work, and in the household. The stigma resulted in feelings of depression, loneliness, isolation, and the desire to quit one's job. DISCUSSION: COVID-19 HCWs from all countries experienced all forms of stigmatization related to their work as a COVID-19 frontliner. This affected their mental well-being, which in turn affects job performance and quality of care, there is a high need to develop stigma reduction tools for HCWs.

Fragment-based in silico design of SARS-CoV-2 main protease inhibitors.

3CLpro is essential for SARS-CoV-2 replication and infection; its inhibition using small molecules is a potential therapeutic strategy. In this study, a comprehensive crystallography-guided fragment-based drug discovery approach was employed to design new inhibitors for SARS-CoV-2 3CLpro. All small molecules co-crystallized with SARS-CoV-2 3CLpro with structures deposited in the Protein Data Bank were used as inputs. Fragments sitting in the binding pocket (87) were grouped into eight geographical types. They were interactively coupled using various synthetically reasonable linkers to generate larger molecules with divalent binding modes taking advantage of two different fragments' interactions. In total, 1,251 compounds were proposed, and 7,158 stereoisomers were screened using Glide (standard precision and extra precision), AutoDock Vina, and Prime MMGBSA. The top 22 hits having conformations approaching the linear combination of their constituent fragments were selected for MD simulation on Desmond. MD simulation suggested 15 of these did adopt conformations very close to their constituent pieces with far higher binding affinity than either constituent domain alone. These structures could provide a starting point for the further design of SARS-CoV-2 3CLpro inhibitors with improved binding, and structures are provided.

Effect of Berberis vulgaris L. root extract on ifosfamide-induced in vivo toxicity and in vitro cytotoxicity.

Ifosfamide is a widely used chemotherapeutic agent having broad-spectrum efficacy against several tumors. However, nephro, hepato, neuro cardio, and hematological toxicities associated with ifosfamide render its use limited. These side effects could range from organ failure to life-threatening situations. The present study aimed to evaluate the attenuating efficiency of Berberis vulgaris root extract (BvRE), a potent nephroprotective, hepatoprotective, and lipid-lowering agent, against ifosfamide-induced toxicities. The study design comprised eight groups of Swiss albino rats to assess different dose regimes of BvRE and ifosfamide. Biochemical analysis of serum (serum albumin, blood urea nitrogen, creatinine, alanine transaminase, aspartate transaminase, alkaline phosphatase, lactate dehydrogenase, total cholesterol, and triglycerides) along with complete blood count was performed. Kidney, liver, brain, and heart tissue homogenates were used to find malondialdehyde, catalase, and glutathione S-transferase levels in addition to the acetylcholinesterase of brain tissue. The results were further validated with the help of the histopathology of the selected organs. HeLa cells were used to assess the effect of BvRE on ifosfamide cytotoxicity in MTT assay. The results revealed that pre- and post-treatment regimens of BvRE, as well as the combination therapy exhibited marked protective effects against ifosfamide-induced nephro, hepato, neuro, and cardiotoxicity. Moreover, ifosfamide depicted a synergistic in vitro cytotoxic effect on HeLa cells in the presence of BvRE. These results corroborate that the combination therapy of ifosfamide with BvRE in cancer treatment can potentiate the anticancer effects of ifosfamide along with the amelioration of its conspicuous side effects.