Background: Acceptance of the COVID-19 vaccine will play a major role in combating the pandemic. Healthcare workers (HCWs) are among the first group to receive vaccination, so it is important to consider their attitudes about COVID-19 vaccination to better address barriers to widespread vaccination acceptance. Methods: We conducted a cross sectional study to assess the attitude of HCWs toward COVID-19 vaccination. Data were collected between 7 October and 9 November 2020. We received 4080 responses out of which 3479 were complete responses and were included in the final analysis. Results: 36% of respondents were willing to take the vaccine as soon as it became available while 56% were not sure or would wait to review more data. Only 8% of HCWs do not plan to get vaccine. Vaccine acceptance increased with increasing age, education, and income level. A smaller percentage of female (31%), Black (19%), Lantinx (30%), and rural (26%) HCWs were willing to take the vaccine as soon as it became available than the overall study population. Direct medical care providers had higher vaccine acceptance (49%). Safety (69%), effectiveness (69%), and speed of development/approval (74%) were noted as the most common concerns regarding COVID-19 vaccination in our survey.

The aim of this study was to determine the mechanisms of curcumin-induced human breast cancer cell apoptosis. From quantitative image analysis data showing an increase in the percentage of cells with a sub-G0/G1 DNA content, we demonstrated curcumin-induced apoptosis in the breast cancer cell line MCF-7, in which expression of wild-type p53 could be induced. Apoptosis was accompanied by an increase in p53 level as well as its DNA-binding activity followed by Bax expression at the protein level. Further experiments using p53-null MDAH041 cell as well as low and high p53-expressing TR9-7 cell, in which p53 expression is under tight control of tetracycline, established that curcumin induced apoptosis in tumor cells via a p53-dependent pathway in which Bax is the downstream effector of p53. This property of curcumin suggests that this molecule could have a possible therapeutic potential in breast cancer patients. ß 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.

Curcumin (diferuloylmethane) is known to induce apoptosis in tumor cells. In asynchronous cultures, with time-lapse video-micrography in combination with quantitative fluorescence microscopy, we have demonstrated that curcumin induces apoptosis at G 2 phase of cell cycle in deregulated cyclin D1-expressed mammary epithelial carcinoma cells, leaving its normal counterpart unaffected. In our search toward delineating the molecular mechanisms behind such differential activities of curcumin, we found that it selectively increases p53 expression at G 2 phase of carcinoma cells and releases cytochrome c from mitochondria, which is an essential requirement for apoptosis. Further experiments using p53-null as well as dominant-negative and wildtype p53-transfected cells have established that curcumin induces apoptosis in carcinoma cells via a p53-dependent pathway. On the other hand, curcumin reversibly inhibits normal mammary epithelial cell cycle progression by down-regulating cyclin D1 expression and blocking its association with Cdk4/Cdk6 as well as by inhibiting phosphorylation and inactivation of retinoblastoma protein. In addition, curcumin significantly up-regulates cell cycle inhibitory protein (p21Waf-1) in normal cells and arrests them in G 0 phase of cell cycle. Therefore, these cells escape from curcumin-induced apoptosis at G 2 phase. Interestingly, these processes remain unaffected by curcumin in carcinoma cells where cyclin D1 expression is high. Similarly, in ectopically overexpressed system, curcumin cannot down-regulate cyclin D1 and thus block cell cycle progression. Hence, these cells progress into G 2 phase and undergo apoptosis. These observations together suggest that curcumin may have a possible therapeutic potential in breast cancer patients.

Vaccine reluctance among healthcare workers (HCW) can have widespread negative ramifications, including modeling behavior for the general population and challenges with maintaining a healthy workforce so we can respond to a resurgence of the pandemic. We previously reported that only one-third of HCW were willing to take the vaccine as soon as it became available prior to its Emergency Use Authorization (EUA). Here, we re-examine the attitude toward COVID-19 vaccines among HCW several months after the vaccines have been made widely available. In this study, only 7.9% (n = 107) of respondents were hesitant to take the first or second dose of the vaccine. Younger age (18–40 years) and lower level of education attainment (GED or less) were associated with higher vaccine hesitancy, whereas self-identified Asian racial identity was associated with greater acceptance of COVID-19 vaccination. Among the vaccine-hesitant group, more respondents noted mistrust of regulatory authorities (45.3%), government (48.6%), and pharmaceutical companies (50%) than mistrust of doctors (25.4%). Nearly two-thirds of respondents were concerned that vaccination may be ineffective against new strains and booster doses may be required; however, vaccine-hesitant respondents’ acceptance of a hypothetical booster dose was only 14.3%. Overall, vaccine hesitancy was observed to have demographic predictors similar to those previously reported; the hesitancy of some US HCW to receive booster doses may reflect a general hesitancy to receive other forms of vaccination.

Cancer patients often exhibit loss of proper cell-mediated immunity and reduced effector T-cell population in the circulation. Thymus is a major site of T-cell maturation, and tumors induce thymic atrophy to evade cellular immune response. Here, we report severe thymic hypocellularity along with decreased thymic integrity in tumor bearer. In an effort to delineate the mechanisms behind such thymic atrophy, we observed that tumor-induced oxidative stress played a critical role, as it perturbed nuclear factor-KB (NF-KB) activity. Tumor-induced oxidative stress increased cytosolic IKBA retention and inhibited NF-KB nuclear translocation in thymic T cells. These NF-KB-perturbed cells became vulnerable to tumor-secreted tumor necrosis factor (TNF)-A (TNF-A)-mediated apoptosis through the activation of TNF receptorassociated protein death domain-associated Fas-associated protein death domain and caspase-8. Interestingly, TNF-Adepleted tumor supernatants, either by antibody neutralization or by TNF-A-small interfering RNA transfection of tumor cells, were unable to kill T cell effectively. When T cells were overexpressed with NF-KB, the cells became resistant to tumor-induced apoptosis. In contrast, when degradationdefective IKBA (IKBA super-repressor) was introduced into T cells, the cells became more vulnerable, indicating that inhibition of NF-KB is the reason behind such tumor/TNF-Amediated apoptosis. Curcumin could prevent tumor-induced thymic atrophy by restoring the activity of NF-KB. Further investigations suggest that neutralization of tumor-induced oxidative stress and restoration of NF-KB activity along with the reeducation of the TNF-A signaling pathway can be the mechanism behind curcumin-mediated thymic protection. Thus, our results suggest that unlike many other anticancer agents, curcumin is not only devoid of immunosuppressive effects but also acts as immunorestorer in tumor-bearing host.

Coronavirus 2019 (COVID-19) has created a global pandemic that is devastating human lives, public healthcare systems, and global economies. Multiple effective and safe COVID-19 vaccines have been developed at an unprecedented speed due to the efforts of the scientific community, and collaboration between the federal government and pharmaceutical companies. However, the continued exclusion of pregnant and lactating women from the COVID anti-viral and vaccine trials has created the paradox of a lack of empirical evidence in a high-risk population. Based on the experience of similar prior vaccines, animal developmental and reproductive toxicology studies, and preliminary findings from human studies, various healthcare professional advisory committees (Advisory Committee on Immunization Practices, American College of Obstetricians and Gynecologists, Society for Maternal-Fetal Medicine, and Academy of Breastfeeding Medicine) have issued guidance supporting COVID-19 vaccination in pregnant and lactating women. In this article, we summarize the available data on the efficacy and safety profile of COVID-19 vaccination in pregnant and lactating women, review the challenges of vaccine hesitancy, and include recommendations for healthcare providers.

BackgroundAcceptance of the COVID-19 vaccine will play a major role in combating the pandemic. Healthcare workers (HCWs) are amongst the first group to receive vaccination, so it is important to consider their attitudes about COVID-19 vaccination to better address barriers to widespread vaccination acceptance.MethodsWe conducted a cross sectional study to assess the attitude of HCWs toward COVID-19 vaccination. Data was collected between October 7th and November 9th, 2020. We received 4080 responses out of which 3479 were complete responses and were included in final analysis.Results36% of respondents were willing to take the vaccine as soon as it became available while 56% were not sure or would wait to review more data. Vaccine acceptance increased with increasing age, education, and income level. Lower acceptance was noted in females (31%), Black (10%), Latinx (30%) and Conservative/Republican (21%) HCWs, and those working in a rural setting (26%). Direct medical care providers had higher vaccine acceptance (49%). Safety (69%), effectiveness (69%) and speed of development/approval (74%) were noted as the most common concerns regarding COVID-19 vaccination in our survey.ConclusionImmediate acceptance of a COVID-19 vaccine is low, with the majority of HCWs choosing to wait to review more data before deciding on personal vaccination. Overall attitudes toward vaccination were positive but specific concerns regarding COVID-19 vaccine are prevalent. Differences in vaccine acceptance were noted between individual and group characteristics which should be addressed to avoid exacerbating health inequities.

Developing safe and effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at a breakneck speed has been an exceptional human achievement. It remains our best hope of containing the coronavirus disease 2019 (COVID-19) pandemic. However, newer, more aggressive SARS-CoV-2 viral strains, as well as the possibility of fading immunity following vaccination, have prompted health officials to investigate the necessity for additional immunization. This has put further pressure on disregarded human life in lower-income countries that already have minimal access to COVID-19 vaccines. The Centers for Disease Control and Prevention (CDC) have recommended a third COVID-19 vaccine dose in immunocompromised individuals in a recent announcement. Governments and health care officials need to develop usage guidelines for COVID-19 vaccine booster doses while considering the dangers of potential waning immunity and new viral strains and prioritizing vulnerable populations everywhere, including those living in lower-income countries.