Formulation and validation of probioticated foxtail millet laddu as a source of antioxidant for biological system using response surface methodology.

Probiotics play a critical role in supporting a healthy gut microbiome, which significantly impacts overall health and well-being. While there has been an increase in the availability of probiotic foods in recent years, there may still be limited options and accessibility in certain regions. This study focused on formulating a traditional Indian sweet called laddu enriched with millet and Lactobacillus acidophilus. The formulation of laddu ingredients was optimized using Design Expert software to create an optimal product for testing. The probiotic Lactobacillus acidophilus culture was incorporated into the laddu in three forms: lyophilized, microencapsulated powder, and natural curd. The probiotic foxtail laddu was selected based on specific criteria such as color, odor, and texture. The nutritional analysis revealed that the laddu contained approximately 64.46 g of carbohydrates, 15.13 g of protein, and 5.06 g of fat per 100 g of laddu. A microbial count analysis was performed over a two-month storage period to assess the viability of the incorporated Lactobacillus acidophilus. The results showed that the lyophilized and microencapsulated culture demonstrated good viability, with counts of 6.10 ± 0.09 log CFU/g and 7.43 ± 0.02 log CFU/g, respectively, when stored at 4 °C. In comparison, storage at room temperature resulted in counts of 5.41 ± 0.08 log CFU/g and 6.97 ± 0.02 log CFU/g at the end of the storage period. Based on the findings, the probiotic millet laddu developed in this study has the potential to be a value-added food product that can enhance the overall health of consumers. Incorporating probiotics into traditional food items like laddu offers a convenient and enjoyable way to promote gut health and improve the product's nutritional value.

Gout and coronavirus disease-19 (COVID-19): the risk of diagnosis and death in the UK Biobank

BackgroundData on outcomes for people with gout and COVID-19 are extremely few. Our primary objective was to assess whether gout is a risk factor for diagnosis of COVID-19 and death related to COVID-19. The secondary objectives were to test for sex- and drug-specific differences in risk. MethodsWe used data from the UK Biobank that included 15,560 people with gout. Multivariable-adjusted logistic regression was employed in the following analyses using a case-control study design: Analysis A, to test for association between gout and COVID-19 diagnosis (n=459,837); Analysis B, to test for association between gout and death related to COVID-19 in a case-control cohort of people who died or survived with COVID-19 (n=16,336); Analysis C, to test for association between gout and death related to COVID-19 in the entire UK Biobank cohort (n=459,837); Analysis D, to stratify by prescription of urate-lowering therapy (ULT) and colchicine on the risk of death related to COVID-19 in a subset of the UK Biobank cohort with medication data (n=341,398). FindingsGout was associated with diagnosis of COVID-19 in analysis A (OR=1.2 [1.1 ; 1.3]) but not with risk of death in the COVID-19-diagnosed group in analysis B. In analysis C gout associated with risk of death related to COVID-19 in the unadjusted model (OR=3.9 [3.3 ; 4.7]), in Model 1 adjusted for demographic factors (OR=1.8 [1.5 ; 2.1]) and in the fully adjusted Model 2 (OR=1.3 [1.1 ; 1.6]). In Analysis C risk was higher in women than men in Model 1 adjusted for demographic factors (OR=3.5 [2.4 ; 5.0] and OR=1.5 [1.2 ; 1.8], respectively) with the difference maintained after additional adjustment for eight metabolic co-morbidities (ORMen=1.2 [0.9 ; 1.5], ORWomen=1.9 [1.3 ; 2.9]). There were no statistically significant differences in risk of death related to COVID-19 according to prescription of ULT or colchicine. InterpretationGout is a risk factor for death related to COVID-19 using the UK Biobank cohort with an increased risk in women with gout that was also driven by risk factors outside metabolic co-morbidities of gout. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThere are no studies investigating the risk of COVID-19 diagnosis and risk of death with COVID-19 in people with gout. Added value of this studyThe findings provide evidence that gout is a risk factor for diagnosis of COVID-19 and that gout is a risk factor for death with COVID-19, independent of included co-morbidities. Women with gout are at a higher risk of death with COVID-19 than men with gout. Implications of the available evidenceThe new evidence demonstrate that gout is a risk factor for death from COVID-19, particularly in women. This information will inform clinical decision-making in people with gout diagnosed with COVID-19. Future research should focus on replicating these findings, including a focus on understanding key factor(s) explaining the increased risk of death with COVID-19 in women with gout.

Single Prime hAd5 Spike (S) + Nucleocapsid (N) Dual Antigen Vaccination of Healthy Volunteers Induces a Ten-Fold Increase in Mean S- and N- T-Cell Responses Equivalent to T-Cell Responses from Patients Previously Infected with SARS-CoV-2

In response to the need for a safe, efficacious vaccine that elicits vigorous T cell as well as humoral protection against SARS-CoV-2 infection, we have developed a dual-antigen COVID-19 vaccine comprising both the viral spike (S) protein modified to increase cell-surface expression (S-Fusion) and nucleocapsid (N) protein with an Enhanced T-cell Stimulation Domain (N-ETSD) to enhance MHC class I and II presentation and T-cell responses. The antigens are delivered using a human adenovirus serotype 5 (hAd5) platform with E1, E2b, and E3 regions deleted that has been shown previously in cancer vaccine studies to be safe and effective in the presence of pre-existing hAd5 immunity. The findings reported here are focused on human T-cell responses due to the likelihood that such responses will sustain efficacy against emerging variants, a hypothesis supported by our in silico prediction of T-cell epitope HLA binding for both the first-wave SARS-CoV-2 A strain and the B.1.351 strain K417N, E484K, and N501Y spike and T201I N variants. We demonstrate the hAd5 S-Fusion + N-ETSD vaccine antigens expressed by previously SARS-CoV-2-infected patient dendritic cells elicit Th1 dominant activation of autologous patient T cells, indicating the vaccine antigens have the potential to elicit immune responses in previously infected patients. For participants in our open-label Phase 1b study of the vaccine (NCT04591717; https://clinicaltrials.gov/ct2/show/NCT04591717), the magnitude of Th-1 dominant S- and N-specific T-cell responses after a single prime subcutaneous injection were comparable to T-cell responses from previously infected patients. Furthermore, vaccinated participant T-cell responses to S were similar for A strain S and a series of spike variant peptides, including S variants in the B.1.1.7 and B.1.351 strains. The findings that this dual-antigen vaccine elicits SARS-CoV-2-relevant T-cell responses and that such cell-mediated protection is likely to be sustained against emerging variants supports the testing of this vaccine as a universal booster that would enhance and broaden existing immune protection conferred by currently approved S-based vaccines.

Gout, rheumatoid arthritis and the risk of death from COVID-19: an analysis of the UK Biobank

ObjectivesTo assess whether gout and / or rheumatoid arthritis (RA) are risk factors for coronavirus disease 19 (COVID-19) diagnosis. To assess whether gout and / or RA are risk factors for death with COVID-19. MethodsWe used data from the UK Biobank. Multivariable-adjusted logistic regression was employed in the following analyses: Analysis A, to test for association between gout or RA and COVID-19 diagnosis (n=473,139); Analysis B, to test for association between gout or RA and death with COVID-19 in a case-control cohort of people who died or survived with COVID-19 (n=2,059); Analysis C, to test for association with gout or RA and death with COVID-19 in the entire UK Biobank cohort (n=473,139) ResultsRA, but not gout, associated with COVID-19 diagnosis in analysis A. Neither RA nor gout associated with risk of death in the COVID-19-diagnosed group in analysis B. However RA associated with risk of death related to COVID-19 using the UK Biobank cohort in analysis C independent of comorbidities and other measured risk factors (OR=1.9 [95% CI 1.2 ; 3.0]). Gout was not associated with death related to COVID-19 in the same UK Biobank analysis (OR=1.2 [95% CI 0.8 ; 1.7]). ConclusionRheumatoid arthritis is a risk factor for death with COVID-19 using the UK Biobank cohort. These findings require replication in larger data sets that also allow inclusion of a wider range of factors. Key messagesInformation on the risk of death from COVID-19 for people with gout and rheumatoid arthritis is scarce. In an analysis of the UK Biobank there is an increased risk of death related to COVID-19 for people with rheumatoid arthritis independent of included co-morbidities, but not gout. The findings need to be replicated in other datasets where the influence of therapies for rheumatoid arthritis can be tested.

Prevalence and Longevity of SARS-CoV-2 Antibodies in Healthcare Workers: A Single Center Study

Understanding SARS-CoV-2 antibody prevalence as a marker of prior infection in a spectrum of healthcare workers (HCWs) may guide risk stratification and enactment of better health policies and procedures. The present study reported on cross-sectional study to determine the prevalence and longevity of SARS-CoV-2 antibodies in HCWs at a regional hospital system in Orange County, California, between May and August, 2020. Data from HCWs (n=3,458) were included in the analysis. Data from first responders (n=226) were also analyzed for comparison. A blood sample was collected at study enrollment and 8-week follow-up. Information on job duties, location, COVID-19 symptoms, polymerase chain reaction test history, travel since January 2020, and household contacts with COVID-19 was collected. Comparisons to estimated community prevalence were also evaluated. Observed antibody prevalence was 0.93% and 2.58% at initial and 8-week follow-up, respectively, for HCWs, and 5.31% and 4.35% for first responders. For HCWs, significant differences (p < .05) between negative vs. positive at initial assessment were found for age, race, fever, and loss of smell, and at 8-week follow-up for age, race, and all symptoms. Antibody positivity persisted at least 8 weeks in this cohort. Among 75 HCWs with self-reported prior PCR-confirmed COVID-19, 35 (46.7%) were antibody negative. Significant differences between negative vs. positive were observed in age and frequency of symptoms. This study found considerably lower SARS-CoV-2 antibody prevalence among HCWs compared with prior published studies. This may be explained by better safety measures in the workplace, heightened awareness inside and outside of the workplace, possibly lower susceptibility due to innate immunity and other biological heterogeneity, and low COVID-19 prevalence in the community itself. HCWs with initial positive results had persistent positive serologies at 8 weeks. Further research is warranted to investigate factors influencing such lower prevalence in our HCWs.

SARS-CoV-2 antibody prevalence in health care workers: Preliminary report of a single center study

SARS-CoV-2 has driven a pandemic crisis. Serological surveys have been conducted to establish prevalence for covid-19 antibody in various cohorts and communities. However, the prevalence among healthcare workers is still being analyzed. The present study reports on initial sero-surveillance conducted on healthcare workers at a regional hospital system in Orange County, California, during May and June, 2020. Study participants were recruited from the entire hospital employee workforce and the independent medical staff. Data were collected for job title, location, covid-19 symptoms, a PCR test history, travel record since January 2020, and existence of household contacts with covid-19. A blood sample was collected from each subject for serum analysis for IgG antibodies to SARS- CoV-2. Of 3,013 tested individuals, a total 2,932 were included in the analysis due to some missing data. Observed prevalence of 1.06% (31 antibody positive cases), adjusted prevalence of 1.13% for test sensitivity and specificity were identified. Significant group differences between positive vs. negative were observed for age (z = 2.65, p = .008), race (p = .037), presence of fever (p < .001) and loss of smell (p < .001). Possible explanation for this low prevalence includes a relatively low local geographic community prevalence ([~]4.4%) at the time of testing, the hospitals timely procurement of personal protective equipment, rigorous employee education, patient triage and treatment protocol development and implementation. In addition, possible greater presence of cross- reactive adaptive T cell mediated immunity in healthcare workers vs. the general population may have contributed. Determining antibody prevalence in front-line workers, and duration of antibody presence may help stratify the workforce for risk, establish better health place policies and procedures, and potentially better mitigate transmission.

First 12 patients with coronavirus disease 2019 (COVID-19) in the United States

IntroductionMore than 93,000 cases of coronavirus disease (COVID-19) have been reported worldwide. We describe the epidemiology, clinical course, and virologic characteristics of the first 12 U.S. patients with COVID-19. MethodsWe collected demographic, exposure, and clinical information from 12 patients confirmed by CDC during January 20-February 5, 2020 to have COVID-19. Respiratory, stool, serum, and urine specimens were submitted for SARS-CoV-2 rRT-PCR testing, virus culture, and whole genome sequencing. ResultsAmong the 12 patients, median age was 53 years (range: 21-68); 8 were male, 10 had traveled to China, and two were contacts of patients in this series. Commonly reported signs and symptoms at illness onset were fever (n=7) and cough (n=8). Seven patients were hospitalized with radiographic evidence of pneumonia and demonstrated clinical or laboratory signs of worsening during the second week of illness. Three were treated with the investigational antiviral remdesivir. All patients had SARS-CoV-2 RNA detected in respiratory specimens, typically for 2-3 weeks after illness onset, with lowest rRT-PCR Ct values often detected in the first week. SARS-CoV-2 RNA was detected after reported symptom resolution in seven patients. SARS-CoV-2 was cultured from respiratory specimens, and SARS-CoV-2 RNA was detected in stool from 7/10 patients. ConclusionsIn 12 patients with mild to moderately severe illness, SARS-CoV-2 RNA and viable virus were detected early, and prolonged RNA detection suggests the window for diagnosis is long. Hospitalized patients showed signs of worsening in the second week after illness onset.