Dietary composition of adult eosinophilic esophagitis patients is related to disease severity.

BACKGROUND: In addition to the elimination diet, dietary composition may influence disease severity in patients with eosinophilic esophagitis (EoE) through modulation of the immune response. AIM: To explore the immunomodulatory role of nutrition before and during elimination diet in adult EoE patients. METHODS: Nutritional intake was assessed in 39 Dutch adult EoE patients participating in the Supplemental Elemental Trial (Dutch trial registry NL6014, NTR6778) using 3-day food diaries. In this randomized controlled trial, diagnosed patients received either a four-food elimination diet alone (FFED) or FFED with addition of an amino acid-based formula for 6 weeks. Multiple linear regression analyses were performed to assess associations between the intake of nutrients and food groups per 1000 kCal and peak eosinophil count/high power field (PEC), both at baseline and after 6 weeks. RESULTS: At baseline, we found a statistically significant negative (thus favorable) relationship between the intake of protein, total fat, phosphorus, zinc, vitamin B12, folate, and milk products and PEC (p < .05), while calcium (p = .058) and full-fat cheese/curd (p = .056) were borderline (favorably) significant. In contrast, total carbohydrates, prepacked fruit juice, and white bread were significantly positively (unfavorable) related to PEC (p < .05), while ultra-processed meals (p = .059) were borderline (unfavorably) significant. After dietary intervention, coffee/tea were significantly negatively (favorably) related to PEC, hummus/legumes were significantly positively (unfavorably) related with PEC, while peanuts were borderline significantly positively related (p = .058). CONCLUSION: Dietary composition may be related to inflammation in adult EoE patients. High-quality and anti-inflammatory diets may be a promising adjuvant therapy in the dietary management of EoE.

Paclitaxel as HIPEC-Drug after Surgical Cytoreduction for Ovarian Peritoneal Metastases: A Randomized Phase III Clinical Trial (HIPECOVA).

Multidisciplinary strategies have transformed the management of advanced ovarian cancer. We aimed to evaluate the effectiveness of paclitaxel in hyperthermic intraperitoneal chemotherapy (HIPEC) following surgical cytoreduction for ovarian peritoneal metastases in a randomized phase III trial conducted between August 2012 and December 2019. Seventy-six patients were randomized to either the HIPEC or no HIPEC group. Although median values for the primary endpoints (recurrence-free survival (RFS) and overall survival (OS)) revealed superior outcomes for the HIPEC (RFS: 23 months, OS: 48 months) over the control group (RFS: 19 months, OS: 46 months), these differences were not statistically significant (p = 0.22 and p = 0.579). Notably, the HIPEC group demonstrated significantly higher 5-year OS and 3-year RFS rates (47.2% and 47.5%) compared to patients without HIPEC (34.5% and 21.3%). Stratification according to Peritoneal Surface Disease Severity Score (PSDSS) showed improved OS and RFS for patients with lower PSDSS (I-II) in the HIPEC-treated group (p = 0.033 and p = 0.042, respectively). The Clavien-Dindo classification of adverse event grades revealed no significant differences between HIPEC and controls (p = 0.482). While overall results were not statistically significant, our long-term follow-up emphasized the potential benefit of HIPEC-associated cytoreduction with paclitaxel, particularly in selected ovarian cancer patients with lower PSDSS indices.

Head and Neck Cancer: A Study on the Complex Relationship between QoL and Swallowing Function.

Head and neck squamous cell carcinoma (HNSCC) is linked to significant morbidity, adversely affecting survival and functional capacity. Post-treatment challenges such as pain, dysphonia, and dysphagia are common, prompting increased attention in survivorship research. Quality of Life (QoL) questionnaires, especially the MD Anderson Dysphagia Inventory (MDADI), are prevalent outcome measures in clinical studies but often lack parallel objective swallowing function evaluations, leading to potential outcome discrepancies. This study aimed to illuminate the relationship between subjective QoL (EQ-5D-5L and MDADI) measures and objective swallowing function (evaluated via Fiberoptic Endoscopic Evaluation of Swallowing, FEES) in patients with HNSCC. The analysis revealed a notable discordance between objective measures of swallowing function, such as the Penetration-Aspiration Scale (PAS) and residue ratings in the vallecula or piriform sinus, and patients' subjective QoL assessments (p = 0.21). Despite the lack of correlation, swallowing-related QoL, as measured by the MDADI, was more indicative of disease severity than generic QoL assessments. Generic QoL scores did not demonstrate substantial variation between patients. In contrast, MDADI scores significantly declined with advancing tumor stage, multimodal therapy, and reliance on feeding tubes. However, the clinical significance of this finding was tempered by the less than 10-point difference in MDADI scores. The findings of this study underline the limitations of QoL measures as standalone assessments in patients with HNSCC, given their reliance on patient-perceived impairment. While subjective QoL is a crucial aspect of evaluating therapeutic success and patient-centric outcomes, it may fail to capture critical clinical details such as silent aspirations. Consequently, QoL assessments should be augmented by objective evaluations of swallowing function in clinical research and practice to ensure a holistic understanding of patient well-being and treatment impact.

Ellagic acid effects on disease severity, levels of cytokines and T-bet, RORγt, and GATA3 genes expression in multiple sclerosis patients: a multicentral-triple blind randomized clinical trial.

Background: Multiple sclerosis (MS) is a chronic autoimmune disease. Ellagic acid is a natural polyphenol and affects the fate of neurons through its anti-inflammatory and antioxidant properties. The present study aimed to investigate ellagic acid effects on disease severity, the expression of involved genes in the pathogenesis of MS, and the levels of related cytokines. Methods: The present study was a triple-blind clinical trial. Eligible patients were randomly assigned to two groups: Ellagic acid (25 subjects) for 12 weeks, receiving 180 mg of Ellagic acid (Axenic, Australia) and the control group (25 subjects) receiving a placebo, before the main meals. Before and after the study, the data including general information, foods intake, physical activity, anthropometric data, expanded disability status scale (EDSS), general health questionnaire (GHQ) and pain rating index (PRI), fatigue severity scale (FSS) were assessed, as well as serum levels of interferon-gamma (IFNγ), interleukin-17 (IL-17), interleukin-4 (IL-4) and transforming growth factor-beta (TGF-ß), nitric-oxide (NO) using enzyme-linked immunoassay (ELISA) method and expression of T-box transcription factor (Tbet), GATA Binding Protein 3 (GATA3), retinoic acid-related orphan receptor-γt (RORγt) and Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) genes were determined using Real-Time Quantitative Reverse Transcription PCR (RT-qPCR) method. Findings: Ellagic acid supplementation led to a reduction in IFNγ, IL-17, NO and increased IL-4 in the ellagic acid group, however in the placebo group no such changes were observed (-24.52 ± 3.79 vs. -0.05 ± 0.02, p < 0.01; -5.37 ± 0.92 vs. 2.03 ± 1.03, p < 0.01; -18.03 ± 1.02 vs. -0.06 ± 0.05, p < 0.01, 14.69 ± 0.47 vs. -0.09 ± 0.14, p < 0.01, respectively). Ellagic acid supplementation had no effect on TGF-ß in any of the study groups (p > 0.05). Also, the Tbet and RORγt genes expression decreased, and the GATA3 gene expression in the group receiving ellagic acid compared to control group significantly increased (0.52 ± 0.29 vs. 1.51 ± 0.18, p < 0.01, 0.49 ± 0.18 vs. 1.38 ± 0.14, p < 0.01, 1.71 ± 0.39 vs. 0.27 ± 0.10, p < 0.01). Also, ellagic acid supplementation led to significant decrease in EDSS, FSS and GHQ scores (p < 0.05), and no significant changes observed in PRI score (p > 0.05). Conclusion: Ellagic acid supplementation can improve the health status of MS patients by reduction of the inflammatory cytokines and Tbet and RORγt gene expression, and increment of anti-inflammatory cytokines and GATA3 gene expression.Clinical trial registration: (https://en.irct.ir/trial/53020), IRCT20120415009472N22.

Systemic treatments for atopic dermatitis (eczema): Systematic review and network meta-analysis of randomized trials.

BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin condition with multiple systemic treatments and uncertainty regarding their comparative impact on AD outcomes. OBJECTIVE: We sought to systematically synthesize the benefits and harms of AD systemic treatments. METHODS: For the 2023 American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, Web of Science, and GREAT databases from inception to November 29, 2022, for randomized trials addressing systemic treatments and phototherapy for AD. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-related quality of life, flares, and harms. The Grading of Recommendations Assessment, Development and Evaluation approach informed certainty of evidence ratings. This review is registered in the Open Science Framework (https://osf.io/e5sna). RESULTS: The 149 included trials (28,686 patients with moderate-to-severe AD) evaluated 75 interventions. With high-certainty evidence, high-dose upadacitinib was among the most effective for 5 of 6 patient-important outcomes; high-dose abrocitinib and low-dose upadacitinib were among the most effective for 2 outcomes. These Janus kinase inhibitors were among the most harmful in increasing adverse events. With high-certainty evidence, dupilumab, lebrikizumab, and tralokinumab were of intermediate effectiveness and among the safest, modestly increasing conjunctivitis. Low-dose baricitinib was among the least effective. Efficacy and safety of azathioprine, oral corticosteroids, cyclosporine, methotrexate, mycophenolate, phototherapy, and many novel agents are less certain. CONCLUSIONS: Among individuals with moderate-to-severe AD, high-certainty evidence demonstrates that high-dose upadacitinib is among the most effective in addressing multiple patient-important outcomes, but also is among the most harmful. High-dose abrocitinib and low-dose upadacitinib are effective, but also among the most harmful. Dupilumab, lebrikizumab, and tralokinumab are of intermediate effectiveness and have favorable safety.

Role of Metals on SARS-CoV-2 Infection: a Review of Recent Epidemiological Studies.

PURPOSE OF REVIEW: Metals and metalloids are known for their nutritional as well as toxic effects in humans. In the context of the SARS-CoV-2 pandemic, understanding the role of metals on COVID-19 infection is becoming important due to their role in infectious diseases. During the past 2 years, a significant number of studies have examined the impact of metals and metalloids on COVID-19 morbidity and mortality. We conducted a systematic review of peer-reviewed manuscripts on the association of metals and metalloids with SARS-CoV-2 infection and COVID-19 severity published since the onset of the pandemic. RECENT FINDINGS: We searched for epidemiological studies available through the PubMed database published from January 2020 to December 2022. Of 92 studies identified, 20 met our inclusion criteria. These articles investigated the association of zinc (Zn), iron (Fe), selenium (Se), manganese (Mn), cadmium (Cd), arsenic (As), copper (Cu), magnesium (Mg), chromium (Cr), and/or lead (Pb) levels on SARS-CoV-2 infection and/or COVID-19 severity. Of the ten metals and metalloids of interest that reported either positive, negative, or no associations, Zn yielded the highest number of articles (n = 13), followed by epidemiological studies on Se (n = 7) and Fe (n = 5). Elevated serum Zn and Se were associated with reduced COVID-19 severity and mortality. Similarly, higher levels of serum Fe were associated with lower levels of cellular damage and symptoms of SARS-CoV-2 infection and with faster recovery from COVID-19. On the other hand, higher serum and urinary Cu and serum Mg levels were associated with higher COVID-19 severity and mortality. Along with the positive or negative effects, some studies reported no impact of metals on SARS-CoV-2 infection. This systematic review suggests that metals, particularly Zn, Fe, and Se, may help reduce the severity of COVID-19, while Cu and Mg may aggravate it. Our review suggests that future pandemic mitigation strategies may evaluate the role of Zn, Se, and Fe as potential therapeutic interventions.

The effect of 1-hydroxy-vitamin D treatment in hospitalized patients with COVID-19: A retrospective study.

BACKGROUND & AIMS: The efficacy of vitamin D supplementation in coronavirus disease 2019 (COVID-19) remains unclear. This study aimed to evaluate the effect of 1-hydroxy-vitamin D on the prevention of severe disease and mortality in patients hospitalized for COVID-19. METHODS: This retrospective study included 312 patients with COVID-19 who were admitted to our hospital between April 2021 and October 2021 (primarily the Delta variant) and between July 2022 and September 2022 (primarily Omicron variant). Serum 25-hydroxyvitamin D (25(OH)D) levels were measured at the time of admission and 1-hydroxy-vitamin D was prescribed by the treating physicians. The patients were divided into two groups: those administered 1-hydroxy-vitamin D (Vit D group) and those who were not (control group). The composite primary endpoint was the need for additional respiratory support, including high-flow oxygen therapy or invasive mechanical ventilation, and in-hospital mortality rate. RESULTS: Of 312 patients, 122 (39%) received 1-hydroxy-vitamin D treatment. Although the median age was not significantly higher in the Vit D group than in the control group (66 vs. 58 years old, P = 0.06) and there was no significant difference in the proportion of vitamin D deficiency (defined as serum 25(OH)D level less than 20 ng/mL, 77% vs. 65%, P = 0.07), patients in the control group had a more severe baseline profile compared to the Vit D group according to the Japanese disease severity definition for COVID-19 (P = 0.01). The proportion of those requiring more respiratory support and in-hospital mortality was significantly lower in the Vit D group than in the control group (6% vs. 14%, P = 0.01 log-rank test). After propensity score matching, a statistically significant difference in the primary endpoint was observed (P = 0.03 log-rank test). CONCLUSIONS: 1-hydroxy-vitamin treatment may improve outcomes in hospitalized patients with COVID-19, reducing composite outcomes including the need for additional respiratory support and in-hospital mortality.

Virulence of Novel Ralstonia pseudosolanacearum (Phylotype I) Strains from Rose, Blueberry, and Mandevilla on Seed Potato.

Potato (Solanum tuberosum L.) ranks fourth among the most important staple food in the world. Ralstonia solanacearum (phylotype [phy] IIB, sequevar [seq] 1 and 2), also known as R3B2, the causal agent of brown rot disease on potato, is extremely damaging, causing great economical losses to potato in temperate regions. It is thought that members of Ralstonia pseudosolanacearum (phy I) are not pathogenic at low temperatures and are usually found in warmer climates. R. pseudosolanacearum strain PD 7123 (seq 33) isolated from roses in the Netherlands, strain P824 (seq 13) isolated from blueberry, and strain P781 (seq 14) from mandevilla in Florida are phylogenetically closely related and could share the same host. The virulence and ability of these novel strains to multiply latently in potato in temperate regions is unknown. The objective of this work was to assess the virulence and presence of latent infections of the mentioned R. pseudosolanacearum strains on three commercial seed potato cultivars under warmer (28°C) and temperate (20°C) temperatures. At 28°C, all three R. pseudosolanacearum strains caused severe symptoms on all potato cultivars. Overall disease severity on potato was lower at 20°C than 28°C, but major differences in virulence of the three strains were observed at 42 days postinoculation (dpi) among potato cultivars. All asymptomatic potato plants and most of their daughter tubers had latent infections at 20°C. Altogether, these results show that the phy I strains from rose, blueberry, and mandevilla may pose a threat to potato production in temperate climates and the worldwide movement of seed potatoes.[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

The association of clinically relevant variables with chest radiograph lung disease burden quantified in real-time by radiologists upon initial presentation in individuals hospitalized with COVID-19.

OBJECTIVES: We aimed to correlate lung disease burden on presentation chest radiographs (CXR), quantified at the time of study interpretation, with clinical presentation in patients hospitalized with coronavirus disease 2019 (COVID-19). MATERIAL AND METHODS: This retrospective cross-sectional study included 5833 consecutive adult patients, aged 18 and older, hospitalized with a diagnosis of COVID-19 with a CXR quantified in real-time while hospitalized in 1 of 12 acute care hospitals across a multihospital integrated healthcare network between March 24, 2020, and May 22, 2020. Lung disease burden was quantified in real-time by 118 radiologists on 5833 CXR at the time of exam interpretation with each lung annotated by the degree of lung opacity as clear (0%), mild (1-33%), moderate (34-66%), or severe (67-100%). CXR findings were classified as (1) clear versus disease, (2) unilateral versus bilateral, (3) symmetric versus asymmetric, or (4) not severe versus severe. Lung disease burden was characterized on initial presentation by patient demographics, co-morbidities, vital signs, and lab results with chi-square used for univariate analysis and logistic regression for multivariable analysis. RESULTS: Patients with severe lung disease were more likely to have oxygen impairment, an elevated respiratory rate, low albumin, high lactate dehydrogenase, and high ferritin compared to non-severe lung disease. A lack of opacities in COVID-19 was associated with a low estimated glomerular filtration rate, hypernatremia, and hypoglycemia. CONCLUSIONS: COVID-19 lung disease burden quantified in real-time on presentation CXR was characterized by demographics, comorbidities, emergency severity index, Charlson Comorbidity Index, vital signs, and lab results on 5833 patients. This novel approach to real-time quantified chest radiograph lung disease burden by radiologists needs further research to understand how this information can be incorporated to improve clinical care for pulmonary-related diseases.. An absence of opacities in COVID-19 may be associated with poor oral intake and a prerenal state as evidenced by the association of clear CXRs with a low eGFR, hypernatremia, and hypoglycemia.

The Role of Diet and Specific Nutrients during the COVID-19 Pandemic: What Have We Learned over the Last Three Years?

Nutrients and diets have an important impact on our immune system and infection risk and a huge number of papers have been published dealing with various aspects of nutrition in relation to SARS-CoV-2 infection risk or COVID-19 severity. This narrative review aims to give an update on this association and tries to summarize some of the most important findings after three years of pandemic. The analysis of major studies and systematic reviews leads to the conclusion that a healthy plant-based diet reduces the risks for SARS-CoV-2 infection and especially COVID-19 severity. Regarding micronutrients, vitamin D is to the fore, but also zinc, vitamin C and, to some extent, selenium may play a role in COVID-19. Furthermore, omega-3-fatty acids with their anti-inflammatory effects also deserve attention. Therefore, a major aim of societal nutritional efforts in future should be to foster a high quality plant-based diet, which not only exerts beneficial effects on the immune system but also reduces the risk for non-communicable diseases such as type 2 diabetes or obesity which are also primary risk factors for worse COVID-19 outcomes. Another aim should be to focus on a good supply of critical immune-effective nutrients, such as vitamin D and zinc.

The Role of Vitamin D in Basal Ganglia Diseases.

OBJECTIVE: Vitamin D (VitD) has been shown to influence several cellular processes in the brain. The extent to which VitD plays a role in the pathomechanism of neuronal loss and dysfunction in basal ganglia diseases (BGDs) is still debated. There is yet to be a comprehensive study that provides an overview of all of the most relevant BGDs. METHODS: PubMed, and Google Scholar were systematically searched for observational studies that investigated the association between serum VitD levels and BGDs up to March 2022. RESULTS: We extracted 60 studies, but with a great variety of design and quality. VitD deficiency appears to be common in most BGDs, but only in Parkinson's disease (PD) has a causal association been fully examined. There is some evidence that low VitD serum levels influence symptom severity, most notably in restless legs syndrome (RLS), PD, and tic disorders. The effects of vitamin D supplementation were studied in three BGDs, with results mostly favorable for RLS, ambiguous for tics, and mostly unfavorable for PD. CONCLUSIONS: There are still various elements of BGDs with insufficient, ambiguous, or altogether absent evidence, and further high-quality research is required. However, there appears to be sufficient scientific justification already to recommend that practitioners treating BGDs check serum VitD levels and supplement as appropriate.

Risk Factors Affecting the Outcomes of CT-Guided Radiofrequency Thermocoagulation of Thoracic Sympathetic Nerve in the Treatment of Primary Palm Hyperhidrosis.

BACKGROUND: Primary palm hyperhidrosis (PPH) is a chronic disease characterized by uncontrolled palm-sweating exceeding physiological needs. It negatively impacts the quality of life of the patients and can lead to different degrees of psychological problems. Currently, there are a variety of treatment options for PPH, of which thoracotomy is a first-line treatment that has shown good efficacy. However, since it is an invasive procedure requiring general anesthesia and is often associated with high costs and serious complications, better alternatives should be explored. Computed tomography (CT)-guided percutaneous puncture of radiofrequency thermocoagulation (RF-TC) of the thoracic sympathetic nerve is a promising alternative treatment. It is a minimally invasive procedure that can be performed under local anesthesia and is associated with rapid recovery. However, the factors affecting the duration of the surgery-related benefits and outcomes of CT-guided percutaneous RF-TC of the thoracic sympathetic nerve are unclear. OBJECTIVES: To investigate the factors influencing the outcomes of CT-guided percutaneous RF-TC of the thoracic sympathetic nerve in patients with PPH. STUDY DESIGN: A retrospective study. SETTING: This study was conducted at the Pain Department of Jiaxing University Affiliated Hospital (Jiaxing, China). METHODS: After approval by the Ethics Committee of the Affiliated Hospital of Jiaxing College, the data of 232 corresponding patients were assessed. The Kaplan-Meier method was used for survival analysis. Univariate and multivariate analyses were performed to identify factors associated with PPH and to construct a nomogram for predicting postoperative recurrence. Time-independent receiver operating characteristic (ROC) curve analyses were performed to assess the nomogram's predictive capacity. RESULTS: In the one-year survival analysis model, gender (HR = 1.573, 95%CI: 0.844 to 2.934), age (HR = 0.965, 95%CI: 0.915 to 1.018), disease course (HR = 0.960, 95%CI: 0.908 to 1.015), palm temperature difference (HR = 0.377, 95%CI: 0.287 to 0.495), perfusion index difference (HR = 0.590, 95%CI: 0.513 to 0.680) and hyperhidrosis disease severity scale (HR = 1.963, 95%CI: 0.769 to 5.011) were identified as statistically significant factors in univariate analysis, while palm temperature difference (HR = 0.589, 95%CI: 0.369 to 0.941) and perfusion index difference (HR = 0.357, 95%CI: 0.588 to 0.968) were the independent factors in the multivariate Cox proportional hazards risk model. In the 2-year survival analysis model, palm temperature difference (HR = 0.353, 95%CI: 0.261 to 0.478), perfusion index difference (HR = 0.589, 95%CI: 0.510 to 0.680) and hyperhidrosis disease severity scale (HR = 1.964, 95%CI: 0.771 to 5.006) were the statistically significant factors while palm temperature difference (HR = 0.507, 95%CI: 0.321 to 0.799) and perfusion index difference (HR = 0.789, 95%CI: 0.625 to 0.995) were the independent factors. LIMITATIONS: This single-center retrospective study was limited by its small sample size, short follow-up time, and the possibility of bias resulting from the non-random patient selection. CONCLUSION: Palm temperature difference and perfusion index difference were independent risk factors associated with prolonging the surgical benefits and reducing postoperative recurrence of CT-guided RF-TC of the sympathetic nerves in patients with PPH.

Understanding Racial Disparities in COVID-19-Related Complications: Protocol for a Mixed Methods Study.

BACKGROUND: In the United States, the COVID-19 pandemic has magnified the disproportionate and long-standing health disparities experienced by Black communities. Although it is acknowledged that social determinants of health (SDOH) rather than biological factors likely contribute to this disparity, few studies using rigorous analytic approaches in large, information-rich community-based data sets are dedicated to understanding the underlying drivers of these racial disparities. OBJECTIVE: The overall aim of our study is to elucidate the mechanisms by which racial disparities in severe COVID-19 outcomes arise, using both quantitative and qualitative methods. METHODS: In this protocol, we outline a convergent parallel mixed methods approach to identifying, quantifying, and contextualizing factors that contribute to the dramatic disparity in COVID-19 severity (ie, hospitalization, mortality) in Black versus white COVID-19 patients within the integrated health care system of Kaiser Permanente Georgia (KPGA). Toward this end, we will generate two quantitative cohorts of KPGA members with a confirmed COVID-19 diagnosis between January 1, 2020, and September 30, 2021: (1) an electronic medical record (EMR) cohort including routinely captured data on diagnoses, medications, and laboratory values, and a subset of patients hospitalized at Emory Healthcare to capture additional in-hospital data; and (2) a survey cohort, where participants will answer a range of questions related to demographics (eg, race, education), usual health behaviors (eg, physical activity, smoking), impact of COVID-19 (eg, job loss, caregiving responsibilities), and medical mistrust. Key outcomes of interest for these two cohorts include hospitalization, mortality, intensive care unit admission, hospital readmission, and long COVID-19. Finally, we will conduct qualitative semistructured interviews to capture perceptions of and experiences of being hospitalized with COVID-19 as well as related interactions with KPGA health care providers. We will analyze and interpret the quantitative and qualitative data separately, and then integrate the qualitative and quantitative findings using a triangulation design approach. RESULTS: This study has been funded by a Woodruff Health Sciences grant from December 2020 to December 2022. As of August 31, 2022, 31,500 KPGA members diagnosed with COVID-19 have been included in the EMR cohort, including 3028 who were hospitalized at Emory Healthcare, and 482 KPGA members completed the survey. In addition, 20 KPGA members (10 Black and 10 white) have been interviewed about their experiences navigating care with COVID-19. Quantitative and qualitative data cleaning and coding have been completed. Data analysis is underway with results anticipated to be published in December 2022. CONCLUSIONS: Results from this mixed methods pilot study in a diverse integrated care setting in the southeastern United States will provide insights into the mechanisms underpinning racial disparities in COVID-19 complications. The quantitative and qualitative data will provide important context to generate hypotheses around the mechanisms for racial disparities in COVID-19, and may help to inform the development of multilevel strategies to reduce the burden of racial disparities in COVID-19 and its ongoing sequelae. Incorporating contextual information, elucidated from qualitative interviews, will increase the efficacy, adoption, and sustainability of such strategies. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/38914.

Foliar Silicon Spray before Summer Cutting Propagation Enhances Resistance to Powdery Mildew of Daughter Plants.

Silicon (Si) has beneficial effects on not only plant growth but also against biotic and abiotic stresses. However, a few studies focus on how Si application helps strawberry (Fragaria × ananassa Duch.) resist powdery mildew. The aim of this work was to find out the optimal Si application method before cutting propagation to enhance the resistance to powdery mildew in strawberry "daughter" plants. Naturally infected "mother" plants of 'Sulhyang', 'Maehyang', and 'Kuemsil' strawberries were supplied with Si. Potassium silicate (K2SiO3) at a final concentration of 75 mg·L-1 Si was either added to the medium for drenching or sprayed to the leaves of the "mother" or "daughter" plant, or soluble Si fertilizer was used to dress the "mother" plant. The Si application significantly increased the shoot fresh weight of the "daughter" plants. Supplemental Si also increased the contents of phosphorus (P), potassium (K), and magnesium (Mg). In addition, the Si treatment decreased the damage of powdery mildew by increased level of proline content and suppressive reactive oxygen species. After applying Si, the length and density of hyphae on the leaf surface decreased. In addition, the infected area of "daughter" plant leaves covered with powdery mildew decreased. This study also demonstrated that Si increased the expression of resistance-gene and decreased the expression of susceptibility-gene of strawberry. Overall, Si application promoted the growth of the "daughter" plants regardless of the application method. Direct foliar Si spray to the "daughter" plants before cutting propagation is recommended to increase their resistance to powdery mildew.

Title: Understanding a Low Vitamin D State in the Context of COVID-19.

While a low vitamin D state has been associated with an increased risk of infection by SARS-CoV-2 in addition to an increased severity of COVID-19 disease, a causal role is not yet established. Here, we review the evidence relating to i) vitamin D and its role in SARS-CoV-2 infection and COVID-19 disease ii) the vitamin D status in the Irish adult population iii) the use of supplemental vitamin D to treat a deficient status and iv) the application of the Bradford-Hill causation criteria. We conclude that reverse causality probably makes a minimal contribution to the presence of low vitamin D states in the setting of COVID-19. Applying the Bradford-Hill criteria, however, the collective literature supports a causal association between low vitamin D status, SARS-CoV-2 infection, and severe COVID-19 (respiratory failure, requirement for ventilation and mortality). A biologically plausible rationale exists for these findings, given vitamin D's role in immune regulation. The thresholds which define low, deficient, and replete vitamin D states vary according to the disease studied, underscoring the complexities for determining the goals for supplementation. All are currently unknown in the setting of COVID-19. The design of vitamin D randomised controlled trials is notoriously problematic and these trials commonly fail for a number of behavioural and methodological reasons. In Ireland, as in most other countries, low vitamin D status is common in older adults, adults in institutions, and with obesity, dark skin, low UVB exposure, diabetes and low socio-economic status. Physiological vitamin D levels for optimal immune function are considerably higher than those that can be achieved from food and sunlight exposure alone in Ireland. A window exists in which a significant number of adults could benefit from vitamin D supplementation, not least because of recent data demonstrating an association between vitamin D status and COVID-19. During the COVID pandemic, we believe that supplementation with 20-25ug (800-1000 IU)/day or more may be required for adults with apparently normal immune systems to improve immunity against SARS-CoV-2. We expect that higher monitored doses of 37.5-50 ug (1,500-2,000)/day may be needed for vulnerable groups (e.g., those with obesity, darker skin, diabetes mellitus and older adults). Such doses are within the safe daily intakes cited by international advisory agencies.

Essential metals, vitamins and antioxidant enzyme activities in COVID-19 patients and their potential associations with the disease severity.

The role of micronutrient deficiency in the pathogenesis of COVID-19 has been reviewed in the literature; however, the data are limited and conflicting. This study investigated the association between the status of essential metals, vitamins, and antioxidant enzyme activities in COVID-19 patients and disease severity. We recruited 155 patients, who were grouped into four classes based on the Adults guideline for the Management of Coronavirus Disease 2019 at King Faisal Specialist & Research Centre (KFSH&RC): asymptomatic (N = 16), mild (N = 49), moderate (N = 68), and severe (N = 22). We measured serum levels of copper (Cu), zinc (Zn), selenium (Se), vitamin D3, vitamin A, vitamin E, total antioxidant capacity, and superoxide dismutase (SOD). Among the patients, 30%, 25%, 37%, and 68% were deficient in Se (< 70.08 µg/L), Zn (< 0.693 µg/mL), vitamin A (< 0.343 µg/mL), and vitamin D3 (< 20.05 µg/L), respectively, and SOD activity was low. Among the patients, 28% had elevated Cu levels (> 1.401 µg/mL, KFSH&RC upper reference limit). Multiple regression analysis revealed an 18% decrease in Se levels in patients with severe symptoms, which increased to 30% after adjusting the model for inflammatory markers. Regardless of inflammation, Se was independently associated with COVID-19 severity. In contrast, a 50% increase in Cu levels was associated with disease severity only after adjusting for C-reactive protein, reflecting its possible inflammatory and pro-oxidant role in COVID-19 pathogenesis. We noted an imbalance in the ratio between Cu and Zn, with ~ 83% of patients having a Cu/Zn ratio > 1, which is an indicator of inflammation. Cu-to-Zn ratio increased to 45% in patients with mild symptoms and 34%-36% in patients with moderate symptoms compared to asymptomatic patients. These relationships were only obtained when one of the laboratory parameters (lymphocyte or monocyte) or inflammatory markers (neutrophil-to-lymphocyte ratio) was included in the regression model. These findings suggest that Cu/Zn might further exacerbate inflammation in COVID-19 patients and might be synergistically associated with disease severity. A 23% decrease in vitamin A was seen in patients with severe symptoms, which disappeared after adjusting for inflammatory markers. This finding may highlight the potential role of inflammation in mediating the relationship between COVID-19 severity and vitamin A levels. Despite our patients' low status of Zn, vitamin D3, and antioxidant enzyme (SOD), there is no evidence of their role in COVID-19 progression. Our findings reinforce that deficiency or excess of certain micronutrients plays a role in the pathogenesis of COVID-19. More studies are required to support our results.

Introduction to biological rhythms: A brief history of chronobiology and its relevance to parasite immunology.

Almost every living organism on earth is exposed to a fluctuating environment, for example, light:dark cycles, food availability and seasonal photoperiods. Most species have therefore evolved internal timing mechanisms allowing them to anticipate these rhythmic environmental changes, obtaining a survival advantage. Circadian (24 h) rhythms, in particular, regulate multiple aspects of physiology, including sleep/wake activity, feeding rhythms and immune function. Recent studies have identified circadian rhythms in symptoms of parasite infections, rhythms in parasite schizogony and evidence that certain parasites can manipulate host rhythms. Furthermore, efficacy of anti-parasite medications can also be modulated by timing of drug administration. Understanding the interactions between host rhythms, parasite rhythms and disease severity is crucial to fully understand how to combat infections and reduce pathology. The aim of this review is, therefore, to provide an introduction to the field of biological rhythms, give a brief history of chronobiology research and discuss the relevance of biological rhythms to parasite immunology.

Clinical correlates of serum 25-hydroxyvitamin D in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) patients have lower levels of serum 25-hydroxyvitamin D (25(OH)D) than the general population. Previous studies have suggested a negative association between 25(OH)D and clinical features of PD, but the data are inconsistent. MATERIALS AND METHODS: We conducted a cross-sectional, observational study. Serum 25(OH)D, disease (Hoehn-Yahr stage [HY]) and clinical symptom (Unified Parkinson Disease Rating Scale [UPDRS]) severity and global cognitive functions (Mini-Mental State Examination [MMSE]) were studied in 500 consecutive PD patients not using vitamin D supplements. Information on sunlight exposure and dietary intakes (using a 66-item food frequency questionnaire) were also collected. A convenient sample of age and sex-matched community healthy controls (N = 100) was included as a control group. RESULTS: PD patients had lower 25(OH)D serum levels than controls. Deficiency status (<20 ng/mL) was found in 65.6% of patients. 25(OH)D levels were independently correlated to sunlight exposure (P = .002) and vitamin D intake (P = .009). In multivariate models, using a Mendelian randomization approach, lower serum 25(OH)D was associated with more severe disease (HY, P = .035), worse clinical symptoms (UPDRS Part-III total score [P = .006] and dopaminergic [P = .033] and non-dopaminergic subscores [P = .001]) and greater global cognitive function impairment (P = .041). Neither cognitive functions nor clinical features were associated with reduced intake of vitamin D and sunlight exposure. CONCLUSION: : Serum 25(OH)D was negatively correlated with disease and symptoms severity, as well as with global cognitive functions. Our study adds to the evidence that low 25(OH)D may affect the progression of PD negatively. Intervention studies in this area are required.

SARS-CoV-2: Can sunlight exposure reduce the risk of developing severe consequences of COVID-19?

Herein it is proposed that sufficient exposure to sunlight (UVB) modulates host gene expression, offering protection against severe consequences of COVID-19. This could be in addition to sunlight (UVB)-mediated protection by directly inactivating the virus and limiting the viral load. It is suggested that inhibition of CCR2, DPP9, HSPA1L, IFNAR2, OAS1, and TYK2 may, in part, explain UVB-mediated protection against severe consequences of COVID-19.

Vitamin D status is not associated with clinical severity of COVID-19 in pregnant women.

PURPOSE: To investigate the association between vitamin D status and the clinical severity of COVID-19 in pregnant women. METHODS: This prospective case-control study included 147 pregnant women with COVID-19 and 300 matched controls. Serum 25-hydroxyvitamin (25(OH)D) concentrations were measured on admission. Patients with mild-to-moderate disease (n = 114, 77.6%) and severe-to-critical disease (n = 33, 22.4%) were classified as symptomatic patients who did not require oxygen support and those who received oxygen support, respectively. SARS-CoV-2 positivity rates, clinical severity of COVID-19, and pulmonary involvement were compared according to vitamin D status. RESULTS: Serum 25(OH)D concentrations were found to be 36.6 ± 26.8 and 31.3 ± 20.7 nmol/L in pregnant women infected with SARS-CoV-2 and healthy controls, respectively (p = 0.001). The clinical severity of pregnant women with COVID-19 did not differ concerning vitamin D deficiency (RR = 0.568, 95% CI [0.311-1.036]; p = 0.065), even after excluding patients on vitamin supplementation (RR = 0.625, 95% CI [0.275-1.419]; p = 0.261). Testing positive for SARS-CoV-2 was not related to vitamin D status in the overall cohort of pregnant women (RR = 0.767, 95% CI [0.570-1.030]; p = 0.078). Pulmonary involvement of COVID-19 was found to be similar between patients with vitamin D deficiency and adequate vitamin D levels (RR = 0.954; 95% CI [0.863-1.055]; p = 0.357). CONCLUSION: The clinical severity and pulmonary involvement of COVID-19 may not be associated with vitamin D status in pregnant women. Vitamin D deficiency/adequacy rates were comparable in pregnant women infected with SARS-CoV-2 and healthy pregnant women.