Exploring SARS-CoV-2 infection and vaccine-induced immunity in chronic myeloid leukemia patients: insights from real-world data in Brazil and the United States.

This study investigates COVID-19 outcomes and immune response in chronic myeloid leukemia (CML) patients post-SARS-CoV-2 vaccination, comparing effectiveness of various vaccine options. Data from 118 CML patients (85 in Brazil, 33 in the US) showed similar infection rates prior (14% Brazil, 9.1% US) and post-vaccination (24.7% vs. 27.3%, respectively). In Brazil, AstraZeneca and CoronaVac were the most commonly used vaccine brands, while in the US, Moderna and Pfizer-BioNTech vaccines dominated. Despite lower seroconversion in the Brazilian cohort, all five vaccine brands analyzed prevented severe COVID-19. Patients who received mRNA and recombinant viral vector vaccines (HR: 2.20; 95%CI 1.07-4.51; p < .031) and those that had achieved at least major molecular response (HR: 1.51; 95% CI 1.01-3.31; p < .0001) showed higher seroconversion rates. Our findings suggest that CML patients can generate antibody responses regardless of the vaccine brand, thereby mitigating severe COVID-19. This effect is more pronounced in patients with well-controlled disease.

Gene Regulatory Network Analysis of Post-Mortem Lungs Unveils Novel Insights into COVID-19 Pathogenesis.

The novel coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged as one of the most significant global health crises in recent history. The clinical characteristics of COVID-19 patients have revealed the possibility of immune activity changes contributing to disease severity. Nevertheless, limited information is available regarding the immune response in human lung tissue, which is the primary site of infection. In this study, we conducted an extensive analysis of lung tissue to screen for differentially expressed miRNAs and mRNAs in five individuals who died due to COVID-19 and underwent a rapid autopsy, as well as seven control individuals who died of other causes unrelated to COVID-19. To analyze the host response gene expression, miRNA microarray and Nanostring's nCounter XT gene expression assay were performed. Our study identified 37 downregulated and 77 upregulated miRNAs in COVID-19 lung biopsy samples compared to the controls. A total of 653 mRNA transcripts were differentially expressed between the two sample types, with most transcripts (472) being downregulated in COVID-19-positive specimens. Hierarchical and PCA K-means clustering analysis showed distinct clustering between COVID-19 and control samples. Enrichment and network analyses revealed differentially expressed genes important for innate immunity and inflammatory response in COVID-19 lung biopsies. The interferon-signaling pathway was highly upregulated in COVID-19 specimens while genes involved in interleukin-17 signaling were downregulated. These findings shed light on the mechanisms of host cellular responses to COVID-19 infection in lung tissues and could help identify new targets for the prevention and treatment of COVID-19 infection.

The associations between dental disease and systemic health.

Understanding the relationship between a patient's systemic and oral health is key for clinicians. The aim of this study was to determine if there is an association between specific findings in a dental exam, such as class V carious lesions, and the American Society of Anesthesiologists (ASA) classification as a proxy for systemic health. A retrospective chart review was performed on all patient charts that met inclusion criteria including detailed, complete, and vetted charts obtained over a three-year period in the predoctoral clinic of a United States dental college. Findings recorded at the initial exam included the decayed, missing or filled teeth (DMFT) score, the location of carious lesions and restorations, the presence of periodontal disease, the number of endodontically treated teeth and the number of fractured teeth or restorations. We found no association found between DMFT score and ASA status but did find that ASA I patients had a higher degree of occlusal carious lesions and that ASA III patients were more likely to have interproximal restorations and fractured teeth. We found associations between a greater number of missing teeth and the presence of periodontal disease with worsening ASA status. Our data suggest that ASA classification cannot be used as a reliable predictor for the health of a patient's dentition or the number of cervical caries. However, the data does demonstrate a positive correlation between the number of missing teeth and ASA status, promoting the idea that the number of missing teeth is a crude prognosticator of systemic health. This information can be used by physicians and dentists to help understand the relationships between a patient's dental and systemic health.

Ethno-demographic disparities in humoral responses to the COVID-19 vaccine among healthcare workers.

The COVID-19 pandemic had a profound impact on global health, but rapid vaccine administration resulted in a significant decline in morbidity and mortality rates worldwide. In this study, we sought to explore the temporal changes in the humoral immune response against SARS-CoV-2 healthcare workers (HCWs) in Augusta, GA, USA, and investigate any potential associations with ethno-demographic features. Specifically, we aimed to compare the naturally infected individuals with naïve individuals to understand the immune response dynamics after SARS-CoV-2 vaccination. A total of 290 HCWs were included and assessed prospectively in this study. COVID status was determined using a saliva-based COVID assay. Neutralizing antibody (NAb) levels were quantified using a chemiluminescent immunoassay system, and IgG levels were measured using an enzyme-linked immunosorbent assay method. We examined the changes in antibody levels among participants using different statistical tests including logistic regression and multiple correspondence analysis. Our findings revealed a significant decline in NAb and IgG levels at 8-12 months postvaccination. Furthermore, a multivariable analysis indicated that this decline was more pronounced in White HCWs (odds ratio [OR] = 2.1, 95% confidence interval [CI] = 1.07-4.08, p = 0.02) and IgG (OR = 2.07, 95% CI = 1.04-4.11, p = 0.03) among the whole cohort. Booster doses significantly increased IgG and NAb levels, while a decline in antibody levels was observed in participants without booster doses at 12 months postvaccination. Our results highlight the importance of understanding the dynamics of immune response and the potential influence of demographic factors on waning immunity to SARS-CoV-2. In addition, our findings emphasize the value of booster doses to ensure durable immunity.

Reduction of SARS-CoV-2 salivary viral load with pre-procedural mouth rinses: a randomised, controlled, clinical trial.

Introduction The purpose of this study was to test the short-term efficacy of four commercial mouthwashes versus water in reducing SARS-CoV-2 viral load in the oral cavity over clinically relevant time points.Methods In total, 32 subjects that were proven SARS-CoV-2-positive via polymerase chain reaction (PCR)-based diagnostic test were recruited and randomised into five parallel arms. Cycle threshold (Ct) values were compared in saliva samples between the groups, as well as within the groups at baseline (pre-rinse), zero hours, one hour and two hours post-rinse, using SARS-CoV-2 reverse transcription-PCR analysis.Results We observed a significant increase in Ct values in saliva samples collected immediately after rinsing with all the four mouthwashes - 0.12% chlorhexidine gluconate, 1.5% hydrogen peroxide, 1% povidone iodine, or Listerine - compared to water. A sustained increase in Ct values for up to two hours was only observed in the Listerine and chlorohexidine gluconate groups. We were not able to sufficiently power this clinical trial, so the results remain notional but encouraging and supportive of findings in other emerging mouthwash studies on COVID-19, warranting additional investigations.Conclusions Our evidence suggests that in a clinical setting, prophylactic rinses with Listerine or chlorhexidine gluconate can potentially reduce SARS-CoV-2 viral load in the oral cavity for up to two hours. While limited in statistical power due to the difficulty in obtaining this data, we advocate for pre-procedural mouthwashing, like handwashing, as an economical and safe additional precaution to help mitigate the transmission of SARS-CoV-2 from a potentially infected patient to providers.

Pain Levels Did Not Differ Following Uncomplicated Third Molar Extractions Utilizing Liposomal Bupivacaine Versus Standard Bupivacaine.

PURPOSE: Operations in the oral cavity are often characterized by an acute period of postoperative pain historically mitigated via opioids and other analgesics. The purpose of the study was to determine if liposomal bupivacaine infiltration (LBI) following uncomplicated extraction of bilateral, mandibular third molars will significantly reduce postoperative pain when compared to standard bupivacaine. MATERIALS AND METHODS: The study was designed as a parallel-arm randomized clinical trial. The sample size was calculated for the primary outcome variable: postoperative pain levels measured at 48-hours. Using a power analysis, a sample size of n = 13 for each group was required. Patients meeting the inclusion/exclusion criteria requiring exodontia from November 4, 2018, to June 16, 2022, were recruited out of the oral and maxillofacial surgery clinic. The patients were randomized and divided into 2 groups. Group A was administered 0.50% bupivacaine (with 1:200,000 epinephrine) via infiltration while group B underwent LBI. The primary outcome of interest was postoperative pain levels followed by the secondary outcomes of postoperative narcotic analgesic use, return to oral function, and satisfaction. Patient demographics and characteristics were analyzed as potential covariates utilizing the Fisher exact test and t test for continuous outcomes, respectively. RESULTS: Thirty patients were recruited for the study. The average age of patients receiving the third molar operation was 24.1 ± 5.8 years. Of the 30, 62.5% were female, and 37.5% were male. Seventy-five percent of the patients were Caucasian, 20.8% were African American, and 4.2% were Asian. Forty-eight-hour postoperative interviews revealed mean pain levels of 2.5 ± 2.8 in the control group and 2.9 ± 2.3 in the LBI group (P = .730) as measured on a visual analog scale. The 48-hour postoperative interview identified a mean of 1.9 ± 2.1 narcotic pills used in the control group and 2.5 ± 5.0 pills used in the LBI group (P = .693). CONCLUSIONS: Mandibular LBIs following bilateral mandibular third molar extractions showed no statistically significant advantage over the standard bupivacaine at either time point analyzed. Furthermore, no statistically significant difference was found regarding narcotic use between the 2 groups.

RBPJ in mouse Sertoli cells is required for proper regulation of the testis stem cell niche.

Stem cells are influenced by their surrounding microenvironment, or niche. In the testis, Sertoli cells are the key niche cells directing the population size and differentiation fate of spermatogonial stem cells (SSCs). Failure to properly regulate SSCs leads to infertility or germ cell hyperplasia. Several Sertoli cell-expressed genes, such as Gdnf and Cyp26b1, have been identified as being indispensable for the proper maintenance of SSCs in their niche, but the pathways that modulate their expression have not been identified. Although we have recently found that constitutively activating NOTCH signaling in Sertoli cells leads to premature differentiation of all prospermatogonia and sterility, suggesting that there is a crucial role for this pathway in the testis stem cell niche, a true physiological function of NOTCH signaling in Sertoli cells has not been demonstrated. To this end, we conditionally ablated recombination signal binding protein for immunoglobulin kappa J region (Rbpj), a crucial mediator of NOTCH signaling, in Sertoli cells using Amh-cre. Rbpj knockout mice had: significantly increased testis sizes; increased expression of niche factors, such as Gdnf and Cyp26b1; significant increases in the number of pre- and post-meiotic germ cells, including SSCs; and, in a significant proportion of mice, testicular failure and atrophy with tubule lithiasis, possibly due to these unsustainable increases in the number of germ cells. We also identified germ cells as the NOTCH ligand-expressing cells. We conclude that NOTCH signaling in Sertoli cells is required for proper regulation of the testis stem cell niche and is a potential feedback mechanism, based on germ cell input, that governs the expression of factors that control SSC proliferation and differentiation.