Methicillin-Resistant Staphylococcus aureus Cellulitis Causing Meningitis From Hematogenous Dissemination: A Case Report.

Methicillin-resistant Staphylococcus aureus meningitis is commonly associated with surgical procedures that closely interact with the central nervous system; however, hematogenous spread via bacteremia is rarely reported. Here, we present a case of methicillin-resistant Staphylococcus aureus meningitis as a complication of a diabetic foot infection that disseminated into a bloodstream infection causing infective endocarditis, discitis, vertebral osteomyelitis, and meningitis that was successfully treated with intravenous daptomycin and rifampin.

Exogenous Cushing Syndrome and Hip Fracture Due to Over-the-Counter Supplement (Artri King).

The most common cause of Cushing syndrome (CS) is exposure to exogenous glucocorticoids. There is an increasing incidence of adulterated over-the-counter (OTC) supplements containing steroids. We present a case of Artri King (AK)-induced CS in a 40-year-old woman who presented with an intertrochanteric fracture of her right femur. Laboratory testing revealed suppressed cortisol and adrenocorticotropic hormone, which was consistent with suppression of the hypothalamic-pituitary-adrenal (HPA) axis. Following the cessation of the AK supplement, the patient's HPA axis recovered, and the clinical manifestations of CS improved. This case emphasizes the need for better regulation of OTC supplements and the need for cautious use.

No evidence of fetal defects or anti-syncytin-1 antibody induction following COVID-19 mRNA vaccination

The impact of coronavirus disease 2019 (COVID-19) mRNA vaccination on pregnancy and fertility has become a major topic of public interest. We investigated two of the most widely propagated claims to determine 1) whether COVID-19 mRNA vaccination of mice during early pregnancy is associated with an increased incidence of birth defects or growth abnormalities, and 2) whether COVID-19 mRNA-vaccinated human volunteers exhibit elevated levels of antibodies to the human placental protein syncytin-1. Using a mouse model, we found that intramuscular COVID-19 mRNA vaccination during early pregnancy at gestational age E7.5 did not lead to differences in fetal size by crown-rump length or weight at term, nor did we observe any gross birth defects. In contrast, injection of the TLR3 agonist and double-stranded RNA mimic polyinosinic-polycytidylic acid, or poly(I:C), impacted growth in utero leading to reduced fetal size. No overt maternal illness following either vaccination or poly(I:C) exposure was observed. We also found that term fetuses from vaccinated murine pregnancies exhibit high circulating levels of anti-Spike and anti-RBD antibodies to SARS-CoV-2 consistent with maternal antibody status, indicating transplacental transfer. Finally, we did not detect increased levels of circulating anti-syncytin-1 antibodies in a cohort of COVID-19 vaccinated adults compared to unvaccinated adults by ELISA. Our findings contradict popular claims associating COVID-19 mRNA vaccination with infertility and adverse neonatal outcomes.

COVID-19 Vaccine Uptake among U.S. Child Care Providers

STRUCUTRED ABSTRACTO_ST_ABSObjectivesC_ST_ABSEnsuring a high COVID-19 vaccine uptake among U.S. child care providers is crucial to mitigating the public health implications of child-to-staff and staff-to-child transmission of SARS-CoV-2; however, the vaccination rate among this group is unknown. MethodsTo characterize the vaccine uptake among U.S. child care providers, we conducted a cross-sectional survey of the child care workforce. Providers were identified through various national databases and state registries. A link to the survey was sent via email between May 26 and June 23, 2021. Out of 44,771 potential respondents, 21,663 responded (48.4%). ResultsOverall COVID-19 vaccine uptake among U.S. child care providers (78.1%, 95% CI [77.3% to 78.9%]) was higher than that of the U.S. adult population (65%). Vaccination rates varied from 53.5% to 89.4% between states. Vaccine uptake differed significantly (p < .01) based on respondent age (70.0% for ages 25-34, 91.5% for ages 75-84), race (70.0% for Black or African Americans, 92.5% for Asian-Americans), annual household income (70.7% for <$35,000, 85.0% for>$75,000), and childcare setting (72.9% for home-based, 79.7% for center-based). ConclusionsCOVID-19 vaccine uptake among U.S. child care providers was higher than that of the general U.S. adult population. Those who were younger, lower income, Black or African American, resided in states either in the Mountain West or the South, and/or worked in home-based childcare programs reported the lowest rates of vaccination; state public health leaders and lawmakers should prioritize these subgroups for placement on the policy agenda to realize the largest gains in vaccine uptake among providers. Tables of Contents SummaryThis article describes the results of a national survey of childcare providers to determine the overall COVID-19 vaccine uptake and the gaps in vaccine coverage. Whats Known on This SubjectEnsuring a high COVID-19 vaccine uptake among U.S. child care providers is crucial to mitigating the public health implications of child-to-staff and staff-to-child transmission of SARS-CoV-2; however, the vaccination rate among this group is unknown. What This Study AddsWhile the vaccine uptake among U.S. child care providers was higher than that of U.S. adults, certain subgroups continue to warrant focused attention for outreach and/or placement on the policy agenda.

COVID-19 vaccine perceptions: An observational study on Reddit

ObjectivesAs COVID-19 vaccinations accelerate in many countries, narratives skeptical of vaccination have also spread through social media. Open online forums like Reddit provide an opportunity to quantitatively examine COVID-19 vaccine perceptions over time. We examine COVID-19 misinformation on Reddit following vaccine scientific announcements. MethodsWe collected all posts on Reddit from January 1 2020 - December 14 2020 (n=266,840) that contained both COVID-19 and vaccine-related keywords. We used topic modeling to understand changes in word prevalence within topics after the release of vaccine trial data. Social network analysis was also conducted to determine the relationship between Reddit communities (subreddits) that shared COVID-19 vaccine posts, and the movement of posts between subreddits. ResultsThere was an association between a Pfizer press release reporting 90% efficacy and increased discussion on vaccine misinformation. We observed an association between Johnson and Johnson temporarily halting its vaccine trials and reduced misinformation. We found that information skeptical of vaccination was first posted in a subreddit (r/Coronavirus) which favored accurate information and then reposted in subreddits associated with antivaccine beliefs and conspiracy theories (e.g. conspiracy, LockdownSkepticism). ConclusionsOur findings can inform the development of interventions where individuals determine the accuracy of vaccine information, and communications campaigns to improve COVID-19 vaccine perceptions. Such efforts can increase individual- and population-level awareness of accurate and scientifically sound information regarding vaccines and thereby improve attitudes about vaccines. Further research is needed to understand how social media can contribute to COVID-19 vaccination services. FundingStudy was funded by the Yale Institute for Global Health and the Whitney and Betty MacMillan Center for International and Area Studies at Yale University. The funding bodies had no role in the design, analysis or interpretation of the data in the study.

Rapid review of social contact patterns during the COVID-19 pandemic

BackgroundPhysical distancing measures aim to reduce person-to-person contact, a key driver of transmission of respiratory infections such as SARS-CoV-2. In response to unprecedented restrictions on human contact during the COVID-19 pandemic, a number of studies measured social contact patterns under the implementation of physical distancing measures. This rapid review aims to synthesize empirical data on the changing social contact patterns during the COVID-19 pandemic. MethodWe conducted a systematic review using PubMed, Medline, Embase and Google Scholar following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We descriptively compared the distribution of contacts observed during the pandemic to pre-COVID data across countries to explore changes in contact patterns during physical distancing measures. ResultsWe identified 12 studies that reported social contact patterns during the COVID-19 pandemic. The majority of studies (11/12) collected data during the initial mitigation period in the spring of 2020 marked by government-declared lockdowns and the most stringent physical distancing measures. Some studies collected additional data after relaxation of initial mitigation. Most study settings reported a mean of between 2-5 contacts per person per day, a substantial reduction compared to pre-COVID rates which ranged from 7-26 contacts per day in similar settings. This reduction was particularly pronounced for contacts outside of the home. Consequently, levels of assortative mixing by age substantially declined. After relaxation of initial mitigation, mean contact rates subsequently increased but did not return to pre-COVID levels. Increases in contacts post-relaxation were driven by working-age adults. ConclusionInformation on changes in contact patterns during physical distancing measures can guide more realistic representations of contact patterns in mathematical models for SARS-CoV-2 transmission.

Saliva viral load is a dynamic unifying correlate of COVID-19 severity and mortality

While several clinical and immunological parameters correlate with disease severity and mortality in SARS-CoV-2 infection, work remains in identifying unifying correlates of coronavirus disease 2019 (COVID-19) that can be used to guide clinical practice. Here, we examine saliva and nasopharyngeal (NP) viral load over time and correlate them with patient demographics, and cellular and immune profiling. We found that saliva viral load was significantly higher in those with COVID-19 risk factors; that it correlated with increasing levels of disease severity and showed a superior ability over nasopharyngeal viral load as a predictor of mortality over time (AUC=0.90). A comprehensive analysis of immune factors and cell subsets revealed strong predictors of high and low saliva viral load, which were associated with increased disease severity or better overall outcomes, respectively. Saliva viral load was positively associated with many known COVID-19 inflammatory markers such as IL-6, IL-18, IL-10, and CXCL10, as well as type 1 immune response cytokines. Higher saliva viral loads strongly correlated with the progressive depletion of platelets, lymphocytes, and effector T cell subsets including circulating follicular CD4 T cells (cTfh). Anti-spike (S) and anti-receptor binding domain (RBD) IgG levels were negatively correlated with saliva viral load showing a strong temporal association that could help distinguish severity and mortality in COVID-19. Finally, patients with fatal COVID-19 exhibited higher viral loads, which correlated with the depletion of cTfh cells, and lower production of anti-RBD and anti-S IgG levels. Together these results demonstrated that viral load - as measured by saliva but not nasopharyngeal -- is a dynamic unifying correlate of disease presentation, severity, and mortality over time.

Kinetics of antibody responses dictate COVID-19 outcome

Recent studies have provided insights into innate and adaptive immune dynamics in coronavirus disease 2019 (COVID-19). Yet, the exact feature of antibody responses that governs COVID-19 disease outcomes remain unclear. Here, we analysed humoral immune responses in 209 asymptomatic, mild, moderate and severe COVID-19 patients over time to probe the nature of antibody responses in disease severity and mortality. We observed a correlation between anti-Spike (S) IgG levels, length of hospitalization and clinical parameters associated with worse clinical progression. While high anti-S IgG levels correlated with worse disease severity, such correlation was time-dependent. Deceased patients did not have higher overall humoral response than live discharged patients. However, they mounted a robust, yet delayed response, measured by anti-S, anti-RBD IgG, and neutralizing antibody (NAb) levels, compared to survivors. Delayed seroconversion kinetics correlated with impaired viral control in deceased patients. Finally, while sera from 89% of patients displayed some neutralization capacity during their disease course, NAb generation prior to 14 days of disease onset emerged as a key factor for recovery. These data indicate that COVID-19 mortality does not correlate with the cross-sectional antiviral antibody levels per se, but rather with the delayed kinetics of NAb production.

The Impact of Impulsivity and Emotional Dysregulation on Comorbid Bipolar Disorder and Borderline Personality Disorder.

The symptomatic overlap between borderline personality disorder (BPD) and bipolar disorder (BD) is a topic of scientific and academic debates. Emotional dysregulation and impulsivity are common features of both disorders. Several studies have shown that both BPD and BD lie on a spectrum; others have suggested that they are separate entities that coexist.  BPD is characterized by impulsive and dangerous behaviors such as driving recklessly, inappropriate sexual behavior, eating disorders, and substance abuse. BD, during a manic episode, is known for their impulsive and risk-taking behavior like hypersexuality, excessive spending, and substance abuse.  The current literature review aims to provide an overview of the impact of impulsivity and emotional dysregulation on comorbid bipolar disorder and borderline personality disorder. Our study results showed that patients with comorbid BPD and BD struggle with impulsive actions and have difficulty controlling their emotions. They are also highly susceptible to anxiety disorders like obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and somatoform disorders. Patients with comorbid BPD and BD struggle with severe psychosocial morbidity and an increased risk of suicide. In patients with only one disease, misdiagnosis is a common phenomenon due to the overlapping symptoms of BPD and BD.

Does Catheter Ablation Lower the Long-Term Risk of Stroke and Mortality in Patients with Atrial Fibrillation? A Concise Review of the Current State of Knowledge.

Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide and carries a significant risk of morbidity and mortality. Multiple trials have highlighted the benefit of catheter ablation over medical therapy in restoring sinus rhythm and improving quality of life. Whether it reduces long-term risk of stroke and mortality is still unclear. We performed a literature search using the PubMed database to review the current state of knowledge regarding the long-term outcomes of stroke and mortality in ablated patients compared to patients who receive medical therapy. Our review mainly consisted of recent randomized controlled trials and large observational studies.  Results from large observational studies show that catheter ablation significantly reduces the risk of stroke in high-risk patients and mortality compared to medical therapy. However, randomized controlled trials have only demonstrated a mortality benefit in patients with comorbid systolic heart failure. In patients with paroxysmal AF, ablation therapy significantly limits the progression to persistent AF and has a higher efficacy in restoring sinus rhythm. Maintenance of sinus rhythm is the most important factor associated with lower long term risk of stroke and mortality. Large randomized controlled trials similar to the Catheter Ablation Versus Anti-arrhythmic Drug Therapy for Atrial Fibrillation (CABANA) trial are still needed to clarify whether catheter ablation is superior over medical therapy in improving the long-term outcomes of stroke and mortality.

Catheter Ablation vs. Medical Treatment in Patients With Atrial Fibrillation.

Atrial fibrillation has become the most commonly seen cardiac arrhythmia in clinical practice affecting almost 5.6 million Americans with that number expected to rise in the near future. The current literature review is aimed to assess the efficacy of catheter ablation in the treatment of patients with atrial fibrillation when compared to standard medical therapy. A PubMed search for studies of "Atrial Fibrillation" found 83,251 articles. Following the application of inclusion/exclusion criteria, we identified 44 articles of relevance that compared catheter ablation and medical therapy in the treatment of atrial fibrillation. These 44 articles included 20 Observational studies, eight randomized clinical trials, three clinical trials, five cohort studies, and eight review articles. Our review determined that catheter ablation was associated with a much lower rate of reoccurrence of atrial fibrillation when compared to medical therapy, as well as decreased cardiovascular outpatient visits and thromboembolic complications. The effect of quality on life when compared to medical treatment, however, was found to be inconclusive.

Efficacy and Safety of Direct Factor Xa Inhibitors Versus Warfarin in Prevention of Primary and Secondary Ischemic Strokes in Non-Valvular Atrial Fibrillation: A Literature Review.

Ischemic stroke remains a major cause of mortality and morbidity in patients with atrial fibrillation. The use of appropriate anticoagulants reduces the risk of ischemic stroke in these patients. The current literature review is aimed to analyze the follow-up efficacy and safety of direct factor Xa inhibitors versus warfarin in the prevention of primary and secondary ischemic stroke, risk of major and minor bleedings, and food and drug interaction in patients with atrial fibrillation (AF). We selected PubMed as our database and we found 83,611 articles using the regular keyword 'atrial fibrillation'. We found 2,224 articles using the regular keywords 'direct factor Xa inhibitors' and 'atrial fibrillation'. Finally, we obtained 326 studies using MeSH keywords: atrial fibrillation, direct factor Xa inhibitors, and warfarin. Ultimately, 46 articles were selected after applying the inclusion/exclusion criteria. All studies were randomized controlled trials (RCT) or clinical trials. Analysis of all studies showed that direct factor Xa inhibitors are superior to warfarin in the prevention of ischemic stroke in patients with non-valvular AF, with a lower rate of major and minor bleeding events and lower foods and drug interaction. Unlike warfarin, direct factor Xa inhibitors do not need frequent blood monitoring and dose adjustment. We found that warfarin and other vitamin K inhibitors may promote the calcification of heart valves and coronary arteries. There is some evidence that direct factor Xa inhibitors may slightly reverse these calcifications in coronary arteries and heart valves.

Sex differences in immune responses to SARS-CoV-2 that underlie disease outcomes

A growing body of evidence indicates sex differences in the clinical outcomes of coronavirus disease 2019 (COVID-19)1-4. However, whether immune responses against SARS-CoV-2 differ between sexes, and whether such differences explain male susceptibility to COVID-19, is currently unknown. In this study, we examined sex differences in viral loads, SARS-CoV-2-specific antibody titers, plasma cytokines, as well as blood cell phenotyping in COVID-19 patients. By focusing our analysis on patients with mild to moderate disease who had not received immunomodulatory medications, our results revealed that male patients had higher plasma levels of innate immune cytokines and chemokines including IL-8, IL-18, and CCL5, along with more robust induction of non-classical monocytes. In contrast, female patients mounted significantly more robust T cell activation than male patients during SARS-CoV-2 infection, which was sustained in old age. Importantly, we found that a poor T cell response negatively correlated with patients age and was predictive of worse disease outcome in male patients, but not in female patients. Conversely, higher innate immune cytokines in female patients associated with worse disease progression, but not in male patients. These findings reveal a possible explanation underlying observed sex biases in COVID-19, and provide important basis for the development of sex-based approach to the treatment and care of men and women with COVID-19.

Detection of SARS-CoV-2 RNA by multiplex RT-qPCR

The current RT-qPCR assay recommended for SARS-CoV-2 testing in the United States requires analysis of three genomic targets per sample: two viral and one host. To simplify testing and reduce the volume of required reagents, we developed a multiplex RT-qPCR assay to detect SARS-CoV-2 in a single reaction. We used existing N1, N2, and RP primer and probe sets by the CDC, but substituted fluorophores to allow multiplexing of the assay. The cycle threshold (Ct) values of our multiplex RT-qPCR were comparable to those obtained by the singleplex assay adapted for research purposes. Low copies (>500 copies / reaction) of SARS-CoV-2 RNA were consistently detected by the multiplex RT-qPCR. Our novel multiplex RT-qPCR improves upon current singleplex diagnostics by saving reagents, costs, time and labor.

Longitudinal immunological analyses reveal inflammatory misfiring in severe COVID-19 patients

Recent studies have provided insights into the pathogenesis of coronavirus disease 2019 (COVID-19)1-4. Yet, longitudinal immunological correlates of disease outcome remain unclear. Here, we serially analysed immune responses in 113 COVID-19 patients with moderate (non-ICU) and severe (ICU) disease. Immune profiling revealed an overall increase in innate cell lineages with a concomitant reduction in T cell number. We identify an association between early, elevated cytokines and worse disease outcomes. Following an early increase in cytokines, COVID-19 patients with moderate disease displayed a progressive reduction in type-1 (antiviral) and type-3 (antifungal) responses. In contrast, patients with severe disease maintained these elevated responses throughout the course of disease. Moreover, severe disease was accompanied by an increase in multiple type 2 (anti-helminths) effectors including, IL-5, IL-13, IgE and eosinophils. Unsupervised clustering analysis of plasma and peripheral blood leukocyte data identified 4 immune signatures, representing (A) growth factors, (B) type-2/3 cytokines, (C) mixed type-1/2/3 cytokines, and (D) chemokines that correlated with three distinct disease trajectories of patients. The immune profile of patients who recovered with moderate disease was enriched in tissue reparative growth factor signature (A), while the profile for those with worsened disease trajectory had elevated levels of all four signatures. Thus, we identified development of a maladapted immune response profile associated with severe COVID-19 outcome and early immune signatures that correlate with divergent disease trajectories.

Surface Functionalization of Iron Oxide Nanoparticles with Gallic Acid as Potential Antioxidant and Antimicrobial Agents.

In this research, we report the size-controlled synthesis and surface-functionalization of magnetite with the natural antioxidant gallic acid (GA) as a ligand, using in situ and post-synthesis methods. GA functionalization provided narrow size distribution, with an average particle size of 5 and 8 nm for in situ synthesis of gallic acid functionalized magnetite IONP@GA1 and IONP@GA2, respectively, which are ultra-small particles as compared to unfunctionalized magnetite (IONP) and post functionalized magnetite IONP@GA3 with average size of 10 and 11 nm respectively. All the IONPs@GA samples were found hydrophilic with stable aggregation state. Prior to commencement of experimental lab work, PASS software was used to predict the biological activities of GA and it is found that experimental antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and antimicrobial studies using well diffusion method are in good agreement with the simulated results. Furthermore, the half maximal inhibitory concentration (IC50) values of DPPH antioxidant assay revealed a 2-4 fold decrease as compared to unfunctionalized IONP. In addition to antioxidant activity, all the three IONP@GA proved outstanding antimicrobial activity while testing on different bacterial and fungal strains. The results collectively indicate the successful fabrication of novel antioxidant, antimicrobial IONP@GA composite, which are magnetically separable, efficient, and low cost, with potential applications in polymers, cosmetics, and biomedical and food industries.