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Patients with rheumatoid arthritis are commonly stratified by ACPA serology, with positivity being associated with more severe disease and joint destruction. Here the authors present a single cell RNA sequencing resource comparing peripheral blood and synovial tissue cells from patients with ACPA+ versus ACPA- rheumatoid arthritis.

Few studies provide detailed findings about the health disparities of women being told by a physician whether they have ever had a human papillomavirus (HPV) infection. This study sought to characterize the prevalence and characteristics associated with women age 18 to 59 years in the United States who report being told they were infected with HPV. This study used data from the National Health and Nutritional Examination Survey. Descriptive statistics were computed on study variables and multiple logistic regression analyses were conducted to explore the association of the study variables with the outcome variable. Sampling weights were applied to produce national estimates of prevalence. The sample consisted of 1,669 females, representative of 75,107,170 females in the United States population. Around 11.5% reported being told that they had an HPV infection, of which 60.9% were White, and 82.9% were born in the United States. White women are 2.0 times more likely to be told they have HPV than Asian women and 2.8 times more likely than Black women. United States-born women were 2.1 times more likely told they had an HPV infection than those foreign born. This study found that among U.S. women, less than 12% reported ever having been told they have had an HPV infection. Epidemiologic findings suggest gaps between ever being told of a previous infection and being diagnosed with a clinically relevant HPV infection. Despite epidemiologic data indicating higher HPV prevalence among those less educated and women of color, these groups were less likely to report ever being told they have an HPV infection than White women, and those with a college degree suggesting communication gaps among these subgroups about HPV infection that might exist. Strategies to address potential gaps in communication among these subgroups can potentially reduce the economic burden and health disparities related to HPV infection.

Abstract Background Little is known about how meal-specific food intake contributes to overall diet quality during pregnancy, which is related to numerous maternal and child health outcomes. Food networks are probabilistic graphs using partial correlations to identify relationships among food groups in dietary intake data, and can be analyzed at the meal level. This study investigated food networks across meals in pregnant women and explored differences by overall diet quality classification. Methods Women were asked to complete three 24-h dietary recalls throughout pregnancy (n = 365) within a prospective cohort study in the US. Pregnancy diet quality was evaluated using the Healthy Eating Index-2015 (HEI, range 0-100), calculated across pregnancy. Networks from 40 food groups were derived for women in the highest and lowest HEI tertiles at each participant-labeled meal (i.e., breakfast, lunch, dinner, snacks) using Gaussian graphical models. Network composition was qualitatively compared across meals and between HEI tertiles. Results In both HEI tertiles, breakfast food combinations comprised ready-to-eat cereals with milk, quick breads with sweets (e.g., pancakes with syrup), and bread with cheese and meat. Vegetables were consumed at breakfast among women in the high HEI tertile only. Combinations at lunch and dinner were more varied, including vegetables with oils (e.g., salads) in the high tertile and sugary foods with nuts, fruits, and milk in the low tertile at lunch; and cooked grains with fats (e.g., pasta with oil) in the high tertile and potatoes with vegetables and meat in the low tertile at dinner. Fried potatoes, sugar-sweetened beverages, and sandwiches were consumed together at all main meals in the low tertile only. Foods were consumed individually at snacks in both tertiles; the most commonly consumed food were fruits in the high HEI tertile and cakes & cookies in the low tertile. Conclusions In this cohort of pregnant women, food network analysis indicated that food combinations differed by meal and between HEI tertiles. Meal-specific patterns that differed between diet quality tertiles suggest potential targets to improve food choices at meals; the impact of meal-based dietary modifications on intake of correlated foods and on overall diet quality should be investigated in simulations and intervention studies. Trial registration PEAS was registered with number NCT02217462 in Clinicaltrials.gov on August 13, 2014.

Abstract To compare lupus pathogenesis in disparate tissues, we analyzed gene expression profiles of human discoid lupus erythematosus (DLE) and lupus nephritis (LN). We found common increases in myeloid cell-defining gene sets and decreases in genes controlling glucose and lipid metabolism in lupus-affected skin and kidney. Regression models in DLE indicated increased glycolysis was correlated with keratinocyte, endothelial, and inflammatory cell transcripts, and decreased tricarboxylic (TCA) cycle genes were correlated with the keratinocyte signature. In LN, regression models demonstrated decreased glycolysis and TCA cycle genes were correlated with increased endothelial or decreased kidney cell transcripts, respectively. Less severe glomerular LN exhibited similar alterations in metabolism and tissue cell transcripts before monocyte/myeloid cell infiltration in some patients. Additionally, changes to mitochondrial and peroxisomal transcripts were associated with specific cells rather than global signal changes. Examination of murine LN gene expression demonstrated metabolic changes were not driven by acute exposure to type I interferon and could be restored after immunosuppression. Finally, expression of HAVCR1, a tubule damage marker, was negatively correlated with the TCA cycle signature in LN models. These results indicate that altered metabolic dysfunction is a common, reversible change in lupus-affected tissues and appears to reflect damage downstream of immunologic processes.

Objectives Predictive models for critical events in the intensive care unit (ICU) might help providers anticipate patient deterioration. At the heart of predictive model development lies the ability to accurately label significant events, thereby facilitating the use of machine learning and similar strategies. We conducted this study to establish the validity of an automated system for tagging respiratory and hemodynamic deterioration by comparing automatic tags to tagging by expert reviewers. Methods This retrospective cohort study included 72,650 unique patient stays collected from Electronic Medical Records of the University of Massachusetts’ eICU. An enriched subgroup of stays was manually tagged by expert reviewers. The tags generated by the reviewers were compared to those generated by an automated system. Results The automated system was able to rapidly and efficiently tag the complete database utilizing available clinical data. The overall agreement rate between the automated system and the clinicians for respiratory and hemodynamic deterioration tags was 89.4% and 87.1%, respectively. The automatic system did not add substantial variability beyond that seen among the reviewers. Conclusions We demonstrated that a simple rule-based tagging system could provide a rapid and accurate tool for mass tagging of a compound database. These types of tagging systems may replace human reviewers and save considerable resources when trying to create a validated, labeled database used to train artificial intelligence algorithms. The ability to harness the power of artificial intelligence depends on efficient clinical validation of targeted conditions; hence, these systems and the methodology used to validate them are crucial.

Surgical site occurrences (SSOs) affect up to or over 25% of patients undergoing operative procedures, with the subset of surgical site infections (SSIs) being the most common. Commercially available closed incision negative pressure therapy (ciNPT) may offer surgeons an additional option to manage clean, closed surgical incisions. We conducted an extensive literature search for studies describing ciNPT use and assembled a diverse panel of experts to create consensus recommendations for when using ciNPT may be appropriate. A literature search of MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials using key words 'prevention', 'negative pressure wound therapy (NPWT)', 'active incisional management', 'incisional vacuum therapy', 'incisional NPWT', 'incisional wound VAC', 'closed incisional NPWT', 'wound infection', and 'SSIs' identified peer-reviewed studies published from 2000 to 2015. During a multidisciplinary consensus meeting, the 12 experts reviewed the literature, presented their own ciNPT experiences, identified risk factors for SSOs and developed comprehensive consensus recommendations. A total of 100 publications satisfied the search requirements for ciNPT use. A majority presented data supporting ciNPT use. Numerous publications reported SSI risk factors, with the most common including obesity (body mass index ≥30 kg/m2 ); diabetes mellitus; tobacco use; or prolonged surgical time. We recommend that the surgeon assess the individual patient's risk factors and surgical risks. Surgeons should consider using ciNPT for patients at high risk for developing SSOs or who are undergoing a high-risk procedure or a procedure that would have highly morbid consequences if an SSI occurred.

COVID-19 manifests a spectrum of respiratory symptoms, with the more severe often requiring hospitalization. To identify markers for disease progression, we analyzed longitudinal gene expression data from patients with confirmed SARS-CoV-2 infection admitted to the intensive care unit (ICU) for acute hypoxic respiratory failure (AHRF) as well as other ICU patients with or without AHRF and correlated results of gene set enrichment analysis with clinical features. The results were then compared with a second dataset of COVID-19 patients separated by disease stage and severity. Transcriptomic analysis revealed that enrichment of plasma cells (PCs) was characteristic of all COVID-19 patients whereas enrichment of interferon (IFN) and neutrophil gene signatures was specific to patients requiring hospitalization. Furthermore, gene expression results were used to divide AHRF COVID-19 patients into 2 groups with differences in immune profiles and clinical features indicative of severe disease. Thus, transcriptomic analysis reveals gene signatures unique to COVID-19 patients and provides opportunities for identification of the most at-risk individuals.

BackgroundCOVID-19 spreads via aerosol droplets. The dental profession is at high risk of contracting the virus since their work includes treatment procedures that produce aerosols. Teledentistry offers an opportunity to mitigate the risk to dental personnel by allowing dentists to provide care without direct patient contact. ObjectiveThe purpose of this scoping review was to examine the implementation, challenges, strategies, and innovations related to teledentistry during the COVID-19 pandemic lockdown. MethodsThis scoping review evaluated teledentistry use during the pandemic by searching for articles in PubMed and Google Scholar using the search terms teledentistry, tele-dentistry, covid-19, coronavirus, telehealth, telemedicine, and dentistry. Inclusion criteria consisted of articles published in English from March 1, 2020, to April 1, 2022, that were relevant to dentistry and its specialties, and that included some discussion of teledentistry and COVID-19. Specifically, the review sought to explore teledentistry implementation, challenges, strategies to overcome challenges, and innovative ideas that emerged during the pandemic. It followed the 2020 Preferred Reporting Items for Systematic reviews and Meta-Analyses for Scoping Reviews (PRISMA-ScR). This approach is organized into 5 distinct steps: formulating a defined question, using the question to develop inclusion criteria to identify relevant studies, an approach to appraise the studies, summarizing the evidence using an explicit methodology, and interpreting the findings of the review. ResultsA total of 32 articles was included in this scoping review and summarized by article type, methodology and population, and key points about the aims; 9 articles were narrative review articles, 10 were opinion pieces, 4 were descriptive studies, 3 were surveys, 2 were integrative literature reviews, and there was 1 each of the following: observational study, systematic review, case report, and practice brief. Teledentistry was used both synchronously and asynchronously for virtual consultations, often employing commercial applications such as WhatsApp, Skype, and Zoom. Dental professionals most commonly used teledentistry for triage, to reduce in-person visits, and for scheduling and providing consultations remotely. Identified challenges included patient and clinician acceptance of teledentistry, having adequate infrastructure, reimbursement, and security concerns. Strategies to address these concerns included clinician and patient training and utilizing Health Insurance Portability and Accountability Act-compliant applications. Benefits from teledentistry included providing care for patients during the pandemic and extending care to areas lacking access to dental care. ConclusionsPandemic lockdowns led to new teledentistry implementations, most commonly for triage but also for follow-up and nonprocedural care. Teledentistry reduced in-person visits and improved access to remote areas. Challenges such as technology infrastructure, provider skill level, billing issues, and privacy concerns remain.

Objectives This study investigates the association of daily physical exercise with pain symptoms in endometriosis. We also examined whether an individual’s typical weekly (ie, habitual) exercise frequency influences (ie, moderates) the relationship between their pain symptoms on a given day (day t) and previous-day (day t-1) exercise.Participants The sample included 90 382 days of data from 1009 participants (~85% non-Hispanic white) living with endometriosis across 38 countries.Study design This was an observational, retrospective study conducted using data from a research mobile app (Phendo) designed for collecting self-reported data on symptoms and self-management of endometriosis.Primary outcome measures The two primary outcomes were the composite day-level pain score that includes pain intensity and location, and the change in this score from previous day (Δ-score). We applied generalised linear mixed-level models to examine the effect of previous-day exercise and habitual exercise frequency on these outcomes. We included an interaction term between the two predictors to assess the moderation effect, and adjusted for previous-day pain, menstrual status, education level and body mass index.Results The association of previous-day (day t-1) exercise with pain symptoms on day t was moderated by habitual exercise frequency, independent of covariates (rate ratio=0.96, 95% CI=0.95 to 0.98, p=0.0007 for day-level pain score, B=−0.14, 95% CI=−0.26 to −0.016, p=0.026 for Δ-score). Those who regularly engaged in exercise at least three times per week were more likely to experience favourable pain outcomes after having a bout of exercise on the previous day.Conclusions Regular exercise might influence the day-level (ie, short-term) association of pain symptoms with exercise. These findings can inform exercise recommendations for endometriosis pain management, especially for those who are at greater risk of lack of regular exercise due to acute exacerbation in their pain after exercise.

Abstract Background Depression, stress, and poor-quality sleep are common during pregnancy and postpartum, but the relationship of these factors with reward-related eating is not well understood. This observational cohort study examines associations of depression, stress, and sleep quality with self-reported reward-related eating in pregnancy and postpartum. Methods Participants were enrolled at

Abstract Background Orthodontics prevent and treat facial, dental, and occlusal anomalies. Untreated orthodontic problems can lead to significant dental public health issues, making it important to understand expenditures for orthodontic treatment. This study examined orthodontic expenditures and trends in the United States over 2 decades. Methods This study used data collected by the Medical Expenditure Panel Survey to examine orthodontic expenditures in the United States from 1996 to 2016. Descriptive statistics for orthodontic expenditures were computed and graphed across various groups. Trends in orthodontic expenditures were adjusted to the 2016 United States dollar to account for inflation and deflation over time. Sampling weights were applied in estimating per capita and total expenditures to account for non-responses in population groups. Results Total orthodontic expenditures in the United States almost doubled from $11.5 billion in 1996 to $19.9 billion in 2016 with the average orthodontic expenditure per person increasing from $42.69 in 1996 to $61.52 in 2016. Black individuals had the lowest per capita orthodontic visit expenditure at $30.35. Out-of-pocket expenses represented the highest total expenditure and although the amount of out-of-pocket expenses increased over the years, they decreased as a percentage of total expenditures. Public insurance increased the most over the study period but still accounted for the smallest percentage of expenditures. Over the course of the study, several annual decreases were interspersed with years of increased spending Conclusion While government insurance expenditure increased over the study period, out of pocket expenditures remained the largest contributor. Annual decreases in expenditure associated with economic downturns and result from the reliance on out-of-pocket payments for orthodontic care. Differences in spending among groups suggest disparities in orthodontic care among the US population.

Atrial fibrillation (AF) is the most common heart rhythm disorder in the Western world. Between the years 2010 and 2019, the global prevalence of AF rose from 33.5 million to 59 million, highlighting the importance of developing equitable treatments for patients. The disease is associated with symptoms such as palpitations, dizziness, fatigue, shortness of breath, and cognitive dysfunction. In addition, AF increases the risk of developing a stroke and heart failure. Despite new insights into risk factors that can lead to the development of AF, the success of current treatments is suboptimal. Numerous risk factors, such as hypertension, diabetes, and obesity, have been associated with the development and progression of AF. As these can be lifestyle-related risk factors, lifestyle modification may be a solution to reduce AF-related symptoms as well as episodes. Research results show that certain dietary changes can reduce AF and numerous risk factors for AF. Increasing attention is being given to Mediterranean and whole, plant-based eating patterns, which emphasize eating grains, legumes, vegetables, fruits, and nuts, while excluding most—or all—animal products. Hence, what are the beneficial aspects of a Mediterranean and plant-based diet which consists mainly of unprocessed foods? In the current review, we discuss the outcomes of diet-based treatments. Moreover, other diet-related treatments, brought up by patient initiatives, are highlighted. These patient-initiated studies include L-glutamine and electrolytes as options to manage AF. Also, we highlight the emerging importance of valuing patient needs and a quality-of-life-centered approach to medicine. As indicated by recent studies and patient experiences, citizen science can create inclusive solutions that lead to patient empowerment and a holistic approach for AF management. [ABSTRACT FROM AUTHOR]

Background: The coronavirus (COVID-19) pandemic created challenges for healthcare providers, especially dental professionals in practices and universities. This study investigated dental students' concerns about COVID-19 and whether institutional communication influenced pandemic-related stressors. Methods: An online survey designed to elicit dental students' concerns about COVID-19 was distributed to all dental students enrolled at a private non-profit academic institution in the Western United States from 26 April 2021 to 25 August 2021. Descriptive statistics were used to characterize the respondents, and Chi-square test and z-test analyses were used to compare students' experiences. Results: A total of 92 dental students answered the survey. The respondents' ages ranged from 22 to 47 years. Slightly more than half (50.5%) were male and 93.3% were non-Hispanic or non-Latino. Over one-fourth of the students (27.5%) reported that they either often or always felt anxious that they might become infected with the COVID-19 virus, with 16.3% of the students expressing concern about contracting COVID-19 while on campus. There were no statistically significant differences in anxiety levels about contracting COVID-19 from clinic patients or while on campus between the group of students who perceived the institution communicated effectively and those who did not. However, students who felt that the dental school clearly communicated COVID-19 protocols were more likely to believe that students took protocols seriously and expressed less concern about contracting COVID-19 by touching dental school items. Conclusions: About one-quarter of dental students expressed high levels of anxiety about being infected with COVID-19. Clear communication about COVID-19 protocols reduced students' fear of contracting COVID-19 from dental school items and strengthened their belief that other students followed protocols. [ABSTRACT FROM AUTHOR]

Introduction: Most research examining vitamin D and dental caries focuses on children and younger adults. This study investigated the association between vitamin D levels and dental caries in older adults using data from the United States National Health and Nutrition Examination Survey from 2011 to 2016. Methods: Data were analyzed from 2723 participants aged 65 years and older who completed both dental examinations and serum 25(OH)D tests. Dental caries assessments included the decayed, missing, and filled teeth (DMFT) index and the presence of untreated dental caries. Vitamin D levels were measured as serum 25(OH)D concentrations and categorized as severely deficient (<25 nmol/L), deficient (25–49.9 nmol/L), insufficient (50–74.9 nmol/L), and normal (≥75 nmol/L). Logistic regression and Poisson regression models were used to assess the association between vitamin D levels and dental caries, adjusting for demographic factors. Results: The mean DMFT score was 17.73 ± 8.34, with 35.1% of participants having untreated dental caries. Vitamin D deficiency was associated with a 1.44 times higher likelihood of untreated caries (95% CI: 1.15, 1.81), which weakened after adjustment for demographic factors (adjusted OR: 1.23, 95% CI: 0.97, 1.55). Severe vitamin D deficiency correlated with a 1.13 times higher DMFT score (95% CI: 1.06, 1.20), with the association remaining similar after adjustment (adjusted RR: 1.12, 95% CI: 1.05, 1.20). Significant differences in vitamin D levels were observed across gender, race/ethnicity, and country of birth. Conclusions: This study suggests the potential importance of adequate vitamin D levels for maintaining dental health among older adults. Vitamin D deficiency is associated with a higher risk of poorer DMFT scores. Public health strategies that include vitamin D screening and supplementation, particularly for high-risk groups, may improve oral health outcomes in the older adult population. Further research is needed to elucidate the mechanisms by which vitamin D influences dental health and the potential for vitamin D supplementation to reduce the burden of dental caries in older adults. [ABSTRACT FROM AUTHOR]

Objectives: (1) Assess the frequency and severity of long‐term swallowing and voice complaints, follow‐up care, risk factors for the development of long‐term swallowing and voice complications in patients who underwent anterior transcervical approach (ACA). (2) Determine incidence of long‐term swallowing and voice complications requiring follow‐up otolaryngologic care and assess the frequency of otolaryngologic follow‐up for postoperative swallowing and voice complaints. Methods: Retrospective cohort study of patients between January 2017 and March 2020 who underwent ACA. Demographic information, data from preoperative evaluation, operative records, and data from postoperative visits were collected. Patients were contacted to complete the Eating Assessment Tool and the "Impairment" subset of the Voice Symptoms Scale. Results: A total of 48 patients (10.6%) followed up with a head and neck surgeon for swallowing complaints and 31 patients (6.8%) for voice complaints. Otolaryngology follow‐up for swallowing complaints among patients with at least 3 and 12 months of follow‐up was 16.4% and 17.8%, respectively. Otolaryngology follow‐up for voice complaints among patients with at least 3 and 12 months of follow‐up was 11.7% and 11.9%, respectively. Swallowing function was abnormal in 40.7% at least 3 months after surgery and in 41.8% 12 months after. Voice function was abnormal in 55.7% of respondents at least 3 months after surgery and in 54.5% of respondents 12 months after. Conclusions: ACA is associated with otolaryngologic complications that include dysphagia and dysphonia. This study demonstrates that long‐term swallowing and voice dysfunction appear to persist longer than what is noted by patient utilization of follow‐up otolaryngologic care. Level of Evidence: 4 Laryngoscope, 134:3201–3205, 2024 [ABSTRACT FROM AUTHOR]

Abstract SARS-CoV2 is a previously uncharacterized coronavirus and causative agent of the COVID-19 pandemic. The host response to SARS-CoV2 has not yet been fully delineated, hampering a precise approach to therapy. To address this, we carried out a comprehensive analysis of gene expression data from the blood, lung, and airway of COVID-19 patients. Our results indicate that COVID-19 pathogenesis is driven by populations of myeloid-lineage cells with highly inflammatory but distinct transcriptional signatures in each compartment. The relative absence of cytotoxic cells in the lung suggests a model in which delayed clearance of the virus may permit exaggerated myeloid cell activation that contributes to disease pathogenesis by the production of inflammatory mediators. The gene expression profiles also identify potential therapeutic targets that could be modified with available drugs. The data suggest that transcriptomic profiling can provide an understanding of the pathogenesis of COVID-19 in individual patients.

Abstract Background The purpose of this descriptive study is to outline the Roseman University of Health Sciences (RUHS) College of Dental Medicines’ Patient Assistance Fund development, organization and outcomes. The description and reported results provide insight to others considering similar health professions programs. Methods The Patient Assistance Fund (PAF) affords dental students an opportunity to petition for and obtain financial assistance for their most disadvantaged patients. In this study, two sources of data were collected and used with a quantitative analysis for data collected as part of the PAFs operation and a qualitative analysis to evaluate the patient experiences. Results A total of 16 student advocates, consisting of 6 males and 10 females from the D3 and D4 classes made 26 presentations to the PAF board committee. The combined amount requested from the PAF was $47,428.00 (“Cost of Treatment Plan”) representing an average request per patient of $1824.15 (range $324.00 to $4070.00). The approved procedures and treatment plans totaled $21,278.36 (“Cost of Approved Procedures”) with an average of $818.40 (range $204.00 to $2434.00) per patient. Patients and students expressed a high degree of satisfaction with the program. Conclusions This study provides an overview of the structure, funding sources, expenditures and patient services supported by a dental student managed patient assistance fund. The experiences at RUHS College of Dental Medicine (CODM) suggest that other healthcare professions schools can develop similar type programs that yield benefit both to students and to patients in need.

Abstract Introduction Hospital readmission rates are an indicator of the health care quality provided by hospitals. Applying machine learning (ML) to a hospital readmission database offers the potential to identify patients at the highest risk for readmission. However, few studies applied ML methods to predict hospital readmission. This study sought to assess ML as a tool to develop prediction models for all-cause 90-day hospital readmission for dental patients. Methods Using the 2013 Nationwide Readmissions Database (NRD), the study identified 9260 cases for all-cause 90-day index admission for dental patients. Five ML classification algorithms including decision tree, logistic regression, support vector machine, k-nearest neighbors, and artificial neural network (ANN) were implemented to build predictive models. The model performance was estimated and compared by using area under the receiver operating characteristic curve (AUC), and accuracy, sensitivity, specificity, and precision. Results Hospital readmission within 90 days occurred in 1746 cases (18.9%). Total charges, number of diagnosis, age, number of chronic conditions, length of hospital stays, number of procedures, primary expected payer, and severity of illness emerged as the top eight important features in all-cause 90-day hospital readmission. All models had similar performance with ANN (AUC = 0.743) slightly outperforming the rest. Conclusion This study demonstrates a potential annual saving of over $500 million if all of the 90-day readmission cases could be prevented for 21 states represented in the NRD. Among the methods used, the prediction model built by ANN exhibited the best performance. Further testing using ANN and other methods can help to assess important readmission risk factors and to target interventions to those at the greatest risk.

ABSTRACT Atopic dermatitis (AD) is associated with a deficiency of skin lipids, increased populations of Staphylococcus aureus in the microbiome, and structural defects in the stratum corneum (SC), the outermost layer of human skin. However, the pathogenesis of AD is ambiguous, as it is unclear whether observed changes are the result of AD or contribute to the pathogenesis of the disease. Previous studies have shown that S. aureus is capable of permeating across isolated human SC tissue when lipids are depleted to levels consistent with AD conditions. In this study, we expand upon this discovery to determine the mechanisms and implications of bacterial penetration into the SC barrier. Specifically, we establish if bacteria are permeating intercellularly or employing a combination of both inter- and intracellular travel. The mechanical implications of bacterial invasion, lipid depletion, and media immersion are also evaluated using a newly developed, physiologically relevant, temperature-controlled drip chamber. Results reveal for the first time that S. aureus can be internalized by corneocytes, indicating transcellular movement through the tissue during permeation, consistent with previous theoretical models. S. aureus also degrades the mechanical integrity of human SC, particularly when the tissue is partially depleted of lipids. These observed mechanical changes are likely the cause of broken or ruptured tissue seen as exudative lesions in AD flares. This work further highlights the necessity of lipids in skin microbial barrier function. IMPORTANCE Millions of people suffer from the chronic inflammatory skin disease atopic dermatitis (AD), whose symptoms are associated with a deficiency of skin lipids that exhibit antimicrobial functions and increased populations of the opportunistic pathogen Staphylococcus aureus. However, the pathogenesis of AD is ambiguous, and it remains unclear if these observed changes are merely the result of AD or contribute to the pathogenesis of the disease. In this article, we demonstrate the necessity of skin lipids in preventing S. aureus from penetrating the outermost barrier of human skin, thereby causing a degradation in tissue integrity. This bacterial permeation into the viable epidermis could act as an inflammatory trigger of the disease. When coupled with delipidated AD tissue conditions, bacterial permeation can also explain increased tissue fragility, potentially causing lesion formation in AD patients that results in further enhancing bacterial permeability across the stratum corneum and the development of chronic conditions.

Objective:Rheumatoid arthritis is a chronic inflammatory autoimmune disease that can lead to synovial damage, persistent joint pain, and functional disability. Our objective was to evaluate baseline synovial transcriptome from early inflammatory arthritis patients (EIA) and identify pretreatment biomarkers that could potentially provide insights into long-term functional outcomes of rheumatoid arthritis (RA).MethodsSynovial biopsies from clinically inflamed knee joints were procured from either 17 EIA patients before initiation of disease modifying anti-rheumatic drug (DMARD) therapy (DMARD-naïve EIA) using the minimally invasive closed needle biopsy technique or advanced RA patients undergoing arthroplasty. Affymetrix Human Genome U133 Plus 2 microarray platform was used to profile the synovial transcriptome. The cohort was followed clinically for a median of 12.3 years, and patient data was collected at each visit. Short-term and long-term clinical outcomes were determined by assessing RA-associated clinical parameters Statistical adjustments were made to account for asynchronous clinical visits and duration of follow up.ResultsBased on the transcriptomic analysis, we identified 5 differentially expressed genes (DEGs), including matrix metalloproteinase (MMP)-1 (fibroblast collagenase) and MMP-3 (stromelysin-1) in DMARD-naïve EIA patients, relative to advanced RA patients (q < 0.05). Dichotomous expression of MMP-1 and MMP-3 mRNA and protein was confirmed by qPCR and immunohistochemistry respectively, based on which DMARD-naïve EIA subjects were classified as MMP-high or MMP-low. Hierarchical clustering of transcriptomic data identified 947 DEGs between MMP-high and MMP-low cohorts. Co-expression and IPA analysis of DEGs in the MMP-high cohort showed an enrichment of genes that participated in metabolic or biochemical functions and intracellular immune signaling were regulated through NF-κB and β-catenin complexes and correlated with markers of systemic inflammation. Analysis of short-term clinical outcomes in MMP-high cohort showed a significant reduction in the DAS-CRP scores relative to baseline (P