A Positive Feedback Loop Exists between Estradiol and IL-6 and Contributes to Dermal Fibrosis.

Systemic sclerosis (SSc) is characterized by dermal fibrosis with a female predominance, suggesting a hormonal influence. Patients with SSc have elevated interleukin (IL)-6 levels, and post-menopausal women and older men also have high estradiol (E2) levels. In the skin, IL-6 increases the enzymatic activity of aromatase, thereby amplifying the conversion of testosterone to E2. Therefore, we hypothesized that an interplay between E2 and IL-6 contributes to dermal fibrosis. We used primary dermal fibroblasts from healthy donors and patients with diffuse cutaneous (dc)SSc, and healthy donor skin tissues stimulated with recombinant IL-6 and its soluble receptor (sIL-6R) or E2. Primary human dermal fibroblasts and tissues from healthy donors stimulated with IL-6+sIL-6R produced E2, while E2-stimulated dermal tissues and fibroblasts produced IL-6. Primary dermal fibroblasts from healthy donors treated with IL-6+sIL-6R and the aromatase inhibitor anastrozole (ANA) and dcSSc fibroblasts treated with ANA produced less fibronectin (FN), type III collagen A1 (Col IIIA1), and type V collagen A1 (Col VA1). Finally, dcSSc dermal fibroblasts treated with the estrogen receptor inhibitor fulvestrant also generated less FN, Col IIIA1, and Col VA1. Our data show that IL-6 exerts its pro-fibrotic influence in human skin in part through E2 and establish a positive feedback loop between E2 and IL-6.

Airway protection & patterns of dysphagia in infants with down syndrome: Videofluoroscopic swallow study findings & correlations.

INTRODUCTION: Down syndrome is a genetic condition that affects 1:737 births. Along with cardiac, otolaryngologic, and developmental anomalies, infants with Down syndrome can have swallowing difficulties resulting in respiratory infections. This study aims to characterize the airway protection and dysphagia seen in infants with Down syndrome. METHODS: This is a retrospective chart review of infants with Down syndrome who underwent videofluoroscopic swallow studies (VFSS) from 2008 to 2018 at a tertiary children's hospital. Demographic data and VFSS findings were collected. RESULTS: 89.8% (114/127) of infants presented with at least one element of oral dysphagia, while 72.4% (92/127) had at least one element of pharyngeal dysphagia. Sucking skills were classified as abnormal in 63.7% of the patients and bolus formation-control was determined to be deficient (abnormal) in 62.2% of the patients. Oral residuals were present in 37.8% of the patients. With regard to pharyngeal phase, the swallow initiation was considered abnormal in 53.5% of the patients. Pharyngeal residue was present in 17.3% and pharyngo-nasal reflux was present in 27.5% of the patients. CONCLUSIONS: Swallowing assessments in infants with Down syndrome suspected of dysphagia should be considered, especially in those with any alterations in pulmonary health.

Community grand rounds: re-engineering community and academic partnerships in health education-a partnership and programmatic evaluation.

BACKGROUND: Community participation in population health improvement can assist university researchers in targeting intervention resources more effectively and efficiently, leading to more effective implementation of interventions, because of joint ownership of both process and product. Two academic health centers partnered with community based organizations to develop a bidirectional educational seminar series called "Community Grand Rounds" (CGR), which identified health concerns of Chicago's South Side residents and provided information regarding university and community resources that addressed community health concerns. OBJECTIVES: We evaluated the community consultants' perceptions of the quality and effectiveness of the planning and implementation of the seminars that resulted from the partnership. METHODS: We conducted one-on-one interviews and focus groups with community consultants to assess their perceptions of the partnership using a tailored version of a previously developed individual and focus group interview instrument. Analysis of the interview text was conducted using grounded theory where themes were coded as they emerged. CONCLUSIONS: CGR is an effective mechanism for providing needed community health information in an easily accessible format. Additional work is needed to determine whether this format represents a sustainable community-university partnership.

Clinical importance of purulence in methicillin-resistant Staphylococcus aureus skin and soft tissue infections.

BACKGROUND: The so-called community-associated methicillin-resistant Staphylococcus aureus (MRSA) strains are more frequently susceptible to non-ss-lactam antibiotics (including clindamycin) than health care-associated MRSA strains. We assessed whether predictive clinical characteristics of presumptive MRSA infections can be identified to guide choice of empiric antibiotic therapy. METHODS: A clinical syndrome was assigned to each inpatient and outpatient at the University of Chicago Medical Center with an MRSA infection in 2004 to 2005. Antimicrobial susceptibilities and molecular characteristics of MRSA isolates were assessed. Patients were stratified by lesion characteristics. RESULTS: Of MRSA isolates from 262 patients with purulent skin and soft tissue infections (SSTIs), 231 (88%) were susceptible to clindamycin, 253 (97%) contained staphylococcal chromosomal cassette mec (SCCmec) IV, and 245 (94%) contained Panton-Valentine leukocidin (pvl) genes, characteristics associated with community-associated MRSA strains. The presence of a purulent SSTI had a positive predictive value of 88% for a clindamycin-susceptible MRSA isolate. Among 87 isolates from a nonpurulent SSTI, 44% were susceptible to clindamycin and 34% contained pvl genes. In 179 invasive MRSA disease isolates, 33% were clindamycin-susceptible and 26% carried pvl genes. CONCLUSIONS: A purulent MRSA SSTI strongly predicted the presence of a clindamycin-susceptible MRSA isolate. Presence of the pvl genes was almost universal among MRSA isolates causing purulent SSTIs; this was less common in nonpurulent SSTIs and other clinical syndromes.

What is community-associated methicillin-resistant Staphylococcus aureus?

BACKGROUND: A community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infection has been defined as an MRSA infection in a patient who lacks specific risk factors for healthcare exposure. We sought to determine whether the absence or presence of these risk factors still predicts the phenotypic or genotypic characteristics of MRSA strains. METHODS: All clinical MRSA isolates were prospectively collected at the University of Chicago Hospitals from July 2004 through June 2005. Patients were interviewed and/or their medical records were reviewed. Isolates underwent genotyping and susceptibility testing. Data on patients and isolates were stratified in accordance with 8 frequently cited criteria for the identification of CA-MRSA and compared for concordance. RESULTS: Among 616 unique patients from whom MRSA isolates were recovered, 404 (65.6%) had risk factors for healthcare exposure. Of the 404 isolates recovered from these patients, 166 (41.1%) were clindamycin susceptible, 190 (47.0%) carried staphylococcal cassette chromosome mec (SCCmec) type IV, 145 (35.9%) carried the Panton-Valentine leukocidin genes (PVL+), and 162 (40.1%) were identified as sequence type (ST) 8 by multilocus sequence typing (MLST), all of which are characteristics commonly attributed to CA-MRSA strains. CONCLUSIONS: Association with the healthcare environment now has little predictive value for distinguishing patients with infection due to multidrug resistant MRSA isolates from those infected by CA-MRSA isolates, that is, isolates that are clindamycin-susceptible, PVL+, ST8, and/or contain SCCmec type IV. Defining CA-MRSA by the absence of risk factors for healthcare exposure greatly underestimates the burden of epidemic CA-MRSA disease.

Why is discrimination stressful? The mediating role of cognitive appraisal.

This study attempts to shed light on past findings that experiences of racial and gender discrimination are associated with poor psychological and physical health outcomes by investigating the role of cognitive appraisal as a mediator of the relationship between experiences of discrimination and affective stress reactions. African American female college students (N = 115) imagined themselves in an audiotaped scenario in which they overheard 2 European American male classmates make negative evaluations of them. Participants then completed measures of causal attributions, cognitive appraisal, and affective stress reactions. Multiple regression analyses supported the hypotheses that attributions to racism and to discrimination that combines racism and sexism were associated with increased stress reactions. This relationship was mediated by cognitive appraisals of centrality.

POSaM: a fast, flexible, open-source, inkjet oligonucleotide synthesizer and microarrayer.

DNA arrays are valuable tools in molecular biology laboratories. Their rapid acceptance was aided by the release of plans for a pin-spotting microarrayer by researchers at Stanford. Inkjet microarraying is a flexible, complementary technique that allows the synthesis of arrays of any oligonucleotide sequences de novo. We describe here an open-source inkjet arrayer capable of rapidly producing sets of unique 9,800-feature arrays.