Vaginal Transcriptional Signatures of the Neutrophil-Driven Immune Response Correlate With Clinical Severity During Recurrent Vulvovaginal Candidiasis.

Problem: Recurrent vulvovaginal candidiasis (RVVC) affects 5%-10% of all women, negatively impacting their reproductive health and quality of life. Herein, we investigated the molecular effects of RVVC on the vaginal mucosa of otherwise healthy women.

Method Of Study: Gene expression analysis was performed on vaginal tissue biopsies from women with RVVC, including those with a current episode of vulvovaginal candidiasis (VVC, n = 19) and women between infections (culture negative RVVC [CNR], n = 8); women asymptomatically colonized with Candida albicans (asymptomatic [AS], n = 7); and healthy controls (n = 18).

Spatial transcriptomics unveils estrogen-modulated immune responses and structural alterations in the ectocervical mucosa of depot medroxyprogesterone acetate users.

The injectable contraceptive, depot medroxyprogesterone acetate (DMPA), is associated with compromised cervical mucosal barriers. High-resolution spatial transcriptomics is applied here to reveal the spatial localization of these altered molecular markers. Ectocervical tissue samples from Kenyan sex workers using DMPA, or non-hormonal contraceptives, underwent spatial transcriptomics and gene set enrichment analyses.

Implementation of a penicillin allergy protocol in open abdominal wall reconstruction: Preoperative optimization program.

Introduction: Beta-lactam prophylaxis is the first-line preoperative antibiotic in open abdominal wall reconstruction. However, of the 11% patients reporting a penicillin allergy (PA), most receive second-line, non-β-lactam prophylaxis. Previously, abdominal wall reconstruction research from our institution demonstrated increased wound complications, readmissions, and reoperations with non-β-lactam prophylaxis.

Assessment of combined α-GAL enzyme activity and lyso-GL3 for Fabry disease screening in women with chronic kidney disease.

Introduction: The spectrum of clinical presentation of Fabry disease (FD) in women is broad and challenging. The aim is to evaluate the effectiveness of an alternative screening method for FD in women.

Methods: A collaborative multicenter cross-sectional study to evaluate the sensitivity and specificity of the combination of two tests (α-GAL enzyme activity assay and lyso-GL3 assay) for the diagnosis of FD in women.

Luminal H O promotes ER Ca dysregulation and toxicity of palmitate in insulin-secreting INS-1E cells.

The endoplasmic reticulum (ER) lumen is not only the major site for the assembly and folding of newly synthesized proteins but also the main intracellular Ca store. Ca ions are involved in versatile biochemical processes, including posttranslational processing and folding of nascent proteins. Disruption of ER Ca homeostasis is usually accompanied by an ER stress response that can ultimately lead to apoptosis if unresolved.

Video Messaging to Increase Vascularized Composite Allograft Donation Willingness in United States Military Veterans.

Unlabelled: Expansion of vascularized composite allograft (VCA) transplantation depends on the public's willingness to donate VCA organs, including face, extremities, and genitourinary organs. This study evaluated the effectiveness of video messaging on VCA donation willingness in US military veterans, a key stakeholder in VCA transplantation.

Methods: Participants (n = 556) were randomized to 1 of 3 VCA video messaging interventions (informational, testimonial, or blended), a general (non-VCA) organ donation video message, or a control (nondonation) video message.

Small-molecule SUMO inhibition for biomarker-informed B-cell lymphoma therapy.

Aberrant activity of the SUMOylation pathway has been associated with MYC overexpression and poor prognosis in aggressive B-cell lymphoma (BCL) and other malignancies. Recently developed small-molecule inhibitors of SUMOylation (SUMOi) target the heterodimeric E1 SUMO activation complex (SAE1/UBA2). Here, we report that activated MYC signaling is an actionable molecular vulnerability in vitro and in a preclinical murine in vivo model of MYC-driven BCL.

Comparative Morphological, Metabolic and Transcriptome Analyses in , , and Zebrafish Mutants Identified a Functional Non-Redundancy of the Elmo Proteins.

The ELMO protein family consists of the homologues ELMO1, ELMO2 and ELMO3. Several studies have shown that the individual ELMO proteins are involved in a variety of cellular and developmental processes. However, it has poorly been understood whether the Elmo proteins show similar functions and act redundantly.

Activated SUMOylation restricts MHC class I antigen presentation to confer immune evasion in cancer.

Activated SUMOylation is a hallmark of cancer. Starting from a targeted screening for SUMO-regulated immune evasion mechanisms, we identified an evolutionarily conserved function of activated SUMOylation, which attenuated the immunogenicity of tumor cells. Activated SUMOylation allowed cancer cells to evade CD8+ T cell-mediated immunosurveillance by suppressing the MHC class I (MHC-I) antigen-processing and presentation machinery (APM).

pdx1 Knockout Leads to a Diabetic Nephropathy- Like Phenotype in Zebrafish and Identifies Phosphatidylethanolamine as Metabolite Promoting Early Diabetic Kidney Damage.

The pdx1-/- zebrafish mutant was recently established as a novel animal model of diabetic retinopathy. In this study, we investigate whether knockout of pdx1 also leads to diabetic kidney disease (DKD). pdx1-/- larvae exhibit several signs of early DKD, such as glomerular hypertrophy, impairments in the filtration barrier corresponding to microalbuminuria, and glomerular basement membrane (GBM) thickening.

Elevated 4-hydroxynonenal induces hyperglycaemia via Aldh3a1 loss in zebrafish and associates with diabetes progression in humans.

Increased methylglyoxal (MG) formation is associated with diabetes and its complications. In zebrafish, knockout of the main MG detoxifying system Glyoxalase 1, led to limited MG elevation but significantly elevated aldehyde dehydrogenases (ALDH) activity and aldh3a1 expression, suggesting the compensatory role of Aldh3a1 in diabetes. To evaluate the function of Aldh3a1 in glucose homeostasis and diabetes, aldh3a1 zebrafish mutants were generated using CRISPR-Cas9.

Attitudes Toward Organ, Tissue, and Vascularized Composite Allograft (VCA) Donation and Transplantation: A Survey of United States Military Veterans.

Background: There are 20 million living US armed forces veterans; however, the organ donation attitudes of veterans have not been examined.

Methods: Over a 17-month period, a convenience sample of 1517 veterans in New England completed a survey to assess attitudes about organ, tissue, and vascularized composite allograft (VCA) donation.

Results: Most veterans (96%) supported the donation of organs and tissue for transplantation, and 59% were registered as an organ and tissue donor.

Structural Identity of Galactooligosaccharide Molecules Selectively Utilized by Single Cultures of Probiotic Bacterial Strains.

Various β-galactosidase enzymes catalyze the trans-glycosylation reaction with lactose. The resulting galactooligosaccharide (GOS) mixtures are widely used in infant nutrition to stimulate growth of beneficial gut bacteria. GOS consists mainly of compounds with a degree of polymerization (DP) varying from 2-8 and with diverse glycosidic linkages.

Increasing Organ Donor Designation Rates in Adolescents: A Cluster Randomized Trial.

To evaluate the effectiveness of video messaging on adolescent organ donor designation rates. We randomized adolescent driver education classes in Massachusetts, between July 2015 and February 2018, to receive 1 of 3 organ donation video messaging interventions (informational, testimonial, or blended). Adolescents completed questionnaires before and after the intervention and at 1-week follow-up; we compared their registration status at time of obtaining driver's license with that of a regionally matched historical comparison group.

Establishing an Antimicrobial Stewardship Collaborative Across a Large, Diverse Health Care System.

Unlabelled: Alarming trends in antibiotic resistance sparked a National Action Plan endorsing antimicrobial stewardship programs (ASPs) in health care facilities. Atrium Health consists of 28 acute care facilities with varying levels of ASP maturity. The organization sought to establish an ASP collaborative across a diverse network by uniting local resources with a central advisory team.

Structural and functional characterization of a family GH53 β-1,4-galactanase from Bacteroides thetaiotaomicron that facilitates degradation of prebiotic galactooligosaccharides.

Galactooligosaccharides (GOS) are prebiotic compounds synthesized from lactose using bacterial enzymes and are known to stimulate growth of beneficial bifidobacteria in the human colon. Bacteroides thetaiotaomicron is a prominent human colon commensal bacterial species that hydrolyzes GOS using an extracellular Glycosyl Hydrolase (GH) family GH53 endo-galactanase enzyme (BTGH53), releasing galactose-based products for growth. Here we dissect the molecular basis for GOS activity of this B.

Stimulatory effects of novel glucosylated lactose derivatives GL34 on growth of selected gut bacteria.

Previously we structurally characterized five glucosylated lactose derivatives (F1-F5) with a degree of polymerization (DP) of 3-4 (GL34), products of Lactobacillus reuteri glucansucrases, with lactose and sucrose as substrates. Here, we show that these GL34 compounds are largely resistant to the hydrolytic activities of common carbohydrate-degrading enzymes. Also, the ability of single strains of gut bacteria, bifidobacteria, lactobacilli, and commensal bacteria, to ferment the GL34 compounds was studied.

Cross-Feeding among Probiotic Bacterial Strains on Prebiotic Inulin Involves the Extracellular -Inulinase of Lactobacillus paracasei Strain W20.

Probiotic gut bacteria employ specific metabolic pathways to degrade dietary carbohydrates beyond the capabilities of their human host. Here, we report how individual commercial probiotic strains degrade prebiotic (inulin type) fructans. First, a structural analysis of commercial fructose oligosaccharide-inulin samples was performed.

Analysis of Hearing and Tinnitus in Workers Exposed to Occupational Noise.

Introduction: Noise is one of the harmful agents to health that is present in the various branches of economic activity. Hearing loss and tinnitus are among the most frequently reported complaints by workers exposed to occupational noise.

Objective: To analyze the hearing and tinnitus in normal-hearing workers exposed to occupational noise.

Impressions That Last: Particularly Negative and Positive Experiences Reported by Parents Five Years after the End of a Child's Successful Cancer Treatment or Death.

Objective: To describe the experience of parenting a child diagnosed with cancer by examining particularly negative and positive experiences reported by parents of childhood cancer survivors and parents of children lost to cancer.

Methods: 168 parents (88 mothers, 80 fathers) participated. Data were collected five years after the end of successful treatment or the child's death.

Impact of a rapid multiplex polymerase chain reaction blood culture identification technology on outcomes in patients with vancomycin-resistant Enterococcal bacteremia.

Background: Early appropriate antibiotic selection is associated with favorable clinical outcomes. We evaluated the clinical impact of rapid detection of vancomycin-resistant Enterococcal bacteremia (VREB) by the FilmArray blood culture identification (BCID) panel coupled with antimicrobial stewardship program (ASP) interventions.

Methods: Hospitalized adult patients with VREB identified by conventional methods (CM) were compared to patients with VREB identified by BCID.

Posttraumatic Stress in Parents of Children Diagnosed with Cancer: Hyperarousal and Avoidance as Mediators of the Relationship between Re-Experiencing and Dysphoria.

Background: Increased understanding of the relationships between different symptom clusters involved in posttraumatic stress symptoms (PTSS) could guide empirical research and clinical practice. The objective of the present study was to investigate whether hyperarousal and avoidance mediated the relationship between re-experiencing and dysphoria in parents of children diagnosed with cancer.

Methods: Longitudinal data from parents of children receiving cancer therapy were used.

Lactobacillus reuteri Strains Convert Starch and Maltodextrins into Homoexopolysaccharides Using an Extracellular and Cell-Associated 4,6-α-Glucanotransferase.

Exopolysaccharides (EPS) of lactic acid bacteria (LAB) are of interest for food applications. LAB are well-known to produce α-glucan from sucrose by extracellular glucansucrases. Various Lactobacillus reuteri strains also possess 4,6-α-glucanotransferase (4,6-α-GTase) enzymes.

A Parallel Randomized Clinical Trial Examining the Return of Urinary Continence after Robot-Assisted Radical Prostatectomy with or without a Small Intestinal Submucosa Bladder Neck Sling.

Purpose: Urinary continence is a driver of quality of life after radical prostatectomy. In this study we evaluated the impact of a biological bladder neck sling on the return of urinary continence after robot-assisted radical prostatectomy.

Materials And Methods: This study compared early continence in patients undergoing robot-assisted radical prostatectomy with a sling and without a sling in a 2-group, 1:1, parallel, randomized controlled trial.