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1.
Violence Against Women ; : 10778012241254856, 2024 May 29.
Article En | MEDLINE | ID: mdl-38807541

Identity-based discrimination experiences have been associated with intimate partner aggression (IPA) use, yet very little research has examined sexist discrimination. This study explored whether women's experiences of sexist discrimination are associated with their IPA use. Participants were 626 predominantly white, cisgender, heterosexual women who completed self-report measures online. Women's sexist experiences were significantly and positively correlated with their IPA use, even after controlling for recent stressful experiences and gender-based violence exposures. Psychological distress symptoms significantly mediated the relation between sexist experiences and IPA use. The findings demonstrate the importance of considering the role of sexism in women's IPA.

2.
J Healthc Qual ; 2024 May 17.
Article En | MEDLINE | ID: mdl-38759142

ABSTRACT: Providing timely and effective care for patients with sepsis is challenging due to delays in recognition and intervention. The Surviving Sepsis Campaign has developed bundles that have been shown to reduce sepsis mortality. However, hospitals have not consistently adhered to these bundles, resulting in suboptimal outcomes. To address this, a multimodal quality improvement sepsis program was implemented from 2017 to 2022 in a large urban tertiary hospital. The aim of this program was to enhance the Severe Sepsis and Septic Shock Management Bundle compliance and reduce sepsis mortality. At baseline, the Severe Sepsis and Septic Shock Management Bundle compliance rates were low, at 25%, with a sepsis observed/expected mortality ratio of 1.14. Our interventions included the formation of a multidisciplinary committee, the appointment of sepsis champions, the implementation of sepsis alerts and order sets, the formation of a Code Sepsis team, real-time audits, and peer-to-peer education. By 2022, compliance rose to 62%, and the observed/expected mortality ratio decreased to 0.73. Our approach led to improved outcomes and hospital rankings. These findings underscore the efficacy of a comprehensive sepsis care initiative, emphasizing the importance of interdisciplinary collaboration. A multimodal hospital-wide sepsis performance program is feasible and can contribute to improved outcomes. However, further research is necessary to determine the specific impact of individual strategies on sepsis outcomes.

3.
Prev Med Rep ; 41: 102699, 2024 May.
Article En | MEDLINE | ID: mdl-38560596

Objective: Recess contributes meaningfully to physical activity (PA), but recess time has declined. The study's purpose was to report PA by age, gender, and playground feature to inform potential playground configurations more conducive to PA during recess. Methods: Using the System for Observing Play and Leisure Activity in the Youth, kindergarten through 5th grade recesses were observed on at least four days at four schools in Little Rock, Arkansas, United States during May 2023. Target playground features were ball courts, grass, pavement, play structures, and swings. To provide inferential analysis, a comparison of conditional means across playground features, age, and gender was conducted using linear regression with robust standard errors clustered by school. Results: 3,356 playground scans (intercoder correlation = 0.93) were collected and aggregated by school, day, gender, age (grade), and target feature for a sample size of 292 observations. The gender gap was widest among 4-5th graders, 79 % (95 % CI: 72, 86) for males and 64 % (95 % CI: 58, 70) for females. Among females, PA was highest on swings [82 % (95 % CI: 77, 86)] and lowest on paved areas [56 % (95 % CI: 43, 69)]. Among males, it was highest on both swings [81 % (95 % CI: 75, 86)] and ball courts [83 % (95 % CI: 77, 89)] and lowest on grassy areas [64 % (95 % CI: 60, 67)]. Conclusion: Swings, courts, and play structures were associated with a higher proportion of children being engaged in PA. Research is needed to identify whether physical improvements to facilitate access to these features increase PA.

4.
Violence Against Women ; 30(6-7): 1564-1585, 2024 May.
Article En | MEDLINE | ID: mdl-36635951

Twenty-five survivors completed anonymous surveys about reporting sexual and gender-based misconduct to their public university's Title IX office, including case characteristics, perceptions of the reporting and response process (e.g., helpfulness, respect), and experiences of institutional betrayal and support. Measures and open-ended responses described varied misconduct incidents, reporting behaviors, case outcomes, process issues, and negative process consequences. Additionally, process perceptions correlated with institutional betrayal and support. Findings illuminate how survivors' Title IX process perceptions relate to experiencing harm or support from larger institutions, and offer insights into developing a Title IX process which maintains student rights and dignity regardless of outcome.


Sex Offenses , Humans , Universities , Sexual Behavior , Students
5.
Commun Biol ; 6(1): 1274, 2023 12 16.
Article En | MEDLINE | ID: mdl-38104185

NLRP1, while the first inflammasome described, has only recently begun to gain significant attention in disease pathology, inflammation research, and potentially, as a therapeutic target. Recently identified human variants provide key insights into NLRP1 biology while its unique expression in barrier cells such as keratinocytes and airway epithelial cells has aligned with new, human specific agonists. This differentiates NLRP1 from other inflammasomes such as NLRP3 and identifies it as a key therapeutic target in inflammatory diseases. Indeed, recent discoveries highlight that NLRP1 may be the predominant inflammasome in human barrier cells, its primary role akin to NLRP3, to respond to cellular stress. This review focuses on recent studies identifying new human-specific NLRP1 mechanisms of activation of, gain-of-function human variants and disease, its role in responding to cellular stress, and discuss potential advances and the therapeutic potential for NLRP1.


Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein , Humans , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Inflammasomes/metabolism , Adaptor Proteins, Signal Transducing/genetics , Adaptor Proteins, Signal Transducing/metabolism , NLR Proteins/genetics , NLR Proteins/metabolism , Apoptosis Regulatory Proteins/genetics , Apoptosis Regulatory Proteins/metabolism
6.
Front Hum Neurosci ; 17: 1251194, 2023.
Article En | MEDLINE | ID: mdl-38021248

Exposure and response prevention (ERP) therapy, a form of cognitive-behavioral therapy, is a first-line, evidence-based treatment for obsessive-compulsive disorder (OCD) for adults and children. It is effective for the majority of those who engage in it, but treatment adherence can be challenging for some due to the stress involved in the treatment as well as different life circumstances that arise. To help improve treatment adherence, NOCD, a provider of video teletherapy ERP, identifies those at risk of non-adherence using a prediction algorithm trained on a data set of N = 13,809 and provides targeted peer support interventions by individuals ("Member Advocates") who successfully completed ERP treatment for OCD. Member Advocates, using lived OCD experience as well as experience with ERP, engage at-risk patients through digital messaging to engage, educate, and encourage patients in the early stages of treatment. From June 2022 to August 2022, N = 815 patients deemed at risk were reached out to and n = 251 responded and engaged with the Member Advocates. In the at-risk patients who engaged, the intervention resulted in a significant mean 30.4% more therapy hours completed compared to those who did not engage. Additionally, engaged patients had greater reductions in OCD severity. These results have implications for how data science, digital interventions, and strategic peer-to-peer communication and support can be combined to enhance the effectiveness of treatment.

7.
Mol Vis ; 29: 102-116, 2023.
Article En | MEDLINE | ID: mdl-37859806

Purpose: The purpose of this study was to evaluate the elastic modulus, keratocyte-fibroblast-myocyte transformation, and haze formation of the corneal stroma following combined phototherapeutic keratectomy (PTK) and epithelium-off UV-A/riboflavin corneal collagen crosslinking (CXL) using an in vivo rabbit model. Methods: Rabbits underwent PTK and CXL, PTK only, or CXL 35 days before PTK. Rebound tonometry, Fourier-domain optical coherence tomography, and ultrasound pachymetry were performed on days 7, 14, 21, 42, 70, and 90 post-operatively. Atomic force microscopy, histologic inflammation, and immunohistochemistry for α-smooth muscle actin (α-SMA) were assessed post-mortem. Results: Stromal haze formation following simultaneous PTK and CXL was significantly greater than in corneas that received PTK only and persisted for more than 90 days. No significant difference in stromal haze was noted between groups receiving simultaneous CXL and PTK and those receiving CXL before PTK. Stromal inflammation did not differ between groups at any time point, although the intensity of α-SMA over the number of nuclei was significantly greater at day 21 between groups receiving simultaneous CXL and PTK and those receiving CXL before PTK. The elastic modulus was significantly greater in corneas receiving simultaneous CXL and PTK compared with those receiving PTK alone. Conclusions: We showed that stromal haze formation and stromal stiffness is significantly increased following CXL, regardless of whether it is performed at or before the time of PTK. Further knowledge of the biophysical cues involved in determining corneal wound healing duration and outcomes will be important for understanding scarring following CXL and for the development of improved therapeutic options.


Photorefractive Keratectomy , Animals , Rabbits , Photorefractive Keratectomy/methods , Cornea/pathology , Wound Healing , Collagen , Corneal Stroma/pathology , Riboflavin , Inflammation/pathology , Cross-Linking Reagents/pharmacology , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Ultraviolet Rays
8.
Popul Space Place ; 29(5)2023 Jul.
Article En | MEDLINE | ID: mdl-37822803

Given the importance of understanding health outcomes at fine spatial scales, iterative proportional fitting (IPF), a form of small area estimation, was applied to a fixed number of health-related variables (obesity, overweight, diabetes) taken from regionalized 2019 survey responses (n = 5474) from the Idaho Behavioral Risk Factor Surveillance System (BRFSS). Using associated county-level American Community Survey (ACS) census data, a set of constraints, which included age categorization, race, sex, and education level, were used to create county-level weighting matrices for each variable, for each of the seven (7) Idaho public health districts. Using an optimized modeling construction technique, we identified significant constraints and grouping splits for each variable/region, resulting in estimates that were internally and externally validated. Externally validated model results for the most populated counties showed correlations ranging from .79 to .85, with p values all below .05. Estimates indicated higher levels of obesity and overweight individuals for midsouth and southwestern Idaho counties, with a cluster of higher diabetes estimates in the center of the state (Gooding, Lincoln, Minidoka, and Jerome counties). Alternative external sources for health outcomes aligned extremely well with our estimates, with wider confidence intervals in more rural counties with sparse populations.

9.
World J Gastrointest Pathophysiol ; 14(4): 71-85, 2023 Aug 24.
Article En | MEDLINE | ID: mdl-37727283

BACKGROUND: The Centers for Disease Control and Prevention estimate that Clostridioides difficile (C. difficile) causes half a million infections (CDI) annually and is a major cause of total infectious disease death in the United States, causing inflammation of the colon and potentially deadly diarrhea. We recently reported the isolation of ADS024, a Bacillus velezensis (B. velezensis) strain, which demonstrated direct in vitro bactericidal activity against C. difficile, with minimal collateral impact on other members of the gut microbiota. In this study, we hypothesized that in vitro activities of ADS024 will translate in vivo to protect against CDI challenge in mouse models. AIM: To investigate the in vivo efficacy of B. velezensis ADS024 in protecting against CDI challenge in mouse models. METHODS: To mimic disruption of the gut microbiota, the mice were exposed to vancomycin prior to dosing with ADS024. For the mouse single-dose study, the recovery of ADS024 was assessed via microbiological analysis of intestinal and fecal samples at 4 h, 8 h, and 24 h after a single oral dose of 5 × 108 colony-forming units (CFU)/mouse of freshly grown ADS024. The single-dose study in miniature swine included groups that had been pre-dosed with vancomycin and that had been exposed to a dose range of ADS024, and a group that was not pre-dosed with vancomycin and received a single dose of ADS024. The ADS024 colonies [assessed by quantitative polymerase chain reaction (qPCR) using ADS024-specific primers] were counted on agar plates. For the 28-d miniature swine study, qPCR was used to measure ADS024 levels from fecal samples after oral administration of ADS024 capsules containing 5 × 109 CFU for 28 consecutive days, followed by MiSeq compositional sequencing and bioinformatic analyses to measure the impact of ADS024 on microbiota. Two studies were performed to determine the efficacy of ADS024 in a mouse model of CDI: Study 1 to determine the effects of fresh ADS024 culture and ADS024 spore preparations on the clinical manifestations of CDI in mice, and Study 2 to compare the efficacy of single daily doses vs dosing 3 times per day with fresh ADS024. C. difficile challenge was performed 24 h after the start of ADS024 exposure. To model the human distal colon, an anerobic fecal fermentation system was used. MiSeq compositional sequencing and bioinformatic analyses were performed to measure microbiota diversity changes following ADS024 treatment. To assess the potential of ADS024 to be a source of antibiotic resistance, its susceptibility to 18 different antibiotics was tested. RESULTS: In a mouse model of CDI challenge, single daily doses of ADS024 were as efficacious as multiple daily doses in protecting against subsequent challenge by C. difficile pathogen-induced disease. ADS024 showed no evidence of colonization based on the observation that the ADS024 colonies were not recovered 24 h after single doses in mice or 72 h after single doses in miniature swine. In a 28-d repeat-dose study in miniature swine, ADS024 was not detected in fecal samples using plating and qPCR methods. Phylogenetic analysis performed in the human distal colon model showed that ADS024 had a selective impact on the healthy human colonic microbiota, similarly to the in vivo studies performed in miniature swine. Safety assessments indicated that ADS024 was susceptible to all the antibiotics tested, while in silico testing revealed a low potential for off-target activity or virulence and antibiotic-resistance mechanisms. CONCLUSION: Our findings, demonstrating in vivo efficacy of ADS024 in protecting against CDI challenge in mouse models, support the use of ADS024 in preventing recurrent CDI following standard antibiotic treatment.

10.
FEBS Open Bio ; 13(8): 1434-1446, 2023 08.
Article En | MEDLINE | ID: mdl-37392453

Neutrophils are an essential component of the innate immune system; however, uncontrolled neutrophil activity can lead to inflammation and tissue damage in acute and chronic diseases. Despite inclusion of neutrophil presence and activity in clinical evaluations of inflammatory diseases, the neutrophil has been an overlooked therapeutic target. The goal of this program was to design a small molecule regulator of neutrophil trafficking and activity that fulfilled the following criteria: (a) modulates neutrophil epithelial transmigration and activation, (b) lacks systemic exposure, (c) preserves protective host immunity, and (d) is administered orally. The result of this discovery program was ADS051 (also known as BT051), a low permeability, small molecule modulator of neutrophil trafficking and activity via blockade of multidrug resistance protein 2 (MRP2)- and formyl peptide receptor 1 (FPR1)-mediated mechanisms. ADS051, based on a modified scaffold derived from cyclosporine A (CsA), was designed to have reduced affinity for calcineurin with low cell permeability and, thus, a greatly reduced ability to inhibit T-cell function. In cell-based assays, ADS051 did not inhibit cytokine secretion from activated human T cells. Furthermore, in preclinical models, ADS051 showed limited systemic absorption (<1% of total dose) after oral administration, and assessment of ADS051 in human, cell-based systems demonstrated inhibition of neutrophil epithelial transmigration. In addition, preclinical toxicology studies in rats and monkeys receiving daily oral doses of ADS051 for 28 days did not reveal safety risks or ADS051-related toxicity. Our results to date support the clinical development of ADS051 in patients with neutrophil-mediated inflammatory diseases.


Inflammation , Neutrophils , Humans , Rats , Animals , Inflammation/drug therapy
11.
Front Psychol ; 14: 1164725, 2023.
Article En | MEDLINE | ID: mdl-37484083

Conspiracy theories are alternate viewpoints of provided explanations; sensational stories revolving around small groups exerting control for nefarious reasons. Recent events and research have outlined myriad negative social and personal outcomes for those who endorse them. Prior research suggests several predictors of susceptibility to conspiracy theories, including narcissistic personality traits (grandiosity, need for uniqueness), cognitive processes (critical thinking, confirmation bias) and lack of education. The aim of the current paper was to explore how facets of narcissism predict susceptibility to conspiracy theories. It was expected that narcissism would be a positive predictor, but education and cognitive reflection would act as protective factors, reducing this effect. Study one utilized an international survey (N = 323) to investigate the role of education as a protective tool in the relationship between narcissistic traits and conspiratorial beliefs. Support was found for the hypotheses that individuals with higher levels of grandiosity, vulnerable narcissism, a strive for uniqueness, and a strive for supremacy predicted higher levels of conspiracy endorsement. Higher education and STEM education were associated with lower levels of conspiracy endorsement, however all significant moderations indicated that for narcissistic individuals, education increased their likelihood of adopting conspiracy beliefs, contrary to expectation. To investigate this further, study two analyzed a large-scale publicly available dataset (N = 51,404) to assess the relationship between narcissism, critical thinking skills (specifically cognitive reflection) and conspiracy beliefs pertaining to the COVID-19 pandemic. As expected, analysis found narcissism and poor cognitive reflection (intuitive thinking) as predictors of conspiracy beliefs. Higher levels of cognitive reflection were found to be protective, moderating and reducing the impact of narcissism on endorsement of conspiracy theories. The findings suggest that cognitive reflection, but not education protect against narcissistic conspiracy belief. Moreover, that cognitive reflection may have a lessened effect against conspiracy theories adopted for social or ideological reasons. These findings improve understanding of both the role and limitations of education/critical thinking skills as protective factors against conspiracy theory endorsement.

12.
Vet Ophthalmol ; 2023 Jul 23.
Article En | MEDLINE | ID: mdl-37485736

Captive fish populations, such as those encompassing aquarium and pet fish, offer significant economic value and are integral to conservation, research, and education. However, these ornamental fish exhibit a reduced ability to protect their ocular surfaces, and our understanding of the ocular diseases that affect them remains limited. Although corneal neoplasms in carp are uncommon, identifying their distinct characteristics is crucial in selecting appropriate therapeutic interventions that aim to preserve vision, prevent the ocular loss, and ultimately ensure the survival of the affected fish. This study provides clinical and histopathological details of various proliferative corneal masses in Cyprininae species, including five koi (Cyprinus carpio) and four goldfish (Carassius auratus). It discusses a spectrum of neoplasms, including soft tissue sarcoma, spindle cell sarcoma, chromatophoroma, and papilloma, in addition to conditions like exuberant granulation tissue and proliferative carp pox. These findings bear significant implications for clinical decision-making and treatment, offering valuable insights into the incidence and characteristics of corneal tumors in captive fish, which could inform further studies in this area.

13.
Clin Transl Immunology ; 12(6): e1455, 2023.
Article En | MEDLINE | ID: mdl-37360982

Objectives: Inflammasomes induce maturation of the inflammatory cytokines IL-1ß and IL-18, whose activity is associated with the pathophysiology of a wide range of infectious and inflammatory diseases. As validated therapeutic targets for the treatment of acute and chronic inflammatory diseases, there has been intense interest in developing small-molecule inhibitors to target inflammasome activity and reduce disease-associated inflammatory burden. Methods: We examined the therapeutic potential of a novel small-molecule inhibitor, and associated derivatives, termed ADS032 to target and reduce inflammasome-mediated inflammation in vivo. In vitro, we characterised ADS032 function, target engagement and specificity. Results: We describe ADS032 as the first dual NLRP1 and NLRP3 inhibitor. ADS032 is a rapid, reversible and stable inflammasome inhibitor that directly binds both NLRP1 and NLRP3, reducing secretion and maturation of IL-1ß in human-derived macrophages and bronchial epithelial cells in response to the activation of NLPR1 and NLRP3. ADS032 also reduced NLRP3-induced ASC speck formation, indicative of targeting inflammasome formation. In vivo, ADS032 reduced IL-1ß and TNF-α levels in the serum of mice challenged i.p. with LPS and reduced pulmonary inflammation in an acute model of lung silicosis. Critically, ADS032 protected mice from lethal influenza A virus challenge, displayed increased survival and reduced pulmonary inflammation. Conclusion: ADS032 is the first described dual inflammasome inhibitor and a potential therapeutic to treat both NLRP1- and NLRP3-associated inflammatory diseases and also constitutes a novel tool that allows examination of the role of NLRP1 in human disease.

14.
Invest Ophthalmol Vis Sci ; 64(4): 22, 2023 04 03.
Article En | MEDLINE | ID: mdl-37074694

Purpose: We sought to define the role of Wwtr1 in murine ocular structure and function and determine the role of mechanotransduction in Fuchs' endothelial corneal dystrophy (FECD), with emphasis on interactions between corneal endothelial cells (CEnCs) and Descemet's membrane (DM). Methods: A Wwtr1 deficient mouse colony was established, and advanced ocular imaging, atomic force microscope (AFM), and histology/immunofluorescence were performed. Corneal endothelial wound healing was assessed using cryoinjury and phototherapeutic keratectomy in Wwtr1 deficient mice. Expression of WWTR1/TAZ was determined in the corneal endothelium from normal and FECD-affected patients; WWTR1 was screened for coding sequence variants in this FECD cohort. Results: Mice deficient in Wwtr1 had reduced CEnC density, abnormal CEnC morphology, softer DM, and thinner corneas versus wildtype controls by 2 months of age. Additionally, CEnCs had altered expression and localization of Na/K-ATPase and ZO-1. Further, Wwtr1 deficient mice had impaired CEnC wound healing. The WWTR1 transcript was highly expressed in healthy human CEnCs comparable to other genes implicated in FECD pathogenesis. Although WWTR1 mRNA expression was comparable between healthy and FECD-affected patients, WWTR1/TAZ protein concentrations were higher and localized to the nucleus surrounding guttae. No genetic associations were found in WWTR1 and FECD in a patient cohort compared to controls. Conclusions: There are common phenotypic abnormalities seen between Wwtr1 deficient and FECD-affected patients, suggesting that Wwtr1 deficient mice could function as a murine model of late-onset FECD. Despite the lack of a genetic association between FECD and WWTR1, aberrant WWTR1/TAZ protein subcellular localization and degradation may play critical roles in the pathogenesis of FECD.


Endothelial Cells , Fuchs' Endothelial Dystrophy , Humans , Mice , Animals , Endothelial Cells/metabolism , Mechanotransduction, Cellular , Fuchs' Endothelial Dystrophy/pathology , Endothelium, Corneal/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Transcriptional Coactivator with PDZ-Binding Motif Proteins , Adaptor Proteins, Signal Transducing/metabolism
15.
Mol Ther Methods Clin Dev ; 28: 272-283, 2023 Mar 09.
Article En | MEDLINE | ID: mdl-36819978

Recombinant adeno-associated virus (rAAV) is a clinically proven viral vector for delivery of therapeutic genes to treat rare diseases. Improving rAAV manufacturing productivity and vector quality is necessary to meet clinical and commercial demand. These goals will require an improved understanding of the cellular response to rAAV production, which is poorly defined. We interrogated the kinetic transcriptional response of HEK293 cells to rAAV production following transient plasmid transfection, under manufacturing-relevant conditions, using RNA-seq. Time-series analyses identified a robust cellular response to transfection and rAAV production, with 1,850 transcripts differentially expressed. Gene Ontology analysis determined upregulated pathways, including inflammatory and antiviral responses, with several interferon-stimulated cytokines and chemokines being upregulated at the protein level. Literature-based pathway prediction implicated multiple pathogen pattern sensors and signal transducers in up-regulation of inflammatory and antiviral responses in response to transfection and rAAV replication. Systematic analysis of the cellular transcriptional response to rAAV production indicates that host cells actively sense vector manufacture as an infectious insult. This dataset may therefore illuminate genes and pathways that influence rAAV production, thereby enabling the rational design of next-generation manufacturing platforms to support safe, effective, and affordable AAV-based gene therapies.

16.
Exp Eye Res ; 226: 109303, 2023 01.
Article En | MEDLINE | ID: mdl-36343671

PURPOSE: Fuchs endothelial corneal dystrophy (FECD) is a progressive corneal disease that impacts the structure and stiffness of the Descemet's membrane (DM), the substratum for corneal endothelial cells (CECs). These structural alterations of the DM could contribute to the loss of the CECs resulting in corneal edema and blindness. Oxidative stress and transforming growth factor-ß (TGF-ß) pathways have been implicated in endothelial cell loss and endothelial to mesenchymal transition of CECs in FECD. Ascorbic acid (AA) is found at high concentrations in FECD and its impact on CEC survival has been investigated. However, how TGF-ß and AA effect the composition and rigidity of the CEC's matrix remains unknown. METHODS: In this study, we investigated the effect of AA, TGF-ß1 and TGF-ß3 on the deposition, ultrastructure, stiffness, and composition of the extracellular matrix (ECM) secreted by primary bovine corneal endothelial cells (BCECs). RESULTS: Immunofluorescence and electron microscopy post-decellularization demonstrated a robust deposition and distinct structure of ECM in response to treatments. AFM measurements showed that the modulus of the matrix in BCECs treated with TGF-ß1 and TGF-ß3 was significantly lower than the controls. There was no difference in the stiffness of the matrix between the AA-treated cell and controls. Gene Ontology analysis of the proteomics results revealed that AA modulates the oxidative stress pathway in the matrix while TGF-ß induces the expression of matrix proteins collagen IV, laminin, and lysyl oxidase homolog 1. CONCLUSIONS: Molecular pathways identified in this study demonstrate the differential role of soluble factors in the pathogenesis of FECD.


Fuchs' Endothelial Dystrophy , Transforming Growth Factor beta1 , Animals , Cattle , Transforming Growth Factor beta1/metabolism , Endothelial Cells/metabolism , Transforming Growth Factor beta3/metabolism , Fuchs' Endothelial Dystrophy/metabolism , Transforming Growth Factor beta/metabolism , Endothelium, Corneal/metabolism
17.
Vet Ophthalmol ; 26 Suppl 1: 125-133, 2023 Apr.
Article En | MEDLINE | ID: mdl-36478371

OBJECTIVES: This study aimed to define the antimicrobial peptide (AMP) expression pattern of the equine ocular surface and amniotic membrane using a targeted qPCR approach and 3'Tag-sequencing. It will serve as a reference for future studies of ocular surface innate immunity and amniotic membrane therapies. PROCEDURES: A targeted qPCR approach was used to investigate the presence of orthologs for three of the most highly expressed beta-defensins (DEFB1, DEFB4B, and DEFB103A) of the human ocular surface and amniotic membrane in equine corneal epithelium, conjunctiva, and amniotic membrane. 3'Tag-sequencing was performed on RNA from one sample of corneal epithelium, conjunctiva, and amniotic membrane to further characterize their AMP expression. RESULTS: Equine corneal epithelium, conjunctiva, and amniotic membrane expressed DEFB1, DEFB4B, and DEFB103A. DEFB103A was expressed at the highest amounts in corneal epithelium, while DEFB4B was most highly expressed in conjunctiva and amniotic membrane. 3'Tag-sequencing from all three tissues confirmed these findings and identified expression of five additional beta-defensins, 11 alpha-defensins and two cathelicidins, with the alpha-defensins showing higher normalized read counts than the beta-defensins. CONCLUSIONS: This study identified AMP expression in the equine cornea and conjunctiva, suggesting that they play a key role in the protection of the equine eye, similar to the human ocular surface. We also determined that equine amniotic membrane expresses a substantial number of AMPs suggesting it could potentiate an antimicrobial effect as a corneal graft material. Future studies will focus on defining the antimicrobial activity of these AMPs and determining their role in microbial keratitis.


Anti-Infective Agents , alpha-Defensins , beta-Defensins , Humans , Animals , Horses , beta-Defensins/genetics , beta-Defensins/metabolism , alpha-Defensins/metabolism , Amnion/metabolism , Cornea/metabolism , Conjunctiva/metabolism
18.
Violence Against Women ; 29(2): 229-252, 2023 02.
Article En | MEDLINE | ID: mdl-35763550

Intimate partner violence survivors (N = 122) reported on formal help-seeking before and after their male partners enrolled in a Relationship Violence Intervention Program (RVIP). At baseline, only 20% of survivors had ever received domestic abuse (DA) counseling. DA counseling was more common among survivors with more extensive partner abuse exposures, and for black women residing in suburban versus urban communities. New help-seeking was associated with survivor perceptions of the abusive partner's stage of change. RVIP impact may be enhanced through culturally sensitive survivor outreach that is responsive to a broad range of needs and includes repeated contact over time.


Intimate Partner Violence , Spouse Abuse , Male , Female , Humans , Spouse Abuse/psychology , Violence , Intimate Partner Violence/psychology , Counseling , Survivors/psychology
19.
Global Spine J ; : 21925682221139822, 2022 Nov 21.
Article En | MEDLINE | ID: mdl-36411068

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: Intraoperative neurophysiological monitoring (IONM) is widely used in spinal neurosurgery, particularly for intramedullary tumours. However, its validity in intradural extramedullary (IDEM) spinal tumours is less clearly defined, this being the focus of this study. METHODS: We compared outcomes for patients that underwent resection of IDEM tumours with and without IONM between 2010 and 2020. Primary outcomes were postoperative American Spinal Injury Association (ASIA) scores. Other factors assessed were use of intraoperative ultrasound, drain placement, postoperative complications, postoperative Eastern Cooperative Oncology Group (ECOG) score, extent of resection, length of hospital stay, discharge location and recurrence. RESULTS: 163 patients were included, 71 patients in the IONM group and 92 in the non-IONM group. No significant differences were noted in baseline demographics. For preoperative ASIA D patients, 44.0% remained ASIA D and 49.9% improved to ASIA E in the IONM group, compared to 39.7% and 30.2% respectively in the non-IONM group. For preoperative ASIA E patients, 50.3% remained ASIA E and 44.0% deteriorated to ASIA D in the IONM group, compared to 30.2% and 39.7% respectively in the non-IONM group (all other patients deteriorated further). Length of inpatient stay was significantly shorter in the IONM group (P = .043). There were no significant differences in extent of resection, postoperative complications, discharge location or tumour recurrence. CONCLUSIONS: Research focusing on the use of IONM in IDEM tumour surgery remains scarce. Our study supports the use of IONM during surgical excision of IDEM tumours.

20.
Sci Rep ; 12(1): 18980, 2022 11 08.
Article En | MEDLINE | ID: mdl-36348026

Acute primary angle closure glaucoma is a potentially blinding ophthalmic emergency requiring prompt treatment to lower the elevated intraocular pressure in humans and dogs. The PACG in most of canine breeds is epidemiologically similar to humans with older and female patients overrepresented with the condition. The American Cocker Spaniel (ACS) is among the most common breeds observed with PACG development in dogs. This study initially sought to identify genetic risk factors to explain the high prevalence of PACG in ACSs by using a case-control breed-matched genome-wide association study. However, the GWAS failed to identify candidate loci associated with PACG in this breed. This study then assessed intrinsic ocular morphologic traits that may relate to PACG susceptibility in this breed. Normal ACSs without glaucoma have a crowded anterior ocular segment and narrow iridocorneal angle and ciliary cleft, which is consistent with anatomical risk factors identified in humans. The ACSs showed unique features consisting of posterior bowing of iris and longer iridolenticular contact, which mirrors reverse pupillary block and pigment dispersion syndrome in humans. The ACS could hold potential to serve as an animal model of naturally occurring PACG in humans.


Glaucoma, Angle-Closure , Glaucoma, Open-Angle , Dogs , Humans , Animals , Female , Glaucoma, Angle-Closure/genetics , Glaucoma, Angle-Closure/veterinary , Glaucoma, Angle-Closure/complications , Genome-Wide Association Study , Plant Breeding , Iris , Glaucoma, Open-Angle/complications , Acute Disease , Intraocular Pressure
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