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1.
bioRxiv ; 2024 Jun 02.
Article in English | MEDLINE | ID: mdl-38854050

ABSTRACT

Protein arginylation is an essential posttranslational modification (PTM) catalyzed by arginyl-tRNA-protein transferase 1 (ATE1) in mammalian systems. Arginylation features a post-translational conjugation of an arginyl to a protein, making it extremely challenging to differentiate from translational arginine residues with the same mass in a protein sequence. Here we present a general activity-based arginylation profiling (ABAP) platform for the unbiased discovery of arginylation substrates and their precise modification sites. This method integrates isotopic arginine labeling into an ATE1 assay utilizing biological lysates (ex vivo) rather than live cells, thus eliminating translational bias derived from the ribosomal activity and enabling bona fide arginylation identification using isotopic features. ABAP has been successfully applied to an array of peptide, protein, cell, patient, and animal tissue samples using 20 µg sample input, with 229 unique arginylation sites revealed from human proteomes. Representative sites were validated and followed up for their biological functions. The developed platform is globally applicable to the aforementioned sample types and therefore paves the way for functional studies of this difficult-to-characterize protein modification.

2.
Int J Mol Sci ; 25(11)2024 May 23.
Article in English | MEDLINE | ID: mdl-38891864

ABSTRACT

According to the World Health Organization (WHO), breast cancer (BC) is the deadliest and the most common type of cancer worldwide in women. Several factors associated with BC exert their effects by modulating the state of stress. They can induce genetic mutations or alterations in cell growth, encouraging neoplastic development and the production of reactive oxygen species (ROS). ROS are able to activate many signal transduction pathways, producing an inflammatory environment that leads to the suppression of programmed cell death and the promotion of tumor proliferation, angiogenesis, and metastasis; these effects promote the development and progression of malignant neoplasms. However, cells have both non-enzymatic and enzymatic antioxidant systems that protect them by neutralizing the harmful effects of ROS. In this sense, antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), thioredoxin reductase (TrxR), and peroxiredoxin (Prx) protect the body from diseases caused by oxidative damage. In this review, we will discuss mechanisms through which some enzymatic antioxidants inhibit or promote carcinogenesis, as well as the new therapeutic proposals developed to complement traditional treatments.


Subject(s)
Antioxidants , Breast Neoplasms , Reactive Oxygen Species , Humans , Antioxidants/metabolism , Antioxidants/therapeutic use , Breast Neoplasms/metabolism , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Female , Reactive Oxygen Species/metabolism , Oxidative Stress , Peroxiredoxins/metabolism , Animals , Glutathione Peroxidase/metabolism , Catalase/metabolism , Superoxide Dismutase/metabolism
3.
Infection ; 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38856806

ABSTRACT

PURPOSE: Most data regarding infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI) comes from TAVI registries, rather than IE dedicated cohorts. The objective of our study was to compare the clinical and microbiological profile, imaging features and outcomes of patients with IE after SAVR with a biological prosthetic valve (IE-SAVR) and IE after TAVI (IE-TAVI) from 6 centres with an Endocarditis Team (ET) and broad experience in IE. METHODS: Retrospective analysis of prospectively collected data. From the time of first TAVI implantation in each centre to March 2021, all consecutive patients admitted for IE-SAVR or IE-TAVI were prospectively enrolled. Follow-up was monitored during admission and at 12 months after discharge. RESULTS: 169 patients with IE-SAVR and 41 with IE-TAVI were analysed. Early episodes were more frequent among IE-TAVI. Clinical course during hospitalization was similar in both groups, except for a higher incidence of atrioventricular block in IE-SAVR. The most frequently causative microorganisms were S. epidermidis, Enterococcus spp. and S. aureus in both groups. Periannular complications were more frequent in IE-SAVR. Cardiac surgery was performed in 53.6% of IE-SAVR and 7.3% of IE-TAVI (p=0.001), despite up to 54.8% of IE-TAVI patients had an indication. No differences were observed about death during hospitalization (32.7% vs 35.0%), and at 1-year follow-up (41.8% vs 37.5%), regardless of whether the patient underwent surgery or not. CONCLUSION: Patients with IE-TAVI had a higher incidence of early prosthetic valve IE. Compared to IE-SAVR, IE-TAVI patients underwent cardiac surgery much less frequently, despite having surgical indications. However, in-hospital and 1-year mortality rate was similar between both groups.

4.
Cancer ; 2024 May 25.
Article in English | MEDLINE | ID: mdl-38795024

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) screening is underused, particularly among low-income and minoritized populations, for whom the coronavirus disease 2019 (COVID-19) pandemic has challenged progress in achieving equity. METHODS: A hub-and-spoke model was used. The hub was a nonacademic organization and the spokes were three community health center (CHC) systems overseeing numerous clinic sites. Via a cluster-randomized trial design, nine clinic sites were randomized to intervention and 16 clinic sites were randomized to usual care. Patient-level interventions included invitation letters, mailed fecal immunochemical tests (FITs), and call/text-based reminders. Year 1 intervention impact, which took place during the COVID-19 pandemic, was assessed as the proportion completing screening among individuals not up to date at baseline, which compared intervention and nonintervention clinics accounting for intraclinic cluster variation; confidence intervals (CIs) around differences not including 0 were interpreted as statistically significant. RESULTS: Among 26,736 patients who met eligibility criteria, approximately 58% were female, 55% were Hispanic individuals, and 44% were Spanish speaking. The proportion completing screening was 11.5 percentage points (ppts) (95% CI, 6.1-16.9 ppts) higher in intervention versus usual care clinics. Variation in differences between intervention and usual care clinics was observed by sex (12.6 ppts [95% CI, 7.2-18.0 ppts] for females; 8.8 ppts [95% CI, 4.7-13.9 ppts] for males) and by racial and ethnic group (13.8 ppts [95% CI, 7.0-20.6 ppts] for Hispanic individuals; 13.0 ppts [95% CI, 3.6-22.4 ppts] for Asian individuals; 11.3 ppts [95% CI, 5.8-16.8 ppts] for non-Hispanic White individuals; 6.1 ppts [95% CI, 0.8-10.4 ppts] for Black individuals). CONCLUSIONS: A regional mailed FIT intervention was effective for increasing CRC screening rates across CHC systems serving diverse, low-income populations.

5.
Article in English | MEDLINE | ID: mdl-38763866

ABSTRACT

INTRODUCTION: Dalbavancin (DBV), a novel lipoglycopeptide with activity against Gram-positive bacterial infections, is approved for the treatment of acute bacterial skin and skin structure infections (ABSSSIs). It has linear dose-related pharmacokinetics allowing a prolonged interval between doses. It would be a good option for the treatment of patients with Gram-positive cardiovascular infections. METHODS: Retrospective analysis of patients with cardiovascular infection (infective endocarditis, bacteremia, implantable electronic device infection) treated with DBV at Hospital Clínico San Carlos (Madrid) for 7 years (2016-2022). Patients were divided in two study groups: 1) Infective endocarditis (IE), 2) Bacteremia. Epidemiological, clinical, microbiological and therapeutic data were analyzed. RESULTS: A total of 25 patients were treated with DBV for cardiovascular infection. IE was the most common indication (68%), followed by bacteremia (32%) with male predominance in both groups (64% vs 62%) and median age of 67,7 and 57,5 years, respectively. 100% of blood cultures were positive to Gram-positive microorganisms (Staphylococcus spp., Streptococcus spp. or Enterococcus spp.) in both study groups. Previously to DBV, all patients received other antibiotic therapy, both in the group of IE (median: 80 days) as in bacteremia (14,8 days). The main reason for the administration of DBV was to continue intravenous antimicrobial therapy outside the hospital in both the EI group (n = 15) and the bacteremia group (n = 8). DBV was used as consolidation therapy in a once- or twice-weekly regimen. Microbiological and clinical successes were reached in 84% of cases (n = 21), 76,4% in IE group and 100% in bacteremia group. No patient documented adverse effects during long-term dalbavancin treatment. CONCLUSION: DBV is an effective and safety treatment as consolidation antibiotic therapy in IE and bacteremia produced by Gram-positive microorganisms.

6.
J Chem Phys ; 160(20)2024 May 28.
Article in English | MEDLINE | ID: mdl-38818896

ABSTRACT

Perovskite solar cells have demonstrated exceptional development over the past decade, but their stability remains a challenge toward the application of this technology. Several strategies have been used to address this, and the use of host-guest complexation has recently attracted more interest. However, this approach has primarily been exploited in conventional perovskite solar cells based on n-i-p architectures, while its use in inverted p-i-n devices remains unexplored. Herein, we employ representative crown ether, dibenzo-24-crown-8, for interfacial host-guest complexation in inverted perovskite solar cells based on methylammonium and methylammonium-free formamidinium-cesium halide perovskite compositions. Upon post-treatment of the perovskite films, we observed nanostructures on the surface that were associated with the reduced amount of trap states at the interface with the electron transport layer. As a result, we demonstrate improved efficiencies and operational stabilities following ISOS-D-2I and ISOS-L-2I protocols, demonstrating the viability of this approach to advance device stability.

7.
Circ Res ; 134(10): 1292-1305, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38618716

ABSTRACT

BACKGROUND: During myocardial ischemia/reperfusion (I/R) injury, high levels of matrix Ca2+ and reactive oxygen species (ROS) induce the opening of the mitochondrial permeability transition pore (mPTP), which causes mitochondrial dysfunction and ultimately necrotic death. However, the mechanisms of how these triggers individually or cooperatively open the pore have yet to be determined. METHODS: Here, we use a combination of isolated mitochondrial assays and in vivo I/R surgery in mice. We challenged isolated liver and heart mitochondria with Ca2+, ROS, and Fe2+ to induce mitochondrial swelling. Using inhibitors of the mPTP (cyclosporine A or ADP) lipid peroxidation (ferrostatin-1, MitoQ), we determined how the triggers elicit mitochondrial damage. Additionally, we used the combination of inhibitors during I/R injury in mice to determine if dual inhibition of these pathways is additivity protective. RESULTS: In the absence of Ca2+, we determined that ROS fails to trigger mPTP opening. Instead, high levels of ROS induce mitochondrial dysfunction and rupture independently of the mPTP through lipid peroxidation. As expected, Ca2+ in the absence of ROS induces mPTP-dependent mitochondrial swelling. Subtoxic levels of ROS and Ca2+ synergize to induce mPTP opening. Furthermore, this synergistic form of Ca2+- and ROS-induced mPTP opening persists in the absence of CypD (cyclophilin D), suggesting the existence of a CypD-independent mechanism for ROS sensitization of the mPTP. These ex vivo findings suggest that mitochondrial dysfunction may be achieved by multiple means during I/R injury. We determined that dual inhibition of the mPTP and lipid peroxidation is significantly more protective against I/R injury than individually targeting either pathway alone. CONCLUSIONS: In the present study, we have investigated the relationship between Ca2+ and ROS, and how they individually or synergistically induce mitochondrial swelling. Our findings suggest that Ca2+ mediates mitochondrial damage through the opening of the mPTP, although ROS mediates its damaging effects through lipid peroxidation. However, subtoxic levels both Ca2+ and ROS can induce mPTP-mediated mitochondrial damage. Targeting both of these triggers to preserve mitochondria viability unveils a highly effective therapeutic approach for mitigating I/R injury.


Subject(s)
Lipid Peroxidation , Mice, Inbred C57BL , Mitochondria, Heart , Mitochondria, Liver , Mitochondrial Membrane Transport Proteins , Mitochondrial Permeability Transition Pore , Myocardial Reperfusion Injury , Reactive Oxygen Species , Animals , Lipid Peroxidation/drug effects , Mitochondrial Permeability Transition Pore/metabolism , Reactive Oxygen Species/metabolism , Mice , Mitochondria, Heart/metabolism , Mitochondria, Heart/drug effects , Mitochondria, Heart/pathology , Male , Myocardial Reperfusion Injury/metabolism , Myocardial Reperfusion Injury/prevention & control , Myocardial Reperfusion Injury/pathology , Mitochondrial Membrane Transport Proteins/metabolism , Mitochondria, Liver/metabolism , Mitochondria, Liver/pathology , Mitochondria, Liver/drug effects , Calcium/metabolism , Mitochondrial Swelling/drug effects
8.
Materials (Basel) ; 17(8)2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38673070

ABSTRACT

This work focuses on the synthesis and properties of quaternary ZnSnP2-yAsy chalcopyrite solid solutions. Full miscibility of the solid solution is achieved using ball milling followed by hot press sintering. The measured electrical conductivity increases substantially with As substitution from 0.03 S cm-1 for ZnSnP2 to 10.3 S cm-1 for ZnSnAs2 at 715 K. Band gaps calculated from the activation energies show a steady decrease with increasing As concentration from 1.4 eV for ZnSnP2 to 0.7 eV for ZnSnAs2. The Seebeck coefficient decreases significantly with As substitution from nearly 1000 µV K-1 for ZnSnP2 to -100 µV K-1 for ZnSnAs2 at 650 K. Thermal conductivity is decreased for the solid solutions due to alloy phonon scattering, compared to the end members with y = 0 and y = 2, with the y = 0.5 and y = 1.0 samples exhibiting the lowest values of 1.4 W m-1 K-1 at 825 K. Figure of merit values are increased for the undoped solid solutions at lower temperatures when compared to the end members due to the decreased thermal conductivity, with the y = 0.5 sample reaching zT = 1.6 × 10-3 and y = 1 reaching 2.1 × 10-3 at 700 K. The largest values of the figure of merit zT for the undoped series was found for y = 2 with zT = 2.8 × 10-3 at 700 K due to the increasing n-type Seebeck coefficient. Boltztrap calculations reveal that p-doping could yield zT values above unity at 800 K in case of ZnSnAs2, comparable with ZnSnP2.

9.
NPJ Syst Biol Appl ; 10(1): 38, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38594351

ABSTRACT

Acute myeloid leukemia (AML) is characterized by uncontrolled proliferation of poorly differentiated myeloid cells, with a heterogenous mutational landscape. Mutations in IDH1 and IDH2 are found in 20% of the AML cases. Although much effort has been made to identify genes associated with leukemogenesis, the regulatory mechanism of AML state transition is still not fully understood. To alleviate this issue, here we develop a new computational approach that integrates genomic data from diverse sources, including gene expression and ATAC-seq datasets, curated gene regulatory interaction databases, and mathematical modeling to establish models of context-specific core gene regulatory networks (GRNs) for a mechanistic understanding of tumorigenesis of AML with IDH mutations. The approach adopts a new optimization procedure to identify the top network according to its accuracy in capturing gene expression states and its flexibility to allow sufficient control of state transitions. From GRN modeling, we identify key regulators associated with the function of IDH mutations, such as DNA methyltransferase DNMT1, and network destabilizers, such as E2F1. The constructed core regulatory network and outcomes of in-silico network perturbations are supported by survival data from AML patients. We expect that the combined bioinformatics and systems-biology modeling approach will be generally applicable to elucidate the gene regulation of disease progression.


Subject(s)
Leukemia, Myeloid, Acute , Nucleophosmin , Humans , Gene Regulatory Networks/genetics , Isocitrate Dehydrogenase/genetics , Leukemia, Myeloid, Acute/genetics , Carcinogenesis
10.
Front Public Health ; 12: 1291332, 2024.
Article in English | MEDLINE | ID: mdl-38550328

ABSTRACT

Background: To date, the United States (US) leads the world in the number of infections and deaths due to the Coronavirus Disease 2019 (COVID-19). Racial and ethnic disparities in COVID-19 morbidity and mortality are staggering. Age-adjusted data show that AA and Latino individuals have had higher rates of death over most of the pandemic and during surges. Project 2VIDA! is community-based participatory research (CBPR) that was developed to address individual, social, and contextual factors related to access and acceptance of the COVID-19 vaccine among African American and Latino communities in Southern California. This paper describes the study protocol and overarching objectives. Methods and design: Project 2VIDA! is a multilevel intervention that builds on the principals of CBPR and is designed to increase uptake of the COVID-19 vaccine among African American and Latino individuals (≥16 years and older) in San Diego County. The intervention was developed with a working group comprised of representatives from community and academia and centers on targeted COVID-19 individual awareness and education, linkage to medical and supportive services, COVID-19 community outreach and health promotion and offering the COVID-19 vaccine through community pop-up clinics. Discussion: Findings from 2VIDA! will provide data on the impact, feasibility, and acceptability of the intervention which are all crucial for the adaptation, refinement, and improvement of vaccine outreach interventions for COVID-19 and other vaccine preventable infectious diseases that severely impact African American and Latino communities. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT05022472?term=Project+2VIDA&draw=2&rank=1, NCT05022472.


Subject(s)
COVID-19 Vaccines , COVID-19 , Adult , Humans , California/epidemiology , COVID-19/epidemiology , COVID-19/prevention & control , United States , Clinical Trial Protocols as Topic
11.
Hum Vaccin Immunother ; 20(1): 2326781, 2024 Dec 31.
Article in English | MEDLINE | ID: mdl-38497273

ABSTRACT

The COVID-19 pandemic disproportionately affected racial and ethnic minority communities across the United States (U.S.). Despite the disproportionate burden of COVID-19 faced by communities of color, Black and Hispanic communities are less likely to be fully vaccinated than White non-Hispanic Persons. Health inequity and vaccine hesitancy are complex phenomena that require multilevel responses tailored to the unique needs of each community, a process that inherently necessitates a high level of community engagement in order to develop the most effective health interventions. Building on the principles of community based participatory research (CBPR) and with the support of the National Institutes of Health (NIH), Project 2VIDA! was born. A multidisciplinary collaborative of academic researchers, community members, and clinicians whose aim is to foster sustainable partnerships to reduce the burden of COVID-19 in Hispanic and Black communities across Southern California. Our model was designed to meet our community members where they were - whether on their lunch break or picking their children from school. This CBPR model has been well received by community members. Future health interventions focused on reducing health disparities should prioritize the role of the community, leverage the voices of key community partners, and be grounded in equitable power sharing.


Subject(s)
COVID-19 , Community-Based Participatory Research , Child , Humans , United States , Trust , Ethnic and Racial Minorities , Ethnicity , Pandemics , Vaccination Hesitancy , Health Status Disparities , Minority Groups , Health Inequities , COVID-19/prevention & control
12.
Article in English | MEDLINE | ID: mdl-38466645

ABSTRACT

OBJECTIVES: A growing body of research shows that early-life exposure to war has adverse effects on later-life health. Research has emphasized the importance of exposure timing implicating domain-specific developmental processes and associated critical/sensitive periods. This study looks at the impacts of early childhood war exposure and the repercussions for later-life physical and functional health, with a focus on time of exposure as a source of variability. METHODS: We use residential histories from the Survey of Health Ageing, and Retirement in Europe linked to external data on the location and timing of hostilities to examine the impact of early-life exposure to World War II on later-life physical and functional health. RESULTS: Exposure to war increases the risk of objective (grip strength, chair rise, and peak expiratory flow) and self-reported (mobility limitations and activities of daily living) measures of functional health. Effects are especially pronounced for those born during the war and for those with more prolonged exposures. There is little evidence that the impact of war is mediated by war-related hardships, socioeconomic conditions, health behaviors, or adult chronic disease. DISCUSSION: Our results suggest early-life exposure to war has a lasting impact on physical functional health. Exposure appears to largely operate via direct effects, indicative of altered initial development of physical capacity in early life. Because exposure was so pervasive among some cohorts of older individuals, understanding the health of present older European populations requires wrestling with the residual consequences of wartime exposure at the start of their lives.


Subject(s)
Activities of Daily Living , Humans , Male , Female , Europe , Aged , Middle Aged , War Exposure/adverse effects , War Exposure/statistics & numerical data , World War II , Health Status , Mobility Limitation , Hand Strength , Adverse Childhood Experiences/statistics & numerical data , Health Surveys , Aging/psychology , Aging/physiology
13.
Rev Invest Clin ; 76(1): 37-44, 2024.
Article in English | MEDLINE | ID: mdl-38442374

ABSTRACT

Background: Osteoarthritis is a frequent rheumatic disease. Some single-nucleotide polymorphisms of the gene associated with fat mass and obesity are associated with increased body mass index and knee osteoarthritis. Objective: The objective of this study was to analyze the association of single nucleotide polymorphism rs1477196 of the fat mass and obesity gene with primary knee osteoarthritis. Methods: This observational and cross-sectional study included 347 Mexican participants. We performed the genotypification analysis with TaqMan® probe C_2031262_10 for rs1477196 (Thermo Fisher Scientific). Multivariate analysis included covariables such as age, type 2 diabetes, obesity, and postmenopause. Results: Type 2 diabetes, obesity, and postmenopause were associated with primary knee osteoarthritis in female participants. We did not find an association between rs1477196 and obesity. In the codominant and dominant genetic models, rs1477196 was significantly associated with primary knee osteoarthritis only in the female group, including in the model adjusted by other covariables (odds ratio = 2.517; 1.035-6.123; p = 0.042 and odds ratio = 2.387; 1.054-5.407; p = 0.037, respectively). The interaction between rs1477196 and obesity was significantly associated with primary knee osteoarthritis in female participants (p = 0.039 and p = 0.043). Conclusions: Our findings suggest that the rs1477196 variant of the fat and obesity mass gene may be associated with the risk of primary knee osteoarthritis in women.


Subject(s)
Alpha-Ketoglutarate-Dependent Dioxygenase FTO , Diabetes Mellitus, Type 2 , Osteoarthritis, Knee , Female , Humans , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics , Cross-Sectional Studies , Mexico , Obesity/epidemiology , Obesity/genetics , Osteoarthritis, Knee/epidemiology , Osteoarthritis, Knee/genetics , Polymorphism, Single Nucleotide
14.
Plants (Basel) ; 13(5)2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38475490

ABSTRACT

In the pursuit of identifying the novel resin glycoside modulators glucose-6-phosphatase and α-glucosidase enzymes, associated with blood sugar regulation, methanol-soluble extracts from the flowers of Ipomoea murucoides (cazahuate, Nahuatl), renowned for its abundance of glycolipids, were employed. The methanol-soluble extracts were fractionated by applying the affinity-directed method with glucose-6-phosphatase enzymes from a rat's liver and α-glucosidase enzymes from its intestines. Mass spectrometry and nuclear magnetic resonance were employed to identify the high-affinity compound as a free ligand following the release from the enzymatic complex. Gel permeation through a spin size-exclusion column allowed the separated high-affinity molecules to bind to glucose-6-phosphatase and α-glucosidase enzymes in solution, which led to the identification of some previously reported resin glycosides in the flowers of cazahuate, where a glycolipid mainly structurally related to murucoidin XIV was observed. In vitro studies demonstrated the modulating properties of resin glycosides on the glucose-6-phosphatase enzyme. Dynamic light scattering revealed conformational variations induced by resin glycosides on α-glucosidase enzyme, causing them to become more compact, akin to observations with the positive control, acarbose. These findings suggest that resin glycosides may serve as a potential source for phytotherapeutic agents with antihyperglycemic properties.

15.
Rev. invest. clín ; 76(1): 37-44, Jan.-Feb. 2024. tab
Article in English | LILACS-Express | LILACS | ID: biblio-1560127

ABSTRACT

ABSTRACT Background: Osteoarthritis is a frequent rheumatic disease. Some single-nucleotide polymorphisms of the gene associated with fat mass and obesity are associated with increased body mass index and knee osteoarthritis. Objective: The objective of this study was to analyze the association of single nucleotide polymorphism rs1477196 of the fat mass and obesity gene with primary knee osteoarthritis. Methods: This observational and cross-sectional study included 347 Mexican participants. We performed the genotypification analysis with TaqMan® probe C_2031262_10 for rs1477196 (Thermo Fisher Scientific). Multivariate analysis included covariables such as age, type 2 diabetes, obesity, and postmenopause. Results: Type 2 diabetes, obesity, and postmenopause were associated with primary knee osteoarthritis in female participants. We did not find an association between rs1477196 and obesity. In the codominant and dominant genetic models, rs1477196 was significantly associated with primary knee osteoarthritis only in the female group, including in the model adjusted by other covariables (odds ratio = 2.517; 1.035-6.123; p = 0.042 and odds ratio = 2.387; 1.054-5.407; p = 0.037, respectively). The interaction between rs1477196 and obesity was significantly associated with primary knee osteoarthritis in female participants (p = 0.039 and p = 0.043). Conclusions: Our findings suggest that the rs1477196 variant of the fat and obesity mass gene may be associated with the risk of primary knee osteoarthritis in women.

16.
Am J Kidney Dis ; 83(6): 739-749, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38218454

ABSTRACT

RATIONALE & OBJECTIVE: People with low socioeconomic status are disproportionately affected by kidney failure, and their adverse outcomes may stem from unmet health-related social needs. This study explored hemodialysis patient perspectives on health-related social needs and recommendations for intervention. STUDY DESIGN: Qualitative study using semistructured interviews. SETTINGS & PARTICIPANTS: Thirty-two people with low socioeconomic status receiving hemodialysis at 3 hemodialysis facilities in Austin, Texas. ANALYTICAL APPROACH: Interviews were analyzed for themes and subthemes using the constant comparative method. RESULTS: Seven themes and 21 subthemes (in parentheses) were identified: (1) kidney failure was unexpected (never thought it would happen to me; do not understand dialysis); (2) providers fail patients (doctors did not act; doctors do not care); (3) dialysis is detrimental (life is not the same; dialysis is all you do; dialysis causes emotional distress; dialysis makes you feel sick); (4) powerlessness (dependent on others; cannot do anything about my situation); (5) financial resource strain (dialysis makes you poor and keeps you poor; disability checks are not enough; food programs exist but are inconsistent; eat whatever food is available; not enough affordable housing; unstable housing affects health and well-being); (6) motivation to keep going (faith, support system, will to live); and (7) interventions should promote self-efficacy (navigation of community resources, support groups). LIMITATIONS: Limited quantitative data such as on dialysis vintage, and limited geographic representation. CONCLUSIONS: Dialysis exacerbates financial resource strain, and health-related social needs exacerbate dialysis-related stress. The participants made recommendations to address social needs with an emphasis on increasing support and community resources for this population. PLAIN-LANGUAGE SUMMARY: People receiving dialysis often experience health-related social needs, such as food and housing needs, but little is known about how these impact patients' health and well-being or how to best address them. We interviewed people receiving dialysis about how health-related social needs affect them and what they think dialysis facilities can do to help them address those needs. The participants reported that they often lose their independence after starting dialysis and health-related social needs are common, exacerbate their stress and emotional distress, and reduce their sense of well-being. Dialysis facilities may be able to enhance the experience of these patients by facilitating connections with local resources and providing opportunities for patients to support one another.


Subject(s)
Qualitative Research , Renal Dialysis , Humans , Male , Female , Renal Dialysis/psychology , Middle Aged , Aged , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/psychology , Adult , Health Services Needs and Demand , Needs Assessment , Texas , Interviews as Topic
17.
Heliyon ; 9(12): e22229, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38046145

ABSTRACT

Background: Cardiac implantable electronic device (CIED) procedures can be associated with serious complications, including infection with significant mortality and morbidity, necessitating removal of the device and prolonged hospitalization. One potential pathophysiological mechanism is pocket contamination at the time of device implantation. Therefore, steps taken to prevent contamination at this stage can potentially reduce CIED infections.The barrier dressing, an adhesive material applied to the skin, has the potential to reduce the colonization of the surgical site with host flora that can predispose to infection. There are a limited number of randomized prospective studies on barrier dressing use during various surgeries, but it has never been systematically studied in CIED implantation. Objectives: Do Barrier Dressings Reduce Cardiac Implantable Device Infection? (BARRIER-PROTECT trial; NCT04591366) is a single-centre, prospective, double-armed, single-blinded, randomized controlled trial designed to evaluate the use of an intra-operative adhesive barrier dressing to reduce the risk of end-of-procedure pocket swab positivity. We hypothesize that adhesive draping during implant procedures will reduce the risk of contamination from the skin flora. Also, we aim to investigate if the end-of-procedure pocket swab culture positivity can be used as a potential surrogate marker of CIED infection. Methods and Design: Patients undergoing a second or later procedure on the same device pocket (pulse generator change, lead/pocket revision or upgrade) will be enrolled. Eligible and consenting patients will be equally randomized to the use of barrier dressing or not using an automated web-based system. Patients, but not the operator, will be blinded to the arm. The person performing the pocket swabs will also be blinded. The primary endpoint is the end-of-procedure pocket swab culture positivity. The main secondary endpoint is the CIED infection rate. Discussion: This is the first randomized controlled trial to assess the effectiveness of using a barrier adhesive draping on reducing the end-of-procedure pocket swab culture positivity. In this study, we are exploring a low-cost intervention that may significantly reduce CIED infection. Also, having a valid surrogate marker for CIED infection at the time of implant will facilitate design of future clinical trials.

18.
Mob DNA ; 14(1): 20, 2023 Nov 30.
Article in English | MEDLINE | ID: mdl-38037122

ABSTRACT

BACKGROUND: Despite their origins as selfish parasitic sequences, some transposons in the human genome have been co-opted to serve as regulatory elements, contributing to the evolution of transcriptional networks. Most well-characterized examples of transposon-derived regulatory elements derive from endogenous retroviruses (ERVs), due to the intrinsic regulatory activity of proviral long terminal repeat regions. However, one subclass of transposable elements, the Long Interspersed Nuclear Elements (LINEs), have been largely overlooked in the search for functional regulatory transposons, and considered to be broadly epigenetically repressed. RESULTS: We examined the chromatin state of LINEs by analyzing epigenomic data from human immune cells. Many LINEs are marked by the repressive H3K9me3 modification, but a subset exhibits evidence of enhancer activity in human immune cells despite also showing evidence of epigenetic repression. We hypothesized that these competing forces of repressive and activating epigenetic marks might lead to inducible enhancer activity. We investigated a specific L1M2a element located within the first intron of Interferon Alpha/Beta Receptor 1 (IFNAR1). This element shows epigenetic signatures of B cell-specific enhancer activity, despite being repressed by the Human Silencing Hub (HUSH) complex. CRISPR deletion of the element in B lymphoblastoid cells revealed that the element acts as an enhancer that regulates both steady state and interferon-inducible expression of IFNAR1. CONCLUSIONS: Our study experimentally demonstrates that an L1M2a element was co-opted to function as an interferon-inducible enhancer of IFNAR1, creating a feedback loop wherein IFNAR1 is transcriptionally upregulated by interferon signaling. This finding suggests that other LINEs may exhibit cryptic cell type-specific or context-dependent enhancer activity. LINEs have received less attention than ERVs in the effort to understand the contribution of transposons to the regulatory landscape of cellular genomes, but these are likely important, lineage-specific players in the rapid evolution of immune system regulatory networks and deserve further study.

19.
ACS Appl Mater Interfaces ; 15(48): 56547-56555, 2023 Dec 06.
Article in English | MEDLINE | ID: mdl-38006332

ABSTRACT

In the quest for more efficient and cost-effective electrocatalytic systems, careful selection of catalysts and substrates plays a pivotal role. This study introduces an approach by synthesizing and depositing NiFe-layered double hydroxide (NiFe-LDH) catalysts on commercial AISI 304 substrates by using a low-temperature spray-coating technique. Through systematic investigations, the influence of processing conditions, such as the synthesis, ultrasonic power for having a stable nanoparticle's dispersion, and spray cycle optimization on the electrochemical and morphological properties of the coatings, is thoroughly explored. The results showcase exceptional catalytic performance, achieving an overpotential of 230 mV at 10 mA/cm2, with enhanced stability even at high current densities of 500 mA/cm2. The study highlights the significance of meticulous processing optimization and presents a scalable methodology that holds great potential for developing catalysts for oxygen evolution reactions (OER) and facilitates their integration into industrial processes.

20.
BMC Res Notes ; 16(1): 292, 2023 Oct 26.
Article in English | MEDLINE | ID: mdl-37885027

ABSTRACT

OBJECTIVES: The interferon-triggered innate immune response has been observed to be under strong diversifying selection to counteract the many pathogens hosts have to defend against. In particular, rewiring of gene transcription regulation allows organisms to rapidly acquire new phenotypes by removing and adding genes into the innate immune gene network. Dissecting the molecular processes by which this rewiring takes place, either by changing the DNA regulatory elements or by changing the activity of the regulators across species, is key to better understand this evolutionary process. DATA DESCRIPTION: To better comprehend the evolutionary dynamics that have occurred in the initial transcriptional response to interferon in primates, we present Precision Run-On (PRO-seq) datasets made after 1 h of interferon-α2 stimulation on human and rhesus macaque lymphoblastoid cell lines. Further, we tested the difference between using either species' cognate interferon versus using the other orthologous interferon to account for any potential impacts in the interaction of the orthologous interferons with their cellular membrane receptors. This data provides insights into the regulatory mechanisms that drive species-specific responses to environmental perturbations, such as the one driven by the interactions of pathogens and their hosts.


Subject(s)
Immunity, Innate , Interferons , Animals , Humans , Interferons/pharmacology , Macaca mulatta/genetics , Cell Line
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