RESUMEN
BACKGROUND: The prostaglandin receptor PTGER4 facilitates homeostasis in the gut. Previous reports indicate that goblet cells, marked by SPINK4 expression, might be affected by PTGER4 activity. Current evidence suggests that prostaglandin E2 (PGE2) produced by mesenchymal stromal cells (MSC) stimulates PTGER4 in epithelial cells during inflammatory conditions. Here, we investigate the subcellular mechanisms and mRNA levels downstream of PTGER4 activity in epithelial cells. METHODS: Mucosal cells, organoids, and MSC were obtained from patient biopsies harvested by endoscopy. Using independent and co-cultures, we manipulated the activity of PTGER4, the downstream enzymes, and mRNA levels, by using PGE2, in combination with chemical inhibitors, L-161982, H89, LB100, DAPT, LMK-235, or with butyrate. Immunofluorescence, single cell sequencing, RNAscope, ELISA, real time PCR, and Western blotting were used to examine these samples. RESULTS: SPINK4 mRNA levels were increased in organoids by co-culture with MSC or exogenous stimulation with PGE2 that could be blocked by L-161982 or LMK-235, PTGER4 or HDAC4 inhibitors, respectively. Expression of PTGER4 was co-localized with JAM-A in the basolateral surfaces in rectal epithelial cells grown as organoids. PGE2 treatment of rectal organoids decreased HDAC4, 5, and 7 phosphorylation levels that could be blocked by L-161982 treatment. Butyrate treatment, or addition of L-161982, increased the phosphorylated levels of HDAC4, 5, and 7. CONCLUSIONS: These findings suggest a mechanism during mucosal injury whereby MSC production of PGE2 increases HDAC4, 5, and 7 activities in epithelial cells by upregulating PTGER4 signaling, ultimately increasing SPINK4 mRNA levels and extracellular release of SPINK4.
Asunto(s)
Dinoprostona , Células Epiteliales , Histona Desacetilasas , ARN Mensajero , Subtipo EP4 de Receptores de Prostaglandina E , Transducción de Señal , Humanos , Subtipo EP4 de Receptores de Prostaglandina E/metabolismo , Subtipo EP4 de Receptores de Prostaglandina E/genética , Histona Desacetilasas/metabolismo , Histona Desacetilasas/genética , Transducción de Señal/efectos de los fármacos , Células Epiteliales/metabolismo , Células Epiteliales/efectos de los fármacos , Células Epiteliales/citología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Dinoprostona/metabolismo , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Organoides/metabolismo , Organoides/citología , Organoides/efectos de los fármacosRESUMEN
Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common hereditary kidney diseases. In addition to renal involvement, vascular complications including intracranial arterial, aortic aneurysms and dissections are common in these patients. We report the case of a 35-year-old male patient with ADPKD who presented with hematuria and was diagnosed with two intrarenal arterial pseudoaneurysms. Endovascular embolization using coils was performed to resolve these symptoms. Vascular complications are often encountered in patients with ADPKD; hence, sufficient clinical suspicion and timely diagnosis can help manage the disease. The most common causes of hematuria in ADPKD patients are cyst hemorrhage or infection; however, vascular aneurysms should also be considered a possibility.
RESUMEN
Lung cancer is one of the most fatal malignancies, with the highest death rate (â¼19%), and the NSCLC type accounts for â¼85% of lung cancers. In the search for new treatments, antimicrobial peptides have received much attention due to their propensity for selective destruction of cancer cells. In the current study, we evaluated the efficacy of the metastasis-specific tumour-homing-TMTP1 peptide against lung cancer using inhalable hybrid nano-assemblies of the PEG-PLGA copolymer as a carrier for pulmonary delivery which was assessed for aerodynamic and physicochemical properties, along with the peptide-release profile, physical stability, cellular uptake and biocompatibility, generation of reactive oxygen species, cell migration, autophagic flux, and apoptotic cell death in A549 lung cancer cells. Optimization of inhaled dose, lung retention, and efficacy studies was conducted to evaluate the formulation in an NNK (nicotine-derived nitrosamine ketone) induced tumour-bearing lung cancer murine model. After inhalation, the formulation with nano-scale physiognomies showed good lung deposition, retention, and metabolic stability. The inhalable nano-assemblies have shown enhanced generation of reactive oxygen species with increased autophagy flux and apoptotic cell death. Pre-clinical animal trials show substantial tumour regression by inhalable TMTP1-based nano-formulation with limited side effects. Our results on metastasis targeting and tumour-homing peptide TMTP1 demonstrate its effective tumour targeting and tumour-killing efficacy and provide a reference for the development of new therapeutics for NSCLC.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Humanos , Animales , Ratones , Administración por Inhalación , Células A549 , Antineoplásicos/química , Antineoplásicos/farmacología , Polietilenglicoles/química , Nanopartículas/química , Portadores de Fármacos/química , Apoptosis/efectos de los fármacos , Sistemas de Liberación de Medicamentos , Proliferación Celular/efectos de los fármacos , Tamaño de la Partícula , Especies Reactivas de Oxígeno/metabolismo , PoliésteresRESUMEN
Lung carcinoma, particularly non-small-cell lung cancer (NSCLC), accounts for a significant portion of cancer-related deaths, with a fatality rate of approximately 19 %. Niclosamide (NIC), originally an anthelmintic drug, has attracted attention for its potential in disrupting cancer cells through various intracellular signaling pathways. However, its effectiveness is hampered by limited solubility, reducing its bioavailability. This study investigates the efficacy of NIC against lung cancer using inhalable hybrid nano-assemblies with chitosan-functionalized Poly (ε-caprolactone) (PCL) as a carrier for pulmonary delivery. The evaluation encompasses various aspects such as aerodynamic and physicochemical properties, drug release kinetics, cellular uptake, biocompatibility, cell migration, autophagic flux, and apoptotic cell death in A549 lung cancer cells. Increasing NIC dosage correlates with enhanced inhibition of cell proliferation, showing a dose-dependent profile (approximately 75 % inhibition efficiency at 20 µg/mL of NIC). Optimization of inhaled dosage and efficacy is conducted in a murine model of NNK-induced tumor-bearing lung cancer. Following inhalation, NIC-CS-PCL-NA demonstrates significant lung deposition, retention, and metabolic stability. Inhalable nano-assemblies promote autophagy flux and induce apoptotic cell death. Preclinical trials reveal substantial tumor regression with minimal adverse effects, underscoring the potential of inhalable NIC-based nano-formulation as a potent therapeutic approach for NSCLC, offering effective tumor targeting and killing capabilities.
Asunto(s)
Apoptosis , Autofagia , Carcinoma de Pulmón de Células no Pequeñas , Quitosano , Neoplasias Pulmonares , Niclosamida , Niclosamida/farmacología , Niclosamida/química , Niclosamida/administración & dosificación , Quitosano/química , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Humanos , Apoptosis/efectos de los fármacos , Animales , Autofagia/efectos de los fármacos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Ratones , Células A549 , Administración por Inhalación , Nanopartículas/química , Proliferación Celular/efectos de los fármacos , Portadores de Fármacos/química , Antineoplásicos/farmacología , Antineoplásicos/química , Liberación de Fármacos , Poliésteres/químicaRESUMEN
Introduction: Lower statin utilization is reported among women compared to men, however large-scale studies evaluating gender disparities in LDL-C management in individuals with ASCVD and its subtypes remain limited, particularly across age and racial/ethnic subgroups. In this study, we address this knowledge gap using data from a large US healthcare system. Methods: All adult patients with established ASCVD in the Houston Methodist Learning Health System Registry during 2016-2022 were included. Statin use and dose were extracted from the database. The association between gender and statin utilization was evaluated using multivariate logistic regression analyses in patients with ASCVD overall, across ASCVD subtypes, and by age, racial/ethnic subgroups, and socioeconomic risk factors. Results: A total of 97,819 patients with prevalent ASCVD were included. Women with ASCVD had lower utilization of any statin (64.3% vs 72.6 %; p < 0.001) and high-intensity statin (29.8% vs 42.5 % p < 0.001) compared with men. In fully adjusted models, women had 40 % lower odds of any (adjusted odds ratio [aOR]:0.58, 95 % CI 0.57-0.60) and high-intensity statin use (aOR:0.59, 0.57-0.61) relative to men. Women were also less likely to have guideline-recommended LDL-C < 70 mg/dL (30.2% vs 42.7 %; p < 0.01). These differences persisted across age, racial/ethnic and socioeconomic subgroups. Conclusion: Significant gender disparities exist in contemporary lipid management among patients with ASCVD, with women being less likely to receive any and high-intensity statin and achieving guideline defined LDL-C goal compared with men across age and racial/ethnic subgroups. These disparities underscore the need to further understand potential socioeconomic drivers of the observed lower statin uptake in women.
RESUMEN
Hypertension is a major risk factor for cardiovascular disease, cognitive decline, and frailty. Given the increasing burden of hypertension in the aging population, it is imperative to improve hypertension management in that population. Apart from variations in treatment goals, challenges such as polypharmacy, medication side effects, and therapeutic inertia hinder adherence to guideline-directed medical therapies among older people. Effective public health messaging is essential for spreading evidence-based guidelines, raising awareness among clinicians, enhancing patient education and health literacy, and implementing community-based strategies to tackle hypertension. This review examines the current state of public messaging on hypertension in older adults.
Asunto(s)
Hipertensión , Salud Pública , Humanos , Hipertensión/terapia , Anciano , Antihipertensivos/uso terapéutico , Alfabetización en Salud , Educación del Paciente como AsuntoRESUMEN
Bryophyllum pinnatum (Lam.) Oken, a multipurpose medicinal herb, has drawn much interest for its therapeutic qualities from both traditional and modern medicine systems. Many active secondary metabolites, such as bufadienolides, triterpenes, phenols, alkaloids, glycosides, lipids, flavonoids, and organic acids, are responsible for the plant's curative properties. B. pinnatum exhibits a noteworthy significance in oncological research by exhibiting its ability to modify numerous pathways, which may suggest a potential anticancer impact. The herb is recommended for treating lithiasis, a common cause of renal failure, due to its effectiveness in dissolving stones and avoiding crystal formation. The plant has a major impact on diabetes, especially type II diabetes. Moreover, the versatility of B. pinnatum extends to its examination in connection to COVID-19. However, caution is warranted, as B. pinnatum has been reported to possess toxicity attributed to the presence of bufadienolides in its metabolic profile. A comprehensive investigation is essential to thoroughly understand and confirm the synthesis of potentially hazardous compounds. This is crucial for minimizing their presence and ensuring the safe consumption of B. pinnatum among diverse populations of organisms. This review highlights the various medical uses of B. pinnatum, including its ability to effectively treat kidney and liver diseases, as well as its anti-leishmanial, neuropharmacological, antibacterial, immunosuppressive, anti-tumour, and cytotoxic effects. While extensively employed in both traditional and scientific domains, the plant's complete medicinal potential, molecular mechanisms, safety profile, and pharmacodynamics remain ambiguous, rendering it an ideal candidate for pioneering research endeavours.
RESUMEN
BACKGROUND: Cardiomyopathy (CDM) in pregnancy is associated with maternal morbidity and mortality. OBJECTIVES: To explore trends and clinical outcomes in CDM subtypes during delivery hospitalizations. METHODS: We used the National Inpatient Sample database to identify delivery hospitalizations between 2005-2020 by CDM subtypes: peripartum (PPCM), dilated (DCM), hypertrophic (HCM), and restrictive (RCM). Maternal and fetal outcomes were identified using International Classification of Diseases, 9th and 10th Revision, Clinical Modification codes. Baseline characteristics and temporal trends of CDM subtypes were analyzed. Maternal cardiovascular, pregnancy, and fetal outcomes were evaluated by CDM subtype using univariate logistic regression. The primary outcome was in-hospital mortality. RESULTS: During 2005-2020, 37,125 out of 61,811,842 delivery hospitalizations were complicated by CDM. Among CDM-related delivery hospitalizations, the most prevalent were DCM (46%), followed by PPCM (45.6%), HCM (4.6%), and RCM (3.9%). The rates of in-hospital mortality (1.7%), adverse cardiovascular events such as acute heart failure (17%), cardiogenic shock (3.4%), and cardiac arrest (3.1%), and adverse pregnancy outcomes such as preeclampsia (14.2%) and preterm labor (11%), were highest among PPCM (all p < 0.0001). The prevalence of PPCM (49.1% to 38.5%) decreased while the prevalence of HCM (2.7% to 8.8%) and DCM (48% to 52.2%) increased over time. CONCLUSIONS: Over a 15-year period, PPCM had higher rates of in-hospital mortality, cardiovascular events, and adverse pregnancy outcomes compared to other CDM subtypes. While the prevalence of PPCM decreased over time, the prevalence of HCM and DCM increased. Hence, further research on cardiomyopathies during pregnancy and prospective studies on this vulnerable patient cohort are urgently needed.
RESUMEN
Over a span of 34 years (1987-2019), an in-depth analysis of PM10, SO2, and NO2 trends across India was conducted using data from the National Ambient Air Quality Monitoring Programme's manual monitoring stations in 336 cities. The study encompassed six geographical regions over three time blocks, revealing a correlation between the expansion of monitoring networks and the nation's economic growth. Regions like the densely populated Indo-Gangetic Plains (IGP) and Central India consistently hosted more monitoring stations, while the Himalayan and Northeast regions saw substantial increases from initial scarcity. SO2 concentrations showed a declining trend, while NO2 levels remained relatively stable with intermittent fluctuations. Conversely, national average PM10 concentrations exhibited an upward trajectory, notably spiking by 128 % between 2006 and 2009 due to economic activities, construction, network expansion, the 2009 drought, and heightened coal consumption. Spatially, pollutant concentrations across three blocks demonstrated improved SO2 levels, several cities exceeding NO2 standards, and persistently high PM10 levels in the IGP. PM10 levels in block 3 were lower than in block 2, reflecting effective policy interventions. State rankings, however, did not consistently reflect pollutant trends across blocks. Regionally, the IGP consistently had the highest PM10 concentrations, while the Northeast recorded the lowest. Population-weighted exposure levels indicated an overall increase in public exposure to PM10. Analysis of major city per region aligned with national trends, as evidenced by Delhi (IGP), Guwahati (Northeast), Vadodara (Northwest), and Bhopal (Central) showing increased PM10 concentrations since 2006, followed by intermittent declines. In contrast, Shimla (Himalayan) and Chennai (Southern) exhibited distinct patterns. Major industrial cities such as Parwanoo, Bongaigaon, Angul and Talcher, and Visakhapatnam mirrored national trends, with PM10 levels rising since 2009, highlighting the significant impact of industrial activities on air quality. This research underscores the need for targeted, effective mitigation strategies based on spatial and temporal pollutant trends.
Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Ciudades , Monitoreo del Ambiente , Material Particulado , India , Contaminación del Aire/estadística & datos numéricos , Monitoreo del Ambiente/métodos , Contaminantes Atmosféricos/análisis , Material Particulado/análisis , Dióxido de Azufre/análisis , Dióxido de Nitrógeno/análisisRESUMEN
Moringa oleifera is widely grown throughout the tropics and increasingly used for its therapeutic and nutraceutical properties. These properties are attributed to potent antioxidant and metabolism regulators, including glucosinolates/isothiocyanates as well as flavonoids, polyphenols, and phenolic acids. Research to date largely consists of geographically limited studies that only examine material available locally. These practices make it unclear as to whether moringa samples from one area are superior to another, which would require identifying superior variants and distributing them globally. Alternatively, the finding that globally cultivated moringa material is essentially functionally equivalent means that users can easily sample material available locally. We brought together accessions of Moringa oleifera from four continents and nine countries and grew them together in a common garden. We performed a metabolomic analysis of leaf extracts (MOLE) using an LC-MSMS ZenoTOF 7600 mass spectrometry system. The antioxidant capacity of leaf samples evaluated using the Total Antioxidant Capacity assay did not show any significant difference between extracts. MOLE samples were then tested for their antioxidant activity on C2C12 myotubes challenged with an oxidative insult. Hydrogen peroxide (H2O2) was added to the myotubes after pretreatment with different extracts. H2O2 exposure caused an increase in cell death that was diminished in all samples pretreated with moringa extracts. Our results show that Moringa oleifera leaf extract is effective in reducing the damaging effect of H2O2 in C2C12 myotubes irrespective of geographical origin. These results are encouraging because they suggest that the use of moringa for its therapeutic benefits can proceed without the need for the lengthy and complex global exchange of materials between regions.
Asunto(s)
Antioxidantes , Metabolómica , Moringa oleifera , Fibras Musculares Esqueléticas , Extractos Vegetales , Hojas de la Planta , Moringa oleifera/química , Moringa oleifera/metabolismo , Hojas de la Planta/química , Hojas de la Planta/metabolismo , Antioxidantes/farmacología , Antioxidantes/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/química , Metabolómica/métodos , Animales , Ratones , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/efectos de los fármacos , Línea Celular , Peróxido de Hidrógeno/metabolismo , Estrés Oxidativo/efectos de los fármacos , Metaboloma/efectos de los fármacosRESUMEN
Background and objective Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a significant global health concern, with India being a hotspot for the disease burden. Central nervous system (CNS) tuberculosis, though comprising a smaller proportion of total TB cases, is associated with significant morbidity and mortality. This study aimed to explore the utility of diffusion tensor imaging (DTI) in assessing the microstructural changes in white matter tracts associated with CNS tuberculosis. Materials and methods This study was conducted over two years at the All India Institute of Medical Sciences, Rishikesh. We employed a cross-sectional observational design and included patients with definite or highly probable tuberculous meningitis, alongside healthy controls. Results Our findings revealed a significant reduction in fractional anisotropy (FA) values in various white matter tracts of patients with CNS tuberculosis compared to healthy individuals. This reduction in FA correlated with the severity of tuberculous meningitis, particularly in the corpus callosum. Additionally, DTI highlighted distinct patterns of white matter involvement around intraparenchymal lesions, suggesting potential implications for clinical outcomes. The study emphasizes the utility of FA values in grading disease severity and prognosticating treatment outcomes in CNS tuberculosis. Conclusions Overall, this study provides valuable insights into the microstructural alterations in white matter tracts associated with CNS tuberculosis, highlighting the potential of DTI in early diagnosis, grading disease severity, and monitoring treatment response. We believe these findings will pave the way for further research to optimize the clinical management of this debilitating disease.
RESUMEN
INTRODUCTION: The determination of one's blood group is dictated by the inheritance-based diversity in the presence or absence of RBC antigens on the surface. Extended Rhesus (Rh) antigens are the most clinically relevant antigens of blood group systems after the ABO blood group system in transfusion medicine. The aim of this study was to serologically assess the prevalence of extended Rh antigens across diverse blood group systems. METHODS: A total of 2043 samples were tested for the ABO blood group and Rh typing with monoclonal antisera. The Rh phenotyping (C, c, E, e ) was performed on all the samples. RESULTS: The most frequently observed ABO blood group was O (36.5%), while AB (13.6%) was identified as the least prevalent. Positive Rh D antigen was found in 91.6% of tested samples, while 8.4% were Rh D-negative. The most frequently encountered antigen was e, followed by D, while the least prevalent was E. DISCUSSION: Establishing a Rh phenotype repository for blood donors and conducting Rh phenotype assessments as part of pretransfusion testing before initiating the initial blood transfusion for each patient could significantly lower the patients' incidence of alloimmunization.
RESUMEN
BACKGROUND: Elevated levels of lipoprotein(a) (Lp(a)) are independently associated with an increased risk of atherosclerotic cardiovascular disease events. However, the mechanisms driving this association are poorly understood. We aimed to evaluate the association between Lp(a) and coronary plaque characteristics in a contemporary US cohort without clinical atherosclerotic cardiovascular disease, undergoing coronary computed tomography angiography, the noninvasive gold standard for the assessment of coronary atherosclerosis. METHODS: We used baseline data from the Miami Heart Study-a community-based, prospective cohort study-which included asymptomatic adults aged 40 to 65 years evaluated using coronary computed tomography angiography. Those taking any lipid-lowering therapies were excluded. Elevated Lp(a) was defined as ≥125 nmol/L. Outcomes included any plaque, coronary artery calcium score >0, maximal stenosis ≥50%, presence of any high-risk plaque feature (positive remodeling, spotty calcification, low-attenuation plaque, napkin ring), and the presence of ≥2 high-risk plaque features. RESULTS: Among 1795 participants (median age, 52 years; 54.3% women; 49.6% Hispanic), 291 (16.2%) had Lp(a) ≥125 nmol/L. In unadjusted analyses, individuals with Lp(a) ≥125 nmol/L had a higher prevalence of all outcomes compared with Lp(a) <125 nmol/L, although differences were only statistically significant for the presence of any coronary plaque and ≥2 high-risk features. In multivariable models, elevated Lp(a) was independently associated with the presence of any coronary plaque (odds ratio, 1.40, [95% CI, 1.05-1.86]) and with ≥2 high-risk features (odds ratio, 3.94, [95% CI, 1.82-8.52]), although only 35 participants had this finding. Among participants with a coronary artery calcium score of 0 (n=1200), those with Lp(a) ≥125 nmol/L had a significantly higher percentage of any plaque compared with those with Lp(a) <125 nmol/L (24.2% versus 14.2%; P<0.001). CONCLUSIONS: In this contemporary analysis, elevated Lp(a) was independently associated with the presence of coronary plaque. Larger studies are needed to confirm the strong association observed with the presence of multiple high-risk coronary plaque features.
Asunto(s)
Enfermedades Asintomáticas , Biomarcadores , Angiografía por Tomografía Computarizada , Angiografía Coronaria , Enfermedad de la Arteria Coronaria , Lipoproteína(a) , Placa Aterosclerótica , Humanos , Persona de Mediana Edad , Femenino , Masculino , Lipoproteína(a)/sangre , Florida/epidemiología , Estudios Prospectivos , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/diagnóstico , Adulto , Biomarcadores/sangre , Anciano , Factores de Riesgo , Vasos Coronarios/diagnóstico por imagen , Regulación hacia Arriba , Valor Predictivo de las Pruebas , Medición de Riesgo , Prevalencia , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/epidemiología , Calcificación Vascular/sangreRESUMEN
Background: Relationships between the social determinants of health (SDOH) and cardiovascular health (CVH) of cancer survivors are underexplored. Objectives: This study sought to investigate associations between the SDOH and CVH of adult cancer survivors. Methods: Data from the U.S. National Health Interview Survey (2013-2017) were used. Participants reporting a history of cancer were included, excluding those with only nonmelanotic skin cancer, or with missing data for any domain of SDOH or CVH. SDOH was quantified with a 6-domain, 38-item score, consistent with the Centers for Disease Control and Prevention recommendations (higher score indicated worse deprivation). CVH was quantified based on the American Heart Association's Life's Essential 8, but due to unavailable detailed dietary data, a 7-item CVH score was used, with a higher score indicating worse CVH. Survey-specific multivariable Poisson regression was used to test associations between SDOH quartiles and CVH. Results: Altogether, 8,254 subjects were analyzed, representing a population of 10,887,989 persons. Worse SDOH was associated with worse CVH (highest vs lowest quartile: risk ratio 1.30; 95% CI: 1.25-1.35; P < 0.001), with a grossly linear relationship between SDOH and CVH scores. Subgroup analysis found significantly stronger associations in younger participants (P interaction = 0.026) or women (P interaction = 0.001) but without significant interactions with race (P interaction = 0.051). Higher scores in all domains of SDOH were independently associated with worse CVH (all P < 0.001). Higher SDOH scores were also independently associated with each component of the CVH score (all P < 0.05 for highest SDOH quartile). Conclusions: An unfavorable SDOH profile was independently associated with worse CVH among adult cancer survivors in the United States.
RESUMEN
Women are disproportionately affected by symptoms of angina with nonobstructive coronary arteries (ANOCA) which is associated with significant mortality and economic impact. Although distinct endotypes of ANOCA have been defined, it is underdiagnosed and is often incompletely characterized when identified. Patients are often unresponsive to traditional therapeutic options, which are typically antianginal, and the current ability to guide treatment modification by specific pathways is limited. Studies have associated specific genetic loci, transcriptomic features, and biomarkers with ANOCA. Such panomic data, in combination with known imaging and invasive diagnostic techniques, should be utilized to define more precise pathophysiologic subtypes of ANOCA in women, which will in turn help to identify targeted, effective therapies. A precision medicine-based approach to managing ANOCA incorporating these techniques in women has the potential to significantly improve their clinical care.
RESUMEN
Hypertensive disorders of pregnancy (HDP) complicate 13% to 15% of pregnancies in the United States. Historically marginalized communities are at increased risk, with preeclampsia and eclampsia being the leading cause of death in this population. Pregnant individuals with HDP require more frequent and intensive monitoring throughout the antepartum period outside of routine standard of care prenatal visits. Additionally, acute rises in blood pressure often occur 3 to 6 days postpartum and are challenging to identify and treat, as most postpartum individuals are usually scheduled for their first visit 6 weeks after delivery. Thus, a multifaceted approach is necessary to improve recognition and treatment of HDP throughout the peripartum course. There are limited studies investigating interventions for the management of HDP, especially within the United States, where maternal mortality is rising, and in higher-risk groups. We review the state of current management of HDP and innovative strategies such as blood pressure self-monitoring, telemedicine, and community health worker intervention.
RESUMEN
BACKGROUND: The non-toxic self-crosslinked hydrogel films designed from biocompatible materials allow for controlled drug release and have gathered remarkable attention from healthcare professionals as wound dressing materials. Thus, in the current study the chitosan (CS) film is infused with oil-in-water Pickering emulsion (PE) loaded with bioactive compound quercetin (Qu) and stabilized by dialdehyde cellulose nanocrystal-silver nanoparticles (DCNC-AgNPs). The DCNC-AgNPs play a dual role in stabilizing PE and are involved in the self-crosslinking with CS films. Also, this film could combine the advantage of the controlled release and synergistic wound-healing effect of Qu and AgNPs. RESULTS: The DCNC-AgNPs were synthesized using sodium periodate oxidation of CNC. The DCNC-AgNPs were used to stabilize oil-in-water PE loaded with Qu in its oil phase by high speed homogenization. Stable PEs were prepared by 20% v/v oil: water ratio with maximum encapsulation of Qu in the oil phase. The Qu-loaded PE was then added to CS solution (50% v/v) to prepare self-crosslinked films (CS-PE-Qu). After grafting CS films with PE, the surface and cross-sectional SEM images show an inter-penetrated network within the matrix between DCNC and CS due to the formation of a Schiff base bond between the reactive aldehyde groups of DCNC-AgNPs and amino groups of CS. Further, the addition of glycerol influenced the extensibility, swelling ratio, and drug release of the films. The fabricated CS-PE-Qu films were analyzed for their wound healing and tissue regeneration potential using cell scratch assay and full-thickness excisional skin wound model in mice. The as-fabricated CS-PE-Qu films showed great biocompatibility, increased HaCat cell migration, and promoted collagen synthesis in HDFa cells. In addition, the CS-PE-Qu films exhibited non-hemolysis and improved wound closure rate in mice compared to CS, CS-Qu, and CS-blank PE. The H&E staining of the wounded skin tissue indicated the wounded tissue regeneration in CS-PE-Qu films treated mice. CONCLUSION: Results obtained here confirm the wound healing benefits of CS-PE-Qu films and project them as promising biocompatible material and well suited for full-thickness wound healing in clinical applications.
Asunto(s)
Quitosano , Emulsiones , Hidrogeles , Nanopartículas del Metal , Quercetina , Plata , Piel , Cicatrización de Heridas , Quercetina/química , Quercetina/farmacología , Cicatrización de Heridas/efectos de los fármacos , Quitosano/química , Animales , Emulsiones/química , Ratones , Humanos , Piel/efectos de los fármacos , Piel/lesiones , Nanopartículas del Metal/química , Plata/química , Hidrogeles/química , Materiales Biocompatibles/química , Vendajes , Liberación de Fármacos , Sistemas de Liberación de Medicamentos/métodos , Celulosa/química , Masculino , Regeneración/efectos de los fármacos , Células HaCaT , Oxidación-Reducción , MetilgalactósidosRESUMEN
BACKGROUND: Cardiovascular health literacy (CVHL) and social determinants of health (SDoH) play interconnected and critical roles in shaping cardiovascular health (CVH) outcomes. However, awareness of CVH risk has declined markedly, from 65% of women being aware that cardiovascular disease (CVD) is the leading cause of death for women in 2009 to just 44% being aware in 2019. The American Heart Association Research Goes Red (RGR) initiative seeks to develop an open-source, longitudinal, dynamic registry that will help women to be aware of and participate in research studies, and to learn about CVD prevention. We proposed to leverage this platform, particularly among Black and Hispanic women of reproductive age, to address CVHL gaps and advance health equity. METHODS: The primary objective of the study is to evaluate the cross-sectional association of CVHL, SDoH using a polysocial score, and CVH in women of reproductive age at increased risk of developing hypertension (HTN). To achieve this we will use a cross-sectional study design, that engages women already enrolled in the RGR registry (registry-enrolled). To enhance the racial and ethnic/social economic diversity of the cohort, we will additionally enroll 300 women from the Baltimore and Washington D.C. community into the Social Determinants of the Risk of Hypertension in Women of Reproductive Age (SAFE HEART) Study. Community-enrolled and registry-enrolled women will undergo baseline social phenotyping including detailed SDoH questionnaire, CVH metrics assessment, and CVHL assessment. The secondary objective is to assess whether a 4-month active health education intervention will result in a change in CVHL in the 300 community-enrolled women. DISCUSSION: The SAFE HEART study examines the association between CVHL, SDoH, and CVH, with a focus on racial and ethnic minority groups and socioeconomically disadvantaged women of reproductive age, and the ability to improve these parameters by an educational intervention. These findings will inform the future development of community-engaged strategies that address CVHL and SDoH among women of reproductive age.