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1.
Res Sq ; 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38883799

RESUMEN

Microglia are the resident immune cells of the central nervous system (CNS). We and others have shown that the inflammatory response of microglia is partially regulated by the immunoproteasome, an inducible form of the proteasome responsible for the generation of major histocompatibility complex (MHC) class I epitopes. While the role of the proteasome in the adaptive immune system is well established, emerging evidence suggests the immunoproteasome may have discrete functions in the innate immune response. Here, we show that inhibiting the immunoproteasome reduces the IFNγ-dependent induction of complement activator C1q, suppresses phagocytosis, and alters the cytokine expression profile in a microglial cell line and microglia derived from human inducible pluripotent stem cells. Moreover, we show that the immunoproteasome regulates the degradation of IκBα, a modulator of NF-κB signaling. Finally, we demonstrate that NADH prevents induction of the immunoproteasome, representing a potential pathway to suppress immunoproteasome-dependent immune responses.

2.
Genes (Basel) ; 15(5)2024 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-38790257

RESUMEN

BACKGROUND: Sjögren's disease (SjD) is a common systemic autoimmune disease that affects mainly women. Key pathologic features include the infiltration of exocrine glands by lymphocytes and the activation of B lymphocytes with the production of autoantibodies. We aimed to analyze the transcriptome of circulating B cells from patients with SJD and healthy controls to decipher the B-cell-specific contribution to SJD. METHODS: RNA from peripheral blood B cells of five untreated female patients with SjD and positive ANA, positive anti-SSA (both Ro-52 and Ro-60), positive anti-SSB and positive rheumatoid-factor, and five healthy controls was subjected to whole-transcriptome sequencing. A false discovery rate of < 0.1 was applied to define differentially expressed genes (DEG). RESULTS: RNA-sequencing identified 56 up and 23 down DEG. Hierarchal clustering showed a clear separation between the two groups. Ingenuity pathway analysis revealed that these genes may play a role in interferon signaling, chronic mycobacterial infection, and transformation to myeloproliferative disorders. CONCLUSIONS: We found upregulated expression of type-I and type-II interferon (IFN)-induced genes, as well as genes that may contribute to other concomitant conditions, including infections and a higher risk of myeloproliferative disorders. This adds insight into the autoimmune process and suggests potential targets for future functional and prognostic studies.


Asunto(s)
Linfocitos B , Perfilación de la Expresión Génica , Síndrome de Sjögren , Transcriptoma , Humanos , Síndrome de Sjögren/genética , Síndrome de Sjögren/inmunología , Femenino , Linfocitos B/inmunología , Linfocitos B/metabolismo , Persona de Mediana Edad , Perfilación de la Expresión Génica/métodos , Interferones/genética , Interferones/metabolismo , Adulto , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Autoanticuerpos/genética , Anciano
3.
Artículo en Inglés | MEDLINE | ID: mdl-38702491

RESUMEN

BACKGROUND: Healthcare disparities adversely affect clinical outcomes in racial and ethnic minorities. Chronic pancreatitis (CP) is a complex disorder, and pressures for time and cost-containment may amplify the disparity for minorities in this condition. This study aimed to assess ethno-racial differences in the clinical outcomes of CP patients cared for at our institution. METHODS: This is a study of CP patients with available ethno-racial information followed at our pancreas center. We reviewed their demographics, comorbidities, clinical outcomes, and resource utilization: pain, frequent flares (≥ 2/year), local complications, psychosocial variables, exocrine, and endocrine insufficiency, imaging, endoscopic procedures, and surgeries. The outcomes underwent logistic regression to ascertain association(s) with covariates and were expressed as odds ratio (95% confidence intervals). RESULTS: Of the 445 CP patients, there were 23 Hispanics, 330 Non-Hispanic Whites, 47 Non-Hispanic Blacks, 16 Asian Americans, and 29 patients from Other/mixed races. Over a median follow-up of 7 years, no significant differences in the pain profile (p = 0.36), neuromodulator use (p = 0.94), and opioid use for intermittent (p = 0.34) and daily pain (p = 0.80) were observed. Frequent flares were associated with Hispanic ethnicity [2.98(1.20-7.36); p = 0.02], despite adjustment for smoking [2.21(1.11-4.41); p = 0.02)] and alcohol [1.88(1.06-3.35); p = 0.03]. Local complications (pseudocysts, mesenteric thrombosis, and biliary obstruction), exocrine and endocrine dysfunction, and healthcare resource utilization (cross-sectional imaging, endoscopic procedures, celiac blocks, or surgeries) were comparable across all ethno-racial groups. CONCLUSIONS: Although no significant differences in clinical outcomes, and health resource utilization were noted across ethno-racial groups, Hispanic ethnicity had significant association with CP flares. This study calls for further investigation of an understudied minority population with CP.

4.
Dig Dis Sci ; 69(6): 2247-2255, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38649654

RESUMEN

BACKGROUND AND AIM: Food access is an important social determinant of health and refers to geographical and infrastructural aspects of food availability. Using publicly available data on food access from the United States Department of Agriculture (USDA), geospatial analyses can identify regions with variable food access, which may impact acute pancreatitis (AP), an acute inflammatory condition characterized by unpredictable outcomes and substantial mortality. This study aimed to investigate the association of clinical outcomes in patients with AP with geospatial food access. METHODS: We examined AP-related hospitalizations at a tertiary center from January 2008 to December 2018. The physical addresses were geocoded through ArcGIS Pro2.7.0 (ESRI, Redlands, CA). USDA Food Access Research Atlas defined low food access as urban areas with 33% or more of the population residing over one mile from the nearest food source. Regression analyses enabled assessment of the association between AP outcomes and food access. RESULTS: The study included 772 unique patients with AP residing in Massachusetts with 931 AP-related hospitalizations. One hundred and ninety-eight (25.6%) patients resided in census tracts with normal urban food access and 574 (74.4%) patients resided in tracts with low food access. AP severity per revised Atlanta classification [OR 1.88 (95%CI 1.21-2.92); p = 0.005], and 30-day AP-related readmission [OR 1.78(95%CI 1.11-2.86); p = 0.02] had significant association with food access, despite adjustment for demographics, healthcare behaviors, and comorbidities (Charlson Comorbidity Index). However, food access lacked significant association with AP-related mortality (p = 0.40) and length of stay (LOS: p = 0.99). CONCLUSION: Low food access had a significant association with 30-day AP-related readmissions and AP severity. However, mortality and LOS lacked significant association with food access. The association between nutrition, lifestyle, and AP outcomes warrants further prospective investigation.


Asunto(s)
Pancreatitis , Humanos , Masculino , Femenino , Pancreatitis/mortalidad , Pancreatitis/epidemiología , Pancreatitis/terapia , Persona de Mediana Edad , Adulto , Massachusetts/epidemiología , Anciano , Hospitalización/estadística & datos numéricos , Abastecimiento de Alimentos/estadística & datos numéricos , Estudios Retrospectivos , Readmisión del Paciente/estadística & datos numéricos , Índice de Severidad de la Enfermedad
5.
Am J Gastroenterol ; 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38417043

RESUMEN

INTRODUCTION: Moderate-to-severe inflammatory bowel disease treatment transitioned from step-up therapy to induction of remission with a biologic agent, but insurance coverage varies. METHODS: Top 50 insurance companies were searched for publicly available policies for 5 biologic/small molecule agents. Data regarding coverage requirements were compared with American College of Gastroenterology/American Gastroenterological Association guidelines. RESULTS: Thirty-four insurers had public policies. Adherence to American College of Gastroenterology/American Gastroenterological Association guidelines ranged from 5.8% to 58.8%. Only 14.71% and 17.65% of policies permitted any first-line biologic therapy in Crohn's disease and in ulcerative colitis. DISCUSSION: Nearly every insurance company required failure of steroids and immunomodulators before biologic therapy. Further work is required to improve patient access to standard-of-care treatment.

6.
Pancreas ; 53(2): e187-e192, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38127842

RESUMEN

OBJECTIVE: Our study aimed to determine the prevalence of sexual dysfunction (SD) and its association with quality of life (QOL) in men with chronic pancreatitis (CP). MATERIALS AND METHODS: Male patients with CP were prospectively enrolled in our pancreas center and completed the following 4 validated questionnaires: International Index of Erectile Function 5, Erectile Hardness Score, Pancreatitis Quality of Life Instrument, and Short Form Survey. Patients were classified as having mild, moderate, or severe SD based on review of questionnaires. RESULTS: Thirty patients were enrolled in the study, of which 18 patients had SD (mild in 9, moderate in 1, and severe in 8 patients). No significant differences were seen demographic or clinical characteristics in patients with and without SD. Patients with SD had more abdominal pain compared with those without SD (94.4% vs 83.3%, P = 0.001). No significant differences were noted in QOL metrics between the 2 groups. CONCLUSIONS: This pilot study shows that SD is present in 60% males with CP. No difference was noted in the QOL of patients with and without SD, albeit limited by our small sample size. Physicians caring for CP patients should routinely inquire for symptoms of SD and offer a urology referral if indicated.


Asunto(s)
Pancreatitis Crónica , Disfunciones Sexuales Fisiológicas , Humanos , Masculino , Femenino , Calidad de Vida , Proyectos Piloto , Disfunciones Sexuales Fisiológicas/epidemiología , Disfunciones Sexuales Fisiológicas/etiología , Pancreatitis Crónica/complicaciones , Encuestas y Cuestionarios
7.
Nutrients ; 15(21)2023 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-37960149

RESUMEN

Vegetables are an essential component of a healthy dietary pattern in children; however, their consumption is often insufficient due to lack of preference. To address this, the influence of combining vegetables (mixed peas and carrots-MPACs) with potatoes, a generally liked food, on overall vegetable consumption among children aged 7-13 years was explored. The research involved a cross-over study design with 65 participants who completed five lunchtime meal conditions, each with different combinations of MPACs and potatoes versus a control (MPACs with a wheat roll). The meals were provided in a cafeteria setting, and plate waste was used to measure vegetable consumption. Anthropometric data and other variables were also measured. Notably, self-reported hunger did not significantly differ between conditions. Meal condition was a significant predictor of MPACs (F = 5.20; p = 0.0005), with MPAC consumption highest when combined with shaped potato faces in the same bowl (+8.77 g compared to serving MPACs and shaped potato faces in separate bowls) and lowest when combined with diced potatoes in the same bowl (-2.85 g compared to serving MPACs and diced potatoes in separate bowls). The overall model for MPAC consumption was influenced by age, height z-score, body fat percentage z-score, and condition (likelihood ratio = 49.1; p < 0.0001). Age had the strongest correlation with vegetable consumption (r = 0.38), followed by male gender, height z-score (r = 0.30), and body fat z-score (r = -0.15). The results highlight the positive impact of combining potatoes with vegetables in school meals, particularly when using shaped potato faces. These findings emphasize the potential of potatoes as a valuable vegetable option in promoting healthier eating habits among children. Additionally, future research could explore the impact of different potato combinations and investigate other factors influencing meal consumption in school settings.


Asunto(s)
Solanum tuberosum , Verduras , Niño , Humanos , Masculino , Estudios Cruzados , Dieta , Conducta Alimentaria , Frutas , Femenino , Adolescente
8.
Ann Gastroenterol ; 36(6): 624-629, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38023973

RESUMEN

Background: As marijuana use is rising among patients with inflammatory bowel disease (IBD), so is interest in its potential use as a therapeutic agent. We sought to survey IBD patients regarding marijuana use, self-reported impact on IBD symptoms, and perceptions of safety. Methods: A multicenter anonymous survey was administered to patients with IBD between October 2020 and June 2021. The 70-question survey collected demographic variables, clinical variables, attitudes about marijuana, and perceptions of its safety and efficacy in IBD. Participants were classified by their marijuana use: "rarely/never," "current," and "former". Percentage and chi-square tests were used to compare categorical variables between the 3 groups, and means and 2-group ANOVA were used for continuous variables. Results: Of 181 patients surveyed, 166 were eligible for the study. Of these, 70 (42.2%) participants were rare/never marijuana users, 44 (26.5%) were current users, and 52 (31.3%) were former users. Fifty-three percent thought marijuana would help with IBD inflammation and 80% thought it would help with IBD pain. Over 70% of patients from all groups thought marijuana had a low-to-moderate risk of harm, and 69.6% of the participants who never or rarely used marijuana thought marijuana was addictive, compared to 20.5% of the current users and 44% of the former marijuana users. Conclusions: While many patients thought marijuana use helps with IBD-related pain and inflammation, many expressed concerns about addiction to marijuana and a possible risk of harm. Further studies are needed to examine the benefit and harm of marijuana in IBD.

9.
Neurooncol Adv ; 5(1): vdad123, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37841698

RESUMEN

Background: Neurofibromatosis type 2 (NF2)-related schwannomatosis is an autosomal dominant tumor-predisposition syndrome characterized by bilateral vestibular schwannomas (VS). In patients with VS associated with NF2, vascular endothelial growth factor A inhibitor, bevacizumab, is a systemic treatment option. The aim of this study is to retrospectively evaluate NF2 patient responses to bevacizumab on VS growth and symptom progression. Methods: This is a retrospective analysis of patients seen at the Mayo Clinic Rochester Multidisciplinary NF2 Clinic. Results: Out of 76 patients with NF2 evaluated between 2020 and 2022, we identified 19 that received treatment with bevacizumab. Thirteen of these patients discontinued bevacizumab after median treatment duration of 12.2 months. The remaining 6 patients are currently receiving bevacizumab treatment for a median duration of 9.4 months as of March, 2023. Fifteen patients had evaluable brain MRI data, which demonstrated partial responses in 5 patients, stable disease in 8, and progression in 2. Within 6 months of bevacizumab discontinuation, 5 patients had rebound growth of their VS greater than 20% from their previous tumor volume, while 3 did not. Three patients with rebound growth went on to have surgery or irradiation for VS management. Conclusions: Our single-institution experience confirms prior studies that bevacizumab can control progression of VS and symptoms associated with VS growth. However, we note that there is the potential for rapid VS growth following bevacizumab discontinuation, for which we propose heightened surveillance imaging and symptom monitoring for at least 6 months upon stopping anti-VEGF therapy.

10.
Int J Mol Sci ; 24(13)2023 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-37446382

RESUMEN

Sperm cells must undergo a complex maturation process after ejaculation to be able to fertilize an egg. One component of this maturation is hyperpolarization of the membrane potential to a more negative value. The ion channel responsible for this hyperpolarization, SLO3, was first cloned in 1998, and since then much progress has been made to determine how the channel is regulated and how its function intertwines with various signaling pathways involved in sperm maturation. Although Slo3 was originally thought to be present only in the sperm of mammals, recent evidence suggests that a primordial form of the gene is more widely expressed in some fish species. Slo3, like many reproductive genes, is rapidly evolving with low conservation between closely related species and different regulatory and pharmacological profiles. Despite these differences, SLO3 appears to have a conserved role in regulating sperm membrane potential and driving large changes in response to stimuli. The effect of this hyperpolarization of the membrane potential may vary among mammalian species just as the regulation of the channel does. Recent discoveries have elucidated the role of SLO3 in these processes in human sperm and provided tools to target the channel to affect human fertility.


Asunto(s)
Canales de Potasio de Gran Conductancia Activados por el Calcio , Semen , Animales , Masculino , Humanos , Potenciales de la Membrana/fisiología , Canales de Potasio de Gran Conductancia Activados por el Calcio/metabolismo , Semen/metabolismo , Espermatozoides/metabolismo , Transducción de Señal , Mamíferos/metabolismo
11.
Pancreatology ; 23(3): 299-305, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36870814

RESUMEN

BACKGROUND: While acute pancreatitis (AP) contributes significantly to hospitalizations and costs, most cases are mild with minimal complications. In 2016, we piloted an observation pathway in the emergency department (ED) for mild AP and showed reduced admissions and length of stay (LOS) without increased readmissions or mortality. After 5 years of implementation, we evaluated outcomes of the ED pathway and identified predictors of successful discharge. METHODS: We reviewed a prospectively enrolled cohort of patients with mild AP presenting to a tertiary care center ED between 10/2016 and 9/2021, evaluating LOS, charges, imaging, and 30-day readmission, and assessed predictors of successful ED discharge. Patients were divided into two main groups: successfully discharged via the ED pathway ("ED cohort") and admitted to the hospital ("admission cohort"), with subgroups to compare outcomes, and multivariate analysis to determine predictors of discharge. RESULTS: Of 619 AP patients, 419 had mild AP (109 ED cohort, 310 admission cohort). The ED cohort was younger (age 49.3 vs 56.3,p < 0.001), had lower Charlson Comorbidity Index (CCI) (1.30 vs 2.43, p < 0.001), shorter LOS (12.3 h vs 116 h, p < 0.001), lower charges (mean $6768 vs $19886, p < 0.001) and less imaging, without differences in 30-day readmissions. Increasing age (OR: 0.97; p < 0.001), increasing CCI (OR: 0.75; p < 0.001) and biliary AP (OR: 0.10; p < 0.001) were associated with decreased ED discharge, while idiopathic AP had increased ED discharge (OR: 7.8; p < 0.001). CONCLUSIONS: After appropriate triage, patients with mild AP (age <50, CCI <2, idiopathic AP) can safely discharge from the ED with improved outcomes and cost savings.


Asunto(s)
Pancreatitis , Alta del Paciente , Humanos , Persona de Mediana Edad , Pancreatitis/terapia , Enfermedad Aguda , Hospitalización , Readmisión del Paciente , Tiempo de Internación , Servicio de Urgencia en Hospital , Estudios Retrospectivos , Literatura de Revisión como Asunto
12.
Res Sq ; 2023 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-36945376

RESUMEN

Throughout the menstrual cycle, spontaneous mild contractions in the inner layer of the uterine smooth muscle cause uterine peristalsis, which plays a critical role in normal menstruation and fertility. Disruptions in peristalsis patterns may occur in women experiencing subfertility, abnormal uterine bleeding, ovulatory dysfunction, endometriosis, and other disorders. However, current tools to measure uterine peristalsis in humans have limitations that hamper their research or clinical utilities. Here, we describe an electrophysiological imaging system to noninvasively quantify the four-dimensional (4D) electrical activation pattern during human uterine peristalsis with high spatial and temporal resolution and coverage. We longitudinally imaged 4968 uterine peristalses in 17 participants with normal gynecologic anatomy and physiology over 34 hours and 679 peristalses in 5 participants with endometriosis over 12.5 hours throughout the menstrual cycle. Our data provide quantitative evidence that uterine peristalsis changes in frequency, direction, duration, magnitude, and power throughout the menstrual cycle and is disrupted in endometriosis patients. Moreover, our data suggest that disrupted uterine peristalsis contributes to excess retrograde menstruation and infertility in patients with endometriosis and potentially contributes to infertility in this cohort.

13.
Am J Physiol Lung Cell Mol Physiol ; 324(4): L536-L549, 2023 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-36852927

RESUMEN

Interstitial macrophages (IMs) reside in the lung tissue surrounding key structures including airways, vessels, and alveoli. Recent work has described IM heterogeneity during homeostasis, however, there are limited data on IMs during inflammation. We sought to characterize IM origin, subsets, and transcriptomic profiles during homeostasis and lipopolysaccharide (LPS) induced acute lung inflammation. During homeostasis, we used three complementary methods, spectral flow cytometry, single-cell RNA-sequencing, and gene regulatory network enrichment, to demonstrate that IMs can be divided into two core subsets distinguished by surface and transcriptional expression of folate receptor ß (Folr2/FRß). These subsets inhabited distinct niches within the lung interstitium. Within FRß+ IMs we identified a subpopulation marked by coexpression of LYVE1. During acute LPS-induced inflammation, lung IM numbers expand. Lineage tracing revealed IM expansion was due to recruitment of monocyte-derived IMs. At the peak of inflammation, recruited IMs were comprised two unique subsets defined by expression of genes associated with interferon signaling and glycolytic pathways. As recruited IMs matured, they adopted the overall transcriptional state of FRß- resident IMs but retained expression in several origin-specific genes, such as IL-1ß. FRß+ IMs were of near-pure resident origin. Taken together our data show that during LPS-induced inflammation, there are distinct populations of IMs that likely have unique functions. FRΒ+ IMs comprise a stable, resident population, whereas FRß- ΙΜs represent a mixed population of resident and recruited IMs.


Asunto(s)
Receptor 2 de Folato , Neumonía , Humanos , Monocitos/metabolismo , Lipopolisacáridos/farmacología , Lipopolisacáridos/metabolismo , Macrófagos/metabolismo , Neumonía/inducido químicamente , Neumonía/genética , Neumonía/metabolismo , Inflamación/genética , Inflamación/metabolismo , Análisis de Secuencia de ARN/métodos , Receptor 2 de Folato/metabolismo
14.
J Educ Health Promot ; 12: 421, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38333164

RESUMEN

BACKGROUND: In medical school and residency, clinical experiences influence trainee's decisions on what medical specialty they choose. Most trainees have limited access to opportunities to engage in the field of reproductive endocrinology and infertility (REI). Due to the COVID-19 pandemic and the shutdown of away electives, exposure to REI was especially limited. This study aims to evaluate the effectiveness of a live Q and A webinar on improving trainees' access to mentorship and knowledge of the path to becoming a reproductive endocrinology and infertility (REI) physician. MATERIALS AND METHODS: This study is a prospective paired cohort study. Medical students and OBGYN residents participated in a global Q and A webinar featuring REI physicians and fellows. 70 pre- and post-webinar surveys were included in the analysis. Paired nonparametric tests (Wilcoxon signed-rank test) were performed to assess whether post-webinar knowledge was significantly different from pre-webinar knowledge. RESULTS: Of the 268 registrants, 162 (60%) attended the live webinar. A majority of the respondents who completed both surveys were female (90%) and allopathic medical students (80%). Seventy-seven percent reported receiving only minimal advice about an REI career from their medical school or residency program, while 22% reported receiving some advice, and 1% extensive advice. Thirty-four percent had previously shadowed an REI physician and 23% had rotated in an REI office. Post-webinar significantly more trainees had a better understanding of the REI field, the path required to become an REI physician, opportunities to find mentors in the field, opportunities that are conducive to learning more about REI, and applying for rotations in the REI field (p = <.00001). Eighty-two percent agreed that their interest in REI increased due to this webinar. CONCLUSIONS: A webinar featuring REI physicians and fellows was effective in providing mentorship and career advisement for prospective REI trainees who otherwise expressed having limited access to the field.

15.
Am J Physiol Lung Cell Mol Physiol ; 323(1): L69-L83, 2022 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-35670474

RESUMEN

The acute respiratory distress syndrome (ARDS) is a major healthcare problem, accounting for significant mortality and long-term disability. Approximately 25% of patients with ARDS will develop an overexuberant fibrotic response, termed fibroproliferative ARDS (FP-ARDS) that portends a poor prognosis and increased mortality. The cellular pathological processes that drive FP-ARDS remain incompletely understood. We have previously shown that the transmembrane receptor-type tyrosine phosphatase protein tyrosine phosphatase-α (PTPα) promotes pulmonary fibrosis in preclinical murine models through regulation of transforming growth factor-ß (TGF-ß) signaling. In this study, we examine the role of PTPα in the pathogenesis of FP-ARDS in a preclinical murine model of acid (HCl)-induced acute lung injury. We demonstrate that although mice genetically deficient in PTPα (Ptpra-/-) are susceptible to early HCl-induced lung injury, they exhibit markedly attenuated fibroproliferative responses. In addition, early profibrotic gene expression is reduced in lung tissue after acute lung injury in Ptpra-/- mice, and stimulation of naïve lung fibroblasts with the BAL fluid from these mice results in attenuated fibrotic outcomes compared with wild-type littermate controls. Transcriptomic analyses demonstrate reduced extracellular matrix (ECM) deposition and remodeling in mice genetically deficient in PTPα. Importantly, human lung fibroblasts modified with a CRISPR-targeted deletion of PTPRA exhibit reduced expression of profibrotic genes in response to TGF-ß stimulation, demonstrating the importance of PTPα in human lung fibroblasts. Together, these findings demonstrate that PTPα is a key regulator of fibroproliferative processes following acute lung injury and could serve as a therapeutic target for patients at risk for poor long-term outcomes in ARDS.


Asunto(s)
Lesión Pulmonar Aguda , Fibrosis Pulmonar , Proteínas Tirosina Fosfatasas Clase 4 Similares a Receptores , Síndrome de Dificultad Respiratoria , Lesión Pulmonar Aguda/metabolismo , Lesión Pulmonar Aguda/patología , Animales , Pulmón/metabolismo , Ratones , Monoéster Fosfórico Hidrolasas/metabolismo , Fibrosis Pulmonar/patología , Proteínas Tirosina Fosfatasas Clase 4 Similares a Receptores/metabolismo , Síndrome de Dificultad Respiratoria/metabolismo , Síndrome de Dificultad Respiratoria/patología , Factor de Crecimiento Transformador beta/metabolismo
16.
J Assist Reprod Genet ; 39(7): 1571-1576, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35713749

RESUMEN

PURPOSE: To study patient satisfaction with new patient telehealth visits in a reproductive endocrinology and infertility (REI) office. METHODS: A cross-sectional study in a university-based fertility clinic was completed including all new patients seen via telehealth between March 1, 2021, and August 19, 2021. Primary outcomes were perceived patient satisfaction, access, and preferences to telehealth visits. RESULTS: A total of 351 participants were contacted, 61.8% (n = 217) agreed to participate in the study, and 28.8% (n = 101) completed the survey. There were no significant differences in age, BMI, distance from clinic, or length of infertility with response to survey. Ninety-three percent of responders would use telehealth services again and were satisfied with the telehealth system. Telehealth improved access to healthcare for 88% and travel time for 96%. The median distance from clinic was 24 miles, and there was no significance difference in preference for telehealth visits over in person visits (p = 0.696). CONCLUSIONS: In the era of COVID-19, healthcare implementation has dramatically changed with a drastic increase in telehealth services. Based on our survey, majority of patients were satisfied with telehealth visits and believed it saved travel time while improving access to REI care. Despite no differences in patient preference for in person versus telehealth depending on their distance from clinic, this is reassuring because patients are satisfied with telehealth for reasons other than distance from clinic.


Asunto(s)
COVID-19 , Infertilidad , Telemedicina , COVID-19/epidemiología , Estudios Transversales , Humanos , Satisfacción del Paciente , Satisfacción Personal
19.
Pancreas ; 51(9): 1167-1170, 2022 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37078941

RESUMEN

OBJECTIVE: Up to 30% of acute pancreatitis (AP) cases do not have an established etiology (idiopathic AP [IAP]). We evaluated the characteristics and outcomes of hospitalized IAP patients compared with those with established AP cause (non-IAP). METHODS: A retrospective study of AP patients admitted to a single center from 2008 to 2018 was performed. Patients were divided into IAP and non-IAP groups. Outcomes included mortality, 30-day and 1-year readmission, length of stay (LOS), intensive care unit admissions, and complications. RESULTS: Of 878 AP patients, 338 had IAP and 540 non-IAP (234 gallstone, 178 alcohol). Groups had similar demographics, Charlson Comorbidity Index, and pancreatitis severity. The IAP patients had more 1-year readmissions (0.64 vs 0.55, P = 0.006) but similar 30-day readmissions and mortality. Patients with IAP had shorter LOS (4.98 vs 5.99 days, P = 0.01), and fewer intensive care unit admissions (3.25% vs 6.85%, P = 0.03) and extrapancreatic complications (15.4% vs 25.2%, P = 0.001). There was no difference in pain level between groups. CONCLUSIONS: The IAP patients tend to have more readmissions in 1 year, but less severe presentations, shorter LOS, and fewer complications. Readmission rates may be related to lack of defined etiology and treatment to prevent recurrence.


Asunto(s)
Pancreatitis , Humanos , Pancreatitis/complicaciones , Pancreatitis/diagnóstico , Pancreatitis/terapia , Estudios Retrospectivos , Enfermedad Aguda , Hospitalización , Tiempo de Internación
20.
PLoS One ; 16(12): e0260718, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34855868

RESUMEN

Cardiovascular risk stratification is often performed in patients considered for renal transplantation. In a single center, we sought to examine the association between abnormal stress testing with imaging and post-renal transplant major adverse cardiovascular events (MACE) using multivariable logistic regression. From January 2006 to May 2016 232 patients underwent renal transplantation and 59 (25%) had an abnormal stress test result. Compared to patients with a normal stress test, patients with an abnormal stress test had a higher prevalence of dyslipidemia, diabetes mellitus, obesity, coronary artery disease (CAD), and heart failure. Among those with an abnormal result, 45 (76%) had mild, 10 (17%) moderate, and 4 (7%) severe ischemia. In our cohort, 9 patients (3.9%) had MACE at 30-days post-transplant, 5 of whom had an abnormal stress test. The long-term MACE rate, at a median of 5 years, was 32%. After adjustment, diabetes (OR 2.37, 95% CI 1.12-5.00, p = 0.02), CAD (OR: 3.05, 95% CI 1.30-7.14, p = 0.01) and atrial fibrillation (OR: 5.86, 95% CI 1.86-18.44, p = 0.002) were independently associated with long-term MACE, but an abnormal stress test was not (OR: 0.83, 95% CI 0.37-1.92, p = 0.68). In conclusion, cardiac stress testing was not an independent predictor of long-term MACE among patients undergoing renal transplant.


Asunto(s)
Enfermedades Cardiovasculares/complicaciones , Prueba de Esfuerzo , Trasplante de Riñón , Insuficiencia Renal Crónica/complicaciones , Adulto , Fibrilación Atrial/complicaciones , Fibrilación Atrial/epidemiología , Enfermedades Cardiovasculares/epidemiología , Complicaciones de la Diabetes/epidemiología , Complicaciones de la Diabetes/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Insuficiencia Renal Crónica/patología , Insuficiencia Renal Crónica/terapia , Estudios Retrospectivos , Factores de Riesgo
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