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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.
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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.
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Pancreatite , Humanos , Masculino , Feminino , Pancreatite/mortalidade , Pancreatite/epidemiologia , Pancreatite/terapia , Pessoa de Meia-Idade , Adulto , Massachusetts/epidemiologia , Idoso , Hospitalização/estatística & dados numéricos , Abastecimento de Alimentos/estatística & dados numéricos , Estudos Retrospectivos , Readmissão do Paciente/estatística & dados numéricos , Índice de Gravidade de DoençaRESUMO
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.
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Receptor 2 de Folato , Pneumonia , Humanos , Monócitos/metabolismo , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/metabolismo , Macrófagos/metabolismo , Pneumonia/induzido quimicamente , Pneumonia/genética , Pneumonia/metabolismo , Inflamação/genética , Inflamação/metabolismo , Análise de Sequência de RNA/métodos , Receptor 2 de Folato/metabolismoRESUMO
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.
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Pancreatite , Alta do Paciente , Humanos , Pessoa de Meia-Idade , Pancreatite/terapia , Doença Aguda , Hospitalização , Readmissão do Paciente , Tempo de Internação , Serviço Hospitalar de Emergência , Estudos Retrospectivos , Literatura de Revisão como AssuntoRESUMO
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.
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Canais de Potássio Ativados por Cálcio de Condutância Alta , Sêmen , Animais , Masculino , Humanos , Potenciais da Membrana/fisiologia , Canais de Potássio Ativados por Cálcio de Condutância Alta/metabolismo , Sêmen/metabolismo , Espermatozoides/metabolismo , Transdução de Sinais , Mamíferos/metabolismoRESUMO
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.
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Lesão Pulmonar Aguda , Fibrose Pulmonar , Proteínas Tirosina Fosfatases Classe 4 Semelhantes a Receptores , Síndrome do Desconforto Respiratório , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Animais , Pulmão/metabolismo , Camundongos , Monoéster Fosfórico Hidrolases/metabolismo , Fibrose Pulmonar/patologia , Proteínas Tirosina Fosfatases Classe 4 Semelhantes a Receptores/metabolismo , Síndrome do Desconforto Respiratório/metabolismo , Síndrome do Desconforto Respiratório/patologia , Fator de Crescimento Transformador beta/metabolismoRESUMO
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.
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COVID-19 , Infertilidade , Telemedicina , COVID-19/epidemiologia , Estudos Transversais , Humanos , Satisfação do Paciente , Satisfação PessoalRESUMO
BACKGROUND: Regeneration of complex patterned structures is well described among, although limited to a small sampling of, amphibians. This limitation impedes our understanding of the full range of regenerative competencies within this class of vertebrates, according to phylogeny, developmental life stage, and age. To broaden the phylogenetic breath of this research, we characterized the regenerative capacity of the Texas blind salamander (Eurycea rathbuni), a protected salamander native to the Edwards Aquifer of San Marcos, Texas and colonized by the San Marcos Aquatic Resource Center. As field observations suggested regenerative abilities in this population, the forelimb stump of a live captured female was amputated in the hopes of restoring the structure, and thus locomotion in the animal. Tails were clipped from two males to additionally document tail regeneration. RESULTS: We show that the Texas blind salamander exhibits robust limb and tail regeneration, like all other studied Plethodontidae. Regeneration in this species is associated with wound epithelium formation, blastema formation, and subsequent patterning and differentiation of the regenerate. CONCLUSIONS: The study has shown that the Texas blind salamander is a valuable model to study regenerative processes, and that therapeutic surgeries offer a valuable means to help maintain and conserve this vulnerable species.
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Membro Anterior/fisiologia , Regeneração/fisiologia , Cauda/fisiologia , Urodelos/fisiologia , Animais , Diferenciação Celular/fisiologia , Feminino , Masculino , Filogenia , Urodelos/crescimento & desenvolvimentoRESUMO
OBJECTIVE: MicroRNA-126-3p (miR-126) is required for angiogenesis during organismal development or the repair of injured arterial vasculature. The role of miR-126 in lung microvascular endothelial cells, which are essential for gas exchange and for lung injury repair and regeneration, remains poorly understood. Considering the significant heterogeneity of endothelial cells from different vascular beds, we aimed to determine the role of miR-126 in regulating lung microvascular endothelial cell function and to elucidate its downstream signaling pathways. Approach and Results: Overexpression and knockdown of miR-126 in primary human lung microvascular endothelial cells (HLMVEC) were achieved via transfections of miR-126 mimics and antisense inhibitors. Increasing miR-126 levels in HLMVEC reduced cell proliferation, weakened tube formation, and increased cell apoptosis, whereas decreased miR-126 levels stimulated cell proliferation and tube formation. Whole-genome RNA sequencing revealed that miR-126 was associated with an antiangiogenic and proapoptotic transcriptomic profile. Using validation assays and knockdown approaches, we identified that the effect of miR-126 on HLMVEC angiogenesis was mediated by the LAT1 (L-type amino acid transporter 1), via regulation of mTOR (mammalian target of rapamycin) signaling. Furthermore, downregulation of miR-126 in HLMVEC inhibited cell apoptosis and improved endothelial tube formation during exposure to environmental insults such as cigarette smoke. CONCLUSIONS: miR-126 inhibits HLMVEC angiogenic function by targeting the LAT1-mTOR signaling axis, suggesting that miR-126 inhibition may be useful for conditions associated with microvascular loss, whereas miR-126 augmentation may help control unwanted microvascular angiogenesis.
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Células Endoteliais/metabolismo , Transportador 1 de Aminoácidos Neutros Grandes/metabolismo , Pulmão/irrigação sanguínea , MicroRNAs/metabolismo , Microvasos/metabolismo , Neovascularização Fisiológica , Proteínas ADAM/genética , Proteínas ADAM/metabolismo , Apoptose , Movimento Celular , Proliferação de Células , Células Cultivadas , Regulação da Expressão Gênica , Humanos , Transportador 1 de Aminoácidos Neutros Grandes/genética , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , MicroRNAs/genética , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismoRESUMO
Idiopathic pulmonary fibrosis (IPF) is a progressive, often fatal, fibrosing lung disease for which treatment remains suboptimal. Fibrogenic cytokines, including transforming growth factor-ß (TGF-ß), are central to its pathogenesis. Protein tyrosine phosphatase-α (PTPα) has emerged as a key regulator of fibrogenic signaling in fibroblasts. We have reported that mice globally deficient in PTPα (Ptpra-/-) were protected from experimental pulmonary fibrosis, in part via alterations in TGF-ß signaling. The goal of this study was to determine the lung cell types and mechanisms by which PTPα controls fibrogenic pathways and whether these pathways are relevant to human disease. Immunohistochemical analysis of lungs from patients with IPF revealed that PTPα was highly expressed by mesenchymal cells in fibroblastic foci and by airway and alveolar epithelial cells. To determine whether PTPα promotes profibrotic signaling pathways in lung fibroblasts and/or epithelial cells, we generated mice with conditional (floxed) Ptpra alleles (Ptpraf/f). These mice were crossed with Dermo1-Cre or with Sftpc-CreERT2 mice to delete Ptpra in mesenchymal cells and alveolar type II cells, respectively. Dermo1-Cre/Ptpraf/f mice were protected from bleomycin-induced pulmonary fibrosis, whereas Sftpc-CreERT2/Ptpraf/f mice developed pulmonary fibrosis equivalent to controls. Both canonical and noncanonical TGF-ß signaling and downstream TGF-ß-induced fibrogenic responses were attenuated in isolated Ptpra-/- compared with wild-type fibroblasts. Furthermore, TGF-ß-induced tyrosine phosphorylation of TGF-ß type II receptor and of PTPα were attenuated in Ptpra-/- compared with wild-type fibroblasts. The phenotype of cells genetically deficient in PTPα was recapitulated with the use of a Src inhibitor. These findings suggest that PTPα amplifies profibrotic TGF-ß-dependent pathway signaling in lung fibroblasts.
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Fibroblastos/metabolismo , Pulmão/metabolismo , Proteínas Tirosina Fosfatases Classe 4 Semelhantes a Receptores/metabolismo , Transdução de Sinais/fisiologia , Fator de Crescimento Transformador beta/metabolismo , Animais , Bleomicina/farmacologia , Células Cultivadas , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Fibroblastos/efeitos dos fármacos , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/metabolismo , Pulmão/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação/efeitos dos fármacos , Fosforilação/fisiologia , Transdução de Sinais/efeitos dos fármacosRESUMO
Fibroblast growth factors (FGF) are essential signaling proteins that regulate diverse cellular functions in developmental and metabolic processes. In Drosophila, the FGF homolog, branchless (bnl) is expressed in a dynamic and spatiotemporally restricted pattern to induce branching morphogenesis of the trachea, which expresses the Bnl-receptor, breathless (btl). Here we have developed a new strategy to determine bnl- expressing cells and study their interactions with the btl-expressing cells in the range of tissue patterning during Drosophila development. To enable targeted gene expression specifically in the bnl expressing cells, a new LexA based bnl enhancer trap line was generated using CRISPR/Cas9 based genome editing. Analyses of the spatiotemporal expression of the reporter in various embryonic stages, larval or adult tissues and in metabolic hypoxia, confirmed its target specificity and versatility. With this tool, new bnl expressing cells, their unique organization and functional interactions with the btl-expressing cells were uncovered in a larval tracheoblast niche in the leg imaginal discs, in larval photoreceptors of the developing retina, and in the embryonic central nervous system. The targeted expression system also facilitated live imaging of simultaneously labeled Bnl sources and tracheal cells, which revealed a unique morphogenetic movement of the embryonic bnl- source. Migration of bnl- expressing cells may create a dynamic spatiotemporal pattern of the signal source necessary for the directional growth of the tracheal branch. The genetic tool and the comprehensive profile of expression, organization, and activity of various types of bnl-expressing cells described in this study provided us with an important foundation for future research investigating the mechanisms underlying Bnl signaling in tissue morphogenesis.
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Movimento Celular/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Fatores de Crescimento de Fibroblastos/genética , Regulação da Expressão Gênica no Desenvolvimento , Morfogênese/genética , Traqueia/metabolismo , Animais , Animais Geneticamente Modificados , Sistemas CRISPR-Cas , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/embriologia , Drosophila melanogaster/metabolismo , Embrião de Mamíferos/citologia , Embrião de Mamíferos/embriologia , Embrião de Mamíferos/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Perfilação da Expressão Gênica/métodos , Hipóxia , Hibridização In Situ , Larva/genética , Larva/metabolismo , Microscopia Confocal , Técnicas de Cultura de Órgãos , Proteínas Tirosina Quinases/genética , Proteínas Tirosina Quinases/metabolismo , Receptores de Fatores de Crescimento de Fibroblastos/genética , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Imagem com Lapso de Tempo/métodos , Traqueia/citologia , Traqueia/embriologiaRESUMO
In Latin America (LA), HIV prevalence among MSM is estimated at thirty times greater than in the general male population. Little is known about the role of social support or disclosure status in relation to the HIV care continuum among LA MSM. Using multivariable logistic generalized estimation equations, we assessed the impact of social support satisfaction and disclosure status on engagement in HIV care, ART initiation, and ART adherence with data from an online, multinational sample of HIV infected MSM in Latin America (N = 2,350). 80.0% were engaged in HIV care, 71% initiated ART, and among those, 37% reported missing at least one dose in the past month. In multivariable models, compared to being very satisfied with social support, being somewhat satisfied (aOR = 0.73, 95% CI 0.56, 0.95) or somewhat dissatisfied (aOR = 0.83, 95% CI 0.70, 0.98) were associated with reduced odds of reporting 100% ART adherence. Disclosure of status was associated with a greater odds of HIV care engagement (OR = 1.63, 95% CI 1.28, 2.07) and ART initiation (OR = 1.55, 95% CI 1.30, 1.84). Greater satisfaction with social support and comfort disclosing HIV status to these sources were associated with improved engagement in HIV care and greater initiation of ART among MSM in LA.
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Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Homossexualidade Masculina/psicologia , Adesão à Medicação/psicologia , Parceiros Sexuais , Apoio Social , Adulto , Continuidade da Assistência ao Paciente , Revelação , HIV , Infecções por HIV/epidemiologia , Infecções por HIV/psicologia , Humanos , América Latina/epidemiologia , Masculino , Adulto JovemRESUMO
Adding alum to poultry litter is a best management practice used to stabilize P in less soluble forms, reducing nonpoint-source P runoff. However, little research has been conducted on how alum additions to litter affect subsequent leaching of P from soil. The objective of this study was to evaluate the effects of alum-treated versus untreated poultry litter on P leaching from soil cores receiving long-term poultry litter applications. Two intact soil cores were taken from each of 52 plots in a long-term study with 13 treatments: a control, four rates each of untreated and alum-treated litter (2.24, 4.49, 6.72, and 8.96 Mg ha), and four rates of ammonium nitrate (65, 130, 195, and 260 kg N ha). One core from each plot received the same fertilizer as for the previous 20 yr, whereas the other was unfertilized in the study year, resulting in a total of 25 treatments. Cores were exposed to natural rainfall, and P leaching was measured for 1 yr. The average soluble reactive P concentrations in the leachate varied from 0.16 to 0.44 mg P L in fertilized alum-treated cores, whereas leachate from cores fertilized with untreated litter ranged from 0.40 to 2.64 mg P L. At the highest litter rate (8.96 Mg ha), alum reduced total dissolved P and total P concentrations in leachate by 83 and 80%, respectively, compared with untreated litter. These results indicate that alum additions to poultry litter significantly reduced soluble and total P fractions in leachate.
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Compostos de Alúmen/química , Esterco , Fósforo/química , Animais , Fósforo/análise , Aves Domésticas , SoloRESUMO
BACKGROUND: Diabetic patients are associated with impaired peripheral microvascular function after cardiopulmonary bypass (CPB) and cardiac surgery. We hypothesized that upregulation of the inducible cyclooxygenase 2 (COX-2) contributes to altered microvascular reactivity of peripheral arterioles in diabetic patients undergoing CPB and cardiac surgery. METHODS: Skeletal muscle samples of nondiabetic (ND) patients and patients with diabetes mellitus (DM; n = 8 per group) undergoing cardiac surgery were harvested before and after CPB. The protein expression/localization of COX-2 was assayed by Western blotting and immunohistochemistry. Peripheral arterioles were dissected from the harvested skeletal muscle tissue samples, the isolated arterioles (80-180 µm) were cannulated and pressurized, and changes in diameter were measured with video microscopy. In-vitro relaxation responses of precontracted arterioles were examined in the presence of the endothelium-dependent vasodilator bradykinin (10-10 to 10-6M) and in the presence or absence of the selective COX-2 inhibitor NS398 (10-5M). RESULTS: The post-CPB protein levels of the inducible COX-2 were significantly increased compared with pre-CPB values in both the ND and DM groups (P < 0.05), whereas, this increase was higher in DM than that of ND (P < 0.05). In the DM arterioles, not the ND vessels, bradykinin-induced relaxation response was inhibited in the presence of the specific COX-2 inhibitor NS398 at baseline (P < 0.05). After CPB, bradykinin-induced relaxation response of the ND and DM arterioles was inhibited in the presence of the specific COX-2 inhibitor NS398, but this effect was more pronounced in the diabetic patients (P < 0.05). CONCLUSIONS: Diabetes and CPB are associated with upregulation in COX-2 expression/activation in human peripheral microvasculature. This alteration may lead to altered peripheral microvascular reactivity in diabetic patients undergoing cardiac surgery.
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Arteríolas/enzimologia , Ponte Cardiopulmonar/efeitos adversos , Ciclo-Oxigenase 2/metabolismo , Complicações do Diabetes/enzimologia , Complicações Pós-Operatórias/enzimologia , Idoso , Arteríolas/fisiopatologia , Bradicinina , Ciclo-Oxigenase 1/metabolismo , Complicações do Diabetes/fisiopatologia , Feminino , Humanos , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/fisiopatologia , VasodilataçãoRESUMO
BACKGROUND: Thrombelastography (TEG) is a viscoelastic hemostatic assay. We have observed that end-stage renal disease (ESRD) and trauma-induced coagulopathy (TIC) produce distinctive TEG tracings. We hypothesized that rigorously definable TEG patterns could discriminate between healthy controls and patients with ESRD and TIC. METHODS: TEG was performed on blood from ESRD patients (n = 54) and blood from trauma patients requiring a massive blood transfusion (n = 16). Plots of independent TEG parameters were analyzed for patterns coupled to disease state, compared with controls. Decision trees for taxonomic classification were then built using the "R-Project" statistical software. RESULTS: Minimally overlapping clusters of TEG results were observed for the three patient groups when coordinate pairs of maximum amplitude (MA) and TEG-activated clotting time (ACT) were plotted on orthogonal axes. Based on these groupings, a taxonomical classification tree was constructed using MA and TEG ACT. Branch points were set at an ACT of 103 s, and these branches subdivided for MA at 60.8 mm for the high ACT branch and 72.6 mm for the low ACT branch, providing a correct classification rate of 93.4%. CONCLUSIONS: ESRD and TIC demonstrate distinct TEG patterns. The coagulopathy of ESRD is typified by a prolonged enzymatic phase of clot formation, with normal-to-elevated final clot strength. Conversely, TIC is typified by prolonged clot formation and weakened clot strength. Our taxonomic categorization constitutes a rigorous system for the algorithmic interpretation of TEG based on cluster analysis. This will form the basis for clinical decision support software for viscoelastic hemostatic assays.
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Falência Renal Crônica/sangue , Tromboelastografia , Ferimentos e Lesões/sangue , Análise por Conglomerados , Humanos , Tempo de Coagulação do Sangue TotalRESUMO
BACKGROUND: Worksite wellness initiatives for health promotion and health education have demonstrated effectiveness in improving employee health and wellness. We examined the effects of a multifaceted health promotion campaign on organizational capacity to meet requirements to become CEO Cancer Gold Standard Accredited. METHODS: We conducted an online survey to assess perceived organizational values and support for the five CEO Cancer Gold Standard Pillars for cancer prevention: tobacco cessation; physical activity; nutrition; cancer screening and early detection; and accessing information on cancer clinical trials. Baseline and follow-up surveys were sent 6-months apart to faculty, staff, and students at a school of public health to test the impact of a multifaceted health promotion campaign on perceived organizational change. Descriptive analyses were used to characterize percent improvement. Multivariate logistic regression analyses were used to control for participants' university status. RESULTS: The current organizational culture highly supported tobacco cessation at both time points. Significant improvements (p < .05) from baseline to follow-up were observed for questions measuring organizational values for 'prevention, screening, and early detection of cancer' and 'accessing cancer treatment and clinical trials'. CONCLUSIONS: Health promotion and education efforts using multiple approaches were effective to improve perceived organizational values and support for cancer prevention and early detection, and increase access to information about cancer clinical trials. Future studies are needed to examine broader impacts of implementing worksite health promotion initiatives.
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Promoção da Saúde/organização & administração , Neoplasias/prevenção & controle , Saúde Ocupacional , Cultura Organizacional , Inovação Organizacional , Faculdades de Saúde Pública/organização & administração , Dieta , Detecção Precoce de Câncer , Exercício Físico , Feminino , Humanos , Masculino , Políticas , Abandono do Hábito de Fumar , Fatores Socioeconômicos , Estudantes , Local de TrabalhoRESUMO
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.
Assuntos
Linfócitos B , Perfilação da Expressão Gênica , Síndrome de Sjogren , Transcriptoma , Humanos , Síndrome de Sjogren/genética , Síndrome de Sjogren/imunologia , Feminino , Linfócitos B/imunologia , Linfócitos B/metabolismo , Pessoa de Meia-Idade , Perfilação da Expressão Gênica/métodos , Interferons/genética , Interferons/metabolismo , Adulto , Autoanticorpos/imunologia , Autoanticorpos/sangue , Autoanticorpos/genética , IdosoRESUMO
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.
Assuntos
Pancreatite Crônica , Disfunções Sexuais Fisiológicas , Humanos , Masculino , Feminino , Qualidade de Vida , Projetos Piloto , Disfunções Sexuais Fisiológicas/epidemiologia , Disfunções Sexuais Fisiológicas/etiologia , Pancreatite Crônica/complicações , Inquéritos e QuestionáriosRESUMO
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.