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1.
Am J Geriatr Psychiatry ; 31(1): 14-21, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36167652

RESUMO

OBJECTIVES: In response to the needs of dementia caregivers during the COVID-19 pandemic, the NYU Langone Alzheimer's Disease and Related Disorders Family Support Program (FSP) quickly transitioned to providing most services online. To understand how dementia caregivers experienced FSP services after the switch to video telehealth, we conducted qualitative interviews of spouse or partner dementia caregivers. PARTICIPANTS: Ten participants were recruited from a convenience sample of dementia spouse or partner caregivers who used one or more online FSP services offered during the pandemic. DESIGN: Caregivers engaged in semi-structured interviews held via videoconference between May and June 2020. Qualitative analysis of interviews was conducted according to the principles of framework analysis. RESULTS: Caregivers reported high satisfaction with the FSP pre-pandemic and continued to feel supported when services were provided online. They transitioned to video telehealth services with little difficulty. CONCLUSIONS: While video telehealth is frequently cited as beneficial for those in rural communities, socioeconomically disadvantaged groups, or homebound individuals, our findings suggest that video telehealth is also advantageous for dementia caregivers, given their unique barriers, including lack of time due to caregiving responsibilities, lack of respite care for the person with dementia, and the additional burdens of travel time to access in-person services.


Assuntos
COVID-19 , Demência , Telemedicina , Humanos , Cuidadores , Pandemias , Demência/epidemiologia
2.
Nature ; 551(7679): 218-222, 2017 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-29120424

RESUMO

The freezing of water affects the processes that determine Earth's climate. Therefore, accurate weather and climate forecasts hinge on good predictions of ice nucleation rates. Such rate predictions are based on extrapolations using classical nucleation theory, which assumes that the structure of nanometre-sized ice crystallites corresponds to that of hexagonal ice, the thermodynamically stable form of bulk ice. However, simulations with various water models find that ice nucleated and grown under atmospheric temperatures is at all sizes stacking-disordered, consisting of random sequences of cubic and hexagonal ice layers. This implies that stacking-disordered ice crystallites either are more stable than hexagonal ice crystallites or form because of non-equilibrium dynamical effects. Both scenarios challenge central tenets of classical nucleation theory. Here we use rare-event sampling and free energy calculations with the mW water model to show that the entropy of mixing cubic and hexagonal layers makes stacking-disordered ice the stable phase for crystallites up to a size of at least 100,000 molecules. We find that stacking-disordered critical crystallites at 230 kelvin are about 14 kilojoules per mole of crystallite more stable than hexagonal crystallites, making their ice nucleation rates more than three orders of magnitude higher than predicted by classical nucleation theory. This effect on nucleation rates is temperature dependent, being the most pronounced at the warmest conditions, and should affect the modelling of cloud formation and ice particle numbers, which are very sensitive to the temperature dependence of ice nucleation rates. We conclude that classical nucleation theory needs to be corrected to include the dependence of the crystallization driving force on the size of the ice crystallite when interpreting and extrapolating ice nucleation rates from experimental laboratory conditions to the temperatures that occur in clouds.

3.
Can J Urol ; 26(1): 9664-9674, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30797250

RESUMO

INTRODUCTION: The optimal patient positioning for percutaneous nephrolithotomy (PCNL) based on the complexity of stone burden is not yet defined. Thus, we aimed to evaluate the intraoperative parameters, effectiveness and complications of patients undergoing PCNL between the endoscopic-guided prone split-leg PCNL (ePSL) and the supine PCNL by stratifying patients according to Guy's stone score (GSS). MATERIALS AND METHODS: A retrospective chart review was conducted of patients undergoing PCNL at two high-volume tertiary referral centers. At one center, patients underwent PCNL using the ePSL technique, while at the second center, patients underwent PCNL in supine. Patient demographics and stone characteristics, operative details, complications and effectiveness were compared between groups. The impact of obesity was also investigated. RESULTS: Of 830 subjects, a total of 449 (54%) underwent PCNL in ePSL and 381 (46%) in supine. The ePSL group had a greater mean age and body mass index. No statistical differences were found in gender, serum chemistry and Charlson comorbidity index. After stratifying patients by GSS, the differences in baseline stone burden between PSL and supine lost significance and both groups could be compared. Complications were not statistically different between both groups. Univariate analysis demonstrated that multiple tracts and lower pole access were more prevalent in supine. In addition, for GSS1-3, ePSL was correlated with reduced operative time, radiation exposure, length of hospital stay and need for secondary procedure. Multivariate analysis correlated ePSL with lower radiation exposure and need for secondary procedures (p = 0.01). In comparison to the whole trial population, the same tendencies were appreciated for obese cohort. CONCLUSIONS: This is the first report focusing on the performance differences between ePSL and supine PCNL stratified by GSS. Both techniques are safe, with a low rate of complications. For GSS1-3, ePSL reduces radiation exposure and requires less need for both multiple access and secondary procedure.


Assuntos
Endoscopia , Cálculos Renais/cirurgia , Nefrolitotomia Percutânea/métodos , Posicionamento do Paciente/métodos , Idoso , Feminino , Humanos , Cálculos Renais/complicações , Cálculos Renais/patologia , Perna (Membro) , Masculino , Pessoa de Meia-Idade , Nefrolitotomia Percutânea/classificação , Obesidade/complicações , Complicações Pós-Operatórias/epidemiologia , Decúbito Ventral , Estudos Retrospectivos , Decúbito Dorsal
4.
J Am Chem Soc ; 140(47): 16071-16086, 2018 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-30379074

RESUMO

Zeolites and mesoporous silicas are porous materials with important applications in catalysis, gas storage, and separation. Zeolite crystals form in the presence of cationic surfactants that act as structure directing agents (SDAs). The way SDAs control the nucleation and polymorphs selection in zeolites is not fully understood. The formation of mesoporous silica is templated by liquid crystalline mesophases that result from frustrated attraction between silicates and long-chain SDAs. Experiments indicate that surfactants C nH2 n+1(CH3)3N+ with n > 6 yield mesoporous silicas, and the one with n = 6 produces a zeolite. This suggests that the driving force toward mesophase formation is also present for small organocations, but is overcome by the ability of silica to wrap a crystal lattice around them. Here we use molecular dynamics simulations to investigate whether the existence of metastable mesophases can play a role in the nucleation and polymorph selection of zeolitic crystals. As a proof of concept, we investigate the phase behavior of simple mesogenic mixtures of SDAs and a network former T that favors tetracoordinated crystals. We represent the network-former T by Stillinger-Weber models of water and silicon, in lieu of silica, because a computationally efficient silica potential that would allow for the spontaneous nucleation of zeolites in molecular dynamics simulations is not yet available. The mixtures of T and SDA produce a rich phase diagram that encompasses the sII clathrate and at least six zeolites, including sigma-2 (SGT). We find that the nucleation of SGT is not assisted by a mesophase. The nucleation of the other five zeolites of this study, however, is facilitated by the existence of metastable mesophases that decrease the nucleation barriers and direct the selection of the crystal polymorph. Together with the experimental support for mesophases in mixtures of silicates and SDAs, our results for model systems suggest that metastable mesophases could play a prominent role in promoting the nucleation and polymorph selection of some zeolites.

5.
J Surg Res ; 196(2): 285-293, 2015 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-25846727

RESUMO

BACKGROUND: We previously identified a correlation between increased expression of the phosphoinositide 3-kinase (PI3K) regulatory subunit p85α and improved survival in human pancreatic ductal adenocarcinoma (PDAC). The purpose of this study was to investigate the impact of changes in p85α expression on response to chemotherapy and the regulation of p85α by microRNA-21 (miR-21). MATERIALS AND METHODS: PDAC tumor cells overexpressing p85α were generated by viral transduction, and the effect of p85α overexpression on sensitivity to gemcitabine was tested by MTT assay. Primary human PDAC tumors were stained for p85α and miR-21 via immunohistochemistry and in situ hybridization, respectively. Additionally, PDAC cells were treated with miR-21 mimic, and changes in p85α and phospho-AKT were assessed by Western blot. Finally, a luciferase reporter assay system was used to test direct regulation of p85α by miR-21. RESULTS: Higher p85α expression resulted in increased sensitivity to gemcitabine (P < 0.01), which correlated with decreased PI3K-AKT activation. Human tumors demonstrated an inverse correlation between miR-21 and p85α expression levels (r = -0.353, P < 0.001). In vitro, overexpression of miR-21 resulted in decreased levels of p85α and increased phosphorylation of AKT. Luciferase reporter assays confirmed the direct regulation of p85α by miR-21 (P < 0.01). CONCLUSIONS: Our results demonstrate that p85α expression is a determinant of chemosensitivity in PDAC. Additionally, we provide novel evidence that miR-21 can influence PI3K-AKT signaling via its direct regulation of p85α. These data provide insight into potential mechanisms for the known relationship between increased p85α expression and improved survival in PDAC.


Assuntos
Carcinoma Ductal Pancreático/metabolismo , Classe Ia de Fosfatidilinositol 3-Quinase/metabolismo , MicroRNAs/metabolismo , Neoplasias Pancreáticas/metabolismo , Antimetabólitos Antineoplásicos/uso terapêutico , Carcinoma Ductal Pancreático/tratamento farmacológico , Linhagem Celular Tumoral , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Células HEK293 , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Gencitabina
6.
J Surg Oncol ; 112(4): 396-402, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26303811

RESUMO

BACKGROUND: Lymph node (LN) involvement is a well-known poor prognostic factor in patients with pancreatic ductal adenocarcinoma (PDAC). However, there have been conflicting results on the significance of the mechanism of LN involvement, "direct" tumor invasion versus "metastatic," disease on patient survival. METHODS: Clinicopathologic records from all patients who underwent resection for PDAC from 1990 to 2014 at a single-institution were reviewed. RESULTS: Of the 385 total patients, there was tumor invasion outside of the pancreas in 289 (75.1%) patients. Overall, 239 (62.1%) had node-positive disease: 220 (92.0%) by "metastatic" involvement, 14 (5.9%) by "direct" tumor extension, and five (2.1%) by a mix of "metastatic" and "direct". There were no significant differences in clinicopathologic factors associated with PDAC survival between "metastatic" and "direct" LN patients. The median overall survival for the whole cohort was 31.1 months. Compared to overall survival in patients with LN-negative disease (median 40.7 months), those with LNs involved by "metastatic" spread was significantly shorter (median 25.7 months, P < 0.001), yet "direct" LN extension was similar (median 48.1 months, P = 0.719). CONCLUSIONS: The mechanism of LN involvement affects PDAC prognosis. Patients with LNs involved by direct extension have similar survival to those with node-negative disease.


Assuntos
Adenocarcinoma/mortalidade , Carcinoma Ductal Pancreático/mortalidade , Linfonodos/patologia , Pancreatectomia/mortalidade , Neoplasias Pancreáticas/mortalidade , Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/secundário , Carcinoma Ductal Pancreático/cirurgia , Feminino , Seguimentos , Humanos , Excisão de Linfonodo , Linfonodos/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Adulto Jovem
7.
J Surg Oncol ; 110(8): 952-9, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25132574

RESUMO

BACKGROUND AND OBJECTIVES: MicroRNA-21 (miR-21) is upregulated and inversely associated with survival in many cancer types, including pancreatic ductal adenocarcinoma (PDAC). We studied the predictive value of miR-21 levels for gemcitabine or 5-fluorouracil (5-FU) response in tumor cells (TCs) or cancer associated fibroblasts (CAFs) in a cohort of PDAC patients from the RTOG 9704 trial. METHODS: MiR-21 expression in CAFs and TCs, determined by in situ hybridization, of the 229 PDAC subset from RTOG 9704 was correlated with (i) histopathology characteristics using a chi-square test; and (ii) patient overall survival (OS) using the Cox proportional hazards model. RESULTS: MiR-21 was strongly expressed in TCs and CAFs in 137/182 (75%) and 152/181 (84%) PDACs, respectively. MiR-21 expression in CAFs for the group given 5-FU for OS: (i) approached significance in a univariate analysis (hazard ratio [HR], 1.57; 95% confidence interval [CI], 0.95-2.57; P = 0.07); and (ii) was significant in the multivariate model (HR, 1.70; 95% CI, 1.03-2.82; P = 0.038). CONCLUSIONS: MiR-21 expression in CAFs was associated with decreased OS in PDAC patients who received 5-FU, but not gemcitabine. These findings begin to identify stromal miR-21 as a marker to guide chemotherapy choice in PDAC patients.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antimetabólitos Antineoplásicos/uso terapêutico , Carcinoma Ductal Pancreático/tratamento farmacológico , Fluoruracila/uso terapêutico , MicroRNAs/fisiologia , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/genética , Feminino , Humanos , Masculino , MicroRNAs/análise , Pessoa de Meia-Idade , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Modelos de Riscos Proporcionais , Análise Serial de Tecidos
8.
J Chem Phys ; 140(8): 084506, 2014 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-24588184

RESUMO

Cross-nucleation is a phenomenon where a new crystal nucleates and grows upon the surface of a different polymorph. Previous studies indicate that faster growth rate of the new crystal is a necessary but not sufficient condition for cross-nucleation. The thermodynamic stability of the different polymorphs can also affect cross-nucleation by modulating the rates of crystal growth. The interplay between thermodynamic stability of the polymorphs involved, the growth rate of the crystals, and the need for creation of an interfacial transition layer that seamlessly connects the two structures has not yet been fully elucidated. Predicting cross-nucleation is particularly challenging for clathrate hydrates, for which there are sometimes several polymorphs with similar stability and for which growth rates are not known. In this work, we use molecular dynamics simulations to investigate which factor (stability, growth rate, or formation of interfacial transition layer) controls cross-nucleation between the four known Frank-Kasper clathrate hydrate polymorphs: sI, sII, TS, and HS-I. We investigate the growth and cross-nucleation of these four hydrates filled with a set of guest molecules that produce different order of stabilities for the four crystal structures. We determine that the growth rate of sII clathrate is the fastest, followed by TS, HS-I, and sI. We find that cross-nucleation into or from sII clathrates is preceded by the formation of an interfacial transition layer at the seed crystal/liquid interface because sII does not share a crystal plane with sI, HS-I, or TS. Cross-nucleation between the latter three can occur seamlessly and is determined only by their growth rates. Our results indicate that nucleation of an interfacial transition layer between non-matching polymorphs can control cross-nucleation or lack thereof under conditions of small driving force. Under conditions of sufficient supercooling clathrate hydrate polymorphs cross-nucleate into the fastest growing phase even if that new phase is less stable and does not share a common crystal plane with the initial polymorph.

9.
Front Cardiovasc Med ; 11: 1352675, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38380176

RESUMO

Cardiovascular disease (CVD) is the leading cause of death worldwide and accounts for roughly 1 in 5 deaths in the United States. Women in particular face significant disparities in their cardiovascular care when compared to men, both in the diagnosis and treatment of CVD. Sex differences exist in the prevalence and effect of cardiovascular risk factors. For example, women with history of traditional cardiovascular risk factors including hypertension, tobacco use, and diabetes carry a higher risk of major cardiovascular events and mortality when compared to men. These discrepancies in terms of the relative risk of CVD when traditional risk factors are present appear to explain some, but not all, of the observed differences among men and women. Sex-specific cardiovascular disease research-from identification, risk stratification, and treatment-has received increasing recognition in recent years, highlighting the current underestimated association between CVD and a woman's obstetric and reproductive history. In this comprehensive review, sex-specific risk factors unique to women including adverse pregnancy outcomes (APO), such as hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus, preterm delivery, and newborn size for gestational age, as well as premature menarche, menopause and vasomotor symptoms, polycystic ovarian syndrome (PCOS), and infertility will be discussed in full detail and their association with CVD risk. Additional entities including spontaneous coronary artery dissection (SCAD), coronary microvascular disease (CMD), systemic autoimmune disorders, and mental and behavioral health will also be discussed in terms of their prevalence among women and their association with CVD. In this comprehensive review, we will also provide clinicians with a guide to address current knowledge gaps including implementation of a sex-specific patient questionnaire to allow for appropriate risk assessment, stratification, and prevention of CVD in women.

10.
Am J Obstet Gynecol MFM ; 6(3): 101295, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38278176

RESUMO

Ischemic heart disease is a crucial issue during pregnancy. The term is composed of both preexisting conditions and acute coronary syndrome in pregnancy, including pregnancy-associated myocardial infarction, which can have a significant effect on maternal and fetal outcomes. This review provides a complete guide to managing ischemic heart disease in pregnant women, emphasizing the importance of multidisciplinary care and individualized treatment strategies. Cardiovascular disease, particularly ischemic heart disease, is now the leading cause of maternal mortality worldwide. Pregnancy introduces unique physiological changes that increase the risk of acute myocardial infarction, with pregnancy-associated myocardial infarction cases often associated with factors, such as advanced maternal age, chronic hypertension, and preexisting cardiovascular conditions. This review distinguishes between preexisting ischemic heart disease and pregnancy-associated myocardial infarction. It will emphasize the various etiologies of pregnancy-associated myocardial infarction, including coronary atherosclerosis and plaque rupture presenting as ST-elevation myocardial infarction, non-ST-elevation myocardial infarction, and other nonatherosclerotic causes, including spontaneous coronary artery dissection, vasospasm, and embolism. Our study discusses the practical management of ischemic heart disease in pregnancy, with a focus on preconception counseling, risk assessment, and tailored antenatal planning for women with preexisting ischemic heart disease. Moreover, this document focuses on the challenges of diagnosing cardiovascular disease, especially when presented with nonclassical risk factors and presentation. It provides insight into the appropriate diagnostic testing methods, such as electrocardiogram, cardiac biomarkers, and echocardiography. In addition, the review covers various treatment strategies, from medical management to more invasive procedures, including coronary angiography, percutaneous coronary intervention, and coronary artery bypass graft. Special attention is given to medication safety during pregnancy, including anticoagulation, beta-blockers, and antiplatelet agents. The complexities of delivery planning in women with ischemic heart disease are discussed, advocating for a multidisciplinary team-based approach and careful consideration of the timing and mode of delivery. Furthermore, the roles of breastfeeding and postpartum care are explored, emphasizing the long-term benefits and the suitability of various medications during lactation. Lastly, this review provides crucial insights into the management of ischemic heart disease in pregnancy, stressing the need for heightened awareness, prompt diagnosis, and tailored management to optimize maternal and fetal health outcomes.


Assuntos
Infarto do Miocárdio , Isquemia Miocárdica , Doenças Vasculares , Feminino , Humanos , Gravidez , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/epidemiologia , Isquemia Miocárdica/etiologia , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/terapia , Fatores de Risco , Medição de Risco
11.
Front Cardiovasc Med ; 11: 1354158, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38545346

RESUMO

Cardiogenic shock (CS) is a time-sensitive and hemodynamically complex syndrome with a broad spectrum of etiologies and clinical presentations. Despite contemporary therapies, CS continues to maintain high morbidity and mortality ranging from 35 to 50%. More recently, burgeoning observational research in this field aimed at enhancing the early recognition and characterization of the shock state through standardized team-based protocols, comprehensive hemodynamic profiling, and tailored and selective utilization of temporary mechanical circulatory support devices has been associated with improved outcomes. In this narrative review, we discuss the pathophysiology of CS, novel phenotypes, evolving definitions and staging systems, currently available pharmacologic and device-based therapies, standardized, team-based management protocols, and regionalized systems-of-care aimed at improving shock outcomes. We also explore opportunities for fertile investigation through randomized and non-randomized studies to address the prevailing knowledge gaps that will be critical to improving long-term outcomes.

12.
Gastroenterology ; 143(4): 1061-72, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22705178

RESUMO

BACKGROUND & AIMS: Immune cells of the liver must be able to recognize and react to pathogens yet remain tolerant to food molecules and other nonpathogens. Dendritic cells (DCs) are believed to contribute to hepatic tolerance. Lipids have been implicated in dysfunction of DCs in cancer. Therefore, we investigated whether high lipid content in liver DCs affects induction of tolerance. METHODS: Mouse and human hepatic nonparenchymal cells were isolated by mechanical and enzymatic digestion. DCs were purified by fluorescence-activated cell sorting or with immunomagnetic beads. DC lipid content was assessed by flow cytometry, immune fluorescence, and electron microscopy and by measuring intracellular component lipids. DC activation was determined from surface phenotype and cytokine profile. DC function was assessed in T-cell, natural killer (NK) cell, and NKT cell coculture assays as well as in vivo. RESULTS: We observed 2 distinct populations of hepatic DCs in mice and humans based on their lipid content and expression of markers associated with adipogenesis and lipid metabolism. This lipid-based dichotomy in DCs was unique to the liver and specific to DCs compared with other hepatic immune cells. However, rather than mediate tolerance, the liver DC population with high concentrations of lipid was immunogenic in multiple models; they activated T cells, NK cells, and NKT cells. Conversely, liver DCs with low levels of lipid induced regulatory T cells, anergy to cancer, and oral tolerance. The immunogenicity of lipid-rich liver DCs required their secretion of tumor necrosis factor α and was directly related to their high lipid content; blocking DC synthesis of fatty acids or inhibiting adipogenesis (by reducing endoplasmic reticular stress) reduced DC immunogenicity. CONCLUSIONS: Human and mouse hepatic DCs are composed of distinct populations that contain different concentrations of lipid, which regulates immunogenic versus tolerogenic responses in the liver.


Assuntos
Antígenos CD/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Lipídeos/análise , Fígado/imunologia , Fígado/metabolismo , Adipogenia , Animais , Antígenos CD1d/metabolismo , Apoptose , Antígeno B7-1/metabolismo , Antígeno B7-2/metabolismo , Antígeno CD11b/metabolismo , Antígenos CD40/metabolismo , Células Cultivadas , Células Dendríticas/química , Humanos , Tolerância Imunológica , Molécula 1 de Adesão Intercelular/metabolismo , Células Matadoras Naturais/fisiologia , Antígenos Comuns de Leucócito/metabolismo , Metabolismo dos Lipídeos , Fígado/química , Ativação Linfocitária , Camundongos , Células T Matadoras Naturais/fisiologia , Fenótipo , Linfócitos T/fisiologia , Linfócitos T Reguladores/fisiologia , Fator de Necrose Tumoral alfa/metabolismo
13.
Gastroenterology ; 141(5): 1915-26.e1-14, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21801698

RESUMO

BACKGROUND & AIMS: The cellular mediators of acute pancreatitis are incompletely understood. Dendritic cells (DCs) can promote or suppress inflammation, depending on their subtype and context. We investigated the roles of DC in development of acute pancreatitis. METHODS: Acute pancreatitis was induced in CD11c.DTR mice using caerulein or L-arginine; DCs were depleted by administration of diphtheria toxin. Survival was analyzed using Kaplan-Meier method. RESULTS: Numbers of major histocompatibility complex II(+)CD11c(+) DCs increased 100-fold in pancreata of mice with acute pancreatitis to account for nearly 15% of intrapancreatic leukocytes. Intrapancreatic DCs acquired a distinct immune phenotype in mice with acute pancreatitis; they expressed higher levels of major histocompatibility complex II and CD86 and increased production of interleukin-6, membrane cofactor protein-1, and tumor necrosis factor-α. However, rather than inducing an organ-destructive inflammatory process, DCs were required for pancreatic viability; the exocrine pancreas died in mice that were depleted of DCs and challenged with caerulein or L-arginine. All mice with pancreatitis that were depleted of DCs died from acinar cell death within 4 days. Depletion of DCs from mice with pancreatitis resulted in neutrophil infiltration and increased levels of systemic markers of inflammation. However, the organ necrosis associated with depletion of DCs did not require infiltrating neutrophils, activation of nuclear factor-κB, or signaling by mitogen-activated protein kinase or tumor necrosis factor-α. CONCLUSIONS: DCs are required for pancreatic viability in mice with acute pancreatitis and might protect organs against cell stress.


Assuntos
Células Dendríticas/fisiologia , Pâncreas/patologia , Pâncreas/fisiopatologia , Pancreatite/patologia , Pancreatite/fisiopatologia , Sobrevivência de Tecidos/fisiologia , Doença Aguda , Animais , Arginina/efeitos adversos , Ceruletídeo/efeitos adversos , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Células Dendríticas/patologia , Toxina Diftérica/farmacologia , Modelos Animais de Doenças , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Interleucina-6/metabolismo , Estimativa de Kaplan-Meier , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pancreatite/induzido quimicamente , Fenótipo , Fatores de Tempo
14.
Hepatology ; 54(3): 959-68, 2011 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-21574173

RESUMO

UNLABELLED: Acetaminophen (APAP) overdose is one of the most frequent causes of acute liver failure in the United States and is primarily mediated by toxic metabolites that accumulate in the liver upon depletion of glutathione stores. However, cells of the innate immune system, including natural killer (NK) cells, neutrophils, and Kupffer cells, have also been implicated in the centrilobular liver necrosis associated with APAP. We have recently shown that dendritic cells (DCs) regulate intrahepatic inflammation in chronic liver disease and, therefore, postulated that DC may also modulate the hepatotoxic effects of APAP. We found that DC immune-phenotype was markedly altered after APAP challenge. In particular, liver DC expressed higher MHC II, costimulatory molecules, and Toll-like receptors, and produced higher interleukin (IL)-6, macrophage chemoattractant protein-1 (MCP-1), and tumor necrosis factor alpha (TNF-α). Conversely, spleen DC were unaltered. However, APAP-induced centrilobular necrosis, and its associated mortality, was markedly exacerbated upon DC depletion. Conversely, endogenous DC expansion using FMS-like tyrosine kinase 3 ligand (Flt3L) protected mice from APAP injury. Our mechanistic studies showed that APAP liver DC had the particular capacity to prevent NK cell activation and induced neutrophil apoptosis. Nevertheless, the exacerbated hepatic injury in DC-depleted mice challenged with APAP was independent of NK cells and neutrophils or numerous immune modulatory cytokines and chemokines. CONCLUSION: Taken together, these data indicate that liver DC protect against APAP toxicity, whereas their depletion is associated with exacerbated hepatotoxicity.


Assuntos
Acetaminofen/toxicidade , Analgésicos não Narcóticos/toxicidade , Células Dendríticas/fisiologia , Fígado/efeitos dos fármacos , Animais , Células Dendríticas/imunologia , Imunofenotipagem , Mediadores da Inflamação/fisiologia , Células Matadoras Naturais/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/fisiologia
15.
Am J Surg ; 223(5): 939-944, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34474917

RESUMO

BACKGROUND: A minority of patients with gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) is diagnosed at younger age. This population-based study explores the broad clinical and pathologic features of the youngest 5% of adult patients with GEP-NETs. METHODS: A retrospective study of the National Cancer Database (NCDB) of patients with a primary GEP-NET was performed. Patients were stratified by age. Kaplan-Meier and multivariate Cox proportional hazards analyses were performed. RESULTS: We identified 31,983 patients with a diagnosis of a GEP-NET and only 5% of patients were under the age of 35. Young patients were found to have greater proportions of localized, well differentiated disease. On multivariate analysis, young age, well differentiated histology, early stage, and surgical intervention were associated with lower risk of mortality. CONCLUSIONS: Young patients with GEP-NETs tend to have earlier stage of presentation and well differentiated tumors, which may be most amenable to surgical intervention.


Assuntos
Neoplasias Intestinais , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Neoplasias Gástricas , Humanos , Neoplasias Intestinais/patologia , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirurgia , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Adulto Jovem
16.
Biochim Biophys Acta ; 1798(7): 1289-300, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20067758

RESUMO

Fluorescence microscopy has become a powerful and standard complementary technique in the study of amphiphilic films at the air-water interface. For nearly three decades the coupling of traditional thermodynamic measurements with direct visualization has provided a better understanding of self-assembled Langmuir monolayers and their application in the study of the physical properties of membranes and interfaces. As an introduction we provide a brief overview of this established technique and demonstrate its continued utility in the recent observation of novel phase behavior in monolayers of 25-hydroxycholesterol (25-OH) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). We then focus our review on new analysis techniques which take advantage of the ability to store, process, and analyze large sets of images. We pay particular attention to efforts measuring the line tension between coexisting two dimensional fluid phases in the Langmuir monolayer. Using non-perturbative methods, we can measure fundamental mechanical properties of these two dimensional systems. Finally, we highlight the use of Model Convolution Microscopy as a new tool to provide insight on the experimental limits in these studies.


Assuntos
Processamento de Imagem Assistida por Computador , Membranas Artificiais , Microscopia de Fluorescência/métodos , Modelos Químicos , 1,2-Dipalmitoilfosfatidilcolina/química , Animais , Humanos , Hidroxicolesteróis/química
17.
Eur J Ophthalmol ; 31(6): 3074-3079, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33349030

RESUMO

PURPOSE: To assess the vision-related quality of life in adult patients with a history of primary congenital glaucoma. METHODS: In a cross-sectional hospital-based study eligible patients with a history of primary congenital glaucoma aged more than 18 were recruited in the study. Patients with secondary glaucoma and monocular patients were excluded. All patients underwent a complete ophthalmologic examination. The subjects were requested to answer a Persian approved version of the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) questionnaire. RESULTS: A total of 23 congenital glaucoma patients have enrolled in the study. The mean age was 29.22 (9.3 SD) and mean IOP was 13.82 (5.19 SD) and 15.69 (5.26 SD) in right and left eyes, respectively. The mean number of medications was 1.13 (1.25 SD) in the right and 1.30 (1.18 SD) in the left eyes. Among all scores of NEI-VFQ-25, the lowest score belonged to mental health 53.71 (29.72) and the highest score was color vision score 83.69 (20.79). We found a significant influence of visual field defect on many subscales including general health and general vision (p = 0.007, R = +0.65) and (p = 0.002, R = +0.71) respectively. The Mean Defect (MD) was associated with low social functioning and peripheral vision too (p = 0.035, R = +0.53) and (p = 0.001, R = +0.76) respectively. Age had a negative impact on the general vision subscale (p = 0.003, R = -0.59). CONCLUSION: Our study showed that visual field defect was strongly associated with many subscales scores in (NEI VFQ-25) questionnaire.


Assuntos
Glaucoma , Qualidade de Vida , Adulto , Estudos Transversais , Humanos , Perfil de Impacto da Doença , Inquéritos e Questionários , Visão Ocular , Acuidade Visual
18.
Front Endocrinol (Lausanne) ; 11: 624251, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33613455

RESUMO

Renal neuroendocrine neoplasms are rare, with descriptions of cases limited to individual reports and small series. The natural history of this group of neuroendocrine neoplasms is poorly understood. In this study, we queried the Surveillance, Epidemiology and End Results (SEER) database over a four-decade period where we identified 166 cases of primary renal neuroendocrine neoplasms. We observed a 5-year overall survival of 50%. On multivariate analysis, survival was influenced by stage, histology, and if surgery was performed. We observed that patients managed by operative management had a greater frequency of localized or regional stage disease as well as a greater frequency of neuroendocrine tumor, grade 1 histology; whereas those managed non-operatively tended to have distant disease and histologies of neuroendocrine carcinoma, NOS and small cell neuroendocrine carcinoma. This is the largest description of patients with renal neuroendocrine neoplasms. Increased survival was observed in patients with earlier stage and favorable histologies.


Assuntos
Neoplasias Renais/classificação , Neoplasias Renais/mortalidade , Tumores Neuroendócrinos/classificação , Tumores Neuroendócrinos/mortalidade , Programa de SEER/tendências , Adulto , Idoso , Feminino , Humanos , Neoplasias Renais/diagnóstico , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Tumores Neuroendócrinos/diagnóstico , Taxa de Sobrevida/tendências
19.
Transl Vis Sci Technol ; 8(5): 27, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31637107

RESUMO

PURPOSE: To explore factors influencing the inner plexiform layer (IPL) in healthy subjects and to test the hypothesis that IPL thickness is preferentially decreased in glaucoma as compared with ganglion cell layer (GCL) thickness. METHODS: Ninety-nine glaucomatous eyes and 66 healthy eyes (165 subjects) underwent macular spectral-domain optical coherence tomography (SD-OCT) imaging and GCL and IPL were segmented creating 8 × 8 arrays of 3° × 3° superpixels. The central 24 superpixels were categorized into three levels of eccentricity (∼1.5°, 4.5°, and 7.5° from the foveal center). Linear mixed models were used to determine predictive parameters for IPL thickness in healthy subjects and to explore the influence of diagnosis of glaucoma on IPL thickness taking into account the effect of GCL thickness and other covariates. RESULTS: Being located at 4.5° eccentricity predicted thicker IPL compared with 1.5° eccentricity (P < 0.001) in multivariable models in healthy subjects, whereas older age (P = 0.001) and Asian ethnicity (P = 0.021) were associated with thinner IPL. Diagnosis of glaucoma was not associated with thinner IPL regardless of eccentricity after accounting for age and ethnicity. The results were similar when only eyes with mean deviation greater than -6 dB were analyzed. CONCLUSIONS: Ethnicity and distance from the fovea are the main determinants of IPL thickness in the central macula. Preferential thinning of the macular IPL, compared with GCL, could not be detected in this study regardless of glaucoma stage. TRANSLATIONAL RELEVANCE: There is no evidence for preferential thinning of the macular IPL in glaucoma compared with GCL based on currently available SD-OCT-imaging technology.

20.
Sci Rep ; 9(1): 5425, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30932002

RESUMO

The prevalence of urinary stone disease (USD) is rapidly rising. However, the factors driving this increase are unknown. Recent microbiome studies suggest that dysbiosis may in part contribute to the increasing prevalence. The objective of the current study was to determine the nature and location of dysbiosis associated with USD. We conducted microbiome analysis from the gastrointestinal and urinary tracts, along with a metabolomic analysis of the urinary metabolome, from subjects with an active episode of USD or no history of the disease. Higher rates of antibiotic use among USD patients along with integrated microbiome and metabolomic results support the hypothesis that USD is associated with an antibiotic-driven shift in the microbiome from one that protects against USD to one that promotes the disease. Specifically, our study implicates urinary tract Lactobacillus and Enterobacteriaceae in protective and pathogenic roles for USD, respectively, which conventional, culture-based methods of bacterial analysis from urine and kidney stones would not necessarily detect. Results suggest that antibiotics produce a long-term shift in the microbiome that may increase the risk for USD, with the urinary tract microbiome holding more relevance for USD than the gut microbiome.


Assuntos
Disbiose/microbiologia , Microbioma Gastrointestinal , Sistema Urinário/microbiologia , Urolitíase/microbiologia , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Metabolômica , Fatores de Risco
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