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PURPOSE: The effect of different types of lipid emulsion may guide therapy of patients with intestinal failure (IF) to limit morbidity such as intestinal failure-associated liver disease (IFALD). METHODS: A retrospective chart review of pediatric patients with IF who received soybean oil lipid emulsion (SL) or mixed oil lipid emulsion (ML) was performed. Data over 1 year were collected. RESULTS: Forty-five patients received SL and 34 received ML. There were no differences in the incidence (82 versus 74%, P = 0.35) or resolution (86 versus 92%, P = 0.5) of IFALD between the cohorts. The median dose of ML was higher compared to SL (2 versus 1 g/kg/day, P < 0.001). If resolved, IFALD resolved rapidly in the ML cohort compared to the SL cohort (67 versus 37 days, P = 0.01). Weight gain was higher in the ML compared to the SL cohort at resolution of IFALD or 1 year from diagnosis of IF (P = 0.009). CONCLUSION: The administration of ML did not alter the incidence or resolution of IFALD compared to SL in pediatric IF. There was rapid resolution of IFALD and enhanced weight gain in the ML cohort compared to SL in pediatric IF.
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Enteropatias , Insuficiência Intestinal , Hepatopatias , Falência Hepática , Humanos , Criança , Emulsões Gordurosas Intravenosas/uso terapêutico , Nutrição Parenteral , Estudos Retrospectivos , Enteropatias/tratamento farmacológico , Hepatopatias/complicações , Falência Hepática/complicações , Óleo de Soja/uso terapêutico , Aumento de Peso , Óleos de PeixeRESUMO
BACKGROUND: Hypoglycemia in neonates is common and contributes to 4.0-5.8% of neonatal intensive care unit (NICU) admissions. In utero nicotine exposure is underexplored as a potential contributor to neonatal hypoglycemia. Rat models have shown that in utero nicotine exposure can be associated with a reduction in pancreatic beta cell mass, leading to glucose dysregulation. The primary aim of this work is to study the risk of developing hypoglycemia after birth in a population of in utero nicotine-exposed neonates. METHODS: We conducted a retrospective matched cohort study that augmented an existing dataset of neonates admitted to a level IV NICU with household-based in utero nicotine exposure (Nâ=â335). Neonates in the control group parents denied household smoking (Nâ=â325), were born within a 6-month timeframe, and were within a birthweight of 50 grams of a nicotine-exposed neonate. Data reviewed included gestational age, growth parameters, maternal history of diabetes, and glucose levels within the first three hours of life per unit protocol. RESULTS: 660 neonates were included in the analysis. In utero nicotine exposure demonstrated a 94.3% posterior probability (PP) for greater hypoglycemia risk (RRâ=â1.185, 95% CrIâ=â[0.953, 1.445]). A 94.6% PP was demonstrated when neonates who were small for gestational age, intrauterine growth-restricted, and born to diabetic mothers were excluded (nâ=â482; RRâ=â1.271, 95% CrIâ=â[0.946, 1.669]). CONCLUSION: Nicotine exposure in utero was found to be a potential risk factor for developing hypoglycemia after birth. Mechanisms of action should be explored, and additional research on in utero nicotine exposure risks should follow.
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Hipoglicemia , Doenças do Recém-Nascido , Recém-Nascido , Feminino , Humanos , Ratos , Animais , Nicotina/efeitos adversos , Estudos Retrospectivos , Estudos de Coortes , Hipoglicemia/induzido quimicamente , Doenças do Recém-Nascido/epidemiologia , Retardo do Crescimento Fetal , GlucoseRESUMO
OBJECTIVE: To explore the use of an episode grouper to more accurately identify the complete set of surgical services typically provided in a surgical episode of care and the corresponding range of prices, using colectomy for cancer as the example. BACKGROUND: Price transparency is an important policy issue that will require surgeons to better understand the components and cost of care. METHODS: This study uses the Episode Grouper for Medicare business logic to construct colectomy surgical episodes of care for cancer using Medicare claims data for the Boston Hospital Referral Region from 2012 to 2015. Descriptive statistics show the mean reimbursement based on patient severity and stage of surgery, along with the number of unique clinicians billing for care and the mix of services provided. RESULTS: The Episode Grouper for Medicare episode grouper identified 3182 colectomies in Boston between 2012 and 2015, with 1607 done for cancer. The mean Medicare allowed amount per case is $29,954 and varies from $26,605 to $36,850 as you move from low to high-severity cases. The intrafacility stage is the most expensive ($23,175 on average) compared with the pre ($780) and post ($6,479) facility stages. There is tremendous heterogeneity in the service mix. CONCLUSIONS: Episode groupers are a potentially valuable tool for identifying variations in service mix and teaming patterns that correlate with a total price. By looking at patient care holistically, stakeholders can identify opportunities for price transparency and care redesign that have heretofore been hidden.
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Bass , Neoplasias , Cirurgiões , Idoso , Humanos , Estados Unidos , Animais , Cuidado Periódico , MedicareRESUMO
BACKGROUND: Outcomes data of intramedullary nail fixation (IMN) constructs for complex Schatzker VI tibial plateau fractures are scant in the literature. This study compares the clinical and radiographic outcomes of IMN, dual plate, and single plate constructs for Schatzker IV tibial plateau fractures. METHODS: Retrospective cohort study of sixty-two patients at a University-based Level 1 trauma center who underwent open reduction internal fixation for Schatzker VI tibial plateau fracture. Constructs evaluated were IMN (with or without raft screws), dual plating, and single plating. Demographic, clinical, and radiographic outcomes were recorded. All fractures were additionally classified based on the OTA classification for sub analyses. Mean follow-up was 13.2 (SD 13.3) months. Predictors of construct selection and outcomes were evaluated with bivariate logistic regression. Outcomes were compared between groups with independent samples t-tests and Chi Square tests. RESULTS: No significant demographic differences were found between IMN, dual plate or single plate construct cohorts. There was a higher proportion of open fractures within the IMN construct group versus the dual plate cohort (21.1% vs 3.6%). No statistically significant differences in radiographic outcomes were observed between cohort groups except for small but statistically significant differences in condylar width (CW) ratio change and tibial slope; when fracture cohorts were sub analyzed by specific OTA classification, there were no significant differences in any radiographic outcomes. There was a significant difference between the ratio of OTA 41C1, C2 and C3 fractures regarding treatment allocation (p = 0.004), favoring dual plate fixation for OTA 41C3 fractures. There were no significant differences found between treatment cohorts in terms of all cause complications (p > 0.05). IMN and single plate constructs were utilized when posteromedial condyle fractures were nondisplaced or minimally displaced. CONCLUSION: Intramedullary nail fixation with or without supplemental raft screws produced similar short-term clinical and radiographic results compared to dual and single plate constructs among patients with Schatzker VI fracture types, regardless of OTA classification. Level of Evidence Level III retrospective cohort.
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Fraturas da Tíbia , Fraturas do Planalto Tibial , Humanos , Estudos Retrospectivos , Fixação Interna de Fraturas/métodos , Placas Ósseas , Fraturas da Tíbia/diagnóstico por imagem , Fraturas da Tíbia/cirurgia , Resultado do TratamentoRESUMO
Clinical implementation of online adaptive radiation therapy requires initial and ongoing performance assessment of the underlying auto-segmentation and adaptive planning algorithms, although a straightforward and efficient process for this in phantom is lacking. The purpose of this work was to investigate robustness and repeatability of the artificial intelligence-assisted online segmentation and adaptive planning process on the Varian Ethos adaptive platform, and to develop an end-to-end test strategy for online adaptive radiation therapy. Five synthetic deformations were generated and applied to a computed tomography image of an anthropomorphic pelvis phantom, and reference treatment plans were generated from each of the resulting deformed images. The undeformed phantom was repeatedly imaged, and the online adaptive process was performed including auto-segmentation, review and manual correction of contours, and adaptive plan creation. One adaptive fractions in five different deformation scenarios were performed. The manually corrected contours had a high degree of consistency (> 93% Dice similarity coefficient and < 1.0 mm mean surface distance) across repeated fractions, with no significant variation across the synthetic deformation instance except for bowel (p = 0.026, one-way ANOVA). Adaptive treatment plans also resulted in highly consistent dose-volume values for targets and organs at risk. A straightforward and efficient process was developed and used to quantify a set of organ specific contouring and dosimetric action levels to help establish uncertainty bounds for an end-to-end test on the Varian Ethos system.
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Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada , Inteligência Artificial , Humanos , Órgãos em Risco , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Reprodutibilidade dos TestesRESUMO
Platelet-rich plasma (PRP) has been investigated to promote wound healing in a variety of tissues. Thrombin, another essential component of wound healing, is sometimes combined with PRP to generate a fibrin clot in order to retain the sample at the delivery site and to stimulate growth factor release. Using a fully autologous approach, autologous serum (AS) with thrombin activity can be prepared using a one-step procedure by supplementing with ethanol (E+ AS) to prolong room temperature stability or prepared ethanol free (E- AS) by utilizing a two-step procedure to prolong stability. The objective of this study was to evaluate potential wound healing mechanisms of these two preparations using commercially available devices. A variety of tests were conducted to assess biocompatibility and growth factor release from PRP at various ratios. It was found that E- AS contained greater leukocyte viability in the product (97.1 ± 2.0% compared to 41.8 ± 11.5%), supported greater bone marrow mesenchymal stem cell proliferation (3.7× vs 0.8× at a 1:4 ratio and 3.6× vs 1.6× at a 1:10 ratio), and stimulated release of growth factors and cytokines from PRP to a greater extent than E+ AS. Of the 36 growth factors and cytokines evaluated, release of 27 of them were significantly reduced by the presence of ethanol in at least one of the tested configurations. It is concluded that the high concentrations of ethanol needed to stabilize point of care autologous thrombin preparations could be detrimental to normal wound healing processes.
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Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Lesões dos Tecidos Moles/tratamento farmacológico , Trombina/farmacologia , Cicatrização/efeitos dos fármacos , Adulto , Idoso , Contagem de Células , Feminino , Hemostáticos/farmacologia , Humanos , Leucócitos/patologia , Masculino , Células-Tronco Mesenquimais/patologia , Pessoa de Meia-Idade , Lesões dos Tecidos Moles/metabolismo , Lesões dos Tecidos Moles/patologia , Adulto JovemRESUMO
Australian freshwaters have relatively low water hardness and different calcium (Ca) to magnesium (Mg) ratios compared with those in Europe. The hardness values of a substantial proportion of Australian freshwaters fall below the application boundary of the existing European nickel biotic ligand models (Ni BLMs) of 2 mg Ca/L. Toxicity testing was undertaken using Hydra viridissima to assess the predictive ability of the existing Ni BLM for this species in extremely soft waters. This testing revealed an increased competitive effect of Ca and Mg with Ni for binding to the biotic ligand in soft water (<10 mg CaCO3 /L) than at higher water hardness. Modifications were made to the Ni BLM by increasing the binding constants for Ca and Mg at the biotic ligand to account for softer waters encountered in Australia and the more important competitive effect of Ca and Mg on Ni toxicity. To validate the modified Ni BLM, ecotoxicity testing was performed on 5 Australian test species in 5 different natural Australian waters. Overall, no single water chemistry parameter was able to indicate the trends in toxicity to all of the test species. The modified Ni BLMs were able to predict the toxicity of Ni to the test species in the validation studies in natural waters better than the existing Ni BLMs. The present study suggests that the overarching mechanisms defining Ni bioavailability to freshwater species are globally similar and that Ni BLMs can be used in all freshwater systems with minor modifications. Environ Toxicol Chem 2018;37:2566-2574. © 2018 SETAC.
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Organismos Aquáticos/efeitos dos fármacos , Água Doce , Modelos Teóricos , Níquel/toxicidade , Animais , Austrália , Disponibilidade Biológica , Cálcio/análise , Hydra/efeitos dos fármacos , Ligantes , Magnésio/análise , Reprodutibilidade dos Testes , Especificidade da Espécie , Testes de Toxicidade , Poluentes Químicos da ÁguaRESUMO
Neonatal purpura fulminans (PF) is a life-threatening disorder caused by congenital or acquired deficiencies of protein C (PC) or S. PF presents as a cutaneous manifestation of disseminated intravascular coagulation. We describe a case of PF in a newborn with left leg ischemia and undetectable PC levels soon after birth. Despite anticoagulation therapy and PC concentrate, left foot amputation was required. Genetic testing of PROC for congenital PC deficiency was normal. This case highlights the course of PF due to acquired PC deficiency in a newborn treated with PC concentrate which is rarely described in the literature.
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Doenças do Recém-Nascido , Deficiência de Proteína C , Púrpura Fulminante , Humanos , Recém-Nascido , Doenças do Recém-Nascido/sangue , Doenças do Recém-Nascido/genética , Masculino , Deficiência de Proteína C/sangue , Deficiência de Proteína C/genética , Púrpura Fulminante/sangue , Púrpura Fulminante/genéticaRESUMO
BACKGROUND: Standardized definitions and methods of surveillance for local recurrence of nonmelanoma skin cancer are critical in determining cure rates attributed to treatment modalities. OBJECTIVE: We sought to offer a standard definition of local recurrence after surgical treatment of nonmelanoma skin cancer and to propose an acceptable surveillance period and tracking methods. METHODS: A literature search was performed for background definitions of local recurrence and tracking methods. The American College of Mohs Surgery (ACMS) Registry and Outcomes Committee then conducted a modified Delphi process to arrive at consensus definitions. RESULTS: We define local recurrence as a tumor with comparable histology, with contiguity to the surgical scar after treatment, and that arises within the area of the previously treated tumor. LIMITATIONS: This project reports the results of a modified Delphi method process involving members of the ACMS. The model described may not be useful for nonexcision type treatments such as topical chemotherapy, electrodessication and curettage, or radiation treatment. CONCLUSIONS: Previous definitions of recurrence and surveillance methods after surgical treatment of nonmelanoma skin cancer are variable and nonstandard. We describe consensus standards for defining and tracking recurrence that should allow for consistent scientific evaluation and development of performance data in skin cancer outcomes registries.
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Carcinoma Basocelular/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Cirurgia de Mohs , Recidiva Local de Neoplasia/diagnóstico , Neoplasias Cutâneas/diagnóstico , Algoritmos , Carcinoma Basocelular/patologia , Carcinoma Basocelular/cirurgia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Cicatriz/patologia , Consenso , Técnica Delphi , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Margens de Excisão , Modelos Teóricos , Metástase Neoplásica , Segunda Neoplasia Primária/diagnóstico , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Design de Software , Resultado do TratamentoRESUMO
RATIONALE: The Precursor Acquisition Independent From Ion Count (PAcIFIC) method is a data-independent acquisition technique capable of identifying proteins over eight orders of magnitude in a single analysis in human plasma. Widespread application of this technique in proteomic studies is hindered by its time-intensive nature. There exists a need to explore strategies to increase the throughput of the PAcIFIC method. METHODS: The PAcIFIC acquisition technique was optimized for use with an Orbitrap mass spectrometer fitted with a captive spray ionization (CSI) source. Chromatographic methods, PAcIFIC acquisition parameters, for example, channels interrogated per chromatographic gradient, time span of chromatographic gradient, and sample loading amount, were investigated to achieve a maximum number of peptide and protein identifications on a yeast proteome where protein copy number had been previously determined. RESULTS: A 24-hour CSI PAcIFIC method was developed with minimal reduction of peptide and protein identifications from the 4.2-day nano-electrospray ionization (nESI) PAcIFIC method. Analysis of a yeast cell lysate with the 4.2-day nESI PAcIFIC method resulted in 13,468 peptide and 2120 protein identifications. A 24-hour CSI PAcIFIC method resulted in 11,277 peptide and 1753 protein identifications. Increased sample loading of the CSI system allowed for an 8% increase in peptide and protein identifications. CONCLUSIONS: A dramatic decrease in the overall analysis time of the PAcIFIC method (24 h with CSI versus 100.8 h with nESI) was achieved with minimal reduction of peptide and protein identifications. Furthermore, the CSI PAcIFIC method demonstrated a high degree of sensitivity and capability of identifying proteins across a large dynamic range observed with the nESI PAcIFIC method (CSI PAcIFIC identified proteins as low as 46 molecules per cell).
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Proteínas Fúngicas/química , Espectrometria de Massas/métodos , Proteômica/métodos , Leveduras/química , Proteínas Fúngicas/metabolismo , Humanos , Peptídeos/química , Peptídeos/metabolismo , Leveduras/metabolismoRESUMO
All-trans-retinoic acid (atRA) is the active metabolite of vitamin A. The liver is the main storage organ of vitamin A, but activation of the retinoic acid receptors (RARs) in mouse liver and in human liver cell lines has also been shown. AlthoughatRA treatment improves mitochondrial function in skeletal muscle in rodents, its role in modulating mitochondrial function in the liver is controversial, and little data are available regarding the human liver. The aim of this study was to determine whetheratRA regulates hepatic mitochondrial activity.atRA treatment increased the mRNA and protein expression of multiple components of mitochondrialß-oxidation, tricarboxylic acid (TCA) cycle, and respiratory chain. Additionally,atRA increased mitochondrial biogenesis in human hepatocytes and in HepG2 cells with and without lipid loading based on peroxisome proliferator activated receptor gamma coactivator 1αand 1ßand nuclear respiratory factor 1 mRNA and mitochondrial DNA quantification.atRA also increasedß-oxidation and ATP production in HepG2 cells and in human hepatocytes. Knockdown studies of RARα, RARß, and PPARδrevealed that the enhancement of mitochondrial biogenesis andß-oxidation byatRA requires peroxisome proliferator activated receptor delta. In vivo in mice,atRA treatment increased mitochondrial biogenesis markers after an overnight fast. Inhibition ofatRA metabolism by talarozole, a cytochrome P450 (CYP) 26 specific inhibitor, increased the effects ofatRA on mitochondrial biogenesis markers in HepG2 cells and in vivo in mice. These studies show thatatRA regulates mitochondrial function and lipid metabolism and that increasingatRA concentrations in human liver via CYP26 inhibition may increase mitochondrial biogenesis and fatty acidß-oxidation and provide therapeutic benefit in diseases associated with mitochondrial dysfunction.
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Mitocôndrias Hepáticas/metabolismo , Dinâmica Mitocondrial/efeitos dos fármacos , PPAR delta/agonistas , Transdução de Sinais , Tretinoína/metabolismo , Regulação para Cima , Animais , Benzotiazóis/farmacologia , Células Cultivadas , Inibidores das Enzimas do Citocromo P-450/farmacologia , Sistema Enzimático do Citocromo P-450/química , Sistema Enzimático do Citocromo P-450/metabolismo , Feminino , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/enzimologia , Hepatócitos/metabolismo , Humanos , Masculino , Camundongos , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/enzimologia , Biogênese de Organelas , PPAR delta/antagonistas & inibidores , PPAR delta/genética , PPAR delta/metabolismo , Interferência de RNA , Receptores do Ácido Retinoico/agonistas , Receptores do Ácido Retinoico/antagonistas & inibidores , Receptores do Ácido Retinoico/genética , Receptores do Ácido Retinoico/metabolismo , Ácido Retinoico 4 Hidroxilase , Receptor alfa de Ácido Retinoico , Triazóis/farmacologia , Regulação para Cima/efeitos dos fármacosRESUMO
OBJECTIVES: Postprandial atherogenic lipoproteins, characterizing high-risk patients, correlate positively with cardiovascular events. Although the effect of niacin on fasting lipids is well established, its impact on atheroprotective reverse cholesterol transport (RCT) pathway and on functional features of circulating lipoproteins during the postprandial state remains indeterminate. APPROACH AND RESULTS: We evaluated RCT pathway during postprandial phase in dyslipidemic patients displaying a low high-density lipoprotein (HDL) cholesterol phenotype. Ten subjects on stable statin therapy received 1 g/20 mg extended-release niacin/laropiprant (ERN/LRPT) for 4 weeks followed by 2 g/40 mg ERN/LRPT for additional 8 weeks. At each experimental period, postprandial hypertriglyceridemia and major steps of RCT, including cholesterol efflux from human macrophages, cholesteryl ester transfer protein-mediated cholesteryl ester transfer, and hepatic HDL-cholesteryl ester selective uptake were evaluated. Equally, the capacity of postprandial HDL particles isolated from patients before and after ERN/LRPT treatment to mediate RCT to feces was evaluated in vivo in human apolipoprotein B/cholesteryl ester transfer protein double transgenic mouse model. Compared with baseline, ERN/LRPT significantly reduced postprandial hypertriglyceridemia (incremental area under the curve-triglyceride: -53%; P=0.02). Postprandial increase in endogenous plasma cholesteryl ester transfer protein activity was completely abolished after ERN/LRPT treatment. Despite a slight reduction in plasma cholesterol efflux capacity from human THP-1 macrophages, evaluation of global RCT efficacy by combining both ex vivo and in vivo approaches indicate that postprandial HDL particles formed under ERN/LRPT therapy displayed a greater capacity for HDL-mediated RCT to feces. CONCLUSIONS: ERN/LRPT treatment efficiently attenuates atherogenic postprandial lipemia and stimulates HDL-mediated cholesterol return to the liver and elimination into feces during postprandial phase, thus maintaining an efficient removal of cholesterol from the body.
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Anticolesterolemiantes/uso terapêutico , Colesterol/sangue , Dislipidemias/tratamento farmacológico , Indóis/uso terapêutico , Fígado/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Niacina/uso terapêutico , Período Pós-Prandial , Idoso , Animais , Apolipoproteína B-100/genética , Apolipoproteína B-100/metabolismo , Transporte Biológico , Células CHO , Linhagem Celular Tumoral , Proteínas de Transferência de Ésteres de Colesterol/genética , Proteínas de Transferência de Ésteres de Colesterol/metabolismo , HDL-Colesterol/sangue , Cricetulus , Combinação de Medicamentos , Dislipidemias/sangue , Dislipidemias/diagnóstico , Fezes/química , Feminino , Humanos , Fígado/metabolismo , Macrófagos/metabolismo , Masculino , Camundongos Transgênicos , Pessoa de Meia-Idade , Fatores de Tempo , Transfecção , Resultado do TratamentoRESUMO
The ability of the thymus gland to convert bone marrow-derived progenitor cells into single positive (SP) T-cells is well known. In this review we present evidence that the thymus, in addition to producing SP T-cells, also has a pathway for the production of double negative (DN) T-cells. The existence of this pathway was noted during our examination of relevant literature to determine the cause of sex steroid-induced thymocyte loss. In conducting this search our objective was to answer the question of whether thymocyte loss is the end product of a typical interaction between the reproductive and immune systems, or evidence that the two systems are incompatible. We can now report that "thymocyte loss" is a normal process that occurs during the production of DN T-cells. The DN T-cell pathway is unique in that it is mediated by thymic mast cells, and becomes functional following puberty. Sex steroids initiate the development of the pathway by binding to an estrogen receptor alpha located in the outer membrane of the mast cells, causing their activation. This results in their uptake of extracellular calcium, and the production and subsequent release of histamine and serotonin. Lymphatic vessels, located in the subcapsular region of the thymus, respond to the two vasodilators by undergoing a substantial and preferential uptake of gamma/delta and alpha/beta DN T- cells. These T- cells exit the thymus via efferent lymphatic vessels and enter the lymphatic system.The DN pathway is responsible for the production of three subsets of gamma/delta DN T-cells and one subset of alpha/beta DN T-cells. In postpubertal animals approximately 35 % of total thymocytes exit the thymus as DN T-cells, regardless of sex. In pregnant females, their levels undergo a dramatic increase. Gamma/delta DN T-cells produce cytokines that are essential for the maintenance of pregnancy.
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Linfócitos T/fisiologia , Timócitos/fisiologia , Timo/fisiologia , Animais , Diferenciação Celular , Feminino , Humanos , Gravidez , Linfócitos T/citologia , Timócitos/citologia , Timo/citologiaRESUMO
DOG1 is a highly sensitive marker for gastrointestinal stromal tumor (GIST) and is in the routine diagnostic antibody repertoire of many surgical pathology laboratories. Moreover, GIST is well recognized by both pathologists and clinicians in the differential diagnosis of intra-abdominal and pelvic neoplasms. Low-grade fibromyxoid sarcoma (LGFMS) is, however, much less frequently anticipated, particularly when occurring at unusual sites, because of its rarity and bland histology, particularly on core biopsy. We describe a case of a 53-year-old male with a large pelvic and pararectal mass, which on biopsy showed a moderately cellular spindle cell neoplasm within fibrous stroma. Immunohistochemistry at the referring center showed diffuse and strong expression of DOG1 with negativity for other markers. After referral to a tertiary center, repeat DOG1 immunohistochemistry again showed diffuse expression, but MUC4 was also positive, and this was confirmed to be LGFMS, harboring FUS-CREB3L2 fusion transcripts by reverse transcription-polymerase chain reaction and FUS rearrangement with fluorescence in situ hybridization. In view of this we assessed DOG1 expression in 10 other LGFMS (all MUC4 positive, and 9 molecularly confirmed to harbor FUS-CREB3L2 fusion transcripts and/or FUS or EWSR1 gene rearrangement), of which 5 showed DOG1 expression in up to 75% of tumor cells, varying in intensity from weak to strong. While LGFMS and GIST are generally morphologically dissimilar, less typical variants of each exist, and both can contain bland spindled cells within fibrous stroma. As the morphologic spectrum of LGFMS is wide, and as it can occur in unusual sites and may not be well recognized by general pathologists and non-soft tissue pathologists, we highlight the potential for diagnostic confusion with GIST owing to aberrant DOG1 expression. This is clinically pertinent, as the management and prognosis of these 2 neoplasms differs significantly.
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Neoplasias Abdominais/diagnóstico , Biomarcadores Tumorais/metabolismo , Canais de Cloreto/metabolismo , Fibrossarcoma/diagnóstico , Tumores do Estroma Gastrointestinal/diagnóstico , Proteínas de Neoplasias/metabolismo , Neoplasias Pélvicas/diagnóstico , Neoplasias Abdominais/genética , Neoplasias Abdominais/metabolismo , Anoctamina-1 , Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Biomarcadores Tumorais/genética , Diagnóstico Diferencial , Fibrossarcoma/genética , Fibrossarcoma/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Mucina-4/metabolismo , Gradação de Tumores , Neoplasias Pélvicas/genética , Neoplasias Pélvicas/metabolismoRESUMO
BACKGROUND: Familial hypercholesterolaemia (FH) is a hereditary disorder predisposing to premature coronary heart disease (CHD) and is until now mainly diagnosed clinically on the basis of a classical phenotype. Its prevalence varies and is estimated around 1 in 200-500; in patients with established CHD the prevalence is less well documented. METHODS AND RESULTS: In EUROASPIRE IV data were collected in coronary patients from 24 European countries by means of a standardized interview, bioclinical examination and venous blood sampling. Potential FH was estimated using an adapted version of the Dutch Lipid Clinic Network Criteria. Among the 7044 patients eligible for analysis, the prevalence of potential FH was 8.3%; 7.5% in men and 11.1% in women. The prevalence was inversely related to age with a putative prevalence of 1:5 in those with CHD <50 yrs of age in both sexes. Even among women aged 70 the prevalence was 1:10. Irrespective of age and gender, prevalence differed substantially between European regions; potential FH patients were more likely to smoke, had higher triglycerides levels and their blood pressure was less well controlled. The use of cardioprotective drugs and the prevalences of diabetes, obesity and central obesity were similar. CONCLUSIONS: The prevalence of potential FH in coronary patients is high; the results underscore the need to promote identification of FH in CHD patients and to improve their risk factor profile.
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Doença das Coronárias/epidemiologia , Doença das Coronárias/terapia , Hiperlipoproteinemia Tipo II/epidemiologia , Hiperlipoproteinemia Tipo II/terapia , Distribuição por Idade , Fatores Etários , Idoso , Comorbidade , Doença das Coronárias/diagnóstico , Doença das Coronárias/genética , Estudos Transversais , Europa (Continente)/epidemiologia , Feminino , Predisposição Genética para Doença , Inquéritos Epidemiológicos , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genética , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Fenótipo , Prevalência , Fatores de Risco , Distribuição por Sexo , Fatores Sexuais , Resultado do TratamentoRESUMO
The aim of this study was to investigate if the anti-androgen, flutamide, and the estrogen, 17ß-estradiol work together to feminize juvenile Murray rainbowfish (Melanotaenia fluviatilis). Fish (60 days post-hatch) were exposed to 25 ng/L 17ß-estradiol (E2), 25 µg/L flutamide (Flu low), 250 µg/L flutamide (Flu high), E2 + Flu low and E2 + Flu high. After 35 days of exposure, concentrations of sex steroid hormones, 17ß-estradiol and 11-keto testosterone (11-KT), were determined in the head; and vitellogenin (VTG) concentration was measured in the tail. The abdomens were used for histological investigation of the gonads. Treatment with E2 + Flu high resulted in reduction in body weights and lengths in males and condition factor in females. Intersex was noted in Flu high and E2 + Flu high treatments. Exposures to E2 and/or Flu (low and high) resulted in precocious oocyte development but inhibited sperm development. The 17ß-estradiol levels decreased significantly in the heads of both sexes after exposures to E2 and/or Flu (high and low). Flu high and E2 alone increased the 11-KT levels in both sexes. However, E2 + Flu low decreased 11-KT levels in males and increased them in females. Flutamide (low and high) induced VTG protein in the tails of both sexes. In males, VTG was not induced in the tail after exposure to E2. No significant effect of flutamide on E2-induced VTG concentration was noted. We conclude that co-treatment with flutamide and 17ß-estradiol does not lead to additive reproductive impairment in juvenile Murray rainbowfish.
Assuntos
Antagonistas de Androgênios/efeitos adversos , Estradiol/efeitos adversos , Peixes , Flutamida/efeitos adversos , Reprodução/efeitos dos fármacos , Animais , Transtornos do Desenvolvimento Sexual/induzido quimicamente , Relação Dose-Resposta a Droga , Estrogênios/efeitos adversos , Feminino , Hormônios Esteroides Gonadais/metabolismo , Gônadas/efeitos dos fármacos , Gônadas/fisiopatologia , Masculino , Oogênese/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Testosterona/análogos & derivados , Testosterona/metabolismo , Vitelogeninas/metabolismo , Poluentes Químicos da ÁguaRESUMO
BACKGROUND: Parkinson's disease patients are more likely to be hospitalized, have higher rates of hospital complications, and have an increased risk of deterioration during hospitalization. Length of stay is an important underlying factor for these increased risks. We aimed to investigate potential medication errors that may occur during hospitalization and its impact on length of hospital stay. METHODS: A cross-sectional chart review of 339 consecutive hospital encounters from 212 PD subjects was performed. Medication errors were defined as wrong timing or omission of administration for dopaminergic drugs and administration of contraindicated dopamine blockers. An analysis of covariance was applied to examine whether these medication errors were related to increased length of hospital stays. RESULTS: A significant effect for dopaminergic administration (p<0.01) on length of hospital stay was observed. Subjects who had delayed administration or missed at least one dose stayed longer (M=8.2 days, SD=8.9 vs. M=3.6 days SD=3.4). Contraindicated dopamine blocking agents were administered in 23% (71/339) of cases, and this was also significantly related to an increased length of stay (M=8.2 days, SD=8.9 vs. M=3.6 days SD=3.4), p<0.05. Participants who received a contraindicated dopamine blocker stayed in the hospital longer (M=7.5 days, SD=9.1) compared to those who did not (M=5.9 days, SD=6.8). Neurologists were consulted in 24.5% of encounters. Specialty consultation had no effect on the medication related errors. CONCLUSIONS: Missing dopaminergic dosages and administration of dopamine blockers occur frequently in hospitalized Parkinson's disease patients and this may impact length of stay. These potentially modifiable factors may reduce the risk of a longer stay related to hospitalization.
Assuntos
Antiparkinsonianos/administração & dosagem , Antipsicóticos/uso terapêutico , Dopaminérgicos/administração & dosagem , Antagonistas de Dopamina/efeitos adversos , Hospitalização , Erros de Medicação , Doença de Parkinson/tratamento farmacológico , Acidentes por Quedas/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Antipsicóticos/efeitos adversos , Contraindicações , Estudos Transversais , Antagonistas de Dopamina/administração & dosagem , Esquema de Medicação , Registros Eletrônicos de Saúde , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Encaminhamento e Consulta/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
Composite hemangioendothelioma (HE) is a rare vascular neoplasm of intermediate malignant potential that predominantly occurs within the dermis or subcutis of the extremities, and occurs in a wide age range. It is locally aggressive with a high rate of local recurrence, and more rarely regional lymph node or distant metastasis. Histologically, it is composed of a complex admixture of benign, intermediate and malignant vascular components. Although composite HE may contain angiosarcoma-like areas, its prognosis is better than that of pure angiosarcoma. We describe a case of composite HE presenting as a submandibular mass in a 43 year-old male, which included areas of prominent 'high grade' epithelioid angiosarcoma. This adds to the range of anatomic sites of these neoplasms, highlights the importance of recognition of the head and neck as a potential site, and emphasizes the importance of accurate diagnosis for correct management (including of long term follow up) and prognostication.
Assuntos
Hemangioendotelioma/patologia , Neoplasias da Glândula Submandibular/patologia , Adulto , Biomarcadores Tumorais/análise , Humanos , Imuno-Histoquímica , MasculinoRESUMO
BACKGROUND: As both lifetime and daily use of marijuana remain prevalent among US adolescents and are likely to increase, given the legalisation of marijuana in a number of states, their correlates with other negative (including delinquent) behaviours have been studied. Most of this research has been carried out with general-population-based samples. Thus, little is known about this association among court-involved and detained juveniles. AIMS: This study aimed to assess lifetime and daily marijuana use among detainees aged 10-16 years. Our hypotheses were that such use would be higher among youth who had been in detention than in general population samples and that it would be associated with other mental health indicators and criminal justice indicators, such as total number of detentions and number and types of charges. METHODS: The records of a random 20% sample of all juveniles in detention in Connecticut's state facilities were studied. Data extracted included self-reported information on lifetime and daily use of marijuana, mental health indicators, lifetime psychiatric diagnoses and criminal justice indicators. RESULTS: Rates of both lifetime (54%) and daily (16%) use of marijuana in this sample of 371 young people were substantially higher than previous studies have reported in general population samples. As a group, daily users of marijuana demonstrated a more negative mental health profile but did not differ from the rest of the sample in their criminal justice indicators. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Our findings suggest that it is unlikely that cannabis use by young offenders can serve as an independent factor in understanding the frequency and severity of delinquency, although it might be associated with the severity of mental health disorder or dysfunction among them.