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1. The study evaluated the effect of dietary metabolisable energy (ME) content and crude protein (CP) level on the growth performance and behaviour of ducks.2. A total of 720, Cherry Valley ducks were allocated to 36 pens in groups of 20 birds. For the initial period, from 1 to 21 d age, six diets, containing a standard (SME), low (LME) and high (HME) ME of 12.14, 11.93 and 12.35 MJ/kg, and standard (SCP) or high (HCP) CP contents of 210 or 220 g/kg diet, respectively, were mixed. For the period from 22 to 42 d age, the diets contained ME of 12.98 (SME), 12.77 (LME), 13.19 (HME) MJ/kg and the levels of CP were 170 (SCP) or 180 (HCP) g/kg, respectively.3. An ME by CP interaction was seen from 1 to 21 d age in ducks fed HME + HCP diet, which had greater weight gain than those fed LME + SCP (P < 0.05). Compared to LME + SCP, dietary HME decrease feeding but increased walking behaviour compared to LME + SCP and SME + SCP (P < 0.05). High CP in LME and SME diets increased drinking behaviour (P < 0.05), but there was no change in HME diet. Compared to LME, feeding HME reduced ground pecking (P < 0.05). Feeding HME reduced feeding behaviour (P < 0.05) from 22 to 42 d age. During the same period, standing behaviour was reduced in HCP + LME (P < 0.05). Drinking was reduced in LME + SCP compared to SME + HCP and HME + HCP (P < 0.05).4. A diet formulated with HME and HCP is effective for enhancing growth performance of ducks aged 1-21 d and saving time for feeding or ground pecking, which may induce spending more time on other activities.
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Galinhas , Patos , Animais , Fenômenos Fisiológicos da Nutrição Animal , Dieta/veterinária , Aumento de PesoRESUMO
OBJECTIVE: To determine the effects of acute (≤7 days) femoral head ischemia on the proximal femoral growth plate and metaphysis in a piglet model of Legg-Calvé-Perthes disease (LCPD). We hypothesized that qualitative and quantitative histological assessment would identify effects of ischemia on endochondral ossification. DESIGN: Unilateral femoral head ischemia was surgically induced in piglets, and femurs were collected for histological assessment at 2 (n = 7) or 7 (n = 5) days post-ischemia. Samples were assessed qualitatively, and histomorphometry of the growth plate zones and primary spongiosa was performed. In a subset of samples at 7 days, hypertrophic chondrocytes were quantitatively assessed and immunohistochemistry for TGFß1 and Indian hedgehog was performed. RESULTS: By 2 days post-ischemia, there was significant thinning of the proliferative and hypertrophic zones, by 63 µm (95% CI -103, -22) and -19 µm (95% CI -33, -5), respectively. This thinning persisted at 7 days post-ischemia. Likewise, at 7 days post-ischemia, the primary spongiosa was thinned to absent by an average of 311 µm (95% CI -542, -82) in all ischemic samples. TGFß1 expression was increased in the hypertrophic zone at 7 days post-ischemia. CONCLUSIONS: Alterations to the growth plate zones and metaphysis occurred by 2 days post-ischemia and persisted at 7 days post-ischemia. Our findings suggest that endochondral ossification may be disrupted at an earlier time point than previously reported and that growth disruption may occur in the piglet model as occurs in some children with LCPD.
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Doença de Legg-Calve-Perthes , Animais , Suínos , Doença de Legg-Calve-Perthes/patologia , Cabeça do Fêmur/patologia , Lâmina de Crescimento/patologia , Proteínas Hedgehog , IsquemiaRESUMO
OBJECTIVE: To determine if the quantitative MRI techniques T2 and T1ρ mapping are sensitive to ischemic injury to epiphyseal cartilage in vivo in a piglet model of Legg-Calvé-Perthes disease using a clinical 3T MRI scanner. We hypothesized that T2 and T1ρ relaxation times would be increased in the epiphyseal cartilage of operated vs contralateral-control femoral heads 1 week following onset of ischemia. DESIGN: Unilateral femoral head ischemia was surgically induced in eight piglets. Piglets were imaged 1 week post-operatively in vivo at 3T MRI using a magnetization-prepared 3D fast spin echo sequence for T2 and T1ρ mapping and a 3D gradient echo sequence for cartilage segmentation. Ischemia was confirmed in all piglets using gadolinium contrast-enhanced MRI. Median T2 and T1ρ relaxation times were measured in the epiphyseal cartilage of the ischemic and control femoral heads and compared using paired t-tests. Histological assessment was performed on a subset of five piglets. RESULTS: T2 and T1ρ relaxation times were significantly increased in the epiphyseal cartilage of the operated vs control femoral heads (ΔT2 = 11.9 ± 3.7 ms, 95% CI = [8.8, 15.0] ms, P < 0.0001; ΔT1ρ = 12.8 ± 4.1 ms, 95% CI = [9.4, 16.2] ms, P < 0.0001). Histological assessment identified chondronecrosis in the hypertrophic and deep proliferative zones within ischemic epiphyseal cartilage. CONCLUSIONS: T2 and T1ρ mapping are sensitive to ischemic injury to the epiphyseal cartilage in vivo at clinical 3T MRI. These techniques may be clinically useful to assess injury and repair to the epiphyseal cartilage to better stage the extent of ischemic damage in Legg-Calvé-Perthes disease.
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Cartilagem Articular , Doença de Legg-Calve-Perthes , Animais , Cartilagem/patologia , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/patologia , Cabeça do Fêmur/diagnóstico por imagem , Cabeça do Fêmur/patologia , Lâmina de Crescimento/diagnóstico por imagem , Lâmina de Crescimento/patologia , Isquemia/diagnóstico por imagem , Isquemia/etiologia , Doença de Legg-Calve-Perthes/diagnóstico por imagem , Doença de Legg-Calve-Perthes/patologia , Imageamento por Ressonância Magnética/métodos , SuínosRESUMO
AIM: This study aimed to evaluate an association between colorectal neoplasm (CRN) and skeletal muscle mass using three widely accepted skeletal muscle mass indices (SMIs) in a large population at average risk. METHOD: We performed a cross-sectional study using a screening colonoscopy database of 33 958 asymptomatic subjects aged 40-75 years. Appendicular skeletal muscle mass (ASM) was measured using a bioelectrical impedance analyser. ASM adjusted for height squared (ASM/ht2 ), weight (ASM/wt) and body mass index (ASM/BMI) were used as indices for muscle mass. Logistic regression models were used to evaluate the association between SMIs and CRN. RESULTS: In a multivariable-adjusted model, the risk of an advanced CRN increased linearly with decreasing quartiles for all three SMIs. The adjusted odds ratios (ORs) for advanced CRN in quartiles 1, 2 and 3 of ASM/wt compared with that in quartile 4 were 1.279, 1.196 and 1.179, respectively (Ptrend = 0.017); for ASM/BMI, ORs were 1.307, 1.144 and 1.091, respectively (Ptrend = 0.002); and for ASM/ht2 , ORs were 1.342, 1.169 and 1.062, respectively (Ptrend = 0.002). The risk of distally located advanced CRN was higher in quartile 1 than in quartile 4 for all three SMIs (ASM/wt, OR = 1.356; ASM/BMI, OR = 1.383; ASM/ht2 , OR = 1.430). CONCLUSION: Our study demonstrated that low skeletal muscle mass was consistently associated with the presence of advanced CRN in a population at average risk regardless of the operational definition of the SMI, and it was particularly associated with distal advanced CRN.
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Neoplasias Colorretais , Sarcopenia , Índice de Massa Corporal , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Estudos Transversais , Humanos , Músculo Esquelético , Sarcopenia/complicações , Sarcopenia/diagnóstico por imagem , Sarcopenia/epidemiologiaRESUMO
In 1997, it was predicted that an electronically excited atom or molecule placed in a loosely bound chemical system (such as a hydrogen-bonded or van-der-Waals-bonded cluster) could efficiently decay by transferring its excess energy to a neighbouring species that would then emit a low-energy electron. This intermolecular Coulombic decay (ICD) process has since been shown to be a common phenomenon, raising questions about its role in DNA damage induced by ionizing radiation, in which low-energy electrons are known to play an important part. It was recently suggested that ICD can be triggered efficiently and site-selectively by resonantly core-exciting a target atom, which then transforms through Auger decay into an ionic species with sufficiently high excitation energy to permit ICD to occur. Here we show experimentally that resonant Auger decay can indeed trigger ICD in dimers of both molecular nitrogen and carbon monoxide. By using ion and electron momentum spectroscopy to measure simultaneously the charged species created in the resonant-Auger-driven ICD cascade, we find that ICD occurs in less time than the 20 femtoseconds it would take for individual molecules to undergo dissociation. Our experimental confirmation of this process and its efficiency may trigger renewed efforts to develop resonant X-ray excitation schemes for more localized and targeted cancer radiation therapy.
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Elétrons , Monóxido de Carbono/química , Dano ao DNA/efeitos da radiação , Elétrons/uso terapêutico , Íons , Cinética , Neoplasias/radioterapia , Nitrogênio/química , Análise Espectral , Fatores de Tempo , Raios XRESUMO
Background: The possibility of an association between early menopause and the risk of non-alcoholic fatty liver disease (NAFLD) is as yet unclear.Methods: The subjects consisted of 4354 postmenopausal women who participated in the 2010-2012 Korea National Health and Nutrition Examination Survey. Early, normal, and late menopause were defined as age at menopause <45 years, 45-54 years, and ≥55 years, respectively. NAFLD was defined by a hepatic steatosis index of >36.Results: When compared with normal menopausal women, early or late menopausal women had no significant differences in the odds ratios (ORs) of NAFLD: OR = 1.05, 95% confidence interval (CI), 0.83-1.32 and OR = 1.02, 95% CI, 0.75-1.39, respectively. These results remained similar after adjustment for known risk factors for NAFLD, reproductive factors, and comorbidities. The OR for NAFLD per 1-year increase in age at menopause was 1.01 (95% CI, 0.99-1.03; p = 0.329). The prevalence of advanced fibrosis was 2.1% (95% CI, 0.7-6.4%), 2.2% (95% CI, 1.3-3.8%), and 3.9% (95% CI, 1.2-12.2%) in early, normal, and late menopausal women, respectively.Conclusions: This study provides no evidence for an association of early menopause with NAFLD risk. However, NAFLD-related advanced fibrosis is highly prevalent in postmenopausal women.
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Menopausa Precoce , Hepatopatia Gordurosa não Alcoólica/etiologia , Pós-Menopausa , Adulto , Idoso , Estudos de Casos e Controles , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Prevalência , República da Coreia/epidemiologiaRESUMO
OBJECTIVE: Juvenile ischemic osteonecrosis (JIO) of the femoral head is one of the most serious hip disorders causing a permanent deformity of the femoral head in childhood. We recently reported that interleukin 6 (IL6) is predominantly increased in the hip synovial fluid of patients with JIO and that articular chondrocytes are primary source of IL6. This study investigated whether an inhibition of IL6 receptor improves cartilage preservation and bone healing in JIO. METHOD: A small animal model (i.e., 6-week-old mouse) of JIO was treated with either saline or tocilizumab, an IL6 receptor blocker, for 6 weeks. RESULTS: TUNEL-positive chondrocytes in the articular cartilage were reduced by the tocilizumab treatment, concomitant with the increase in cartilage matrix. The levels of a cartilage anabolic marker Sox9 was significantly increased in the articular cartilage of mice treated with tocilizumab. Micro-CT assessment showed tocilizumab treatment significantly increased trabecular epiphyseal bone volume (P = 0.001, n = 10), thickness (P = 0.007) and number (P = 0.014) and decreased bone separation (P = 0.002) and its deformity (P = 0.003). A bone formation marker, BMP2, and an angiogenic marker, vascular endothelial growth factor (VEGF), were both significantly increased by tocilizumab treatment under hypoxia using human chondrocytes while the bone resorption marker, RANKL/OPG ratio, was reduced. CONCLUSION: Tocilizumab treatment following ischemic osteonecrosis has cartilage anabolic effect and increases bone volume in JIO mouse model. The findings lead to a possible application of tocilizumab for preclinical study using a large animal model of JIO and a clinical trial to validate this treatment.
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Anticorpos Monoclonais Humanizados/farmacologia , Remodelação Óssea/efeitos dos fármacos , Cartilagem Articular/patologia , Osteonecrose/patologia , Receptores de Interleucina-6/antagonistas & inibidores , Animais , Anticorpos Monoclonais Humanizados/uso terapêutico , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/metabolismo , Células Cultivadas , Condrócitos/efeitos dos fármacos , Condrócitos/patologia , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos/métodos , Fêmur/metabolismo , Fêmur/patologia , Interleucina-6/metabolismo , Metabolismo/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Terapia de Alvo Molecular/métodos , Osteonecrose/tratamento farmacológico , Receptores de Interleucina-6/fisiologia , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOX9/metabolismo , Regulação para Cima/efeitos dos fármacos , Microtomografia por Raio-XRESUMO
Because of the proven prognostic value of Ki-67 as a proliferation marker in several types of solid cancers, our goal is to develop and validate a multiparameter flow cytometric assay for the determination of the Ki-67 expression in hemato-oncological diseases. The aim of the present study was to establish the reference values for the fraction of Ki-67 positive cells in and during maturation of individual hematopoietic cell lineages present in normal bone marrow. Aspirates derived from femoral heads of 50 patients undergoing a hip replacement were used for the flow cytometric quantification of Ki-67 expression in the different hematopoietic cell populations of healthy bone marrow. Furthermore, the proliferative index was investigated in detail for the maturation steps during erythro-, myelo-, and monopoiesis using recently described immunophenotypic profiles in combination with a software-based maturation tool. Reference values for the proliferative index were established for different relevant hematopoietic cell populations in healthy bone marrow. During maturation, the size of the Ki-67 positive fraction was the highest in the most immature compartment of the myeloid, monocytic, and erythroid cell lineages, followed by a steady decline upon cell maturation. While proerythroblasts showed a proliferative activity of almost 100%, the myelo- and monoblast showed a lower proliferative index of on average of 50%, indicating that a relatively large proportion of these cells exist in a quiescent state. In conclusion, we can state that when using a novel combination of immunophenotypic markers, the proliferation marker (Ki-67) and a software-based maturation tool, it was possible to determine the proliferative fractions in the diverse hematopoietic cell lineages in bone marrow, in particular during maturation. Using this approach, the proliferative indices for the normal myelo-, mono-, and erythropoiesis were determined, which can be used as a reference in future studies of hematologic malignancies originating from bone marrow. © 2018 International Society for Advancement of Cytometry.
Assuntos
Medula Óssea/patologia , Diferenciação Celular/fisiologia , Linhagem da Célula/fisiologia , Proliferação de Células/fisiologia , Células-Tronco Hematopoéticas/patologia , Idoso , Biomarcadores/metabolismo , Medula Óssea/metabolismo , Células da Medula Óssea/metabolismo , Células da Medula Óssea/patologia , Células Eritroides/metabolismo , Células Eritroides/patologia , Feminino , Citometria de Fluxo/métodos , Células-Tronco Hematopoéticas/metabolismo , Humanos , Imunofenotipagem/métodos , Antígeno Ki-67/metabolismo , Masculino , Monócitos/metabolismo , Monócitos/patologia , Células Mieloides/metabolismo , Células Mieloides/patologiaRESUMO
WHAT IS KNOWN AND OBJECTIVE: Fosphenytoin (FOS) administered intravenously offers several benefits over intravenously administered phenytoin, including a faster infusion rate, decreased pain and irritation at the infusion site, and fewer cardiovascular complications. However, some studies suggest that the intravenous administration of FOS in some patients may also induce adverse cardiovascular events. Here, we investigated the clinical characteristics of patients who experienced hypotension following an intravenous infusion of a FOS loading dose. METHODS: We reviewed the medical records of consecutive patients who received an intravenous (IV) dose of FOS between July 2013 and June 2015. Various clinical and demographic parameters were analysed, including comorbidities, drug history, seizure aetiology and type, incidence of hypotension/cardiac arrhythmia and the dosing data (ie the total dose, concentration and FOS IV infusion rate). Hypotension was defined as a ≥20 mm Hg decrease in systolic blood pressure or a ≥10 mm Hg decrease in diastolic blood pressure during or after FOS IV infusion. These parameters were compared between patients with and without hypotension. RESULTS AND DISCUSSION: Of the 28 included patients, 11 (39%) had hypotension associated with an IV infusion of FOS, two of whom also had an atrioventricular block. Most patients (22/28, 79%) who received an IV infusion of FOS had status epilepticus (SE). The presence of SE was significantly associated with the development of hypotension (P=.026); hypotension occurred in half of the patients with SE, but did not occur in six patients without SE. Hypotension was also associated with old age (≥60 years, P=.034) and the presence of a systemic infection (P=.04). WHAT IS NEW AND CONCLUSION: Our study shows that hypotension associated with an IV infusion of FOS is not a rare adverse event, especially in patients with SE. Moreover, we found that old age and the presence of a systemic infection increased the risk of hypotension. These findings suggest that FOS should be infused under careful cardiovascular monitoring, especially in patients who are at higher risk of developing hypotension.
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Anticonvulsivantes/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Hipotensão/induzido quimicamente , Fenitoína/análogos & derivados , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anticonvulsivantes/administração & dosagem , Feminino , Humanos , Hipotensão/epidemiologia , Incidência , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Fenitoína/administração & dosagem , Fenitoína/efeitos adversos , Estudos Retrospectivos , Fatores de RiscoRESUMO
Solid pseudopapillary neoplasm (SPN) of the pancreas is considered a low-malignant neoplasm with a good prognosis. However, 5% to 15% of patients with SPNs develop metastatic disease, most commonly in the liver. Metastatic hepatic malignancies that show pseudocystic features are rare. Here we describe the case of a middle-aged female with a cystic liver metastasis from SPN. To the best of our knowledge, SPN with a single cystic liver metastasis has not been described, although these tumours frequently undergo haemorrhagic-cystic degeneration. Thus, in these patients the marked cystic change could be misinterpreted as a benign lesion.
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Carcinoma Papilar/diagnóstico , Cistos/diagnóstico , Neoplasias Hepáticas/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Carcinoma Papilar/secundário , Cistos/patologia , Diagnóstico Diferencial , Feminino , Humanos , Neoplasias Hepáticas/secundário , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologiaRESUMO
OBJECTIVE: Bitter taste receptors (TAS2Rs) are expressed in the extraoral tissues, where they possess various physiological functions. This study is to characterize TAS2Rs expression in normal and allergic nasal mucosa and analyse nasal symptom after challenge with bitter tastes to evaluate their pathophysiological function in normal and allergic nasal mucosa. METHODS: The expression levels of TAS2Rs (TAS2R4, 5, 7, 10, 14, 39, and 43) in nasal mucosa were investigated by real-time PCR, Western blot, and immunohistochemistry. The expression levels of TAS2Rs and Ca(2+) imaging in cultured epithelial cells were measured after stimulation with type 2 cytokines (IL-4, IL-5, and IL-13) or bitter tastes. Nasal symptoms in control subjects and allergic rhinitis patients using visual analogue score and acoustic rhinometry were evaluated before and after stimulation with bitter tastes. Vascular diameter of rat nasal septum was measured before and after treatment with bitter tastes. RESULTS: TAS2Rs tested here were expressed in nasal mucosa where they were commonly distributed in superficial epithelium, submucosal glands, and endothelium. Their expression levels are increased in allergic nasal mucosa and up-regulated in cultured epithelial cells simulated with type 2 cytokines. After treatment with bitter tastes, intracellular Ca(2+) signalling was increased in cultured epithelial cells, and vascular constriction was found in rat nasal septum. Increased nasal patency was observed in human nasal mucosa without pain or sneezing. CONCLUSION AND CLINICAL RELEVANCE: TAS2Rs are constitutively expressed in human nasal mucosa and their expression levels are increased in allergic nasal mucosa, where they could potentially contribute to shrinkage of normal and allergic nasal mucosa.
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Regulação da Expressão Gênica , Mucosa Nasal/imunologia , Mucosa Nasal/metabolismo , Receptores Acoplados a Proteínas G/genética , Rinite Alérgica/etiologia , Rinite Alérgica/patologia , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Mucosa Nasal/patologia , Transporte Proteico , Ratos , Receptores Acoplados a Proteínas G/metabolismo , Rinite Alérgica/metabolismo , Transdução de SinaisRESUMO
Even though the study of ion-atom collisions is a mature field of atomic physics, large discrepancies between experiment and theoretical calculations are still common. Here we present experimental results with high momentum resolution on the single ionization of helium induced by 1-MeV protons, and we compare these to theoretical calculations. The overall agreement is strikingly good, and even the first Born approximation yields good agreement between theory and experiment. This has been expected for several decades, but so far has not been accomplished. The influence of projectile coherence effects on the measured data is briefly discussed in terms of an ongoing dispute on the existence of nodal structures in the electron angular emission distributions.
RESUMO
We investigate the temporal evolution of molecular frame angular distributions of Auger electrons emitted during ultrafast dissociation of HCl following a resonant single-photon excitation. The electron emission pattern changes its shape from that of a molecular σ orbital to that of an atomic p state as the system evolves from a molecule into two separated atoms.
RESUMO
The Mediterranean Fynbos vegetation of South Africa is well known for its high levels of diversity, endemism, and the existence of very distinct plant communities on different soil types. Studies have documented the broad taxonomic classification and diversity patterns of soil microbial diversity, but none has focused on the community assembly processes. We hypothesised that bacterial phylogenetic community structure in the Fynbos is highly governed by deterministic processes. We sampled soils in four Fynbos vegetation types and examined bacterial communities using Illumina HiSeq platform with the 16S rRNA gene marker. UniFrac analysis showed that the community clustered strongly by vegetation type, suggesting a history of evolutionary specialisation in relation to habitats or plant communities. The standardised beta mean nearest taxon distance (ses. ß NTD) index showed no association with vegetation type. However, the overall phylogenetic signal indicates that distantly related OTUs do tend to co-occur. Both NTI (nearest taxon index) and ses. ß NTD deviated significantly from null models, indicating that deterministic processes were important in the assembly of bacterial communities. Furthermore, ses. ß NTD was significantly higher than that of null expectations, indicating that co-occurrence of related bacterial lineages (over-dispersion in phylogenetic beta diversity) is determined by the differences in environmental conditions among the sites, even though the co-occurrence pattern did not correlate with any measured environmental parameter, except for a weak correlation with soil texture. We suggest that in the Fynbos, there are frequent shifts of niches by bacterial lineages, which then become constrained and evolutionary conserved in their new environments. Overall, this study sheds light on the relative roles of both deterministic and neutral processes in governing bacterial communities in the Fynbos. It seems that deterministic processes play a major role in assembling the bacterial community, with neutral processes playing a more minor role.
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Bactérias/classificação , Filogenia , Microbiologia do Solo , Bactérias/genética , Bactérias/isolamento & purificação , Biodiversidade , DNA Bacteriano/genética , Ecossistema , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Solo/química , África do SulRESUMO
OBJECTIVE: Promoter hypermethylation and the BRAF(V) (600E) mutation are both involved in thyroid tumorigenesis. We conducted a pilot study on the diagnosis of thyroid nodules by analysis of promoter hypermethylation status with reference to BRAF(V) (600E) mutation and cytopathology results using formalin-fixed, paraffin-embedded (FFPE) tissues and liquid-based preparation (LBP) thyroid fine needle aspiration (FNA) samples to predict more reliably the possibility of papillary carcinoma. METHODS: We initially performed MethyLight analysis for 30 genes that are known to be hypermethylated in malignancies using 164 papillary carcinomas and 77 benign tissue samples. Five genes selected from the tissue analysis were subsequently analysed in 75 surgically proven benign and 66 surgically proven papillary carcinoma LBP FNA samples. Samples that showed two or more positive results among the five genes were classified as methylation positive. We also analysed the BRAF(V) (600E) mutation status of the FNA samples. RESULTS: We identified five genes that were significantly hypermethylated in malignant tissues: PTGS2, HOXA1, TMEFF2, p16 and PTEN. With respect to diagnostic potential, results obtained using the BRAF(V) (600E) mutation test combined with cytological examination were not significantly different from those obtained with cytological examination only. Combining methylation analyses with cytological examination or performing all three tests for diagnoses did not improve significantly the negative predictive values and sensitivity, but a significant decrease in positive predictive value and specificity was observed. CONCLUSION: Further studies are needed on larger samples to assess the potential value of methylation analysis of thyroid FNA.
Assuntos
Carcinoma Papilar/diagnóstico , Citodiagnóstico , Metilação de DNA/genética , Neoplasias/diagnóstico , Proteínas Proto-Oncogênicas B-raf/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina , Carcinoma Papilar/genética , Carcinoma Papilar/patologia , Inibidor p16 de Quinase Dependente de Ciclina , Ciclo-Oxigenase 2/genética , Feminino , Proteínas de Homeodomínio/genética , Humanos , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Mutação , Proteínas de Neoplasias/genética , Neoplasias/genética , Neoplasias/patologia , PTEN Fosfo-Hidrolase/genética , Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/patologia , Fatores de Transcrição/genéticaRESUMO
Non-essential amino acid L-glutamine (Gln) possesses anti-inflammatory activity via deactivating cytosolic phospholipase A2 (cPLA2 ). We showed previously that Gln deactivated cPLA2 indirectly via dephosphorylating p38 mitogen-activated protein kinase (MAPK), the major kinase for cPLA2 phosphorylation, through inducing MAPK phosphatase-1 (MKP-1). In this study, we investigated the precise mechanism underlying Gln deactivation of cPLA2 . In lipopolysaccharide (LPS)-treated mice, Gln injection resulted in dephosphorylation of phosphorylated cPLA2 (p-cPLA2 ), which coincided with rapid Gln induction of MKP-1. MKP-1 small interfering RNA (siRNA) abrogated the ability of Gln to induce MKP-1 as well as the dephosphorylation of cPLA2 . Co-immunoprecipitation and in-situ proximity ligation assay revealed a physical interaction between MKP-1 and p-cPLA2 . In a murine model of allergic asthma, we also demonstrated the physical interaction between MKP-1 and p-cPLA2 . Furthermore, Gln suppressed various allergic asthma phenotypes, such as neutrophil and eosinophil recruitments into the airway, airway levels of T helper type 2 (Th2) cytokines [interleukin (IL)-4, IL-5 and IL-13], airway hyperresponsiveness, mucin production and metabolites (leukotriene B4 and platelet-activating factor) through inhibiting cPLA2 in a MKP-1-dependent manner. These data suggest that MKP-1 uses cPLA2 , in addition to p38, as a substrate, which further potentiates the anti-inflammatory action of Gln.
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Glutamina/farmacologia , Fosfolipases A2 Citosólicas/antagonistas & inibidores , Animais , Asma/imunologia , Asma/metabolismo , Asma/patologia , Células Cultivadas , Fosfatase 1 de Especificidade Dupla/metabolismo , Ativação Enzimática/efeitos dos fármacos , Feminino , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Macrófagos Alveolares/efeitos dos fármacos , Macrófagos Alveolares/enzimologia , Camundongos , Fosfolipases A2 Citosólicas/metabolismo , Fosforilação/efeitos dos fármacos , Ligação ProteicaRESUMO
OBJECTIVE: Vascular optical tomographic imaging (VOTI) is a novel imaging modality that is capable of detecting hemoglobin concentrations in tissue. VOTI is non-invasive, non-ionizing and does not require contrast injection. This technology was applied to the diagnosis of peripheral arterial disease (PAD) within lower extremities of diabetic patients with calcified arteries. This could be of substantial benefit as these patients suffer from comorbidities such as arterial incompressibility, which complicates diagnosis and monitoring. METHODS: Forty individuals (10 non-diabetic patients with PAD, 10 diabetic patients with PAD, and 20 healthy volunteers) were enrolled in a diagnostic pilot study using the VOTI system. The patients were imaged during at high pressure cuff occlusion. RESULTS: The VOTI system was capable of quantifying the blood volume changes within the foot during the thigh cuff occlusion and outputting diagnostic parameters, such as change in hemoglobin concentration, enabling the assessment of foot perfusion. This study resulted in a statistically significant difference between the healthy cohort and both the non-diabetic and the diabetic PAD cohorts (p = .006, p = .006). Receiver operating characteristic (ROC) curve analysis showed that PAD diagnosis could be made with over 80% sensitivity or specificity depending on the characteristic cutoff point. In addition, VOTI was capable of providing the locations of under-perfused regions within the foot and evaluating the severity of arterial disease, even within diabetic patients with calcified arteries, who are traditionally difficult to diagnose. CONCLUSION: VOTI can effectively diagnose PAD independently of arterial compressibility, making it very useful for assessing vascular disease in diabetic patients.
Assuntos
Pé Diabético/diagnóstico , Doença Arterial Periférica/diagnóstico , Tomografia Óptica/métodos , Idoso , Algoritmos , Índice Tornozelo-Braço , Pé Diabético/fisiopatologia , Desenho de Equipamento , Feminino , Pé/irrigação sanguínea , Hemoglobinas/análise , Humanos , Masculino , Doença Arterial Periférica/fisiopatologia , Projetos Piloto , Curva ROC , Sensibilidade e Especificidade , Tomografia Óptica/instrumentaçãoRESUMO
Formation of magnetite in anaerobic sediments is thought to be enhanced by the activities of iron-reducing bacteria. Geobacter has been implicated as playing a major role, as in culture its cells are often associated with extracellular magnetite grains. We studied the bacterial community associated with magnetite grains in sediment of a freshwater pond in South Korea. Magnetite was isolated from the sediment using a magnet. The magnetite-depleted fraction of sediment was also taken for comparison. DNA was extracted from each set of samples, followed by PCR for 16S bacterial ribosomal RNA (rRNA) gene and HiSeq sequencing. The bacterial communities of the magnetite-enriched and magnetite-depleted fractions were significantly different. The enrichment of three abundant operational taxonomic units (OTUs) suggests that they may either be dependent upon the magnetite grain environment or may be playing a role in magnetite formation. The most abundant OTU in magnetite-enriched fractions was Geobacter, bolstering the case that this genus is important in magnetite formation in natural systems. Other major OTUs strongly associated with the magnetite-enriched fraction, rather than the magnetite-depleted fraction, include a Sulfuricella and a novel member of the Betaproteobacteria. The existence of distinct bacterial communities associated with particular mineral grain types may also be an example of niche separation and coexistence in sediments and soils, which cannot usually be detected due to difficulties in separating and concentrating minerals.
Assuntos
Óxido Ferroso-Férrico/análise , Sedimentos Geológicos/microbiologia , Microbiota/genética , Lagoas/microbiologia , Sequência de Bases , Primers do DNA/genética , Geobacter/genética , Sedimentos Geológicos/química , Dados de Sequência Molecular , RNA Ribossômico 16S/genética , Reação em Cadeia da Polimerase em Tempo Real , República da Coreia , Análise de Sequência de DNA , Especificidade da EspécieRESUMO
An 8-year-old girl with a renal transplant was admitted for myalgia and muscle weakness in both legs over the previous 2 weeks. She also had fever and intermittent epigastric pain. Based on these clinical manifestations, and laboratory and histopathological findings, the diagnosis was coincidence of late-onset cytomegalovirus (CMV)-induced myositis and gastritis in an immunocompromised child with a renal transplant. After administration of intravenous ganciclovir for 3 weeks, her symptoms resolved, with normalization of abnormal muscle enzymes, including lactate dehydrogenase, creatine kinase, aspartate aminotransferase, and the disappearance of CMV viremia.
Assuntos
Infecções por Citomegalovirus/complicações , Ganciclovir/uso terapêutico , Gastrite/etiologia , Transplante de Rim/efeitos adversos , Miosite/etiologia , Antivirais/uso terapêutico , Criança , Infecções por Citomegalovirus/tratamento farmacológico , Feminino , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/administração & dosagem , Imunossupressores/farmacologia , Viremia/sangue , Viremia/tratamento farmacológicoRESUMO
The transporter 1 ATP-binding cassette sub-family B (MDR/TAP) gene (TAP1) is located in the major histocompatibility complex class II region, and forms a heterodimer that plays a key role in endogenous antigen presentation pathways. Investigation of polymorphisms identified in these loci has revealed an association with several autoimmune disorders. Alopecia areata (AA) is a common autoimmune disease resulting from T cell-induced damage to hair follicles. The present study documents for the first time a comparison between the allelic and genotypic frequencies of TAP1 single nucleotide polymorphisms (SNPs) in patients with AA and those of a control group, using a direct sequencing method. Our results suggest an association between a promoter SNP (rs2071480) and susceptibility to this disease.