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BACKGROUND: Grade 3 neuroendocrine neoplasms (NENs) of gastroenteropancreatic (GEP) origin with Ki-67 indices <55% do not respond well to platinum-based chemotherapy. The combination of capecitabine and temozolomide (CAPTEM) has shown favorable responses in grade 1-2 NENs, but has rarely been studied in patients with grade 3 NENs. PATIENTS AND METHODS: This open-label, single-arm phase II trial included patients with unresectable or metastatic grade 3 NENs of GEP origin with Ki-67 indices <55% enrolled between June 2017 and July 2020. Patients received oral capecitabine 750 mg/m2 twice daily on days 1 to 14 and oral temozolomide 200 mg/m2 once daily on days 10 to 14 every 4 weeks. Histologic findings were centrally reviewed after the completion of enrollment. The primary endpoint was overall response rate, and the secondary endpoints were progression-free survival (PFS), overall survival (OS), and adverse events. RESULTS: Of the 30 patients included in the full analysis set, 1 (3.3%) achieved complete response, 8 (26.7%) had partial responses, and 14 (46.7%) had stable disease, making the overall response rate 30.0%. At a median follow-up of 19.2 months, the median PFS was 5.9 months and the median OS was not reached. Patients with well-differentiated NENs showed significantly better median PFS (9.3 months versus 3.5 months, P = 0.005) and median OS (not reached versus 6.2 months, P = 0.004) than patients with poorly differentiated tumors. Expression of O6-methyl-guanine methyltransferase protein did not correlate with clinical outcomes. The most common grade 3-4 adverse events were thrombocytopenia (10%), anemia (6.7%), and nausea (6.7%). CONCLUSIONS: CAPTEM was effective and well tolerated in patients with grade 3 GEP-NENs with Ki-67 indices <55%, with superior efficacy outcomes compared with the historical controls receiving platinum-based chemotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica , Tumores Neuroendócrinos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/efeitos adversos , Humanos , Antígeno Ki-67 , Tumores Neuroendócrinos/tratamento farmacológico , Temozolomida/uso terapêuticoRESUMO
OBJECTIVE: We aimed to investigate mechano-sensitivity at the afferent nerve fibers projecting to degenerated intervertebral disc (IVD) and nociceptive behaviour in a rat model of low back pain (LBP). DESIGN: Animal model with LBP was established by lumbar 4/5 IVD puncture and nucleus pulposus aspiration. In vivo single nerve recordings (n = 121) were introduced to measure discharge frequency at the afferent nerve fiber innervating the IVD during mechanical stimulations (von Frey filament or intradiscal pressure). Nerve growth factor (NGF) expression levels in the IVD (n = 20) were assessed by Western blot. LBP-related behaviour (n = 22) was assessed by measuring changes in rearing, mechanical paw-withdrawal threshold, and dynamic weight bearing in a freely walking rat. Inhibitory effect of morphine on the neuronal excitability (n = 19) and painful behaviour (n = 28) was also assessed. RESULTS: Compared to those with sham or naïve IVD, animal group with degenerated IVD displayed the sensitized neuronal responses and painful behaviour, with hyperexcitability of the afferent nerve fibers in any range of mechanical stimulations (von Frey filament stimulation; 1, 2, and 26 g; intradiscal pressure, 1,500-3,000 mm Hg), strong upregulation of NGF (200-250 % increase), and LBP-like behaviour such as failure of rearing, front limbs-dependent walking pattern, and hypersensitivity in hind-paws. However, the neuronal hyperexcitability and pain behaviour were attenuated after local (30 µM) or systemic (3 mg kg-1) morphine administration. CONCLUSIONS: Our study suggests that enhanced mechano-sensitivity at the afferent nerve fiber innervating degenerated IVD is deeply correlated with LBP development, which supports the hypothesis that hyperexcited responses at the nerve fibers represent a decisive source of LBP.
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Degeneração do Disco Intervertebral/complicações , Disco Intervertebral/inervação , Dor Lombar/etiologia , Fibras Nervosas/metabolismo , Fator de Crescimento Neural/biossíntese , Neurônios Aferentes/metabolismo , Nociceptividade/fisiologia , Animais , Western Blotting , Modelos Animais de Doenças , Degeneração do Disco Intervertebral/diagnóstico , Dor Lombar/diagnóstico , Dor Lombar/fisiopatologia , Vértebras Lombares , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Recurrence of pancreatic cancer after primary pancreatectomy occurs in the vast majority of patients. The role of surgical treatment for recurrent pancreatic cancer is not well established. METHODS: Patients who underwent primary pancreatectomy with curative intent from 2000 to 2014 at a single large-volume centre were evaluated retrospectively. CT or PET was used to select patients with an isolated recurrence. The clinicopathological features and survival outcomes were compared according to treatment modalities. RESULTS: Of the 1610 patients with pancreatic cancer who underwent resection, 1346 (83·6 per cent) were diagnosed with recurrent pancreatic cancer. Recurrence was locoregional in 366 patients (27·2 per cent), distant multifocal in 251 (18·6 per cent), distant isolated in 188 (14·0 per cent), locoregional plus distant in 153 (11·4 per cent) and peritoneal seeding in 388 (28·8 per cent). Of the 1346 patients with recurrence, 197 (14·6 per cent) had isolated recurrence; of these, 48 (24·4 per cent of all isolated recurrences; 3·6 per cent of all recurrences) underwent resection. Median survival of the 197 patients after diagnosis of isolated recurrence was 14·7 months; it was longer in patients who underwent surgical resection than among those treated non-surgically (23·5 versus 12·0 months; P = 0·014). Multivariable analysis showed that chemotherapy and resection for recurrence were associated with better prognosis. Median survival after recurrence was longest in the 23 patients with isolated pulmonary recurrence (33·3 months). Survival after recurrence was better in patients who underwent resection of isolated recurrence in the remnant pancreas (median 28·0 versus 12·0 months, P = 0·010) and lung (median 36·5 versus 9·5 months; P = 0·010) than in those who did not undergo resection. CONCLUSION: Surgical resection may be considered an option for treatment of patients with isolated recurrent pancreatic cancer.
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Adenocarcinoma/terapia , Recidiva Local de Neoplasia/terapia , Neoplasias Pancreáticas/terapia , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/mortalidade , Pancreatectomia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/mortalidade , Tomografia por Emissão de Pósitrons , Reoperação , Estudos Retrospectivos , Análise de Sobrevida , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND: Several studies have demonstrated that 11C-methionine positron-emission tomography provides information on prognosis. PURPOSE: We performed a systematic review and meta-analysis of the prognostic value of the metabolic and volumetric parameters of 11C-methionine-PET for gliomas. DATA SOURCES: A systematic search was performed using the following combination of keywords: "methionine," "PET," "glioma," and "prognosis." STUDY SELECTION: The inclusion criteria were the use of 11C-methionine-PET as an imaging tool, studies limited to gliomas, studies including metabolic parameters (tumor-to-normal ratio) and/or volumetric parameters (metabolic tumor volume), and studies reporting survival data. The electronic search first identified 181 records, and 14 studies were selected. DATA ANALYSIS: Event-free survival and overall survival were the outcome measures of interest. The effect of the tumor-to-normal ratio and metabolic tumor volume on survival was determined by the effect size of the hazard ratio. Hazard ratios were extracted directly from each study when provided or determined by analyzing the Kaplan-Meier curves. DATA SYNTHESIS: The combined hazard ratios of the tumor-to-normal ratio for event-free survival was 1.74 with no significance and that of the tumor-to-normal ratio for overall survival was 2.02 with significance. The combined hazard ratio of the metabolic tumor volume for event-free survival was 2.72 with significance and that of the metabolic tumor volume for overall survival was 3.50 with significance. LIMITATIONS: The studies selected were all retrospective, and there were only 4 studies involving the metabolic tumor volume. CONCLUSIONS: The present meta-analysis of 11C-methionine-PET suggests that the tumor-to-normal ratio for overall survival and the metabolic tumor volume for event-free survival and overall survival are significant prognostic factors for patients with gliomas.
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Neoplasias Encefálicas/diagnóstico por imagem , Glioma/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Adulto , Idoso , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/mortalidade , Intervalo Livre de Doença , Feminino , Glioma/metabolismo , Glioma/mortalidade , Glioma/patologia , Humanos , Masculino , Metionina , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosRESUMO
We examined the spatial distributions of 226Ra, 228Ra, 134Cs, and 137Cs concentrations (activities) in seawater off the western and southern Korean Peninsula in July 2014. Radium-228 (and 226Ra) concentrations in water samples varied widely from 5 to 14 mBq/L (2-4 mBq/L), showing a negative correlation with salinity, particularly at the surface off the western Korean Peninsula. This indicates that the seawaters in this area are fundamentally comprised of 228Ra-poor and high-saline Kuroshio Current water and 228Ra-rich and low-saline water (e.g., continental shelf water), with various mixing ratios. Although Fukushima Dai-ichi Nuclear Power Plant (FDNPP)-derived 134Cs was below the detection limit (<0.08 mBq/L) in waters off the western Korean Peninsula, low level 134Cs (0.1-0.2 mBq/L) was detected in waters off the southern Korean Peninsula accompanied by higher 137Cs concentrations (1.6-1.9 mBq/L) relative to that off the western Korean Peninsula. Combined with the lower radium concentrations, the detection of 134Cs is explained by mixing of FDNPP-derived radiocesium-contaminated Kuroshio Current water.
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Radioisótopos de Césio/análise , Acidente Nuclear de Fukushima , Monitoramento de Radiação , Rádio (Elemento)/análise , Poluentes Radioativos da Água/análise , Japão , Água do Mar/químicaRESUMO
BACKGROUND: Very limited information exists on the ruminal degradation kinetics of nutrients in garlic stalk. The present study aimed to survey the annual yield of garlic stalk in Korea and determine its feed-nutritive value for ruminants. METHODS: In Experiment 1, garlic stalk was incubated in situ in the rumen of two Hanwoo steers (360 ± 15 kg body weight) and removed after 12, 24, or 48 h to determine the ruminal degradation kinetics of DM and NDF. Rice straw was also included for comparison. In Experiment 2, In Experiment 2, six male Corriedale sheep were randomized to two dietary treatments to determine the apparent digestibility of nutrients in garlic stalk. Diets included a control ration without garlic stalk (60% concentrate mix +40% ryegrass) or a treatment ration (70% control diet +30% garlic stalk). RESULTS: The Korean national yield of garlic stalk (sun-dried basis) in 2016 was estimated to be 31,910 tons, with the southern coastal regions producing the highest quantity. Compared with rice straw, garlic stalk had lower NDF, higher ADF, and greater effective degradabilities of DM and NDF, resulting in a greater TDN value (56.3%), which was higher than that obtained for rice straw (43.7%). CONCLUSION: These results provide basic information on the ruminal DM and NDF degradation kinetics of garlic stalk, which would be helpful for the efficient utilization of this by-product in ruminant diets.
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OBJECTIVES: To determine differences in arch forms derived from the root apices locations between individuals with <2 mm maxillary crowding and controls. SETTING AND SAMPLE POPULATION: The Department of Orthodontics, Pusan National University. Cone-beam computed tomography (CBCT) images of 102 patients in the control group and 95 patients in the crowding group. MATERIALS AND METHODS: X, Y and Z coordinates of the tip of the crowns and the apex of the root of the maxillary teeth (except second molars) were determined on the CBCT images. The acquired three-dimensional (3D) coordinates were converted into two-dimensional (2D) coordinates via projection on the palatal plane, and the Procrustes analysis was employed to process the converted 2D coordinates. The mean shape of the arch form derived from the location of the tip of the crowns and the apex of the root was compared between groups using the statistical shape analysis. RESULTS: There was a statistically significant difference (P = .046) between the groups for the mean shape of the root apex arch form, but the difference was small and clinically irrelevant as it is minor compared to the degree of crowding. CONCLUSIONS: Maxillary arch from at the level of the maxillary apices only shows minor differences between crowded and non-crowded dentitions.
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Tomografia Computadorizada de Feixe Cônico , Má Oclusão/diagnóstico por imagem , Má Oclusão/patologia , Maxila/diagnóstico por imagem , Maxila/patologia , Raiz Dentária/diagnóstico por imagem , Raiz Dentária/patologia , Feminino , Humanos , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença , Adulto JovemRESUMO
BACKGROUND: Severe damage to the tooth, periodontal ligament, and pulpal tissue often occurs with intrusive luxation, and outcomes are quite unpredictable because of the variable ways in which the injury may occur, which influences both the choice of treatment and prognosis. CASE REPORT: This case presents a novel method for the management of an intruded permanent maxillary central incisor with an immature apex. At first, watchful waiting for spontaneous re-eruption was the chosen treatment option. A palatal gingivectomy was performed and endodontic access was established, following which, an intracanal medicament of calcium hydroxide was applied. A root canal treatment was completed, and apexification with mineral trioxide aggregate was performed. Re-eruption failed to reach completion, so complete repositioning was performed with the aid of orthodontics for two months. CONCLUSION: The present case illustrates the partial re-eruption of a severely intruded immature permanent tooth with the use of interim medication in the root canal. This case also shows complete re-eruption with the aid of timely orthodontic repositioning after apexification.
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Incisivo/lesões , Avulsão Dentária/terapia , Apexificação , Criança , Dentição Permanente , Feminino , Humanos , Incisivo/diagnóstico por imagem , Maxila , Ortodontia Corretiva , Tratamento do Canal Radicular , Avulsão Dentária/diagnóstico por imagem , Erupção DentáriaRESUMO
A new experiment is described to detect a permanent electric dipole moment of the proton with a sensitivity of 10-29 e â cm by using polarized "magic" momentum 0.7 GeV/c protons in an all-electric storage ring. Systematic errors relevant to the experiment are discussed and techniques to address them are presented. The measurement is sensitive to new physics beyond the standard model at the scale of 3000 TeV.
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Background: Inflammatory stimuli can induce neutrophils to release nuclear DNA combined with histones into the extracellular space, forming neutrophil extracellular traps. Because inflammation contributes to diabetic retinopathy, it is plausible that neutrophil extracellular trap formation actively occurs in diabetic retinopathy. This case-control study investigated the clinical relevance of circulating levels of neutrophil extracellular trap components as risk factors of diabetic retinopathy, and further evaluated whether glucose induced neutrophil extracellular trap formation in vitro using whole blood from healthy volunteers. Methods: Circulating levels of DNA-histone complexes, cell free double-stranded DNA, and polymorphonuclear neutrophil elastase, considered to be markers of neutrophil extracellular trap formation, were measured in patients with diabetic retinopathy (n=28) and without (n=62) and in 28 healthy controls. Results: Circulating DNA-histone complex and polymorphonuclear neutrophil elastase levels were significantly increased in patients with diabetic retinopathy compared with those without retinopathy. Multivariable logistic regression analysis, adjusted for glycated hemoglobin levels and fasting blood glucose, revealed that DNA-histone complex and polymorphonuclear neutrophil elastase levels were significant independent risk factors of retinopathy. In vitro experiments also showed that glucose significantly increased markers of neutrophil extracellular trap formation in a dose-dependent manner. Conclusions: Markers of neutrophil extracellular trap formation were independent risk factors of diabetic retinopathy. This finding provides a new insight into the potential therapeutic and preventive approaches to dampen neutrophil extracellular trap formation.
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Retinopatia Diabética/sangue , Armadilhas Extracelulares/metabolismo , Neutrófilos/metabolismo , Elastase Pancreática/metabolismo , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
OBJECTIVE: Hepatic ischemia-reperfusion injury (IRI) is considered a major cause of hepatic damage in liver surgery. The aim of this study was to investigate the effect of the remote ischemic perconditioning method on hepatic IRI in a rat model. METHODS: Seventeen rats underwent hepatic IRI for 30 minutes followed by reperfusion, and were divided into 3 groups: group I, only hepatic IRI (n = 5); group II, hepatic IRI with remote perconditioning (n = 7); and group III, hepatic IRI with remote postconditioning (n = 5). RESULTS: For Bax/ß-actin, mean values of the 3 groups (±standard deviation) were 1.29 ± 0.26 (group I), 0.89 ± 0.15 (group II), and 1.02 ± 0.23 (group III). The level of Bax/ß-actin in group II was significantly lower than in group I (P < .01). The cleaved Caspase-3/ß-actin ratio for groups I, II, and III was 0.93 ± 0.22, 0.46 ± 0.16, and 0.63 ± 0.22, respectively. The level of cleaved Caspase-3/ß-actin in groups II and III were significantly lower than in group I (P < .01 and P < .05, respectively). The Bcl-2/ß-actin ratio for groups I, II, and III was 1.01 ± 0.09, 1.19 ± 0.39, and 1.20 ± 0.12, respectively. However, there were no significant difference between groups II and III and group I. CONCLUSIONS: The remote perconditioning on rat hepatic IRI downregulated the Bax and cleaved Caspase-3 expression.
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Caspase 3/metabolismo , Precondicionamento Isquêmico/métodos , Fígado/irrigação sanguínea , Traumatismo por Reperfusão/prevenção & controle , Proteína X Associada a bcl-2/metabolismo , Animais , Biomarcadores/metabolismo , Regulação para Baixo , Fígado/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismoRESUMO
In the first experiment, the effect of two novel Lactobacillus plantarum strains was studied on the fermentation of spent mushroom substrate (SMS) through 10d of ensiling. Based on lactic acid production and lactic acid bacteria population, L. plantarum KU5 was identified as the best strain for fermentation with a 5-L bag silo. Spent mushroom substrate was ensiled with 0.5% (v/w) L. plantarum KU5 without or with 5% molasses. Silages treated with microbial inoculant and molasses had the lowest pH and the highest fermentative odors. In a second set of experiments similar to the above 5-L silo study, the simultaneous application of L. plantarum KU5 inoculant and molasses to 80-L silos improved fermentability and aerobic stability of SMS silages. For similar treatment using ton-bag silos, aerobic stability decreased and NH3-N content increased dramatically. In conclusion, sawdust-based SMS for animal use was successfully ensiled with L. plantarum KU5 inoculant and molasses.
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Agaricales , Inoculantes Agrícolas , Lactobacillus plantarum/metabolismo , Melaço , Silagem/microbiologia , Aerobiose , Animais , Fermentação , Resíduos Industriais , Ácido Láctico/análise , Ácido Láctico/metabolismo , Silagem/análiseRESUMO
BACKGROUND: The aim of the present study was to determine the effects of feeding trace mineralsfortified mixed microbial culture (TMC) on ruminal fermentation, nutrient digestibility, blood electrolyte status, nitrogen balance, and trace mineral balance in sheep. METHODS: Mixed microbes [0.6 % (v/w) of Enterobacter sp., Bacillus sp., Lactobacillus sp., and Saccharomyces sp.] were cultured with 99 % feedstuffs and 0.4 % trace minerals including zinc and copper for ensiling. Six sheep (a mean body weight of 46.5 ± 1.2 kg) were fed two diets: a control diet (concentrate mix and rye straw) and an experimental diet (a control diet + 3.1 % TMC). RESULTS: TMC feeding did not induce negative effects on ruminal fermentation, nutrient digestibility, blood electrolytes, and nitrogen balance in sheep. Feeding with TMC increased the intake of trace minerals (p < 0.05) and did not affect absorption of trace minerals in the whole digestive tract. Feeding with TMC increased fecal excretion and absorbable intake, and retention of zinc and copper (p < 0.05) by 71 % and 77 %, respectively. CONCLUSION: Feeding with TMC resulted in higher zinc and copper bioavailability and retention without any adverse effects on sheep performance.
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AIMS: The purpose of the study was to investigate whether closed intramedullary (IM) nailing with percutaneous cement augmentation is better than conventional closed nailing at relieving pain and suppressing tumours in patients with metastases of the femur and humerus. PATIENTS AND METHODS: A total of 43 patients (27 men, 16 women, mean age 63.7 years, standard deviation (sd) 12.2; 21 to 84) underwent closed IM nailing with cement augmentation for long bone metastases. A further 27 patients, who underwent conventional closed IM nailing, served as controls. Pain was assessed using a visual analogue scale (VAS) score pre-operatively (pre-operative VAS), one week post-operatively (immediate post-operative VAS), and at six weeks post-operatively (follow-up post-operative VAS). Progression of the tumour was evaluated in subgroups of patients using F-18-fludeoxyglucose (F-18-FDG) positron emission tomography (PET)/computed tomography (CT) and/or bone scintigraphy (BS), at a mean of 8.8 and 7.2 months post-operatively, respectively. RESULTS: The mean pain scores of patients who underwent closed nailing with cement augmentation were significantly lower than those of the control patients post-operatively (immediate post-operative VAS: 3.8, sd 0.9 versus 6.0, sd 0.9; follow-up post-operative VAS: 3.3, sd 2.5 versus 6.6, sd 2.2; all p < 0.001). The progression of the metastasis was suppressed in 50% (10/20) of patients who underwent closed nailing with augmentation, but in only 8% (1/13) of those in the control group. CONCLUSION: Percutaneous cement augmentation of closed IM nailing improves the relief of pain and limits the progression of the tumour in patients with metastases to the long bones. TAKE HOME MESSAGE: Percutaneous cement augmentation while performing closed IM nailing has some advantages for long bone metastases. Cite this article: Bone Joint J 2016;98-B:703-9.
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Cimentos Ósseos/uso terapêutico , Neoplasias Ósseas/secundário , Fraturas do Fêmur/cirurgia , Fixação Intramedular de Fraturas , Fraturas Espontâneas/cirurgia , Fraturas do Úmero/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/cirurgia , Dor do Câncer/etiologia , Dor do Câncer/cirurgia , Estudos de Casos e Controles , Progressão da Doença , Feminino , Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/etiologia , Fraturas Espontâneas/diagnóstico por imagem , Fraturas Espontâneas/etiologia , Humanos , Fraturas do Úmero/diagnóstico por imagem , Fraturas do Úmero/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Escala Visual Analógica , Adulto JovemRESUMO
BACKGROUND: Literature is lacking on the effects of feeding by-product feed (BF)-based silage on rumen fermentation parameters, nutrient digestion and nitrogen (N) retention in sheep. Therefore, this study was conducted to determine the effect of replacing rye straw with BF-based silage as a roughage source on ruminal parameters, total-tract apparent nutrient digestibility, and N balance in sheep. METHODS: The by-product feed silage was composed of spent mushroom substrate (SMS) (45 %), recycled poultry bedding (RPB) (21 %), rye straw (11 %), rice bran (10.8 %), corn taffy residue (10 %), protected fat (1.0 %), bentonite (0.6 %), and mixed microbial additive (0.6 %). Six sheep were assigned randomly to either the control (concentrate mix + rye straw) or a treatment diet (concentrate mix + BF-based silage). RESULTS: Compared with the control diet, feeding a BF-based silage diet resulted in similar ruminal characteristics (pH, acetate, propionate, and butyrate concentrations, and acetate: propionate ratio), higher (p < 0.05) ruminal NH3-N, higher (p < 0.05) ether extract digestibility, similar crude protein digestibility, lower (p < 0.05) dry matter, fiber, and crude ash digestibilities, and higher (p < 0.05) N retention (g/d). CONCLUSION: The BF-based silage showed similar energy value, higher protein metabolism and utilization, and lower fiber digestion in sheep compared to the control diet containing rye straw.
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Endometriosis is a major cause of infertility and pelvic pain, affecting more than 10% of reproductive-aged women. Progesterone resistance has been observed in the endometrium of women with this disease, as evidenced by alterations in progesterone-responsive gene and protein expression. cAMPResponse Element-Binding 3-like protein 1 (Creb3l1) has previously been identified as a progesterone receptor (PR) target gene in mouse uterus via high density DNA microarray analysis. However, CREB3L1 function has not been studied in the context of endometriosis and uterine biology. In this study, we validated progesterone (P4) regulation of Creb3l1 in the uteri of wild-type and progesterone receptor knockout (PRKO) mice. Furthermore, we observed that CREB3L1 expression was significantly higher in secretory phase human endometrium compared to proliferative phase and that CREB3L1 expression was significantly decreased in the endometrium of women with endometriosis. Lastly, by transfecting CREB3L1 siRNA into cultured human endometrial stromal cells (hESCs) prior to hormonal induction of in vitro decidualization, we showed that CREB3L1 is required for the decidualization process. Interestingly, phosphorylation of ERK1/2, critical factor for decidualization, was also significantly reduced in CREB3L1-silenced hESCs. It is known that hESCs from patients with endometriosis show impaired decidualization and that dysregulation of the P4-PR signaling axis is linked to a variety of endometrial diseases including infertility and endometriosis. Therefore, these results suggest that CREB3L1 is required for decidualization in mice and humans and may be linked to the pathogenesis of endometriosis in a P4-dependent manner.
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Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Endometriose/genética , Endométrio/metabolismo , Proteínas do Tecido Nervoso/genética , Progesterona/farmacologia , Receptores de Progesterona/genética , Adulto , Animais , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/antagonistas & inibidores , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Endometriose/metabolismo , Endometriose/patologia , Endometriose/cirurgia , Endométrio/patologia , Feminino , Regulação da Expressão Gênica , Humanos , Histerectomia , Ciclo Menstrual/efeitos dos fármacos , Ciclo Menstrual/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteínas do Tecido Nervoso/antagonistas & inibidores , Proteínas do Tecido Nervoso/metabolismo , Cultura Primária de Células , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Receptores de Progesterona/deficiência , Transdução de Sinais , Células Estromais/efeitos dos fármacos , Células Estromais/metabolismo , Células Estromais/patologiaRESUMO
This study was conducted to determine the effects of feeding a trace minerals-fortified microbial culture (TMC) on the performance and carcass characteristics of late-fattening Hanwoo steers. A mixture of microbes (0.6% [v/w] of Enterobacter sp., Bacillus sp., Lactobacillus sp., and Saccharomyces sp.) was cultured with 99% feedstuff for ensiling and 0.4% trace minerals (zinc, selenium, copper, and cobalt). Sixteen late-fattening steers (mean age, 21.8 months) were allocated to two diets: a control diet (concentrate mix and rice straw) and a treated diet (control diet+3.3% TMC). At a mean age of 31.1 months, all the steers were slaughtered. The addition of TMC to the diet did not affect the average daily weight gain of the late fattening steers, compared with that of control steers. Moreover, consuming the TMC-supplemented diet did not affect cold carcass weight, yield traits such as back fat thickness, longissimus muscle area, yield index or yield grade, or quality traits such as meat color, fat color, texture, maturity, marbling score, or quality grade. However, consumption of a TMC-supplemented diet increased the concentrations of zinc, selenium, and sulfur (p<0.05) in the longissimus muscle. With respect to amino acids, animals consuming TMC showed increased (p<0.05) concentrations of lysine, leucine, and valine among essential amino acids and a decreased (p<0.05) concentration of proline among non-essential amino acids. In conclusion, the consumption of a TMC-supplemented diet during the late-fattening period elevated the concentrations of certain trace minerals and essential amino acids in the longissimus muscle, without any deleterious effects on performance and other carcass characteristics of Hanwoo steers.
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BACKGROUND AND PURPOSE: Crossed cerebellar diaschisis, not only a secondary result of supratentorial infarction but also an indicator of clinical outcomes, has frequently been reported on PET and SPECT but has been rarely described with arterial spin-labeling MR imaging. The purpose of this study was to determine the ability of arterial spin-labeling MR imaging to evaluate crossed cerebellar diaschisis compared with that of SPECT. To our knowledge, this is the first study to validate arterial spin-labeling in crossed cerebellar diaschisis by using SPECT as a reference standard. MATERIALS AND METHODS: This study included 16 patients in whom crossed cerebellar diaschisis was shown on SPECT and 10 control subjects in whom crossed cerebellar diaschisis was not shown on SPECT. During the qualitative analysis, asymmetric cerebellar perfusion on arterial spin-labeling was divided into 1 of the following 3 grades by 2 blinded observers: the affected cerebellum was isointense compared with the unaffected cerebellum (grade I), it was slightly hypointense (grade II), or it was markedly hypointense (grade III). In the quantitative analysis, asymmetry indices were calculated by using SPECT and arterial spin-labeling images. For statistical analysis, κ statistics, the interobserver correlation coefficient, the independent t test, Pearson correlation, and linear regression analysis were used. RESULTS: Almost all the diagnoses of crossed cerebellar diaschisis on SPECT were noted on arterial spin-labeling in both qualitative and quantitative analyses with good interobserver agreement (κ = 0.961; interobserver correlation coefficient, 0.806). The mean asymmetry index of arterial spin-labeling (26.06 ± 9.00) was significantly larger than that for SPECT (15.28 ± 5.34; P < .001). There was a significant positive correlation between the asymmetry indices obtained for SPECT and those for arterial spin-labeling (r = 0.77 [95% CI, 0.443-0.916]; P < .001). The relationship of asymmetry indices between SPECT and arterial spin-labeling (x, y) was calculated as y = 6.2131 + 1.2986x (R(2) = 0.592; P < .001). CONCLUSIONS: Arterial spin-labeling can be a noninvasive alternative to SPECT for evaluating crossed cerebellar diaschisis.
Assuntos
Doenças Cerebelares/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Adulto , Idoso , Artérias/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Marcadores de SpinRESUMO
PURPOSE OF INVESTIGATION: The authors investigated the expression patterns of interleukin (IL)-lß and tumor necrosis factor (TNF)-α, cytokines associated with peritoneal inflammatory reactions, and of B cell leukemia lymphoma (Bcl)-6 and B lymphocyte inducer of maturation program (Blimp)-1, transcriptional factors associated with immunoglobulin (Ig) production; the concentrations of Igs, and their correlation, in patients with and without endometriosis. MATERIALS AND METHODS: The authors analyzed the peritoneal fluid of 98 patients, 46 with endometriosis, and 52 with benign tumors. RESULTS: IL-1 and TNF-α mRNAs and IgG and IgA concentrations were higher in the endometriosis group, but the differences were not statistically significant. However, Bcl-6 mRNA level was significantly lower and Blimp-1 mRNA level was significantly higher in the endometriosis group with significant correlations among transcriptional factors, Igs, and cytokines (p < 0.05). CONCLUSION: Peritoneal immune responses in patients with endometriosis may be due to increased IgG and IgA concentrations, as well as to changes in expression of proinflammatory cytokines and transcriptional factors.
Assuntos
Líquido Ascítico/metabolismo , Proteínas de Ligação a DNA/metabolismo , Endometriose/metabolismo , Proteínas Repressoras/metabolismo , Adulto , Citocinas , Endometriose/imunologia , Feminino , Humanos , Imunoglobulina A/metabolismo , Imunoglobulina G/metabolismo , Interleucina-1beta/metabolismo , Masculino , Pessoa de Meia-Idade , Cavidade Peritoneal , Peritônio/imunologia , Fator 1 de Ligação ao Domínio I Regulador Positivo , Proteínas Proto-Oncogênicas c-bcl-6 , Fator de Necrose Tumoral alfa/metabolismoRESUMO
This study was conducted to determine the effects of feeding by-product feed (BF)-based silage on the performance, blood metabolite parameters, and carcass characteristics of Hanwoo steers. The BF-based silage was composed of 50% spent mushroom substrate, 21% recycled poultry bedding, 15% cut ryegrass straw, 10.8% rice bran, 2% molasses, 0.6% bentonite, and 0.6% microbial additive (on a wet basis), and ensiled for over 5 d. Fifteen steers were allocated to three diets during the growing and fattening periods (3.1 and 9.8 months, respectively): a control diet (concentrate mix and free access to rice straw), a 50% BF-based silage diet (control diet+50% of maximum BF-based silage intake), and a 100% BF-based silage diet (the same amount of concentrate mix and ad libitum BF-based silage). The BF-based silage was fed during the growing and fattening periods, and was replaced with larger particles of rice straw during the finishing period. After 19.6 months of the whole period all the steers were slaughtered. Compared with feeding rice straw, feeding BF-based silage tended (p = 0.10) to increase the average daily gain (27%) and feed efficiency (18%) of the growing steers, caused by increased voluntary feed intake. Feeding BF-based silage had little effect on serum constituents, electrolytes, enzymes, or the blood cell profiles of fattening steers, except for low serum Ca and high blood urea concentrations (p<0.05). Feeding BF-based silage did not affect cold carcass weight, yield traits such as back fat thickness, longissimus muscle area, yield index or yield grade, or quality traits such as meat color, fat color, texture, maturity, marbling score, or quality grade. However, it improved good quality grade (1(+) and 1(++)) appearance rates (60% for the control group vs 100% for the BF-based silage-fed groups). In conclusion, cheap BF-based silage could be successfully used as a good quality roughage source for beef cattle.