RESUMEN
Transcription machinery depends on the temporal formation of protein-DNA complexes. Recent experiments demonstrated that not only the formation but also the lifetime of such complexes can affect the transcriptional machinery. In parallel, in vitro single-molecule studies showed that nucleoid-associated proteins (NAPs) leave the DNA rapidly as the bulk concentration of the protein increases via facilitated dissociation (FD). Nevertheless, whether such a concentration-dependent mechanism is functional in a bacterial cell, in which NAP levels and the 3d chromosomal structure are often coupled, is not clear a priori. Here, by using extensive coarse-grained molecular simulations, we model the unbinding of specific and nonspecific dimeric NAPs from a high-molecular-weight circular DNA molecule in a cylindrical structure mimicking the cellular confinement of a bacterial chromosome. Our simulations confirm that physiologically relevant peak protein levels (tens of micromolar) lead to highly compact chromosomal structures. This compaction results in rapid off rates (shorter DNA residence times) for specifically DNA-binding NAPs, such as the factor for inversion stimulation, which mostly dissociate via a segmental jump mechanism. Contrarily, for nonspecific NAPs, which are more prone to leave their binding sites via 1d sliding, the off rates decrease as the protein levels increase. The simulations with restrained chromosome models reveal that chromosome compaction is in favor of faster dissociation but only for specific proteins, and nonspecific proteins are not affected by the chromosome compaction. Overall, our results suggest that the cellular concentration level of a structural DNA-binding protein can be highly intermingled with its DNA residence time.
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Proteínas de Unión al ADN , ADN , Proteínas Bacterianas/metabolismo , Sitios de Unión , Cromosomas Bacterianos/metabolismo , ADN/química , ADN Bacteriano/química , Proteínas de Unión al ADN/metabolismoRESUMEN
1. The present study was conducted to evaluate the effects of conditioning times and processed sodium bentonite (PSB)-based pellet binder (G. Bind™) on pellet quality, performance, small intestine morphology, and nutrient retention in growing broiler chickens (d 11-24).2. A total of 540, one-day-old male broiler chicks were fed a commercial starter diet (d 1-10). On day 11, birds were assigned to a 2 × 3 factorial arrangement including two conditioning times (2 and 4 min) and three levels of PSB (0, 7.5 and 15 g/kg) with six replicates of 15 chicks each. Feed intake and weight gain were recorded to calculate growth performance. The jejunal segment and excreta samples were collected to determine intestinal morphology and nutrient retention, respectively.3. Diets produced with 2 min conditioning time and containing 15 g/kg PSB increased (P < 0.05) pellet durability index and hardness. Conditioning time and PSB levels had no significant effect on growth performance. The inclusion of PSB to broilers diet increased (P < 0.05) energy usage of the pelleting machine. Chickens fed the diet conditioned for 2 min and containing 15 g/kg PSB had the lowest (P < 0.05) relative jejunal length. Two minutes conditioning of diets containing 15 g/kg PSB increased (P < 0.05) apparent metabolisable energy retention in broilers.4. It was concluded that 2 min conditioning of diet containing 15 g/kg PSB improved pellet quality and nutrient retention of broiler chickens, while the main effects of conditioning time and PSB levels were controversial in most evaluated parameters.
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Alimentación Animal/normas , Bentonita/farmacología , Pollos/crecimiento & desarrollo , Animales , Peso Corporal , Pollos/anatomía & histología , Ingestión de Alimentos , Manipulación de Alimentos/métodos , Yeyuno/anatomía & histología , Yeyuno/metabolismo , Masculino , Factores de TiempoRESUMEN
1. This study was carried out to evaluate the effect of steam-conditioning time and different levels of processed sodium bentonite (PSB) on pellet quality, growth performance, intestinal development and morphology, and nutrient digestibilities in broilers during finisher period (d 24-45). 2. A total of 810 male chicks were reared in commercial conditions on floor pens till d 24. Then, birds were weighed and used in a completely randomised design experiment with a 3 × 3 factorial arrangement, including three levels of conditioning times (0, 2 and 4 min) and three PSB levels (0, 7.5 and 15 g/kg diet). Each of the 9 diets fed to 6 replicates group of 15 birds each. 3. The results showed that 2-min steam conditioning and 15 g/kg PSB supplementation significantly increased pellet durability index (PDI) and hardness, and decreased electrical consumption of pelleting. Diets had no significant effects on body weight, feed intake and feed conversion ratio. Although dietary treatments did not influence relative weight and length of three segments of small intestine, 2-min steam conditioning significantly improved villus height (VH) and crypt depth. Steam conditioning of diet for 2 min significantly increased apparent metabolisable energy (AME), ether extract (EE), calcium (Ca) and dry matter (DM) retention in birds measured during 38-42 d of age. 4. It could be concluded that 2-min steam conditioning improved PDI and hardness, VH and nutrient retention (AME, EE, Ca and DM), but did not affect growth performance in broilers during finisher period.
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Alimentación Animal/análisis , Bentonita/análisis , Pollos/fisiología , Manipulación de Alimentos , Calidad de los Alimentos , Vapor/análisis , Fenómenos Fisiológicos Nutricionales de los Animales/efectos de los fármacos , Animales , Pollos/anatomía & histología , Pollos/crecimiento & desarrollo , Dieta/veterinaria , Digestión/efectos de los fármacos , Metabolismo Energético/efectos de los fármacos , Intestinos/anatomía & histología , Intestinos/efectos de los fármacos , Masculino , Presión , Distribución Aleatoria , Sodio/análisis , Factores de TiempoRESUMEN
BACKGROUND: The aim of this randomized controlled triple blind trial was to compare the efficacy of clonidine with dexamethasone versus ondansetron with dexamethasone for postoperative pain, nausea and vomiting prevention in orthognathic surgery patients. MATERIAL AND METHODS: In this clinical trial study, 30 consecutive patients with skeletal class III deformities were candidates for orthognathic surgery in Qaem hospital, Mashhad University of medical sciences, Mashhad, Iran from March to November 2017. These subjects were randomly assigned to two equal number groups, ondansetron or clonidine. Patients received either oral ondansetron 8mg or oral clonidine 150µg as premedication, 1 hour before the surgery (both dissolved in 20 cc of water). Also both groups received intravenous dexamethasone 8mg (1 hour preoperatively and every 4 hours intraoperatively). RESULTS: In this study, a total of 30 patients (14 males and 16 females) with a mean age of 23.9 ± 3.9 were investigated. The incidence of postoperative nausea in women was more than men (p=0.003), also the correlation between the incidence of PON and the surgery duration ≥ 3 hours was statistically significant (p = 0.050). The frequency of postoperative nausea (PON) in the ondansetron group was less than clonidine (53.3% vs 73.3% respectively). There was no postoperative vomiting (POV) in the ondansetron group, but 6.7% of cases in clonidine group suffered POV. Post-operative nausea in ondansetron group occurred significantly later than clonidine (525.0±233.2 vs 100.0±34.0 min; p <0.001). On the other hand, the incidence time of post-operative severe pain or in other word the analgesia time in clonidine group was significantly more than ondansetron one (875/0±68/5 vs 614.3±159.1 min; p <0.001). CONCLUSION: Ondansetron with dexamethasone premedication was more effective in controlling PONV after orthognathic surgery compared to clonidine with dexamethasone group.
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Analgésicos/uso terapéutico , Antieméticos/uso terapéutico , Clonidina/uso terapéutico , Ondansetrón/uso terapéutico , Procedimientos Quirúrgicos Ortognáticos , Dolor Postoperatorio/prevención & control , Náusea y Vómito Posoperatorios/prevención & control , Adolescente , Adulto , Método Doble Ciego , Femenino , Humanos , Masculino , Resultado del Tratamiento , Adulto JovenRESUMEN
We investigated the effects of milk protein concentrate (MPC) and milk protein concentrate hydrolysate (MPCH) as antioxidant agents in rats. Six groups of healthy (non-diabetic) and type-II diabetic rats were used: (1) healthy rats (control), (2) alloxan-induced rats (diabetic control group), (3) healthy rats treated orally with MPC, (4) diabetic rats treated orally with MPC, (5) healthy rats treated orally with MPCH, and (6) diabetic rats treated orally with MPCH. We concluded that treatment with MPC or MPCH reduced the level of thiobarbituric acid reactive substances in healthy and diabetic rats. Treatment with MPC or MPCH improved activities of antioxidant enzymes (catalase, superoxide dismutase, reduced glutathione, glutathione-S-transferase, and glutathione peroxidase) in healthy and diabetic rats. From the present data, we concluded that both MPC and MPCH contain potent antioxidants and could improve the health of rats or other animals with diabetes mellitus.
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Aloxano , Hidrolisados de Proteína , Animales , Antioxidantes , Glucemia/metabolismo , Catalasa/metabolismo , Diabetes Mellitus Experimental , Glutatión/metabolismo , Glutatión Peroxidasa , Leche/química , Proteínas de la Leche , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismo , Sustancias Reactivas al Ácido TiobarbitúricoRESUMEN
BACKGROUND: Major liver resection is associated with haemodynamic, hepatic and renal changes as a result of the procedure. AIM: To compare Desflurane (D) versus Sevoflurane (S) on hepatic, renal functions, haemodynamics and perioperative course for cirrhotic patients undergoing major liver resection. PATIENTS AND METHODS: A prospective randomized control study with 50 patients (Child A) (D, n = 25 and S, n = 25). End tidal D or S adjusted with Entropy (40-60). Haemodynamics monitored with invasive blood pressure and trans-oesophageal Doppler (TED). Liver and kidney function tests, blood Glutathione-S-transferase (GST), urinary microalbuminuria (Microalb) were assayed. Extubation time and anaesthetic consumption were recorded. RESULTS: Systemic vascular resistance (SVR) post-resection and stroke volume of D vs S were 835.04 ± 12.02 vs 778.16 ± 11.97 dyn.sec.cm(-5), P < 0.01, and 85.72 ± 2.95 vs 76.16 ± 6.52 ml, P < 0.01 respectively. Doppler corrected flow time (FTc) between groups were comparable (P > 0.05). No difference post-operatively regarding hepatic and renal functions, and urine Microalb (14.76 ± 3.95 vs l4.24 ± 8.65 µg/ml, P = 0.78), but a statistically difference was found with GST (0.046 ± [symbols: see text], vs 0.043 ± [symbols: see text] IU/ml, P < 0.01). Despite a higher D consumption (73 ± 17 vs 64 ± 22 ml, P = 0.102), cost in Egyptian pounds (LE) was lower with D (141.14 ± 32.90 vs 320.60 ± 114.01, LE, P < 0.01). Extubation time and ICU stay with D vS (4.52 ± 2 vs 7.72 ± 2 min, P < 0.01) and (1.40 0.50 vs 1.64 ± 0.48, days P = 0.09) respectively. CONCLUSION: Neither D nor S were clinically superior to the other with respect to liver and kidneys functions, but D was found to preserve better the haemodynamic parameters and enhance recovery at a lower cost.
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Anestésicos por Inhalación/farmacología , Hepatectomía , Isoflurano/análogos & derivados , Cirrosis Hepática/cirugía , Éteres Metílicos/farmacología , Desflurano , Método Doble Ciego , Ecocardiografía Transesofágica , Femenino , Glutatión Transferasa/sangre , Hemodinámica , Humanos , Isoflurano/farmacología , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , SevofluranoRESUMEN
A 73-year-old woman underwent an awake craniotomy for the resection of a supratentorial brain tumour. We provided sedation for the surgery using a dexmedetomidine target controlled infusion using the Dyck pharmacokinetic model. Using a target controlled infusion allowed more rapid titration to the desired plasma level compared with a manual infusion, without any unexpected cardiovascular, respiratory or other complications. Rapid titration of sedation during awake craniotomy is desirable, allowing deeper sedation during stimulating parts of the surgery, followed by lighter sedation - or absence of sedation - during cortical mapping. While this can be performed manually, we found utilising the Dyck model in this case simple and quick to use, avoiding the need to manually calculate infusion rates. We believe this is the first report of using a target controlled infusion model to administer dexmedetomidine for awake craniotomy, and suggest it could be considered as an alternative to administering a manual infusion.
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AIM: The primary aim was to determine the prognostic significance of apoptosis in colorectal tumour cells and tumour-associated stroma. A secondary aim was to determine whether apoptosis was related to immune surveillance. METHODS: Immunohistochemistry was performed using monoclonal antibodies recognising cleaved caspase-3 (CC3), cleaved poly (ADP-ribose) polymerase (PARP), p53, Bcl2, MHC-II, B cells (CD16), macrophages (CD68) and T cells (CD3), on a tissue microarray of 462 colorectal tumours. RESULTS: Kaplan-Meier analysis demonstrated that patients with high expression of CC3 in the tumour or CC3 or cleaved PARP in tumour-associated stroma have a good prognosis. This suggests that tumour stroma is promoting tumourigenesis and that high levels of death within the stroma breaks this link. CC3 levels in the tumour correlated with cleaved PARP and MHC-II expression but not with CD16, CD68, CD3, p53 or Bcl2 expression. CC3 levels on tumour-associated stroma also correlated with cleaved PARP and MHC-II expression but not with CD16, CD68, CD3, p53 or Bcl2 expression. Tumour cells express MHC-II in response to IFN-γ, suggesting that this may be one of the initiators of apoptosis within the good prognosis tumours. Although 73% of the MHC-II-positive tumour had high levels of apoptosis, many tumours had high levels of apoptosis in the absence of MHC-II, implying that this is only one of many causes of apoptosis within tumours. On multivariate analysis, using Cox's proportional hazards model, tumour stage, vascular invasion and expression of CC3 in tumour-associated stroma were shown to be independent markers of prognosis. CONCLUSION: This study shows that a high level of apoptosis within colorectal tumour-associated stroma is an independent marker of good prognosis.
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Caspasa 3/metabolismo , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/mortalidad , Anciano , Apoptosis/fisiología , Biomarcadores de Tumor/metabolismo , Estudios de Cohortes , Neoplasias Colorrectales/patología , Femenino , Humanos , Masculino , Pronóstico , Modelos de Riesgos Proporcionales , Precursores de Proteínas/metabolismo , Procesamiento Proteico-Postraduccional , Células del Estroma/metabolismo , Células del Estroma/patología , Análisis de SupervivenciaRESUMEN
Reports on the isolation of mesencnymal stromal cells (MSCs) from granulocyte colony stimulating factor mobilized peripheral blood (G-CSF-mobilized PB) using regular culturing techniques are controversial. Enrichment techniques such as CD133 isolation have increased the success rates. CD271 is a well-known marker for enrichment of MSCs from bone marrow (BM). In the present study, we aimed to find out whether CD271 enrichment can help isolation of MSCs from G-CSF-mobilized PB. Five G-CSF-mobilized PB samples were collected from the remnant parts of the bags used for BM transplantation. Five BM samples were used as the control. Mononuclear cells (MNCs) from both resources were collected and underwent magnetic sorting for CD271-positive cells. The isolated cells were cultured, undergoing flowcytometry and differentiation assays to determine if they fulfill MSCs characteristics. CD271-positive portion of G-CSF-mobilized PB did not yield any cell outgrowth but the BM counterpart could successfully form MSC colonies. Although the percentage of CD271+ cells showed no difference between BM-MNCs and G-CSF-mobilized PB-MNCs, hematopoietic markers such as CD45, CD34 and CD133 composed a higher percentage of CD271-positive cells in the G-CSF-mobilized PB group. Results obtained indicated that CD271 enrichment does not help isolation of MSCs from G-CSF-mobilized PB. In this source, almost all of the CD271+ cells are from hematopoietic origin and the frequency of MSCs is so low that possibly during the process of cell isolation most of them are lost and the isolation fails.
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Células de la Médula Ósea/citología , Técnicas de Cultivo de Célula , Células Madre Mesenquimatosas/citología , Proteínas del Tejido Nervioso/genética , Receptores de Factor de Crecimiento Nervioso/genética , Células de la Médula Ósea/metabolismo , Diferenciación Celular/genética , Citometría de Flujo , Factor Estimulante de Colonias de Granulocitos/genética , Factor Estimulante de Colonias de Granulocitos/metabolismo , Humanos , Leucocitos Mononucleares , Células Madre Mesenquimatosas/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Receptores de Factor de Crecimiento Nervioso/metabolismoRESUMEN
Electrocyclic reactions are characterized by the concerted formation and cleavage of both σ and π bonds through a cyclic structure. This structure is known as a pericyclic transition state for thermal reactions and a pericyclic minimum in the excited state for photochemical reactions. However, the structure of the pericyclic geometry has yet to be observed experimentally. We use a combination of ultrafast electron diffraction and excited state wavepacket simulations to image structural dynamics through the pericyclic minimum of a photochemical electrocyclic ring-opening reaction in the molecule α-terpinene. The structural motion into the pericyclic minimum is dominated by rehybridization of two carbon atoms, which is required for the transformation from two to three conjugated π bonds. The σ bond dissociation largely happens after internal conversion from the pericyclic minimum to the electronic ground state. These findings may be transferrable to electrocyclic reactions in general.
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Although malnutrition is known to be frequent in cancer patients, it has not been described in a selected population of patients with gastrointestinal malignancies under chemotherapy only. Physician judgment about malnutrition and risk factors for malnutrition were also evaluated. All consecutive in- and outpatients of 11 centers were prospectively enrolled in a cross-sectional 14-day period study and classified according to the French health recommendations [Haute Autorité de Santé (HAS)]. Among 313 patients enrolled in 11 centers (mean age = 63 yr; range = 21-93; 67% male) mainly with colorectal (58%), pancreatic (15%), gastric (11%), and hepatobiliary (10%) primary tumors, the prevalence of malnutrition was 52%. Moderate and severe malnutrition was present in 27% and 25% of cases, respectively. Physicians considered it in 36% and 6% of cases, respectively, thereby misclassifying 134 patients (43%). The agreement between the HAS definition and the physicians' judgment was very low (κ = 0.30). Most of the patients who were identified as severely malnourished received no nutritional support. Performance status and pancreatic and gastric cancers were independently associated with malnutrition. Malnutrition levels are high, around 50%, unequally distributed according to the primitive tumor. It is still underestimated by physicians. Weight loss remains a clinically relevant, simple, and reliable marker of malnutrition.
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Neoplasias Gastrointestinales/epidemiología , Desnutrición/epidemiología , Estado Nutricional , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Neoplasias Gastrointestinales/fisiopatología , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Evaluación Nutricional , Apoyo Nutricional/métodos , Pacientes Ambulatorios , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Pérdida de Peso , Adulto JovenRESUMEN
BACKGROUND AND AIMS: Defining and assessing the reproducibility of Crohn's disease [CD] endoscopic lesions is essential in assessing endoscopic healing. METHODS: Twelve endoscopic CD experts from the GETAID defined aphthoid erosions [AE], superficial ulcerations [SU], deep ulcerations [DU], stenosis, and fistulas according to a Delphi-like method. Thirty different GETAID physicians declared if they found acceptable each definition. Intra- and inter-observer agreements were investigated using 100 videos with one tagged specific lesion [AE, SU, DU, or sham lesion] read by 15 independent endoscopists at baseline and 1 month later in a randomised order. Video quality was determined by an external reader. According to kappa estimate [κ ±standard error], intra or inter-observer agreement was qualified as 'moderate' [0.4-0.6], 'substantial' [0.6-0.8], or 'almost perfect' [0.8-1.0]. RESULTS: Among 30 different experts, 83% to 97% found acceptable the definitions retrieved from the Delphi-like method. Intra-observer κ was 0.717 [±0.019] for SU, 0.681 [±0.027] for AE, 0.856 [±0.014] for DU, showing 'substantial' agreement. It was 0.801 [±0.016] for any ulceration [DU or SU]. There was a high variability across readers from 'moderate' to 'almost perfect' agreement. Inter-observer κ was 0.548 [±0.042] for SU, 0.554 [±0.028] for AE 0.694 [±0.041] for DU, and 0.705 [±0.042] for any ulceration. Inter-observer agreement increased when reading the 53 high-quality videos: 0.787 [±0.064] [pâ =â 0.001], 0.607 [±0.043] [pâ =â 0.001], and 0.782 [±0.064][pâ =â 0.001] for DU, AE, and any ulceration, respectively. CONCLUSIONS: Despite variable intra-agreement level across readers, the GETAID definitions for CD endoscopic lesions provided 'substantial' inter-observer agreements, especially in case of high-quality videos.
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Enfermedad de Crohn/diagnóstico , Endoscopía Gastrointestinal , Intestinos , Técnica Delphi , Endoscopía Gastrointestinal/métodos , Endoscopía Gastrointestinal/normas , Endoscopía Gastrointestinal/estadística & datos numéricos , Humanos , Intestinos/diagnóstico por imagen , Intestinos/patología , Microscopía por Video/métodos , Variaciones Dependientes del Observador , Mejoramiento de la Calidad , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Terminología como AsuntoRESUMEN
Conformational isomers (conformers) of molecules play a decisive role in biology and organic chemistry. However, experimental methods for investigating chemical reaction dynamics are typically not conformer-sensitive. We report on a gas-phase megaelectronvolt ultrafast electron diffraction investigation of α-phellandrene undergoing an electrocyclic ring-opening reaction. We directly imaged the evolution of a specific set of α-phellandrene conformers into the product isomer predicted by the Woodward-Hoffmann rules in real space and time. Our experimental results are in quantitative agreement with nonadiabatic quantum molecular dynamics simulations, which provide considerable detail of how conformation influences the time scale and quantum efficiency of photoinduced ring-opening reactions.
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BACKGROUND: Altered DNA repair may be associated with aggressive tumour biology and impact upon response to chemotherapy and radiotherapy. We investigated whether expression of human AP endonuclease (APE1), a key multifunctional protein involved in DNA BER, would impact on clinicopathological outcomes in ovarian, gastro-oesophageal, and pancreatico-biliary cancer. METHODS: Formalin-fixed human ovarian, gastro-oesophageal, and pancreatico-biliary cancers were constructed into TMAs. Expression of APE1 was analysed by IHC and correlated to clinicopathological variables. RESULTS: In ovarian cancer, nuclear APE1 expression was seen in 71.9% (97 out of 135) of tumours and correlated with tumour type (P=0.006), optimal debulking (P=0.009), and overall survival (P=0.05). In gastro-oesophageal cancers previously exposed to neoadjuvant chemotherapy, 34.8% (16 out of 46) of tumours were positive in the nucleus and this correlated with shorter overall survival (P=0.005), whereas cytoplasmic localisation correlated with tumour dedifferentiation (P=0.034). In pancreatico-biliary cancer, nuclear staining was seen in 44% (32 out of 72) of tumours. Absence of cytoplasmic staining was associated with perineural invasion (P=0.007), vascular invasion (P=0.05), and poorly differentiated tumours (P=0.068). A trend was noticed with advanced stage (P=0.077). CONCLUSIONS: Positive clinicopathological correlations of APE1 expression suggest that APE1 is a potential drug target in ovarian, gastro-oesophageal, and pancreatico-biliary cancers.
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Neoplasias del Sistema Biliar/diagnóstico , Carcinoma/diagnóstico , ADN-(Sitio Apurínico o Apirimidínico) Liasa/fisiología , Neoplasias Esofágicas/diagnóstico , Neoplasias Ováricas/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Neoplasias Gástricas/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Sistema Biliar/metabolismo , Neoplasias del Sistema Biliar/mortalidad , Carcinoma/metabolismo , Carcinoma/mortalidad , ADN-(Sitio Apurínico o Apirimidínico) Liasa/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/mortalidad , Femenino , Frecuencia de los Genes , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/mortalidad , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/mortalidad , Polimorfismo de Nucleótido Simple , Pronóstico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidad , Análisis de SupervivenciaRESUMEN
AIMS: Neoadjuvant chemotherapy followed by surgery is the standard of care for patients with gastro-oesophageal adenocarcinoma. Previously, we validated the utility of the tumour regression grade (TRG) as a histopathological marker of tumour downstaging in patients receiving platinum-based neoadjuvant chemotherapy. In this study we profiled key DNA repair and damage signalling factors and correlated them with clinicopathological outcomes, including TRG response. METHODS AND RESULTS: Formalin-fixed human gastro-oesophageal cancers were constructed into tissue microarrays (TMAs). The first set consisted of 142 gastric/gastro-oesophageal cancer cases not exposed to neoadjuvant chemotherapy and the second set consisted of 103 gastric/gastro-oesophageal cancer cases exposed to preoperative platinum-based chemotherapy. Expressions of ERCC1, XPF, FANCD2, APE1 and p53 were investigated using immunohistochemistry. In patients who received neoadjuvant chemotherapy, favourable TRG response (TRG 1, 2 or 3) was associated with improvement in disease-specific survival (P=0.038). ERCC1 nuclear expression correlated with lack of histopathological response (TRG 4 or 5) to neoadjuvant chemotherapy (P=0.006) and was associated with poor disease-specific (P=0.020) and overall survival (P=0.040). CONCLUSIONS: We provide evidence that tumour regression and ERCC1 nuclear protein expression evaluated by immunohistochemistry are promising predictive markers in gastro-oesophageal cancer patients receiving neoadjuvant platinum-based chemotherapy.
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Adenocarcinoma/diagnóstico , Proteínas de Unión al ADN/metabolismo , Endonucleasas/metabolismo , Neoplasias Esofágicas/diagnóstico , Neoplasias Gástricas/diagnóstico , Carga Tumoral/fisiología , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores Farmacológicos/análisis , Biomarcadores Farmacológicos/metabolismo , Biomarcadores de Tumor/metabolismo , Núcleo Celular/metabolismo , Proliferación Celular , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Compuestos de Platino/administración & dosificación , Pronóstico , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Análisis de Supervivencia , Análisis de Matrices Tisulares , Resultado del TratamientoRESUMEN
BACKGROUND: Loss of HLA class I is important in ovarian cancer prognosis but its role as a prognostic indicator in relation to therapy remains unproven. We studied the prognostic potential of this antigen and its significance in relation to platinum therapy. METHODS: A total of 157 primary ovarian cancers were assessed for HLA class I immunohistochemically and linked to a comprehensive database of clinicopathological variables, treatment details, and platinum sensitivity. RESULTS: Tumours expressing high levels of HLA class I had significantly improved survival (P=0.044). There was a 19-month difference in the median overall survival between tumours with high and low antigen expression. HLA class I antigen expression, stage, and platinum sensitivity were independently predictive of prognosis on multivariate analysis. HLA class I antigen was shown to be expressed at higher levels in patients with good overall survival in platinum-resistant patients (P=0.042). HLA class I significantly correlated with overall survival on multivariate analyses (P=0.034). CONCLUSION: Low-level HLA class I expression is an independent prognostic indicator of poor clinical outcome in ovarian cancer. The survival advantage of patients with platinum-resistant tumours expressing high levels of HLA class I suggests that immunotherapy may be of use in these ovarian cancers resistant to standard chemotherapy.
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Antineoplásicos/uso terapéutico , Antígenos de Histocompatibilidad Clase I/análisis , Neoplasias Ováricas/tratamiento farmacológico , Platino (Metal)/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Resistencia a Antineoplásicos , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , PronósticoRESUMEN
AIM: To investigate the relationship between caries etiological factors and occurrence of severe caries among adults in Kuwait. METHODS: Forty-two adult patients with severe caries, attending Kuwait polyclinics, were compared with 36 caries-free subjects in a cross-sectional study. The patients with severe caries were aged 16 years or older and had a minimum of eight open coronal carious cavities, with the involvement of at least one anterior tooth. In addition, their salivary glands had not been compromised by disease or medication. The caries-free subjects had at least 24 standing teeth, and no carious cavities. Salivary flow rates, buffering capacity, frequency of sugar consumption, and oral hygiene index were measured. Mutans streptococci and Lactobacillus counts were determined by the dip-slide method. RESULTS: Fisher's exact test or chi(2) test showed that the patients with severe caries had a significantly higher frequency of sugar consumption, plaque index, Lactobacillus and mutans streptococci counts, as compared with those who were caries-free. In contrast, no significant difference was observed in salivary flow rates or buffering capacity between the two groups of patients. In the multiple logistic regression analysis, only frequency of sugar consumption, oral hygiene, and mutans streptococci count were found to be significantly associated with the occurrence of severe caries. CONCLUSION: Severe caries may occur in Kuwait even among adults whose salivary gland functions have not been compromised.
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Caries Dental/etiología , Glucosa , Índice de Higiene Oral , Saliva/química , Adolescente , Adulto , Estudios Transversales , Femenino , Humanos , Concentración de Iones de Hidrógeno , Kuwait/epidemiología , Lactobacillus/aislamiento & purificación , Masculino , Persona de Mediana Edad , Factores de Riesgo , Streptococcus mutans/aislamiento & purificación , Adulto JovenRESUMEN
BACKGROUND: Standard high-volume polyethylene glycol [PEG] bowel preparations [PEG-4L] are recommended for patients with inflammatory bowel disease [IBD] undergoing colonoscopy. However, low-volume preparations [≤2 L of active volume] are often used in clinical practice. The aim of this study was to evaluate the efficacy, tolerability, and safety of the various bowel preparations for patients with IBD, including low-volume preparations. METHODS: We conducted a French prospective multicentre observational study over a period of 1 month. Patients aged 18-75 years with IBD with an indication of colonoscopy independent of the study were enrolled. The choice of the preparation was left to the investigators, as per their usual protocol. The patients' characteristics, disease, and colonoscopy characteristics were recorded, and they were given self-reported questionnaires. RESULTS: Twenty-five public and private hospitals enrolled 278 patients. Among them, 46 had a disease flare and 41 had bowel stenoses. Bowel preparations for colonoscopy were as follows: 42% received PEG-2L, 29% received sodium picosulfate [Pico], 15% received PEG-4L, and 14% had other preparations. The preparation did not reach the Boston's score efficacy outcome in the PEG-4L group in 51.2% of the patients [p = 0.0011]. The preparation intake was complete for 59.5% in the PEG-4L group, compared with 82.9% in the PEG-2L group and 93.8% in the Pico group [p < 0.0001]. Tolerability, as assessed by the patients' VAS, was significantly better for both Pico and PEG-2L compared with PEG-4L, and better for Pico compared with PEG-2L [p = 0.008; p = 0.0003]. In multivariate analyses, low-volume preparations were independent factors of efficacy and tolerability. Adverse events occurred in 4.3% of the patients. CONCLUSIONS: Preparations with PEG-2L and Pico were equally safe, with better efficacy and tolerability outcomes compared with PEG-4L preparations. The best efficacy/tolerance/safety profile was achieved with the Pico preparation.
Asunto(s)
Catárticos , Colonoscopía/métodos , Enfermedades Inflamatorias del Intestino/diagnóstico , Polietilenglicoles , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Catárticos/administración & dosificación , Catárticos/efectos adversos , Citratos/administración & dosificación , Citratos/efectos adversos , Colitis Ulcerosa/diagnóstico , Colonoscopía/efectos adversos , Enfermedad de Crohn/diagnóstico , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/patología , Masculino , Persona de Mediana Edad , Compuestos Organometálicos/administración & dosificación , Compuestos Organometálicos/efectos adversos , Picolinas/administración & dosificación , Picolinas/efectos adversos , Polietilenglicoles/administración & dosificación , Polietilenglicoles/efectos adversos , Estudios Prospectivos , Adulto JovenRESUMEN
1. An experiment was conducted to study the effect of naked neck gene (Na) on carcase measurements and some immunological responses of chickens. 2. The presence of naked neck gene in a single or double state increased body weight. 3. The naked neck genotypes (NaNa or Nana) exhibited higher relative weight of dressed carcase, drumstick and breast muscles compared to normally feathered individuals (nana). The proportion of abdominal fat was decreased in both naked neck genotypes compared with normally feathered ones. 4. A higher (non-specific) cell-mediated immune response was evoked in Na gene bearing birds. 5. Higher concentrations of antibodies occurred after injection of sheep red blood cells into naked neck birds, particularly at 14 d post-secondary injection. 6. The NaNa birds had a higher heterophil/lymphocyte ratio than Nana and nana siblings.