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BACKGROUND: The DV-QoL is a 17-item questionnaire measuring health-related quality of life in patients affected by symptomatic diverticular disease, covering four domains: physical symptoms, concerns, feelings, and behavioral changes. Given the lack of a diverticulitis-specific questionnaire to be used for German-speaking patients, we prospectively validated the German version of the DV-QoL. METHODS: German-speaking patients with CT-confirmed history of recurrent diverticular disease admitted to a Swiss surgical department completed the German version of the DV-QoL, along with short form-36 (SF-36) and the Gastrointestinal Quality of Life Index (GIQLI). Reliability was examined using exploratory and confirmatory factor analysis, a Martin-Loef test, and Cronbach's alpha. For convergent validity testing, correlations were calculated with the GIQLI and SF-36. Discriminant validity tests included age and gender. RESULTS: We included 121 patients, of whom 77 were admissions for elective surgery and 44 presented with acute diverticulitis treated conservatively. The DV-QoL's total score showed good correlations with the GIQLI (r = - 0.77) and its subscales (r = - 0.76 to - 0.45), as well as with the SF-36's subscales (r = - 0.30 to - 0.57). No relationships were found with age or gender (p < 0.05). The Cronbach's alpha coefficient was 0.89 over all items and 0.69, 0.90, 0.78, and 0.77 for the four separated domains (physical symptoms, cognitions/concerns, feelings, and behavioral changes, respectively). A nonsignificant Martin-Loef test indicated unidimensionality (p = 1), further supported by the exploratory factor analysis, which showed an item information sharing of 65%. CONCLUSION: The German DV-QoL questionnaire can be used as a valid and reliable disease-specific measure for quality of life in patients with recurrent diverticular disease.
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Qualidade de Vida , Traduções , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários/normas , Idoso , Reprodutibilidade dos Testes , Estudos Prospectivos , Idioma , Adulto , Suíça , Diverticulite/psicologia , Alemanha , Análise Fatorial , Idoso de 80 Anos ou mais , RecidivaRESUMO
The nucleation and growth of calcium-silicate-hydrate (C-S-H) is of fundamental importance for the strength development and durability of the concrete. However, the nucleation process of C-S-H is still not fully understood. The present work investigates how C-S-H nucleates by analyzing the aqueous phase of hydrating tricalcium silicate (C3S) by applying inductively coupled plasma-optical emission spectroscopy as well as analytical ultracentrifugation. The results show that the C-S-H formation follows non-classical nucleation pathways associated with the formation of prenucleation clusters (PNCs) of two types. Those PNCs are detected with high accuracy and reproducibility and are two species of the 10 in total, from which the ions (with associated water molecules) are the majority of the species. The evaluation of the density and molar mass of the species shows that the PNCs are much larger than ions, but the nucleation of C-S-H starts with the formation of liquid precursor C-S-H (droplets) with low density and high water content. The growth of these C-S-H droplets is associated with a release of water molecules and a reduction in size. The study gives experimental data on the size, density, molecular mass, and shape and outlines possible aggregation processes of the detected species.
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This study evaluates the impact of an intervention targeting high-risk behaviors among diverse, alcohol-using adults living with HIV (N = 267) from 2009 to 2013 in Miami, FL. The intervention took place in a group setting for eight sessions over 4 weeks and was compared to a didactic health promotion group. Assessments were conducted pre-intervention, post-intervention, and at 3, 6, and 12 months follow-up. Intervention participants (48% of sample) evidenced greater knowledge about HIV, more condom self-efficacy, and greater intentions to use condoms after participation. This was particularly noteworthy because associations among knowledge about HIV, more condom self-efficacy, and greater intentions to use condoms were negatively associated with intervention status at baseline. Participants also reported fewer heavy drinking days after participating in the intervention than those in the control group. Greater HIV knowledge, more condom self-efficacy and intentions to use condoms predicted more condom assertiveness; greater intentions to use condoms predicted fewer unprotected sexual behaviors. These findings underscore the importance of taking a comprehensive, multi-systemic approach to address risky behaviors in high-risk, diverse populations.
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Infecções por HIV , Saúde Holística , Adulto , Cognição , Preservativos , Infecções por HIV/prevenção & controle , Infecções por HIV/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Assunção de Riscos , Comportamento Sexual/psicologiaRESUMO
Cysteine is the simplest thiolated, chiral amino acid and is often used as the anchor for studies of self-assembled monolayers (SAMs) of complex biomolecules such as peptides. Understanding the interaction of SAMs of cysteine with low-energy secondary electrons (SEs) produced by X-rays can further our understanding of radiation damage in biomolecules. In particular, if the electrons are polarized, chiral-selective chemistry could have bearing on the origin of homochirality in nature. In the present paper, we use synchrotron radiation-based X-ray photoelectron spectroscopy to determine the changes that occur in the bonding of self-assembled layers of cysteine on gold as a result of soft X-ray irradiation. To investigate the possibility of chiral selectivity resulting from the interaction of low-energy, spin-polarized SEs (SPSEs), measurements were conducted on cysteine adsorbed on a 3 nm-thick gold layer deposited on a CoPt thin-film multilayer with perpendicular magnetic anisotropy. Time-dependent measurements of the C 1s, N 1s, O 1s, S 2p, and Au 4f core levels are used to follow the changes in surface chemistry and determine reaction cross-sections as a function of SE exposure. Analysis of the data results in cross-sections in the range of 5-7 Mb and suggests possible reaction pathways. Changing the magnetization direction of the CoPt multilayer produces SPSEs with opposite polarity. Some evidence of spin-dependent reactions is indicated but is inconclusive. Possible reasons for the discrepancy are posited.
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OBJECTIVE: Several studies have found an increase in hippocampal volume following electroconvulsive therapy (ECT), but the effect on cortical thickness has been less investigated. We aimed to examine the effects of ECT on cortical thickness and their associations with clinical outcome. METHOD: Using 3 Tesla MRI scanner, we obtained T1-weighted brain images of 18 severely depressed patients at three time points: before, right after and 6 months after a series of ECT. The thickness of 68 cortical regions was extracted using Free Surfer, and Linear Mixed Model was used to analyze the longitudinal changes. RESULTS: We found significant increases in cortical thickness of 26 regions right after a series of ECT, mainly within the frontal, temporal and insular cortex. The thickness returned to the baseline values at 6-month follow-up. We detected no significant decreases in cortical thickness. The increase in the thickness of the right lateral orbitofrontal cortex was associated with a greater antidepressant effect, r = 0.75, P = 0.0005. None of the cortical regions showed any associations with cognitive side effects. CONCLUSION: The increases in cortical thickness induced by ECT are transient. Further multimodal MRI studies should examine the neural correlates of these increases and their relationship with the antidepressant effect.
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Córtex Cerebral/patologia , Transtorno Depressivo/patologia , Transtorno Depressivo/terapia , Eletroconvulsoterapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Córtex Cerebral/diagnóstico por imagem , Transtorno Depressivo/diagnóstico por imagem , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Radiation damage and stimulated desorption of nucleotides 2'-deoxyadenosine 5'-monophosphate (dAMP), adenosine 5'-monophosphate (rAMP), 2'-deoxycytidine 5'-monophosphate (dCMP), and cytidine 5'-monophosphate (rCMP) deposited on Au have been measured using x-rays as both the probe and source of low energy secondary electrons. The fluence dependent behavior of the O-1s, C-1s, and N-1s photoelectron transitions was analyzed to obtain phosphate, sugar, and nucleobase damage cross sections. Although x-ray induced reactions in nucleotides involve both direct ionization and excitation, the observed bonding changes were likely dominated by the inelastic energy-loss channels associated with secondary electron capture and transient negative ion decay. Growth of the integrated peak area for the O-1s component at 531.3 eV, corresponding to cleavage of the C-O-P phosphodiester bond, yielded effective damage cross sections of about 23 Mb and 32 Mb (1 Mb = 10-18 cm2) for AMP and CMP molecules, respectively. The cross sections for sugar damage, as determined from the decay of the C-1s component at 286.4 eV and the glycosidic carbon at 289.0 eV, were slightly lower (about 20 Mb) and statistically similar for the r- and d- forms of the nucleotides. The C-1s component at 287.6 eV, corresponding to carbons in the nucleobase ring, showed a small initial increase and then decayed slowly, yielding a low damage cross section (â¼5 Mb). Although there is no statistical difference between the sugar forms, changing the nucleobase from adenine to cytidine has a slight effect on the damage cross section, possibly due to differing electron capture and transfer probabilities.
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Dano ao DNA , Elétrons , Nucleotídeos/química , TermodinâmicaRESUMO
BACKGROUND: Obesity is strongly associated with prevalence of obstructive sleep apnea (OSA), and weight loss has been shown to reduce disease severity. OBJECTIVE: To investigate whether liraglutide 3.0 mg reduces OSA severity compared with placebo using the primary end point of change in apnea-hypopnea index (AHI) after 32 weeks. Liraglutide's weight loss efficacy was also examined. SUBJECTS/METHODS: In this randomized, double-blind trial, non-diabetic participants with obesity who had moderate (AHI 15-29.9 events h(-1)) or severe (AHI ⩾30 events h(-1)) OSA and were unwilling/unable to use continuous positive airway pressure therapy were randomized for 32 weeks to liraglutide 3.0 mg (n=180) or placebo (n=179), both as adjunct to diet (500 kcal day(-1) deficit) and exercise. Baseline characteristics were similar between groups (mean age 48.5 years, males 71.9%, AHI 49.2 events h(-1), severe OSA 67.1%, body weight 117.6 kg, body mass index 39.1 kg m(-2), prediabetes 63.2%, HbA1c 5.7%). RESULTS: After 32 weeks, the mean reduction in AHI was greater with liraglutide than with placebo (-12.2 vs -6.1 events h(-1), estimated treatment difference: -6.1 events h(-1) (95% confidence interval (CI), -11.0 to -1.2), P=0.0150). Liraglutide produced greater mean percentage weight loss compared with placebo (-5.7% vs -1.6%, estimated treatment difference: -4.2% (95% CI, -5.2 to -3.1%), P<0.0001). A statistically significant association between the degree of weight loss and improvement in OSA end points (P<0.01, all) was demonstrated post hoc. Greater reductions in glycated hemoglobin (HbA1c) and systolic blood pressure (SBP) were seen with liraglutide versus placebo (both P<0.001). The safety profile of liraglutide 3.0 mg was similar to that seen with doses ⩽1.8 mg. CONCLUSIONS: As an adjunct to diet and exercise, liraglutide 3.0 mg was generally well tolerated and produced significantly greater reductions than placebo in AHI, body weight, SBP and HbA1c in participants with obesity and moderate/severe OSA. The results confirm that weight loss improves OSA-related parameters.
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Hipoglicemiantes/uso terapêutico , Liraglutida/uso terapêutico , Obesidade/complicações , Obesidade/tratamento farmacológico , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/tratamento farmacológico , Adolescente , Adulto , Fármacos Antiobesidade/farmacologia , Fármacos Antiobesidade/uso terapêutico , Método Duplo-Cego , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/farmacologia , Liraglutida/farmacologia , Masculino , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Polissonografia , Estudos Prospectivos , Apneia Obstrutiva do Sono/fisiopatologia , Resultado do Tratamento , Estados Unidos/epidemiologia , Redução de Peso/efeitos dos fármacos , Adulto JovemRESUMO
X-ray magnetic circular dichroism (XMCD) measurements on single-crystal and powder samples of Ba_{0.6}K_{0.4}Mn_{2}As_{2} show that the ferromagnetism below T_{C}≈100 K arises in the As 4p conduction band. No XMCD signal is observed at the Mn x-ray absorption edges. Below T_{C}, however, a clear XMCD signal is found at the As K edge which increases with decreasing temperature. The XMCD signal is absent in data taken with the beam directed parallel to the crystallographic c axis indicating that the orbital magnetic moment lies in the basal plane of the tetragonal lattice. These results show that the previously reported itinerant ferromagnetism is associated with the As 4p conduction band and that distinct local-moment antiferromagnetism and itinerant ferromagnetism with perpendicular easy axes coexist in this compound at low temperature.
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BACKGROUND: Current histopathological staging procedures in colon carcinomas depend on midline division of the lymph nodes with one section of haematoxylin & eosin (H&E) staining only. By this method, tumour deposits outside this transection line may be missed and could lead to understaging of a high-risk group of stage UICC II cases, which recurs in â¼20% of cases. A new diagnostic semiautomated system, one-step nucleic acid amplification (OSNA), detects cytokeratin (CK) 19 mRNA in lymph node metastases and enables the investigation of the whole lymph node. The objective of this study was to assess whether histopathological pN0 patients can be upstaged to stage UICC III by OSNA. METHODS: Lymph nodes from patients who were classified as lymph node negative after standard histopathology (single (H&E) slice) were subjected to OSNA. A result revealing a CK19 mRNA copy number >250, which makes sure to detect mainly macrometastases and not isolated tumour cells (ITC) or micrometastases only, was regarded as positive for lymph node metastases based on previous threshold investigations. RESULTS: In total, 1594 pN0 lymph nodes from 103 colon carcinomas (median number of lymph nodes per patient: 14, range: 1-46) were analysed with OSNA. Out of 103 pN0 patients, 26 had OSNA-positive lymph nodes, resulting in an upstaging rate of 25.2%. Among these were 6/37 (16.2%) stage UICC I and 20/66 (30.3%) stage UICC II patients. Overall, 38 lymph nodes were OSNA positive: 19 patients had one, 3 had two, 3 had three, and 1 patient had four OSNA-positive lymph nodes. CONCLUSIONS: OSNA resulted in an upstaging of over 25% of initially histopathologically lymph node-negative patients. OSNA is a standardised, observer-independent technique, allowing the analysis of the whole lymph node. Therefore, sampling bias due to missing investigation of certain lymph node tissue can be avoided, which may lead to a more accurate staging.
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Adenocarcinoma/secundário , Neoplasias do Colo/patologia , Metástase Linfática/genética , Estadiamento de Neoplasias/métodos , Técnicas de Amplificação de Ácido Nucleico , RNA Mensageiro/análise , RNA Neoplásico/análise , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/cirurgia , Adulto , Idoso , Quimioterapia Adjuvante , Colectomia , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Neoplasias do Colo/cirurgia , Europa (Continente) , Reações Falso-Negativas , Feminino , Humanos , Linfonodos/química , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Estudos Prospectivos , RNA Mensageiro/genética , RNA Neoplásico/genética , Coloração e Rotulagem , Adulto JovemRESUMO
We have performed a comparison of the radiation damage occurring in DNA adsorbed on gold in two different configurations, when the DNA is thiolated and bound covalently to the substrate and when it is unthiolated and interacts with the substrate through the bases. Both molecules were found to organize so as to protrude from the surface at ~45 degrees. Changes in the time-dependent C 1s and O 1s X-ray photoelectron (XP) spectra resulting from irradiation were interpreted to arise from cleavage of the phosphodiester bond and possibly COH desorption. By fitting the time-dependent XP spectra to a simple kinetic model, time constants were extracted, which were converted to cross sections and quantum yields for the damage reaction. The radiation induced damage is significantly higher for the thiolated DNA. N 1s X-ray absorption spectrum revealed the N-C=N LUMO is more populated in the unthiolated molecule, which is due to a higher degree of charge transfer from the substrate to this LUMO in the unthiolated case. Since the N-C=N LUMO of the thiolated molecule is comparatively less populated, it is more effective in capturing low energy electrons resulting in a higher degree of damage.
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Dano ao DNA/efeitos da radiação , DNA/efeitos da radiação , Elétrons , Ouro/química , Compostos de Sulfidrila/química , DNA/química , Espectroscopia Fotoeletrônica , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície , Espectroscopia por Absorção de Raios X , Raios XRESUMO
BACKGROUND: Abdominal wall reconstruction in large incisional hernia/laparostoma poses a particular challenge. A loss of domain is the extreme form of intestinal volume displacement. The challenge lies in overcoming retraction of the lateral abdominal muscles. OBJECTIVE: Experienced surgeons have access to a variety of techniques aimed at gaining lateral length along the abdominal wall or reducing suture tension at the midline. These techniques are intended to facilitate reconstruction even in complex cases and are outlined in this article from a practical perspective. MATERIAL AND METHODS: The application of botulinum toxin A (BTA) and progressive pneumoperitoneum (PPP) are described as preoperative methods to gain abdominal wall length. Peritoneal flaps, intraoperative fascial traction (IFT) and component separation including transversus abdominis muscle release (TAR) are available for the surgical reconstruction of the abdominal wall. Bridging and the intraperitoneal onlay mesh approach are fallback techniques. All these techniques were integrated into a practical algorithm for complex abdominal wall reconstruction including preoperative and postoperative care and assessed by the authors with respect to effort, effectiveness and complexity. RESULTS AND CONCLUSION: In the opinion of the authors, the status of complex abdominal wall reconstruction is currently best described by a combination of the most effective and proven techniques in terms of a "categorical algorithm". The combination of BTA, IFT and TAR presently appears to be the most effective method; however, experience and expertise are a prerequisite.
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Parede Abdominal , Toxinas Botulínicas Tipo A , Hérnia Ventral , Humanos , Hérnia Ventral/cirurgia , Herniorrafia/métodos , Parede Abdominal/cirurgia , Músculos Abdominais/cirurgia , SuturasRESUMO
INTRODUCTION AND IMPORTANCE: Due to therapeutic advances and improvements in follow-up care, the diagnosis and treatment of extrahepatic metastases of hepatocellular carcinoma [HCC] have gained clinical significance. However, adrenal gland metastases of HCC remain a rare clinical encounter. Several systemic and local treatment options are discussed in current literature. Adrenalectomy in cases of isolated adrenal metastases with well-controlled intrahepatic lesions has been shown to benefit patients in case series. PRESENTATION OF THE CASE: This 65-year-old patient presented with suspected metachronous left sided adrenal metastasis seven years after bisegmentectomy for HCC and after undergoing trans-arterial chemoembolization [TACE] for multifocal intrahepatic recurrences while being listed for liver transplantation "beyond Milan criteria". Adrenalectomy was suggested for histopathological confirmation of the suspected metastasis and re-consideration for liver transplant. The resection was performed laparoscopically and metastasis of HCC was confirmed in histopathological analysis. Postoperatively, the patient recovered quickly. However, the patient decided against re-listing for liver transplantation. CLINICAL DISCUSSION: Current literature suggests, that minimally-invasive adrenalectomy should be considered in patients with no more than two extrahepatic lesions, a Child-Pugh-Score of less than A5, low alpha-fetoprotein [AFP] levels <100 ng/ml and size <3 cm. The oncological goal should be to achieve a tumor free extrahepatic situation with a potential oncological benefit. CONCLUSION: Our patient presented as an ideal candidate for resection of the adrenal gland metastasis and could have been re-assessed postoperatively for liver transplantation. Still, more research is needed to improve patient-selection for metastasectomy in HCC.
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OBJECTIVE: To explore the relationship between brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF), cerebral deep white matter lesions (DWMLs), and measures of white matter integrity in patients with late-onset depression, with respect to vascular risk factors. METHOD: We examined 22 patients with late-onset depression and 22 matched controls. Quantification of plasma BDNF and VEGF levels were performed with enzyme-linked immunosorbent assay (ELISA) kits. Measures of white matter integrity comprised apparent diffusion coefficient (ADC) and fractional anisotropy (FA), obtained by diffusion tensor imaging (DTI). Effects of DWMLs, FA, ADC, and vascular risk factors on BDNF and VEGF were assessed using multiple linear regression. RESULTS: The BDNF and VEGF levels did not differ significantly between groups. With pooled data for patients and controls, the BDNF level was positively associated with both number (t = 2.14, P = 0.039) and volume (t = 2.04, P = 0.048) of prefrontal DWMLs and negatively associated with FA in prefrontal normal-appearing white matter (t = -2.40, P = 0.02), adjusted for age and gender. Smoking and hypercholesterolemia was positively associated with the BDNF (t = 2.36, P = 0.023) and VEGF levels (t = 2.28, P = 0.028), respectively. CONCLUSION: Our results suggest a role for BDNF in the complex pathophysiologic mechanisms underlying DWMLs in both normal aging and late-onset depression.
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Envelhecimento , Fator Neurotrófico Derivado do Encéfalo/sangue , Transtorno Depressivo Maior , Lobo Frontal/patologia , Leucoencefalopatias , Fator A de Crescimento do Endotélio Vascular/sangue , Idade de Início , Idoso , Envelhecimento/sangue , Envelhecimento/patologia , Anisotropia , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/patologia , Imagem de Tensor de Difusão , Feminino , Humanos , Leucoencefalopatias/sangue , Leucoencefalopatias/patologia , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Isolated optic nerve sheath meningocele is a rare affection defined as the cystic enlargement of the optic nerve sheath filled with cerebrospinal fluid. We report the case of a 39-year-old woman presenting with bilateral meningocele uncovered during a routine examination for headache complaints. A 5-year follow-up validated the lesion's clinical and imaging stability. Magnetic resonance imaging (MRI) is an essential tool in the diagnosis of this pathology, alongside characteristic symptoms indicating that the meningocele might have progressively expanded into the orbit. In this case we present a therapeutic approach based on pathophysiological hypotheses and review of the literature.
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BACKGROUND: There are no established biomarkers to identify tumour recurrence in stage II colon cancer. As shown previously, the enzymatic activity of the cyclin-dependent kinases 1 and 2 (CDK1 and CDK2) predicts outcome in breast cancer. Therefore, we investigated whether CDK activity identifies tumour recurrence in colon cancer. METHODS: In all, 254 patients with completely resected (R0) UICC stage II colon cancer were analysed retrospectively from two independent cohorts from Munich (Germany) and Leiden (Netherlands). None of the patients received adjuvant treatment. Development of distant metastasis was observed in 27 patients (median follow-up: 86 months). Protein expression and activity of CDKs were measured on fresh-frozen tumour samples. RESULTS: Specific activity (SA) of CDK1 (CDK1SA), but not CDK2, significantly predicted distant metastasis (concordance index=0.69, 95% confidence interval (CI): 0.55-0.79, P=0.036). Cutoff derivation by maximum log-rank statistics yielded a threshold of CDK1SA at 11 (SA units, P=0.029). Accordingly, 59% of patients were classified as high-risk (CDK1SA ≥11). Cox proportional hazard analysis revealed CDK1SA as independent prognostic variable (hazard ratio=6.2, 95% CI: 1.44-26.9, P=0.012). Moreover, CKD1SA was significantly elevated in microsatellite-stable tumours. CONCLUSION: Specific activity of CDK1 is a promising biomarker for metastasis risk in stage II colon cancer.
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Neoplasias do Colo/enzimologia , Quinases Ciclina-Dependentes/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Neoplasias do Colo/patologia , Primers do DNA , Feminino , Imunofluorescência , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos , Adulto JovemRESUMO
We present the refinement of the crystal structure of charge-ordered LuFe2O4, based on single-crystal x-ray diffraction data. The arrangement of the different Fe-valence states, determined with bond-valence-sum analysis, corresponds to a stacking of charged Fe bilayers, in contrast with the polar bilayers previously suggested. This arrangement is supported by an analysis of x-ray magnetic circular dichroism spectra, which also evidences a strong charge-spin coupling. The nonpolar bilayers are inconsistent with charge order based ferroelectricity.
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OBJECTIVE: To determine whether long-term course of treated major depression has an effect on the structure of the brain and the hippocampal volume. METHOD: An 11-year follow-up procedure was used with data collection at baseline and again at follow-up. Tensor-based morphometry (TBM) and automatic hippocampal volume measure was performed on different datasets. The baseline dataset consisted of T1-weighted magnetic resonance images (MRIs) of 24 in-patients suffering from major depression and 33 healthy controls. The second dataset consisted of T1-weighted MRIs of 31 remitted depressive patients and 36 healthy controls. The longitudinal dataset consisted of 19 patients and 19 matched healthy controls present at both the first and the second dataset. Brain segmentation and hippocampal segmentation were fully automated and were based on a spatial normalization to the International Consortium of Brain Mapping (ICBM) non-linear model. RESULTS: Depressed patients were found to have smaller temporal lobes bilaterally, medulla and right hippocampus at baseline. However, these changes were not found at follow-up 11 years later. Moreover, these changes did not significantly correlate with the illness outcome. CONCLUSION: Brain structure changes seem to be state dependent in major depression, only occurring in acute episode of major depression and normalizing after remission.
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Encéfalo/patologia , Transtorno Depressivo Maior/patologia , Hipocampo/patologia , Adulto , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Escalas de Graduação PsiquiátricaRESUMO
Although tissue injury and inflammation are considered essential for the induction of angiogenesis, the molecular controls of this cascade are mostly unknown. Here we show that a macrophage-derived peptide, PR39, inhibited the ubiquitin-proteasome-dependent degradation of hypoxia-inducible factor-1alpha protein, resulting in accelerated formation of vascular structures in vitro and increased myocardial vasculature in mice. For the latter, coronary flow studies demonstrated that PR39-induced angiogenesis resulted in the production of functional blood vessels. These findings show that PR39 and related compounds can be used as potent inductors of angiogenesis, and that selective inhibition of hypoxia-inducible factor-1alpha degradation may underlie the mechanism of inflammation-induced angiogenesis.
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Peptídeos Catiônicos Antimicrobianos , Proteínas de Ligação a DNA/metabolismo , Endotélio Vascular/fisiologia , Isquemia Miocárdica/fisiopatologia , Neovascularização Fisiológica/fisiologia , Proteínas Nucleares/metabolismo , Peptídeos/fisiologia , Animais , Aorta , Capilares/efeitos dos fármacos , Capilares/fisiologia , Bovinos , Hipóxia Celular , Células Cultivadas , Vasos Coronários/efeitos dos fármacos , Cisteína Endopeptidases/metabolismo , Endotélio Vascular/citologia , Coração/fisiologia , Humanos , Fator 1 Induzível por Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia , Técnicas In Vitro , Macrófagos/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Complexos Multienzimáticos/metabolismo , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Isquemia Miocárdica/patologia , Peptídeos/genética , Peptídeos/farmacologia , Complexo de Endopeptidases do Proteassoma , Proteínas Recombinantes/metabolismo , Suínos , Fatores de Transcrição/metabolismo , Ubiquitinas/metabolismo , Veias Umbilicais , Fator de von Willebrand/genéticaRESUMO
CD39, or vascular adenosine triphosphate diphosphohydrolase, has been considered an important inhibitor of platelet activation. Unexpectedly, cd39-deficient mice had prolonged bleeding times with minimally perturbed coagulation parameters. Platelet interactions with injured mesenteric vasculature were considerably reduced in vivo and purified mutant platelets failed to aggregate to standard agonists in vitro. This platelet hypofunction was reversible and associated with purinergic type P2Y1 receptor desensitization. In keeping with deficient vascular protective mechanisms, fibrin deposition was found at multiple organ sites in cd39-deficient mice and in transplanted cardiac grafts. Our data indicate a dual role for adenosine triphosphate diphosphohydrolase in modulating hemostasis and thrombotic reactions.
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Adenosina Trifosfatases , Antígenos CD/metabolismo , Apirase/metabolismo , Coagulação Sanguínea , Plaquetas/fisiologia , Deleção de Genes , Hemostasia , Animais , Antígenos CD/genética , Apirase/deficiência , Apirase/genética , Arteríolas/patologia , Tempo de Sangramento , Plaquetas/citologia , Plaquetas/patologia , Células Cultivadas , Endotélio Vascular/citologia , Endotélio Vascular/enzimologia , Endotélio Vascular/metabolismo , Feminino , Fibrina/metabolismo , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Transplante de Coração/imunologia , Transplante de Coração/patologia , Masculino , Mesentério/irrigação sanguínea , Camundongos , Camundongos Knockout , Agregação Plaquetária , Ratos , Receptores Purinérgicos P2/fisiologia , Receptores Purinérgicos P2Y1 , Tromboplastina/metabolismo , Trombose/patologiaRESUMO
We have examined the morphology, cytochemistry, and biochemistry of mouse leukocyte subsets by analyzing cloned leukocyte populations specialized to perform different immunologic functions. Cloned cells expressing high-affinity plasma membrane receptors for IgE and mediating natural killer (NK) lysis and cloned antigen-specific suppressor T cells contained prominent osmiophilic cytoplasmic granules similar by ultrastructure to those of mouse basophils. Both clones also incorporated 35SO4 into granule-associated sulfated glycosaminoglycans, expressed a characteristic ultrastructural pattern of nonspecific esterase activity, incorporated exogenous [3H]5-hydroxytryptamine, and contained cytoplasmic deposits of particulate glycogen. By contrast, cloned inducer T cells lacked cytoplasmic granules and glycogen, incorporated neither 35SO4 nor [3H]5-hydroxytryptamine, and differed from the other clones in pattern of nonspecific esterase activity. These findings establish that certain cloned cells with NK activity and cloned suppressor T cells express morphologic and biochemical characteristics heretofore associated with basophilic granulocytes. However, these clones differ in surface glycoprotein expression and immunologic function, and the full extent of the similarities and differences among these populations and basophils remains to be determined.