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1.
Quality of life in stroke survivor–caregiver dyads: a new conceptual framework and longitudinal study protocol
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2.
Lorena Martin-Morales Sara Manzano Maria Rodrigo-Faus Adrian Vicente-Barrueco Victor Lorca Gonzalo Núñez-Moreno Paloma Bragado Almudena Porras Trinidad Caldes Pilar Garre Alvaro Gutierrez-Uzquiza 《International journal of cancer. Journal international du cancer》2023,152(2):283-297
Matrix metalloproteinase-11 (MMP11) is an enzyme with proteolytic activity against matrix and nonmatrix proteins. Although most MMPs are secreted as inactive proenzymes and are later activated extracellularly, MMP11 is activated intracellularly by furin within the constitutive secretory pathway. It is a key factor in physiological tissue remodeling and its alteration may play an important role in the progression of epithelial malignancies and other diseases. TCGA colon and colorectal adenocarcinoma data showed that upregulation of MMP11 expression correlates with tumorigenesis and malignancy. Here, we provide evidence that a germline variant in the MMP11 gene (NM_005940: c.232C>T; p.(Pro78Ser)), identified by whole exome sequencing, can increase the tumorigenic properties of colorectal cancer (CRC) cells. P78S is located in the prodomain region, which is responsible for blocking MMP11's protease activity. This variant was detected in the proband and all the cancer-affected family members analyzed, while it was not detected in healthy relatives. In silico analyses predict that P78S could have an impact on the activation of the enzyme. Furthermore, our in vitro analyses show that the expression of P78S in HCT116 cells increases tumor cell invasion and proliferation. In summary, our results show that this variant could modify the structure of the MMP11 prodomain, producing a premature or uncontrolled activation of the enzyme that may contribute to an early CRC onset in these patients. The study of this gene in other CRC cases will provide further information about its role in CRC development, which might improve patient treatment in the future. 相似文献
3.
Dane Scantling Robert Kucejko John Williamson Alvaro Galvez Amanda Teichman Ryan Gruner Nicholas Serniak Brendan McCracken 《Injury》2019,50(1):54-60
Background
Most elderly trauma patients suffer blunt head injury and many utilize antithrombotic (AT) medications. The utility of delayed CT-head (D-CTH) in neurologically intact elderly patients using AT who have an intracranial hemorrhage (ICH) on presentation is unknown. We hypothesized that D-CTH would not alter clinical management and aimed to evaluate the role of D-CTH in this population.Methods
A retrospective cohort study was performed. Patients ≥65 years sustaining blunt head injuries from January 2010 to July 2017 were identified using our level 1 trauma center database. AT-patients presenting with ICH who underwent D-CTH were included. Patients with worsened ICH were compared to those with stable to improved ICH on D-CTH. AT-patients were compared to a cohort of non-AT patients. Fisher’s Exact and Mann-Whitney U tests were utilized and a power analysis conducted.Results
137?A?T and 34 non-AT patients were identified. There was no difference in hemorrhage progression or appearance of new ICH. No patient had a change in management from D-CTH in either cohort. AT-patients were slightly older (p?<?0.001), but cohorts were otherwise similar.50 AT-patients with worsened ICH were compared to 87 with stable ICH. There was no difference in cohort demographics. Hemorrhage progression did not vary with type of AT used but did increase if multiple types of synchronous ICH were present (p?<?0.001).Conclusions
Our data supports abstaining from routine D-CTH of elderly ICH patients with an intact neurologic examination who are utilizing aspirin, clopidogrel or warfarin. Conclusions cannot be drawn regarding new oral anticoagulants (NOACs) given low enrollment. Further multicenter study is required to provide adequate power and detect small levels of management change. 相似文献4.
Nonlinear sensory cortex response to simultaneous tactile stimuli in writer's cramp. 总被引:1,自引:0,他引:1
Terence D Sanger Alvaro Pascual-Leone Daniel Tarsy Gottfried Schlaug 《Movement disorders》2002,17(1):105-111
Writer's cramp is a task-specific dystonia that leads to involuntary hand postures during writing. Abnormalities of sensory processing may play a pathophysiological role in this disorder. Electrophysiology studies in a monkey model of focal dystonia have revealed de-differentiation of sensory maps and the existence of single cells in hand regions of area 3b with enlarged receptive fields that extend to the surfaces of more than one digit. These changes may lead to abnormal processing of simultaneous sensory inputs. To study abnormal processing of simultaneous sensory information in adult humans with writer's cramp, we used functional magnetic resonance imaging to compare the response in primary sensory cortex with simultaneous tactile stimulation of the index and middle finger, with the response to stimulation of each finger alone. We tested five patients with writer's cramp and seven unaffected (normal) subjects. In the normal subjects, a linear combination of the activation patterns for individual finger stimulation predicts the pattern of activity for combined stimulation with 12% error. In writer's cramp patients, the linear combination predicted the combined stimulation pattern with 30% error. Results indicate a nonlinear interaction between the sensory cortical response to individual finger stimulation in writer's cramp. This altered interaction may contribute to the motor abnormalities. 相似文献
5.
Exacerbation of Partial Seizures and Onset of Nonepileptic Myoclonus with Carbamazepine 总被引:4,自引:3,他引:1
A child had two to three generalized tonic-clonic (GTC) seizures per week unresponsive to phenobarbital (PB) and valproate (VPA). Interictal EEG demonstrated left occipital spikes. When carbamazepine (CBZ) therapy was started, he developed very frequent (4-6/day) complex partial seizures (CPS) characterized on ictal EEG by focal right temporal lobe discharges. The seizure exacerbation, which was associated with development of nonepileptic, multifocal myoclonus, resolved 24 h after CBZ was discontinued. The exacerbation occurred with therapeutic CBZ serum levels, but may have been related to the toxic levels of carbamazepine-10, 11-epoxide (CBZE). 相似文献
6.
Juan M. Bellón MD Julia Buján MD Natalio G. Honduvilla MD Alvaro Hernando MD Jacinto Navlet MD 《Annals of vascular surgery》1995,9(3):266-273
Various methods of cryopreservation of human endothelial cells (EC) were studied to determine their viability and behavior when seeded onto vascular prostheses made of polytetrafluoroethylene (PTFE). Three different protocols were used: (1) cyropreservation of whole umbilical vein, (2) cyropreservation of freshly extracted umbilical EC in suspension, and (3) cryopreservation of EC derived from a first subculture. Fresh EC and EC from a first subculture were used as controls. The viability and growth of these cells in culture media were studied, and basal prostacyclin levels were determined. The cells were assessed morphologically after they were seeded onto PTFE discs. Our results showed that the cryopreservation method that maintained the greatest viability was that in which previously cultured EC were used. Basal prostacyclin levels were significantly different following cyropreservation. However, when these cells were seeded onto PTFE discs their behavior was similar to that of fresh EC.We thank W. L. Gore & Associates for supplying the prostheses used in this study.Supported by a grant from the Comision Interministerial de Cieucia y Tecnologia SAF 92/0875. 相似文献
7.
CONTEXT AND OBJECTIVE: The safety and efficacy of drug-eluting stents reduce the need for surgical revascularization. The objective of the present study was to investigate whether paclitaxel or rapamycin-eluting stent are effective in avoiding the need for coronary-artery bypass grafting. METHODS: This was a systematic review of the literature using the methodology of the Cochrane Collaboration. The type of study considered was controlled randomized trials; the type of intervention was drug-eluting or bare-metal stents; and the main outcome investigated was coronary-artery bypass grafting. RESULTS: The ten studies included in this systematic review did not show any statistically significant difference between the drug-eluting stents and the bare-metal stents with regard to the outcome of coronary-artery bypass grafting (confidence interval: 0.31 to 1.42). CONCLUSION: The surgical revascularization rate was not reduced by the use of drug-eluting stents. 相似文献
8.
Jason T. Siegel M.A. Eusebio M. Alvaro PhD. M.P.H. Michael Burgoon PhD. 《The Journal of adolescent health》2003,33(6):458-461
This research is supported in part by Arizona Disease Control and Research Commission (ADCRC), Grant #9904 (M. Burgoon, PI). This study assesses how adolescent nonsmokers, at-risk smokers, and smokers differ in perceptions of smoking harms, benefits, and safety. While small differences exist when comparing attitudes and knowledge concerning short- and long-term benefits of smoking, large differences arise when attitudes and knowledge concerning the short-term benefits and the safety of casual smoking are compared. 相似文献
9.
The tumor marker CA 15.3 was studied in 85 patients with liver cirrhosis. Nine patients (10.6%) had abnormal levels of CA 15.3 with the highest values in cases of Child's C patients. However, Child's classes were not significantly associated with the level of the antigen. We found significant correlations with some laboratory tests, especially IgA. All patients with an elevated CA 15.3 value also had abnormal levels of IgA, and multivariate analysis showed that IgA was the only independent factor associated with CA 15.3. Although IgA is a marker of alcoholic liver disease, other markers of alcoholism were not associated with CA 15.3. Cytolysis and cholestasis were not significantly associated with the CA 15.3 level, but liver dysfunction seemed to be involved. Liver disease does not substantially limit the usefulness of CA 15.3 in the cancer patient who also has liver cirrhosis, since both the percentage of abnormal values and the elevation of the serum levels are moderate in cirrhotic patients. 相似文献
10.
Elena del Olmo Carmen del Arco Alvaro Díaz Julio Pascual Guadalupe Mengod José M. Palacios Angel Pazos 《The European journal of neuroscience》1996,8(1):53-60
The pattern of pre- and postnatal appearance of 5-HT1D receptors throughout the different areas of the human brain was studied by quantitative in vitro autoradiography, using [125 I]GTI (serotonin O -carboxymethyl-glycyl-[125 I]tyrosinamide) as a ligand. The anatomical distribution of 5-HT1D receptors in neonatal, infant and children's brain was in good agreement with that observed in the adult, the basal ganglia and substantia nigra being the most intensely labelled areas. The development of these receptors throughout the human brain was mainly postnatal: low densities of [125 I]GTI binding sites were observed at the fetal/neonatal stage in most regions analyzed, in contrast with the high levels of labelling found in infant and children's brains. Indeed, in a number of regions, including the globus pallidus, substantia nigra and visual cortex, a peak of overexpression of 5-HT1D receptors was observed in the first decade of life. Such overexpression could support a regulatory role for 5-HT1D receptors in advanced periods of the CNS developmental process. Our results also indicate that the administration of drugs acting on 5-HT1D receptors during the early postnatal period of life could result in modifications of their properties, as these receptors are already functional in this period. 相似文献