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1.
Clin Radiol ; 79(5): 393-398, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38383253

RESUMEN

AIM: To provide reference values of the dimensions of the left and right atrium (RA) obtained using the biplane and monoplane methods, respectively, on two- and four-chamber views, which represent the standard projections acquired in clinical practice, and correlation with body surface area (BSA), age, and gender. MATERIALS AND METHODS: Healthy volunteers, M:F = 1:1, including five participants per gender and age decile from 20 to 70 years, who underwent cardiovascular magnetic resonance imaging (CMR) were enrolled prospectively. Normal atrial reference values were calculated for male and female subpopulations and stratified by age. Atrial areas and volumes were assessed both as absolute values and indexed to BSA. Differences among genders and correlation with age were assessed. Intra- and interobserver reproducibility were assessed in a subpopulation. RESULTS: Fifty participants (mean age 43.3 ± 14 years, 25 men) were evaluated. Image analysis took <1 minute for each subject (mean time 30 ± 5 seconds). Intra- and interobserver reproducibility were excellent (ICC >0.85 for all datasets). RA areas were significantly higher in males (p=0.0001). The left atrial (LA) surface did not show significant differences among genders. Atrial areas normalised to BSA did not show significant gender differences. Both right and left absolute atrial volumes turned out to be significantly higher in males (p=0.0001 and p=0.0047, respectively), and normalised to BSA remained significantly different only for the RA (p=0.0006). Neither atrial volume nor areas showed significant correlation with age. CONCLUSIONS: The monoplane method is a fast and reproducible technique to assess atrial dimensions. Absolute atrial dimensions show significant variations among genders. Gender-specific reference ranges for atrial dimensions are recommended.


Asunto(s)
Atrios Cardíacos , Imagen por Resonancia Magnética , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Adulto Joven , Anciano , Valores de Referencia , Voluntarios Sanos , Reproducibilidad de los Resultados , Atrios Cardíacos/diagnóstico por imagen
2.
BMC Nurs ; 21(1): 252, 2022 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-36076220

RESUMEN

BACKGROUND: An essential component of becoming a professional nurse is a perspective of global health issues and an awareness of diverse populations. Collaborative online international learning (COIL) using digital technologies, offers meaningful and rewarding opportunities to develop international partnerships between nurses from other countries, without economic, organisational or geographical barriers. Despite reported advantages of using COIL, few COIL interventions have been identified in the nursing literature. The aims of this study are to develop, implement and evaluate a COIL program between Australian and Canadian pre-registration nursing students. METHODS: The study will utilize a mixed methods approach incorporating pre and post-test surveys, focus groups, and semi-structured interviews of key stakeholders. The design will adhere to The State University of New York (SUNY) COIL's criteria for intercultural/international learning opportunities. Participants will be recruited from nursing programs at an Australian Training and Further Education Institute and a Canadian college. Bennett's stages of intercultural competence will provide the theoretical framework for the research. Four specific research interventions will be developed for this project. For students, there will be an online virtual community to allow students and teachers to communicate, socially connect and share resources with each other. Virtual reality simulations will be employed within a virtual global classroom to promote collaborative, intercultural learning. For faculty, a virtual community of practice will provide a platform for faculty to share education and research ideas and participate in collaborate research opportunities. DISCUSSION: This study will evaluate the outcomes of a nursing COIL program. It will measure participants' views on COIL, its contribution to student learning, changes in cultural awareness, organisational impact and research productivity. It will provide nursing students with the opportunity to become global leaders in nursing care and for faculty to develop international research skills and outputs. The findings from the study will allow further refinement of future nursing COIL programs.

3.
Cereb Cortex ; 29(5): 2072-2083, 2019 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-29912300

RESUMEN

We investigated, in 445 healthy adults whose Heschl's gyrus (HG) gyrification patterns had been previously identified, how an in vivo MRI marker of intracortical myelination of HG and the planum temporale (PT) varied as a function of HG gyrification pattern and, in cases of duplication, of anatomical characteristics of the second HG (H2). By measuring the MRI T1/T2 ratio in regions of interest covering the first HG (H1), H2 in cases of common stem (H2CSD), or complete posterior duplication (H2CPD) and the PT, we showed that H1 had the highest T1/T2 values, while the PT had the lowest. The major impact of duplication was a decrease in both H1 and PT T1/T2 values in cases of left CPD. Concerning H2, the right and left T1/T2 values of right H2CSD were closer to those of H1, and those of left H2CPD were closer to those of PT. After adjusting for verbal skills, rhyming performance was not associated with T1/T2 values in left regions, but it decreased with increasing right PT T1/T2 values. These results reveal the existence of hemispheric differences in H2 myelination and underline the importance of neuroimaging markers of intracortical myelination for investigating brain structure-function relationships.


Asunto(s)
Corteza Auditiva/fisiología , Vaina de Mielina/fisiología , Lóbulo Parietal/fisiología , Conducta Verbal/fisiología , Adulto , Corteza Auditiva/anatomía & histología , Femenino , Lateralidad Funcional , Humanos , Masculino , Lóbulo Parietal/anatomía & histología , Fonética , Adulto Joven
4.
Epidemiol Infect ; 146(7): 879-887, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29633676

RESUMEN

In May 2016 a Norovirus (NoV) gastroenteritis outbreak involved a high school class visiting a seaside resort near Taormina (Mascali, Sicily). Twenty-four students and a teacher were affected and 17 of them showed symptoms on the second day of the journey, while the others got ill within the following 2 days. Symptoms included vomiting, diarrhoea and fever, and 12 students required hospitalisation. Stool samples tested positive for NoV genome by Real-Time polymerase chain reaction assay in all 25 symptomatic subjects. The GII.P2/GII.2 NoV genotype was linked to the outbreak by ORF1/ORF2 sequence analysis. The epidemiological features of the outbreak were consistent with food/waterborne followed by person-to-person and/or vomit transmission. Food consumed at a shared lunch on the first day of the trip was associated to illness and drinking un-bottled tap water was also considered as a risk factor. The analysis of water samples revealed the presence of bacterial indicators of faecal contamination in the water used in the resort as well as in other areas of the municipal water network, linking the NoV gastroenteritis outbreak to tap water pollution from sewage leakage. From a single water sample, an amplicon whose sequence corresponded to the capsid genotype recovered from patients could be obtained.


Asunto(s)
Infecciones por Caliciviridae/epidemiología , Brotes de Enfermedades , Agua Potable/virología , Gastroenteritis/epidemiología , Norovirus/fisiología , Enfermedades Transmitidas por el Agua/epidemiología , Adolescente , Infecciones por Caliciviridae/virología , Femenino , Gastroenteritis/virología , Humanos , Masculino , Sicilia/epidemiología , Enfermedades Transmitidas por el Agua/virología
5.
Org Biomol Chem ; 14(10): 2938-43, 2016 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-26876038

RESUMEN

G-quadruplex structures formed by oligodeoxyribonucleotides TGGU(NH2)GGT (AM, U(NH2) = 5-amino-2'-deoxyuridine), TGGU(Br)GGT (BR, U(Br) = 5-bromo-2'-deoxyuridine) and TGGTGGT (TH) have been investigated through circular dichroism, nuclear magnetic resonance, gel electrophoresis and molecular modeling techniques. Collected data indicate that all 7-mer oligonucleotides form tetramolecular parallel G-quadruplex structures with all residues adopting anti glycosidic bonds. In the case of AM, data suggest the occurrence of a novel U(NH2)-tetrad characterized by eight hydrogen bonds that stabilizes the G-quadruplex structure more efficiently than U(Br)- and T-tetrads.


Asunto(s)
G-Cuádruplex , Conformación de Ácido Nucleico , Pirimidinas/química , Dicroismo Circular , Enlace de Hidrógeno , Espectroscopía de Resonancia Magnética , Modelos Moleculares
6.
Pathol Biol (Paris) ; 62(2): 100-7, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24674658

RESUMEN

OBJECTIVES: This work deals with the conformational and thermal characterization of a synthetic peptide (S4) released during the proteolysis of human tropoelastin by the matrix metalloproteinase-12 that was shown to form amyloid-like fibres under certain conditions. MATERIALS AND METHODS: S4 peptides were synthesized by solid-phase methodology and aggregated in solution at 80°C. Fourier transform-infrared spectroscopy (FT-IR) was used to access the secondary structure. Thermal characterization was performed by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). RESULTS: The DSC study of the soluble linear peptide S4 in solution in TBS reveals the irreversible aggregation into amyloid fibres. FT-IR, DSC and TGA analyses performed on freeze-dried samples evidence differences between the linear peptide and its associated amyloid-like fibres, both on the conformation and the physical structure. When S4 peptides are aggregated, the prominent conformation scanned by FT-IR is the cross ß-structure, corresponding to TGA to an increase of the thermal stability. Moreover, the DSC thermograms of S4 fibres are characteristic of a highly ordered structure, in contrast to the DSC thermograms of S4 linear peptides, characteristic of an amorphous structure. Finally, the DSC analysis of differently hydrated S4 fibres brings to the fore the specific thermal answer of the wet interfaces of the cross ß-fibres. CONCLUSION: FT-IR and thermal techniques are well suited to evidence conformational and structural differences between the soluble peptide and its amyloid form.


Asunto(s)
Amiloide/química , Proteínas Amiloidogénicas/química , Fragmentos de Péptidos/química , Tropoelastina/química , Secuencia de Aminoácidos , Proteínas Amiloidogénicas/síntesis química , Rastreo Diferencial de Calorimetría , Liofilización , Calor , Humanos , Metaloproteinasa 12 de la Matriz/metabolismo , Datos de Secuencia Molecular , Fragmentos de Péptidos/síntesis química , Agregado de Proteínas , Conformación Proteica , Desnaturalización Proteica , Solubilidad , Espectroscopía Infrarroja por Transformada de Fourier , Relación Estructura-Actividad , Termogravimetría , Humectabilidad
7.
Clin Psychol Rev ; 107: 102357, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38065010

RESUMEN

BACKGROUND: Identification of the early warning signs (EWS) of relapse is key to relapse prevention in schizophrenia spectrum disorders, however, limitations to their precision have been reported. Substantial methodological innovations have recently been applied to the prediction of psychotic relapse and to individual psychotic symptoms. However, there has been no systematic review that has integrated findings across these two related outcomes and no systematic review of EWS of relapse for a decade. METHOD: We conducted a systematic review of EWS of psychotic relapse and the behavioural antecedents of worsening psychotic symptoms. Traditional EWS and ecological momentary assessment/intervention studies were included. We completed meta-analyses of the pooled sensitivity and specificity of EWS in predicting relapse, and for the prediction of relapse from individual symptoms. RESULTS: Seventy two studies were identified including 6903 participants. Sleep, mood, and suspiciousness, emerged as predictors of worsening symptoms. Pooled sensitivity and specificity of EWS in predicting psychotic relapse was 71% and 64% (AUC value = 0.72). There was a large pooled-effect size for the model predicting relapse from individual symptom which did not reach statistical significance (d = 0.81, 95%CIs = -0.01, 1.63). CONCLUSIONS: Important methodological advancements in the prediction of psychotic relapse in schizophrenia spectrum disorders are evident with improvements in the precision of prediction. Further efforts are required to translate these advances into effective clinical innovations.


Asunto(s)
Esquizofrenia , Humanos , Trastornos Psicóticos/diagnóstico , Recurrencia , Esquizofrenia/diagnóstico , Esquizofrenia/patología , Psicología del Esquizofrénico , Brote de los Síntomas
8.
Nat Genet ; 21(3): 297-301, 1999 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-10080183

RESUMEN

Lysinuric protein intolerance (LPI, MIM 222700) is an autosomal recessive multisystem disorder found mainly in Finland and Italy. On a normal diet, LPI patients present poor feeding, vomiting, diarrhoea, episodes of hyperammoniaemic coma and failure to thrive. Hepatosplenomegaly, osteoporosis and a life-threatening pulmonary involvement (alveolar proteinosis) are also seen. LPI is caused by defective cationic amino acid (CAA) transport at the basolateral membrane of epithelial cells in kidney and intestine. Metabolic derangement is characterized by increased renal excretion of CAA, reduced CAA absorption from intestine and orotic aciduria. The gene causing LPI was assigned using linkage analysis to chromosome 14q11.2 near the T-cell receptor alpha/delta chains locus, and a critical region has been defined. We have identified two new transcripts (SLC7A8 and SLC7A7) homologous to amino acid transporters, highly expressed in kidney and mapping in the LPI critical region. Mutational analysis of both transcripts revealed that SLC7A7 (for solute carrier family 7, member 7) is mutated in LPI. In five Italian patients, we found either an insertion or deletion in the coding sequence, which provides evidence of a causative role of SLC7A7 in LPI. Furthermore, we detected a splice acceptor change resulting in a frameshift and premature translation termination in four unrelated Finnish patients. This mutation may represent the founder LPI allele in Finland.


Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos/genética , Proteínas Portadoras/genética , Proteínas de la Membrana/genética , Mutación , Secuencia de Aminoácidos , Sistemas de Transporte de Aminoácidos Básicos , Antígenos CD/genética , Antígenos CD/metabolismo , Transporte Biológico , Southern Blotting , Proteínas Portadoras/metabolismo , Cromosomas Artificiales de Levadura , Clonación Molecular , Consanguinidad , Etiquetas de Secuencia Expresada , Femenino , Finlandia , Efecto Fundador , Proteína-1 Reguladora de Fusión , Haplotipos , Homocigoto , Humanos , Italia , Lisina/orina , Masculino , Proteínas de la Membrana/metabolismo , Datos de Secuencia Molecular , Linaje
9.
Biointerphases ; 18(2): 021001, 2023 03 10.
Artículo en Inglés | MEDLINE | ID: mdl-36898958

RESUMEN

Tumor invasion is likely driven by the product of intrinsic and extrinsic stresses, reduced intercellular adhesion, and reciprocal interactions between the cancer cells and the extracellular matrix (ECM). The ECM is a dynamic material system that is continuously evolving with the tumor microenvironment. Although it is widely reported that cancer cells degrade the ECM to create paths for migration using membrane-bound and soluble enzymes, other nonenzymatic mechanisms of invasion are less studied and not clearly understood. To explore tumor invasion that is independent of enzymatic degradation, we have created an open three-dimensional (3D) microchannel network using a novel bioconjugated liquid-like solid (LLS) medium to mimic both the tortuosity and the permeability of a loose capillary-like network. The LLS is made from an ensemble of soft granular microgels, which provides an accessible platform to investigate the 3D invasion of glioblastoma (GBM) tumor spheroids using in situ scanning confocal microscopy. The surface conjugation of the LLS microgels with type 1 collagen (COL1-LLS) enables cell adhesion and migration. In this model, invasive fronts of the GBM microtumor protruded into the proximal interstitial space and may have locally reorganized the surrounding COL1-LLS. Characterization of the invasive paths revealed a super-diffusive behavior of these fronts. Numerical simulations suggest that the interstitial space guided tumor invasion by restricting available paths, and this physical restriction is responsible for the super-diffusive behavior. This study also presents evidence that cancer cells utilize anchorage-dependent migration to explore their surroundings, and geometrical cues guide 3D tumor invasion along the accessible paths independent of proteolytic ability.


Asunto(s)
Microgeles , Humanos , Movimiento Celular , Invasividad Neoplásica/patología , Matriz Extracelular/metabolismo , Colágeno Tipo I , Línea Celular Tumoral , Microambiente Tumoral
10.
Acta Diabetol ; 59(8): 1073-1082, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35641837

RESUMEN

AIMS: We present an innovative method based on haptics for the evaluation of the sense of touch in the hand, in people affected by type 1 diabetes. METHODS: Forty individuals affected by diabetes and 20 healthy controls took part in the study; the diabetes group was further divided into two subgroups based on vibration sensitivity in the lower limb. By means of a novel haptic device, tactile sensitivity in the fingertip was measured as the ability of the participants to discriminate slip motion speed. RESULTS: Tactile sensitivity was significantly lower in individuals affected by diabetes as compared to controls. Depending on the subgroup, the difference from the controls was equal to 0.11 (95% CI from 0.029 to 0.186) and to 0.267 (95% CI from 0.198 to 0.336). Within the diabetes group, tactile sensitivity correlated with vibration sensitivity in the upper (p = 0.001) and lower limb (p = 0.003). A significant relationship between nerve conduction parameters and tactile sensitivity was found (p = 0.03). Finally, we combined the different predictors (clinical, vibratory and electroneurography data) by using cluster analysis; tactile sensitivity was found to be significantly different between different clusters (p = 0.004). CONCLUSIONS: Early signs of tactile dysfunction in the hand were found in individuals affected by diabetes, even in absence of diabetic neuropathy. The protocol presented in this study is a promising tool for the assessment of tactile dysfunction in the hand in people affected by type 1 diabetes.


Asunto(s)
Diabetes Mellitus Tipo 1 , Percepción del Tacto , Diabetes Mellitus Tipo 1/complicaciones , Tecnología Háptica , Humanos , Tacto/fisiología , Percepción del Tacto/fisiología , Vibración
11.
Eur Heart J Cardiovasc Imaging ; 23(9): e308-e322, 2022 08 22.
Artículo en Inglés | MEDLINE | ID: mdl-35808990

RESUMEN

Autoimmune rheumatic diseases (ARDs) involve multiple organs including the heart and vasculature. Despite novel treatments, patients with ARDs still experience a reduced life expectancy, partly caused by the higher prevalence of cardiovascular disease (CVD). This includes CV inflammation, rhythm disturbances, perfusion abnormalities (ischaemia/infarction), dysregulation of vasoreactivity, myocardial fibrosis, coagulation abnormalities, pulmonary hypertension, valvular disease, and side-effects of immunomodulatory therapy. Currently, the evaluation of CV involvement in patients with ARDs is based on the assessment of cardiac symptoms, coupled with electrocardiography, blood testing, and echocardiography. However, CVD may not become overt until late in the course of the disease, thus potentially limiting the therapeutic window for intervention. More recently, cardiovascular magnetic resonance (CMR) has allowed for the early identification of pathophysiologic structural/functional alterations that take place before the onset of clinically overt CVD. CMR allows for detailed evaluation of biventricular function together with tissue characterization of vessels/myocardium in the same examination, yielding a reliable assessment of disease activity that might not be mirrored by blood biomarkers and other imaging modalities. Therefore, CMR provides diagnostic information that enables timely clinical decision-making and facilitates the tailoring of treatment to individual patients. Here we review the role of CMR in the early and accurate diagnosis of CVD in patients with ARDs compared with other non-invasive imaging modalities. Furthermore, we present a consensus-based decision algorithm for when a CMR study could be considered in patients with ARDs, together with a standardized study protocol. Lastly, we discuss the clinical implications of findings from a CMR examination.


Asunto(s)
Enfermedades Autoinmunes , Enfermedades Cardiovasculares , Síndrome de Dificultad Respiratoria , Enfermedades Reumáticas , Enfermedades Autoinmunes/complicaciones , Enfermedades Cardiovasculares/diagnóstico por imagen , Enfermedades Cardiovasculares/etiología , Consenso , Humanos , Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética/efectos adversos , Enfermedades Reumáticas/complicaciones , Enfermedades Reumáticas/diagnóstico por imagen
12.
Climacteric ; 14(1): 18-24, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20979461

RESUMEN

OBJECTIVES: To describe the effects of low-dose hormonal replacement therapy (HRT) on quality of life, metabolic parameters and blood pressure in postmenopausal women. METHODS: Postmenopausal women untreated with HRT or sex steroids in the previous 12 months were randomized to treatment with 17ß-estradiol (1 mg/day) plus drospirenone (2 mg/day) (E2+DRSP) or to calcium (controls). Quality of life was evaluated by the Women's Health Questionnaire (WHQ) at baseline and after 6 and 12 weeks of treatment. Anthropometric, metabolic and blood pressure measurements were performed before and after 3 months of treatment. RESULTS: WHQ domain scores for vasomotor and somatic symptoms, anxiety/fears, depressed mood, sexual behavior and sleep problems decreased significantly in the E2+DRSP group relative to both baseline and control values (p < 0.05). Body mass index was unchanged, while waist circumference decreased significantly (p < 0.001) after E2+DRSP treatment. Significant decreases were also observed after E2+DRSP treatment for blood insulin values, insulin resistance (estimated by homeostasis model assessment) and systolic blood pressure (p < 0.001, all). In subjects with systolic blood pressure < 130 mmHg at baseline, no changes in systolic values were registered, while women with baseline high-normal systolic blood pressure (130-139 mmHg) showed significant decreases (p < 0.0069). E2+DRSP did not modify diastolic blood pressure values. In the calcium-treatment group, there were no significant changes in WHQ scores or in anthropometric, metabolic or blood pressure measurements. CONCLUSION: In postmenopausal women, E2+DRSP administration improves vasomotor symptoms and general aspects of quality of life and may positively influence cardiovascular risk factors.


Asunto(s)
Androstenos/administración & dosificación , Estradiol/administración & dosificación , Estrógenos/administración & dosificación , Terapia de Reemplazo de Hormonas , Antagonistas de Receptores de Mineralocorticoides/administración & dosificación , Calidad de Vida , Ansiedad , Presión Sanguínea , Depresión/epidemiología , Miedo , Femenino , Humanos , Insulina/sangre , Resistencia a la Insulina , Persona de Mediana Edad , Posmenopausia , Estudios Prospectivos , Conducta Sexual , Trastornos del Sueño-Vigilia/epidemiología , Sístole , Circunferencia de la Cintura
13.
Proteins ; 76(2): 461-76, 2009 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-19241470

RESUMEN

Elastin-derived peptides (EDPs) have been intensively studied in view of their widely diverse biological activities. These are triggered both in normal and tumor cells, through peptide anchoring at the surface of the elastin-binding protein (EBP), a subunit of the elastin/laminin receptor. In this study, we investigated both the structure of the Sgal peptide, representing the elastin-binding domain of EBP, and its interaction with EDPs, through a combination of experimental and theoretical methods. Although the conformation of the Sgal peptide is highly flexible, we detected a type I beta-turn at the QDEA sequence. This represents the best structured motif in the entire Sgal peptide, which might therefore contribute to its binding activity. We further propose a novel three-dimensional model for the interaction between the Sgal peptide and EDPs; folding of the EDPs at the GXXP motif, in a conformation close to a type VIII beta-turn, provides the efficient contact of the protein with the Q residue of the Sgal peptide. This residue is exposed to the peptide surface, because of the beta-turn structure of the QDEA residues in the peptide sequence. We further show that this complex is stabilized by three hydrogen bonds involving EDPs backbone atoms.


Asunto(s)
Elastina/química , Fragmentos de Péptidos/química , Receptores de Laminina/química , Receptores de Laminina/metabolismo , Secuencia de Aminoácidos , Sitios de Unión , Dicroismo Circular , Elastina/metabolismo , Enlace de Hidrógeno , Modelos Moleculares , Datos de Secuencia Molecular , Fragmentos de Péptidos/metabolismo , Conformación Proteica
14.
J Cell Biol ; 134(1): 241-53, 1996 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-8698818

RESUMEN

Upon ligand binding, the alpha6beta4 integrin becomes phosphorylated on tyrosine residues and combines sequentially with the adaptor molecules Shc and Grb2, linking to the ras pathway, and with cytoskeletal elements of hemidesmosomes. Since alpha6beta4 is expressed in a variety of tissues regulated by the EGF receptor (EGFR), we have examined the effect of EGF on the cytoskeletal and signaling functions of alpha6beta4. Experiments of immunoblotting with anti-phosphotyrosine antibodies and immunoprecipitation followed by phosphoamino acid analysis and phosphopeptide mapping showed that activation of the EGFR causes phosphorylation of the beta4 subunit at multiple tyrosine residues, and this event requires ligation of the integrin by laminins or specific antibodies. Immunoprecipitation experiments indicated that stimulation with EGF does not result in association of alpha6beta4 with Shc. In contrast, EGF can partially suppress the recruitment of Shc to ligated alpha6beta4. Immunofluorescent analysis revealed that EGF treatment does not induce increased assembly of hemidesmosomes, but instead causes a deterioration of these adhesive structures. Finally, Boyden chamber assays indicated that exposure to EGF results in upregulation of alpha6beta4-mediated cell migration toward laminins. We conclude that EGF-dependent signals suppress the association of activated alpha6beta4 with both signaling and cytoskeletal molecules, but upregulate alpha6beta4-dependent cell migration. The changes in alpha6beta4 function induced by EGF may play a role during wound healing and tumorigenesis.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Proteínas Adaptadoras del Transporte Vesicular , Antígenos CD/fisiología , Factor de Crecimiento Epidérmico/fisiología , Receptores ErbB/fisiología , Adhesión Celular , Movimiento Celular , Polaridad Celular , Células Cultivadas , Desmosomas/ultraestructura , Proteína Adaptadora GRB2 , Humanos , Integrina alfa6 , Integrina beta4 , Ligandos , Fosforilación , Fosfotirosina/metabolismo , Proteínas/metabolismo , Receptores de Laminina/fisiología , Proteínas Adaptadoras de la Señalización Shc , Transducción de Señal , Proteína Transformadora 1 que Contiene Dominios de Homología 2 de Src
15.
Climacteric ; 12 Suppl 1: 32-5, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19811238

RESUMEN

Climacteric complaints are the main indication for hormone replacement therapy (HRT) in the clinical practice. Observational studies demonstrating a protective effect of HRT on cardiovascular disease (CVD) were conducted in early menopausal, young, symptomatic women. Vasomotor symptoms correlate with lower level of plasma antioxidant activity, an increased cardiovascular reactivity to stressful situations, elevated cholesterol, higher sympathetic nerve activity, impaired flow-mediated dilation, hypertension and a higher risk of aortic calcification. All the available findings indicate that hot flushes can be seen as a marker for underlying vascular changes among mid-life, otherwise healthy, climacteric women. Thus, young, healthy symptomatic postmenopausal women differ from those without vasomotor symptoms with regard to cardiovascular risk factors. Therefore, responses to HRT can change in terms of cardiovascular outcomes according to the baseline vasomotor complaints. This point may explain, at least in part, the negative/null effects of HRT on cardiovascular disease observed in the trials where HRT was given to largely asymptomatic, elderly women.


Asunto(s)
Enfermedades Cardiovasculares/prevención & control , Terapia de Reemplazo de Estrógeno , Sistema Vasomotor/efectos de los fármacos , Sistema Vasomotor/fisiopatología , Antioxidantes/metabolismo , Enfermedades Cardiovasculares/sangre , Colesterol/sangre , Climaterio , Femenino , Sofocos/tratamiento farmacológico , Humanos , Posmenopausia , Factores de Riesgo
16.
Sci Rep ; 9(1): 3446, 2019 03 05.
Artículo en Inglés | MEDLINE | ID: mdl-30837604

RESUMEN

Electrospinning is an attractive method to generate drug releasing systems. In this work, we encapsulated the cell death-inducing drug Diclofenac (DCF) in an electrospun poly-L-lactide (PLA) scaffold. The scaffold offers a system for a sustained and controlled delivery of the cytotoxic DCF over time making it clinically favourable by achieving a prolonged therapeutic effect. We exposed human dermal fibroblasts (HDFs) to the drug-eluting scaffold and employed multiphoton microscopy and fluorescence lifetime imaging microscopy. These methods were suitable for non-invasive and marker-independent assessment of the cytotoxic effects. Released DCF induced changes in cell morphology and glycolytic activity. Furthermore, we showed that drug release can be influenced by adding dimethyl sulfoxide as a co-solvent for electrospinning. Interestingly, without affecting the drug diffusion mechanism, the resulting PLA scaffolds showed altered fibre morphology and enhanced initial DCF burst release. The here described model could represent an interesting way to control the diffusion of encapsulated bio-active molecules and test them using a marker-independent, non-invasive approach.


Asunto(s)
Portadores de Fármacos , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Supervivencia Celular/efectos de los fármacos , Diclofenaco/administración & dosificación , Diclofenaco/química , Diclofenaco/farmacología , Fibroblastos/efectos de los fármacos , Humanos , Poliésteres/química
17.
J Virol Methods ; 268: 48-52, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30902644

RESUMEN

Rotavirus, adenovirus, norovirus and astrovirus are considered to be among the major causes of sporadic cases and outbreaks of acute gastroenteritis globally. Rapid and accurate identification of enteric viruses is still a challenge for the clinical laboratory. Recently, several molecular platforms for the detection of viral enteric pathogens have become available. In this study, the diagnostic accuracy of InGenius Gastrointestinal Viral (GV) Elite Panel, a newly developed one-step multiplex real-time RT-PCR assay simultaneously detecting rotavirus, adenovirus and astrovirus, was evaluated retrospectively analyzing an archival collection of 128 stool samples of children hospitalized with acute gastroenteritis. The overall sensitivity and specificity for the GV assay was 100% and 96.2% for rotavirus, 96.9% and 100% for astrovirus, 100% and 100% for adenovirus, respectively. The InGenius GV assay showed a high concordance with the reference methods and was able to detect all tested genotypes of rotavirus (including G1, G3, G4, G9 and G12P[8] and G2P[4]), adenovirus and astrovirus (AstV-1 and 2). Studies of considerable sample size are required to determine robust Cycle threshold cut-off values to effectively correlate infection to disease. These preliminary results suggest that InGenius GV assay can be recommended as a valuable method for accurate diagnosis of epidemic and sporadic gastroenteritis.


Asunto(s)
Infecciones por Adenoviridae/diagnóstico , Infecciones por Astroviridae/diagnóstico , Gastroenteritis/diagnóstico , Reacción en Cadena de la Polimerasa Multiplex , Infecciones por Rotavirus/diagnóstico , Enfermedad Aguda , Adolescente , Niño , Preescolar , Heces/virología , Femenino , Gastroenteritis/virología , Humanos , Lactante , Recién Nacido , Masculino , Estudios Retrospectivos , Sensibilidad y Especificidad
18.
Hum Reprod ; 23(8): 1957-62, 2008 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-18492703

RESUMEN

BACKGROUND: Asthenozoospermia (AZS) is a common cause of male infertility characterized by reduced forward motility (WHO grade A+B sperm motility <50% or A < 25%) or absent sperm motility in fresh ejaculate. AZS may exist as an isolated disorder, in combination with other sperm anomalies or as part of a syndromic association. Up to date, only a few genes, constituting the cilia/flagella structure, have been associated with isolated AZS in humans, whereas several other genes are known to be involved in syndromic form of AZS, including primary ciliary dyskinesia (PCD) and Kartagener syndrome (KS). Axonemal ultrastructural defects, including absent or shortened arms of dyneins, can be found in >50% of PCD/KS patients. Approximately 90% of KS male patients are affected by AZS. The majority of KS patients can be ascribed to dynein genes mutations. METHODS: Mutation screening of DNAI1, DNAH5 and DNAH11 genes was performed in 90 patients with isolated non-syndromic AZS and 200 controls. RESULTS: We found three mutations (one in each gene) specifically associated with AZS in seven patients (7.8%). Mutations are inherited from the mothers and may be found in familial clusters. No ultrastructural axonemal anomaly was detected in sperm. CONCLUSIONS: We report for the first time a possible association between mutations in dynein genes and isolated AZS. Male carriers of the mutations always exhibit AZS, whereas female carriers manifest no alterations in either fertility or pulmonary clearance.


Asunto(s)
Astenozoospermia/genética , Dineínas/genética , Síndrome de Kartagener/genética , Secuencia de Aminoácidos , Dineínas Axonemales , Secuencia de Bases , Consanguinidad , Humanos , Masculino , Linaje , Especificidad de la Especie
19.
Eur J Trauma Emerg Surg ; 44(3): 411-416, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28643032

RESUMEN

INTRODUCTION: Fall from heights is high energy injuries and constitutes a fraction of all fall-related trauma evaluations while bearing an increase in morbidity and mortality. We hypothesize that despite advancements in trauma care, the overall survivability has not improved in this subset of trauma patients. METHODS: All adult trauma patients treated after sustaining a fall from heights during a 40-month period were retrospectively reviewed. Admission demographics, clinical data, fall height (ft), injury patterns, ISS, GCS, length of stay, and mortality were reviewed. RESULTS: 116 patients sustained a fall from heights, 90.4% accidental. A mean age of 37± 14.7 years, 86% male, and a fall height of 19 ± 10 ft were encountered. Admission GCS was 13 ± 2 with ISS 10 ± 11. Overall LOS was 6.6 ± 14.9 days and an ICU LOS of 2.8 ± 8.9 days. Falls ≥ 25 ft.(16%) had lower GCS 10.4 ± 5.8, increased ISS 22.6 ± 13.8, a fall height 37.9 ± 13.1 ft and associated increased mortality (p < 0.001). Mortality was 5.2%, a mean distance fallen of 39 ± 22 ft. and an ISS of 31.5 ±16.5. Brain injury was the leading cause of death, 50% with open skull fractures. CONCLUSION: Level of height fallen is a good predictor of overall outcome and survival. Despite advances in trauma care, death rates remain unchanged. Safety awareness and injury prevention programs are needed to reduce the risk of high-level falls.


Asunto(s)
Accidentes por Caídas/mortalidad , Heridas y Lesiones/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bases de Datos Factuales , Femenino , Escala de Coma de Glasgow , Humanos , Puntaje de Gravedad del Traumatismo , Tiempo de Internación , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo
20.
Eur J Pain ; 22(1): 161-169, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-28898491

RESUMEN

BACKGROUND: In the neurophysiological assessment of patients with neuropathic pain, laser evoked potentials (LEPs), contact heat evoked potentials (CHEPs) and the evoked potentials by the intraepidermal electrical stimulation via concentric needle electrode are widely agreed as nociceptive specific responses; conversely, the nociceptive specificity of evoked potentials by surface concentric electrode (SE-PREPs) is still debated. METHODS: In this neurophysiological study we aimed at verifying the nociceptive specificity of SE-PREPs. We recorded LEPs, CHEPs and SE-PREPs in eleven healthy participants, before and after epidermal denervation produced by prolonged capsaicin application. We also used skin biopsy to verify the capsaicin-induced nociceptive nerve fibre loss in the epidermis. RESULTS: We found that whereas LEPs and CHEPs were suppressed after capsaicin-induced epidermal denervation, the surface concentric electrode stimulation of the same denervated skin area yielded unchanged SE-PREPs. CONCLUSION: The suppression of LEPs and CHEPs after nociceptive nerve fibre loss in the epidermis indicates that these techniques are selectively mediated by nociceptive system. Conversely, the lack of SE-PREP changes suggests that SE-PREPs do not provide selective information on nociceptive system function. SIGNIFICANCE: Capsaicin-induced epidermal denervation abolishes laser evoked potentials (LEPs) and contact heat evoked potentials (CHEPs), but leaves unaffected pain-related evoked potentials by surface concentric electrode (SE-PREPs). These findings suggest that unlike LEPs and CHEPs, SE-PREPs are not selectively mediated by nociceptive system.


Asunto(s)
Corteza Cerebral/fisiopatología , Potenciales Evocados Somatosensoriales/fisiología , Calor , Potenciales Evocados por Láser/fisiología , Piel/inervación , Adulto , Capsaicina/farmacología , Corteza Cerebral/efectos de los fármacos , Desnervación , Estimulación Eléctrica/métodos , Electroencefalografía , Potenciales Evocados Somatosensoriales/efectos de los fármacos , Femenino , Humanos , Potenciales Evocados por Láser/efectos de los fármacos , Masculino , Tiempo de Reacción/efectos de los fármacos , Tiempo de Reacción/fisiología , Fármacos del Sistema Sensorial/farmacología , Adulto Joven
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