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This paper presents a new method called the functional distributional clustering algorithm (FDCA) that seeks to identify spatially contiguous clusters and incorporate changes in temporal patterns across overcrowded networks. This method is motivated by a graph-based network composed of sensors arranged over space where recorded observations for each sensor represent a multi-modal distribution. The proposed method is fully non-parametric and generates clusters within an agglomerative hierarchical clustering approach based on a measure of distance that defines a cumulative distribution function over temporal changes for different locations in space. Traditional hierarchical clustering algorithms that are spatially adapted do not typically accommodate the temporal characteristics of the underlying data. The effectiveness of the FDCA is illustrated using an application to both empirical and simulated data from about 400 sensors in a 2.5 square miles network area in downtown San Francisco, California. The results demonstrate the superior ability of the the FDCA in identifying true clusters compared to functional only and distributional only algorithms and similar performance to a model-based clustering algorithm.
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PURPOSE: To evaluate the effectiveness of mobile health applications (mHealth apps) containing a physical training component on physical function and physical activity in stroke rehabilitation. MATERIALS AND METHODS: A systematic literature search was conducted in three databases for studies published from inception to 12 July 2022. Clinical trials including mHealth apps with a physical training component were included using outcomes of physical function and physical activity. Quality of life was extracted as a secondary outcome. RESULTS: Five RCTs, two non-RCTs, and four uncontrolled clinical trials were included with a total of 264 stroke survivors. Eleven apps were identified with a physical training component using features of gamification (six apps), exercise prescription (three apps), and physical activity (two apps). Six out of seven studies reported statistically significant improvements in physical function in favor of the experimental group, with the most robust findings for upper extremity function. For physical activity, statistically significant improvements were seen in the experimental groups. Only one study showed significant improvement in quality of life. Overall study quality was fair. CONCLUSIONS: mHealth apps containing a physical training component are promising for physical function and physical activity in stroke rehabilitation. Further research is warranted to confirm these conclusions.Implications for rehabilitationDesign content of mobile apps with a physical training component were focused on gamification, exercise prescription, and physical activityUsing mobile app-delivered therapy seem promising for improving upper extremity function in stroke rehabilitationUsing mobile apps also supported an increase of physical activity in people with strokeStudies using mobile apps should report more specifically the dosage of physical training and adherenceUsing mobile apps seems promising as an additional tool for clinical work, however, more studies are required to understand their effectiveness in stroke rehabilitation.
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Aplicaciones Móviles , Accidente Cerebrovascular , Telemedicina , Humanos , Calidad de Vida , Ejercicio Físico , SobrevivientesRESUMEN
BACKGROUND: Our understanding of the etiology, pathophysiology, phenotypic diversity, and progression of Parkinson's disease has stagnated. Consequently, patients do not receive the best care, leading to unnecessary disability, and to mounting costs for society. The Personalized Parkinson Project (PPP) proposes an unbiased approach to biomarker development with multiple biomarkers measured longitudinally. Our main aims are: (a) to perform a set of hypothesis-driven analyses on the comprehensive dataset, correlating established and novel biomarkers to the rate of disease progression and to treatment response; and (b) to create a widely accessible dataset for discovery of novel biomarkers and new targets for therapeutic interventions in Parkinson's disease. METHODS/DESIGN: This is a prospective, longitudinal, single-center cohort study. The cohort will comprise 650 persons with Parkinson's disease. The inclusion criteria are purposely broad: age ≥ 18 years; and disease duration ≤5 years. Participants are followed for 2 years, with three annual assessments at the study center. Outcomes include a clinical assessment (including motor and neuro-psychological tests), collection of biospecimens (stool, whole blood, and cerebrospinal fluid), magnetic resonance imaging (both structural and functional), and ECG recordings (both 12-lead and Holter). Additionally, collection of physiological and environmental data in daily life over 2 years will be enabled through the Verily Study Watch. All data are stored with polymorphic encryptions and pseudonyms, to guarantee the participants' privacy on the one hand, and to enable data sharing on the other. The data and biospecimens will become available for scientists to address Parkinson's disease-related research questions. DISCUSSION: The PPP has several distinguishing elements: all assessments are done in a single center; inclusion of "real life" subjects; deep and repeated multi-dimensional phenotyping; and continuous monitoring with a wearable device for 2 years. Also, the PPP is powered by privacy and security by design, allowing for data sharing with scientists worldwide respecting participants' privacy. The data are expected to open the way for important new insights, including identification of biomarkers to predict differences in prognosis and treatment response between patients. Our long-term aim is to improve existing treatments, develop new therapeutic approaches, and offer Parkinson's disease patients a more personalized disease management approach. TRIAL REGISTRATION: Clinical Trials NCT03364894 . Registered December 6, 2017 (retrospectively registered).
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Biomarcadores , Enfermedad de Parkinson , Personas con Discapacidad , Progresión de la Enfermedad , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Medicina de Precisión/métodos , Estudios Prospectivos , Proyectos de InvestigaciónRESUMEN
Field monitoring of groundwater contamination plumes is an important component of managing risks for downgradient receptors and remedial strategies that rely on monitored natural attenuation. Collection of groundwater quality data can however take a considerable effort and be associated with high cost. Here, we investigated the relative merits of analyzing groundwater quality data using spatial compared to spatiotemporal statistical modelling and assessed the accuracy of both methods and implications for data collection requirements. The aim of this was to determine whether the quantity of data collected can be reduced, while retaining the same level of estimation accuracy, by analyzing groundwater contamination data using a spatiotemporal model which "borrows strength" across time, rather than a spatial model for individual sampling events. To capture the variability encountered under field conditions, we used three hypothetical groundwater contamination plumes with increasing complexity, and site data for a large groundwater gasoline additive plume. The results show that spatiotemporal methods can increase efficiency markedly so that, in comparison with repeated spatial analysis, spatiotemporal methods can achieve the same level of performance but with smaller sample sizes.
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Enfermedad Injerto contra Huésped/tratamiento farmacológico , Leucemia Mieloide Aguda/patología , Rituximab/efectos adversos , Adulto , Linfocitos B/inmunología , Linfocitos B/fisiología , Resultado Fatal , Enfermedad Injerto contra Huésped/etiología , Efecto Injerto vs Leucemia/efectos de los fármacos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/terapia , Masculino , Recurrencia , Trasplante HomólogoRESUMEN
22q11.2 deletion syndrome (22q11DS) is one of the most common recurrent copy-number variant disorder, caused by a microdeletion in chromosome band 22q11.2 and occurring with a population prevalence of 1 in 2000. Until today there has been no evidence that the size of the deletion has an influence on the clinical phenotype. Most studies report that 22q11DS is associated with mild or borderline intellectual disability. There are a limited number of reports on 22q11DS subjects with moderate or severe intellectual disability. In this study we describe 63 adult patients with 22q11DS, including 22q11DS patients functioning at a moderate to severe intellectual disabled level. Deletion size was established with an experimental Multiplex ligation-dependent probe amplification (MLPA) mixture (P324) in addition to the commonly used MLPA kit (P250). We compared deletion size with intellectual functioning and presence of psychotic symptoms during life. The use of the experimental MLPA kit gives extra information on deletion size, only when combined with the common MLPA kit. We were able to detect eleven atypical deletions and in two cases the deletion size was shorter than all other "typical ones". We conclude that the use of the experimental kit P324 gives extra information about the deletion size, but only when used together with the standard P250 kit. We did not found any relation of deletion size with intelligence or presence of psychosis.
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Deleción Cromosómica , Variaciones en el Número de Copia de ADN/genética , Síndrome de DiGeorge/genética , Discapacidad Intelectual/genética , Adulto , Síndrome de DiGeorge/fisiopatología , Femenino , Humanos , Discapacidad Intelectual/fisiopatología , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa Multiplex/métodos , Fenotipo , Juego de Reactivos para DiagnósticoRESUMEN
Fitting statistical models to spatiotemporal data requires finding the right balance between imposing smoothness and following the data. In the context of P-splines, we propose a Bayesian framework for choosing the smoothing parameter, which allows the construction of fully automatic data-driven methods for fitting flexible models to spatiotemporal data. An implementation, which is highly computationally efficient and exploits the sparsity of the design and penalty matrices, is proposed. The findings are illustrated using a simulation study and two examples, all concerned with the modelling of contaminants in groundwater. This suggests that the proposed strategy is more stable that competing methods based on the use of criteria such as generalised cross-validation and Akaike's Information Criterion. © 2015 The Authors. Environmetrics Published by John Wiley Sons Ltd.
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BACKGROUND: 22q11 deletion syndrome (22q11DS) is associated with mild or borderline intellectual disability (ID). There are hardly any reports on subjects with 22q11DS with moderate or severe ID, and therefore its behavioural and psychiatric characteristics are unknown. METHOD: We describe behavioural and psychiatric characteristics of 33 adults with 22q11DS and a Full-Scale IQ (FSIQ) below 55. Participants were divided into two groups: one group having a FSIQ ≤ 55 caused by intellectual decline (n = 21) and one group with a FSIQ ≤ 55 who had always functioned at this level (n = 12). RESULTS: High scores on psychopathology sub-scales were found for both subgroups. 22q11DS patients with intellectual decline showed higher rates of co-morbid psychopathology, particularly psychosis. Furthermore, psychosis and intellectual decline were positive correlated. CONCLUSION: This is the first report addressing adult patients with 22q11DS and moderate to severe ID. Overall we found high levels of psychopathology with higher scores of psychopathology in the intellectual decline group. Life time psychosis seems to be related to deterioration.
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Síndrome de Deleción 22q11/fisiopatología , Discapacidad Intelectual/fisiopatología , Inteligencia/fisiología , Trastornos Mentales/fisiopatología , Síndrome de Deleción 22q11/complicaciones , Adulto , Femenino , Humanos , Discapacidad Intelectual/etiología , Masculino , Trastornos Mentales/etiología , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
Most large (over a kilometre in diameter) near-Earth asteroids are now known, but recognition that airbursts (or fireballs resulting from nuclear-weapon-sized detonations of meteoroids in the atmosphere) have the potential to do greater damage than previously thought has shifted an increasing portion of the residual impact risk (the risk of impact from an unknown object) to smaller objects. Above the threshold size of impactor at which the atmosphere absorbs sufficient energy to prevent a ground impact, most of the damage is thought to be caused by the airburst shock wave, but owing to lack of observations this is uncertain. Here we report an analysis of the damage from the airburst of an asteroid about 19 metres (17 to 20 metres) in diameter southeast of Chelyabinsk, Russia, on 15 February 2013, estimated to have an energy equivalent of approximately 500 (±100) kilotons of trinitrotoluene (TNT, where 1 kiloton of TNT = 4.185×10(12) joules). We show that a widely referenced technique of estimating airburst damage does not reproduce the observations, and that the mathematical relations based on the effects of nuclear weapons--almost always used with this technique--overestimate blast damage. This suggests that earlier damage estimates near the threshold impactor size are too high. We performed a global survey of airbursts of a kiloton or more (including Chelyabinsk), and find that the number of impactors with diameters of tens of metres may be an order of magnitude higher than estimates based on other techniques. This suggests a non-equilibrium (if the population were in a long-term collisional steady state the size-frequency distribution would either follow a single power law or there must be a size-dependent bias in other surveys) in the near-Earth asteroid population for objects 10 to 50 metres in diameter, and shifts more of the residual impact risk to these sizes.
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INTRODUCTION: A review of the literature finds that everything concerning the body is a source of self-questioning. However, if a feeling of comfort or of discomfort is perceived within the body, it is difficult to quantify and to define this perception. This is because this feeling is multifactorial and characterized by behaviors and symptoms that are not explicit. METHOD: To resolve this perception, we created a self-reported questionnaire allowing for the estimation of "body satisfaction and global self-perception". RESULTS: We present here the normative values collected with 788 subjects: 541 "non clinical" subjects and 247 "clinical subjects" consisting of inpatients hospitalized for major depressive disorder. In the "non clinical" group, the results show a good stability of scores. However, the female participants of this group have values (39.1) significantly (p<0.03) lower than the male participants (44.8). The evolution according to age showed a peak in physical satisfaction and of global self-perception between the age of 30 and 50. The score of this QSCPGS is very significantly (p<0.0001) higher in the "non clinical" group (43) than in the "clinical group" (-2); this confirms the good validity of the criterion. Finally, the average gains in the total score of the QSCPGS after a relaxation session with 34 depressed subjects are 23.7 (-12.2 before and 11.5 after). DISCUSSION: This very significant advantage indicates that this questionnaire is sensitive to changes connected with a therapeutic intervention. The QSCPGS can thus be useful for the evaluation of body satisfaction or dissatisfaction as well as the mood associated with it; thus, it permits one to clarify the concept of well-being within "non clinical subjects" and to record the modifications provided by therapy, both at a physical level and a level of global self-perception. Future studies must now be submitted in different study groups such as: diverse pathologies, high level sportsmen, (etc.), this will allow us to gather information that will help establish specific therapies or effective preventative measures.
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Imagen Corporal , Trastorno Depresivo Mayor/psicología , Autoimagen , Encuestas y Cuestionarios , Adolescente , Adulto , Anciano , Ansiedad/diagnóstico , Ansiedad/psicología , Ansiedad/terapia , Bélgica , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/terapia , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Psicometría/estadística & datos numéricos , Valores de Referencia , Terapia por Relajación , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
BACKGROUND: We have recently shown that the expression of nestin, a progenitor/stem cell marker protein, is localized in different mesenchymal compartments in human skin including the sweat gland stroma. OBJECTIVES: As other exocrine glands are recognized sources of multipotent stem cell populations with potential for multilineage differentiation, it was our aim to isolate, expand and characterize glandular stem cells from human sweat glands. METHODS: Isolation of human sweat glands was based on mechanical and enzymatic digestion of axillary skin. Cultivation was performed on collagen-coated cell culture dishes and the resulting cell population was investigated at the protein and mRNA level. RESULTS: Outgrowing cells of isolated sweat glands showed a high-proliferation activity and were characterized by nestin expression in more than 80% of the cells. These sweat gland stem cells could be maintained in culture for long periods of time and showed spontaneous differentiation into cells representative of the different germ layers. CONCLUSIONS: This pilot study provides the first, simple protocol for the isolation of adult human nestin-positive stem cells from the sweat gland mesenchyme, which promises to provide an easily accessible and abundantly available, autologous source of multipotent stem cells for cell-based regenerative medicine applications.
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Células Madre Adultas/citología , Proteínas de Filamentos Intermediarios/metabolismo , Células Madre Multipotentes/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Glándulas Sudoríparas/citología , Adulto , Células Madre Adultas/metabolismo , Biomarcadores/metabolismo , Técnicas de Cultivo de Célula/métodos , Separación Celular/métodos , Células Cultivadas/metabolismo , Humanos , Proteínas de Filamentos Intermediarios/genética , Células Madre Multipotentes/citología , Proteínas del Tejido Nervioso/genética , Nestina , Fenotipo , Proyectos Piloto , Glándulas Sudoríparas/metabolismoRESUMEN
Hibernoma is an uncommon benign fatty tumor that arises from the vestiges of fetal brown fat. We present a case report of a hibernoma of the back in a symptomatic 42-year-old man and describe the important clinical, histopathologic, and imaging findings. Computed tomography shows a well-defined hypodense mass with septations. Magnetic resonance imaging shows intermediate T1 and bright T2 signal of the mass and also demonstrates the characteristic marked contrast enhancement.
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Lipoma/patología , Neoplasias de los Tejidos Blandos/patología , Adulto , Dorso/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Tomografía Computarizada por Rayos XRESUMEN
Quality Function Deployment is proposed as an effective design method to integrate ergonomics needs and comfort into hand tool design because it explicitly addresses the translation of customer needs into engineering characteristics. A crucial step during QFD concerns the linking of engineering characteristics to customer needs in the House of Quality by the design team. It is generally assumed (looking at all the QFD success stories) that design teams can accurately predict the correlations between customer needs and engineering characteristics (also referred to as "Whats"/"Hows" correlations). This paper explicitly tests this assumption by comparing the "Whats"/"Hows" correlations estimated by a design team with those observed in a systematic user evaluation study, which has not been done before. Testing the assumption is important, because inaccurate estimates may lead to ergonomically ineffective (re)design of hand tools and a waste of company resources. Results revealed that the design team's correlation estimates were not as accurate as is generally assumed. Twenty-five percent of the estimates differed significantly with those observed in the user evaluation study. Thus, QFD is a useful method to assist design teams in designing ergonomically more comfortable hand tools, but only on the condition that the correlations between customer needs and engineering characteristics are validated, preferably by means of a systematic user evaluation study.
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Diseño de Equipo/métodos , Ergonomía/métodos , Mano/fisiología , Dolor/prevención & control , Adulto , Investigación Empírica , Femenino , Humanos , MasculinoRESUMEN
The velo-cardio-facial syndrome: the spectrum of psychiatric problems and cognitive deterioration at adult age: Deletion 22q11.2 syndrome, or the velo-cardio-facial syndrome (VCFS), is a syndrome with a known but varied clinical and behavioral phenotype. We report 7 patients with 22q11.2 deletion syndrome and an intellectual disability. Aside from the described behavioral phenotype in literature, a moderate, severe or profound intellectual disability may be present. Special attention should be given to cognitive deterioration.
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Síndrome de DiGeorge/psicología , Discapacidad Intelectual/etiología , Trastornos Neurocognitivos/etiología , Trastornos Psicóticos/etiología , Adulto , Trastorno Autístico/etiología , Demencia/etiología , Progresión de la Enfermedad , Femenino , Humanos , Inteligencia , Masculino , Persona de Mediana Edad , Países Bajos , Esquizofrenia/etiologíaRESUMEN
In the current study, the relationship between objective measurements and subjective experienced comfort and discomfort in using handsaws was examined. Twelve carpenters evaluated five different handsaws. Objective measures of contact pressure (average pressure, pressure area and pressure-time (P-t) integral) in static and dynamic conditions, muscle activity (electromyography) of five muscles of the upper extremity, and productivity were obtained during a sawing task. Subjective comfort and discomfort were assessed using the comfort questionnaire for hand tools and a scale for local perceived discomfort (LPD). We did not find any relationship between muscle activity and comfort or discomfort. The P-t integral during the static measurement (beta=-0.24, p<0.01) was the best predictor of comfort and the pressure area during static measurement was the best predictor of LPD (beta=0.45, p<0.01). Additionally, productivity was highly correlated to comfort (beta=0.31, p<0.01) and discomfort (beta=-0.49, p<0.01).
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Ergonomía , Fuerza de la Mano/fisiología , Mano/fisiología , Salud Laboral , Dolor/epidemiología , Adulto , Comportamiento del Consumidor , Diseño de Equipo , Humanos , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Encuestas y Cuestionarios , Análisis y Desempeño de TareasRESUMEN
Velocardiofacial syndrome (VCFS) is a syndrome with a known, but variable clinical and behavioural phenotype. Most reported cases are patients of a relatively young age. The development of the behavioural phenotype and psychopathology in older patients with VCFS is less known. We present a case of a 52 year old male patient with VCFS and a deletion in chromosome band 22q11.2. He presents with typical symptoms reported in the behavioural phenotype, autistic features and an overall deteriorating process, which fulfils the DSMIV criteria for dementia.
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Trastorno Autístico/complicaciones , Trastorno Autístico/genética , Demencia/complicaciones , Demencia/genética , Síndrome de DiGeorge/complicaciones , Síndrome de DiGeorge/genética , Cromosomas Humanos Par 22/genética , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/genética , Demencia/diagnóstico , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Eliminación de Gen , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Fenotipo , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosRESUMEN
The aim of the study was to identify predictors of comfort and discomfort in using hand tools. For this purpose, the comfort questionnaire for hand tools (CQH) was developed based on the results of a previous study. In the current study, four screwdrivers were evaluated on comfort (expected comfort at first sight and comfort after short time use) using the CQH and discomfort (local perceived discomfort). The results showed that expected comfort at first sight was predicted by aesthetics. Additionally, functionality and physical interaction, and adverse body effects were the major predictors of overall comfort after short time use. Discomfort was predicted by adverse body effects only. It is concluded that comfort and discomfort in using hand tools have partly the same underlying factors: discomfort feelings also affect the comfort experience.
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Comportamiento del Consumidor , Diseño de Equipo , Ergonomía , Mano/fisiología , Adulto , Estética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ocupaciones , Análisis de Componente Principal , Encuestas y CuestionariosRESUMEN
BACKGROUND: Microparticles (MP) from endothelial cells (endothelial microparticles; EMP) circulate in disease states, but the processes such as apoptosis or cell activation underlying their release are unclear. OBJECTIVES: We investigated whether adherent (viable) or detached (apoptotic) endothelial cells are the possible source of EMP in vitro, i.e. under control and interleukin (IL)-1alpha activation conditions, and in vivo. METHODS: Adherent and detached endothelial cells, and EMP, were isolated from human umbilical vein endothelial cell cultures (n = 6), treated without or with IL-1alpha (5 ng mL(-1); 24 h). Cell fractions were analyzed by flow cytometry for annexin V binding, propidium iodide (PI) and caspase 3 staining (n = 3). Caspase 3 in EMP was studied using Western blot (n = 6) and flow cytometry (n = 6). Plasma from healthy subjects and systemic lupus erythematosus patients (both n = 3) were analyzed for caspase 3-containing (E)MP. RESULTS: Detached but not adherent cells double-stained for annexin V and PI, confirming the apoptotic conditions of the detached cells and the viable nature of the adherent cells. Caspase 3 was solely present in the detached cells and procaspase 3 in the adherent cells. Caspase 3 was present in EMP from both control and IL-1alpha-treated cultures. Counts of EMP and detached cells, but not adherent cells, highly correlated (r = 0.959, P < 0.0001). In vivo circulating MP from nucleated (endothelial cells, monocytes) and anucleated cells (platelets, erythrocytes) contained caspase 3. CONCLUSIONS: EMP contain caspase 3 and may be mainly derived from detached (apoptotic) endothelial cells in vitro. The presence of caspase 3 in MP from anucleated cell types, however, suggests that its presence may not necessarily be related to apoptosis in vivo but may be associated with caspase 3 activation unrelated to apoptosis.
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Caspasas/fisiología , Células Endoteliales/citología , Anexina A5/farmacología , Apoptosis , Coagulación Sanguínea , Plaquetas/metabolismo , Western Blotting , Estudios de Casos y Controles , Caspasa 3 , Caspasas/metabolismo , Caspasas/farmacología , Adhesión Celular , Supervivencia Celular , Células Cultivadas , Medios de Cultivo Condicionados/farmacología , Endotelio Vascular/citología , Endotelio Vascular/metabolismo , Activación Enzimática , Femenino , Citometría de Flujo , Humanos , Técnicas In Vitro , Interleucina-1/metabolismo , Lupus Eritematoso Sistémico/sangre , Microcirculación , Persona de Mediana Edad , Neovascularización Patológica , Activación Plaquetaria , Propidio/farmacología , Venas Umbilicales/citologíaRESUMEN
The late 20th century trend to delay birth of the first child until the age at which female fecundity or reproductive capacity is lower has increased the incidence of age-related infertility. The trend and its consequences have also stimulated interest in the possible factors in the female and the male that may contribute to the decline in fecundity with age; in the means that exist to predict fecundity; and in the consequences for pregnancy and childbirth. In the female, the number of oocytes decreases with age until the menopause. Oocyte quality also diminishes, due in part to increased aneuploidy because of factors such as changes in spindle integrity. Although older male age affects the likelihood of conception, abnormalities in sperm chromosomes and in some components of the semen analysis are less important than the frequency of intercourse. Age is as accurate as any other predictor of conception with assisted reproductive technology. The decline in fecundity becomes clinically relevant when women reach their mid-30s, when even assisted reproduction treatment cannot compensate for the decline in fecundity associated with delaying attempts at conceiving. Pregnancies among women aged >40 years are associated with more non-severe complications, more premature births, more congenital malformations and more interventions at birth.
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Envejecimiento/fisiología , Fertilidad/fisiología , Técnicas Reproductivas Asistidas/normas , Adulto , Demografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oocitos/fisiología , Embarazo , Factores Sexuales , Espermatozoides/fisiologíaRESUMEN
We investigated the apoptosis gene expression profile of chronic lymphocytic leukemia (CLL) cells in relation to (1) normal peripheral and tonsillar B-cell subsets, (2) IgV(H) mutation status, and (3) effects of cytotoxic drugs. In accord with their noncycling, antiapoptotic status in vivo, CLL cells displayed high constitutive expression of Bcl-2 and Flip mRNA, while Survivin, Bid and Bik were absent. Paradoxically, along with these antiapoptotic genes CLL cells had high-level expression of proapoptotic BH3-only proteins Bmf and Noxa. Treatment of CLL cells with fludarabine induced only the proapoptotic genes Bax and Puma in a p53-dependent manner. Interestingly, the degree of Puma induction was more pronounced in cells with mutated IgVH genes. Thus, disturbed apoptosis in CLL is the net result of both protective and sensitizing aberrations. This delicate balance can be tipped via induction of Puma in a p53-dependent matter, the level of which may vary between groups of patients with a different tendency for disease progression.