RESUMEN
Multi-recurrent high-grade meningiomas remain an unmet medical need in neuro-oncology when iterative surgeries and radiation therapy sessions fail to control tumor growth. Nevertheless, the last 10years have been marked by multiple advances in the comprehension of meningioma tumorigenesis via the discovery of new driver mutations, the identification of activated intracellular signaling pathways, and DNA methylation analyses, providing multiple potential therapeutic targets. Today, Anti-VEGF and mTOR inhibitors are the most used and probably the most active drugs in aggressive meningiomas. Peptide radioactive radiation therapy aims to target SSTR2A receptors, which are strongly expressed in meningiomas, but have an insufficient effect in most aggressive meningiomas, requiring the development of new techniques to increase the dose applied to the tumor. Based on the multiple potential intracellular targets, multiple targeted therapy clinical trials targeting Pi3K-Akt-mTOR and MAP kinase pathways as well as cell cycle and particularly, cyclin D4-6 are ongoing. Recently discovered driver mutations, SMO, Akt, and PI3KCA, offer new targets but are mostly observed in benign meningiomas, limiting their clinical relevance mainly to rare aggressive skull base meningiomas. Therefore, NF2 mutation remains the most frequent mutation and main challenging target in high-grade meningioma. Recently, inhibitors of focal adhesion kinase (FAK), which is involved in tumor cell adhesion, were tested in a phase 2 clinical trial with interesting but insufficient activity. The Hippo pathway was demonstrated to interact with NF2/Merlin and could be a promising target in NF2-mutated meningiomas with ongoing multiple preclinical studies and a phase 1 clinical trial. Recent advances in immune landscape comprehension led to the proposal of the use of immunotherapy in meningiomas. Except in rare cases of MSH2/6 mutation or high tumor mass burden, the activity of PD-1 inhibitors remains limited; however, its combination with various radiation therapy modalities is particularly promising. On the whole, therapeutic management of high-grade meningiomas is still challenging even with multiple promising therapeutic targets and innovations.
Asunto(s)
Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/genética , Meningioma/terapia , Meningioma/metabolismo , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/terapia , Neoplasias Meníngeas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/uso terapéutico , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/uso terapéutico , Recurrencia Local de Neoplasia , MutaciónRESUMEN
Positron emission tomography (PET) is a powerful tool that can help physicians manage primary brain tumours at diagnosis and follow-up. In this context, PET imaging is used with three main types of radiotracers: 18F-FDG, amino acid radiotracers, and 68Ga conjugated to somatostatin receptor ligands (SSTRs). At initial diagnosis, 18F-FDG helps to characterize primary central nervous system (PCNS) lymphomas and high-grade gliomas, amino acid radiotracers are indicated for gliomas, and SSTR PET ligands are indicated for meningiomas. Such radiotracers provide information on tumour grade or type, assist in directing biopsies and help with treatment planning. During follow-up, in the presence of symptoms and/or MRI modifications, the differential diagnosis between tumour recurrence and post-therapeutic changes, in particular radiation necrosis, may be challenging, and there is strong interest in using PET to evaluate therapeutic toxicity. PET may also contribute to identifying specific complications, such as postradiation therapy encephalopathy, encephalitis associated with PCNS lymphoma, and stroke-like migraine after radiation therapy (SMART) syndrome associated with glioma recurrence and temporal epilepsy, originally illustrated in this review. This review summarizes the main contribution of PET to the diagnosis, management, and follow-up of brain tumours, specifically gliomas, meningiomas, and primary central nervous system lymphomas.
Asunto(s)
Neoplasias Encefálicas , Glioma , Linfoma , Neoplasias Meníngeas , Meningioma , Medicina Nuclear , Humanos , Fluorodesoxiglucosa F18 , Meningioma/diagnóstico por imagen , Meningioma/terapia , Recurrencia Local de Neoplasia , Tomografía de Emisión de Positrones/métodos , Glioma/diagnóstico por imagen , Glioma/terapia , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/terapia , Aminoácidos , RadiofármacosRESUMEN
Nuclear medicine with positron emission tomography (PET) and single photon emission computed tomography (SPECT) develops powerful tools in molecular imaging to help clinicians in the challenging diagnosis of parkinsonism. These techniques can provide biomarkers for neurodegenerative parkinsonism and to distinguish Parkinson disease (PD) from atypical parkinsonism. This review summarizes the main SPECT and PET contributions to the diagnosis of parkinsonism. We will also discuss new technologies in the field of nuclear imaging and their potential contribution to the diagnosis of parkinsonian syndromes.
Asunto(s)
Enfermedad de Parkinson , Trastornos Parkinsonianos , Diagnóstico Diferencial , Humanos , Imagen Molecular/métodos , Enfermedad de Parkinson/diagnóstico por imagen , Trastornos Parkinsonianos/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Tomografía Computarizada de Emisión de Fotón Único/métodosRESUMEN
We tested the hypothesis that circadian adaptation to night work is best achieved by combining bright light during the night shift and scheduled sleep in darkness. Fifty-four subjects participated in a shift work simulation of 4 day and 3 night shifts followed by a 38-h constant routine (CR). Subjects received 2,500 lux (Bright Light) or 150 lux (Room Light) during night shifts and were scheduled to sleep (at home in darkened bedrooms) from 0800 to 1600 (Fixed Sleep) or ad libitum (Free Sleep). Dim light melatonin onset (DLMO) was measured before and after the night shifts. Both Fixed Sleep and Bright Light conditions significantly phase delayed DLMO. Treatments combined additively, with light leading to larger phase shifts. Free Sleep subjects who spontaneously adopted consistent sleep schedules adapted better than those who did not. Neither properly timed bright light nor fixed sleep schedules were consistently sufficient to shift the melatonin rhythm completely into the sleep episode. Scheduling of sleep/darkness should play a major role in prescriptions for overcoming shift work-related phase misalignment.
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Trastornos Cronobiológicos/terapia , Ritmo Circadiano/efectos de la radiación , Oscuridad , Luz , Tolerancia al Trabajo Programado , Adaptación Fisiológica/efectos de la radiación , Adulto , Análisis de Varianza , Trastornos Cronobiológicos/sangre , Trastornos Cronobiológicos/fisiopatología , Femenino , Humanos , Masculino , Melatonina/sangre , Sueño , Resultado del Tratamiento , VigiliaRESUMEN
Models of visual search performance typically assume that search proceeds by sampling without replacement. This requires memory for each deployment of attention. We tested this assumption of memory-driven search using a multiple-target search paradigm. We held total set size constant, varied the number of targets in the display, and asked subjects to report whether or not there were at least n targets present, where n was varied by block. This allowed us to measure the time to find each subsequent target. Memory-driven search predicts that reaction time should be a linear function of n. The alternative memory-free search hypothesis predicts an accelerating function. The data falsify the memory-driven hypothesis. They were consistent with the memory-free search hypothesis but would also be consistent with memory for a small number of previously attended locations.
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Atención , Recuerdo Mental , Reconocimiento Visual de Modelos , Aprendizaje Discriminativo , Humanos , Psicofísica , Tiempo de ReacciónRESUMEN
The correlation between climatic conditions and mite numbers in houses from rural areas was studied in 13 agricultural communities (kibbutzim and moshavim) in nine geo-climatic subregions of Israel. Mites were present in 97% of the dust samples. The average number of mites per gram of dust in the different localities ranged between 84 and 2053. The maximum number of mites (7440/g dust) was found in a carpet from a house in Geva Carmel in the northern coastal region. The most prevalent species of mites were Dermatophagoides pteronyssinus and Dermatophagoides farinae, which were found in 85.6% and 71.3% of the samples, respectively. The house dust mites D. pteronyssinus, D. farinae and Euroglyphus maynei constituted 94.8% of the mites. Most of the mites were isolated from the carpets and sofas (37.0% and 33.7%, respectively), and a smaller number from beds (29.3%). The smallest number of mites (< or = 250/g dust) were found at a minimum relative humidity (RH) of 30% and lower, with a maximum temperature of 32 degrees C and higher, i.e. in the Jordan valley and Negev mountains. A greater number of mites (250-500/g dust) were found at a minimum ambient RH of 35-40% and a maximum temperature of 32 degrees C and higher, i.e. the Hula valley. A large number of mites (500-1000/g dust) were found at a minimum RH of 35-40% with a maximum temperature of 30 degrees C and lower, i.e. in the Judean and Samarian range, as well as in upper Galilee. The largest number of mites (1000-2000/g dust) was found at a minimum RH of 45% and higher, with a maximum temperature ranging between 30 and 32 degrees C. These conditions occur in the coastal strip, the coastal plain and in the Judean and Samarian foothills. A monthly examination of two houses in Zova, a kibbutz in the Judean hills next to Jerusalem, and two houses from Palmachim, a kibbutz in the coastal region, revealed that the highest prevalence of mites was found in the months April-November and May-November, respectively. In Zova, the highest number of mites were found during the months of June and July while the highest concentrations of D. pteronyssinus-antigen (Der p I) were measured during the month of September. A positive correlation between mite numbers and the quantity of Der p I in house dust was found.
Asunto(s)
Ácaros , Agricultura , Animales , Clima , Humanos , Israel , Ácaros/clasificación , Densidad de Población , Estaciones del AñoRESUMEN
Humans spend a lot of time searching for things, such as roadside traffic signs, soccer balls or tumours in mammograms. These tasks involve the deployment of attention from one item in the visual field to the next. Common sense suggests that rejected items should be noted in some fashion so that effort is not expended in re-examining items that have been attended to and rejected. However, common sense is wrong. Here we asked human observers to search for a letter 'T' among letters 'L'. This search demands visual attention and normally proceeds at a rate of 20-30 milliseconds per item. In the critical condition, we randomly relocated all letters every 111 milliseconds. This made it impossible for the subjects to keep track of the progress of the search. Nevertheless, the efficiency of the search was unchanged. Theories of visual search all assume that search relies on accumulating information about the identity of objects over time. Such theories predict that search efficiency will be drastically reduced if the scene is continually shuffled while the observer is trying to search through it. As we show that efficiency is not impaired, the standard theories must be revised.
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Memoria/fisiología , Percepción Visual/fisiología , Humanos , Modelos Neurológicos , Tiempo de ReacciónRESUMEN
This paper focuses on two questions: Are Ethiopian high school children who immigrated to Israel achievement motivated? To what extent does the presence or absence of certain components of the achievement construct in the indigenous value system of Ethiopian students affect progress at school? The study is based on pilot research conducted in Israel in 1987 for which the central research questions were: Are elements of motivation to be found in the indigenous value system of Ethiopian students? If so, what is their effect on progress at school? The research is based on a questionnaire administered to 88 Ethiopian students and 85 veteran Israeli students. The main findings of this research are: There are some elements in the socialization of Ethiopian students that can be looked upon as components of achievement motivation. These include a high level of aspiration, the ability to postpone gratification, and obedience. These elements help the Ethiopian children succeed at school. On the other hand, some elements in the socialization of Ethiopian children hinder their progress: conformity restraints on individual creativity and external locus of control.
Asunto(s)
Logro , Comparación Transcultural , Emigración e Inmigración , Motivación , Estudiantes/psicología , Adolescente , Estudios de Casos y Controles , Etiopía/etnología , Familia , Femenino , Identidad de Género , Humanos , Control Interno-Externo , Israel , Masculino , Análisis de Regresión , Conformidad Social , Valores Sociales , SocializaciónRESUMEN
"This article focuses on value inputs at various junctures of the immigrant-absorption process in Israel and their possible implications for the future of the immigrants.... The model of value inputs of the 1990s suggests several directions in which absorption policy may head....One such direction is dominant in other immigration countries: the integration of the stronger immigrants--those whose ability to function in modern Western society is high--is left to market forces.... Another possible paradigm of absorption is one in which the government intervenes selectively to help especially disadvantaged groups....A third orientation depends on the immigration trend. If immigration tapers off, the government will intervene more intensively and extensively in the integration of the 1990s immigrants, particularly at the municipal level." (SUMMARY IN FRE AND SPA)
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Aculturación , Emigración e Inmigración , Política Pública , Valores Sociales , Asia , Asia Occidental , Conducta , Demografía , Países Desarrollados , Israel , Población , Dinámica Poblacional , Psicología , Cambio Social , MigrantesRESUMEN
Transplantation of MHC-matched, allogeneic B10.D2 bone marrow plus T cells into BALB/c recipients ultimately results in chronic graft-vs-host disease (GVHD) and mortality 8 to 12 wk post-transplant. We have identified IL-7-specific mRNA in the spleens of BALB/c bone marrow transplantation (BMT) recipients during the first week post-transplant. The response by T cells from B10.D2-->BALB/c BMT recipients to stimulation with IL-7 in vitro during the early period after transplant was then examined. The findings indicated that within the first week post-transplant, spleen cells removed from recipients injected with allogeneic, but not syngeneic, T cells proliferated vigorously to rIL-7. Both IL-2-dependent and -independent components were identified. Depletion of responding cells before culture with anti-Thy-1.2 Ab virtually eliminated this response. We conclude that transplant of allogeneic T cells is required for the observed IL-7 response, and moreover, such cells proliferate after exposure to this cytokine in vitro. To determine whether IL-7 could have a functional effect on donor T cells, the production of IFN-gamma by T cells from allogeneic BMT recipients stimulated with anti-T cell receptor (i.e., anti-V beta) Ab was examined. IL-7 was demonstrated to enhance IFN-gamma production by donor T cells postallogeneic BMT. These results suggest that a cytokine presumably produced in the host for the physiologic function of hematologic reconstitution is playing an additional role during the early events after allogeneic BMT mediated via the expansion and augmented cytokine production by donor T cells.
Asunto(s)
Trasplante de Médula Ósea/inmunología , Citocinas/metabolismo , Interleucina-7/fisiología , Activación de Linfocitos/fisiología , Linfocitos T/inmunología , Animales , Anticuerpos Monoclonales/inmunología , Secuencia de Bases , Femenino , Enfermedad Injerto contra Huésped/inmunología , Interferón gamma/biosíntesis , Interleucina-7/biosíntesis , Interleucina-7/genética , Interleucina-7/farmacología , Activación de Linfocitos/efectos de los fármacos , Depleción Linfocítica , Ratones , Ratones Endogámicos BALB C , Datos de Secuencia Molecular , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Quimera por Radiación , Receptores de Antígenos de Linfocitos T/inmunología , Bazo/inmunología , Linfocitos T/efectos de los fármacos , Linfocitos T/metabolismo , Linfocitos T/trasplanteRESUMEN
Two dissociations between short- and long-range motion in visual search are reported. Previous research has shown parallel processing for short-range motion and apparently serial processing for long-range motion. This finding has been replicated and it has also been found that search for short-range targets can be impaired both by using bicontrast stimuli, and by prior adaptation to the target direction of motion. Neither factor impaired search in long-range motion displays. Adaptation actually facilitated search with long-range displays, which is attributed to response-level effects. A feature-integration account of apparent motion is proposed. In this theory, short-range motion depends on specialized motion feature detectors operating in parallel across the display, but subject to selective adaptation, whereas attention is needed to link successive elements when they appear at greater separations, or across opposite contrasts.
Asunto(s)
Atención/fisiología , Percepción de Movimiento/fisiología , Adaptación Ocular/fisiología , Adulto , Femenino , Humanos , MasculinoRESUMEN
This article reports on dropouts in four schools in Israel. Two main research questions were addressed: (1) Is it possible to identify a potential dropout through examination of his/her attitudes and competence before the actual act of leaving school? (2) Is there a difference between dropouts and persistent students in different educational settings (academic, vocational, agricultural, and comprehensive high schools)? Significant differences were found in the attitudes of persistent students and dropouts even before the act of dropping out occurred. In the vocational, comprehensive, and agricultural schools, the dropouts scored more positively on the self-estrangement, meaninglessness, and misfeasance scales. In the academic school, the dropouts scored positively on the anxiety scale. Results were interpreted in light of the Mertonian scheme of ends and means as well as the reproduction scheme. The Mertonian scheme was deemed more applicable.
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Trastornos de Ansiedad/psicología , Abandono Escolar/psicología , Logro , Adolescente , Conducta del Adolescente , Trastornos de Ansiedad/etiología , Educación , Femenino , Humanos , Israel , Masculino , Psicología del Adolescente , Instituciones Académicas , AutoimagenRESUMEN
An irregular corneal surface degrades the optical transmission and limits the effectiveness of the potential acuity meter (PAM) in predicting post-keratoplasty visual acuity. The authors investigated the efficacy of using a temporarily placed hard contact lens to neutralize surface irregularities in conjunction with the PAM in predicting post-keratoplasty visual acuity. A prospective evaluation was performed on 40 keratoplasty patients with a mean follow-up of 10.4 months. Of 27 patients with corneas clear enough to permit them to read letters on the PAM chart, 17 (63%) had very accurately predicted visual acuities by this new method, compared to only eight patients (30%) with the PAM alone. Three patients had predicted visions better than final vision, but this was due to a concurrent cataract in two cases and chronic cystoid macular edema (CME) in the third case. This study indicates that temporarily placing a hard contact lens for use with the PAM can increase its accuracy in predicting final visual acuity after penetrating keratoplasty.
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Lentes de Contacto , Trasplante de Córnea , Agudeza Visual , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Lentes Intraoculares , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Valor Predictivo de las Pruebas , Estudios Prospectivos , Pruebas de Visión/instrumentación , Pruebas de Visión/métodosRESUMEN
Children (N = 54) ranging in age from one year four months to five years were offered over 30 items to eat. The items included normal adult foods and exemplars of different adult rejection categories: disgust (e.g. grasshopper, hair), danger (liquid dish soap), inappropriate (e.g. paper, leaf) and unacceptable combinations (e.g. ketchup and cookie). We report a high to moderate level of acceptance (item put into mouth) of substances from all of these categories in the youngest children. Acceptance of disgusting and dangerous substances decreases with increasing age, while acceptance of inappropriate substances remains at moderate levels across the age range studied. Although the youngest children accepted more disgust items, the majority rejected most of the disgust choices. Almost all children at all ages tested accept combinations of foods which, although individually accepted by adults, are rejected in combination. No significant differences were observed between 'normal' children and those with a history of toxin ingestion, although there was a tendency of ingesters to accept more inedible items. In general, the results suggest that a major feature of the development of food selection is learning what not to eat.
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Desarrollo Infantil/fisiología , Formación de Concepto/fisiología , Preferencias Alimentarias , Adulto , Preescolar , Femenino , Humanos , Lactante , Masculino , Pica/fisiopatología , Gusto/fisiologíaRESUMEN
Women with sickle cell anemia have many specialized problems during labor and delivery. A description of the disease and how it affects women during the intrapartum period is presented. Also, the management of potential problems during labor and delivery is described.