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BACKGROUND: Deficits in spatial memory, orientation, and navigation are often neglected early signs of cognitive impairment or loss of vestibular function. Real-world navigation tests require complex setups. In contrast, simple pointing at targets in a three-dimensional environment is a basic sensorimotor ability which provides an alternative measure of spatial orientation and memory at bedside. The aim of this study was to test the reliability of a previously established 3D-Real-World Pointing Test (3D-RWPT) in patients with cognitive impairment due to different neurodegenerative disorders, bilateral vestibulopathy, or a combination of both compared to healthy participants. METHODS: The 3D-RWPT was performed using a static array of targets in front of the seated participant before and, as a transformation task, after a 90-degree body rotation around the yaw-axis. Three groups of patients were enrolled: (1) chronic bilateral vestibulopathy (BVP) with normal cognition (n = 32), (2) cognitive impairment with normal vestibular function (n = 28), and (3) combined BVP and cognitive impairment (n = 9). The control group consisted of age-matched participants (HP) without cognitive and vestibular deficits (n = 67). Analyses focused on paradigm-specific mean angular deviation of pointing in the azimuth (horizontal) and polar (vertical) spatial planes, of the preferred pointing strategy (egocentric or allocentric), and the resulting shape configuration of the pointing array relative to the stimulus array. Statistical analysis was performed using age-corrected ANCOVA-testing with Bonferroni correction and correlation analysis using Spearman's rho. RESULTS: Patients with cognitive impairment employed more egocentric pointing strategies while patients with BVP but normal cognition and HP used more world-based solutions (pBonf 5.78 × 10-3**). Differences in pointing accuracy were only found in the azimuth plane, unveiling unique patterns where patients with cognitive impairment showed decreased accuracy in the transformation tasks of the 3D-RWPT (pBonf < 0.001***) while patients with BVP struggled in the post-rotation tasks (pBonf < 0.001***). Overall azimuth pointing performance was still adequate in some patients with BVP but significantly decreased when combined with a cognitive deficit. CONCLUSION: The 3D-RWPT provides a simple and fast measure of spatial orientation and memory. Cognitive impairment often led to a shift from world-based allocentric pointing strategy to an egocentric performance with less azimuth accuracy compared to age-matched controls. This supports the view that cognitive deficits hinder the mental buildup of the stimulus pattern represented as a geometrical form. Vestibular hypofunction negatively affected spatial memory and pointing performance in the azimuth plane. The most severe spatial impairments (angular deviation, figure frame configuration) were found in patients with combined cognitive and vestibular deficits.
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Vestibulopatía Bilateral , Demencia , Humanos , Memoria Espacial , Reproducibilidad de los Resultados , Trastornos de la Memoria/diagnóstico , Trastornos de la Memoria/etiologíaRESUMEN
Perceptual decision-making is a complex task that requires multiple processing steps performed by spatially distinct brain regions interacting in order to optimize perception and motor response. Most of our knowledge on these processes and interactions were derived from unimodal stimulations of the visual system which identified the lateral intraparietal area and the posterior parietal cortex as critical regions. Unlike the visual system, the vestibular system has no primary cortical areas and it is associated with separate multisensory areas within the temporo-parietal cortex with the parieto-insular vestibular cortex, PIVC, being the core region. The aim of the presented experiment was to investigate the transition from sensation to perception and to reveal the main structures of the cortical vestibular system involved in perceptual decision-making. Therefore, an EEG analysis was performed in 35 healthy subjects during linear whole-body accelerations of different intensities on a motor-driven motion platform (hexapod). We used a discrimination task in order to judge the intensity of the accelerations. Furthermore, we manipulated the expectation of the upcoming stimulus by indicating the probability (25%, 50%, 75%, 100%) of the motion direction. The analysis of the vestibular evoked potentials (VestEPs) showed that the decision-making process leads to a second positive peak (P2b) which was not observed in previous task-free experiments. The comparison of the estimated neural generators of the P2a and P2b components showed significant activity differences in the anterior cingulus, the parahippocampal and the middle temporal gyri. Taking into account the time courses of the P2 components, the physical properties of the stimuli, and the responses given by the subjects we conclude that the P2b likely reflects the transition from the processing of sensory information to perceptual evaluation. Analyzing the decision-uncertainty reported by the subjects, a persistent divergence of the time courses starting at 188 âms after the acceleration was found at electrode Pz. This finding demonstrated that meta-cognition by means of confidence estimation starts in parallel with the decision-making process itself. Further analyses in the time-frequency domain revealed that a correct classification of acceleration intensities correlated with an inter-trial phase clustering at electrode Cz and an inter-site phase clustering of theta oscillations over frontal, central, and parietal cortical areas. The sites where the phase clustering was observed corresponded to core decision-making brain areas known from neuroimaging studies in the visual domain.
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Encéfalo/fisiología , Toma de Decisiones/fisiología , Percepción de Movimiento/fisiología , Propiocepción/fisiología , Ritmo Teta/fisiología , Potenciales Vestibulares Miogénicos Evocados/fisiología , Aceleración , Adulto , Mapeo Encefálico , Electroencefalografía , Femenino , Humanos , Masculino , Vestíbulo del Laberinto/fisiologíaRESUMEN
BACKGROUND AND PURPOSE: Acute vestibular symptoms have a profound impact on patients' well-being. In this study, health-related quality of life (HRQoL) and functional impairment were investigated prospectively in patients with different peripheral and central vestibular disorders during the acute symptomatic stage to decipher the most relevant underlying factors. METHODS: In all, 175 patients with acute vestibular disorders were categorized as central vestibular (CV, n = 40), peripheral vestibular (PV, n = 68) and episodic vestibular disorders (EV, n = 67). All patients completed scores to quantify generic HRQoL (European Quality of Life Score Five Dimensions Five Levels, EQ-5D-5L) and disease-specific HRQoL (Dizziness Handicap Inventory, DHI). Vestibular-ocular motor signs were assessed by video-oculography, vestibular-spinal control by posturography and verticality perception by measurement of subjective visual vertical. RESULTS: Patients with PV had a poorer HRQoL compared to patients with CV and EV (EQ-5D-5L/DHI: PV, 0.53 ± 0.31/56.1 ± 19.7; CV, 0.66 ± 0.28/43.3 ± 24.0; EV, 0.75 ± 0.24/46.7 ± 21.4). After adjusting for age, gender, cardiovascular risk factors and non-vestibular brainstem/cerebellar dysfunction patients with PV persisted to have poorer generic and disease-specific HRQoL (EQ-5D-5L -0.17, DHI +11.2) than patients with CV. Horizontal spontaneous nystagmus was a highly relevant factor for subgroup differences in EQ-5D-5L and DHI, whilst vertical spontaneous nystagmus, subjective visual vertical and sway path were not. EQ-5D-5L decreased significantly with more intense horizontal subjective visual vertical in CV (rho = -0.57) and PV (rho = -0.5) but not EV (rho = -0.13). CONCLUSIONS: Patients with PV have the highest functional impairment of all patients with acute vestibular disorders. Vestibular-ocular motor disturbance in the yaw plane has more impact than vestibular-spinal or vestibular-perceptive asymmetry in the roll and pitch plane, suggesting that horizontal visual stability is the most critical for HRQoL.
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Calidad de Vida , Enfermedades Vestibulares , Mareo , Humanos , Encuestas y Cuestionarios , VértigoRESUMEN
BACKGROUND AND PURPOSE: Most recurrent cervical artery dissection (CeAD) events occur shortly after the acute first CeAD. This study compared the characteristics of recurrent and first CeAD events and searched for associations between subsequent events of an individual person. METHODS: Cervical artery dissection patients with a new CeAD event occurring during a 3-6 month follow-up were retrospectively selected in seven specialized stroke centers. Clinical and vascular characteristics of the initial and the recurrent CeADs were compared. RESULTS: The study sample included 76 patients. Recurrent CeADs were occlusive in one (1.3%) patient, caused cerebral ischaemia in 13 (17.1%) and were asymptomatic in 39 (51.3%) patients, compared to 29 (38.2%) occlusive, 42 (55.3%) ischaemic and no asymptomatic first CeAD events. In 52 (68.4%) patients, recurrent dissections affected both internal carotid arteries or both vertebral arteries, whilst 24 (31.6%) patients had subsequent dissections in both types of artery. Twelve (28.6%) of 42 patients with an ischaemic first dissection had ischaemic symptoms due to the recurrent CeADs, too. However, only one (1.3%) of 34 patients with a non-ischaemic first CeAD suffered ischaemia upon recurrence. CONCLUSION: Recurrent CeAD typically affects the same site of artery. It causes ischaemic events less often than the first CeAD. The risk that patients who presented with solely non-ischaemic symptoms of a first CeAD will have ischaemic symptoms in the case of a recurrent CeAD seems very small.
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Disección de la Arteria Vertebral , Arterias , Disección de la Arteria Carótida Interna/epidemiología , Disección , Humanos , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Disección de la Arteria Vertebral/epidemiologíaRESUMEN
Current evidence points towards a vestibular cortex that involves a multisensory bilateral temporo-parietal-insular network with a handedness-dependent hemispheric lateralization. This study aimed to identify handedness-dependent organizational patterns of (lateralized and non-lateralized) functional subunits within the human vestibular cortex areas. 60 healthy volunteers (30 left-handed and 30 right-handed) were examined on a 3T MR scanner using resting state functional MRI (fMRI). The data was analyzed in four major steps using a functional connectivity based parcellation (fCBP) approach: (1) independent component analysis (ICA) on a whole brain level to identify different resting state networks (RSN); (2) creation of a vestibular informed mask from four whole brain ICs that included reference coordinates of the vestibular network extracted from meta-analyses of vestibular neuroimaging experiments; (3) Re-ICA confined to the vestibular informed mask; (4) cross-correlation of the activated voxels within the vestibular subunits (parcels) to each other (P-to-P) and to the whole-brain RSN (P-to-RSN). This approach disclosed handedness-dependency, inter-hemispheric symmetry, the scale of connectedness to major whole brain RSN and the grade of spatial overlap of voxels within parcels (common/unique) as meaningful discriminatory organizational categories within the vestibular cortex areas. This network consists of multiple inter-hemisphere symmetric (not lateralized), well-connected (many RSN-assignments) multisensory areas (or hubs; e.g., superior temporal gyrus, temporo-parietal intersection) organized around an asymmetric (lateralized, "dominant") and functionally more specialized (few RSN-assignments) core region in the parieto-insular cortex. The latter is in the middle, posterior and inferior insula. In conclusion, the bilateral cortical vestibular network contains not only a handedness-dependent lateralized central region concentrated in the right hemisphere in right-handers and left hemisphere in left-handers, but also surrounding inter-hemisphere symmetric multisensory vestibular areas that seem to be functionally influenced by their neighboring sensory systems (e.g., temporo-parietal intersection by the visual system). One may speculate that the development of an asymmetrical organized vestibular subsystem reflects a more recent phylogenetic evolution of various multisensory vestibular functions. The right hemispheric dominance of spatial orientation and its disorders, spatial neglect and pusher syndrome, may serve as examples.
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Mapeo Encefálico/métodos , Encéfalo/fisiología , Corteza Cerebral/fisiología , Lateralidad Funcional/fisiología , Imagen por Resonancia Magnética/métodos , Red Nerviosa/fisiología , Vestíbulo del Laberinto/fisiología , Adulto , Anciano , Encéfalo/diagnóstico por imagen , Corteza Cerebral/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Red Nerviosa/diagnóstico por imagen , Orientación Espacial/fisiología , Equilibrio Postural/fisiología , Propiocepción/fisiología , Reflejo Vestibuloocular/fisiología , Adulto JovenRESUMEN
The fountain darter Etheostoma fonticola (FOD) is a federally endangered fish listed under the US Endangered Species Act. Here, we identified and characterized a novel aquareovirus isolated from wild fountain darters inhabiting the San Marcos River. This virus was propagated in Chinook salmon embryo (CHSE)-214, rainbow trout gonad-2 and fathead minnow cells at 15°C. The epithelioma papulosum cyprini cell line was refractory at all temperatures evaluated. High throughput sequencing technologies facilitated the complete genome sequencing of this virus utilizing ribosomal RNA-depleted RNA extracted from infected CHSE-214 cells. Conventional PCR primer sets were developed for the detection and confirmation of this virus to assist diagnostic screening methods. Phylogenetic analysis suggests this virus belongs to the Aquareovirus A genus. This research provides requisite initial data critical to support hatchery and refugia biosecurity measures for this endangered species.
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Percas , Filogenia , Reoviridae , Animales , Especies en Peligro de Extinción , Percas/virología , Reoviridae/genética , Reoviridae/aislamiento & purificación , RíosRESUMEN
There are currently different groups of drugs for the pharmacotherapy of vertigo, nystagmus and cerebellar disorders: antiemetics; anti-inflammatories, antimenieres, and antimigraineous medications and antidepressants, anticonvulsants, aminopyridines as well as acetyl-DL-leucine. In acute unilateral vestibulopathy, corticosteroids improve the recovery of peripheral vestibular function, but currently there is not sufficient evidence for a general recommendation. There is insufficient evidence to support the view that 16 mg t. i. d. or 48 mg t. i. d. betahistine has an effect in Menière's disease. Therefore, higher dosages are recommended. In animal studies, it was shown that betahistine increases cochlear blood flow. In vestibular paroxysmia, oxcarbazepine was effective (one randomized controlled trial (RCT)). Aminopyridines are recommended for the treatment of downbeat nystagmus (two RCTs) and episodic ataxia type 2 (EA2, one RCT). There has been no RCT on the efficacy of beta-blockers or topiramate but one RCT on flunarizine in vestibular migraine. Based on clinical experience, a treatment analogous to that for migraine without aura can be recommended. Acetyl-DL-leucine improved cerebellar ataxia (two observational studies); it also accelerated central compensation in an animal model of acute unilateral lesion, but RCTs were negative. There are ongoing RCTs on treatment of vestibular paroxysmia with carbamazepine (VESPA), acute unilateral vestibulopathy with betahistine (BETAVEST), vestibular migraine with metoprolol (PROVEMIG), benign paroxysmal positional vertigo with vitamin D (VitD@BPPV), EA2 with 4-aminopyridine versus acetazolamide (EAT-2-TREAT), and cerebellar ataxias with acetyl-DL-leucine (ALCAT).
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Enfermedades Cerebelosas/tratamiento farmacológico , Nistagmo Patológico/tratamiento farmacológico , Enfermedades Vestibulares/tratamiento farmacológico , Animales , Fármacos del Sistema Nervioso Central/uso terapéutico , Humanos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
The Large Area Telescope on board the Fermi Gamma-ray Space Telescope has collected the largest ever sample of high-energy cosmic-ray electron and positron events since the beginning of its operation. Potential anisotropies in the arrival directions of cosmic-ray electrons or positrons could be a signature of the presence of nearby sources. We use almost seven years of data with energies above 42 GeV processed with the Pass 8 reconstruction. The present data sample can probe dipole anisotropies down to a level of 10^{-3}. We take into account systematic effects that could mimic true anisotropies at this level. We present a detailed study of the event selection optimization of the cosmic-ray electrons and positrons to be used for anisotropy searches. Since no significant anisotropies have been detected on any angular scale, we present upper limits on the dipole anisotropy. The present constraints are among the strongest to date probing the presence of nearby young and middle-aged sources.
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Neglect is a supramodal, clinically relevant disorder, which occurs in the different sensory modalities as well as in the mental representation. The different manifestations of neglect show interindividual and intraindividual variation. Different spatial and attention-related interventions lead to varying degrees of improvement in neglect symptoms but are often not stable in time or transferable to activities of daily living. Representational deficits or body-related aspects to modify personal neglect are rarely a priority in current therapies. Because of the multisensory and motor deficits from our point of view the future of neglect rehabilitation lies in a combined therapy of visual exploration, motor imagery with intensive motor therapy of motor sensory deficits and probably best reinforced by continued neck muscle vibration or allocation of attention to the neglected side.
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Imágenes en Psicoterapia/métodos , Trastornos del Movimiento/rehabilitación , Neurorretroalimentación/métodos , Rehabilitación Neurológica/métodos , Trastornos de la Percepción/rehabilitación , Medicina Basada en la Evidencia/métodos , Humanos , Trastornos del Movimiento/complicaciones , Trastornos del Movimiento/diagnóstico , Evaluación de Resultado en la Atención de Salud/métodos , Trastornos de la Percepción/complicaciones , Trastornos de la Percepción/diagnóstico , Resultado del TratamientoRESUMEN
The dwarf spheroidal satellite galaxies (dSphs) of the Milky Way are some of the most dark matter (DM) dominated objects known. We report on γ-ray observations of Milky Way dSphs based on six years of Fermi Large Area Telescope data processed with the new Pass8 event-level analysis. None of the dSphs are significantly detected in γ rays, and we present upper limits on the DM annihilation cross section from a combined analysis of 15 dSphs. These constraints are among the strongest and most robust to date and lie below the canonical thermal relic cross section for DM of mass â²100 GeV annihilating via quark and τ-lepton channels.
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Depending on the temporal course, three forms of vertigo syndrome can be differentiated: 1) vertigo attacks, e.g. benign paroxysmal positional vertigo (BPPV), Menière's disease and vestibular migraine, 2) acute spontaneous vertigo lasting for days, e.g. acute unilateral vestibulopathy, brainstem or cerebellar infarction and 3) symptoms lasting for months or years, e.g. bilateral vestibulopathy and functional vertigo. The specific therapy of the various syndromes is based on three principles: 1) physical treatment with liberatory maneuvers for BPPV and balance training for vestibular deficits, 2) pharmacotherapy, e.g. for acute unilateral vestibulopathy (corticosteroids) and Menière's disease (transtympanic administration of gentamicin or steroids and high-dose betahistine therapy); placebo-controlled pharmacotherapy studies are currently being carried out for acute unilateral vestibulopathy, vestibular paroxysmia, prophylaxis of BPPV, vestibular migraine, episodic ataxia type 2 and cerebellar ataxia; 3) psychotherapy for functional dizziness.
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Antiinflamatorios/administración & dosificación , Modalidades de Fisioterapia , Psicoterapia/métodos , Vértigo/diagnóstico , Vértigo/terapia , Terapia Combinada/métodos , Medicina Basada en la Evidencia , Humanos , Resultado del TratamientoRESUMEN
The key to diagnosing vertigo and balance disorders is systematic analysis of case history with clinical examination of the vestibular, oculomotor, and cerebral systems in particular. Important criteria for differentiating between the various vertigo syndromes are 1) the time course of symptoms, 2) the type of symptoms, 3) modulating factors, and 4) associated symptoms. For clinical examination of the vestibular system, six important tests are available: assessment of spontaneous nystagmus, head impulse test, dynamic visual acuity, subjective visual verticality, positioning manoeuvre, and the Romberg test/gait analysis with eyes open and closed. On the basis of five clinical signs (vertical divergence, central fixation nystagmus, gaze-evoked nystagmus, saccades, normal head impulse test), the clinical examination is able to differentiate between acute central and peripheral vestibular syndromes with a sensitivity and specificity of over 90%. The most relevant laboratory examinations are caloric irrigation and the video head-impulse test for canal function and the vestibular evoked myogenic potentials for otolith function. Finally, treatment is based upon four therapeutic principles: physiotherapy, pharmacotherapy, psychotherapy, and in rare cases, surgery.
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Anamnesis/métodos , Vértigo/diagnóstico , Vértigo/terapia , Enfermedades Vestibulares/diagnóstico , Enfermedades Vestibulares/terapia , Pruebas de Función Vestibular/métodos , Toma de Decisiones Clínicas/métodos , Diagnóstico Diferencial , Técnicas de Diagnóstico Neurológico , Humanos , Enfermedades Vestibulares/complicacionesRESUMEN
There are currently different groups of drugs for the pharmacotherapy of vertigo, nystagmus and cerebellar disorders: antiemetics; anti-inflammatories, antimenieres, and antimigraineous medications and antidepressants, anticonvulsants, aminopyridines as well as acetyl-DL-leucine. In acute unilateral vestibulopathy, corticosteroids improve the recovery of peripheral vestibular function, but currently there is not sufficient evidence for a general recommendation. There is insufficient evidence to support the view that 16 mg t. i. d. or 48 mg t. i. d. betahistine has an effect in Menière's disease. Therefore, higher dosages are recommended. In animal studies, it was shown that betahistine increases cochlear blood flow. In vestibular paroxysmia, oxcarbazepine was effective (one randomized controlled trial (RCT)). Aminopyridines are recommended for the treatment of downbeat nystagmus (two RCTs) and episodic ataxia type 2 (EA2, one RCT). There has been no RCT on the efficacy of beta-blockers or topiramate but one RCT on flunarizine in vestibular migraine. Based on clinical experience, a treatment analogous to that for migraine without aura can be recommended. Acetyl-DL-leucine improved cerebellar ataxia (two observational studies); it also accelerated central compensation in an animal model of acute unilateral lesion, but RCTs were negative. There are ongoing RCTs on treatment of vestibular paroxysmia with carbamazepine (VESPA), acute unilateral vestibulopathy with betahistine (BETAVEST), vestibular migraine with metoprolol (PROVEMIG), benign paroxysmal positional vertigo with vitamin D (VitD@BPPV), EA2 with 4-aminopyridine versus acetazolamide (EAT-2-TREAT), and cerebellar ataxias with acetyl-DL-leucine (ALCAT).
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Enfermedades Cerebelosas/tratamiento farmacológico , Nistagmo Patológico/tratamiento farmacológico , Enfermedades Vestibulares/tratamiento farmacológico , Animales , HumanosRESUMEN
Alport syndrome is an inherited progressive nephropathy arising from mutations in the type IV collagen genes, COL4A3, COL4A4, and COL4A5. Symptoms also include sensorineural hearing loss and ocular lesions. We determined the molecular basis of Alport syndrome in a non-consanguineous Ashkenazi Jewish family with multiple affected females using linkage analysis and next generation sequencing. We identified a homozygous COL4A3 mutation, c.40_63del, in affected individuals with mutant alleles inherited from each parent on partially conserved haplotypes. Large-scale population screening of 2017 unrelated Ashkenazi Jewish samples revealed a carrier frequency of 1 in 183 indicating that COL4A3 c.40_63del is a founder mutation which may be a common cause of Alport syndrome in this population. Additionally, we determined that heterozygous mutation carriers in this family do not meet criteria for a diagnosis of Thin Basement Membrane Nephropathy and concluded that carriers of c.40_63del are not likely to develop benign familial hematuria.
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Autoantígenos/genética , Colágeno Tipo IV/genética , Etnicidad/genética , Efecto Fundador , Genes Recesivos , Mutación/genética , Nefritis Hereditaria/genética , Secuencia de Bases , Preescolar , Femenino , Ligamiento Genético , Haplotipos/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Tamizaje Masivo , Datos de Secuencia Molecular , LinajeRESUMEN
Recent accurate measurements of cosmic-ray (CR) species by ATIC-2, CREAM, and PAMELA reveal an unexpected hardening in the proton and He spectra above a few hundred GeV, a gradual softening of the spectra just below a few hundred GeV, and a harder spectrum of He compared to that of protons. These newly discovered features may offer a clue to the origin of high-energy CRs. We use the Fermi Large Area Telescope observations of the γ-ray emission from Earth's limb for an indirect measurement of the local spectrum of CR protons in the energy range â¼90 GeV-6 TeV (derived from a photon energy range 15 GeV-1 TeV). Our analysis shows that single power law and broken power law spectra fit the data equally well and yield a proton spectrum with index 2.68±0.04 and 2.61±0.08 above â¼200 GeV, respectively.
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BACKGROUND: Vertigo and dizziness are common symptoms leading patients to consult a physician. The nationally representative "2003 Health Survey" depicts the epidemiology of the symptoms vertigo and dizziness across all of Germany. A breakdown of the data by region is not available. METHODS: Routine data of the Bavarian Association of Statutory Health Insurance Physicians accounting centre ("Kassenärztliche Vereinigung Bayerns", KVB) from 2008 were analysed using multilevel models to investigate individual and regional factors and the relevance of nonspecific regional heterogeneity. RESULTS: Altogether, 866,086 of 9,269,729 (9.34%) inhabitants received an ambulatory diagnosis of vertigo or dizziness, including 1.77 times as many women as men. Visits to the doctor because of vertigo or dizziness increased with age. After adjustments for age and sex, a North-South divide and a higher prevalence in the urban centres were apparent within Bavaria. The majority of patients were seen by their GP and nearby doctors. This held especially true for women. Also older patients were less likely to go to specialists further afield. CONCLUSION: This analysis of the KVB data of patients with vertigo or dizziness underlines the central role that is played by GPs in diagnosis and treatment. In order to correctly diagnose the underlying causes, treat patients or send them to specialists effectively, all doctors need to be trained about this relevant clinical symptom. The insufficient representation of clinically established vertigo disorders by the ICD-10 was problematic. The most frequently coded diagnosis was N95.1 "postmenopausal dizziness".
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Mareo/diagnóstico , Mareo/epidemiología , Medicina General/estadística & datos numéricos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Población Urbana/estadística & datos numéricos , Vértigo/diagnóstico , Vértigo/patología , Adolescente , Adulto , Distribución por Edad , Comorbilidad , Femenino , Alemania/epidemiología , Humanos , Incidencia , Masculino , Visita a Consultorio Médico/estadística & datos numéricos , Factores de Riesgo , Distribución por Sexo , Análisis Espacio-Temporal , Evaluación de Síntomas/estadística & datos numéricos , Adulto JovenRESUMEN
In patients with prostate carcinoma as well as in some other cancer types, the reduction of testosterone levels is desired because the hormone stimulates cancer cell growth. One molecular target for this goal is the inhibition of 17ß-hydroxysteroid dehydrogenase type 3 (17ßHSD3), which produces testosterone from its direct precursor androstenedione. Recent research in this field is trying to harness photopharmacological properties of certain compounds so that the inhibitory effect could be turned on and off by irradiation. Seven new light-switchable diazocines were investigated with regard to their inhibition of 17ßHSD3. For this purpose, transfected HEK-293 cells and isolated microsomes were treated with the substrate and the potential inhibitors with and without irradiation for an incubation period of 3 or 5 h. The amount of generated testosterone was measured by UHPLC and compared between samples and control as well as between irradiated and non-irradiated samples. There was no significant difference between samples with and without irradiation. However, four of the seven diazocines led to a significantly lower testosterone production both in cell and in microsome assays. In some of the irradiated samples, a partial destruction of the diazocines was observed, indicated by an additional UHPLC peak. However, the influence on the inhibition is negligible, because the majority of the substance remained intact. In conclusion, new inhibitors of 17ßHSD3 have been found, but so far without the feature of a light switch, since the configurational alteration of the diazocines by irradiation did not lead to a change in bioactivity. Further modification might help to find a light-switching molecule that inhibits only in one configuration.
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Neoplasias de la Próstata , Testosterona , Masculino , Humanos , Testosterona/metabolismo , Células HEK293 , Neoplasias de la Próstata/metabolismo , 17-Hidroxiesteroide Deshidrogenasas/metabolismo , Androstenodiona/metabolismo , Androstenodiona/uso terapéuticoRESUMEN
Healthy persons exhibit relatively small temporal and spatial gait variability when walking unimpeded. In contrast, patients with a sensory deficit (e.g., polyneuropathy) show an increased gait variability that depends on speed and is associated with an increased fall risk. The purpose of this study was to investigate the role of vision in gait stabilization by determining the effects of withdrawing visual information (eyes closed) on gait variability at different locomotion speeds. Ten healthy subjects (32.2 ± 7.9 years, 5 women) walked on a treadmill for 5-min periods at their preferred walking speed and at 20, 40, 70, and 80 % of maximal walking speed during the conditions of walking with eyes open (EO) and with eyes closed (EC). The coefficient of variation (CV) and fractal dimension (α) of the fluctuations in stride time, stride length, and base width were computed and analyzed. Withdrawing visual information increased the base width CV for all walking velocities (p < 0.001). The effects of absent visual information on CV and α of stride time and stride length were most pronounced during slow locomotion (p < 0.001) and declined during fast walking speeds. The results indicate that visual feedback control is used to stabilize the medio-lateral (i.e., base width) gait parameters at all speed sections. In contrast, sensory feedback control in the fore-aft direction (i.e., stride time and stride length) depends on speed. Sensory feedback contributes most to fore-aft gait stabilization during slow locomotion, whereas passive biomechanical mechanisms and an automated central pattern generation appear to control fast locomotion.
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Retroalimentación Sensorial/fisiología , Marcha/fisiología , Caminata/fisiología , Adulto , Análisis de Varianza , Prueba de Esfuerzo , Femenino , Humanos , Masculino , Análisis de Regresión , Factores de Tiempo , Adulto JovenRESUMEN
Toxicity tests evaluated chronic and sublethal effects of fog oil (FO) on a freshwater endangered fish. FO is released during military training as an obscurant smoke that can drift into aquatic habitats. Fountain darters, Etheostoma fonticola, of four distinct life stages were exposed under laboratory conditions to three forms of FO. FO was vaporized into smoke and allowed to settle onto water, violently agitated with water, and dosed onto water followed by photo-oxidization by ultraviolet irradiation. Single smoke exposures of spawning adult fish did not affect egg production, egg viability, or adult fish survival in 21-day tests. Multiple daily smoke exposures induced mortality after 5 days for larvae fish. Larvae and juvenile fish were more sensitive than eggs in 96-h lethal concentration (LC50) tests with FOwater mixtures and photo-oxidized FO. Water-soluble FO components photo-modified by ultraviolet radiation were the most toxic, thus indicating the value of examining weathering and aging of chemicals for the best determination of environmental impact.