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We report on an opto-mechanical metal mirror design for highly dynamic, diffraction-limited focus shifting. Here, the mechanical geometry of the membrane is of crucial interest as it must provide sufficient optical performance to allow for diffraction limited focussing and have a high mechanical eigenfrequency to provide dynamic motions. The approach is the analytical consideration of the plate theory and provides the basis for a parameterized finite element model. By means of an finite element analysis (FEA), essential steps for the optimization of the mirror design with respect to a wide range of optical power and a high operating frequency are shown. To verify the results of the FE analysis, the deformed surface is decomposed into Zernike coefficients. An analysis of the point spread function is performed to evaluate the optical performance. For dynamic evaluation a modal and a harmonic vibration analysis are conducted. The opto-mechanical design allows a biconical deformation of the mirror surface, enabling the generation of a diffraction-limited spot diameter in the adjustment range of ±1.2 dpt. The surface shape error in this range is 53 nm. The dynamic analysis shows the first excited eigenfrequency at 21.6 kHz and a diffraction-limited operation frequency at 9.5 kHz. This paper provides an alternative design approach for highly dynamic beam oscillation in the Z direction, forming a complement to highly dynamic X-Y scanning systems.
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PURPOSE: The purpose of this study was to establish and characterize age- and gender-specific normative data of the singing voice using the voice range profile for clinical diagnostics. Furthermore, associations between the singing voice and the socioeconomic status were examined. METHODS: Singing voice profiles of 1,578 mostly untrained children aged between 7.0 and 16.11 years were analyzed. Participants had to reproduce sung tones at defined pitches, resulting in maximum and minimum fundamental frequency and sound pressure level (SPL). In addition, maximum phonation time (MPT) was measured. Percentile curves of frequency, SPL and MPT were estimated. To examine the associations of socioeconomic status, multivariate analyses adjusted for age and sex were performed. RESULTS: In boys, the mean of the highest frequency was 750.9 Hz and lowered to 397.1 Hz with increasing age. Similarly, the minimum frequency was 194.4 Hz and lowered to 91.9 Hz. In girls, the mean maximum frequency decreased from 754.9 to 725.3 Hz. The mean minimum frequency lowered from 202.4 to 175.0 Hz. For both sexes, the mean frequency range ∆f showed a constant range of roughly 24 semitones. The MPT increased with age, for boys and girls. There was neither an effect of age nor sex on SPLmin or SPLmax, ranging between 52.6 and 54.1 dBA and between 86.5 and 82.8 dBA, respectively. Socioeconomic status was not associated with the above-mentioned variables. CONCLUSION: To our knowledge, this study is the first to present large normative data on the singing voice in childhood and adolescence based on a high number of measurements. In addition, we provide percentile curves for practical application in clinic and vocal pedagogy which may be applied to distinguish between normal and pathological singing voice.
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Canto , Voz , Adolescente , Criança , Feminino , Humanos , Masculino , Fonação , Qualidade da Voz , Treinamento da VozRESUMO
Neuropsychiatric symptoms and cognitive impairment have been consistently reported in patients with hepatitis C virus (HCV) infection. Since the mechanisms behind remain to be established, the present study attempted to assess whether neuropsychological impairments in HCV-infected patients are accompanied by structural alterations in the brain. Therefore, 19 anti-HCV-antibody-positive women with mild liver disease and 16 healthy controls underwent extensive neuropsychological testing and cranial magnetic resonance imaging (MRI) examination. Nine of the patients and five controls were followed up after 6-7 years. Voxel-based morphometry and magnetization transfer imaging were utilized to study HCV-associated structural gray and white matter changes. The HCV-infected patients had significantly worse fatigue and depression scores and significantly poorer performance on attention and memory tests than controls. The patients displayed gray matter (GM) atrophy in the bilateral insula and thalamus and a profound GM volume increases in the cerebellum. Microstructural GM changes in the insula were also evident by a reduced magnetization transfer ratio. Structural white matter changes were observed along several descending and crossing fiber tracts. Follow-up at 7 years revealed increased GM atrophy in the left amygdala and left parahippocampal regions over time. We conclude that our data provide evidence for structural alterations in the brains of patients with chronic HCV infection. Disturbances of cerebellothalamocortical regions and circuits, linking cerebellar projections to the prefrontal cortex through the thalamus, underpin the emotional and cognitive dysfunction characteristically observed in these patients.
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Disfunção Cognitiva/fisiopatologia , Depressão/fisiopatologia , Fadiga/fisiopatologia , Hepacivirus/patogenicidade , Hepatite C Crônica/fisiopatologia , Adulto , Tonsila do Cerebelo/diagnóstico por imagem , Tonsila do Cerebelo/fisiopatologia , Tonsila do Cerebelo/virologia , Mapeamento Encefálico , Estudos de Casos e Controles , Cerebelo/diagnóstico por imagem , Cerebelo/fisiopatologia , Cerebelo/virologia , Disfunção Cognitiva/complicações , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/virologia , Depressão/complicações , Depressão/diagnóstico por imagem , Depressão/virologia , Fadiga/complicações , Fadiga/diagnóstico por imagem , Fadiga/virologia , Feminino , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/fisiopatologia , Substância Cinzenta/virologia , Hepacivirus/crescimento & desenvolvimento , Hepatite C Crônica/complicações , Hepatite C Crônica/diagnóstico por imagem , Hepatite C Crônica/virologia , Hipocampo/diagnóstico por imagem , Hipocampo/fisiopatologia , Hipocampo/virologia , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Neuroimagem , Testes Neuropsicológicos , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiopatologia , Córtex Pré-Frontal/virologia , Tálamo/diagnóstico por imagem , Tálamo/fisiopatologia , Tálamo/virologia , Substância Branca/diagnóstico por imagem , Substância Branca/fisiopatologia , Substância Branca/virologiaRESUMO
BACKGROUND: Previous studies have already reported associations of media consumption and/or physical activity with school achievement. However, longitudinal studies investigating independent effects of physical activity and media consumption on school performance are sparse. The present study fills this research gap and, furthermore, assesses relationships of the type of secondary school with media consumption and physical activity. METHODS: The consumption of screen-based media (TV/video, game console, PC/internet, and mobile phone) and leisure physical activity (organized and non-organized) of 10 - to 17-year old adolescents participating in the LIFE Child study in Germany were related to their school grades in two major school subjects (Mathematics and German) and in Physical Education. In addition to a cross-sectional analysis at baseline (N = 850), a longitudinal analysis (N = 512) investigated the independent effects of these activities on the school grades achieved 12 months later. All associations were adjusted for age, gender, socio-economic status, year of data assessment, body-mass-index, and school grades at baseline. A further analysis investigated differences in the consumption of screen-based media and physical activity as a function of the type of secondary school (highest vs. lower secondary school). RESULTS: Adolescents of lower secondary schools reported a significantly higher consumption of TV/video and game consoles than adolescents attending the highest secondary school. Independently of the type of school, a better school performance in Mathematics was predicted by a lower consumption of computers/internet, and a better performance in Physical Education was predicted by a lower consumption of TV/video and a higher frequency of non-organized physical activity. However, the association between non-organized physical activity and subsequent grades in Physical Education was significant in girls only. CONCLUSION: The present results suggest that media consumption has a negative effect on school achievement, whereas physical activity has a positive effect, which, however, is restricted to the subject Physical Education. Future studies might explore the relationship between media consumption and school career, for example, the choice or change of the secondary school type, in more detail. TRIAL REGISTRATION: LIFE Child study: ClinicalTrials.gov, clinical trial number NCT02550236.
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Desempenho Acadêmico/estatística & dados numéricos , Exercício Físico , Instituições Acadêmicas/estatística & dados numéricos , Tempo de Tela , Adolescente , Criança , Estudos Transversais , Feminino , Alemanha , Humanos , Estudos Longitudinais , MasculinoRESUMO
Few studies have investigated placebo and nocebo effects in a human sexuality context. Studying placebo and nocebo responses in this context may provide insight into their potential to modulate sexual drive and function. To examine such effects in sexual medicine, 48 healthy, male heterosexual participants were divided into four groups. Each group received instruction to expect stimulating effects, no effect, or an inhibitory effect on sexual functions. Only one group received the dopamine agonist cabergoline; all other groups received placebo or nocebo. Modulations in sexual experience were examined through an established experimental paradigm of sexual arousal and masturbation-induced orgasm during erotic film sequences with instruction to induce placebo or nocebo effects. Endocrine data, appetitive, consummatory, and refractory sexual behavior parameters were assessed using the Arizona Sexual Experience Scale (ASEX) and the Acute Sexual Experience Scale (ASES). Results showed increased levels of sexual function after administration of cabergoline with significant effects for several parameters. Placebo effects were induced only to a small degree. No negative effects on sexual parameters in the nocebo condition were noted. This paradigm could induce only small placebo and nocebo effects. This supports the view that healthy male sexual function seems relatively resistant to negative external influences.
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Efeito Nocebo , Efeito Placebo , Comportamento Sexual , Adulto , Humanos , Libido , Masculino , OrgasmoRESUMO
BACKGROUND: Current models of obsessive compulsive disorder (OCD) propose abnormalities of cortico-striatal circuits that involve the orbitofrontal cortex, anterior cingulate cortex, thalamus and the striatum. Nevertheless, during the last years, results of morphometric studies were contradictory. Since fully automated whole-brain voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) are used to assess structural changes in OCD patients, increased consistent evidence has been reported that brain abnormalities are not limited exclusively to the "affective" orbitofronto-striatal circuit. Moreover, several studies conducted using a symptom dimensional approach demonstrated that different symptoms are mediated by distinct neural systems. METHOD: We investigated structural brain abnormalities in 14 carefully selected adult (≥18 years), male and unmedicated patients with OCD - separately for obsession and compulsion scores (Y-BOCS) - compared to 20 healthy controls as reflected according to white matter changes by fractional anisotropy and apparent diffusion coefficient. Moreover, this is the first study in OCD patients, using magnetization transfer imaging (MTI). This method is said to be more sensitive to subtle structural brain changes than conventional volumetric imaging. RESULTS: In our study, we show a positive correlation between MTR and Y-BOCS obsession scores with an increased integrity of tissue structure in the parietal cortex, including myelination and axonal density reflected by the magnetization transfer ratio (MTR) which was used for the first time in our study. Furthermore, Y-BOCS scores for compulsions correlated negatively with ADC-maps in the left nucleus lentiformis and the cingulum. CONCLUSION: The results support the hypothesis that OCD is a heterogeneous disorder with distinct neural correlates across symptom dimensions and call for a substantial revision of such a model that takes into account the heterogeneity of the disorder.
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Encéfalo/patologia , Imagem de Tensor de Difusão/métodos , Imageamento por Ressonância Magnética/métodos , Transtorno Obsessivo-Compulsivo/patologia , Adulto , Idoso , Anisotropia , Mapeamento Encefálico/métodos , Giro do Cíngulo , Humanos , Masculino , Pessoa de Meia-Idade , Lobo Parietal , Córtex Pré-Frontal , Tálamo , Adulto JovemRESUMO
BACKGROUND: Despite strong evidence that the pathophysiology of Tourette syndrome (TS) involves structural and functional disturbances of the basal ganglia and cortical frontal areas, findings from in vivo imaging studies have provided conflicting results. In this study we used whole brain diffusion tensor imaging (DTI) to investigate the microstructural integrity of white matter pathways and brain tissue in 19 unmedicated, adult, male patients with TS "only" (without comorbid psychiatric disorders) and 20 age- and sex-matched control subjects. RESULTS: Compared to normal controls, TS patients showed a decrease in the fractional anisotropy index (FA) bilaterally in the medial frontal gyrus, the pars opercularis of the left inferior frontal gyrus, the middle occipital gyrus, the right cingulate gyrus, and the medial premotor cortex. Increased apparent diffusion coefficient (ADC) maps were detected in the left cingulate gyrus, prefrontal areas, left precentral gyrus, and left putamen. There was a negative correlation between tic severity and FA values in the left superior frontal gyrus, medial frontal gyrus bilaterally, cingulate gyrus bilaterally, and ventral posterior lateral nucleus of the right thalamus, and a positive correlation in the body of the corpus callosum, left thalamus, right superior temporal gyrus, and left parahippocampal gyrus. There was also a positive correlation between regional ADC values and tic severity in the left cingulate gyrus, putamen bilaterally, medial frontal gyrus bilaterally, left precentral gyrus, and ventral anterior nucleus of the left thalamus. CONCLUSIONS: Our results confirm prior studies suggesting that tics are caused by alterations in prefrontal areas, thalamus and putamen, while changes in the cingulate gyrus seem to reflect secondary compensatory mechanisms. Due to the study design, influences from comorbidities, gender, medication and age can be excluded.
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Giro do Cíngulo/patologia , Córtex Pré-Frontal/patologia , Putamen/patologia , Tálamo/patologia , Tiques/patologia , Síndrome de Tourette/patologia , Adaptação Fisiológica , Adolescente , Imagem de Tensor de Difusão , Feminino , Giro do Cíngulo/fisiopatologia , Humanos , Masculino , Córtex Pré-Frontal/fisiopatologia , Putamen/fisiopatologia , Tálamo/fisiopatologia , Tiques/fisiopatologia , Síndrome de Tourette/fisiopatologia , Adulto JovemRESUMO
BACKGROUND: Idiopathic cervical dystonia is characterized by involuntary spasms, tremors or jerks. It is not restricted to a disturbance in the basal ganglia system because non-conventional voxel-based MRI morphometry (VBM) and diffusion tensor imaging (DTI) have detected numerous regional changes in the brains of patients.In this study scans of 24 patients with cervical dystonia and 24 age-and sex-matched controls were analysed using VBM, DTI and magnetization transfer imaging (MTI) using a voxel-based approach and a region-of-interest analysis. Results were correlated with UDRS, TWSTRS and disease duration. RESULTS: We found structural alterations in the basal ganglia; thalamus; motor cortex; premotor cortex; frontal, temporal and parietal cortices; visual system; cerebellum and brainstem of the patients with dystonia. CONCLUSIONS: Cervical dystonia is a multisystem disease involving several networks such as the motor, sensory and visual systems.
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Encéfalo/patologia , Torcicolo/patologia , Imagem de Tensor de Difusão , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-IdadeRESUMO
Optical parametric amplifiers (OPAs) have the reputation of being average power scalable due to the instantaneous nature of the parametric process (zero quantum defect). This Letter reveals serious challenges originating from thermal load in the nonlinear crystal caused by absorption. We investigate these thermal effects in high average power OPAs based on beta barium borate. Absorption of both pump and idler waves is identified to contribute significantly to heating of the nonlinear crystal. A temperature increase of up to 148 K with respect to the environment is observed and mechanical tensile stress up to 40 MPa is found, indicating a high risk of crystal fracture under such conditions. By restricting the idler to a wavelength range far from absorption bands and removing the crystal coating we reduce the peak temperature and the resulting temperature gradient significantly. Guidelines for further power scaling of OPAs and other nonlinear devices are given.
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BACKGROUND: Besides the defining involvement of upper and lower motor neurons, the involvement of extramotor structures has been increasingly acknowledged in amyotrophic lateral sclerosis (ALS). METHODS: Here we investigated a group of 14 mildly to moderately affected ALS patients and 14 age-matched healthy control participants using cortical thickness analysis. Cortical thickness was determined from high resolution 3D T1 magnetic resonance images and involved semiautomatic segmentation in grey and white matter, cortical alignment and determination of thickness using the Laplace method. In addition to a whole-cortex analysis a region of interest approach was applied. RESULTS: ALS patients showed regions of significant cortical thinning in the pre- and postcentral gyri bilaterally. Further regions of cortical thinning included superior and inferior parietal lobule, angular and supramarginal gyrus, insula, superior frontal, temporal and occipital regions, thus further substantiating extramotor involvement in ALS. A relationship between cortical thickness of the right superior frontal cortex and clinical severity (assessed by the ALS functional rating scale) was also demonstrated. CONCLUSIONS: Cortical thickness is reduced in ALS not only in motor areas but in widespread non-motor cortical areas. Cortical thickness is related to clinical severity.
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Esclerose Lateral Amiotrófica/diagnóstico , Córtex Cerebral/patologia , Imageamento por Ressonância Magnética , Adulto , Idoso , Esclerose Lateral Amiotrófica/epidemiologia , Esclerose Lateral Amiotrófica/patologia , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Tamanho do ÓrgãoRESUMO
BACKGROUND: The growing interest in the secondary use of electronic health record (EHR) data has increased the number of new data integration and data sharing infrastructures. The present work has been developed in the context of the German Medical Informatics Initiative, where 29 university hospitals agreed to the usage of the Health Level Seven Fast Healthcare Interoperability Resources (FHIR) standard for their newly established data integration centers. This standard is optimized to describe and exchange medical data but less suitable for standard statistical analysis which mostly requires tabular data formats. OBJECTIVES: The objective of this work is to establish a tool that makes FHIR data accessible for standard statistical analysis by providing means to retrieve and transform data from a FHIR server. The tool should be implemented in a programming environment known to most data analysts and offer functions with variable degrees of flexibility and automation catering to users with different levels of FHIR expertise. METHODS: We propose the fhircrackr framework, which allows downloading and flattening FHIR resources for data analysis. The framework supports different download and authentication protocols and gives the user full control over the data that is extracted from the FHIR resources and transformed into tables. We implemented it using the programming language R [1] and published it under the GPL-3 open source license. RESULTS: The framework was successfully applied to both publicly available test data and real-world data from several ongoing studies. While the processing of larger real-world data sets puts a considerable burden on computation time and memory consumption, those challenges can be attenuated with a number of suitable measures like parallelization and temporary storage mechanisms. CONCLUSION: The fhircrackr R package provides an open source solution within an environment that is familiar to most data scientists and helps overcome the practical challenges that still hamper the usage of EHR data for research.
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Registros Eletrônicos de Saúde , Informática Médica , Humanos , Linguagens de Programação , Disseminação de Informação , Nível Sete de Saúde , Atenção à SaúdeRESUMO
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder, caused by progressive loss of motor neurons. Changes are widespread in the subcortical white matter in ALS. Diffusion tensor imaging (DTI) detects pathological changes in white matter fibres in vivo, based on alterations in the degree (diffusivity, ADC) and directedness (fractional anisotropy, FA) of proton movement. METHODS: 24 patients with ALS and 24 age-matched controls received 1.5T DTI. FA and ADC were analyzed using statistical parametric mapping. In 15 of the 24 ALS patients, a second DTI was obtained after 6 months. RESULTS: Decreased FA in the corticospinal tract (CST) and frontal areas confirm existing results. With a direct comparison of baseline and follow-up dataset, the progression of upper motor neuron degeneration, reflected in FA decrease, could be captured along the CST and in frontal areas. The involvement of cerebellum in the pathology of ALS, as suspected from functional MRI studies, could be confirmed by a reduced FA (culmen, declive). These structural changes correlated well with disease duration, ALSFRS-R, and physical and executive functions. CONCLUSION: DTI detects changes that are regarded as prominent features of ALS and thus, shows promise in its function as a biomarker. Using the technique herein, we could demonstrate DTI changes at follow-up which correlated well with clinical progression.
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Esclerose Lateral Amiotrófica/patologia , Esclerose Lateral Amiotrófica/fisiopatologia , Mapeamento Encefálico , Córtex Cerebral/patologia , Imagem de Tensor de Difusão , Tratos Piramidais/patologia , Adulto , Idoso , Análise de Variância , Estudos de Casos e Controles , Feminino , Humanos , Estudos Longitudinais , Masculino , Entrevista Psiquiátrica Padronizada , Pessoa de Meia-Idade , Testes Neuropsicológicos , Índice de Gravidade de Doença , Estatística como AssuntoRESUMO
BACKGROUND: Structural changes have been found predominantly in the frontal cortex and in the striatum in children and adolescents with Gilles de la Tourette syndrome (GTS). The influence of comorbid symptomatology is unclear. Here we sought to address the question of gray matter abnormalities in GTS patients with co-morbid obsessive-compulsive disorder (OCD) and/or attention deficit hyperactivity disorder (ADHD) using voxel-based morphometry (VBM) in twenty-nine adult actually unmedicated GTS patients and twenty-five healthy control subjects. RESULTS: In GTS we detected a cluster of decreased gray matter volume in the left inferior frontal gyrus (IFG), but no regions demonstrating volume increases. By comparing subgroups of GTS with comorbid ADHD to the subgroup with comorbid OCD, we found a left-sided amygdalar volume increase. CONCLUSIONS: From our results it is suggested that the left IFG may constitute a common underlying structural correlate of GTS with co-morbid OCD/ADHD. A volume reduction in this brain region that has been previously identified as a key region in OCD and was associated with the active inhibition of attentional processes may reflect the failure to control behavior. Amygdala volume increase is discussed on the background of a linkage of this structure with ADHD symptomatology. Correlations with clinical data revealed gray matter volume changes in specific brain areas that have been described in these conditions each.
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Lobo Frontal/patologia , Lateralidade Funcional , Síndrome de Tourette/patologia , Adolescente , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/patologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Inteligência , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Transtorno Obsessivo-Compulsivo/patologia , Escalas de Graduação Psiquiátrica , Síndrome de Tourette/epidemiologia , Adulto JovemRESUMO
State-of-the-art high power Yb-doped large mode area fibers have been developed to a performance level able to reach the so-called mode instability threshold. In this contribution we will discuss the experimental results regarding the temporal evolution (build up and decay) of this effect to come closer to a comprehensive understanding of its driving mechanisms. Our investigations prove that the relevant time scale for build up and decay of mode instability is in the millisecond range and thus deliver experimental evidence of underlying thermal effects. To the best of our knowledge these are the first systematic, time resolved investigations on that topic.
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BACKGROUND: Clinical trials, epidemiological studies, clinical registries, and other prospective research projects, together with patient care services, are main sources of data in the medical research domain. They serve often as a basis for secondary research in evidence-based medicine, prediction models for disease, and its progression. This data are often neither sufficiently described nor accessible. Related models are often not accessible as a functional program tool for interested users from the health care and biomedical domains. OBJECTIVE: The interdisciplinary project Leipzig Health Atlas (LHA) was developed to close this gap. LHA is an online platform that serves as a sustainable archive providing medical data, metadata, models, and novel phenotypes from clinical trials, epidemiological studies, and other medical research projects. METHODS: Data, models, and phenotypes are described by semantically rich metadata. The platform prefers to share data and models presented in original publications but is also open for nonpublished data. LHA provides and associates unique permanent identifiers for each dataset and model. Hence, the platform can be used to share prepared, quality-assured datasets and models while they are referenced in publications. All managed data, models, and phenotypes in LHA follow the FAIR principles, with public availability or restricted access for specific user groups. RESULTS: The LHA platform is in productive mode (https://www.health-atlas.de/). It is already used by a variety of clinical trial and research groups and is becoming increasingly popular also in the biomedical community. LHA is an integral part of the forthcoming initiative building a national research data infrastructure for health in Germany.
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Estudos Prospectivos , AlemanhaRESUMO
AIMS: Patients with type 2 diabetes mellitus (T2DM) suffer from accelerated coronary artery disease. We assessed the effects of a multifactorial intervention with focus on exercise training on coronary endothelial function, vascular structure, and inflammation in serum and skeletal muscle biopsies, including mRNA expression of diabetes candidate genes. METHODS AND RESULTS: Twenty-three patients were randomized to either 4 weeks in-hospital exercise training (6 x 15 min bicycle/day, 5 days/week) and a hypocaloric diet, followed by a 5 months ambulatory program (30 min ergometer/day, 5 days/week, plus 1 h group exercise/week), or a control group. At the beginning of the study, at 4 weeks, and after 6 months changes in diameter of coronary arteries in response to acetylcholine and mean peak flow velocity were invasively measured; intramural plaques were assessed by intravascular ultrasound. Six months of intervention led to significant improvement of coronary endothelial function, whereas intramural plaque burden remained unchanged. After 4 weeks, endothelial function remained unchanged, however, lowest values for fasting glucose, HbA1c, high-sensitive C-reactive protein, total and LDL-cholesterol, and highest values for mRNA expression in skeletal muscle of p22, gp91, haem oxygenase 1, peroxisome proliferator activator receptor (PPAR) alpha and gamma were observed. There was a continuous increase for AdipoR1, AdipoR2, Glut4, interleukin-6, endothelial nitric oxide synthase, and PPARgamma-coactivator-1alpha mRNA expression in skeletal muscle. CONCLUSION: This is the first study to demonstrate improvement in coronary endothelial function by a multifactorial intervention which focused on exercise training in patients with T2DM. This coincided with improved markers of hyperglycaemia, insulin sensitivity, and inflammation both in serum and skeletal muscle biopsies.
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Doença da Artéria Coronariana/terapia , Diabetes Mellitus Tipo 2/terapia , Angiopatias Diabéticas/terapia , Endotélio Vascular/fisiopatologia , Terapia por Exercício/métodos , Biomarcadores/sangue , Glicemia/metabolismo , Peso Corporal , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/fisiopatologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Dislipidemias/terapia , Feminino , Humanos , Metabolismo dos Lipídeos , Masculino , Músculo Esquelético/metabolismo , RNA Mensageiro/metabolismo , Ultrassonografia de IntervençãoRESUMO
We report on an integrated all-glass pump combiner for ytterbium-doped high power fiber lasers. The combining of multiple pump fibers with an active double clad fiber for high power amplification was successfully achieved by splicing them to a dichromatically coated planar convex lens. The measured coupling efficiency of such a combining scheme was typically in excess of 80%, with 86.5% achieved in maximum. Theoretical analysis is discussed in order to get optimized parameters and to consider the scaling of this type of coupler to higher average powers.
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Purpose: The onset and progression of optic neuropathies like glaucoma often occurs asymmetrically between the two eyes of a patient. Interocular circumpapillary retinal nerve fiber layer thickness (cpRNFLT) differences could detect disease earlier. To apply such differences diagnostically, detailed location specific norms are necessary. Methods: Spectral-domain optical coherence tomography cpRNFLT circle scans from the population-based Leipzig Research Centre for Civilization Diseases-Adult study were selected. At each of the 768 radial scanning locations, normative interocular cpRNFLT difference distributions were calculated based on age and interocular radius difference. Results: A total of 8966 cpRNFLT scans of healthy eyes (4483 patients; 55% female; age range, 20-79 years) were selected. Global cpRNFLT average was 1.53 µm thicker in right eyes (P < 2.2 × 10-16). On 96% of the 768 locations, left minus right eye differences were significant (P < 0.05), varying between +11.6 µm (superonasal location) and -11.8 µm (nasal location). Increased age and difference in interocular scanning radii were associated with an increased mean and variance of interocular cpRNFLT difference at most retinal locations, apart from the area temporal to the inferior RNF bundle where cpRNFLT becomes more similar between eyes with age. Conclusions: We provide pointwise normative distributions of interocular cpRNFLT differences at an unprecedentedly high spatial resolution of 768 A-scans and reveal considerable location specific asymmetries as well as their associations with age and scanning radius differences between eyes. Translational Relevance: To facilitate clinical application, we implement these age- and radius-specific norms across all 768 locations in an open-source software to generate patient-specific normative color plots.
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Fibras Nervosas , Disco Óptico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Retina/diagnóstico por imagem , Células Ganglionares da Retina , Tomografia de Coerência Óptica , Adulto JovemRESUMO
BACKGROUND: Pathophysiological evidence suggests an involvement of fronto-striatal circuits in Tourette syndrome (TS). To identify TS related abnormalities in gray and white matter we used optimized voxel-based morphometry (VBM) and magnetization transfer imaging (MTI) which are more sensitive to tissue alterations than conventional MRI and provide a quantitative measure of macrostructural integrity. METHODS: Volumetric high-resolution anatomical T1-weighted MRI and MTI were acquired in 19 adult, unmedicated male TS patients without co-morbidities and 20 age- and sex-matched controls on a 1.5 Tesla neuro-optimized GE scanner. Images were pre-processed and analyzed using an optimized version of VBM in SPM2. RESULTS: Using VBM, TS patients showed significant decreases in gray matter volumes in prefrontal areas, the anterior cingulate gyrus, sensorimotor areas, left caudate nucleus and left postcentral gyrus. Decreases in white matter volumes were detected in the right inferior frontal gyrus, the left superior frontal gyrus and the anterior corpus callosum. Increases were found in the left middle frontal gyrus and left sensorimotor areas. In MTI, white matter reductions were seen in the right medial frontal gyrus, the inferior frontal gyrus bilaterally and the right cingulate gyrus. Tic severity was negatively correlated with orbitofrontal structures, the right cingulate gyrus and parts of the parietal-temporal-occipital association cortex bilaterally. CONCLUSION: Our MRI in vivo neuropathological findings using two sensitive and unbiased techniques support the hypothesis that alterations in frontostriatal circuitries underlie TS pathology. We suggest that anomalous frontal lobe association and projection fiber bundles cause disinhibition of the cingulate gyrus and abnormal basal ganglia function.
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Giro do Cíngulo/patologia , Vias Neurais/patologia , Córtex Pré-Frontal/patologia , Síndrome de Tourette/patologia , Adolescente , Adulto , Estudos de Casos e Controles , Lateralidade Funcional , Humanos , Imageamento por Ressonância Magnética , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Tamanho do Órgão , Valores de Referência , Adulto JovemRESUMO
OBJECTIVES: The aim of this study was to establish normative data concerning the speaking voice of children and adolescents for clinical diagnostics. STUDY DESIGN: Population-based mixed cross-sectional and longitudinal childhood cohort study. METHODS: Normative data measuring the speaking voice profile of 1352 male and 1274 female participants aged 6 to 17 years were collected. To evaluate the voice range, five different intensity levels as the quietest voicing speaking voice (Level I), conversational voice (Level II), classroom voice (Level III), shouting voice (Level IV), and again the quietest speaking voice (Level V) were investigated. Multivariable analyses were performed to describe the effects of body mass index, Tanner stage, and singing activity on the outcome variables. RESULTS: A clear distinction in frequencies and sound pressure levels between the five different voice levels can be found in both genders. In females the mean fundamental frequency of the conversational voice lowers from 223.3 to 205.8 Hz. In male participants it lowers from 223.3 to 102.3 Hz. The most substantial decrease in the fundamental frequency of the speaking voice in boys occurs at 13.5 years. Girls show an almost continuous decline in their fundamental frequency. Only the Tanner stage showed significant positive relationships with the grade of lowering of the fundamental frequency in both sexes. CONCLUSIONS: It was shown that the investigation of the speaking voice using predefined intensity-levels represents a feasible examination for children and adolescents. This study provides reference data on the range and age-adjusted normative values of the speaking voice.