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Nanocomposite materials consist of nanometer-sized quantum objects such as atoms, molecules, voids or nanoparticles embedded in a host material. These quantum objects can be exploited as a super-structure, which can be designed to create material properties targeted for specific applications. For electromagnetism, such targeted properties include field enhancements around the bandgap of a semiconductor used for solar cells, directional decay in topological insulators, high kinetic inductance in superconducting circuits, and many more. Despite very different application areas, all of these properties are united by the common aim of exploiting collective interaction effects between quantum objects. The literature on the topic spreads over very many different disciplines and scientific communities. In this review, we present a cross-disciplinary overview of different approaches for the creation, analysis and theoretical description of nanocomposites with applications related to electromagnetic properties.
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AIM: We aimed to determine stillbirth, preterm birth, perinatal complications, and the developmental outcome of children born preterm during the COVID-19 pandemic in Germany. METHODS: National data from the perinatal survey of preterm and term infants born in 2017-2020 between 22 March and 31 December were evaluated. Neurodevelopment of preterm infants at 2 years corrected age was tested with the Parent Report of Children's Abilities-Revised questionnaire and by clinical testing with Bayley scales, either before or during the COVID-19 pandemic. Statistical significance was calculated using a Pearson's chi-square-independence test and a linear regression model. RESULTS: In 2020, there was an increase of stillbirths of 0.02% (p = 0.01) and a decrease in preterm births by 0.38% (p < 0.001). No changes were found in a representative subgroup of infants with regard to neurodevelopmental scores (mental developmental index and psychomotor developmental index) or in parent survey data (non-verbal cognition scale and language development scale). CONCLUSION: Increasing rates of stillbirths and decreasing preterm births in Germany were observed. Existing networks might stabilise neurodevelopment of preterm infants during the COVID-19 pandemic.
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COVID-19 , Nacimiento Prematuro , Lactante , Embarazo , Femenino , Niño , Recién Nacido , Humanos , Recien Nacido Prematuro , Nacimiento Prematuro/epidemiología , Desarrollo Infantil , Mortinato/epidemiología , Pandemias , COVID-19/epidemiologíaRESUMEN
Children with cancer require adequate nutritional support to prevent malnutrition. This study investigated the impact of chemotherapy on anthropometrical status and body composition during the first six months of treatment. Anthropometrical status and body composition were measured at diagnosis, utilizing standardized protocols and validated S10 InBody bio-electrical impedance (BIA) measurements and compared to subsequent consecutive monthly follow-up measurements to plot changes over time during the first six months. Statistical significance was defined as p < 0.05. Forty-three newly diagnosed children (median age 4 years, IQR: 2.0-7.6; male-female ratio 1:0.9; 53% haematological malignancies and 47% solid tumors) were included. Prevalence of malnutrition varied, with under-nutrition 14% (mid-upper arm circumference (MUAC)/body mass index (BMI)), over-nutrition 9.3% (BMI) and stunting 7% at diagnosis. MUAC (14%) identified fewer participants with underlying muscle store depletion than BIA (41.8%). Chemotherapy exposure acutely exacerbated existing nutritional depletion during the first two months after diagnosis for all variables except fat mass (FM), with contrary effects on cancer type. Haematological malignancies had rapid increases in weight, BMI and FM. All patients had an acute loss of skeletal muscle mass. Nutritional improvement experienced by all cancer types during month two to three of treatment resulted in catch-up growth, with a significant increase in weight (chi2=40.43, p < 0.001), height (chi2=53.79, p < 0.001), BMI (chi2=16.32, p < 0.005), fat free mass (chi2=23.69, p < 0.003) and skeletal muscle mass (chi2=24.19, p < 0.001) after six months. Monthly nutritional assessments, including advanced body composition measurements, are essential to provide timely nutritional interventions to overcome the acute decline in nutritional reserves observed during the first two months of chemotherapy exposure.
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Neoplasias Hematológicas , Desnutrición , Neoplasias , Humanos , Masculino , Niño , Femenino , Preescolar , Antropometría/métodos , Índice de Masa Corporal , Estado Nutricional , Composición Corporal , Desnutrición/epidemiología , Neoplasias/tratamiento farmacológico , Neoplasias Hematológicas/tratamiento farmacológicoRESUMEN
BACKGROUND: Chronic pain is a common non-motor symptom in patients with Parkinson's disease (PD). AIM: To facilitate the diagnosis of pain in PD, we developed a new classification system the Parkinson's disease pain classification system (PD-PCS) and translated the corresponding validated questionnaire into German. METHODS: A causal relationship of the respective pain syndrome with PD can be determined by four questions before assigning it hierarchically into one of three pain categories (neuropathic, nociceptive and nociplastic). RESULTS: In the initial validation study 77% of the patients (122/159) had PD-associated pain comprising 87 (55%) with nociceptive, 36 (22%) with nociplastic and 24 (16%) with neuropathic pain. The study revealed a high validity of the questionnaire and a moderate intrarater and interrater reliability. The questionnaire has been adapted into German and employed in 30 patients. DISCUSSION: The PD-PCS questionnaire is a valid and reliable tool to determine the relationship of a pain syndrome with PD before classifying it according to the underlying category, facilitating further diagnostics and treatment.
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Neuralgia , Enfermedad de Parkinson , Humanos , Neuralgia/complicaciones , Neuralgia/diagnóstico , Neuralgia/terapia , Dimensión del Dolor , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico , Reproducibilidad de los Resultados , Encuestas y CuestionariosRESUMEN
OBJECTIVES: For many years, tumor development has been viewed as a cell-autonomous process; however, today we know that the tumor microenvironment (TME) and especially cancer-associated fibroblasts (CAFs) significantly contribute to tumor progression. Caveolin-1 (Cav-1) is a scaffolding protein which is involved in several cancer-associated processes as important component of the caveolae. Our goal was to shed light on the expression of the two different isoforms of Cav-1 in normal fibroblasts (NFs) and CAFs of patients with oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Fibroblasts from normal mucosa and CAFs were isolated and propagated in vitro. Gene expression of the different Cav-1 isoforms was assessed via quantitative real-time PCR (qPCR) and supplemented by protein expression analysis. RESULTS: We could show that the Cav-1ß isoform is more highly expressed in NFs and CAFs compared to Cav-1α. Furthermore, the different Cav-1 isoforms tended to be differently expressed in different tumor stages. However, this trend could not be seen consistently, which is in line with the ambiguous role of Cav-1 in tumor progression described in literature. Western blotting furthermore revealed that NFs and CAFs might differ in the oligomerization profile of the Cav-1 protein. CONCLUSION: These differences in expression of Cav-1 between NFs and CAFs of patients with OSCC confirm that the protein might play a role in tumor progression and is of interest for further analyses. CLINICAL RELEVANCE: Our findings support a possible role of the two isoforms of Cav-1 in the malignant transformation of OSCC.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Caveolina 1 , Línea Celular Tumoral , Fibroblastos , Humanos , Isoformas de Proteínas , Carcinoma de Células Escamosas de Cabeza y Cuello , Microambiente TumoralRESUMEN
Successful vertical HIV transmission prevention programmes (VTP) have resulted in an expanding population of HIV-exposed uninfected (HEU) infants whose growth, health and neurodevelopmental outcomes could have consequences for future resource allocation. We compared neurodevelopmental and behavioural outcomes in a prospective cohort of 2-3 year old HEU and HIV-unexposed uninfected (HU) children.Women living with and without HIV and their infants were enrolled within three days of birth from a low-risk midwife obstetric unit in Cape Town, South Africa during 2012 and 2013, under WHO Option A VTP guidelines. HIV-uninfected children aged 30-42 months were assessed using the Bayley scales of Infant Development-Third edition (BSID) and Strengths and Difficulties questionnaire (SDQ).Thirty-two HEU and 27 HU children (mean birth weight 3048g vs 3096g) were assessed. HEU children performed as well as HU children on BSID cognitive, language and motor domains. Mean scores fell within the low average range. Mothers of HEU children reported fewer conduct problems but stunting was associated with increased total difficulties on the SDQ.HEU and HU children's performance on the BSID was similar. In this low-risk cohort, HIV exposure did not confer additional risk. Stunting was associated with increased behavioural problems irrespective of HIV exposure.
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Trastornos de la Conducta Infantil/etiología , Desarrollo Infantil/fisiología , Infecciones por VIH/complicaciones , Salud del Lactante/estadística & datos numéricos , Trastornos del Neurodesarrollo/epidemiología , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Efectos Tardíos de la Exposición Prenatal/epidemiología , Fármacos Anti-VIH/uso terapéutico , Lactancia Materna , Trastornos de la Conducta Infantil/psicología , Desarrollo Infantil/efectos de los fármacos , Preescolar , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Lactante , Transmisión Vertical de Enfermedad Infecciosa , Masculino , Madres , Trastornos del Neurodesarrollo/etiología , Pruebas Neuropsicológicas , Embarazo , Complicaciones Infecciosas del Embarazo/virología , Efectos Tardíos de la Exposición Prenatal/virología , Estudios Prospectivos , Sudáfrica/epidemiología , Resultado del TratamientoRESUMEN
Reliable environmental cues, such as photoperiod, act as initial predictive cues that allow birds to time reproduction to match peak food abundance for their offspring. More variable local cues, like temperature, may, however, provide more precise information about the timing of food abundance. Non-migratory birds, in particular, should be sensitive to temperature cues and use them to modulate their reproductive timing. We conducted two experiments to examine the effect of temperature on reproductive condition (gonad size and circulating androgen levels) in non-migratory black-capped chickadees (Poecile atricapillus). First, we exposed groups of birds in outdoor aviaries to three different over-winter temperature treatments and assessed gonad size in the spring. Second, we manipulated temperature in environmental chambers under photostimulatory and non-photostimulatory photoperiodic conditions and assessed gonad size and circulating testosterone levels. Temperature had no independent effect on gonad size or testosterone levels, but when photostimulated birds exposed to warmer conditions became reproductively ready earlier than birds experiencing cooler conditions. We conclude that temperature acts as a supplementary cue that modulates the photoperiod-driven timing of reproduction.
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Aves , Reproducción/fisiología , Animales , Femenino , Masculino , Estaciones del Año , TemperaturaRESUMEN
We present a hybrid microintegrated diode laser module developed for iodine spectroscopy on board a sounding rocket. The laser module is based on a master-oscillator-power-amplifier concept: an extended cavity diode laser serves as the master oscillator, and a ridge-waveguide semiconductor optical amplifier provides the power boost. The module's form factor and mass correspond to 12.5×7.5×2.3cm3 and 750 g, respectively. With an electrical power of 3.75 W supplied to the module, 570 mW of optical power is provided out of a polarization maintaining optical fiber at 1064.490 nm with a technical linewidth of 13 kHz (55 kHz) at a 1 ms (10 ms) time scale. The laser module has successfully passed vibration tests at a level of 8.8g R M S . A nominally identical module has recently been used to demonstrate, for the first time, precision iodine spectroscopy in space.
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BACKGROUND: The results obtained from previous trials regarding the effects of vitamin D supplementation on muscle strength and mobility in postmenopausal women have been inconsistent. This systematic review and meta-analysis of randomised controlled trials (RCTs) aimed to investigate the effect of vitamin D supplementation on muscle strength and mobility in postmenopausal women. METHODS: A comprehensive search on EMBASE, PubMed, MEDLINE and SCOPUS was performed to identify relevant articles published up to 28 March 2019. RCTs published in English measuring the effect of all forms and doses of vitamin D supplementation with or without calcium on muscle strength and mobility outcomes in postmenopausal women were included. RESULTS: In total, 29 eligible studies were included in the systematic review. The pooled findings using a random effects model showed that vitamin D supplementation insignificantly increased hand grip strength (HGS) as the measurement of muscle strength (MD = 0.656; 95% confidence interval = -0.037 to 1.350, P = 0.06). However, it did not affect timed-up-and-go (TUG) as the measurement of mobility (MD = 0.118; 95% confidence interval = -0.655 to 0.892, P = 0.76). The subgroup analyses showed that vitamin D supplementation improved HGS with respect to dosages >1000 IU day-1 (P = 0.016), a treatment duration of 3 months (P Ë 0.001) and subjects with baseline vitamin D <30 ng mL-1 (P = 0.033). CONCLUSIONS: The present review demonstrates that vitamin D supplementation resulted in small but nonsignificant improvements in muscle strength compared to control in postmenopausal women. No significant effect was observed in mobility after vitamin D administration.
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Suplementos Dietéticos , Fuerza Muscular/efectos de los fármacos , Posmenopausia/fisiología , Vitamina D/farmacología , Vitaminas/farmacología , Anciano , Femenino , Fuerza de la Mano/fisiología , Humanos , Persona de Mediana Edad , Rendimiento Físico Funcional , Posmenopausia/efectos de los fármacos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
We describe the concept of a new imaging modality based on the tracking and dynamic modeling of local intensity changes (ICs) observed in conventional ultrasound images collected during a medium-temperature change. We computed the pixel-by-pixel IC from averaged B-mode images that exhibited different behaviors with varying temperature resulting from changes in the speed of sound, which consequently induce changes in the backscattered energy. Moreover, for each pixel, a first-order polynomial model was adjusted to the different temperature-dependent ICs. The representation of the polynomial angular parameter in 2D pixel space was used to obtain a parametric image. The results obtained by simulations and with real B-mode images indicated that this new ultrasound imaging modality was able to enhance the contrast and highlight structures that were poorly visible or even undetected in conventional images. A temperature change of 3°C was found to be sufficient to generate appropriate images with the proposed method. In addition, if a temperature change of 6°C was considered, the thermal dose, measured as the cumulative number of equivalent minutes at 43°C (CEM43°C), was 2.4 CEM43°C, which is a value that is considered safe according to the literature. We provide a proof-of-concept of a new imaging modality that opens new opportunities for the enhancement of ultrasound images and consequently contributes to improvements in ultrasound-based diagnoses. Our approach is based on images returned by commercial ultrasound scanners. Therefore, it can be implemented in any ultrasound system and is independent of specific ultrasound hardware and software data acquisition characteristics.
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Aumento de la Imagen/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Temperatura , Ultrasonografía/métodos , Algoritmos , Animales , Simulación por Computador , Estudios de Factibilidad , Modelos Animales , Modelos Estadísticos , PorcinosRESUMEN
BACKGROUND AND AIM: Cardiovascular disease (CVD) is likely to increase in incidence. Foods with cardioprotective functions, e.g. specific functional food, could reduce CVD risk factors and hence CVD incidence. Little is known about industrially modified foods with cardioprotective functions. METHODS AND RESULTS: In a large German sample (n = 1007), attitudes of consumers in Germany towards industrially produced cardioprotective food were assessed using Cluster analyses. Consumers were contacted via telephone and interviewed using questionnaires. Overall, about 25% knew about industrially produced food with cardioprotective function. Our analysis revealed a small but determined group of consumers who think very skeptical about cardioprotective products, but we also identified a favorable group. These two groups only differed in age, with the skeptical group being ten years older. CONCLUSIONS: The rising number of industrially modified products with potential cardioprotective benefit is met by skepticism and a lack of knowledge by German costumers. If large scale studies show health benefits of these products, these will need to be better communicated to German customers in order to address possible doubts or concerns and to encourage healthy eating habits in consumer eating behavior.
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Enfermedades Cardiovasculares/prevención & control , Comportamiento del Consumidor , Dieta Saludable , Conducta Alimentaria , Industria de Procesamiento de Alimentos , Alimentos Funcionales , Conocimientos, Actitudes y Práctica en Salud , Conducta de Reducción del Riesgo , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/psicología , Femenino , Alemania/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Factores Protectores , Factores de Riesgo , Adulto JovenRESUMEN
Recently two emerging areas of research, attosecond and nanoscale physics, have started to come together. Attosecond physics deals with phenomena occurring when ultrashort laser pulses, with duration on the femto- and sub-femtosecond time scales, interact with atoms, molecules or solids. The laser-induced electron dynamics occurs natively on a timescale down to a few hundred or even tens of attoseconds (1 attosecond = 1 as = 10-18 s), which is comparable with the optical field. For comparison, the revolution of an electron on a 1s orbital of a hydrogen atom is â¼152 as. On the other hand, the second branch involves the manipulation and engineering of mesoscopic systems, such as solids, metals and dielectrics, with nanometric precision. Although nano-engineering is a vast and well-established research field on its own, the merger with intense laser physics is relatively recent. In this report on progress we present a comprehensive experimental and theoretical overview of physics that takes place when short and intense laser pulses interact with nanosystems, such as metallic and dielectric nanostructures. In particular we elucidate how the spatially inhomogeneous laser induced fields at a nanometer scale modify the laser-driven electron dynamics. Consequently, this has important impact on pivotal processes such as above-threshold ionization and high-order harmonic generation. The deep understanding of the coupled dynamics between these spatially inhomogeneous fields and matter configures a promising way to new avenues of research and applications. Thanks to the maturity that attosecond physics has reached, together with the tremendous advance in material engineering and manipulation techniques, the age of atto-nanophysics has begun, but it is in the initial stage. We present thus some of the open questions, challenges and prospects for experimental confirmation of theoretical predictions, as well as experiments aimed at characterizing the induced fields and the unique electron dynamics initiated by them with high temporal and spatial resolution.
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Since transgenic crops expressing Bacillus thuringiensis (Bt) toxins were first released, resistance evolution leading to failure in control of pests populations has been observed in a number of species. Field resistance of the moth Busseola fusca was acknowledged 8 years after Bt maize was introduced in South Africa. Since then, field resistance of this corn borer has been observed at several locations, raising questions about the nature, distribution and dynamics of the resistance trait. Using genetic markers, our study identified four outlier loci clearly associated with resistance. In addition, genetic structure at neutral loci reflected extensive gene flow among populations. A realistically parameterised model suggests that resistance could travel in space at speed of several kilometres a year. Markers at outlier loci delineated a geographic region associated with resistance spread. This was an area of approximately 100 km radius, including the location where resistance was first reported. Controlled crosses corroborated these findings and showed significant differences of progeny survival on Bt plants depending on the origin of the resistant parent. Last, our study suggests diverse resistance mutations, which would explain the widespread occurrence of resistant larvae in Bt fields across the main area of maize production in South Africa.
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Bacillus thuringiensis , Evolución Molecular , Mariposas Nocturnas/genética , Control Biológico de Vectores , Análisis del Polimorfismo de Longitud de Fragmentos Amplificados , Animales , Productos Agrícolas , Flujo Génico , Marcadores Genéticos , Genética de Población , Modelos Genéticos , Mutación , Plantas Modificadas Genéticamente , Sudáfrica , Zea maysRESUMEN
BACKGROUND AND PURPOSE: Prolonged electrocardiogram (ECG) monitoring after ischaemic stroke increases the diagnostic yield of paroxysmal atrial fibrillation (pAF). In order to facilitate the additional workload involved in ECG analysis due to prolonged monitoring times, we investigated the effectiveness of pAF detection with an automated software algorithm (SA) in comparison to the routine staff-based analysis (RA) during standard stroke-unit care. Therefore, patients with acute ischaemic stroke or transitory ischaemic attack presenting with sinus rhythmus on the admission ECG and no history of atrial fibrillation were prospectively included. METHODS: A 24-h Holter ECG assessment was performed using either RA based on a computer-aided evaluation and subsequent review by a cardiologist or a commercially available automated SA. In the case of discordant results concerning the occurrence of pAF between the two methods, the data underwent an independent external rating. RESULTS: Of 809 prospectively enrolled patients, 580 patients fulfilled the inclusion criteria. pAF was ultimately diagnosed in 3.3% of the cohort (19 patients). SA and RA correctly diagnosed pAF in 17 patients resulting in a comparable diagnostic effectiveness of the analysis methods (sensitivity: SA 89.5% vs. RA 89.5%; specificity: SA 99.3% vs. RA 99.1%; κ, 0.686; P < 0.001; 95% confidence interval, 0.525-0.847). RA revealed clinically relevant ECG abnormalities in an additional seven patients. CONCLUSIONS: Although it should not completely replace RA, SA-based evaluation of Holter ECG reaches a high diagnostic effectiveness for the detection of pAF and can be used for a rapid and resource-saving analysis of ECG data to deal with prolonged monitoring times.
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Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico , Isquemia Encefálica/complicaciones , Accidente Cerebrovascular/complicaciones , Anciano , Anciano de 80 o más Años , Algoritmos , Automatización , Estudios de Cohortes , Electrocardiografía Ambulatoria , Femenino , Hospitalización , Humanos , Ataque Isquémico Transitorio/diagnóstico , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Bone health status is largely absent in South Africa, the main reasons being the absence and cost-effectiveness of specific screening equipment for assessing bone mineral density (BMD). Various risk factors seem to play a role, some of which can be modified to change bone health status. Urbanisation is also a public health concern. Changing nutritional, as well as social behaviour, play integral roles in the prevalence and incidence of decreased BMD. Furthermore, human immunodeficiency virus (HIV) specifically, has a negative impact on BMD and although highly active antiretroviral therapy increases the prognosis for HIV-infected individuals, BMD still seem to decrease further. Dual energy X-ray absorptiometry is considered the gold standard for BMD assessment; however, recent developments have provided more cost-effective screening methods, among which heel quantitative ultrasound appears to be the most widely used in resource limited countries such as South Africa.
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Densidad Ósea/fisiología , Huesos/fisiopatología , Infecciones por VIH/fisiopatología , Absorciometría de Fotón , Terapia Antirretroviral Altamente Activa , Composición Corporal/fisiología , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Incidencia , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Factores de Riesgo , Sudáfrica , Tomografía Computarizada por Rayos X , Ultrasonografía/métodosRESUMEN
OBJECTIVES: Recent studies focused on angiogenesis in the pathophysiology of bisphosphonate-associated osteonecrosis of the jaws (BP-ONJ) and identified geranylgeraniol (GGOH) as a feasible option for BP-ONJ therapy. This study investigated the influence of GGOH on microvessel sprouting after BP-incubation in vitro. MATERIALS AND METHODS: Ten experimental set-ups were randomly designed in an in vitro 3D-angiogenesis assay. Two groups included HUVEC cell spheroids with and without (±) GGOH substitution as controls and eight groups pairwise contained either clodronate or the nitrogen-containing bisphosphonates (N-BP) ibandronate, pamidronate, and zoledronate ± GGOH. The size of the cell spheroids including the outbranching sprouts (SpS) as well as the density (SpD) and length of the sprouts (SpL) were analyzed by a grid system after 0, 24, 48, and 72 h. RESULTS: For controls and NN-BP clodronate, no significant differences at any tested parameter and any point of measurement could be detected within the experimental set-ups ± GGOH (p each ≥0.05). For N-BP ibandronate, the experimental set-ups +GGOH showed a significantly increased SpS, SpD, and SpL after 48 and 72 h (p each ≤0.002) compared to the experimental set-ups -GGOH. For N-BPs pamidronate and zoledronate, the experimental set-ups + GGOH demonstrated a significantly increased SpS, SpD, and SpL after 24, 48, and 72 h (p each ≤0.001) compared to the experimental set-ups -GGOH. CONCLUSIONS: The strong negative influence of N-BPs on microvessel sprouting could be significantly reversed by GGOH. CLINICAL RELEVANCE: Since supportive therapeutic options for BP-ONJ are lacking, GGOH might be a promising substitute for BP-ONJ prevention and therapy.
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Osteonecrosis de los Maxilares Asociada a Difosfonatos/tratamiento farmacológico , Conservadores de la Densidad Ósea/efectos adversos , Conservadores de la Densidad Ósea/farmacología , Difosfonatos/efectos adversos , Difosfonatos/farmacología , Diterpenos/farmacología , Microvasos/efectos de los fármacos , Neovascularización Patológica/tratamiento farmacológico , Células Endoteliales de la Vena Umbilical Humana , Humanos , Técnicas In VitroRESUMEN
OBJECTIVE: Mutations in TPM3, encoding Tpm3.12, cause a clinically and histopathologically diverse group of myopathies characterized by muscle weakness. We report two patients with novel de novo Tpm3.12 single glutamic acid deletions at positions ΔE218 and ΔE224, resulting in a significant hypercontractile phenotype with congenital muscle stiffness, rather than weakness, and respiratory failure in one patient. METHODS: The effect of the Tpm3.12 deletions on the contractile properties in dissected patient myofibers was measured. We used quantitative in vitro motility assay to measure Ca(2+) sensitivity of thin filaments reconstituted with recombinant Tpm3.12 ΔE218 and ΔE224. RESULTS: Contractility studies on permeabilized myofibers demonstrated reduced maximal active tension from both patients with increased Ca(2+) sensitivity and altered cross-bridge cycling kinetics in ΔE224 fibers. In vitro motility studies showed a two-fold increase in Ca(2+) sensitivity of the fraction of filaments motile and the filament sliding velocity concentrations for both mutations. INTERPRETATION: These data indicate that Tpm3.12 deletions ΔE218 and ΔE224 result in increased Ca(2+) sensitivity of the troponin-tropomyosin complex, resulting in abnormally active interaction of the actin and myosin complex. Both mutations are located in the charged motifs of the actin-binding residues of tropomyosin 3, thus disrupting the electrostatic interactions that facilitate accurate tropomyosin binding with actin necessary to prevent the on-state. The mutations destabilize the off-state and result in excessively sensitized excitation-contraction coupling of the contractile apparatus. This work expands the phenotypic spectrum of TPM3-related disease and provides insights into the pathophysiological mechanisms of the actin-tropomyosin complex.
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Contracción Muscular , Fibras Musculares Esqueléticas/patología , Enfermedades Musculares/genética , Tropomiosina/genética , Preescolar , Exoma , Femenino , Humanos , Masculino , Enfermedades Musculares/patología , Enfermedades Musculares/fisiopatología , Mutación , Fenotipo , Insuficiencia Respiratoria , Eliminación de SecuenciaRESUMEN
Malignant pleural mesotheliomas (MPM) are very aggressive tumors, which originate from the mesothelial cells of the pleural surface. The main risk factor associated with MPM is exposure to asbestos. The latency period between asbestos exposure and MPM can be 30-60 years. Clinical symptoms and signs are often nonspecifc. The diagnosis of MPM requires an adequate tissue specimen for pathological examination, and video assisted thoracoscopic surgey (VATS) is associated with the highest diagnostic yield. MPM are histologically classified into epitheloid, sacromatoid and biphasic (mixed) sub-types. Accurate staging with invasive tests, if needed, is an important step before an interdisciplinary team can decide on an optimal (multi-modal) treatment approach. A multi-modal treatment approach (surgery, radiation oncology and chemotherapy) is superior to all approaches relying only on a single modality, if the patient qualifies for it from an oncological and functional standpoint. The goal of the surgical therapy is to achieve macroscopic complete resection. There are two competing surgical approaches and philosophies: extrapleural pneumonectomy (EPP) and radical pleurectomy (RP). Over the last years a paradigm shift from EPP to RP occurred and RP is now often the preferred surgical option.
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Mesotelioma/terapia , Neoplasias Pleurales/terapia , Biomarcadores de Tumor/análisis , Terapia Combinada , Diagnóstico Diferencial , Diagnóstico por Imagen , Estudios de Seguimiento , Humanos , Mesotelioma/diagnóstico , Mesotelioma/patología , Síndromes Paraneoplásicos/diagnóstico , Síndromes Paraneoplásicos/patología , Síndromes Paraneoplásicos/terapia , Neoplasias Pleurales/diagnóstico , Neoplasias Pleurales/patologíaRESUMEN
BACKGROUND: History, clinical presentation, lung function testing, radiographs including HRCT and nonsurgical biopsy techniques in most cases provide sufficient information for classification of interstitial lung disease (ILD). However, in a small percentage it is not possible to establish the diagnosis so that lung biopsy may be required. We analyzed under which circumstances a reduction of invasive procedures is reasonable. METHODS: Between January 1997 and December 2009 we examined 3399 specimens from 1299 patients with benign inflammatory and granulomatous diseases in whom ILD was clinically hypothesized. We compared the probability of disease according to Bayes before and after surgery which corresponds to the clinical diagnosis (a priori probability) and the final diagnosis (a posteriori probability). Additionally, procedures, operation related complications and the patients' smoking habits were documented. RESULTS: In 111 patients (8.5â%) surgical evaluation was performed (14 mediastinoscopies, 97 thoracotomies/VATS biopsies). All mediastinoscopies substantiated a epitheloid cell granulomatosis. In 30â% of all VATS procedures a prolonged air leak of more than 4 days was observed. One patient died and one had to get a new chest tube after removal. Changes of a priori/a posteriori probabilities was shown for non-smokers in Wegner's granulomatosis (0.6 vs. 2.2â%) and IPF (16.7 vs. 34.8â%), for smokers in Langerhans' cell histiocytosis (1.4 vs. 7.8â%) and IPF (16.7 vs. 33.3â%). In the majority of cases even a reduction of probability was seen. CONCLUSION: Considering complications and limited diagnostic gain, lung biopsies for diagnosis of ILD should be recommended only in selected patients.
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Biopsia/métodos , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/patología , Medicina Basada en la Evidencia , Femenino , Alemania/epidemiología , Humanos , Enfermedades Pulmonares Intersticiales/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Reproducibilidad de los Resultados , Medición de Riesgo , Sensibilidad y EspecificidadRESUMEN
The photoluminescence intensity of group III nitrides, nanowires, and heterostructures (NWHs) strongly depends on the environmental H(2) and O(2) concentration. We used this opto-chemical transducer principle for the realization of a gas detector. To make this technology prospectively available to commercial gas-monitoring applications, a large-scale laboratory setup was miniaturized. To this end the gas-sensitive NWHs were integrated with electro-optical components for optical addressing and read out within a compact and robust sensor system. This paper covers the entire realization process of the device from its conceptual draft and optical design to its fabrication and assembly. The applied approaches are verified with intermediate results of profilometric characterizations and optical performance measurements of subsystems. Finally the gas-sensing capabilities of the integrated detector are experimentally proven and optimized.