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Future information technology demands ever-faster, low-loss quantum control. Intense light fields have facilitated milestones along this way, including the induction of novel states of matter1-3, ballistic acceleration of electrons4-7 and coherent flipping of the valley pseudospin8. These dynamics leave unique 'fingerprints', such as characteristic bandgaps or high-order harmonic radiation. The fastest and least dissipative way of switching the technologically most important quantum attribute-the spin-between two states separated by a potential barrier is to trigger an all-coherent precession. Experimental and theoretical studies with picosecond electric and magnetic fields have suggested this possibility9-11, yet observing the actual spin dynamics has remained out of reach. Here we show that terahertz electromagnetic pulses allow coherent steering of spins over a potential barrier, and we report the corresponding temporal and spectral fingerprints. This goal is achieved by coupling spins in antiferromagnetic TmFeO3 (thulium orthoferrite) with the locally enhanced terahertz electric field of custom-tailored antennas. Within their duration of one picosecond, the intense terahertz pulses abruptly change the magnetic anisotropy and trigger a large-amplitude ballistic spin motion. A characteristic phase flip, an asymmetric splitting of the collective spin resonance and a long-lived offset of the Faraday signal are hallmarks of coherent spin switching into adjacent potential minima, in agreement with numerical simulations. The switchable states can be selected by an external magnetic bias. The low dissipation and the antenna's subwavelength spatial definition could facilitate scalable spin devices operating at terahertz rates.
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Harnessing the carrier wave of light as an alternating-current bias may enable electronics at optical clock rates1. Lightwave-driven currents have been assumed to be essential for high-harmonic generation in solids2-6, charge transport in nanostructures7,8, attosecond-streaking experiments9-16 and atomic-resolution ultrafast microscopy17,18. However, in conventional semiconductors and dielectrics, the finite effective mass and ultrafast scattering of electrons limit their ballistic excursion and velocity. The Dirac-like, quasi-relativistic band structure of topological insulators19-29 may allow these constraints to be lifted and may thus open a new era of lightwave electronics. To understand the associated, complex motion of electrons, comprehensive experimental access to carrier-wave-driven currents is crucial. Here we report angle-resolved photoemission spectroscopy with subcycle time resolution that enables us to observe directly how the carrier wave of a terahertz light pulse accelerates Dirac fermions in the band structure of the topological surface state of Bi2Te3. While terahertz streaking of photoemitted electrons traces the electromagnetic field at the surface, the acceleration of Dirac states leads to a strong redistribution of electrons in momentum space. The inertia-free surface currents are protected by spin-momentum locking and reach peak densities as large as two amps per centimetre, with ballistic mean free paths of several hundreds of nanometres, opening up a realistic parameter space for all-coherent lightwave-driven electronic devices. Furthermore, our subcycle-resolution analysis of the band structure may greatly improve our understanding of electron dynamics and strong-field interaction in solids.
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The ultrafast scattering dynamics of intersubband polaritons in dispersive cavities embedding GaAs/AlGaAs quantum wells are studied directly within their band structure using a noncollinear pump-probe geometry with phase-stable midinfrared pulses. Selective excitation of the lower polariton at a frequency of â¼25 THz and at a finite in-plane momentum k_{â} leads to the emergence of a narrowband maximum in the probe reflectivity at k_{â}=0. A quantum mechanical model identifies the underlying microscopic process as stimulated coherent polariton-polariton scattering. These results mark an important milestone toward quantum control and bosonic lasing in custom-tailored polaritonic systems in the mid and far infrared.
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The Berlin Grading System assesses clinical severity of moyamoya angiopathy (MMA) by combining MRI, DSA, and cerebrovascular reserve capacity (CVRC). Our aim was to validate this grading system using [15O]H2O PET for CVRC. We retrospectively identified bilateral MMA patients who underwent [15O]H2O PET examination and were treated surgically at our department. Each hemisphere was classified using the Suzuki and Berlin Grading System. Preoperative symptoms and perioperative ischemias were collected, and a logistic regression analysis was performed. A total of 100 hemispheres in 50 MMA patients (36 women, 14 men) were included. Using the Berlin Grading System, 2 (2.8%) of 71 symptomatic hemispheres were categorized as grade I, 14 (19.7%) as grade II, and 55 (77.5%) as grade III. The 29 asymptomatic hemispheres were characterized as grade I in 7 (24.1%) hemispheres, grade II in 12 (41.4%), and grade III in 10 (34.5%) hemispheres. Berlin grades were independent factors for identifying hemispheres as symptomatic and higher grades correlated with increasing proportion of symptomatic hemispheres (p < 0.01). The Suzuki grading did not correlate with preoperative symptoms (p = 0.26). Perioperative ischemic complications occurred in 8 of 88 operated hemispheres. Overall, complications did not occur in any of the grade I hemispheres, but in 9.1% (n = 2 of 22) and 9.8% (n = 6 of 61) of grade II and III hemispheres, respectively. In this study, we validated the Berlin Grading System with the use of [15O]H2O PET for CVRC as it could stratify preoperative symptomatology. Furthermore, we highlighted its relevance for predicting perioperative ischemic complications.
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Revascularização Cerebral , Doença de Moyamoya , Masculino , Humanos , Feminino , Estudos Retrospectivos , Doença de Moyamoya/diagnóstico por imagem , Doença de Moyamoya/cirurgia , Imageamento por Ressonância Magnética , Revascularização Cerebral/efeitos adversos , Tomografia por Emissão de PósitronsRESUMO
Grasshoppers are one of the most predominant insects in the grasslands of the southern Pampas. In this region, Dichroplus elongatus, Dichroplus maculipennis, Dichroplus pratensis and Borellia bruneri are the most abundant species and have the greatest economic importance. This study aimed to assess the relationship between temporal changes in the density of these species and climate variables associated with temperature and rainfall over an 11-year study period., We monitored 22 sites in different areas of Laprida county from 2005 to 2016. A total of 25 grasshopper species were collected. The most abundant species were D. maculipennis and B. bruneri which reached the highest densities from 2008-2009 to 2010-2011. The rainfall accumulated from September (RAS) to the sampling date and the number of rainy days (RD) largely explained the density variation of B. bruneri. Besides RD and RAS, winter rainfall, rainfall accumulated from October to the sampling date, and thermal amplitude of October (TAO) influenced the density of D. maculipennis. Our results indicated that seasons with less rainfall and fewer RD favored these two species' abundance. We identified that the RD and TAO contributed significantly to variations in the density of D. elongatus. In contrast to the other two species, we recorded D. elongatus in seasons with high rainfall and high RD. A better understanding of the climate influence on the life cycle of these economically important insects may identify key factors in their population dynamics which in turn may improve management options.
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Gafanhotos , Animais , Argentina , Clima , Dinâmica Populacional , Estações do AnoRESUMO
INTRODUCTION: For an inguinal hernia repair, meshes with a continuous memory frame made it more easy to position the mesh in the preperitoneal space by anterior approach. We present a case of a sigmoid perforation caused by a fractured nitinol ring of a Rebound HRD Shield mesh. PATIENTS AND METHODS: A 29-years old sports instructor presented to the Emergency Department (ED) with a gnawing abdominal pain in the left lower quadrant. His past medical history noted an inguinal hernia repair on this side. A computed tomography scan showed a broken metal ring of the inguinal mesh perforating the sigmoid, so a laparoscopy was performed. The sigmoid was attached to the abdominal wall partially overlying the preperitoneal mesh and a part of the broken nitinol frame was found perforating the colon. RESULTS: The memory ring of the Rebound mesh is made of nitinol. An alloy well-known in vascular surgery for stenting arteries with high bending and compression forces. In this setting, fracture due to fatigue has already been described, but it is not known in abdominal wall reconstruction. Our patients groin was subject to daily bending and compression forces resulting in breakage of the nitinol ring. CONCLUSION: Particularly in young athletic patients the nitinol ring will be subject to bending forces in the groin and prone to breakage. This can have potentially severe consequences given its location near abdominal organs and neurovascular structures. In our opinion, patients should be informed about the possibility of ring breakage and doctors should consider the risk-benefits well.
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Hérnia Inguinal , Laparoscopia , Adulto , Ligas/efeitos adversos , Colo Sigmoide/diagnóstico por imagem , Colo Sigmoide/cirurgia , Hérnia Inguinal/cirurgia , Herniorrafia/efeitos adversos , Humanos , Telas Cirúrgicas/efeitos adversosRESUMO
We explore the nonlinear response of tailor-cut light-matter hybrid states in a novel regime, where both the Rabi frequency induced by a coherent driving field and the vacuum Rabi frequency set by a cavity field are comparable to the carrier frequency of light. In this previously unexplored strong-field limit of ultrastrong coupling, subcycle pump-probe and multiwave mixing nonlinearities between different polariton states violate the normal-mode approximation while ultrastrong coupling remains intact, as confirmed by our mean-field model. We expect such custom-cut nonlinearities of hybridized elementary excitations to facilitate nonclassical light sources, quantum phase transitions, or cavity chemistry with virtual photons.
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BACKGROUND AND PURPOSE: Post-hypoxic movement disorders and chronic post-hypoxic myoclonus are rare complications after cardiac arrest in adults. Our study investigates the clinical spectrum, neuroimaging results, therapy and prognosis of these debilitating post-hypoxic sequelae. METHODS: This retrospective study included 72 patients from the neurological intensive care unit at a university hospital, who were diagnosed with hypoxic-ischaemic encephalopathy after cardiac arrest between January 2007 and September 2018. Clinical records were screened for occurrence of post-hypoxic movement disorders and chronic post-hypoxic myoclonus. Affected patients were further analysed for applied neuroprognostic tests, administered therapy and treatment response, and the outcome of these movement disorders and neurological function. RESULTS: Nineteen out of 72 screened patients exhibited post-hypoxic motor symptoms. Basal ganglia injury was the most likely neuroanatomical correlate of movement disorders as indicated by T1 hyperintensities and hypometabolism of this region in magnetic resonance imaging and positron emission tomography computed tomography. Levomepromazine and intrathecal baclofen showed first promising and mostly prompt responses to control these post-hypoxic movement disorders and even hyperkinetic storms. In contrast, chronic post-hypoxic myoclonus best responded to co-application of clonazepam, levetiracetam and primidone. Remission rates of post-hypoxic movement disorders and chronic post-hypoxic myoclonus were 58% and 50%, respectively. Affected patients seemed to present a rather good recovery of cognitive functions in contrast to the often more severe physical deficits. CONCLUSIONS: Post-hypoxic movement disorders associated with pronounced basal ganglia dysfunction might be efficiently controlled by levomepromazine or intrathecal baclofen. Their occurrence might be an indicator for a more unfavourable, but often not devastating, neurological outcome.
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Lesões Encefálicas , Parada Cardíaca , Transtornos dos Movimentos , Mioclonia , Adulto , Parada Cardíaca/complicações , Humanos , Transtornos dos Movimentos/diagnóstico por imagem , Transtornos dos Movimentos/etiologia , Mioclonia/diagnóstico por imagem , Mioclonia/tratamento farmacológico , Mioclonia/etiologia , Estudos RetrospectivosRESUMO
The new ATS/ERS/ESCMID/IDSA guideline answers 22 PICO questions on the treatment of lung diseases caused by Mycobacterium avium complex (MAC), M. kansasii, M. xenopi and M. abscessus. NON-TUBERCULOUS MYCOBACTERIA (NTM) LUNG DISEASE: Especially in patients with microscopic detection of acid-fast bacteria in sputum or with cavernous disease manifestation, the start of treatment should not be delayed. Treatment should be based on species-specific resistance testing (according to the CLSI guidelines). In selected patients, adjuvant surgical resection after consultation with an expert is recommended. MAC LUNG DISEASE: Therapy is based on a regimen with at least three drugs including a macrolide (rather azithromycin than clarithromycin) and ethambutol. For patients with cavitation, with pronounced nodular bronchiectatic disease or with macrolide resistance, daily oral therapy should be expanded by parenteral amikacin or streptomycin. Liposomally encapsulated amikacin for inhalation is recommended in patients with treatment failure. Patients with nodular-bronchiectatic disease manifestation should receive oral macrolide-based therapy, which - depending on the extent - can be given 3 times a week. The recommended duration is 12 months after conversion of the sputum culture. M. KANSASII LUNG DISEASE: The triple combination of rifampicin, ethambutol and macrolide (or isoniazid) is recommended for at least 12 months. In patients with rifampicin resistance or intolerance, moxifloxacin is recommended as a replacement. M. XENOPI LUNG DISEASE: The combination of rifampicin, ethambutol and macrolide (and/or moxifloxacin) is recommended for at least 12 months after conversion of the sputum culture. For patients with cavernous disease manifestation, it is recommended to add at least parenteral amikacin and to consult experts. M. ABSCESSUS LUNG DISEASE: At least 3, in the beginning rather 4 drugs are recommended for therapy. The choice of substance should be based on a in vitro resistance test. Macrolides are the basis, but should not be counted in patients with strains with inducible macrolide resistance. Due to the lack of data, no explicit recommendations are made regarding the duration of therapy; a consultation of experts is recommended.
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Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana/efeitos dos fármacos , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Micobactérias não Tuberculosas/isolamento & purificação , Guias de Prática Clínica como Assunto , Escarro/microbiologia , Quimioterapia Combinada , Humanos , Macrolídeos/uso terapêutico , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Micobactérias não Tuberculosas/efeitos dos fármacosRESUMO
The increasing evidence has made it necessary to change international recommendations for the diagnosis and treatment of resistant tuberculosis repeatedly in the recent years. This year, the WHO has published comprehensive recommendations that take into account these developments. The current German tuberculosis guideline was published in 2017 with differing recommendations in some areas. Here the new WHO recommendations of 2020 for rapid diagnosis and therapy of resistant tuberculosis are summarized and the relevant differences are commented for Germany, Austria and Switzerland. A complete re-evaluation of the literature is currently taking place by updating the German-language AWMF 2k guidelines.
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Guias de Prática Clínica como Assunto , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Áustria , Alemanha , Humanos , Suíça , Organização Mundial da SaúdeRESUMO
OBJECTIVE: To compare long term outcome between childhood-onset Anorexia Nervosa (AN) and low-weight Avoidant/Restrictive Food Intake Disorder (ARFID) in regard to psychiatric diagnoses, social and occupational functioning. METHOD: A consecutive series of 56 children originally treated for low-weight restrictive eating disorder (ED) were followed up after a mean of 15.9 years. ARFID-diagnoses were assigned retrospectively. RESULTS: Thirty-seven patients originally had AN and 19 patients were diagnosed retrospectively with ARFID. At follow-up, in the AN-group 21.6% had a current ED, 24.3% had another psychiatric diagnosis, and 54.1% did not have any psychiatric diagnosis. In the ARFID-group, 26.3% had a current ED, 26.3% had another psychiatric diagnosis, and 47.4% had no psychiatric diagnosis. In the ARFID-group ED diagnoses at follow-up were all ARFID, whereas the AN-group showed heterogeneity. Morgan Russell Outcome Assessment Schedule indicated similar outcome in the AN- and ARFID-group. Occupational functioning did not differ significantly between the AN- and ARFID-group. DISCUSSION: The AN-group showed high rate of ED at follow up. The ARFID-group had a similar outcome to AN. In the ARFID-group, all ED-cases at follow up had ARFID, possibly indicating symptomatic stability. Low-weight ARFID should be treated as seriously as childhood onset AN.
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Anorexia Nervosa/psicologia , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Adolescente , Anorexia Nervosa/terapia , Transtornos da Alimentação e da Ingestão de Alimentos/terapia , Feminino , Seguimentos , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Estudos RetrospectivosRESUMO
Globally, millions of tons of coal fly ash (CFA) are generated per year, and the majority of this material is usually stored in stock piles or landfills, and in a long-term, it can be an environmental hazard if rainwater infiltrates the ashes. Long-term leaching studies of Brazilian ashes are scarce. The purpose of this study was to evaluate arsenic, cadmium, molybdenum, lead, and zinc leaching behavior from a Brazilian CFA by a column experiment designed to simulate field conditions: slightly acid rain considering seasonality of precipitation and temperature for a long-term leaching period (336 days). All elements were leached from CFA, except lead. Elements leaching behavior was influenced by leaching time, leaching volume, and temperature. Higher leachability of As and Cd from CFA during warm and wet season was observed. Results indicate a potential risk to soil and groundwater, since ashes are usually stored in uncovered fields on power plants vicinity.
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Cinza de Carvão/química , Monitoramento Ambiental , Metais Pesados/análise , Arsênio/análise , Arsênio/química , Brasil , Cádmio/análise , Cádmio/química , Água Subterrânea , Chumbo/análise , Chumbo/química , Molibdênio/análise , Molibdênio/química , Centrais Elétricas , Solo/química , Instalações de Eliminação de Resíduos , Zinco/análise , Zinco/químicaRESUMO
According to the World Health Organization (WHO), tuberculosis is the leading cause of death attributed to a single microbial pathogen worldwide. In addition to the large number of patients affected by tuberculosis, the emergence of Mycobacterium tuberculosis drug-resistance is complicating tuberculosis control in many high-burden countries. During the past 5 years, the global number of patients identified with multidrug-resistant tuberculosis (MDR-TB), defined as bacillary resistance at least against rifampicin and isoniazid, the two most active drugs in a treatment regimen, has increased by more than 20% annually. Today we experience a historical peak in the number of patients affected by MDR-TB. The management of MDR-TB is characterized by delayed diagnosis, uncertainty of the extent of bacillary drug-resistance, imprecise standardized drug regimens and dosages, very long duration of therapy and high frequency of adverse events which all translate into a poor prognosis for many of the affected patients. Major scientific and technological advances in recent years provide new perspectives through treatment regimens tailor-made to individual needs. Where available, such personalized treatment has major implications on the treatment outcomes of patients with MDR-TB. The challenge now is to bring these adances to those patients that need them most.
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Nosocomial pneumonia (HAP) is a frequent complication of hospital care. Most data are available on ventilator-associated pneumonia. However, infections on general wards are increasing. A central issue are infections with multidrug resistant (MDR) pathogens which are difficult to treat in the empirical setting potentially leading to inappropriate use of antimicrobial therapy.This guideline update was compiled by an interdisciplinary group on the basis of a systematic literature review. Recommendations are made according to GRADE giving guidance for the diagnosis and treatment of HAP on the basis of quality of evidence and benefit/risk ratio.This guideline has two parts. First an update on epidemiology, spectrum of pathogens and antimicrobials is provided. In the second part recommendations for the management of diagnosis and treatment are given. New recommendations with respect to imaging, diagnosis of nosocomial viral pneumonia and prolonged infusion of antibacterial drugs have been added. The statements to risk factors for infections with MDR pathogens and recommendations for monotherapy vs combination therapy have been actualised. The importance of structured deescalation concepts and limitation of treatment duration is emphasized.
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Pneumonia Associada a Assistência à Saúde/diagnóstico , Pneumonia Associada a Assistência à Saúde/terapia , Adulto , Estudos Transversais , Alemanha , Pneumonia Associada a Assistência à Saúde/epidemiologia , HumanosRESUMO
BACKGROUND: Volumetric muscle loss caused by trauma or after tumour surgery exceeds the natural regeneration capacity of skeletal muscle. Hence, the future goal of tissue engineering (TE) is the replacement and repair of lost muscle tissue by newly generating skeletal muscle combining different cell sources, such as myoblasts and mesenchymal stem cells (MSCs), within a three-dimensional matrix. Latest research showed that seeding skeletal muscle cells on aligned constructs enhance the formation of myotubes as well as cell alignment and may provide a further step towards the clinical application of engineered skeletal muscle. In this study the myogenic differentiation potential of MSCs upon co-cultivation with myoblasts and under stimulation with hepatocyte growth factor (HGF) and insulin-like growth factor-1 (IGF-1) was evaluated. We further analysed the behaviour of MSC-myoblast co-cultures in different 3D matrices. RESULTS: Primary rat myoblasts and rat MSCs were mono- and co-cultivated for 2, 7 or 14 days. The effect of different concentrations of HGF and IGF-1 alone, as well as in combination, on myogenic differentiation was analysed using microscopy, multicolour flow cytometry and real-time PCR. Furthermore, the influence of different three-dimensional culture models, such as fibrin, fibrin-collagen-I gels and parallel aligned electrospun poly-ε-caprolacton collagen-I nanofibers, on myogenic differentiation was analysed. MSCs could be successfully differentiated into the myogenic lineage both in mono- and in co-cultures independent of HGF and IGF-1 stimulation by expressing desmin, myocyte enhancer factor 2, myosin heavy chain 2 and alpha-sarcomeric actinin. An increased expression of different myogenic key markers could be observed under HGF and IGF-1 stimulation. Even though, stimulation with HGF/IGF-1 does not seem essential for sufficient myogenic differentiation. Three-dimensional cultivation in fibrin-collagen-I gels induced higher levels of myogenic differentiation compared with two-dimensional experiments. Cultivation on poly-ε-caprolacton-collagen-I nanofibers induced parallel alignment of cells and positive expression of desmin. CONCLUSIONS: In this study, we were able to myogenically differentiate MSC upon mono- and co-cultivation with myoblasts. The addition of HGF/IGF-1 might not be essential for achieving successful myogenic differentiation. Furthermore, with the development of a biocompatible nanofiber scaffold we established the basis for further experiments aiming at the generation of functional muscle tissue.
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Diferenciação Celular/efeitos dos fármacos , Fator de Crescimento de Hepatócito/farmacologia , Fator de Crescimento Insulin-Like I/farmacologia , Células-Tronco Mesenquimais/citologia , Músculo Esquelético/fisiologia , Mioblastos/citologia , Engenharia Tecidual/métodos , Animais , Biomarcadores/metabolismo , Células Cultivadas , Técnicas de Cocultura , Colágeno Tipo I/farmacologia , Citometria de Fluxo , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Desenvolvimento Muscular/efeitos dos fármacos , Desenvolvimento Muscular/genética , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Músculo Esquelético/efeitos dos fármacos , Mioblastos/efeitos dos fármacos , Mioblastos/metabolismo , Nanofibras/ultraestrutura , Poliésteres/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Endogâmicos Lew , Alicerces Teciduais/químicaRESUMO
The genetic basis of Alzheimer's disease (AD) is complex and heterogeneous. Over 200 highly penetrant pathogenic variants in the genes APP, PSEN1, and PSEN2 cause a subset of early-onset familial AD. On the other hand, susceptibility to late-onset forms of AD (LOAD) is indisputably associated to the É4 allele in the gene APOE, and more recently to variants in more than two-dozen additional genes identified in the large-scale genome-wide association studies (GWAS) and meta-analyses reports. Taken together however, although the heritability in AD is estimated to be as high as 80%, a large proportion of the underlying genetic factors still remain to be elucidated. In this study, we performed a systematic family-based genome-wide association and meta-analysis on close to 15 million imputed variants from three large collections of AD families (~3500 subjects from 1070 families). Using a multivariate phenotype combining affection status and onset age, meta-analysis of the association results revealed three single nucleotide polymorphisms (SNPs) that achieved genome-wide significance for association with AD risk: rs7609954 in the gene PTPRG (P-value=3.98 × 10-8), rs1347297 in the gene OSBPL6 (P-value=4.53 × 10-8), and rs1513625 near PDCL3 (P-value=4.28 × 10-8). In addition, rs72953347 in OSBPL6 (P-value=6.36 × 10-7) and two SNPs in the gene CDKAL1 showed marginally significant association with LOAD (rs10456232, P-value=4.76 × 10-7; rs62400067, P-value=3.54 × 10-7). In summary, family-based GWAS meta-analysis of imputed SNPs revealed novel genomic variants in (or near) PTPRG, OSBPL6, and PDCL3 that influence risk for AD with genome-wide significance.
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Doença de Alzheimer/genética , Proteínas de Transporte/genética , Proteínas do Tecido Nervoso/genética , Proteínas Tirosina Fosfatases Classe 5 Semelhantes a Receptores/genética , Receptores de Esteroides/genética , Idade de Início , Idoso , Alelos , Apolipoproteínas E/genética , Proteínas de Transporte/metabolismo , Família , Feminino , Estudos de Associação Genética/métodos , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Genômica , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/metabolismo , Polimorfismo de Nucleotídeo Único , Proteínas Tirosina Fosfatases Classe 5 Semelhantes a Receptores/metabolismo , Receptores de Esteroides/metabolismo , Fatores de Risco , tRNA Metiltransferases/genética , tRNA Metiltransferases/metabolismoRESUMO
Up to 30% of patients with obsessive-compulsive disorder (OCD) exhibit an inadequate response to serotonin reuptake inhibitors (SRIs). To date, genetic predictors of OCD treatment response have not been systematically investigated using genome-wide association study (GWAS). To identify specific genetic variations potentially influencing SRI response, we conducted a GWAS study in 804 OCD patients with information on SRI response. SRI response was classified as 'response' (n=514) or 'non-response' (n=290), based on self-report. We used the more powerful Quasi-Likelihood Score Test (the MQLS test) to conduct a genome-wide association test correcting for relatedness, and then used an adjusted logistic model to evaluate the effect size of the variants in probands. The top single-nucleotide polymorphism (SNP) was rs17162912 (P=1.76 × 10(-8)), which is near the DISP1 gene on 1q41-q42, a microdeletion region implicated in neurological development. The other six SNPs showing suggestive evidence of association (P<10(-5)) were rs9303380, rs12437601, rs16988159, rs7676822, rs1911877 and rs723815. Among them, two SNPs in strong linkage disequilibrium, rs7676822 and rs1911877, located near the PCDH10 gene, gave P-values of 2.86 × 10(-6) and 8.41 × 10(-6), respectively. The other 35 variations with signals of potential significance (P<10(-4)) involve multiple genes expressed in the brain, including GRIN2B, PCDH10 and GPC6. Our enrichment analysis indicated suggestive roles of genes in the glutamatergic neurotransmission system (false discovery rate (FDR)=0.0097) and the serotonergic system (FDR=0.0213). Although the results presented may provide new insights into genetic mechanisms underlying treatment response in OCD, studies with larger sample sizes and detailed information on drug dosage and treatment duration are needed.
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Transtorno Obsessivo-Compulsivo/genética , Adolescente , Adulto , Idoso , Criança , Feminino , Predisposição Genética para Doença , Variação Genética , Estudo de Associação Genômica Ampla , Humanos , Desequilíbrio de Ligação , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Autorrelato , Inibidores Seletivos de Recaptação de Serotonina/metabolismo , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Resultado do TratamentoRESUMO
OBJECTIVE: The BD Odon Device™ is a new instrument for operative vaginal birth with potential for preventing maternal, fetal and newborn morbidity/mortality during a complicated second stage of labour. The device is a plastic sleeve with an air chamber inflated around the baby's head which is gently pulled through the birth canal. The aim was to monitor changes in cerebral circulation during constriction of the neck to evaluate a risk of potential malposition of the device. DESIGN: Randomised prospective study. POPULATION OR SAMPLE: Twelve newborn piglets. METHODS: The anaesthetised piglets were exposed to hypoxia until base excess was -20 mmol/l and/or mean arterial blood pressure had decreased to 20 mmHg. At reoxygenation, an air chamber was inflated around the neck to 300 mmHg and the piglets randomised into three groups: 10 (n = 5), 5 (n = 5) or 2 (n = 2) minutes' occlusion. Cerebral perfusion was evaluated with transcranial contrast-enhanced ultrasound at four time-points, and analysed in the carotid arteries, basal ganglia, cortex and whole brain. Statistical analysis used ANOVA, linear mixed model, Kruskal-Wallis H-test. MAIN OUTCOME MEASURES: Perfusion parameters; peak intensity, time to peak intensity, upslope, mean transit time, area under the curve. RESULTS: The haemodynamic response was comparable between groups. Perfusion parameters showed a slight increase at end hypoxia followed by a decrease during occlusion, especially in the cortex (P = 0.00-0.2). After deflation, perfusion returned towards baseline values. CONCLUSIONS: Simulation of malposition of the Odon Device was performed using a newborn hypoxic piglet model. Considerable compression of the neck vessels was applied, with only a moderate decrease in perfusion and with restoration of haemodynamics/cerebral perfusion after decompression. TWEETABLE ABSTRACT: Malposition of Odon Device™ in a piglet model revealed a reversible decrease in cerebral perfusion during neck constriction.
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Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Extração Obstétrica/instrumentação , Hipóxia-Isquemia Encefálica/diagnóstico por imagem , Animais , Animais Recém-Nascidos , Meios de Contraste , Feminino , Modelos Animais , Gravidez , Distribuição Aleatória , Hexafluoreto de Enxofre , Suínos , UltrassonografiaRESUMO
The objective of this study was to develop a new elaborate method to evaluate infants' liking of foods that could be applied at home and to compare the results of this elaborate method with those of a basic method. Mothers of infants aged 4 to 7 (n = 44) and 12-15 months (n = 46) participated in this study. For the basic method, mothers were asked to assess their infant's global liking at the end of a meal. Then, for the elaborate method, mothers received detailed instructions on how to feed their infant, how infants might express like/dislike and when to stop the meal. During the first nine spoons, they were asked to report the presence/absence of positive and negative behaviours after each spoon, and the infant's initial liking was reported after each triplet of spoons. They also assessed their infant's global liking at the end of the meal. Both methods were applied using three commercial familiar baby foods adapted to each age range. In 4-7-month-olds, the elaborate method showed a significant difference across products for liking, whereas the basic method did not show any difference. In 12-15-month-olds, the elaborate method showed more differences across products for liking than the basic method. In both age groups, negative behaviours, despite being less frequently reported, provided better liking discrimination than positive behaviours. In conclusion, the elaborate method produced better product liking discrimination than the basic method by focusing maternal attention on infants' eating behaviours since the first spoons.
Assuntos
Comportamento Alimentar/psicologia , Preferências Alimentares/psicologia , Alimentos Infantis , Refeições/psicologia , Utensílios de Alimentação e Culinária , Feminino , Humanos , Lactente , Masculino , Mães/psicologia , GravidezRESUMO
Background Optical coherence tomography angiography (OCTA) offers the possibility to visualize, non-invasively, blood vessels of the retina. In vascular tumors, especially hemangioblastomas in Hippel-Lindau disease, new information can be obtained with OCTA concerning structure of the tumor, tumor activity and treatment success. Patients Ten eyes of 10 patients with retinal hemangioblastoma in Hippel-Lindau disease were included. The age of the patients ranged from 19 years to 65 years (median 44 years). Results A total of 10 active and one inactive hemangioblastomas were examined with OCTA. In larger tumors, only the superficial blood flow could be visualized. Four hemangioblastomas were not treated due to their location near the optic nerve head. Six hemangioblastomas in the peripheral retina were treated with laser photocoagulation. In 4 eyes, a reduced blood flow could be shown directly after the treatment. The visualization of the perfusion was partially blocked after laser treatment. Conclusion OCTA enables innovative methods of pre- and postoperative assessment of retinal hemangioblastomas. It has the potential to give new information about the morphology, activity and effects of treatment. Prospective studies with longer follow-up are needed to evaluate the therapeutic relevance of this new imaging method.