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1.
Alzheimers Dement ; 20(5): 3334-3341, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38539061

RESUMEN

INTRODUCTION: Lewy body disease (LBD) is a common primary or co-pathology in neurodegenerative syndromes. An alpha-synuclein seed amplification assay (αSyn-SAA) is clinically available, but clinical performance, especially lower sensitivity in amygdala-predominant cases, is not well understood. METHODS: Antemortem CSF from neuropathology-confirmed LBD cases was tested with αSyn-SAA (N = 56). Diagnostic performance and clinicopathological correlations were examined. RESULTS: Similar to prior reports, sensitivity was 100% for diffuse and transitional LBD (9/9), and overall specificity was 96.3% (26/27). Sensitivity was lower in amygdala-predominant (6/14, 42.8%) and brainstem-predominant LBD (1/6, 16.7%), but early spread outside these regions (without meeting criteria for higher stage) was more common in αSyn-SAA-positive cases (6/7, 85.7%) than negative (2/13, 15.4%). DISCUSSION: In this behavioral neurology cohort, αSyn-SAA had excellent diagnostic performance for cortical LBD. In amygdala- and brainstem-predominant cases, sensitivity was lower, but positivity was associated with anatomical spread, suggesting αSyn-SAA detects early LBD progression in these cohorts. HIGHLIGHTS: A cerebrospinal fluid alpha-synuclein assay detects cortical LBD with high sensitivity/specificity. Positivity in prodromal stages of LBD was associated with early cortical spread. The assay provides precision diagnosis of LBD that could support clinical trials. The assay can also identify LBD co-pathology, which may impact treatment responses.


Asunto(s)
Autopsia , Enfermedad por Cuerpos de Lewy , Sensibilidad y Especificidad , alfa-Sinucleína , Humanos , alfa-Sinucleína/líquido cefalorraquídeo , Enfermedad por Cuerpos de Lewy/líquido cefalorraquídeo , Enfermedad por Cuerpos de Lewy/patología , Femenino , Masculino , Anciano , Estudios de Cohortes , Amígdala del Cerebelo/patología , Anciano de 80 o más Años , Biomarcadores/líquido cefalorraquídeo , Persona de Mediana Edad
2.
Proc Natl Acad Sci U S A ; 117(10): 5196-5203, 2020 03 10.
Artículo en Inglés | MEDLINE | ID: mdl-32098848

RESUMEN

Black carbon (BC) absorbs solar radiation, leading to a strong but uncertain warming effect on climate. A key challenge in modeling and quantifying BC's radiative effect on climate is predicting enhancements in light absorption that result from internal mixing between BC and other aerosol components. Modeling and laboratory studies show that BC, when mixed with other aerosol components, absorbs more strongly than pure, uncoated BC; however, some ambient observations suggest more variable and weaker absorption enhancement. We show that the lower-than-expected enhancements in ambient measurements result from a combination of two factors. First, the often used spherical, concentric core-shell approximation generally overestimates the absorption by BC. Second, and more importantly, inadequate consideration of heterogeneity in particle-to-particle composition engenders substantial overestimation in absorption by the total particle population, with greater heterogeneity associated with larger model-measurement differences. We show that accounting for these two effects-variability in per-particle composition and deviations from the core-shell approximation-reconciles absorption enhancement predictions with laboratory and field observations and resolves the apparent discrepancy. Furthermore, our consistent model framework provides a path forward for improving predictions of BC's radiative effect on climate.

3.
J Microsc ; 286(1): 3-12, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34879153

RESUMEN

Superconducting windings will be necessary in future fusion reactors to generate the strong magnetic fields needed to confine the plasma, and these superconducting materials will inevitably be exposed to neutron damage. It is known that this exposure results in the creation of isolated damage cascades, but the presence of these defects alone is not sufficient to explain the degradation of macroscopic superconducting properties and a quantitative method is needed to assess the subtle lattice damage in between the clusters. We have studied REBCO-coated conductors irradiated with neutrons to a cumulative dose of 3.3 × 1022  n/m2  that show a degradation of both Tc  and Jc values, and use HRTEM analysis to show that this irradiation introduces ∼10 nm amorphous collision cascades. In addition, we introduce a new method for the analysis of these images to quantify the degree of lattice disorder in the apparently perfect matrix between these cascades. This method utilises Fast Fourier and Discrete Cosine Transformations of a statistically relevant number of HRTEM images of pristine, neutron-irradiated and amorphous samples and extracts the degree of randomness in terms of entropy values. Our results show that these entropy values in both mid-frequency band FFT and DCT domains correlate with the expected level of lattice damage, with the pristine samples having the lowest and the fully amorphous regions the highest entropy values.  Our methodology allows us to quantify 'invisible' lattice damage to and correlate these values to the degradation of superconducting properties, and also has relevance for a wider range of applications in the field of electron microscopy where small changes in lattice perfection need to be measured.

4.
Neurobiol Dis ; 148: 105175, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33188920

RESUMEN

Prevalent in approximately 20% of the worldwide human population, the rs6265 (also called 'Val66Met') single nucleotide polymorphism (SNP) in the gene for brain-derived neurotrophic factor (BDNF) is a common genetic variant that can alter therapeutic responses in individuals with Parkinson's disease (PD). Possession of the variant Met allele results in decreased activity-dependent release of BDNF. Given the resurgent worldwide interest in neural transplantation for PD and the biological relevance of BDNF, the current studies examined the effects of the rs6265 SNP on therapeutic efficacy and side-effect development following primary dopamine (DA) neuron transplantation. Considering the significant reduction in BDNF release associated with rs6265, we hypothesized that rs6265-mediated dysfunctional BDNF signaling contributes to the limited clinical benefit observed in a subpopulation of PD patients despite robust survival of grafted DA neurons, and further, that this mutation contributes to the development of aberrant graft-induced dyskinesias (GID). To this end, we generated a CRISPR knock-in rat model of the rs6265 BDNF SNP to examine for the first time the influence of a common genetic polymorphism on graft survival, functional efficacy, and side-effect liability, comparing these parameters between wild-type (Val/Val) rats and those homozygous for the variant Met allele (Met/Met). Counter to our hypothesis, the current research indicates that Met/Met rats show enhanced graft-associated therapeutic efficacy and a paradoxical enhancement of graft-derived neurite outgrowth compared to wild-type rats. However, consistent with our hypothesis, we demonstrate that the rs6265 genotype in the host rat is strongly linked to development of GID, and that this behavioral phenotype is significantly correlated with neurochemical signatures of atypical glutamatergic neurotransmission by grafted DA neurons.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/genética , Trasplante de Células/métodos , Neuronas Dopaminérgicas/trasplante , Discinesias/genética , Animales , Antiparkinsonianos/efectos adversos , Trasplante de Células/efectos adversos , Neuronas Dopaminérgicas/metabolismo , Discinesia Inducida por Medicamentos/etiología , Discinesias/etiología , Embrión de Mamíferos , Técnicas de Sustitución del Gen , Levodopa/efectos adversos , Mesencéfalo/citología , Oxidopamina/toxicidad , Enfermedad de Parkinson Secundaria/inducido químicamente , Ratas , Simpaticolíticos/toxicidad , Proteína 2 de Transporte Vesicular de Glutamato/metabolismo
5.
Opt Express ; 29(14): 21300-21312, 2021 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-34265920

RESUMEN

The superposition of two partially correlated waves is shown to produce fields with drastically altered coherence properties. It is demonstrated, both theoretically and experimentally, that two strongly correlated sources may generate a field with practically zero correlation between certain pairs of points. This anomalous change in coherence is a general phenomenon that takes place in all cases of wave superposition, including Mie scattering, as is shown. Our results are particularly relevant to applications in which it is assumed that highly coherent radiation maintains its spatial coherence on propagation, such as optical systems design and the imaging of extended sources.

6.
Phys Rev Lett ; 126(12): 128002, 2021 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-33834798

RESUMEN

We study experimentally the dynamical behavior of few large tracer particles placed in a quasi-2D granular "gas" made of many small beads in a low-gravity environment. Multiple inelastic collisions transfer momentum from the uniaxially driven gas to the tracers whose velocity distributions are studied through particle tracking. Analyzing these distributions for an increasing system density reveals that translational energy equipartition is reached at the onset of the gas-liquid granular transition corresponding to the emergence of local clusters. The dynamics of a few tracer particles thus appears as a simple and accurate tool to detect this transition. A model is proposed for describing accurately the formation of local heterogeneities.

7.
Phys Rev Lett ; 126(2): 023201, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33512178

RESUMEN

Chirality causes symmetry breaks in a large variety of natural phenomena ranging from particle physics to biochemistry. We investigate one of the simplest conceivable chiral systems, a laser-excited, oriented, effective one-electron Li target. Prepared in a polarized p state with |m|=1 in an optical trap, the atoms are exposed to co- and counterrotating circularly polarized femtosecond laser pulses. For a field frequency near the excitation energy of the oriented initial state, a strong circular dichroism is observed and the photoelectron energies are significantly affected by the helicity-dependent Autler-Townes splitting. Besides its fundamental relevance, this system is suited to create spin-polarized electron pulses with a reversible switch on a femtosecond timescale at an energy resolution of a few meV.

8.
Aesthetic Plast Surg ; 45(3): 907-916, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33469702

RESUMEN

BACKGROUND: This study aimed to evaluate the impact of semi-absorbable mesh on donor-site morbidity and patient-reported outcomes in deep inferior epigastric perforator (DIEP) flap breast reconstruction. METHODS: We conducted a retrospective cohort study of all patients who had DIEP flap breast reconstruction in our department from July 2007 to March 2019. Patients were invited to a comparative follow-up visit and grouped according to donor-site closure: primary fascial closure (the no-mesh group) and fascial reinforcement with semi-absorbable mesh in a subfascial position (the mesh group). The primary outcome of interest was donor-site morbidity, including bulging, hernia formation and rectus abdominis muscle strength. We also surveyed, surgical site complications and patient-reported outcomes using Patient and Observer Scar Assessment Scale v2.0 and BREAST-Q© version 2.0. RESULTS: A total of 191 patients had received DIEP flap breast reconstruction. Eighty-five patients (44.5%) with 108 DIEP flaps (53 patients in the mesh group and 32 patients in the no-mesh group) were included in the study. The mean BMI of the patients was significantly higher in the mesh group (mesh group, 26.9 vs. no-mesh group, 25.0, with p = 0.03). The incidence of hernia was significantly reduced in the mesh group (mesh group, 2.8% vs. no-mesh group, 13.5%, with p = 0.03). The incidence of bulging and the extent of rectus abdominis muscle strength were similar for both groups. Operative surgical site complications were reduced in the mesh group (mesh group, 7.5% vs. no-mesh group, 18.8%). There was no difference in patients' physical well-being and satisfaction with the donor site between groups. Patient-reported scar outcome was significantly better in the no-mesh group (p < 0.001). CONCLUSION: Our novel method of donor-site closure with semi-absorbable mesh in a subfascial position for reinforcement of the anterior rectus fascia on the DIEP donor site is safe. It has no negative impact on surgical site complications and patient-reported outcomes, while reducing the incidence of hernias on the donor-site in DIEP flap breast reconstruction. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Asunto(s)
Mamoplastia , Colgajo Perforante , Arterias Epigástricas/cirugía , Humanos , Mamoplastia/efectos adversos , Morbilidad , Medición de Resultados Informados por el Paciente , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Recto del Abdomen/trasplante , Estudios Retrospectivos , Mallas Quirúrgicas
9.
BMC Surg ; 20(1): 306, 2020 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-33256710

RESUMEN

BACKGROUND: Complex regional pain syndrome (CRPS) is a rare but feared complication in hand surgery. Although multimodal therapy concepts are recommended, there is only low evidence on efficacy of such approaches. Furthermore, recommendations regarding therapy duration are lacking. Aim of this study was to validate the efficacy of an International Classification of Functioning, Disability and Health (ICF)-based multidisciplinary rehabilitation concept for treatment of CRPS of the hand and to find correlations between therapy duration and outcome measures. METHODS: Patients with CRPS of the hand after occupational trauma that underwent an ICF-based rehabilitation program between 2010 and 2014 were included in this retrospective study. Besides demographic data, outcomes included pain (VAS), range of motion assessed by fingertip-to-palm-distance (PTPD) and fingernail-to-table-distance (FTTD) as well as strength in grip, 3-point pinch and lateral pinch. All measures were gathered at admission to and discharge from inpatient rehabilitation therapy as well as at follow-up. Statistical analysis included paired t-test, ANOVA and Pearson's correlation analysis. RESULTS: Eighty-nine patients with a mean age of 45 years were included in this study. Duration of rehabilitation therapy was 53 days on average. All outcomes improved significantly during rehabilitation therapy. Pain decreased from 6.4 to 2.2. PTPD of digit 2 to 5 improved from 2.5, 2.8, 2.6, and 2.3 cm to 1.3, 1.4, 1.2, and 1.1 cm, respectively. FTTD of digit 2 to 5 decreased from 1.5, 1.7, 1.5, and 1.6 cm to 0.6, 0.8, 0.7, and 0.7 cm, respectively. Strength ameliorated from 9.5, 3.7, 2.7 kg to 17.9, 5.6, 5.0 kg in grip, lateral pinch, and 3-point pinch, respectively. Improvement in range of motion significantly correlated with therapy duration. 54% of patients participated at follow-up after a mean of 7.5 months. Outcome measures at follow-up remained stable compared to discharge values without significant differences. CONCLUSION: The ICF-based rehabilitation concept is a reliable and durable treatment option for CRPS of the hand. Range of motion improved continuously with therapy duration and thus may serve as an indicator for optimum length of therapy.


Asunto(s)
Síndromes de Dolor Regional Complejo/rehabilitación , Duración de la Terapia , Mano/fisiopatología , Adulto , Femenino , Fuerza de la Mano , Humanos , Masculino , Persona de Mediana Edad , Rango del Movimiento Articular , Estudios Retrospectivos , Resultado del Tratamiento
10.
Mov Disord ; 34(1): 22-34, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30440081

RESUMEN

The concept that subthalamic nucleus deep brain stimulation (STN DBS) may be disease modifying in Parkinson's disease (PD) is controversial. Several clinical trials that enrolled subjects with late-stage PD have come to disparate conclusions on this matter. In contrast, some clinical studies in early- to midstage subjects have suggested a disease-modifying effect. Dopaminergic innervation of the putamen is essentially absent in PD subjects within 4 years after diagnosis, indicating that any neuroprotective therapy, including STN DBS, will require intervention within the immediate postdiagnosis interval. Preclinical prevention and early intervention paradigms support a neuroprotective effect of STN DBS on the nigrostriatal system via increased brain-derived neurotrophic factor (BDNF). STN DBS-induced increases in BDNF provide a multitude of mechanisms capable of ameliorating dysfunction and degeneration in the parkinsonian brain. A biomarker for measuring brain-derived neurotrophic factor-trkB signaling, though, is not available for clinical research. If a prospective clinical trial were to examine whether STN DBS is disease modifying, we contend the strongest rationale is not dependent on a preclinical neuroprotective effect per se, but on the myriad potential mechanisms whereby STN DBS-elicited brain-derived neurotrophic factor-trkB signaling could provide disease modification. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/farmacología , Estimulación Encefálica Profunda , Enfermedad de Parkinson/tratamiento farmacológico , Trastornos Parkinsonianos/tratamiento farmacológico , Humanos , Fármacos Neuroprotectores , Enfermedad de Parkinson/fisiopatología , Trastornos Parkinsonianos/fisiopatología , Núcleo Subtalámico/metabolismo
11.
J Neurosci ; 37(28): 6786-6796, 2017 07 12.
Artículo en Inglés | MEDLINE | ID: mdl-28607168

RESUMEN

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is the most common neurosurgical treatment for Parkinson's disease motor symptoms. In preclinical models, STN DBS provides neuroprotection for substantia nigra (SN) dopamine neurons and increases BDNF in the nigrostriatal system and primary motor cortex. However, whether BDNF signaling in the SN participates in the neuroprotective effects of DBS remains unknown. We demonstrate that STN DBS in male rats activates signaling downstream of tropomyosin receptor kinase type B (trkB), namely, phosphorylation of Akt and ribosomal protein S6, in SN neurons. Long-term trkB blockade abolished STN DBS-mediated neuroprotection of SN neurons following progressive 6-hydroxydopamine lesion and was associated with decreased phosphorylated ribosomal protein S6 immunoreactivity. Acute trkB blockade in rats with stable nigrostriatal denervation attenuated the forelimb akinesia improvement normally induced by STN DBS. These results suggest that STN DBS increases BDNF-trkB signaling to contribute to the neuroprotective and symptomatic efficacy of STN DBS.SIGNIFICANCE STATEMENT Subthalamic nucleus deep brain stimulation (STN DBS) is increasingly used in mid- to late-stage Parkinson's disease (PD) but with an incomplete knowledge of its molecular mechanisms. STN DBS is neuroprotective against neurotoxicants in animal models and increases BDNF. This study is the first to show that BDNF signaling through the cognate tropomyosin receptor kinase type B (trkB) receptor occurs in substantia nigra pars compacta neurons and is required for neuroprotection. In addition, blockade of trkB unexpectedly reduced the functional benefit of STN DBS on a short timescale that is inconsistent with canonical trkB signaling pathways, suggesting a noncanonical role for trkB in STN DBS-mediated behavioral effects. Together, these data implicate trkB signaling in the symptomatic efficacy and disease-modifying potential of STN DBS.


Asunto(s)
Estimulación Encefálica Profunda , Regeneración Nerviosa/fisiología , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/terapia , Proteínas Tirosina Quinasas/metabolismo , Núcleo Subtalámico/fisiopatología , Animales , Masculino , Enfermedad de Parkinson/diagnóstico , Ratas , Ratas Sprague-Dawley , Receptor trkB , Recuperación de la Función/fisiología , Transducción de Señal
12.
J Neuroinflammation ; 15(1): 129, 2018 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-29716614

RESUMEN

BACKGROUND: Converging evidence suggests a role for microglia-mediated neuroinflammation in Parkinson's disease (PD). Animal models of PD can serve as a platform to investigate the role of neuroinflammation in degeneration in PD. However, due to features of the previously available PD models, interpretations of the role of neuroinflammation as a contributor to or a consequence of neurodegeneration have remained elusive. In the present study, we investigated the temporal relationship of neuroinflammation in a model of synucleinopathy following intrastriatal injection of pre-formed alpha-synuclein fibrils (α-syn PFFS). METHODS: Male Fischer 344 rats (N = 114) received unilateral intrastriatal injections of α-syn PFFs, PBS, or rat serum albumin with cohorts euthanized at monthly intervals up to 6 months. Quantification of dopamine neurons, total neurons, phosphorylated α-syn (pS129) aggregates, major histocompatibility complex-II (MHC-II) antigen-presenting microglia, and ionized calcium-binding adaptor molecule-1 (Iba-1) immunoreactive microglial soma size was performed in the substantia nigra. In addition, the cortex and striatum were also examined for the presence of pS129 aggregates and MHC-II antigen-presenting microglia to compare the temporal patterns of pSyn accumulation and reactive microgliosis. RESULTS: Intrastriatal injection of α-syn PFFs to rats resulted in widespread accumulation of phosphorylated α-syn inclusions in several areas that innervate the striatum followed by significant loss (~ 35%) of substantia nigra pars compacta dopamine neurons within 5-6 months. The peak magnitudes of α-syn inclusion formation, MHC-II expression, and reactive microglial morphology were all observed in the SN 2 months following injection and 3 months prior to nigral dopamine neuron loss. Surprisingly, MHC-II immunoreactivity in α-syn PFF injected rats was relatively limited during the later interval of degeneration. Moreover, we observed a significant correlation between substantia nigra pSyn inclusion load and number of microglia expressing MHC-II. In addition, we observed a similar relationship between α-syn inclusion load and number of microglia expressing MHC-II in cortical regions, but not in the striatum. CONCLUSIONS: Our results demonstrate that increases in microglia displaying a reactive morphology and MHC-II expression occur in the substantia nigra in close association with peak numbers of pSyn inclusions, months prior to nigral dopamine neuron degeneration, and suggest that reactive microglia may contribute to vulnerability of SNc neurons to degeneration. The rat α-syn PFF model provides an opportunity to examine the innate immune response to accumulation of pathological α-syn in the context of normal levels of endogenous α-syn and provides insight into the earliest neuroinflammatory events in PD.


Asunto(s)
Cuerpos de Lewy/patología , Microglía/patología , Degeneración Nerviosa/inducido químicamente , Degeneración Nerviosa/patología , Sustancia Negra/patología , alfa-Sinucleína/toxicidad , Animales , Inyecciones Intraventriculares , Cuerpos de Lewy/efectos de los fármacos , Cuerpos de Lewy/metabolismo , Masculino , Microglía/efectos de los fármacos , Microglía/metabolismo , Degeneración Nerviosa/metabolismo , Ratas , Ratas Endogámicas F344 , Sustancia Negra/efectos de los fármacos , Sustancia Negra/metabolismo , alfa-Sinucleína/administración & dosificación
13.
J Neuroinflammation ; 15(1): 169, 2018 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-29843738

RESUMEN

After publication of the original article [1] it was noted that the name of author, D. Luke Fisher, was erroneously typeset in both the PDF and online formats of the manuscript as Luke D. Fisher.

14.
Mol Psychiatry ; 22(8): 1096-1109, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28584287

RESUMEN

CACNA1C, encoding the Cav1.2 subunit of L-type Ca2+ channels, has emerged as one of the most prominent and highly replicable susceptibility genes for several neuropsychiatric disorders. Cav1.2 channels play a crucial role in calcium-mediated processes involved in brain development and neuronal function. Within the CACNA1C gene, disease-associated single-nucleotide polymorphisms have been associated with impaired social and cognitive processing and altered prefrontal cortical (PFC) structure and activity. These findings suggest that aberrant Cav1.2 signaling may contribute to neuropsychiatric-related disease symptoms via impaired PFC function. Here, we show that mice harboring loss of cacna1c in excitatory glutamatergic neurons of the forebrain (fbKO) that we have previously reported to exhibit anxiety-like behavior, displayed a social behavioral deficit and impaired learning and memory. Furthermore, focal knockdown of cacna1c in the adult PFC recapitulated the social deficit and elevated anxiety-like behavior, but not the deficits in learning and memory. Electrophysiological and molecular studies in the PFC of cacna1c fbKO mice revealed higher E/I ratio in layer 5 pyramidal neurons and lower general protein synthesis. This was concurrent with reduced activity of mTORC1 and its downstream mRNA translation initiation factors eIF4B and 4EBP1, as well as elevated phosphorylation of eIF2α, an inhibitor of mRNA translation. Remarkably, systemic treatment with ISRIB, a small molecule inhibitor that suppresses the effects of phosphorylated eIF2α on mRNA translation, was sufficient to reverse the social deficit and elevated anxiety-like behavior in adult cacna1c fbKO mice. ISRIB additionally normalized the lower protein synthesis and higher E/I ratio in the PFC. Thus this study identifies a novel Cav1.2 mechanism in neuropsychiatric-related endophenotypes and a potential future therapeutic target to explore.


Asunto(s)
Canales de Calcio Tipo L/efectos de los fármacos , Canales de Calcio Tipo L/metabolismo , Animales , Ansiedad , Conducta Animal/efectos de los fármacos , Calcio/metabolismo , Canales de Calcio Tipo L/genética , Modelos Animales de Enfermedad , Factor 2 Eucariótico de Iniciación/genética , Factor 2 Eucariótico de Iniciación/metabolismo , Factores Eucarióticos de Iniciación/genética , Factores Eucarióticos de Iniciación/metabolismo , Predisposición Genética a la Enfermedad/genética , Hipocampo/metabolismo , Humanos , Ratones , Ratones Noqueados , Neuronas/metabolismo , Prosencéfalo/metabolismo , Células Piramidales/metabolismo , Conducta Social
15.
Langmuir ; 34(4): 1783-1794, 2018 01 30.
Artículo en Inglés | MEDLINE | ID: mdl-29286662

RESUMEN

As the quest toward novel materials proceeds, improved characterization technologies are needed. In particular, the atomic thickness in graphene and other 2D materials renders some conventional technologies obsolete. Characterization technologies at wafer level are needed with enough sensitivity to detect strain in order to inform fabrication. In this work, NEXAFS spectroscopy was combined with simulations to predict lattice parameters of graphene grown on copper and further transferred to a variety of substrates. The strains associated with the predicted lattice parameters are in agreement with experimental findings. The approach presented here holds promise to effectively measure strain in graphene and other 2D systems at wafer levels to inform manufacturing environments.

16.
Vox Sang ; 113(1): 60-71, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29082529

RESUMEN

BACKGROUND AND OBJECTIVES: The aim of this survey was to evaluate the knowledge about Patient Blood Management (PBM) principles and practices amongst clinicians working in seven European hospitals participating in a European Blood Alliance (EBA) project. MATERIALS AND METHODS: A web-based questionnaire was sent to 4952 clinicians working in medical, surgery and anaesthesiology disciplines. The responses were analysed, and the overall results as well as a comparison between hospitals are presented. RESULTS: A total of 788 responses (16%) were obtained. About 24% of respondents were not aware of a correlation between preoperative anaemia (POA) and perioperative morbidity and mortality. For 22%, treatment of POA was unlikely to favourably influence morbidity and mortality even before surgery with expected blood loss. More than half of clinicians did not routinely treat POA. 29%, when asked which is the best way to treat deficiency anaemia preoperatively, answered that they did not have sufficient knowledge and 5% chose to 'do nothing'. Amongst those who treated POA, 38% proposed red cell transfusion prior to surgery as treatment. Restrictive haemoglobin triggers for red blood cell transfusion, single unit policy and reduction of number and volumes of blood samples for diagnostic purposes were only marginally implemented. CONCLUSION: Overall, the responses indicated poor knowledge about PBM. Processes to diagnose and treat POA were not generally and homogeneously implemented. This survey should provide further impetus to implement programmes to improve knowledge and practice of PBM.


Asunto(s)
Anemia/terapia , Competencia Clínica , Complicaciones Posoperatorias/prevención & control , Anemia/complicaciones , Manejo de la Enfermedad , Transfusión de Eritrocitos/métodos , Europa (Continente) , Encuestas de Atención de la Salud , Hospitales Universitarios , Humanos , Complicaciones Posoperatorias/etiología
17.
Anim Genet ; 49(4): 329-333, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29797511

RESUMEN

Compromised eggshell quality causes considerable economic losses for the egg industry. Breeding for improved eggshell quality has been very challenging. Eggshell quality is a trait that would greatly benefit from marker-assisted selection, which would allow the selection of sires for their direct contribution to the trait and would also allow implementation of measurements integrating a number of shell parameters that are difficult to measure. In this study, we selected the most promising autosomal quantitative trait loci (QTL) affecting eggshell quality on chromosomes 2, 3, 6 and 14 from earlier experiments and we extended the F2 population to include 1599 F2 females. The study was repeated on two commercial populations: Lohmann Tierzucht Rhode Island Red line (n = 692 females) and a Hy-Line White Plymouth Rock line (n = 290 progeny tested males). We analyzed the selected autosomal QTL regions on the three populations with SNP markers at 4-13 SNPs/Mb density. QTL for eggshell quality were replicated on all studied regions in the F2 population. New QTL were detected for eggshell color on chromosomes 3 and 6. Marker associations with eggshell quality traits were validated in the tested commercial lines on chromosomes 2, 3 and 6, thus paving the way for marker-assisted selection for improved eggshell quality.


Asunto(s)
Pollos/genética , Cáscara de Huevo , Sitios de Carácter Cuantitativo , Animales , Cruzamiento , Femenino , Masculino , Fenotipo , Polimorfismo de Nucleótido Simple
18.
Neuroimage ; 157: 34-44, 2017 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-28572060

RESUMEN

Scientists and clinicians have traditionally targeted single brain regions with stimulation to modulate brain function and disease. However, brain regions do not operate in isolation, but interact with other regions through networks. As such, stimulation of one region may impact and be impacted by other regions in its network. Here we test whether the effects of brain stimulation can be enhanced by simultaneously targeting a region and its network, identified with resting state functional connectivity MRI. Fifteen healthy participants received two types of transcranial direct current stimulation (tDCS): a traditional two-electrode montage targeting a single brain region (left primary motor cortex [M1]) and a novel eight-electrode montage targeting this region and its associated resting state network. As a control, 8 participants also received multifocal tDCS mismatched to this network. Network-targeted tDCS more than doubled the increase in left M1 excitability over time compared to traditional tDCS and the multifocal control. Modeling studies suggest these results are unlikely to be due to tDCS effects on left M1 itself, however it is impossible to completely exclude this possibility. It also remains unclear whether multifocal tDCS targeting a network selectively modulates this network and which regions within the network are most responsible for observed effects. Despite these limitations, network-targeted tDCS appears to be a promising approach for enhancing tDCS effects beyond traditional stimulation targeting a single brain region. Future work is needed to test whether these results extend to other resting state networks and enhance behavioral or therapeutic effects.


Asunto(s)
Conectoma/métodos , Potenciales Evocados Motores/fisiología , Corteza Motora/fisiología , Red Nerviosa/fisiología , Estimulación Transcraneal de Corriente Directa/métodos , Adulto , Electromiografía , Femenino , Humanos , Masculino , Estimulación Transcraneal de Corriente Directa/instrumentación , Estimulación Magnética Transcraneal , Adulto Joven
19.
Geophys Res Lett ; 44(8): 3456-3464, 2017 04 28.
Artículo en Inglés | MEDLINE | ID: mdl-28713180

RESUMEN

We report global observations of high-m poloidal waves during the recovery phase of the 22 June 2015 magnetic storm from a constellation of widely spaced satellites of five missions including Magnetospheric Multiscale (MMS), Van Allen Probes, Time History of Events and Macroscale Interactions during Substorm (THEMIS), Cluster, and Geostationary Operational Environmental Satellites (GOES). The combined observations demonstrate the global spatial extent of storm time poloidal waves. MMS observations confirm high azimuthal wave numbers (m ~ 100). Mode identification indicates the waves are associated with the second harmonic of field line resonances. The wave frequencies exhibit a decreasing trend as L increases, distinguishing them from the single-frequency global poloidal modes normally observed during quiet times. Detailed examination of the instantaneous frequency reveals discrete spatial structures with step-like frequency changes along L. Each discrete L shell has a steady wave frequency and spans about 1 RE , suggesting that there exist a discrete number of drift-bounce resonance regions across L shells during storm times.

20.
Phys Chem Chem Phys ; 19(13): 9045-9052, 2017 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-28304039

RESUMEN

The oxidation kinetics of thin polycrystalline Ni films is of fundamental interest as well as being relevant for potential applications. It was investigated between 250 and 500 °C for 10-150 nm thick films. Even for the thinnest films, oxidation was found to be diffusion controlled. The high density of grain boundaries in the formed NiO layer leads to a tracer diffusion coefficient that is higher than reported in the literature, indicating accelerated Ni diffusion along the grain boundaries. Cr segregation to the bottom interface in doped-NiO films hindered the acceleration of the oxidation of thin films.

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