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1.
Cell ; 163(6): 1348-59, 2015 12 03.
Artículo en Inglés | MEDLINE | ID: mdl-26627734

RESUMEN

Spontaneous electrical activity of neurons in developing sensory systems promotes their maturation and proper connectivity. In the auditory system, spontaneous activity of cochlear inner hair cells (IHCs) is initiated by the release of ATP from glia-like inner supporting cells (ISCs), facilitating maturation of central pathways before hearing onset. Here, we find that ATP stimulates purinergic autoreceptors in ISCs, triggering Cl(-) efflux and osmotic cell shrinkage by opening TMEM16A Ca(2+)-activated Cl(-) channels. Release of Cl(-) from ISCs also forces K(+) efflux, causing transient depolarization of IHCs near ATP release sites. Genetic deletion of TMEM16A markedly reduces the spontaneous activity of IHCs and spiral ganglion neurons in the developing cochlea and prevents ATP-dependent shrinkage of supporting cells. These results indicate that supporting cells in the developing cochlea have adapted a pathway used for fluid secretion in other organs to induce periodic excitation of hair cells.


Asunto(s)
Oído Interno/crecimiento & desarrollo , Células Ciliadas Auditivas/citología , Adenosina Trifosfato/metabolismo , Animales , Anoctamina-1 , Canales de Cloruro/genética , Canales de Cloruro/metabolismo , Oído Interno/citología , Oído Interno/metabolismo , Células Ciliadas Auditivas/metabolismo , Células Laberínticas de Soporte/citología , Células Laberínticas de Soporte/metabolismo , Ratones , Ratones Noqueados , Potasio/metabolismo , Ratas , Ratas Sprague-Dawley , Ganglio Espiral de la Cóclea/citología , Ganglio Espiral de la Cóclea/metabolismo
2.
Nature ; 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39358515

RESUMEN

The brain helps us survive by forming internal representations of the external world1,2. Excitatory cortical neurons are often precisely tuned to specific external stimuli3,4. However, inhibitory neurons, such as parvalbumin-positive (PV) interneurons, are generally less selective5. PV interneurons differ from excitatory neurons in their neurotransmitter receptor subtypes, including AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors (AMPARs)6,7. Excitatory neurons express calcium-impermeable AMPARs that contain the GluA2 subunit (encoded by GRIA2), whereas PV interneurons express receptors that lack the GluA2 subunit and are calcium-permeable (CP-AMPARs). Here we demonstrate a causal relationship between CP-AMPAR expression and the low feature selectivity of PV interneurons. We find low expression stoichiometry of GRIA2 mRNA relative to other subunits in PV interneurons that is conserved across ferrets, rodents, marmosets and humans, and causes abundant CP-AMPAR expression. Replacing CP-AMPARs in PV interneurons with calcium-impermeable AMPARs increased their orientation selectivity in the visual cortex. Manipulations to induce sparse CP-AMPAR expression demonstrated that this increase was cell-autonomous and could occur with changes beyond development. Notably, excitatory-PV interneuron connectivity rates and unitary synaptic strength were unaltered by CP-AMPAR removal, which suggested that the selectivity of PV interneurons can be altered without markedly changing connectivity. In Gria2-knockout mice, in which all AMPARs are calcium-permeable, excitatory neurons showed significantly degraded orientation selectivity, which suggested that CP-AMPARs are sufficient to drive lower selectivity regardless of cell type. Moreover, hippocampal PV interneurons, which usually exhibit low spatial tuning, became more spatially selective after removing CP-AMPARs, which indicated that CP-AMPARs suppress the feature selectivity of PV interneurons independent of modality. These results reveal a new role of CP-AMPARs in maintaining low-selectivity sensory representation in PV interneurons and implicate a conserved molecular mechanism that distinguishes this cell type in the neocortex.

3.
Nature ; 595(7868): 521-525, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34290425

RESUMEN

Whereas ferromagnets have been known and used for millennia, antiferromagnets were only discovered in the 1930s1. At large scale, because of the absence of global magnetization, antiferromagnets may seem to behave like any non-magnetic material. At the microscopic level, however, the opposite alignment of spins forms a rich internal structure. In topological antiferromagnets, this internal structure leads to the possibility that the property known as the Berry phase can acquire distinct spatial textures2,3. Here we study this possibility in an antiferromagnetic axion insulator-even-layered, two-dimensional MnBi2Te4-in which spatial degrees of freedom correspond to different layers. We observe a type of Hall effect-the layer Hall effect-in which electrons from the top and bottom layers spontaneously deflect in opposite directions. Specifically, under zero electric field, even-layered MnBi2Te4 shows no anomalous Hall effect. However, applying an electric field leads to the emergence of a large, layer-polarized anomalous Hall effect of about 0.5e2/h (where e is the electron charge and h is Planck's constant). This layer Hall effect uncovers an unusual layer-locked Berry curvature, which serves to characterize the axion insulator state. Moreover, we find that the layer-locked Berry curvature can be manipulated by the axion field formed from the dot product of the electric and magnetic field vectors. Our results offer new pathways to detect and manipulate the internal spatial structure of fully compensated topological antiferromagnets4-9. The layer-locked Berry curvature represents a first step towards spatial engineering of the Berry phase through effects such as layer-specific moiré potential.

4.
Blood ; 141(13): 1574-1583, 2023 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-35984902

RESUMEN

Although translocation events between chromosome 4 (NSD2 gene) and chromosome 14 (immunoglobulin heavy chain [IgH] locus) (t(4;14)) is considered high risk in newly diagnosed multiple myeloma (NDMM), only ∼30% to 40% of t(4;14) patients are clinically high risk. We generated and compared a large whole genome sequencing (WGS) and transcriptome (RNA sequencing) from 258 t(4;14) (n = 153 discovery, n = 105 replication) and 183 non-t(4;14) NDMM patients with associated clinical data. A landmark survival analysis indicated only ∼25% of t(4;14) patients had an overall survival (OS) <24 months, and a comparative analysis of the patient subgroups identified biomarkers associated with this poor outcome, including translocation breakpoints located in the NSD2 gene and expression of IgH-NSD2 fusion transcripts. Three breakpoints were identified and are designated as: "no-disruption" (upstream of NSD2), "early-disruption" (in the 5' UTR), and "late-disruption" (within the NSD2 gene). Our results show a significant difference in OS based on the location of DNA breakpoints (median OS 28.6 "late-disruption" vs 59.2 "early disruption" vs 75.1 months "no disruption"). These findings have been replicated in an independent replication dataset. Also, univariate and multivariate analysis suggest high-risk markers such as del17p, 1p independently contribute to poor outcome in t(4;14) MM patients.


Asunto(s)
Mieloma Múltiple , Humanos , Mieloma Múltiple/metabolismo , Secuencia de Bases , Translocación Genética , Transcriptoma
5.
Nat Rev Neurosci ; 21(10): 551-564, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32873937

RESUMEN

Astrocytes functionally interact with neurons and with other brain cells. Although not electrically excitable, astrocytes display a complex repertoire of intracellular Ca2+ signalling that evolves in space and time within single astrocytes and across astrocytic networks. Decoding the physiological meaning of these dynamic changes in astrocytic Ca2+ activity has remained a major challenge. This Review describes experimental preparations and methods for recording and studying Ca2+ activity in astrocytes, focusing on the analysis of Ca2+ signalling events in single astrocytes and in astrocytic networks. The limitations of existing experimental approaches and ongoing technical and conceptual challenges in the interpretation of astrocytic Ca2+ events and their spatio-temporal patterns are also discussed.


Asunto(s)
Astrocitos/fisiología , Encéfalo/fisiología , Señalización del Calcio/fisiología , Neuronas/fisiología , Animales , Células Cultivadas , Humanos , Imagen Óptica
6.
Nature ; 573(7775): 539-545, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31534222

RESUMEN

High-grade gliomas are lethal brain cancers whose progression is robustly regulated by neuronal activity. Activity-regulated release of growth factors promotes glioma growth, but this alone is insufficient to explain the effect that neuronal activity exerts on glioma progression. Here we show that neuron and glioma interactions include electrochemical communication through bona fide AMPA receptor-dependent neuron-glioma synapses. Neuronal activity also evokes non-synaptic activity-dependent potassium currents that are amplified by gap junction-mediated tumour interconnections, forming an electrically coupled network. Depolarization of glioma membranes assessed by in vivo optogenetics promotes proliferation, whereas pharmacologically or genetically blocking electrochemical signalling inhibits the growth of glioma xenografts and extends mouse survival. Emphasizing the positive feedback mechanisms by which gliomas increase neuronal excitability and thus activity-regulated glioma growth, human intraoperative electrocorticography demonstrates increased cortical excitability in the glioma-infiltrated brain. Together, these findings indicate that synaptic and electrical integration into neural circuits promotes glioma progression.


Asunto(s)
Encéfalo/fisiopatología , Sinapsis Eléctricas/patología , Fenómenos Electrofisiológicos , Glioma/fisiopatología , Animales , Encéfalo/citología , Membrana Celular/patología , Proliferación Celular , Uniones Comunicantes/patología , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Xenoinjertos , Humanos , Ratones , Ratones Endogámicos NOD , Neuronas/patología , Optogenética , Potasio/metabolismo , Transmisión Sináptica , Células Tumorales Cultivadas
7.
Nature ; 573(7775): 532-538, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31534219

RESUMEN

A network of communicating tumour cells that is connected by tumour microtubes mediates the progression of incurable gliomas. Moreover, neuronal activity can foster malignant behaviour of glioma cells by non-synaptic paracrine and autocrine mechanisms. Here we report a direct communication channel between neurons and glioma cells in different disease models and human tumours: functional bona fide chemical synapses between presynaptic neurons and postsynaptic glioma cells. These neurogliomal synapses show a typical synaptic ultrastructure, are located on tumour microtubes, and produce postsynaptic currents that are mediated by glutamate receptors of the AMPA subtype. Neuronal activity including epileptic conditions generates synchronised calcium transients in tumour-microtube-connected glioma networks. Glioma-cell-specific genetic perturbation of AMPA receptors reduces calcium-related invasiveness of tumour-microtube-positive tumour cells and glioma growth. Invasion and growth are also reduced by anaesthesia and the AMPA receptor antagonist perampanel, respectively. These findings reveal a biologically relevant direct synaptic communication between neurons and glioma cells with potential clinical implications.


Asunto(s)
Neoplasias Encefálicas/fisiopatología , Progresión de la Enfermedad , Glioma/fisiopatología , Sinapsis/patología , Animales , Neoplasias Encefálicas/ultraestructura , Modelos Animales de Enfermedad , Glioma/ultraestructura , Humanos , Ratones , Microscopía Electrónica de Transmisión , Neuronas/fisiología , Receptores AMPA/genética , Receptores AMPA/metabolismo
8.
Proc Natl Acad Sci U S A ; 119(8)2022 02 22.
Artículo en Inglés | MEDLINE | ID: mdl-35165191

RESUMEN

FOXP1 syndrome caused by haploinsufficiency of the forkhead box protein P1 (FOXP1) gene is a neurodevelopmental disorder that manifests motor dysfunction, intellectual disability, autism, and language impairment. In this study, we used a Foxp1+/- mouse model to address whether cognitive and motor deficits in FOXP1 syndrome are associated with mitochondrial dysfunction and oxidative stress. Here, we show that genes with a role in mitochondrial biogenesis and dynamics (e.g., Foxo1, Pgc-1α, Tfam, Opa1, and Drp1) were dysregulated in the striatum of Foxp1+/- mice at different postnatal stages. Furthermore, these animals exhibit a reduced mitochondrial membrane potential and complex I activity, as well as decreased expression of the antioxidants superoxide dismutase 2 (Sod2) and glutathione (GSH), resulting in increased oxidative stress and lipid peroxidation. These features can explain the reduced neurite branching, learning and memory, endurance, and motor coordination that we observed in these animals. Taken together, we provide strong evidence of mitochondrial dysfunction in Foxp1+/- mice, suggesting that insufficient energy supply and excessive oxidative stress underlie the cognitive and motor impairment in FOXP1 deficiency.


Asunto(s)
Factores de Transcripción Forkhead/genética , Discapacidad Intelectual/genética , Trastornos Motores/genética , Proteínas Represoras/genética , Animales , Trastorno del Espectro Autista/genética , Trastorno Autístico/metabolismo , Cognición/fisiología , Modelos Animales de Enfermedad , Factores de Transcripción Forkhead/deficiencia , Factores de Transcripción Forkhead/metabolismo , Haploinsuficiencia/genética , Ratones , Ratones Endogámicos C57BL , Mitocondrias/genética , Mitocondrias/metabolismo , Actividad Motora/genética , Trastornos Motores/metabolismo , Trastornos del Neurodesarrollo/metabolismo , Neurogénesis , Estrés Oxidativo/fisiología , Proteínas Represoras/deficiencia , Proteínas Represoras/metabolismo
9.
Nano Lett ; 24(31): 9520-9527, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39058474

RESUMEN

Van Hove singularities enhance many-body interactions and induce collective states of matter ranging from superconductivity to magnetism. In magic-angle twisted bilayer graphene, van Hove singularities appear at low energies and are malleable with density, leading to a sequence of Lifshitz transitions and resets observable in Hall measurements. However, without a magnetic field, linear transport measurements have limited sensitivity to the band's topology. Here, we utilize nonlinear longitudinal and transverse transport measurements to probe these unique features in twisted bilayer graphene at zero magnetic field. We demonstrate that the nonlinear responses, induced by the Berry curvature dipole and extrinsic scattering processes, intricately map the Fermi surface reconstructions at various fillings. Importantly, our experiments highlight the intrinsic connection of these features with the moiré bands. Beyond corroborating the insights from linear Hall measurements, our findings establish nonlinear transport as a pivotal tool for probing band topology and correlated phenomena.

10.
Nat Methods ; 18(10): 1253-1258, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34594033

RESUMEN

Multiphoton microscopy has become a powerful tool with which to visualize the morphology and function of neural cells and circuits in the intact mammalian brain. However, tissue scattering, optical aberrations and motion artifacts degrade the imaging performance at depth. Here we describe a minimally invasive intravital imaging methodology based on three-photon excitation, indirect adaptive optics (AO) and active electrocardiogram gating to advance deep-tissue imaging. Our modal-based, sensorless AO approach is robust to low signal-to-noise ratios as commonly encountered in deep scattering tissues such as the mouse brain, and permits AO correction over large axial fields of view. We demonstrate near-diffraction-limited imaging of deep cortical spines and (sub)cortical dendrites up to a depth of 1.4 mm (the edge of the mouse CA1 hippocampus). In addition, we show applications to deep-layer calcium imaging of astrocytes, including fibrous astrocytes that reside in the highly scattering corpus callosum.


Asunto(s)
Procesamiento de Imagen Asistido por Computador/métodos , Microscopía de Fluorescencia por Excitación Multifotónica/métodos , Neuroimagen/métodos , Animales , Astrocitos/metabolismo , Señalización del Calcio , Femenino , Proteínas Fluorescentes Verdes , Masculino , Ratones , Ratones Transgénicos , Programas Informáticos , Antígenos Thy-1
11.
J Pediatr ; 275: 114241, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39151604

RESUMEN

OBJECTIVE: To determine the association between indoor air pollution and respiratory morbidities in children with bronchopulmonary dysplasia (BPD) recruited from the multicenter BPD Collaborative. STUDY DESIGN: A cross-sectional study was performed among participants <3 years old in the BPD Collaborative Outpatient Registry. Indoor air pollution was defined as any reported exposure to tobacco or marijuana smoke, electronic cigarette emissions, gas stoves, and/or wood stoves. Clinical data included acute care use and chronic respiratory symptoms in the past 4 weeks. RESULTS: A total of 1011 participants born at a mean gestational age of 26.4 ± 2.2 weeks were included. Most (66.6%) had severe BPD. More than 40% of participants were exposed to ≥1 source of indoor air pollution. The odds of reporting an emergency department visit (OR, 1.7; 95% CI, 1.18-2.45), antibiotic use (OR, 1.9; 95% CI, 1.12-3.21), or a systemic steroid course (OR, 2.18; 95% CI, 1.24-3.84) were significantly higher in participants reporting exposure to secondhand smoke (SHS) compared with those without SHS exposure. Participants reporting exposure to air pollution (not including SHS) also had a significantly greater odds (OR, 1.48; 95% CI, 1.08-2.03) of antibiotic use as well. Indoor air pollution exposure (including SHS) was not associated with chronic respiratory symptoms or rescue medication use. CONCLUSIONS: Exposure to indoor air pollution, especially SHS, was associated with acute respiratory morbidities, including emergency department visits, antibiotics for respiratory illnesses, and systemic steroid use.

12.
Oncology ; : 1-15, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39299227

RESUMEN

Background Preoperative diagnosis of parathyroid cancer (PTTC) where possible allows for en-bloc resection of the tumour, which is associated with excellent prognosis. The rule of > 3 (size of tumour larger than 3cm; corrected calcium more 3mmol/L) as proposed by Schulte and Talat, has a specificity of 95% in predicting malignancy in parathyroid neoplasms. We looked at the impact of rule of 3's in predicting malignancy and outcomes on intervention in a South Asia cohort. Methods Patients who underwent parathyroid surgery between 2010 - 2023 at two tertiary referral centres were assessed. Patients with PTTC were selected and their clinicopathological parameters, treatment modalities, and outcomes were analyzed. Results 13 of 336 (3.8%) patients with a mean age of 61.8 (+/-17.5) years was diagnosed with PC during the study period. The highest mean preoperative values were: PTH (92.4+/-66.27 pmol/L), highest corrected calcium (3.21+/- 0.28 mmol/L) and alkaline phosphatase (419 IU/ml). Nine patients underwent en bloc excision while the other had focussed parathyroidectomy. Recurrences were recorded in 2 (28.5%) patients over a mean follow up period of 69 (+/-48.6) months. One patient with lung metastasis underwent video assisted thoracic surgery (VATS). There was no disease specific mortality in this cohort during the study period. Conclusions In our experience, the predictive rule of 3's has low sensitivity to suspect parathyroid cancer preoperatively, resulting in limited usefulness in clinical practice. Outcomes appear to be less favourable with higher recurrence rates in cases where less than enbloc resection is performed.

13.
Phys Rev Lett ; 132(9): 096302, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38489650

RESUMEN

The valley Hall effect arises from valley-contrasting Berry curvature and requires inversion symmetry breaking. Here, we propose a nonlinear mechanism to generate a valley Hall current in systems with both inversion and time-reversal symmetry, where the linear and second-order charge Hall currents vanish along with the linear valley Hall current. We show that a second-order valley Hall signal emerges from the electric field correction to the Berry curvature, provided a valley-contrasting anisotropic dispersion is engineered. We demonstrate the nonlinear valley Hall effect in tilted massless Dirac fermions in strained graphene and organic semiconductors. Our Letter opens up the possibility of controlling the valley degree of freedom in inversion symmetric systems via nonlinear valleytronics.

14.
Pediatr Res ; 2024 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-39181986

RESUMEN

BACKGROUND: To characterize a cohort of ventilator-dependent infants and children with bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH) and to describe their cardiorespiratory outcomes. METHODS: Subjects with BPD on chronic home ventilation were recruited from outpatient clinics. PH was defined by its presence on ≥1 cardiac catheterization or echocardiogram on or after 36 weeks post-menstrual age. Kaplan-Meier analysis was used to compare the timing of key events. RESULTS: Of the 154 subjects, 93 (60.4%) had PH and of those, 52 (55.9%) required PH-specific medications. The ages at tracheostomy, transition to home ventilator, and hospital discharge were older in those with PH. Most subjects were weaned off oxygen and liberated from the ventilator by 5 years of age, which did not occur later in subjects with PH. The mortality rate after initial discharge was 2.6%. CONCLUSIONS: The majority of infants with BPD-PH receiving chronic invasive ventilation at home survived after initial discharge. Subjects with BPD-PH improved over time as evidenced by weaning off oxygen and PH medications, ventilator liberation, and tracheostomy decannulation. While the presence of PH was not associated with later ventilator liberation or decannulation, the use of PH medications may be a marker of a more protracted disease trajectory. IMPACT STATEMENT: There is limited data on long-term outcomes of children with bronchopulmonary dysplasia (BPD) who receive chronic invasive ventilation at home, and no data on those with the comorbidity of pulmonary hypertension (PH). Almost all subjects with BPD-PH who were on chronic invasive ventilation at home survived after their initial hospital discharge. Subjects with BPD-PH improved over time as evidenced by weaning off oxygen, PH medications, liberation from the ventilator, and tracheostomy decannulation. The presence of PH did not result in later ventilator liberation or decannulation; however, the use of outpatient PH medications was associated with later ventilation liberation and decannulation.

15.
Radiographics ; 44(10): e240037, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39356632

RESUMEN

The past decade has seen exponential advancements in molecular markers and the genetics of tumors, recognizing the limitations of conventional histopathology for grading, classification, and prognostication. Such advances have resulted in changes to classification systems, for example, with the incorporation of objective molecular and genetic information into the 2021 World Health Organization (WHO) classification of central nervous system tumors. The fifth edition of the WHO classification of head and neck tumors (HN5) (beta online version, 2022) also introduced major changes based on molecular markers, including additions, deletions, and reclassifications of entities, with the idea of being more objective and standardized. These changes are highly relevant to therapy decisions, prognosis, and clinical research and for patients with resistant diseases to explore options in clinical trials. The HN5, for the first time, included a radiologist as a member of the writing team to incorporate pertinent imaging findings into the classification. It is important for the radiologist, as an integral part of the multidisciplinary team, to be up to date about these changes for a better understanding of tumor biology, to integrate this into their clinical practice, and to provide more value in their interpretations. The authors provide a basic understanding of pathology and genetics for the radiologist, highlighting the molecular changes in epithelial (including squamous cell) and nonepithelial tumors of the head and neck. The authors also highlight newly recognized and reclassified tumor entities and provide a brief discussion on the genetic tumor syndromes. ©RSNA, 2024 Supplemental material is available for this article. See the invited commentary by Junn and Baugnon in this issue.


Asunto(s)
Biomarcadores de Tumor , Neoplasias de Cabeza y Cuello , Organización Mundial de la Salud , Humanos , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/clasificación
16.
Radiographics ; 44(8): e230124, 2024 08.
Artículo en Inglés | MEDLINE | ID: mdl-39052499

RESUMEN

Kidney failure (KF) refers to a progressive decline in glomerular filtration rate to below 15 ml/min per 1.73 m2, necessitating renal replacement therapy with dialysis or renal transplant. The hemodynamic and metabolic alterations in KF combined with a proinflammatory and coagulopathic state leads to complex multisystemic complications. The imaging hallmark of systemic manifestations of KF is bone resorption caused by secondary hyperparathyroidism. Other musculoskeletal complications include brown tumor, osteosclerosis, calcinosis, soft-tissue calcification, and amyloid arthropathy. Cardiovascular complications and infections are the leading causes of death in KF. Cardiovascular complications include accelerated atherosclerosis, cardiomyopathy, pericarditis, myocardial calcinosis, and venous thromboembolism. Neurologic complications such as encephalopathy, osmotic demyelination, cerebrovascular disease, and opportunistic infections are also frequently encountered. Pulmonary complications include edema and calcifications. Radiography and CT are used in assessing musculoskeletal and thoracic complications, while MRI plays a key role in assessing neurologic and cardiovascular complications. CT iodinated contrast material is generally avoided in patients with KF except in situations where the benefit of contrast-enhanced CT outweighs the risks and in patients already undergoing maintenance dialysis. At MRI, group II gadolinium-based contrast material can be safely administered in patients with KF. The authors discuss the extrarenal systemic manifestations of KF, the choice of imaging modality in their assessment, and imaging findings of complications. ©RSNA, 2024 Supplemental material is available for this article.


Asunto(s)
Insuficiencia Renal , Humanos , Insuficiencia Renal/diagnóstico por imagen , Enfermedades Cardiovasculares/diagnóstico por imagen
17.
Radiographics ; 44(3): e230083, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38329901

RESUMEN

Metabolic syndrome comprises a set of risk factors that include abdominal obesity, impaired glucose tolerance, hypertriglyceridemia, low high-density lipoprotein levels, and high blood pressure, at least three of which must be fulfilled for diagnosis. Metabolic syndrome has been linked to an increased risk of cardiovascular disease and type 2 diabetes mellitus. Multimodality imaging plays an important role in metabolic syndrome, including diagnosis, risk stratification, and assessment of complications. CT and MRI are the primary tools for quantification of excess fat, including subcutaneous and visceral adipose tissue, as well as fat around organs, which are associated with increased cardiovascular risk. PET has been shown to detect signs of insulin resistance and may detect ectopic sites of brown fat. Cardiovascular disease is an important complication of metabolic syndrome, resulting in subclinical or symptomatic coronary artery disease, alterations in cardiac structure and function with potential progression to heart failure, and systemic vascular disease. CT angiography provides comprehensive evaluation of the coronary and systemic arteries, while cardiac MRI assesses cardiac structure, function, myocardial ischemia, and infarction. Liver damage results from a spectrum of nonalcoholic fatty liver disease ranging from steatosis to fibrosis and possible cirrhosis. US, CT, and MRI are useful in assessing steatosis and can be performed to detect and grade hepatic fibrosis, particularly using elastography techniques. Metabolic syndrome also has deleterious effects on the pancreas, kidney, gastrointestinal tract, and ovaries, including increased risk for several malignancies. Metabolic syndrome is associated with cerebral infarcts, best evaluated with MRI, and has been linked with cognitive decline. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material. See the invited commentary by Pickhardt in this issue.


Asunto(s)
Enfermedades Cardiovasculares , Enfermedad de la Arteria Coronaria , Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Síndrome Metabólico , Humanos , Síndrome Metabólico/diagnóstico por imagen , Síndrome Metabólico/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Enfermedades Cardiovasculares/diagnóstico por imagen , Factores de Riesgo
18.
World J Surg ; 48(3): 729-738, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38299448

RESUMEN

BACKGROUND: Pediatric endocrine disorders requiring surgical intervention are rare and so are experienced surgeons dealing with these. The aim of the current study was to investigate disease profile and perioperative outcome of pediatric patients with surgical endocrine disorders in an endocrine surgery unit. METHODS: This retrospective study (Sep 1989-Aug 2019) consisted of pediatric endocrine surgery patients (<18 years) who were managed by a team of pediatric endocrinologists and endocrine surgeons at our center. Patients were divided into three cohorts consisting of a decade each. Clinico-pathologic variables, perioperative events operative and follow-up details were recorded. RESULTS: A total of 332 children were included and their mean age was 14.6 ± 3.9 years (M:F = 1:1.6). Thyroid disorders were most prevalent (59.8%), followed by adrenal (28.2%), parathyroid (10.4%), and pancreas (1.5%). Incidence of benign, malignant, and congenital/developmental disorders were 65.4, 28.1 and 8.3, respectively. Familial association was observed in 8.9% children, which is highest among pheochromocytoma patients. Overall, 201 thyroidectomies + associated procedures, 35 parathyroidectomies, 96 adrenal and paraganglioma resections, and 5 pancreatic procedures were performed. Median hospital stay was 5.6 ± 4.1 days. The number of cases increased significantly over 3 decades. Clinical profile and outcome did not vary except for significant decrease in incidence of malignant pathology (p = 0.04) and increase in VHL cases (p = 0.04) in the last decade though overall increase in familial cases was nonsignificant (p = 0.11). No perioperative mortality was observed except for 3% after adrenalectomy. CONCLUSION: A team of dedicated endocrine surgeons and pediatric endocrinologists is effective in management of pediatric endocrine surgery.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales , Procedimientos Quirúrgicos Endocrinos , Enfermedades del Sistema Endocrino , Feocromocitoma , Cirujanos , Humanos , Niño , Adolescente , Estudios Retrospectivos , Feocromocitoma/cirugía , Enfermedades del Sistema Endocrino/epidemiología , Enfermedades del Sistema Endocrino/cirugía , Neoplasias de las Glándulas Suprarrenales/cirugía
19.
Nano Lett ; 23(15): 6792-6798, 2023 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-37477991

RESUMEN

In this Letter, we provide experimental evidence of the time-reversal symmetric Hall effect in a mesoscopic system, namely, high-mobility graphene-WSe2 heterostructures. This linear, dissipative Hall effect, whose sign depends on the sign of the charge carriers, persists up to room temperature. The magnitude and the sign of the Hall signal can be tuned using an external perpendicular electric field. Our joint experimental and theoretical study establishes that the strain induced by lattice mismatch, or alignment angle inhomogeneity, produces anisotropic bands in graphene while simultaneously breaking the inversion symmetry. The band anisotropy and reduced spatial symmetry lead to the appearance of a time-reversal symmetric Hall effect. Our study establishes graphene-transition metal dichalcogenide-based heterostructures as an excellent platform for studying the effects of broken symmetry on the physical properties of band-engineered two-dimensional systems.

20.
Nano Lett ; 23(3): 902-907, 2023 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-36689192

RESUMEN

Magnetic materials exhibiting topological Dirac fermions are attracting significant attention for their promising technological potential in spintronics. In these systems, the combined effect of the spin-orbit coupling and magnetic order enables the realization of novel topological phases with exotic transport properties, including the anomalous Hall effect and magneto-chiral phenomena. Herein, we report experimental signature of topological Dirac antiferromagnetism in TaCoTe2 via angle-resolved photoelectron spectroscopy and first-principles density functional theory calculations. In particular, we find the existence of spin-orbit coupling-induced gaps at the Fermi level, consistent with the manifestation of a large intrinsic nonlinear Hall conductivity. Remarkably, we find that the latter is extremely sensitive to the orientation of the Néel vector, suggesting TaCoTe2 as a suitable candidate for the realization of non-volatile spintronic devices with an unprecedented level of intrinsic tunability.

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