RESUMEN
Cognitive faculties such as imagination, planning, and decision-making entail the ability to represent hypothetical experience. Crucially, animal behavior in natural settings implies that the brain can represent hypothetical future experience not only quickly but also constantly over time, as external events continually unfold. To determine how this is possible, we recorded neural activity in the hippocampus of rats navigating a maze with multiple spatial paths. We found neural activity encoding two possible future scenarios (two upcoming maze paths) in constant alternation at 8 Hz: one scenario per â¼125-ms cycle. Further, we found that the underlying dynamics of cycling (both inter- and intra-cycle dynamics) generalized across qualitatively different representational correlates (location and direction). Notably, cycling occurred across moving behaviors, including during running. These findings identify a general dynamic process capable of quickly and continually representing hypothetical experience, including that of multiple possible futures.
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Conducta Animal/fisiología , Cognición/fisiología , Toma de Decisiones/fisiología , Hipocampo/fisiología , Potenciales de Acción/fisiología , Animales , Locomoción/fisiología , Masculino , Aprendizaje por Laberinto/fisiología , Red Nerviosa/fisiología , Neuronas/fisiología , Ratas , Ratas Long-Evans , Ritmo Teta/fisiologíaRESUMEN
Understanding the neural basis of speech perception requires that we study the human brain both at the scale of the fundamental computational unit of neurons and in their organization across the depth of cortex. Here we used high-density Neuropixels arrays1-3 to record from 685 neurons across cortical layers at nine sites in a high-level auditory region that is critical for speech, the superior temporal gyrus4,5, while participants listened to spoken sentences. Single neurons encoded a wide range of speech sound cues, including features of consonants and vowels, relative vocal pitch, onsets, amplitude envelope and sequence statistics. Neurons at each cross-laminar recording exhibited dominant tuning to a primary speech feature while also containing a substantial proportion of neurons that encoded other features contributing to heterogeneous selectivity. Spatially, neurons at similar cortical depths tended to encode similar speech features. Activity across all cortical layers was predictive of high-frequency field potentials (electrocorticography), providing a neuronal origin for macroelectrode recordings from the cortical surface. Together, these results establish single-neuron tuning across the cortical laminae as an important dimension of speech encoding in human superior temporal gyrus.
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Corteza Auditiva , Neuronas , Percepción del Habla , Lóbulo Temporal , Humanos , Estimulación Acústica , Corteza Auditiva/citología , Corteza Auditiva/fisiología , Neuronas/fisiología , Fonética , Habla , Percepción del Habla/fisiología , Lóbulo Temporal/citología , Lóbulo Temporal/fisiología , Señales (Psicología) , ElectrodosRESUMEN
BACKGROUND: The aims of this study are to report our experience with treosulfan-based conditioning regimens for patients with non-malignant hematologic conditions, correlating clinical outcomes at different time points post-transplant with treosulfan exposure (AUC). METHODS: This study was a single-center observational study investigating overall survival (OS), disease-free survival (DFS), and event-free survival (EFS) end-points post-transplant. The consequences of treosulfan AUC with respect to toxicity, correction of underlying disease, and long-term chimerism were also explored using pharmacokinetic analysis. RESULTS: Forty-six patients received 49 transplants with treosulfan and fludarabine-based conditioning between 2005 and 2023. Twenty-four patients also received thiotepa. Donor chimerism was assessed on either whole blood or sorted cell lines at different time points post-transplant. Thirty-nine patients received treosulfan pharmacokinetic assessment to evaluate cumulative AUC, with five infants receiving real-time assessment to facilitate daily dose adjustment. OS, DFS, and EFS were 87%, 81%, and 69%, respectively. Median follow-up was 32.1 months (range 0.82-160 months) following transplant. Lower EFS was associated with patient age (<1 year; p = .057) and lower cumulative treosulfan dose (<42 g/m2; p = .003). Stable donor chimerism in B-cell, NK-cell, and granulocyte lineages at 1-year post-transplant were more prevalent in patients receiving thiotepa conditioning. Two infants required daily dose adjustment to treosulfan to avoid high AUC. CONCLUSIONS: Excellent clinical outcomes and stable chimerism were observed in this patient series. The addition of thiotepa conferred no significant toxicity and trended toward sustained ongoing donor engraftment. Correlating treosulfan AUC with long-term patient outcomes is required.
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Busulfano , Trasplante de Células Madre Hematopoyéticas , Acondicionamiento Pretrasplante , Humanos , Busulfano/análogos & derivados , Busulfano/uso terapéutico , Busulfano/farmacocinética , Busulfano/administración & dosificación , Acondicionamiento Pretrasplante/métodos , Masculino , Trasplante de Células Madre Hematopoyéticas/métodos , Femenino , Lactante , Preescolar , Niño , Adolescente , Adulto Joven , Adulto , Resultado del Tratamiento , Estudios Retrospectivos , Vidarabina/análogos & derivados , Vidarabina/uso terapéutico , Vidarabina/administración & dosificación , Tiotepa/uso terapéutico , Tiotepa/administración & dosificación , Tiotepa/farmacocinética , Supervivencia sin Enfermedad , Estudios de Seguimiento , Enfermedades Hematológicas/terapia , Antineoplásicos Alquilantes/uso terapéutico , Antineoplásicos Alquilantes/farmacocinética , Antineoplásicos Alquilantes/administración & dosificaciónRESUMEN
Nephrotic syndrome (NS) is a common kidney disease of childhood, affecting 2-7 children per 100,000. A potentially life-threatening complication affecting children with NS is thromboembolism (TE). However, there remains a paucity of information regarding the burden of TE and its associated risk factors in this population. A systematic review was performed on observational studies examining TE events in children with NS, published in Medline, Embase, CINAHL, and CENTRAL, until May 2021. Meta-analyses were separately conducted on the prevalence of TE within articles exclusively studying children with congenital NS and among articles including all forms of NS. Out of 13,626 articles, 22 were included (14,290 children). The pooled prevalence of symptomatic TE among articles including patients with all forms of NS was 3.60% (95% CI 1.95-5.63), which increased to 8.70% (95% CI 5.11-12.96) in articles with exclusively congenital NS patients. Children with steroid-resistant NS were at a higher risk of TE compared to steroid-sensitive children (OR 4.40, 95% CI 1.34-15.59, p = 0.013). Focal segmental glomerulosclerosis was the most common histology present in patients with TE (51.2%). Children diagnosed with NS have a significant risk of TE, particularly in patients with congenital NS and steroid resistance. IMPACT: The prevalence of symptomatic thromboembolic (TE) events in children with nephrotic syndrome (NS) was 3.60% (95% CI 1.95-5.63), which increased more than two-fold in children with congenital NS to 8.70% (95% CI 5.11-12.96). Potential risk factors for TE events in this population include congenital forms of NS and steroid resistance. This review provides a better estimate of the prevalence of TE in children with NS, while identifying potentially higher-risk populations who may benefit from TE screening and thromboprophylaxis.
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Síndrome Nefrótico , Tromboembolia Venosa , Niño , Humanos , Síndrome Nefrótico/complicaciones , Síndrome Nefrótico/epidemiología , Síndrome Nefrótico/tratamiento farmacológico , Anticoagulantes/uso terapéutico , Tromboembolia Venosa/complicaciones , Esteroides/uso terapéuticoRESUMEN
AIM: To investigate the pharmacokinetics (PK) of intravenous treosulfan in paediatric patients undergoing haematopoietic stem cell transplantation (HSCT) for a broad range of diseases and to explore the impact of different dosing regimens on treosulfan exposure (area under the concentration-time curve, AUC0â∞ ) through dosing simulations. METHODS: A prospective multicentre PK study was conducted using treosulfan concentration data (n = 423) collected from 53 children (median age 3.5, range 0.2-17.0 years) receiving three daily age-guided doses (10-14 g/m2 ). Population PK modelling was performed using NONMEM software, utilising a stepwise forward selection backward elimination method and likelihood-ratio test for screening covariates to describe PK variability. Monte Carlo simulation was used to generate patient PK data for 10 000 virtual paediatric patients and cumulative AUC0â∞ values were evaluated using age, body surface area (BSA) and model-based dosing regimens, targeting 4800 mg*h/L. RESULTS: Treosulfan concentration data were described using a one-compartment PK model with first-order elimination. Population mean (95% CI) estimates for clearance (CL) and volume of distribution (V) were 16.3 (14.9-18.1) L/h and 41.9 (38.8-45.1) L, respectively. Allometrically scaled body weight was the best covariate descriptor for CL and V, and maturational age further explained variability in CL. Dosing simulations indicated that in young patient groups (<2 years), a model-based dosing regimen more accurately achieved the target AUC0â∞ (58.3%) over the age (42.6%) and BSA-based (51.3%) regimens. CONCLUSION: Treosulfan disposition was described through allometric body weight and maturational age descriptors. Model-informed dosing is recommended for patients under 2 years. Treosulfan PK parameters and AUC0â∞ were not influenced by patient disease.
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Busulfano , Trasplante de Células Madre Hematopoyéticas , Niño , Humanos , Lactante , Preescolar , Adolescente , Estudios Prospectivos , Busulfano/farmacocinética , Peso Corporal , Trasplante de Células Madre Hematopoyéticas/efectos adversosRESUMEN
N,N-dimethylacetamide is an excipient used in intravenous busulfan formulations, a drug used in hematopoietic stem cell transplantation conditioning. The aim of this study was to develop and validate a liquid chromatography-tandem mass spectrometry method for simultaneous quantification of N,N-dimethylacetamide, and its metabolite N-monomethylacetamide in plasma from children receiving busulfan. A 4 µl aliquot of patient plasma was extracted using 196 µl 50% methanol solution and quantified against calibrators prepared in the extraction solvent given negligible matrix effects across three concentrations. 9 [H2 ]-N,N-dimethylacetamide was used as an internal standard. Separation of N,N-dimethylacetamide and N-monomethylacetamide was achieved using a Kinetex EVO C18 stationary phase (100 mm × 2.1 mm × 2.6 µm) running an isocratic mobile phase of 30% methanol containing 0.1% formic acid at a flow of 0.2 ml/min over 3.0 min. The injection volume was 1 µl. Calibration curves for N,N-dimethylacetamide and N-monomethylacetamide were linear up to 1200 and 200 µg/L, respectively, with a lower limit of quantification 1 µg/L for both analytes. Calibrator accuracy and precision were within ± 10% of the test parameters across four concentration levels. Analytes were stable over 14 days at three different storage conditions. This method was successfully applied to measure N,N-dimethylacetamide and N-monomethylacetamide concentrations in a total of 1265 plasma samples from 77 children.
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Busulfano , Espectrometría de Masas en Tándem , Niño , Humanos , Espectrometría de Masas en Tándem/métodos , Metanol , Cromatografía Liquida/métodos , Cromatografía Líquida de Alta Presión/métodosRESUMEN
OBJECTIVE: Stress system dysregulation is considered to have an important role in the aetiology of paediatric functional neurological (conversion) disorder. This study examined salivary cortisol and α-amylase awakening responses in children with functional neurological disorder to determine activation patterns of the hypothalamic-pituitary-adrenal axis and sympathetic system. A healthy cortisol awakening response involves a robust increase in cortisol within 30 minutes of awakening. Alpha-amylase awakening response is variable in children. METHODS: Cortisol and α-amylase were measured in saliva from 32 patients with functional neurological disorder (26 girls and 6 boys, aged 11.3-16.1 years) and 31 healthy controls (23 girls and 8 boys, aged 8.6-17.7 years). Saliva samples were collected using a Salivette sampling device at two time points - upon awakening and 30 minutes after awakening. RESULTS: Patients with functional neurological disorder showed a decrease in cortisol awakening response (-4 nmol.min/L) and controls showed an increase (107 nmol.min/L), t(55) = -.4.6, p < 0.001. Within the functional neurological disorder group, 57% showed an attenuated cortisol awakening response and 43% showed an obliterated/reversed cortisol awakening response: Cortisol awakening response was negatively correlated with adverse childhood experiences, r(58) = -0.6, p = 0.002, and subjective distress (total Depression Anxiety and Stress Scales score), r(58) = -0.4, p = 0.050. In controls, cortisol awakening response showed no correlation with adverse childhood experiences and a positive correlation with subjective distress, r(56) = 0.4, p = 0.023. Total cortisol remained similar between the functional neurological disorder and control group. No significant differences were observed between the functional neurological disorder and control group in any of the α-amylase analyses. DISCUSSION: The results suggest dysregulation of the hypothalamic-pituitary-adrenal axis in children with functional neurological disorder. Hypothalamic-pituitary-adrenal dysregulation in children with functional neurological disorder may contribute to comorbid symptoms of fatigue, sleep disturbance and subjective loss of well-being because circadian rhythms and energy metabolism are disrupted. Hypothalamic-pituitary-adrenal dysregulation - and changes in glucocorticoid (cortisol) signalling at the molecular level - may also contribute to increased vulnerability for functional neurological disorder symptoms because of epigenetically mediated changes to neural networks implicated in functional neurological disorder.
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Trastornos de Conversión , Hidrocortisona , Masculino , Femenino , Humanos , Niño , Adolescente , Hidrocortisona/metabolismo , alfa-Amilasas/metabolismo , Sistema Hipotálamo-Hipofisario , Sistema Hipófiso-Suprarrenal , Ritmo Circadiano/fisiología , Trastornos de Conversión/metabolismoRESUMEN
OBJECTIVE: Seizures are common and significantly disabling for patients with brain metastases (BMs). Although resection can provide seizure control, a subset of patients with BMs may continue to suffer seizures postoperatively. Genomic BM characteristics may influence which patients are at risk for postoperative seizures. This work explores correlations between genomic alterations and risk of postoperative seizures following BM resection. METHODS: All patients underwent BM resection at a single institution, with available clinical and sequencing data on more than 500 oncogenes. Clinical seizures were documented pre- and postoperatively. A random forest machine learning classification was used to determine candidate genomic alterations associated with postoperative seizures, and clinical and top genomic variables were correlated with postoperative seizures by using Cox proportional hazards models. RESULTS: There were 112 patients with BMs who underwent 114 surgeries and had at least 1 month of postoperative follow-up. Seizures occurred preoperatively in 26 (22.8%) patients and postoperatively in 25 (21.9%). The Engel classification achieved at 6 months for those with preoperative seizures was class I in 13 (50%); class II in 6 (23.1%); class III in 5 (19.2%), and class IV in 2 (7.7%). In those with postoperative seizures, only 8 (32.0%) had seizures preoperatively, and preoperative seizures were not a significant predictor of postoperative seizures (HR 1.84; 95% CI 0.79-4.37; p = 0.156). On random forest classification and multivariate Cox analysis controlling for factors including recurrence, extent of resection, and number of BMs, CDKN2A alterations were associated with postoperative seizures (HR 3.22; 95% CI 1.27-8.16; p = 0.014). Melanoma BMs were associated with higher risk of postoperative seizures compared with all other primary malignancies (HR 5.23; 95% CI 1.37-19.98; p = 0.016). Of 39 BMs with CDKN2A alteration, 35.9% (14/39) had postoperative seizures, compared to 14.7% (11/75) without CDKN2A alteration. The overall rate of postoperative seizures in melanoma BMs was 42.9% (15/35), compared with 12.7% (10/79) for all other primary malignancies. CONCLUSIONS: CDKN2A alterations and melanoma primary malignancy are associated with increased postoperative seizure risk following resection of BMs. These results may help guide postoperative seizure prophylaxis in patients undergoing resection of BMs.
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Neoplasias Encefálicas , Convulsiones , Humanos , Estudios Retrospectivos , Convulsiones/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/patología , Genómica , Resultado del Tratamiento , Inhibidor p16 de la Quinasa Dependiente de Ciclina/uso terapéuticoRESUMEN
OBJECTIVE: This study aims at constructing a staging system incorporating tumor regression grade and ypN-category (TRG-N) in patients with neoadjuvant therapy before esophagectomy. It is hypothesized that this would prognosticate better than the current American Joint Committee on Cancer (AJCC) postneoadjuvant therapy (ypTNM) stage groups. BACKGROUND: Conventional pathological T-category is defined by the depth of invasion, and may lose prognostic relevance after neoadjuvant therapy. TRG defines treatment response by the degree of tumor regression, and when combined with ypN-category may be more prognostic than AJCC postneoadjuvant therapy (ypTNM) stage groups. METHODS: A training cohort of 210 patients with esophageal squamous cell carcinoma and who had had neoadjuvant therapy before esophagectomy were studied. A validation cohort comprised 107 patients from another hospital. Resected esophagi were assessed by ypT-category and TRG, the latter assigned according to the Becker 4-tier system. These categories were grouped with ypN-category into a TRG-N system. Patients' survival was compared between the current AJCC postneoadjuvant therapy (ypTNM) stage groups and this TRG-N system. RESULTS: In the training cohort, 5-year survival rates according to ypTNM stage I, II, IIIA, IIIB, and IVA were 53%, 39.4%, 47%, 18.3%, and 0%, respectively. For TRG-N stages I, II, III, and IV, the respective figures were 59.6%, 43.5%, 23.8%, and 15.6%. TRG-N stage showed better fit in survival than ypTNM stage groups, indicated by lower Akaike Information Criteria (AIC) and Bayesian Information Criterion values. Similar results were found in the validation cohort. Multivariate analysis showed that TRG-N stage ( P =0.02), age ( P =0.006), and sex ( P =0.005) were independent prognostic factors. CONCLUSION: TRG-N stage shows better prognostication than the AJCC postneoadjuvant therapy (ypTNM) stage groups.
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Adenocarcinoma , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Adenocarcinoma/patología , Teorema de Bayes , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/terapia , Humanos , Ganglios Linfáticos/patología , Terapia Neoadyuvante/métodos , Estadificación de Neoplasias , Pronóstico , Estudios RetrospectivosRESUMEN
OBJECTIVES: To assess interlaboratory variability of total serum bilirubin (TSB) results in newborns. Initiated following a clinical incident in which a neonate was transferred to a tertiary hospital for treatment of severe hyperbilirubinemia but on arrival was reclassified into a lower risk category due to a 20% difference in TSB between laboratories. METHODS: Fresh residual plasma samples from hospital-born infants were pooled to obtain 11 samples across a range of total bilirubin concentrations. Aliquots were light-protected and measured on 7 commercial platforms at 4 accredited medical laboratories. Data from The Royal College of Pathologists of Australasia Quality Assurance Programs' (RCPAQAP) Neonatal Bilirubin program was analysed. RESULTS: Twenty-four to 30% difference in results for individual samples, largely due to calibration differences between assays. When interpreted according to guidelines, results from different platforms would have led to different clinical interventions in some cases. RCPAQAP results showed significant within-method bias but were not shown to be commutable with patient samples. CONCLUSIONS: There are clinically significant method-dependent differences in TSB results from neonatal samples, consistent with our clinical incident. The differences are largely due to lack of standardisation of calibrator values. This has implications for healthcare resource use and possibly for the neurodevelopment of infants. Intervention is needed at a number of levels, including clinical reporting of incidents arising from discordant results, commitment by manufacturers to ensure metrological traceability of methods with sufficiently low uncertainty in the final measurements, and availability of commutable quality assurance material to monitor assay performance, especially at the clinical decision points for neonatal jaundice.
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Hiperbilirrubinemia Neonatal , Ictericia Neonatal , Bilirrubina , Calibración , Humanos , Hiperbilirrubinemia Neonatal/diagnóstico , Hiperbilirrubinemia Neonatal/terapia , Lactante , Recién Nacido , Ictericia Neonatal/terapia , Estándares de ReferenciaRESUMEN
How does an animal know where it is when it stops moving? Hippocampal place cells fire at discrete locations as subjects traverse space, thereby providing an explicit neural code for current location during locomotion. In contrast, during awake immobility, the hippocampus is thought to be dominated by neural firing representing past and possible future experience. The question of whether and how the hippocampus constructs a representation of current location in the absence of locomotion has been unresolved. Here we report that a distinct population of hippocampal neurons, located in the CA2 subregion, signals current location during immobility, and does so in association with a previously unidentified hippocampus-wide network pattern. In addition, signalling of location persists into brief periods of desynchronization prevalent in slow-wave sleep. The hippocampus thus generates a distinct representation of current location during immobility, pointing to mnemonic processing specific to experience occurring in the absence of locomotion.
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Hipocampo/citología , Hipocampo/fisiología , Neuronas/fisiología , Orientación/fisiología , Sueño/fisiología , Percepción Espacial/fisiología , Potenciales de Acción , Animales , Hipocampo/anatomía & histología , Masculino , Modelos Neurológicos , Movimiento , Ratas , Ratas Long-Evans , Memoria Espacial/fisiologíaRESUMEN
AIM: Blood gas analysers which can measure bilirubin in whole blood are commonly available in neonatal intensive care units; however, the accuracy of these measurements is not well established. We sought to determine accuracy of whole blood bilirubin on the Siemens RAPIDPoint 500 blood gas analyser with reference to formal laboratory total serum bilirubin on the Ortho Vitros 5600. METHODS: A method comparison of the bilirubin results from the blood gas analysers compared with the chemistry analysers was performed by data mining of results obtained as part of routine patient care. Results were included if patients underwent bilirubin testing by blood gas analyser and formal TSB, with both samples being collected within 20 min. Retrospective laboratory data was collected over a 28-month period, 1 January 2019 to 1 May 2021. RESULTS: 449 eligible sample pairs were included. A Bland-Altman plot was generated to identify systematic differences between the methods. A mean bias of -11 µmol/L was observed with 95% limits from -60 µmol/L to 38 µmol/L. Some blood gas bilirubin results were up to 70 µmol/L lower than formal TSB measurements around the clinically significant concentration range of 200 to 300 µmol/L. CONCLUSION: Clinicians need to be aware of potential differences between the results from their blood gas analysers compared to formal TSB results. Sole reliance on blood gas bilirubin results which underestimate TSB may lead to under-recognition of neonatal jaundice that meets treatment thresholds. Formal measurement of TSB should be sought to inform decisions regarding treatment of neonatal jaundice.
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Ictericia Neonatal , Bilirrubina , Análisis de los Gases de la Sangre , Minería de Datos , Humanos , Recién Nacido , Tamizaje Neonatal/métodos , Estudios RetrospectivosRESUMEN
The overarching goal of the NIH BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative is to advance the understanding of healthy and diseased brain circuit function through technological innovation. Core principles for this goal include the validation and dissemination of the myriad innovative technologies, tools, methods, and resources emerging from BRAIN-funded research. Innovators, BRAIN funding agencies, and non-Federal partners are working together to develop strategies for making these products usable, available, and accessible to the scientific community. Here, we describe several early strategies for supporting the dissemination of BRAIN technologies. We aim to invigorate a dialogue with the neuroscience research and funding community, interdisciplinary collaborators, and trainees about the existing and future opportunities for cultivating groundbreaking research products into mature, integrated, and adaptable research systems. Along with the accompanying Society for Neuroscience 2019 Mini-Symposium, "BRAIN Initiative: Cutting-Edge Tools and Resources for the Community," we spotlight the work of several BRAIN investigator teams who are making progress toward providing tools, technologies, and services for the neuroscience community. These tools access neural circuits at multiple levels of analysis, from subcellular composition to brain-wide network connectivity, including the following: integrated systems for EM- and florescence-based connectomics, advances in immunolabeling capabilities, and resources for recording and analyzing functional connectivity. Investigators describe how the resources they provide to the community will contribute to achieving the goals of the NIH BRAIN Initiative. Finally, in addition to celebrating the contributions of these BRAIN-funded investigators, the Mini-Symposium will illustrate the broader diversity of BRAIN Initiative investments in cutting-edge technologies and resources.
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Neurociencias/métodos , Investigación , Tecnología , HumanosRESUMEN
There is accumulating evidence that patients with functional neurological symptom disorder (FND) show activation of multiple components of the stress system-the hypothalamic-pituitary-adrenal axis, autonomic nervous system, and brain regions involved in arousal- and emotion-processing. This study aims to examine whether the immune-inflammatory component of the stress system is also activated. C-reactive protein (CRP) blood titre levels were measured in 79 children and adolescents with FND. CRP values ≥ 2 mg/L suggest low-grade inflammation. CRP values > 10 mg/L suggest a disease process. Sixty-six percent of subjects (n = 52) had CRP titres ≥ 2 mg/L. The upward shift in the distribution of CRP levels suggested low-grade inflammation (median CRP concentration was 4.60 mg/L, with 75th and 90th percentiles of 6.1 and 10.3 mg/L, respectively). Elevated CRP titres were not explained by sex, pubertal status, BMI, or medical factors. Confounder analyses suggested that history of maltreatment (χ2 = 2.802, df = 1, p = 0.094, φ = 0.190; ß = 2.823, p = 0.04) and a diagnosis of anxiety (χ2 = 2.731, df = 1, p = 0.098, φ = 0.187; ß = 4.520, p = 0.061) contributed to elevated CRP levels. Future research will need to identify the origins and locations of immune cell activation and the pathways and systems contributing to their activation and modulation. Because functional activity in neurons and glial cells-the brain's innate effector immune cells-is tightly coupled, our finding of elevated CRP titres suggests activation of the immune-inflammatory component of the brain's stress system. A more direct examination of inflammation-related molecules in the brain will help clarify the role of immune-inflammatory processes in FND.
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Proteína C-Reactiva/metabolismo , Enfermedades del Sistema Nervioso/sangre , Enfermedades del Sistema Nervioso/diagnóstico , Trastornos del Neurodesarrollo/sangre , Trastornos del Neurodesarrollo/diagnóstico , Adolescente , Ansiedad/sangre , Ansiedad/diagnóstico , Ansiedad/psicología , Biomarcadores/sangre , Encéfalo/metabolismo , Niño , Femenino , Humanos , Sistema Hipotálamo-Hipofisario/metabolismo , Masculino , Enfermedades del Sistema Nervioso/psicología , Trastornos del Neurodesarrollo/psicología , Sistema Hipófiso-Suprarrenal/metabolismo , Autoinforme/normasRESUMEN
Research on self-compassion and depressive symptoms is growing at an exponential pace. This systematic review provides an in-depth exploration of the relation between self-compassion and depressive symptoms in adolescents. In accordance with PRISMA guidelines, MEDLINE, CINAHL, and PsycINFO databases were systematically searched and 18 studies were identified. Results demonstrate the potentially pertinent role that self-compassion may play in the development, maintenance, and treatment of depression in adolescents, yet reflect on the paucity of research on this topic with respect to mechanisms of change. These studies further highlight how the impact of self-compassion may differ according to gender and age and underscore the need to account for other diversity-related variables, such as ethnic-racial group, socioeconomic status, and sexual orientation. Despite such limitations in the literature, the current findings extend research in adults by providing support for the relevance of self-compassion in adolescence, particularly with respect to the prevention of depressive symptoms.
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Depresión/prevención & control , Empatía , Autoimagen , Adolescente , Adulto , Depresión/psicología , Femenino , Humanos , Masculino , Psicología del AdolescenteRESUMEN
Data sourcesPubMed, Embase, OvidSP, Web of Science, Cochrane and CINAHL databases were searched up to February 2015 with no language restrictions.Study selectionTwo review authors independently assessed tiles and abstracts of the retrieved case-control, cohorts and cross-sectional studies. For the studies to have been included in the meta-analysis, they must have included the total number of hockey players reporting at least one dentofacial injury, the total number of these injuries compared with other types of injuries and quantitative data on characteristics of dentofacial injuries. Recreational and competitive elite level were included.Data extraction and synthesisThe included studies fell into three categories, related to dentofacial injury, mouthguard use or both, and their quality was assessed using the Newcastle-Ottawa Scale (NOS). A random effects model was used to calculate the overall effect size when appropriate; if not, then pooled prevalence was reported. Binary variables were used in order to express the results as Mantel-Haenszel pooled prevalence odds ratios (OR) with 95% confidence intervals (CI) and a p-value of the overall effect. To compare the between-studies differences, a χ2 test was used. The heterogeneity across the studies was evaluated using the I2.ResultsEleven studies were included: six related to dentofacial injury, one related to mouthguard use and four to both. The numbers of field hockey players who presented at least one dentofacial injury was 12.7% (95% CI 8.5% to 17.0%) and 45.2% (95% CI 39.3% to 51.0%) in junior/senior players and elite players, respectively. There were no significant differences with respect to sex. After 2000, 84.5% (95% CI 69.3% to 99.7%) of players regularly wore mouthguards, whereas only 31.4% (95% CI 22.7% to 40.1%) wore mouthguards previous to 2000. The mouthguards were commonly depicted as unnecessary and uncomfortable by players.ConclusionsDentofacial trauma poses a serious problem in field hockey, but a considerable number of players still do not regularly wear mouthguards. The likelihood is that if mouthguard usage were higher, fewer dentofacial injuries would occur during field hockey games and in training.Source of fundingNone declared.
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Traumatismos en Atletas/epidemiología , Hockey/lesiones , Estudios Transversales , Humanos , Protectores Bucales , Traumatismos de los Dientes/epidemiologíaRESUMEN
OBJECTIVE: Broca's aphasia is a syndrome of impaired fluency with retained comprehension. The authors used an unbiased algorithm to examine which neuroanatomical areas are most likely to result in Broca's aphasia following surgical lesions. METHODS: Patients were prospectively evaluated with standardized language batteries before and after surgery. Broca's area was defined anatomically as the pars opercularis and triangularis of the inferior frontal gyrus. Broca's aphasia was defined by the Western Aphasia Battery language assessment. Resections were outlined from MRI scans to construct 3D volumes of interest. These were aligned using a nonlinear transformation to Montreal Neurological Institute brain space. A voxel-based lesion-symptom mapping (VLSM) algorithm was used to test for areas statistically associated with Broca's aphasia when incorporated into a resection, as well as areas associated with deficits in fluency independent of Western Aphasia Battery classification. Postoperative MRI scans were reviewed in blinded fashion to estimate the percentage resection of Broca's area compared to areas identified using the VLSM algorithm. RESULTS: A total of 289 patients had early language evaluations, of whom 19 had postoperative Broca's aphasia. VLSM analysis revealed an area that was highly correlated (p < 0.001) with Broca's aphasia, spanning ventral sensorimotor cortex and supramarginal gyri, as well as extending into subcortical white matter tracts. Reduced fluency scores were significantly associated with an overlapping region of interest. The fluency score was negatively correlated with fraction of resected precentral, postcentral, and supramarginal components of the VLSM area. CONCLUSIONS: Broca's aphasia does not typically arise from neurosurgical resections in Broca's area. When Broca's aphasia does occur after surgery, it is typically in the early postoperative period, improves by 1 month, and is associated with resections of ventral sensorimotor cortex and supramarginal gyri.
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Afasia de Broca , Área de Broca , Humanos , Encéfalo/patología , Imagen por Resonancia Magnética , Mapeo Encefálico , Lóbulo Frontal/patologíaRESUMEN
Penetrating flexible electrode arrays can simultaneously record thousands of individual neurons in the brains of live animals. However, it has been challenging to spatially map and longitudinally monitor the dynamics of large three-dimensional neural networks. Here we show that optimized ultraflexible electrode arrays distributed across multiple cortical regions in head-fixed mice and in freely moving rats allow for months-long stable electrophysiological recording of several thousand neurons at densities of about 1,000 neural units per cubic millimetre. The chronic recordings enhanced decoding accuracy during optogenetic stimulation and enabled the detection of strongly coupled neuron pairs at the million-pair and millisecond scales, and thus the inference of patterns of directional information flow. Longitudinal and volumetric measurements of neural couplings may facilitate the study of large-scale neural circuits.
Asunto(s)
Fenómenos Electrofisiológicos , Roedores , Ratas , Ratones , Animales , Electrodos Implantados , Fenómenos Electrofisiológicos/fisiología , Encéfalo/fisiología , Neuronas/fisiologíaRESUMEN
Objectives: Spine surgery is associated with early impairment of gastrointestinal motility, with postoperative ileus rates of 5-12%. A standardized postoperative medication regimen aimed at early restoration of bowel function can reduce morbidity and cost, and its study should be prioritized. Methods: A standardized postoperative bowel medication protocol was implemented for all elective spine surgeries performed by a single neurosurgeon from March 1, 2022 to June 30, 2022 at a metropolitan Veterans Affairs medical center. Daily bowel function was tracked and medications were advanced using the protocol. Clinical, surgical, and length of stay data are reported. Results: Across 20 consecutive surgeries in 19 patients, mean age was 68.9 years [standard deviation (SD) = 10; range 40-84]. Seventy-four percent reported preoperative constipation. Surgeries consisted of 45% fusion and 55% decompression; lumbar retroperitoneal approaches constituted 30% (10% anterior, 20% lateral). Two patients were discharged in good condition prior to bowel movement after meeting institutional discharge criteria; the other 18 cases all had return of bowel function by postoperative day (POD) 3 (mean = 1.8-days, SD = 0.7). There were no inpatient or 30-day complications. Mean discharge occurred 3.3-days post-surgery (SD = 1.5; range 1-6; home 95%, skilled nursing facility 5%). Estimated cumulative cost of the bowel regimen was $17 on POD 3. Conclusions: Careful monitoring of return of bowel function after elective spine surgery is important for preventing ileus, reducing healthcare cost, and ensuring quality. Our standardized postoperative bowel regimen was associated with return of bowel function within 3 days and low costs. These findings can be utilized in quality-of-care pathways.