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All drugs of abuse induce long-lasting changes in synaptic transmission and neural circuit function that underlie substance-use disorders1,2. Another recently appreciated mechanism of neural circuit plasticity is mediated through activity-regulated changes in myelin that can tune circuit function and influence cognitive behaviour3-7. Here we explore the role of myelin plasticity in dopaminergic circuitry and reward learning. We demonstrate that dopaminergic neuronal activity-regulated myelin plasticity is a key modulator of dopaminergic circuit function and opioid reward. Oligodendroglial lineage cells respond to dopaminergic neuronal activity evoked by optogenetic stimulation of dopaminergic neurons, optogenetic inhibition of GABAergic neurons, or administration of morphine. These oligodendroglial changes are evident selectively within the ventral tegmental area but not along the axonal projections in the medial forebrain bundle nor within the target nucleus accumbens. Genetic blockade of oligodendrogenesis dampens dopamine release dynamics in nucleus accumbens and impairs behavioural conditioning to morphine. Taken together, these findings underscore a critical role for oligodendrogenesis in reward learning and identify dopaminergic neuronal activity-regulated myelin plasticity as an important circuit modification that is required for opioid reward.
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Analgésicos Opioides , Vaina de Mielina , Vías Nerviosas , Plasticidad Neuronal , Recompensa , Área Tegmental Ventral , Animales , Femenino , Masculino , Ratones , Analgésicos Opioides/farmacología , Dopamina/metabolismo , Neuronas Dopaminérgicas/efectos de los fármacos , Neuronas Dopaminérgicas/metabolismo , Neuronas GABAérgicas/metabolismo , Neuronas GABAérgicas/efectos de los fármacos , Ratones Endogámicos C57BL , Morfina/farmacología , Vaina de Mielina/efectos de los fármacos , Vaina de Mielina/metabolismo , Plasticidad Neuronal/efectos de los fármacos , Plasticidad Neuronal/fisiología , Núcleo Accumbens/citología , Núcleo Accumbens/metabolismo , Núcleo Accumbens/fisiología , Núcleo Accumbens/efectos de los fármacos , Oligodendroglía/metabolismo , Oligodendroglía/citología , Oligodendroglía/efectos de los fármacos , Optogenética , Área Tegmental Ventral/fisiología , Área Tegmental Ventral/citología , Área Tegmental Ventral/efectos de los fármacos , Vías Nerviosas/efectos de los fármacos , Linaje de la CélulaRESUMEN
High-grade gliomas (HGG) are deadly diseases for both adult and pediatric patients. Recently, it has been shown that neuronal activity promotes progression of multiple subgroups of HGG. However, epigenetic mechanisms that govern this process remain elusive. Here we report that the chromatin remodeler CHD2 regulates neuron-glioma interactions in diffuse midline glioma (DMG) characterized by onco-histone H3.1K27M. Depletion of CHD2 in H3.1K27M DMG cells compromises cell viability and neuron-to-glioma synaptic connections in vitro, neuron-induced proliferation of H3.1K27M DMG cells in vitro and in vivo, activity-dependent calcium transients in vivo, and extends the survival of H3.1K27M DMG-bearing mice. Mechanistically, CHD2 coordinates with the transcription factor FOSL1 to control the expression of axon-guidance and synaptic genes in H3.1K27M DMG cells. Together, our study reveals a mechanism whereby CHD2 controls the intrinsic gene program of the H3.1K27M DMG subtype, which in turn regulates the tumor growth-promoting interactions of glioma cells with neurons.
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PURPOSE: The purpose of this study is to optimize a dMS-based urinary proteomic technique and evaluate the relationship between urinary proteome content and adaptive changes in bone microarchitecture during BCT. METHODS: Urinary proteomes were analyzed with an optimized dMS technique in two groups of 13 recruits ( N = 26) at the beginning (Pre) and end (Post) of BCT. Matched by age (21 ± 4 yr), sex (16 W), and baseline tibial trabecular bone volume fractions (Tb.BV/TV), these groups were distinguished by the most substantial (High) and minimal (Low) improvements in Tb.BV/TV. Differential protein expression was analyzed with mixed permutation ANOVA and false discovery proportion-based adjustment for multiple comparisons. RESULTS: Tibial Tb.BV/TV increased from pre- to post-BCT in High (3.30 ± 1.64%, P < 0.0001) but not Low (-0.35 ± 1.25%, P = 0.4707). The optimized dMS technique identified 10,431 peptides from 1368 protein groups that represented 165 integrative biological processes. Seventy-four urinary proteins changed from pre- to post-BCT ( P = 0.0019), and neutrophil-mediated immunity was the most prominent ontology. Two proteins (immunoglobulin heavy constant gamma 4 and C-type lectin domain family 4 member G) differed from pre- to post-BCT in High and Low ( P = 0.0006). CONCLUSIONS: The dMS technique can identify more than 1000 urinary proteins. At least 74 proteins are responsive to BCT, and other principally immune system-related proteins show differential expression patterns that coincide with adaptive bone formation.
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Biomarcadores , Hueso Esponjoso , Personal Militar , Proteómica , Humanos , Masculino , Hueso Esponjoso/diagnóstico por imagen , Biomarcadores/orina , Adulto Joven , Tibia/metabolismo , Proteoma , Femenino , AdolescenteRESUMEN
The removal of dental plaque from the gingival margins of the teeth is essential to maintaining periodontal health. Whilst it has been established that electric toothbrushes demonstrate a greater ability to remove plaque, no systematic review has specifically investigated which technology is better for removing plaque from the interdental tooth surfaces, where plaque control may be more difficult. Three databases were searched until October 2023: MEDLINE and DOSSS via EBSCOhost and Embase. Data extraction was carried out on studies which met the inclusion criteria, and a risk of bias assessment was completed. The study findings were combined via a narrative synthesis and a meta-analysis where appropriate. A total of 77 studies were found, out of which 14 were selected and included in the analysis. The mean difference in interproximal plaque reduction, measured using the Rustogi Modified Naval Plaque Index (RMNPI) at 8 weeks, was 0.09 (p < 0.00001) in favor of the oscillating-rotating toothbrush. At 6 and 12 weeks, the mean difference in plaque reduction (RMNPI) was 0.05 (p = 0.0008) and 0.04 (p = 0.0001) in favor of the oscillating-rotating toothbrush, respectively. The studies show a tendency for oscillating-rotating toothbrushes to remove more interproximal plaque than oscillating toothbrushes, especially in a short time (8 weeks).
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For millennia, healing and psychoactive plants have been part of the medicinal and ceremonial fabric of elaborate rituals and everyday religious practices throughout Mesoamerica. Despite the essential nature of these ritual practices to the societal framework of past cultures, a clear understanding of the ceremonial life of the ancient Maya remains stubbornly elusive. Here we record the discovery of a special ritual deposit, likely wrapped in a bundle, located beneath the end field of a Late Preclassic ballcourt in the Helena complex of the Maya city of Yaxnohcah. This discovery was made possible by the application of environmental DNA technology. Plants identified through this analytical process included Ipomoea corymbosa (xtabentun in Mayan), Capsicum sp. (chili pepper or ic in Mayan), Hampea trilobata (jool), and Oxandra lanceolata (chilcahuite). All four plants have recognized medicinal properties. Two of the plants, jool and chilcahuite, are involved in artifact manufacture that have ceremonial connections while chili peppers and xtabentun have been associated with divination rituals. Xtabentun (known to the Aztecs as ololiuhqui) produces highly efficacious hallucinogenic compounds and is reported here from Maya archaeological contexts for the first time.
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Conducta Ceremonial , México , Humanos , Historia Antigua , Plantas Medicinales , Psicotrópicos/historia , ArqueologíaRESUMEN
BACKGROUND: Outpatient visits for nonmelanoma skin cancer (NMSC) and actinic keratoses (AK) have risen steadily in the United States, notably among Medicare beneficiaries. Individuals may delay seeking care for minimally symptomatic conditions until they qualify for Medicare coverage, indicating potential delay of nonurgent screening interventions for uninsured or underinsured patients younger than 65 years. OBJECTIVE: This study investigates whether an atypical increase in outpatient visits for NMSC, AK, or actinic cheilitis (AC) occurs at the age of Medicare transition by utilizing the National Ambulatory Care Survey from 1993 to 2019. MATERIALS AND METHODS: The National Ambulatory Care Survey data were analyzed for patients aged within 5 years of 65 years. Diagnoses were identified using International Classification of Diseases codes. Linear regression and outlier detection were used to identify a relationship between Medicare eligibility and outpatient visits for NMSC and AK/AC. RESULTS: Predicted visits for AK/AC and NMSC increased with age. However, there was no evidence of a disproportionate increase in outpatient visits for NMSC and AK/AC at the age of Medicare eligibility. CONCLUSION: Outside evidence indicates health care utilization increases after Medicare transition. This study's data do not support a corresponding rise in outpatient visits for NMSC and AK/AC at the age of Medicare eligibility.
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Objective: The U.S. Army uses sex-specific circumference-based prediction equations to estimate percent body fat (%BF) to evaluate adherence to body composition standards. The equations are periodically evaluated to ensure that they continue to accurately assess %BF in a diverse population. The objective of this study was to develop and validate alternative field expedient equations that may improve upon the current Army Regulation (AR) body fat (%BF) equations. Methods: Body size and composition were evaluated in a representatively sampled cohort of 1904 active-duty Soldiers (1261 Males, 643 Females), using dual-energy X-ray absorptiometry (%BFDXA), and circumferences obtained with 3D imaging and manual measurements. Sex stratified linear prediction equations for %BF were constructed using internal cross validation with %BFDXA as the criterion measure. Prediction equations were evaluated for accuracy and precision using root mean squared error, bias, and intraclass correlations. Equations were externally validated in a convenient sample of 1073 Soldiers. Results: Three new equations were developed using one to three circumference sites. The predictive values of waist, abdomen, hip circumference, weight and height were evaluated. Changing from a 3-site model to a 1-site model had minimal impact on measurements of model accuracy and performance. Male-specific equations demonstrated larger gains in accuracy, whereas female-specific equations resulted in minor improvements in accuracy compared to existing AR equations. Equations performed similarly in the second external validation cohort. Conclusions: The equations developed improved upon the current AR equation while demonstrating robust and consistent results within an external population. The 1-site waist circumference-based equation utilized the abdominal measurement, which aligns with associated obesity related health outcomes. This could be used to identify individuals at risk for negative health outcomes for earlier intervention.
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Body temperature should be tightly regulated for optimal sleep. However, various extrinsic and intrinsic factors can alter body temperature during sleep. In a free-living study, we examined how sleep and cardiovascular health metrics were affected by sleeping for one week with (Pod ON) vs. without (Pod OFF), an active temperature-controlled mattress cover (the Eight Sleep Pod). A total of 54 subjects wore a home sleep test device (HST) for eight nights: four nights each with Pod ON and OFF (>300 total HST nights). Nightly sleeping heart rate (HR) and heart rate variability (HRV) were collected. Compared to Pod OFF, men and women sleeping at cooler temperatures in the first half of the night significantly improved deep (+14 min; +22% mean change; p = 0.003) and REM (+9 min; +25% mean change; p = 0.033) sleep, respectively. Men sleeping at warm temperatures in the second half of the night significantly improved light sleep (+23 min; +19% mean change; p = 0.023). Overall, sleeping HR (-2% mean change) and HRV (+7% mean change) significantly improved with Pod ON (p < 0.01). To our knowledge, this is the first study to show a continuously temperature-regulated bed surface can (1) significantly modify time spent in specific sleep stages in certain parts of the night, and (2) enhance cardiovascular recovery during sleep.
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OBJECTIVES: Despite being prioritized during initial COVID-19 vaccine rollout, vulnerable individuals at high risk of severe COVID-19 (hospitalization, intensive care unit admission, or death) remain underrepresented in vaccine effectiveness (VE) studies. The RAVEN cohort study (NCT05047822) assessed AZD1222 (ChAdOx1 nCov-19) two-dose primary series VE in vulnerable populations. METHODS: Using the Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub, linked to secondary care, death registration, and COVID-19 datasets in England, COVID-19 outcomes in 2021 were compared in vaccinated and unvaccinated individuals matched on age, sex, region, and multimorbidity. RESULTS: Over 4.5 million AZD1222 recipients were matched (mean follow-up â¼5 months); 68% were ≥50 years, 57% had high multimorbidity. Overall, high VE against severe COVID-19 was demonstrated, with lower VE observed in vulnerable populations. VE against hospitalization was higher in the lowest multimorbidity quartile (91.1%; 95% CI: 90.1, 92.0) than the highest quartile (80.4%; 79.7, 81.1), and among individuals ≥65 years, higher in the 'fit' (86.2%; 84.5, 87.6) than the frailest (71.8%; 69.3, 74.2). VE against hospitalization was lowest in immunosuppressed individuals (64.6%; 60.7, 68.1). CONCLUSIONS: Based on integrated and comprehensive UK health data, overall population-level VE with AZD1222 was high. VEs were notably lower in vulnerable groups, particularly the immunosuppressed.
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COVID-19 , Cuervos , Fragilidad , Humanos , Animales , ChAdOx1 nCoV-19 , Vacunas contra la COVID-19 , Fragilidad/epidemiología , Estudios de Cohortes , ComorbilidadRESUMEN
ABSTRACT: Roberts, BM, Staab, JS, Caldwell, AR, Sczuroski, CE, Staab, JE, Lutz, LJ, Reynoso, M, Geddis, AV, Taylor, KM, Guerriere, KI, Walker, LA, Hughes, JM, and Foulis, SA. Sex does not affect changes in body composition and insulin-like growth factor-I during US Army basic combat training. J Strength Cond Res 38(6): e304-e309, 2024-Insulin-like growth factor 1 (IGF-I) has been implicated as a biomarker of health and body composition. However, whether changes in body composition are associated with changes in IGF-I is unclear. Therefore, we examined the relationship between body composition changes (i.e., fat mass and lean mass) and total serum IGF-I levels in a large cohort of young men ( n = 809) and women ( n = 397) attending US Army basic combat training (BCT). We measured body composition using dual energy x-ray absorptiometry and total serum IGF-I levels during week 1 and week 9 of BCT. We found that pre-BCT lean mass ( r = 0.0504, p = 0.082) and fat mass ( r = 0.0458, p = 0.082) were not associated with pre-BCT IGF-I. Body mass, body mass index, body fat percentage, and fat mass decreased, and lean mass increased during BCT (all p < 0.001). Mean (± SD ) IGF-I increased from pre-BCT (176 ± 50 ng·ml -1 ) to post-BCT (200 ± 50 ng·ml -1 , p < 0.001). Inspection of the partial correlations indicated that even when considering the unique contributions of other variables, increases in IGF-I during BCT were associated with both increased lean mass ( r = 0.0769, p = 0.023) and increased fat mass ( r = 0.1055, p < 0.001) with no sex differences. Taken together, our data suggest that although changes in IGF-I weakly correlated with changes in body composition, IGF-I, in isolation, is not an adequate biomarker for predicting changes in body composition during BCT in US Army trainees.
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Composición Corporal , Factor I del Crecimiento Similar a la Insulina , Personal Militar , Humanos , Masculino , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/análisis , Femenino , Composición Corporal/fisiología , Adulto Joven , Factores Sexuales , Absorciometría de Fotón , Adulto , Estados Unidos , Adolescente , Péptidos Similares a la InsulinaRESUMEN
BACKGROUND: Low-dose computed tomography (lung cancer screening) can reduce lung cancer-specific mortality by 20-24%. Based on this evidence, the United States Preventive Services Task Force recommends annual lung cancer screening for asymptomatic high-risk individuals. Despite this recommendation, utilization is low (3-20%). Lung cancer screening may be particularly beneficial for African American patients because they are more likely to have advanced disease, lower survival, and lower screening rates compared to White individuals. Evidence points to multilevel approaches that simultaneously address multiple determinants to increase screening rates and decrease lung cancer burden in minoritized populations. This study will test the effects of provider- and patient-level strategies for promoting equitable lung cancer screening utilization. METHODS: Guided by the Health Disparities Research Framework and the Practical, Robust Implementation and Sustainability Model, we will conduct a quasi-experimental study with four primary care clinics within a large health system (MedStar Health). Individuals eligible for lung cancer screening, defined as 50-80 years old, ≥ 20 pack-years, currently smoking, or quit < 15 years, no history of lung cancer, who have an appointment scheduled with their provider, and who are non-adherent to screening will be identified via the EHR, contacted, and enrolled (N = 184 for implementation clinics, N = 184 for comparison clinics; total N = 368). Provider participants will include those practicing at the partner clinics (N = 26). To increase provider-prompted discussions about lung screening, an electronic health record (EHR) clinician reminder will be sent to providers prior to scheduled visits with the screening-eligible participants. To increase patient-level knowledge and patient activation about screening, an inreach specialist will conduct a pre-visit phone-based educational session with participants. Patient participants will be assessed at baseline and 1-week post-visit to measure provider-patient discussion, screening intentions, and knowledge. Screening referrals and screening completion rates will be assessed via the EHR at 6 months. We will use mixed methods and multilevel assessments of patients and providers to evaluate the implementation outcomes (adoption, feasibility, acceptability, and fidelity). DISCUSSION: The study will inform future work designed to measure the independent and overlapping contributions of the multilevel implementation strategies to advance equity in lung screening rates. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04675476. Registered December 19, 2020.
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Risk of exertional heat stroke (EHS) is an ongoing challenge for United States military personnel, for athletes and for individuals with occupational stressors that involve prolonged activity in hot environments. Higher body mass index (BMI) is significantly associated with increased risk for EHS in activity duty U.S. Soldiers. During exercise, heat is generated primarily by contracting skeletal muscle (and other metabolically active body mass) and dissipated based on body surface area (BSA). Thus, in compensable environments, a higher BSA·mass-1 may be a benefit to heat dissipation and decrease the risk of EHS. The purpose of the present analysis was to test the hypothesis that BSA·mass-1 ratio is an important biophysical characteristic contributing to the risk of EHS. We employed a matched case-control approach, where each individual with a diagnosis of EHS was matched to five controls who were never diagnosed with EHS but were in the same unit and had the same job title. We used a multivariate conditional logistic regression model including variables of BSA·mass-1, sex, age, military rank, and race. BSA·mass-1 significantly predicted EHS risk (P = 0.006), such that people with higher BSA·mass-1 were at lower risk of developing EHS when controlling for other potential factors such as age and race. This relationship persisted after adjustment for other anthropometric measures of body size including weight, BMI, and BSA. These data suggest that biophysical factors play an important role in EHS risk, particularly in a healthy military-aged cohort of men and women.NEW & NOTEWORTHY With the impacts of climate change yielding higher average ambient temperatures over time, the incidence of EHS for individuals participating in outdoor activities may consequently increase. With the larger sample size in this study compared with prior research in this field, we were able to use various methods that had not been applied before. For example, we were able to mutually adjust for different measurements of body size to understand which metric had the highest association with EHS risk. Understanding factors that may be modifiable may be important for developing interventions to counteract the increased risk of EHS associated with climate change.
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Golpe de Calor , Personal Militar , Masculino , Humanos , Femenino , Anciano , Superficie Corporal , Golpe de Calor/diagnóstico , Regulación de la Temperatura Corporal/fisiología , Ejercicio FísicoRESUMEN
Evidence-based clinical guidelines are essential to maximize patient benefit and to reduce clinical uncertainty and inconsistency in clinical practice. Gaps in the evidence base can be addressed by data acquired in routine practice. At present, there is no international consensus on management of women diagnosed with atypical lesions in breast screening programmes. Here, we describe how routine NHS breast screening data collected by the Sloane atypia project was used to inform a management pathway that maximizes early detection of cancer and minimizes over-investigation of lesions with uncertain malignant potential. A half-day consensus meeting with 11 clinical experts, 1 representative from Independent Cancer Patients' Voice, 6 representatives from NHS England (NHSE) including from Commissioning, and 2 researchers was held to facilitate discussions of findings from an analysis of the Sloane atypia project. Key considerations of the expert group in terms of the management of women with screen detected atypia were: (1) frequency and purpose of follow-up; (2) communication to patients; (3) generalizability of study results; and (4) workforce challenges. The group concurred that the new evidence does not support annual surveillance mammography for women with atypia, irrespective of type of lesion, or woman's age. Continued data collection is paramount to monitor and audit the change in recommendations.
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Neoplasias de la Mama , Toma de Decisiones Clínicas , Femenino , Humanos , Consenso , Incertidumbre , Mama/diagnóstico por imagen , Mama/patología , Mamografía/métodos , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patologíaRESUMEN
Childhood disintegrative disorder is a poorly understood neurobehavioral disorder of early childhood characterized by acute to subacute profound regression in previously developed language, social behavior, and adaptive functions. The etiology of childhood disintegrative disorder remains unknown and treatment is focused on symptomatic management. Interest in neuroinflammatory mechanisms has grown with the increased recognition of autoimmune brain diseases and similarities between the presenting symptoms of childhood disintegrative disorder and pediatric autoimmune encephalitis. Importantly, a diagnosis of pediatric autoimmune encephalitis requires evidence of inflammation on paraclinical testing, which is absent in childhood disintegrative disorder. Here we report 5 children with childhood disintegrative disorder who were initially diagnosed with possible autoimmune encephalitis and treated with immunotherapy. Two children had provocative improvements, whereas 3 did not change significantly on immunotherapy. Additionally, a sixth patient with childhood disintegrative disorder evaluated in our Autoimmune Brain Disease Clinic showed spontaneous improvement and is included to highlight the variable natural history of childhood disintegrative disorder that may mimic treatment responsiveness.
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Inmunoterapia , Niño , Humanos , Progresión de la Enfermedad , Encefalitis/terapia , Encefalitis/inmunología , Inmunoterapia/métodos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Melioidosis, caused by Burkholderia pseudomallei, is a rare but potentially fatal bacterial disease endemic to tropical and subtropical regions worldwide. It is typically acquired through contact with contaminated soil or fresh water. Before this investigation, B. pseudomallei was not known to have been isolated from the environment in the continental United States. Here, we report on three patients living in the same Mississippi Gulf Coast county who presented with melioidosis within a 3-year period. They were infected by the same Western Hemisphere B. pseudomallei strain that was discovered in three environmental samples collected from the property of one of the patients. These findings indicate local acquisition of melioidosis from the environment in the Mississippi Gulf Coast region.
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Burkholderia pseudomallei , Microbiología Ambiental , Melioidosis , Humanos , Burkholderia pseudomallei/genética , Burkholderia pseudomallei/aislamiento & purificación , Melioidosis/epidemiología , Melioidosis/microbiología , Estados Unidos/epidemiologíaRESUMEN
The role of the nervous system in the regulation of cancer is increasingly appreciated. In gliomas, neuronal activity drives tumour progression through paracrine signalling factors such as neuroligin-3 and brain-derived neurotrophic factor1-3 (BDNF), and also through electrophysiologically functional neuron-to-glioma synapses mediated by AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors4,5. The consequent glioma cell membrane depolarization drives tumour proliferation4,6. In the healthy brain, activity-regulated secretion of BDNF promotes adaptive plasticity of synaptic connectivity7,8 and strength9-15. Here we show that malignant synapses exhibit similar plasticity regulated by BDNF. Signalling through the receptor tropomyosin-related kinase B16 (TrkB) to CAMKII, BDNF promotes AMPA receptor trafficking to the glioma cell membrane, resulting in increased amplitude of glutamate-evoked currents in the malignant cells. Linking plasticity of glioma synaptic strength to tumour growth, graded optogenetic control of glioma membrane potential demonstrates that greater depolarizing current amplitude promotes increased glioma proliferation. This potentiation of malignant synaptic strength shares mechanistic features with synaptic plasticity17-22 that contributes to memory and learning in the healthy brain23-26. BDNF-TrkB signalling also regulates the number of neuron-to-glioma synapses. Abrogation of activity-regulated BDNF secretion from the brain microenvironment or loss of glioma TrkB expression robustly inhibits tumour progression. Blocking TrkB genetically or pharmacologically abrogates these effects of BDNF on glioma synapses and substantially prolongs survival in xenograft models of paediatric glioblastoma and diffuse intrinsic pontine glioma. Together, these findings indicate that BDNF-TrkB signalling promotes malignant synaptic plasticity and augments tumour progression.
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Adaptación Fisiológica , Glioma , Plasticidad Neuronal , Sinapsis , Animales , Niño , Humanos , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Proliferación Celular , Progresión de la Enfermedad , Glioma/metabolismo , Glioma/patología , Ácido Glutámico/metabolismo , Neuronas/citología , Neuronas/metabolismo , Receptor trkB/genética , Receptor trkB/metabolismo , Receptores AMPA/metabolismo , Transducción de Señal , Sinapsis/metabolismo , Microambiente Tumoral , OptogenéticaRESUMEN
Experience sculpts brain structure and function. Activity-dependent modulation of the myelinated infrastructure of the nervous system has emerged as a dimension of adaptive change during childhood development and in adulthood. Myelination is a richly dynamic process, with neuronal activity regulating oligodendrocyte precursor cell proliferation, oligodendrogenesis and myelin structural changes in some axonal subtypes and in some regions of the nervous system. This myelin plasticity and consequent changes to conduction velocity and circuit dynamics can powerfully influence neurological functions, including learning and memory. Conversely, disruption of the mechanisms mediating adaptive myelination can contribute to cognitive impairment. The robust effects of neuronal activity on normal oligodendroglial precursor cells, a putative cellular origin for many forms of glioma, indicates that dysregulated or 'hijacked' mechanisms of myelin plasticity could similarly promote growth in this devastating group of brain cancers. Indeed, neuronal activity promotes the pathogenesis of many forms of glioma in preclinical models through activity-regulated paracrine factors and direct neuron-to-glioma synapses. This synaptic integration of glioma into neural circuits is central to tumour growth and invasion. Thus, not only do neuron-oligodendroglial interactions modulate neural circuit structure and function in the healthy brain, but neuron-glioma interactions also have important roles in the pathogenesis of glial malignancies.
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Glioma , Neuronas , Humanos , Neuronas/fisiología , Oligodendroglía/fisiología , Vaina de Mielina/fisiología , Neuroglía/fisiologíaRESUMEN
Introduction: Service members are at risk for pain-related difficulties in functioning and physical injury. Previous studies suggest that mindfulness training (MT) and yoga may prevent these outcomes. The present study was designed to determine the impact of MT and yoga on the health, pain, and injury of Army trainees completing 10 weeks of basic combat training (BCT). Methods: Platoons (≈40 trainees per platoon) were randomized to MT and yoga or training-as-usual in October to December 2020 at a large installation in the US. Self-reported outcomes were health, pain level, and pain impact on training, sleep, mood, and stress. Objective outcomes were injury-related medical encounters and number of diagnoses. The trial was registered at ClinicalTrials. Gov (NCT05550610). Results: Intervention trainees reported significantly better health (OR = 1.05, 95% CI [1.00, 1.10]) and less impact of pain on training (OR = 0.81, 95% CI [0.74, 0.90]), sleep (OR = 0.88, 95% CI [0.81, 0.95]), mood (OR = 0.86, 95% CI [0.78, 0.96]), and stress (OR = 0.88, 95% CI [0.79, 0.98]). There was no significant difference in injury-related medical encounters (AOR = 0.70, 95% CI [0.48, 1.03]), but intervention trainees had fewer diagnoses (OR = 0.67, 95% CI [0.47, 0.95]) and were 30% less likely to have a first medical encounter at any time during BCT. This difference emerged 3 weeks into BCT. Discussion: A combined MT and yoga intervention resulted in better trainee health. The US Army and other organizations requiring resilience under extreme stress should consider implementing MT and yoga to offset risks to employee health.
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Zinc is essential to many important biological processes and the SLC39A family of zinc transporters which help to control zinc levels in cells, are increasingly being implicated in disease states. In order to determine their exact roles in these processes, reliable methods for their successful production are now required. Unfortunately, extensive post-translational modification and temporally specific activation makes visualisation of ZIP family transporters difficult. As such, modifications of common molecular cell biology techniques are necessary to maximise success when studying these proteins. These include zinc stimulation and nocodazole synchronisation to enhance the activation of ZIP7 and ZIP6/ZIP10, respectively. Maximal ZIP6/ZIP10 retention can also be achieved through careful handling of loosely adhered mitotic fractions when harvesting cell cultures for lysis. Transfection can also be used to enhance ZIP visualisation, however consideration of transfection periods and inclusion of sodium butyrate are recommended to enhance transfection efficiency. When probing for ZIP family transporters, we recommend that epitope choice considers post-translational cleavage and phosphorylated protein isoforms. Finally, where expression of a particular ZIP transporter is manipulated, researchers should consider parallel evaluation of related ZIP transporter expression, to account for transporter compensation.