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1.
NPJ Parkinsons Dis ; 10(1): 73, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553493

RESUMO

Pain control after deep brain stimulation (DBS) in Parkinson's disease (PD) remains unclear. Following six months, subthalamic (STN)-DBS reduced sensory complaints related to parkinsonism and bodily discomfort, increasing central beta-endorphin level. Pallidal GPi-DBS decreased bodily discomfort and beta-endorphin levels. Unexplained pain by other conditions and bodily discomfort were negatively correlated with beta-endorphin levels. Thus, DBS regulates central opioids, and prioritizing STN is important for PD patients with significant sensory complications.

2.
ACS Omega ; 8(43): 40321-40340, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37929091

RESUMO

In three-phase gravity separators used in gas and oil production, foaming can occur by either depressurization or injection of gas in the equipment. This formed foam can be harmful, causing various problems such as liquid carry-over, gas carry-under, decreased capacity, and difficulty in level measurement. The mechanism of foam formation by gas injection in separators motivated the present study. Thus, this work proposes the analysis of the influence of certain physical-chemical parameters such as temperature (20-40 °C), pressure (1-10 bar), and types of gases (nitrogen and methane) on the formation of the column and stability of the foam formed, in ISO14 mineral oil + sodium laureth sulfate + water, through gas injection in separator conditions. To carry out this analysis, an experimental apparatus was designed and assembled consisting of a transparent foam formation cell of 0.5 m height and 5 cm internal diameter. Parameters such as foamability, foaminess, and the collapse curve were also evaluated to characterize the foam formed. In addition, simplified models of foam formation and decay by gas injection were proposed based on models already available in the literature, which were validated with the experimentally obtained results. The experimental results showed good agreement when compared to the literature, referring to the behavior of temperature (higher temperature, lower stability), pressure (higher pressure, higher stability), and type of injected gas (dependency on solubility). In addition, maximum errors of 26% (in height) and 11% (decay phase) were obtained for the formation and decay models, respectively.

3.
Int J Mol Sci ; 24(9)2023 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-37175503

RESUMO

Epidural motor cortex stimulation (MCS) is an effective treatment for refractory neuropathic pain; however, some individuals are unresponsive. In this study, we correlated the effectiveness of MCS and refractoriness with the expression of cytokines, neurotrophins, and nociceptive mediators in the dorsal root ganglion (DRG), sciatic nerve, and plasma of rats with sciatic neuropathy. MCS inhibited hyperalgesia and allodynia in two-thirds of the animals (responsive group), and one-third did not respond (refractory group). Chronic constriction injury (CCI) increased IL-1ß in the nerve and DRG, inhibited IL-4, IL-10, and IL-17A in the nerve, decreased ß-endorphin, and enhanced substance P in the plasma, compared to the control. Responsive animals showed decreased NGF and increased IL-6 in the nerve, accompanied by restoration of local IL-10 and IL-17A and systemic ß-endorphin. Refractory animals showed increased TNF-α and decreased IFNγ in the nerve, along with decreased TNF-α and IL-17A in the DRG, maintaining low levels of systemic ß-endorphin. Our findings suggest that the effectiveness of MCS depends on local control of inflammatory and neurotrophic changes, accompanied by recovery of the opioidergic system observed in neuropathic conditions. So, understanding the refractoriness to MCS may guide an improvement in the efficacy of the technique, thus benefiting patients with persistent neuropathic pain.


Assuntos
Analgesia , Neuralgia , Ratos , Animais , Interleucina-10/metabolismo , Interleucina-17/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , beta-Endorfina/metabolismo , Neuralgia/terapia , Neuralgia/metabolismo , Hiperalgesia/terapia , Hiperalgesia/metabolismo , Nervo Isquiático/metabolismo , Gânglios Espinais/metabolismo
4.
Parkinsonism Relat Disord ; 109: 105318, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36842866

RESUMO

INTRODUCTION: Deep brain stimulation (DBS) is a well-established treatment for patients with Parkinson's disease (PD) improving quality of life, motor, and non-motor symptoms. However, non-motor effects in PD subtypes are understudied. We hypothesized that patients with 'postural instability and gait difficulty' (PIGD) experience more beneficial non-motor effects than 'tremor-dominant' patients undergoing DBS for PD. METHODS: In this prospective, observational, international multicentre study with a 6-month follow-up, we assessed the Non-Motor Symptom Scale (NMSS) as primary and the following secondary outcomes: Unified PD Rating Scale-motor examination (UPDRS-III), Scales for Outcomes in PD (SCOPA)-activities of daily living (ADL) and -motor complications, PDQuestionnaire-8 (PDQ-8), and levodopa-equivalent daily dose (LEDD). We analysed within-group longitudinal changes with Wilcoxon signed-rank test and Benjamini-Hochberg correction for multiple comparisons. Additionally, we explored outcome between-group differences of motor subtypes with Mann-Whitney U-tests. RESULTS: In 82 PIGD and 33 tremor-dominant patients included in this study, baseline NMSS total scores were worse in PIGD patients, both groups experienced postoperative improvements of the NMSS sleep/fatigue domain, and between-group differences in postoperative outcomes were favourable in the PIGD group for the NMSS total and miscellaneous domain scores. CONCLUSIONS: This study provides evidence of a favourable outcome of total non-motor burden in PIGD compared to tremor-dominant patients undergoing DBS for PD. These differences of clinical efficacy on non-motor aspects should be considered when advising and monitoring patients with PD undergoing DBS.


Assuntos
Estimulação Encefálica Profunda , Doença de Parkinson , Núcleo Subtalâmico , Humanos , Doença de Parkinson/complicações , Tremor/terapia , Tremor/complicações , Estudos Prospectivos , Qualidade de Vida , Atividades Cotidianas , Núcleo Subtalâmico/fisiologia
5.
Biomedicines ; 11(2)2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36830833

RESUMO

BACKGROUND: Parkinson's disease (PD) is characterized by a progressive loss of nigrostriatal dopaminergic neurons with impaired motor and non-motor symptoms. It has been suggested that motor asymmetry could be caused due to an imbalance in dopamine levels, as visualized by dopamine transporter single emission computed tomography test (DAT-SPECT), which might be related to indirect measures of neurodegeneration, evaluated by the Montreal Cognitive Assessment (MOCA) and α-synuclein levels in the cerebrospinal fluid (CSF). Therefore, this study aimed to understand the correlation between disease laterality, DAT-SPECT, cognition, and α-synuclein levels in PD. METHODS: A total of 28 patients in the moderate-advanced stage of PD were subjected to neurological evaluation, TRODAT-1-SPECT/CT imaging, MOCA, and quantification of the levels of α-synuclein. RESULTS: We found that α-synuclein in the CSF was correlated with global cognition (positive correlation, r2 = 0.3, p = 0.05) and DAT-SPECT concentration in the putamen (positive correlation, r2 = 0.4, p = 0.005), and striatum (positive correlation, r2 = 0.2, p = 0.03), thus working as a neurodegenerative biomarker. No other correlations were found between DAT-SPECT, CSF α-synuclein, and cognition, thus suggesting that they may be lost with disease progression. CONCLUSIONS: Our data highlight the importance of understanding the dysfunction of the dopaminergic system in the basal ganglia and its complex interactions in modulating cognition.

6.
Front Rehabil Sci ; 3: 849333, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36189041

RESUMO

In advanced stages of in Huntington's disease (HD) gait impairments and severe chorea are usually medication-refractory. The long-term effects on gait in HD of physiotherapy ICF-based management post- globus pallidus deep brain stimulation (GPi DBS) are not well-established. Physiotherapy has been recognized as an essential element in HD treatment. Here, we present a case report of a 56-year-old woman with HD on the advanced stage and severe chorea medication-refractory after GPi-DBS. We performed multidisciplinary motor assessments ICF-based to identify the disability at clinical and home-setting, including environmental and personal factors before and after GPi-DBS surgery and at 11-time points follow-up. The surgery was very successful and directly post GPi-DBS, there were a significant improvement in chorea and a substantial decrease in medication dose. A framework ICF- based physiotherapy protocol with external cues was developed to improve gait was delivered post-surgery and was continued three times/week during 18-months. Physiotherapy sessions consisted of a personalized protocol of exercises with functional movements, balance, and gait training with external cues. Improvements in gait were observed in 3-months post-intervention and were more expressive in 6-months follow-up. Our patient improved substantially HD motor symptoms and her quality of life after GPi-DBS intervention and a physiotherapy program ICF-based. The objective outcomes measures used to assess gait have served as endpoints to assessing the patient's motor profile during the pre-operative period. Assessments were helpful to verify the efficacy of the multidisciplinary intervention in long-term. Conclusion: Periodically assessing function and disability using outcome improvements may support clinicians' decisions about DBS, medication adjustments and guide physiotherapists to personalize the ICF-based intervention.

7.
J Contam Hydrol ; 251: 104066, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36054959

RESUMO

Mixing-dependent reactions occur where groundwater and surface water mix in shallow sediments (hyporheic zone) and can attenuate contaminants along upwelling flowpaths, thus reducing transport to surface water. Here we used MODFLOW/SEAM3D to numerically simulate prior laboratory observations of a mixing-dependent reaction between sodium sulfite (Na2SO3) and dissolved oxygen (DO) to produce sodium sulfate (Na2SO4). This reaction is not common in nature but is used as a surrogate for mixing-dependent DO consuming reactions of environmental significance. We evaluated how location and thickness of mixing zones and reaction product production zones dynamically respond to variations in hydraulic and chemical boundary conditions and reaction kinetic rate. Sensitivity analysis showed that location and thickness of mixing zones and reactant production zones were most sensitive to changes in the balance of hydrologic inflow from groundwater and surface water (inflow ratio). Mixing zone thickness for reactive DO calibrated to experimental data was thinner than that for the "DO tracer" (identical source location and concentration as DO but conservative tracer), indicating that as DO is consumed its mixing zone narrows. The SO4 production zone was consistently thicker than the DO mixing zone. Small changes in mixing/production zone thicknesses were linked to large changes in mass consumed and produced, indicating the potential for simpler field metrics like thickness to act as surrogates for more challenging measurements such as contaminant flux or consumption in monitoring natural attenuation. This study improves understanding of the evolution of hyporheic mixing-dependent reaction zones that occur even under steady state hydraulics, emphasizing their complex controls.


Assuntos
Água Subterrânea , Poluentes Químicos da Água , Movimentos da Água , Evolução Química , Água
8.
Front Mol Neurosci ; 14: 718241, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34566577

RESUMO

The endocochlear potential (EP) generated by the stria vascularis (SV) is necessary for hair cell mechanotransduction in the mammalian cochlea. We sought to create a model of EP dysfunction for the purposes of transcriptional analysis and treatment testing. By administering a single dose of cisplatin, a commonly prescribed cancer treatment drug with ototoxic side effects, to the adult mouse, we acutely disrupt EP generation. By combining these data with single cell RNA-sequencing findings, we identify transcriptional changes induced by cisplatin exposure, and by extension transcriptional changes accompanying EP reduction, in the major cell types of the SV. We use these data to identify gene regulatory networks unique to cisplatin treated SV, as well as the differentially expressed and druggable gene targets within those networks. Our results reconstruct transcriptional responses that occur in gene expression on the cellular level while identifying possible targets for interventions not only in cisplatin ototoxicity but also in EP dysfunction.

9.
J Contam Hydrol ; 243: 103885, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34488177

RESUMO

Mixing of surface water and groundwater in shallow sediments is important to biogeochemical cycling and contaminant migration, and is often used to define the hyporheic zone. Yet knowledge of mixing processes in hyporheic zones is supported by surprisingly few rigorous lab or field observations, and differ from those in deeper groundwater by presence of enhanced head gradients, sediment heterogeneity, and temporal fluctuations. In a laboratory sediment (sand) tank we photographed a conservative dye to analyze transverse mixing zones between upwelling groundwater and bidirectional hyporheic exchange flows. We then conducted numerical modeling to investigate processes behind observed phenomena and estimate dispersivities. We found that transverse mixing zones were thin (i.e. mixing thickness measured in direction of steepest concentration gradient, δ, less than 5 cm), consistent with a small calibrated transverse dispersivity (~0.1 mm) and prior lab studies conducted at similar scales. In steady-state experiments and simulations, δ and estimated dispersion coefficients increased with the surface water head drop driving exchange flows. Given relatively constant deeper groundwater heads, increased Δh led to increased mixing zone length for both steady-state and transient conditions, indicating larger bedforms or weaker gaining conditions enhance subsurface mixing. However, Peclet number and flux-related dilution index simultaneously increased and decreased, respectively, indicating that enhancement of subsurface advection outpaced that of dispersion. In transient experiments and simulations, δ was greater than for steady-state, probably from temporary addition of longitudinal dispersion. During transient experiments, δ exhibited temporal noise, perhaps due to the mixing zone moving past varying patterns of sediment packing. Our results provide basic knowledge of mixing zone behavior in hyporheic zones with implications for hyporheic zone definitions, solute transport, mixing-dependent reaction, and water quality.


Assuntos
Água Subterrânea , Movimentos da Água , Qualidade da Água
10.
Brain ; 144(10): 2994-3004, 2021 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-34373901

RESUMO

Motor cortex stimulation via surgically implanted electrodes has been used as an off-label treatment for chronic neuropathic pain, but its efficacy has not been fully established. We aimed to objectively study the efficacy of motor cortex stimulation and characterize potential predictors of response. In this randomized, double-blind, sham-controlled, single centre trial, we recruited 18 patients with chronic neuropathic pain who did not adequately respond to conventional treatment and had a numerical pain rating scale (NRS) score ≥6. Patients were initially assigned to receive 3 months of active ('on') or sham ('off') stimulation in a double-blind cross-over phase. This was followed by a 3-month single-blind phase, and 6 months of open-label follow-up. A meaningful response in our trial was defined as a ≥30% or 2-point reduction in NRS scores during active stimulation. Using Bayesian statistics, we found a 41.4% probability of response towards on versus off motor cortex stimulation. The probability of improvement during active stimulation (double-blind, single-blind and open-label phases) compared to baseline was 47.2-68.5%. Thirty nine per cent of the patients were considered long-term responders, 71.4% of whom had facial pain, phantom limb pain or complex regional pain syndrome. In contrast, 72.7% of non-responders had either post-stroke pain or pain associated with brachial plexus avulsion. Thirty-nine per cent of patients had a substantial postoperative analgesic effect after electrode insertion in the absence of stimulation. Individuals with diagnoses associated with a good postoperative outcome or those who developed an insertional effect had a near 100% probability of response to motor cortex stimulation. In summary, we found that ∼40% of patients responded to motor cortex stimulation, particularly those who developed an insertional effect or had specific clinical conditions that seemed to predict an appropriate postoperative response.


Assuntos
Dor Crônica/terapia , Terapia por Estimulação Elétrica/métodos , Córtex Motor/fisiologia , Neuralgia/terapia , Medição da Dor/métodos , Adulto , Idoso , Dor Crônica/diagnóstico , Dor Crônica/fisiopatologia , Estudos Cross-Over , Método Duplo-Cego , Eletrodos Implantados , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neuralgia/diagnóstico , Neuralgia/fisiopatologia , Método Simples-Cego
11.
Cells ; 10(5)2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-34064617

RESUMO

Persistent pain is a prevalent symptom of Parkinson's disease (PD), which is related to the loss of monoamines and neuroinflammation. Motor cortex stimulation (MCS) inhibits persistent pain by activating the descending analgesic pathways; however, its effectiveness in the control of PD-induced pain remains unclear. Here, we evaluated the analgesic efficacy of MCS together with serotonergic and spinal glial modulation in an experimental PD (ePD) rat model. Wistar rats with unilateral striatal 6-OHDA and MCS were assessed for behavioral immobility and nociceptive responses. The immunoreactivity of dopamine in the substantia nigra and serotonin in the nucleus raphe magnus (NRM) and the neuronal, astrocytic, and microglial activation in the dorsal horn of the spinal cord were evaluated. MCS, without interfering with dopamine loss, reversed ePD-induced immobility and hypernociception. This response was accompanied by an exacerbated increase in serotonin in the NRM and a decrease in neuronal and astrocytic hyperactivation in the spinal cord, without inhibiting ePD-induced microglial hypertrophy and hyperplasia. Taken together, MCS induces analgesia in the ePD model, while restores the descending serotonergic pathway with consequent inhibition of spinal neurons and astrocytes, showing the role of MCS in PD-induced pain control.


Assuntos
Astrócitos/metabolismo , Córtex Motor/fisiologia , Nociceptividade , Doença de Parkinson/metabolismo , Núcleos da Rafe/metabolismo , Serotonina/metabolismo , Aminas/metabolismo , Analgesia , Animais , Comportamento Animal , Modelos Animais de Doenças , Dopamina/metabolismo , Eletrodos , Inflamação , Masculino , Córtex Motor/metabolismo , Neuroglia/metabolismo , Neurônios/metabolismo , Dor/complicações , Manejo da Dor , Ratos , Ratos Wistar , Medula Espinal/metabolismo
12.
Front Hum Neurosci ; 15: 653631, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34177490

RESUMO

Aggressive behaviors comprise verbal and/or physical aggression directed toward oneself, others, or objects and are highly prevalent among psychiatric patients, especially patients diagnosed with autism spectrum disorder and severe intellectual disabilities. Some of these patients are considered refractory to treatment, and functional neurosurgery targeting the amygdala can result in widespread plastic brain changes that might reflect ceasing of some abnormal brain function, offering symptom alleviation. This study investigated cortical thickness changes in refractory aggressive behavior patients that were treated with bilateral amygdala ablation and compared to control patients presenting non-refractory aggressive behavior [three refractory and seven non-refractory patients, all males diagnosed with autism spectrum disorder (ASD) and intellectual disabilities]. The Overt Aggression Scale (OAS) was used to quantify behavior and magnetic resonance imaging was performed to investigate cortical thickness. Before surgery, both groups presented similar total OAS score, however refractory patients presented higher physical aggression against others. After surgery the refractory group showed 88% average reduction of aggressive behavior. Imaging analysis showed that while refractory patients present an overall reduction in cortical thickness compared to non-refractory patients across both timepoints, the local pattern of thickness difference found in areas of the neurocircuitry of aggressive behavior present before surgery is diminished and no longer detected after surgery. These results corroborate the hypotheses on induction of widespread neuronal plasticity following functional neurosurgical procedures resulting in modifications in brain morphology and improvement in behavior. Further studies are necessary to determine the underlying cause of these morphological changes and to better understand and improve treatment options.

13.
Brain Struct Funct ; 226(2): 323-333, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33389040

RESUMO

Understanding the intricate three-dimensional relationship between fiber bundles and subcortical nuclei is not a simple task. It is of paramount importance in neurosciences, especially in the field of functional neurosurgery. The current methods for in vivo and post mortem fiber tract visualization have shortcomings and contributions to the field are welcome. Several tracts were chosen to implement a new technique to help visualization of white matter tracts, using high-thickness histology and dark field images. Our study describes the use of computational fluid dynamic simulations for visualization of 3D fiber tracts segmented from dark field microscopy in high-thickness histological slices (histological mesh tractography). A post mortem human brain was MRI scanned prior to skull extraction, histologically processed and serially cut at 430 µm thickness as previously described by our group. High-resolution dark field images were used to segment the outlines of the structures. These outlines served as basis for the construction of a 3D structured mesh, were a Finite Volume Method (FVM) simulation of water flow was performed to generate streamlines representing the geometry. The simulations were accomplished by an open source computer fluid dynamics software. The resulting simulation rendered a realistic 3D impression of the segmented anterior commissure, the left anterior limb of the internal capsule, the left uncinate fascicle, and the dentato-rubral tracts. The results are in line with clinical findings, diffusion MR imaging and anatomical dissection methods.


Assuntos
Encéfalo/diagnóstico por imagem , Imagem de Tensor de Difusão/métodos , Substância Branca/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Vias Neurais/diagnóstico por imagem
14.
Front Cell Dev Biol ; 8: 841, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32984333

RESUMO

Dental epithelial stem cells give rise to four types of dental epithelial cells: inner enamel epithelium (IEE), outer enamel epithelium (OEE), stratum intermedium (SI), and stellate reticulum (SR). IEE cells further differentiate into enamel-forming ameloblasts, which play distinct roles, and are essential for enamel formation. These are conventionally classified by their shape, although their transcriptome and biological roles are yet to be fully understood. Here, we aimed to use single-cell RNA sequencing to clarify the heterogeneity of dental epithelial cell types. Unbiased clustering of 6,260 single cells from incisors of postnatal day 7 mice classified them into two clusters of ameloblast, IEE/OEE, SI/SR, and two mesenchymal populations. Secretory-stage ameloblasts expressed Amel and Enam were divided into Dspp + and Ambn + ameloblasts. Pseudo-time analysis indicated Dspp + ameloblasts differentiate into Ambn + ameloblasts. Further, Dspp and Ambn could be stage-specific markers of ameloblasts. Gene ontology analysis of each cluster indicated potent roles of cell types: OEE in the regulation of tooth size and SR in the transport of nutrients. Subsequently, we identified novel dental epithelial cell marker genes, namely Pttg1, Atf3, Cldn10, and Krt15. The results not only provided a resource of transcriptome data in dental cells but also contributed to the molecular analyses of enamel formation.

16.
J Biol Chem ; 295(45): 15328-15341, 2020 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-32868297

RESUMO

Dental enamel, the hardest tissue in the human body, is derived from dental epithelial cell ameloblast-secreted enamel matrices. Enamel mineralization occurs in a strictly synchronized manner along with ameloblast maturation in association with ion transport and pH balance, and any disruption of these processes results in enamel hypomineralization. G protein-coupled receptors (GPCRs) function as transducers of external signals by activating associated G proteins and regulate cellular physiology. Tissue-specific GPCRs play important roles in organ development, although their activities in tooth development remain poorly understood. The present results show that the adhesion GPCR Gpr115 (Adgrf4) is highly and preferentially expressed in mature ameloblasts and plays a crucial role during enamel mineralization. To investigate the in vivo function of Gpr115, knockout (Gpr115-KO) mice were created and found to develop hypomineralized enamel, with a larger acidic area because of the dysregulation of ion composition. Transcriptomic analysis also revealed that deletion of Gpr115 disrupted pH homeostasis and ion transport processes in enamel formation. In addition, in vitro analyses using the dental epithelial cell line cervical loop-derived dental epithelial (CLDE) cell demonstrated that Gpr115 is indispensable for the expression of carbonic anhydrase 6 (Car6), which has a critical role in enamel mineralization. Furthermore, an acidic condition induced Car6 expression under the regulation of Gpr115 in CLDE cells. Thus, we concluded that Gpr115 plays an important role in enamel mineralization via regulation of Car6 expression in ameloblasts. The present findings indicate a novel function of Gpr115 in ectodermal organ development and clarify the molecular mechanism of enamel formation.


Assuntos
Ameloblastos/metabolismo , Esmalte Dentário/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Animais , Células Cultivadas , Camundongos , Camundongos Knockout , Ratos , Receptores Acoplados a Proteínas G/deficiência , Receptores Acoplados a Proteínas G/genética
17.
BJPsych Open ; 6(5): e85, 2020 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-32762791

RESUMO

Aggressive behaviour is a highly prevalent and devastating condition in autism spectrum disorder resulting in impoverished quality of life. Gold-standard therapies are ineffective in about 30% of patients leading to greater suffering. We investigated cortical thickness in individuals with autism spectrum disorder with pharmacological-treatment-refractory aggressive behaviour compared with those with non-refractory aggressive behaviour and observed a brain-wide pattern of local increased thickness in key areas related to emotional control and overall decreased cortical thickness in those with refractory aggressive behaviour, suggesting refractoriness could be related to specific morphological patterns. Elucidating the neurobiology of refractory aggressive behaviour is crucial to provide insights and potential avenues for new interventions.

19.
Front Cell Neurosci ; 14: 123, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32528249

RESUMO

Sensory epithelia of the inner ear contain mechanosensory hair cells (HCs) and glia-like supporting cells (SCs), both of which are required for hearing and balance functions. Each of these cell types has unique responses to ototoxic and cytoprotective stimuli. Non-lethal heat stress in the mammalian utricle induces heat shock proteins (HSPs) and protects against ototoxic drug-induced hair cell death. Induction of HSPs in the utricle demonstrates cell-type specificity at the protein level, with HSP70 induction occurring primarily in SCs, while HSP32 (also known as heme oxygenase 1, HMOX1) is induced primarily in resident macrophages. Neither of these HSPs are robustly induced in HCs, suggesting that HCs may have little capacity for induction of stress-induced protective responses. To determine the transcriptional responses to heat shock of these different cell types, we performed cell-type-specific transcriptional profiling using the RiboTag method, which allows for immunoprecipitation (IP) of actively translating mRNAs from specific cell types. RNA-Seq differential gene expression analyses demonstrated that the RiboTag method identified known cell type-specific markers as well as new markers for HCs and SCs. Gene expression differences suggest that HCs and SCs exhibit differential transcriptional heat shock responses. The chaperonin family member Cct8 was significantly enriched only in heat-shocked HCs, while Hspa1l (HSP70 family), and Hspb1 and Cryab (HSP27 and HSP20 families, respectively) were enriched only in SCs. Together our data indicate that HCs exhibit a limited but unique heat shock response, and SCs exhibit a broader and more robust transcriptional response to protective heat stress.

20.
Environ Sci Technol ; 54(6): 3278-3287, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32062974

RESUMO

Floodplain restoration is popular to address excess nutrients, but its ability to enhance photolysis of emerging contaminants has not been evaluated. We used the numerical model MIKE-21 to simulate photolysis reactions within the inundated surface water of restored floodplains along a mid-size river. We examined both "high" and "low" floodplain scenarios where inundation occurs 5% (storms) and 50% (baseflow) of the year, respectively. We simulated photolysis of the pharmaceuticals morphine, codeine, and methamphetamine and, for context, compared it with nitrate removal (denitrification and plant uptake). Pollutant removal due to floodplain restoration was greater for the low floodplain (e.g., 18.8% for morphine) than for the high floodplain (5.6% for morphine) due to greater water exchange relative to channel flow. The fastest- and slowest-reacting pollutants (morphine and methamphetamine, respectively) were always transport- and reaction/kinetics-limited within floodplain surface water, respectively. Yet, those with intermediate decay-rate constants switched from reaction limitation to transport limitation as the floodplain length increased, and removal leveled off at an optimum length of ∼1000 m. However, as the floodplain width increased, the required floodplain length for 30% removal decreased. Optimal restored floodplain conditions for photolysis would maximize light exposure, which may differ from those for nutrients.


Assuntos
Desnitrificação , Rios , Nitratos , Fotólise , Água
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