Despite the best available medical treatments, many patients continue to be disabled by neurologic and psychiatric disorders, resulting in a large unmet need. Advances in imaging and neurophysiology ...over the last two decades have led to a reinterpretation of some neurologic and psychiatric conditions as primarily disorders of circuit function, or “circuitopathies.” These developments have been accompanied by advances in neurosurgical techniques with the increasingly widespread utilization of deep brain stimulation (DBS) to recalibrate dysfunctional circuits. The versatility of DBS as both a probe and modulator of neural circuits is making it a powerful tool to study the human brain, helping provide important details of the pathophysiology of circuit dysfunction. We are currently in a phase of active investigation to determine which circuits and disorders could be treated with DBS. Here we review recent advances in the DBS field and discuss potential future directions in targeted intracranial neuromodulation.
The manifestations of many neurological and psychiatric disorders may arise as a consequence of abnormal activity in specific brain circuits. Here, Lozano and Lipsman review the use of deep brain stimulation to probe and modify activity in those malfunctioning circuits and discuss potential underlying mechanisms.
Microplastics in soils can affect plant performance, as shown in studies using individual plants. However, we currently have no information about potential effects on plant community productivity and ...structure. In a plant community consisting of seven plant species that co-occur in temperate grassland ecosystems, we thus investigated the effect of microplastics (i.e., microfibers) and drought, a factor with which microfibers might interact, on plant productivity and community structure. Our results showed that at the community level, shoot and root mass decreased with drought but increased with microfibers, an effect likely linked to reduced soil bulk density, improved aeration, and better penetration of roots in the soil. Additionally, we observed that microfibers affected plant community structure. Species such as Calamagrostis, invasive in Europe, and the allelophatic Hieracium, became more dominant with microfibers, while species that potentially have the ability to facilitate the establishment of other plant species (e.g., Holcus), decreased in biomass. As microfibers affect plant species dominance, the examination of cascade effects on ecosystem functions should be a high priority for future research.
The study aims were to describe positional differences in the acceleration and sprint profiles of professional football players in match-play, and analyse start speeds required based on the intensity ...of accelerations and decelerations. This longitudinal study was conducted over thirteen competitive microcycles in a professional football team from LaLiga 123. Data were collected through electronic performance tracking systems. Every player was categorised based on the playing position: central defender (CD), full-back (FB), forward (FW), midfielder (MF), and wide midfielder (WMF). In respect of acceleration profile, positional differences were found for all variables (p < 0.05), except average magnitude of accelerations (ACCAVG, p = 0.56) and decelerations (DECAVG, p = 0.76). The sprint profile also showed positional differences for all variables (p < 0.05), apart from sprint duration (p = 0.07). In addition, although low-intensity accelerations required significantly greater start speeds (Vo) than high-intensity accelerations in WMF (0.4 ± 0.2 km/h; p < 0.05) and FW (0.4 ± 0.2 km/h; p < 0.05), no significant differences (p > 0.05) were found in CD, FB, and MF. However, high-intensity decelerations were performed at significantly higher Vo than low-intensity decelerations in MF (2.65 ± 0.1 km/h; p < 0.05), FW (3.3 ± 0.1 km/h; p < 0.05), FB (3.9 ± 0.4 km/h; p < 0.05), WMF (4.3 ± 0.3 km/h; p < 0.05), and CD (4.1 ± 0.7 km/h; p < 0.05). Therefore, positional differences exist for most variables of the acceleration and sprint profiles. In addition, different Vo were observed between high-intensity and low-intensity accelerations as well as high-intensity and low-intensity decelerations.
Summary
Background
Strict avoidance is the only accepted management for cow's milk (CM) allergy. CM oral immunotherapy (CM‐OIT) is under investigation.
Objectives
To evaluate long‐term safety of ...CM‐OIT. To identify clinical/immunological predictors of adverse events.
Methods
Prospective longitudinal epidemiological intervention study. CM‐allergic children aged 5–18 underwent a Spanish‐approved CM‐OIT protocol without premedication. Clinical data, skin prick test (SPT) and specific IgE (sIgE) at baseline and 1 year after OIT were registered. All dose‐related reactions, treatments needed and cofactors involved were recorded. Through survival analysis, we studied the cumulative probability of reactions resolution over time and clinical/immunological risk factors of reactions persistence.
Results
81 children were recruited. Mean follow‐up was 25 months. 95% of children suffered reactions, 91% of which affected a single organ. Reactions were heterogeneously distributed: (a) 60 children (75%) had occasional symptoms which ceased over time. 86% of them reached complete desensitization (200 mL). (b) 20 children (25%) suffered frequent (78% of total reactions), more severe and unpredictable reactions, which persisted during follow‐up or led to withdrawal (6 cases). Reactions persistence was associated with a higher frequency and severity. Kaplan–Meier estimate revealed a cumulative probability of reactions resolution of 25% at 3 months (95% CI: 1.9–4.1) and 50% (95% CI: 6.1–9.9) at 8 months based on all patients. Cox proportional hazards multivariate regression model identified 3 variables (CM‐sIgE ≥ 50 KU L−1, CM‐SPT ≥ 9 mm and Sampson's severity grades 2, 3 and 4 at baseline food challenge) as independent risk factors of reactions persistence. The combination of 2 or 3 of these factors involved hazard ratios to develop persistent reactions of 2.26 (95% CI: 1.14–4.46; P = 0.019) and 6.06 (95% CI: 2.7–13.7; P < 0.001), respectively.
Clinical implications
CM‐OIT was insufficiently safe in 25% of children. The above‐mentioned clinical and immunological parameters would help clinicians to identify highly reactive patients before CM‐OIT. In them, individualized schedules and premedication should be considered.
Microplastics may enter the soil in a wide range of shapes and polymers. However, little is known about the effects that microplastics of different shapes, polymers, and concentration may have on ...soil properties and plant performance. To address this, we selected 12 microplastics representing different shapes (fibers, films, foams, and fragments) and polymers, and mixed them each with soil at a concentration of 0.1, 0.2, 0.3, and 0.4%. A phytometer (
) grew in each pot during 4 weeks. Shoot, root mass, soil aggregation, and microbial activity were measured. All shapes increased plant biomass. Shoot mass increased by ∼27% with fibers, ∼60% with films, ∼45% with foams, and by ∼54% with fragments, as fibers hold water in the soil for longer, films decrease soil bulk density, and foams and fragments can increase soil aeration and macroporosity, which overall promote plant performance. By contrast, all shapes decreased soil aggregation by ∼25% as microplastics may introduce fracture points into aggregates and due to potential negative effects on soil biota. The latter may also explain the decrease in microbial activity with, for example, polyethylene films. Our findings show that shape, polymer type, and concentration are key properties when studying microplastic effects on terrestrial systems.
Summary Background Essential tremor is the most common movement disorder and is often refractory to medical treatment. Surgical therapies, using lesioning and deep brain stimulation in the thalamus, ...have been used to treat essential tremor that is disabling and resistant to medication. Although often effective, these treatments have risks associated with an open neurosurgical procedure. MR-guided focused ultrasound has been developed as a non-invasive means of generating precisely placed focal lesions. We examined its application to the management of essential tremor. Methods Our study was done in Toronto, Canada, between May, 2012, and January, 2013. Four patients with chronic and medication-resistant essential tremor were treated with MR-guided focused ultrasound to ablate tremor-mediating areas of the thalamus. Patients underwent tremor evaluation and neuroimaging at baseline and 1 month and 3 months after surgery. Outcome measures included tremor severity in the treated arm, as measured by the clinical rating scale for tremor, and treatment-related adverse events. Findings Patients showed immediate and sustained improvements in tremor in the dominant hand. Mean reduction in tremor score of the treated hand was 89·4% at 1 month and 81·3% at 3 months. This reduction was accompanied by functional benefits and improvements in writing and motor tasks. One patient had postoperative paraesthesias which persisted at 3 months. Another patient developed a deep vein thrombosis, potentially related to the length of the procedure. Interpretation MR-guided focused ultrasound might be a safe and effective approach to generation of focal intracranial lesions for the management of disabling, medication-resistant essential tremor. If larger trials validate the safety and ascertain the efficacy and durability of this new approach, it might change the way that patients with essential tremor and potentially other disorders are treated. Funding Focused Ultrasound Foundation.
Deep brain stimulation (DBS) has been successfully used to treat movement disorders, such as Parkinson's disease, for more than 25 years and heralded the advent of electrical neuromodulation to treat ...diseases with dysregulated neuronal circuits. DBS is now superseding ablative techniques, such as stereotactic radiofrequency lesions. While serendipity has played a role in developing DBS as a therapy, research during the past two decades has shown that electrical neuromodulation is far more than a functional lesion that can be switched on and off. This understanding broadens the field to enable new types of stimulation, clinical indications, and research. This review highlights the complex effects of DBS from the single cell to the neuronal network. Specifically, we examine the electrical, cellular, molecular, and neurochemical mechanisms of DBS as applied to Parkinson's disease and other emerging applications.
For over 25 years, deep brain stimulation (DBS) has been successfully used to treat movement disorders, i.e. Parkinson's disease. With high precision stereotactic implantation of electrodes, DBS is fast becoming a powerful tool for studying and treating the brain against many different diseases.
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