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Background The literature suggests a beneficial effect of motor imagery (MI) if combined with physical practice, but detailed descriptions of MI training session (MITS) elements and temporal parameters are lacking. The aim of this review was to identify the characteristics of a successful MITS and compare these for different disciplines, MI session types, task focus, age, gender and MI modification during intervention. Methods An extended systematic literature search using 24 databases was performed for five disciplines: Education, Medicine, Music, Psychology and Sports. References that described an MI intervention that focused on motor skills, performance or strength improvement were included. Information describing 17 MITS elements was extracted based on the PETTLEP (physical, environment, timing, task, learning, emotion, perspective) approach. Seven elements describing the MITS temporal parameters were calculated: study duration, intervention duration, MITS duration, total MITS count, MITS per week, MI trials per MITS and total MI training time. Results Both independent reviewers found 96% congruity, which was tested on a random sample of 20% of all references. After selection, 133 studies reporting 141 MI interventions were included. The locations of the MITS and position of the participants during MI were task-specific. Participants received acoustic detailed MI instructions, which were mostly standardised and live. During MI practice, participants kept their eyes closed. MI training was performed from an internal perspective with a kinaesthetic mode. Changes in MI content, duration and dosage were reported in 31 MI interventions. Familiarisation sessions before the start of the MI intervention were mentioned in 17 reports. MI interventions focused with decreasing relevance on motor-, cognitive- and strength-focused tasks. Average study intervention lasted 34 days, with participants practicing MI on average three times per week for 17 minutes, with 34 MI trials. Average total MI time was 178 minutes including 13 MITS. Reporting rate varied between 25.5% and 95.5%. Conclusions MITS elements of successful interventions were individual, supervised and non-directed sessions, added after physical practice. Successful design characteristics were dominant in the Psychology literature, in interventions focusing on motor and strength-related tasks, in interventions with participants aged 20 to 29 years old, and in MI interventions including participants of both genders. Systematic searching of the MI literature was constrained by the lack of a defined MeSH term.

Background Melanoma brain metastasis is associated with an extremely poor prognosis, with a median overall survival of 4–5 months. Since 2011, the overall survival of patients with stage IV melanoma has been significantly improved with the advent of new targeted therapies and checkpoint inhibitors. We analyze the survival outcomes of patients diagnosed with brain metastasis after the introduction of these novel drugs. Methods We performed a retrospective analysis of our melanoma center database and identified 79 patients with brain metastasis between 2011 and 2015. Results The median time from primary melanoma diagnosis to brain metastasis was 3.2 years. The median overall survival duration from the time of initial brain metastasis was 12.8 months. Following a diagnosis of brain metastasis, 39 (49.4%), 28 (35.4%), and 24 (30.4%) patients were treated with anti-CTLA-4 antibody, anti-PD-1 antibody, or BRAF inhibitors (with or without a MEK inhibitor), with a median overall survival of 19.2 months, 37.9 months and 12.7 months, respectively. Factors associated with significantly reduced overall survival included male sex, cerebellar metastasis, higher number of brain lesions, and treatment with whole-brain radiation therapy. Factors associated with significantly longer overall survival included treatment with craniotomy, stereotactic radiosurgery, or with anti-PD-1 antibody after initial diagnosis of brain metastasis. Conclusions These results show a significant improvement in the overall survival of patients with melanoma brain metastasis in the era of novel therapies. In addition, they suggest the activity of anti-PD-1 therapy specifically in the setting of brain metastasis.

Autoreactive memory T lymphocytes are implicated in the pathogenesis of autoimmune diseases. Here we demonstrate that disease-associated autoreactive T cells from patients with type-1 diabetes mellitus or rheumatoid arthritis (RA) are mainly CD4⁺CCR7⁻CD45RA⁻ effector memory T cells ($T_{EM}$cells) with elevated Kv1.3 potassium channel expression. In contrast, T cells with other antigen specificities from these patients, or autoreactive T cells from healthy individuals and disease controls, express low levels of Kv1.3 and are predominantly naíve or central-memory ($T_{CM}$) cells. In$T_{EM}$cells, Kv1.3 traffics to the immunological synapse during antigen presentation where it colocalizes with Kvβ2, SAP97, ZIP,$p56^{Ick}$, and CD4. Although Kv1.3 inhibitors [ShK(L5)-amide (SL5) and PAP1] do not prevent immunological synapse formation, they suppress Ca²⁺-signaling, cytokine production, and proliferation of autoantigen-specific$T_{EM}$cells at pharmacologically relevant concentrations while sparing other classes of T cells. Kv1.3 inhibitors ameliorate pristane-induced arthritis in rats and reduce the incidence of experimental autoimmune diabetes in diabetes-prone (DP-BB/W) rats. Repeated dosing with Kv1.3 inhibitors in rats has not revealed systemic toxicity. Further development of Kv1.3 blockers for autoimmune disease therapy is warranted.

Decompressive craniectomy (DC) is often required to manage rising intracranial pressure after traumatic brain injury (TBI). Syndrome of the trephine (SoT) is a reversible neurologic condition that often occurs following DC as a result of the unrepaired skull. The purpose of the present study is to characterize neurological impairment following TBI in rats with an unrepaired craniectomy versus rats with a closed cranium. Long Evans male rats received a controlled cortical impact (CCI) over the caudal forelimb area (CFA) of the motor cortex. Immediately after CCI, rats received either a hemi-craniectomy (TBI Open Skull Group) or an immediate acrylic cranioplasty restoring cranial anatomy (TBI Closed Skull Group). Motor performance was assessed on a skilled reaching task on post-CCI weeks 1—4, 8, 12, and 16. Three weeks after the CCI injury, the TBI Closed Skull Group demonstrated improved motor performance compared to TBI Open Skull Group. The TBI Closed Skull Group continued to perform better than the TBI Open Skull Group throughout weeks 4, 8, 12 and 16. The protracted recovery of CFA motor performance demonstrated in rats with unrepaired skulls following TBI suggests this model may be beneficial for testing new therapeutic approaches to prevent SoT.

Overactivation of NMDA receptors (NMDARs) is a critical early step in glutamate-evoked excitotoxic injury of CNS neurons. Distinct NMDAR-coupled pathways specified by, for example, receptor location or subunit composition seem to govern glutamate-induced excitotoxic death, but there is much uncertainty concerning the underlying mechanisms of pathway selection. Here we ask whether, and if so how, route-specific vulnerability is coupled to Ca²⁺ overload and mitochondrial dysfunction, which is also a known, central component of exitotoxic injury. In cultured hippocampal neurons, overactivation of only extrasynaptic NMDARs resulted in Ca²⁺ entry strong enough to promote Ca²⁺ overload, which subsequently leads to mitochondrial dysfunction and cell death. Receptor composition per se appears not to be a primary factor for specifying signal coupling, as NR2B inhibition abolished Ca²⁺ loading and was protective only in predominantly NR2B-expressing young neurons. In older neurons expressing comparable levels of NR2A-and NR2B-containing NMDARs, amelioration of Ca²⁺ overload required the inhibition of extrasynaptic receptors containing both NR2 subunits. Prosurvival synaptic stimuli also evoked Ca²⁺ entry through both N2A-and NR2B-containing NMDARs, but in contrast to excitotoxic activation of extrasynaptic NMDARs, produced only low-amplitude cytoplasmic Ca²⁺ spikes and modest nondamaging mitochondrial Ca²⁺ accumulation. The results—showing that the various routes of excitotoxic Ca²⁺ entry converge on a common pathway involving Ca²⁺ overloadinduced mitochondrial dysfunction—reconcile and unify many aspects of the \"route-specific\" and \"calcium load-dependent\" views of exitotoxic injury.

Coral reefs are iconic ecosystems that support diverse, productive communities in both shallow and deep waters. However, our incomplete knowledge of cold-water coral (CWC) niche space limits our understanding of their distribution and precludes a complete accounting of the ecosystem services they provide. Here, we present the results of recent surveys of the CWC mound province on the Blake Plateau off the U.S. east coast, an area of intense human activity including fisheries and naval operations, and potentially energy and mineral extraction. At one site, CWC mounds are arranged in lines that total over 150 km in length, making this one of the largest reef complexes discovered in the deep ocean. This site experiences rapid and extreme shifts in temperature between 4.3 and 10.7 °C, and currents approaching 1 m s −1 . Carbon is transported to depth by mesopelagic micronekton and nutrient cycling on the reef results in some of the highest nitrate concentrations recorded in the region. Predictive models reveal expanded areas of highly suitable habitat that currently remain unexplored. Multidisciplinary exploration of this new site has expanded understanding of the cold-water coral niche, improved our accounting of the ecosystem services of the reef habitat, and emphasizes the importance of properly managing these systems.

Background Reliable control of rehabilitation and assistive devices using High-Density surface Electromyography (HD-sEMG) remains limited by poor robustness to electrode shifts, changes in skin condition, and variability across users. Methods This study evaluates the performance of the Recursive Prosthetic Control Network (RPC-Net)/High-Density Electrode Array (HDE-Array) system, defined in previous studies, under conditions that reflect real-life usage, including electrode repositioning and cross-subject generalization. The first test evaluated whether the RPC-Net/HDE-Array system maintained stable performance when trained without electrode repositioning and evaluated on data from a different session with altered electrode placement. The study further examined whether explicitly incorporating electrode repositioning during training mitigates the performance degradation typically observed when testing is performed in a separate session. Finally, the effects of inter-subject training were assessed. Results Experimental results demonstrate that the RPC-Net/HDE-Array system is highly sensitive to electrode repositioning and skin condition variability when trained under static conditions. However, robustness improves significantly when such variability is included during training. The results indicate that performance improves with an increasing number of subjects in the training pool, provided the training set includes only data from subjects other than the one tested, suggesting a strong dependency on subject-specific patterns Conclusions These findings demonstrate that the RPC-Net/HDE-Array system can achieve robust performance across sessions and users when trained under realistic conditions. This work represents a key step toward practical deployment of muscle-computer interfaces.

The role of place-making and architecture in mobile cultures The relationship of hunter-gatherer societies to the built environment is often overlooked or characterized as strictly utilitarian in archaeological research. Taking on deeper questions of cultural significance and social inheritance, this volume offers a more robust examination of houses as not only places of shelter but also of memory, history, and social cohesion within these communities. Bringing together case studies from Europe, Asia, and North and South America, More Than Shelter from the Storm utilizes a diverse array of methodologies including radiocarbon dating, geoarchaeology, refitting studies, and material culture studies to reframe the conversation around hunter-gatherer houses. Discussing examples of built structures from the Pleistocene through Late Holocene periods, contributors investigate how these societies created a sense of home through symbolic decoration, ritual, and transformative interaction with the landscape. Demonstrating that meaningful relationships with architecture are not limited to sedentary societies that construct permanent houses, the essays in this volume highlight the complexity of mobile cultures and demonstrate the role of place-making and the built environment in structuring their worldviews. Contributors: Brian Andrews | Amy E. Clark | Margaret W. Conkey | Kelly Eldridge | Randy Haas | Knut A. Helskog | Bryan C. Hood | Sebastien Lacombe | Danielle Macdonald | Lisa Maher | Brooke Morgan | Christopher Morgan | Gustavo Neme | Lauren Norman | Matthew O'Brien | Spencer Pelton | Sarah Ranlett | Vladimir Shumkin | Kathleen Sterling | Todd Surovell | Christopher B. Wolff

Deformational plagiocephaly and craniosynostosis are two of the most common neonatal cranial head shape anomalies. Traditionally, both entities were thought to cause aesthetic concerns solely. Recently, many groups have demonstrated that both conditions are strongly associated with developmental delays. The relationship between the abnormal neonatal cranial shape and early developmental delays manifested in both conditions remains poorly understood.