Cingulo-opercular control network and disused motor circuits joined in standby mode.

Whole-brain resting-state functional MRI (rs-fMRI) during 2 wk of upper-limb casting revealed that disused motor regions became more strongly connected to the cingulo-opercular network (CON), an executive control network that includes regions of the dorsal anterior cingulate cortex (dACC) and insula. Disuse-driven increases in functional connectivity (FC) were specific to the CON and somatomotor networks and did not involve any other networks, such as the salience, frontoparietal, or default mode networks. Censoring and modeling analyses showed that FC increases during casting were mediated by large, spontaneous activity pulses that appeared in the disused motor regions and CON control regions. During limb constraint, disused motor circuits appear to enter a standby mode characterized by spontaneous activity pulses and strengthened connectivity to CON executive control regions.

Virtual Experience Toolkit: An End-to-End Automated 3D Scene Virtualization Framework Implementing Computer Vision Techniques.

Virtualization plays a critical role in enriching the user experience in Virtual Reality (VR) by offering heightened realism, increased immersion, safer navigation, and newly achievable levels of interaction and personalization, specifically in indoor environments. Traditionally, the creation of virtual content has fallen under one of two broad categories: manual methods crafted by graphic designers, which are labor-intensive and sometimes lack precision; traditional Computer Vision (CV) and Deep Learning (DL) frameworks that frequently result in semi-automatic and complex solutions, lacking a unified framework for both 3D reconstruction and scene understanding, often missing a fully interactive representation of the objects and neglecting their appearance. To address these diverse challenges and limitations, we introduce the Virtual Experience Toolkit (VET), an automated and user-friendly framework that utilizes DL and advanced CV techniques to efficiently and accurately virtualize real-world indoor scenarios. The key features of VET are the use of ScanNotate, a retrieval and alignment tool that enhances the precision and efficiency of its precursor, supported by upgrades such as a preprocessing step to make it fully automatic and a preselection of a reduced list of CAD to speed up the process, and the implementation in a user-friendly and fully automatic Unity3D application that guides the users through the whole pipeline and concludes in a fully interactive and customizable 3D scene. The efficacy of VET is demonstrated using a diversified dataset of virtualized 3D indoor scenarios, supplementing the ScanNet dataset.

Individual-specific functional connectivity of the amygdala: A substrate for precision psychiatry.

The amygdala is central to the pathophysiology of many psychiatric illnesses. An imprecise understanding of how the amygdala fits into the larger network organization of the human brain, however, limits our ability to create models of dysfunction in individual patients to guide personalized treatment. Therefore, we investigated the position of the amygdala and its functional subdivisions within the network organization of the brain in 10 highly sampled individuals (5 h of fMRI data per person). We characterized three functional subdivisions within the amygdala of each individual. We discovered that one subdivision is preferentially correlated with the default mode network; a second is preferentially correlated with the dorsal attention and fronto-parietal networks; and third subdivision does not have any networks to which it is preferentially correlated relative to the other two subdivisions. All three subdivisions are positively correlated with ventral attention and somatomotor networks and negatively correlated with salience and cingulo-opercular networks. These observations were replicated in an independent group dataset of 120 individuals. We also found substantial across-subject variation in the distribution and magnitude of amygdala functional connectivity with the cerebral cortex that related to individual differences in the stereotactic locations both of amygdala subdivisions and of cortical functional brain networks. Finally, using lag analyses, we found consistent temporal ordering of fMRI signals in the cortex relative to amygdala subdivisions. Altogether, this work provides a detailed framework of amygdala-cortical interactions that can be used as a foundation for models relating aberrations in amygdala connectivity to psychiatric symptoms in individual patients.

Biomaterials and Regenerative Medicine in Pain Management.

PURPOSE OF REVIEW: Pain presents a unique challenge due to the complexity of the biological pathways involved in the pain perception, the growing concern regarding the use of opioid analgesics, and the limited availability of optimal treatment options. The use of biomaterials and regenerative medicine in pain management is being actively explored and showing exciting progress in improving the efficacy of conventional pharmacotherapy and as novel non-pharmacological therapy for chronic pain caused by degenerative diseases. In this paper we review current clinical applications, and promising research in the use of biomaterials and regenerative medicine in pain management. RECENT FINDINGS: Regenerative therapies have been developed to repair damaged tissues in back, joint, and shoulder that lead to chronic and inflammatory pain. Novel regenerative biomaterials have been designed to incorporate biochemical and physical pro-regenerative cues that augment the efficacy of regenerative therapies. New biomaterials improve target localization with improved tunability for controlled drug delivery, and injectable scaffolds enhance the efficacy of regenerative therapies through improving cellular migration. Advanced biomaterial carrier systems have been developed for sustained and targeted delivery of analgesic agents to specific tissues and organs, showing improved treatment efficacy, extended duration of action, and reduced dosage. Targeting endosomal receptors by nanoparticles has shown promising anti-nociception effects. Biomaterial scavengers are designed to remove proinflammatory reactive oxygen species that trigger nociceptors and cause pain hypersensitivity, providing a proactive approach for pain management. Pharmacotherapy remains the method of choice for pain management; however, conventional analgesic agents are associated with adverse effects. The relatively short duration of action when applied as free drug limited their efficacy in postoperative and chronic pain treatment. The application of biomaterials in pain management is a promising strategy to improve the efficacy of current pharmacotherapy through sustained and targeted delivery of analgesic agents. Regenerative medicine strategies target the damaged tissue and provide non-pharmacological alternatives to manage chronic and inflammatory pain. In the future, the successful development of regenerative therapies that completely repair damaged tissues will provide a more optimal alternative for the treatment of chronic pain caused. Future studies will leverage on the increasing understanding of the molecular mechanisms governing pain perception and transmission, injury response and tissue regeneration, and the development of new biomaterials and tissue regenerative methods.

Trait-like variants in human functional brain networks.

Resting-state functional magnetic resonance imaging (fMRI) has provided converging descriptions of group-level functional brain organization. Recent work has revealed that functional networks identified in individuals contain local features that differ from the group-level description. We define these features as network variants. Building on these studies, we ask whether distributions of network variants reflect stable, trait-like differences in brain organization. Across several datasets of highly-sampled individuals we show that 1) variants are highly stable within individuals, 2) variants are found in characteristic locations and associate with characteristic functional networks across large groups, 3) task-evoked signals in variants demonstrate a link to functional variation, and 4) individuals cluster into subgroups on the basis of variant characteristics that are related to differences in behavior. These results suggest that distributions of network variants may reflect stable, trait-like, functionally relevant individual differences in functional brain organization.

Towards the Automation of Infrared Thermography Inspections for Industrial Maintenance Applications.

The maintenance of industrial equipment extends its useful life, improves its efficiency, reduces the number of failures, and increases the safety of its use. This study proposes a methodology to develop a predictive maintenance tool based on infrared thermographic measures capable of anticipating failures in industrial equipment. The thermal response of selected equipment in normal operation and in controlled induced anomalous operation was analyzed. The characterization of these situations enabled the development of a machine learning system capable of predicting malfunctions. Different options within the available conventional machine learning techniques were analyzed, assessed, and finally selected for electronic equipment maintenance activities. This study provides advances towards the robust application of machine learning combined with infrared thermography and augmented reality for maintenance applications of industrial equipment. The predictive maintenance system finally selected enables automatic quick hand-held thermal inspections using 3D object detection and a pose estimation algorithm, making predictions with an accuracy of 94% at an inference time of 0.006 s.

Organization of Propagated Intrinsic Brain Activity in Individual Humans.

Spontaneous infra-slow (<0.1 Hz) fluctuations in functional magnetic resonance imaging (fMRI) signals are temporally correlated within large-scale functional brain networks, motivating their use for mapping systems-level brain organization. However, recent electrophysiological and hemodynamic evidence suggest state-dependent propagation of infra-slow fluctuations, implying a functional role for ongoing infra-slow activity. Crucially, the study of infra-slow temporal lag structure has thus far been limited to large groups, as analyzing propagation delays requires extensive data averaging to overcome sampling variability. Here, we use resting-state fMRI data from 11 extensively-sampled individuals to characterize lag structure at the individual level. In addition to stable individual-specific features, we find spatiotemporal topographies in each subject similar to the group average. Notably, we find a set of early regions that are common to all individuals, are preferentially positioned proximal to multiple functional networks, and overlap with brain regions known to respond to diverse behavioral tasks-altogether consistent with a hypothesized ability to broadly influence cortical excitability. Our findings suggest that, like correlation structure, temporal lag structure is a fundamental organizational property of resting-state infra-slow activity.

No "Wearing-Off Effect" Seen in Quarterly or Monthly Dosing of Fremanezumab: Subanalysis of a Randomized Long-Term Study.

OBJECTIVE: To evaluate whether quarterly or monthly administration of fremanezumab for migraine prevention exhibits a pattern of decreased efficacy toward the end of the dosing interval (wearing-off effect). BACKGROUND: The main goals of migraine preventive treatment are to reduce the frequency, severity, and duration of migraine attacks, and migraine-associated disability. Wearing-off refers to the phenomenon whereby clinical symptoms return or worsen before the next dose of a drug is due and has been reported previously with migraine preventive medications. DESIGN AND METHODS: This was a long-term, 12-month, multicenter, randomized, double-blind, parallel-group phase 3 study (NCT02638103) that included chronic (CM) and episodic migraine (EM) patients who rolled over from the 12-week phase 3 HALO CM (NCT02621931) and EM trials (NCT02629861), as well as an additional subset of 312 new patients. Patients with CM or EM received fremanezumab either monthly or quarterly. In this post hoc analysis, for selected months, the difference in the average number of migraine days between weeks 1-2 and weeks 3-4, between weeks 1-3 and week 4, and between weeks 1-2 and weeks 11-12 were calculated. RESULTS: A total of 1890 patients (CM, 1110; EM, 780) were enrolled. At months 3, 6, 9, and 15, there were no substantial differences in mean weekly migraine days between weeks 1-2 and weeks 3-4 or between weeks 1-3 and week 4 with quarterly or monthly fremanezumab in the CM or EM subgroups. There were no substantial increases in mean weekly migraine days between weeks 1-2 and weeks 11-12 during the first quarter of treatment (months 1-3) or the second quarter of treatment (months 4-6) with quarterly or monthly fremanezumab in the CM or EM subgroups. Across both dosing subgroups in CM and EM patients, the mean weekly number of migraine days decreased substantially (30%-42%) during the first 2 weeks; decreases in weekly migraine days remained steady during the last 2 weeks of the first quarter, with a similar maintenance of response during the second quarter. CONCLUSIONS: This analysis of data from a long-term, phase 3 study showed that patients receiving quarterly fremanezumab or monthly fremanezumab did not experience a wearing-off effect toward the end of the dosing interval.

Bladder and urethral dysfunction in multiparous and mature rabbits correlates with abnormal activity of pubococcygeus and bulbospongiosus muscles.

AIMS: To evaluate the combined effect of age and multiparity on the micturition reflex, including pelvic floor muscle activation. METHODS: Young and mature nulliparous rabbits were compared to young and mature multiparas (n = 6 per group). Cystometrograms and urethral pressure (UP) were performed while simultaneously recording the electromyogram (EMG) activity of the pubococcygeus and bulbospongiosus muscles to establish their functional correlation to urological function. RESULTS: Multiparity and age significantly influence the bladder and UP affecting the voiding efficiency and intercontraction interval. Such interaction also reduced the UP threshold, timing, and duration. Other bladder and urethral variables were predominantly affected only by age. Urodynamic alterations correlated with abnormal patterns or absent EMG activity of the pubococcygeus and bulbospongiosus muscles. CONCLUSIONS: The present findings strongly suggest that multiparity and age affects specific pelvic floor muscle reflex activation during micturition, and may contribute to alterations in bladder and urethral function. This data broadens our understanding of the critical role of the appropriate activity of the individual pelvic floor muscles in micturition.

Evolution of perioperative quality of life in patients under enhanced recovery after surgery care in colorectal cancer.

BACKGROUND: the Enhanced Recovery After Surgery (ERAS) protocols aim to improve postoperative outcomes by obtaining a functional rehabilitation after surgery. The purpose of this study was to evaluate the impact of ERAS on the quality of life (QOL) of patients undergoing colorectal cancer surgeries. METHODS: a cohort observational study was designed of patients with colorectal cancer undergoing elective surgeries during a one-year period. Patients were included when the ERAS protocol was fully achieved for all the interventions, including the expected hospital discharge day. Patient reported outcomes (PROs) were evaluated by the EORTC QLQ-C30 and the QLQ-CR29 questionnaires on three different occasions: baseline before surgery and on postoperative days 7 and 30. RESULTS: the study included 40 patients who completed QOL evaluations with a mean age of 70 ± 11 years. There were no statistical differences between preoperative and postoperative QOL scores. By subgroups of QOL items, a significant decrease was observed in physical activity and role functioning when comparing preoperative vs postoperative status, whereas the cognitive, social and emotional functioning scales were similar or improved over time. CONCLUSIONS: in our experience, surgery under ERAS protocols did not have an impact on decreasing global QOL in patients undergoing elective colorectal cancer surgery. The use of ERAS protocols in colorectal surgery achieves a positive influence, not only by decreasing surgical-related complications but also in terms of functional recovery, by decreasing the negative effects of surgery on patient QOL.

High-fidelity mapping of repetition-related changes in the parietal memory network.

fMRI studies of human memory have identified a "parietal memory network" (PMN) that displays distinct responses to novel and familiar stimuli, typically deactivating during initial encoding but robustly activating during retrieval. The small size of PMN regions, combined with their proximity to the neighboring default mode network, makes a targeted assessment of their responses in highly sampled subjects important for understanding information processing within the network. Here, we describe an experiment in which participants made semantic decisions about repeatedly-presented stimuli, assessing PMN BOLD responses as items transitioned from experimentally novel to repeated. Data are from the highly-sampled subjects in the Midnight Scan Club dataset, enabling a characterization of BOLD responses at both the group and single-subject level. Across all analyses, PMN regions deactivated in response to novel stimuli and displayed changes in BOLD activity across presentations, but did not significantly activate to repeated items. Results support only a portion of initially hypothesized effects, in particular suggesting that novelty-related deactivations may be less susceptible to attentional/task manipulations than are repetition-related activations within the network. This in turn suggests that novelty and familiarity may be processed as separable entities within the PMN.

Transregulation of microRNA miR-21 promoter by AP-1 transcription factor in cervical cancer cells.

BACKGROUND: Gene expression profiles have demonstrated that miR-21 expression is altered in almost all types of cancers and it has been classified as an oncogenic microRNA. Persistent HPV infection is the main etiologic agent in cervical cancer and induces genetic instability, including disruption of microRNA gene expression. In the present study, we analyzed the underlying mechanism of how AP-1 transcription factor can active miR-21 gene expression in cervical cancer cells. METHODS: To identify that c-Fos and c-Jun regulate the expression of miR-21 we performed RT-qPCR and western blot assays. We analyzed the interaction of AP-1 with miR-21 promoter by EMSA and ChIP assays and determined the mechanism of its regulation by reporter construct plasmids. We identified the nuclear translocation of c-Fos and c-Jun by immunofluorescence microscopy assays. RESULTS: We demonstrated that c-Fos and c-Jun proteins are expressed and regulate the expression of miR-21 in cervical cancer cells. DNA sequence analysis revealed the presence of AP-1 DNA-binding sites in the human miR-21 promoter region. EMSA analyses confirmed the interactions of the miR-21 upstream transcription factor AP-1. ChIP assays further showed the binding of c-Fos to AP-1 sequences from the miR-21 core promoter in vivo. Functional analysis of AP-1 sequences of miR-21 in reporter plasmids demonstrated that these sequences increase the miR-21 promoter activation. CONCLUSIONS: Our findings suggest a physical interaction and functional cooperation between AP-1 transcription factor in the miR-21 promoter and may explain the effect of AP-1 on miR-21 gene expression in cervical cancer cells.

Spatiotemporal variations of organochlorine pesticides in an apex predator: Influence of government regulations and farming practices.

BACKGROUND: Intensification of agricultural practices has caused several negative effects to the environment. The use of fertilizers and pesticides may alter geochemical cycles or cause direct wildlife intoxication. Detrimental effects of organochlorine pesticides (OCPs) have forced the authorities to ban or restrict its use. This study evaluates the variation in levels of OCPs in a sentinel species in relation to changes in government regulations and the spatial configuration of agricultural practices around the nests. METHODS: Between 2003 and 2007, we analysed OCP levels in 256 blood samples of Eurasian Eagle-owl (Bubo bubo) chicks nesting in area of intensive commercial agriculture with historical frequent use of pesticides, in South-eastern Spain. We studied year-to-year variations in OCP concentrations and their relation with land use configuration around raptor nests by Generalized Linear Mixed Models (GLMM). RESULTS: OCPs were detected in 100% samples surveyed in 2003 and 2004, while dropped to 27% in 2005, 6.8% in 2006 and 6.3% in 2007, coinciding with the ban of OCPs. The presence of the main OCPs was related to agricultural practices. In particular, endosulfan and lindane were related to irrigated crops and urban areas, while DDT-related compounds and dieldrin were associated with dry land farming. CONCLUSIONS: OCP concentrations in blood samples of Eurasian Eagle-owls may respond quickly to the implementations of new regulations about the use of agricultural products. This raptor was confirmed as a good sentinel species allowing rapid detection of changes in pesticides use.

Adult mouse sensory neurons on microelectrode arrays exhibit increased spontaneous and stimulus-evoked activity in the presence of interleukin-6.

Following inflammation or injury, sensory neurons located in the dorsal root ganglia (DRG) may exhibit increased spontaneous and/or stimulus-evoked activity, contributing to chronic pain. Current treatment options for peripherally mediated chronic pain are highly limited, driving the development of cell- or tissue-based phenotypic (function-based) screening assays for peripheral analgesic and mechanistic lead discovery. Extant assays are often limited by throughput, content, use of tumorigenic cell lines, or tissue sources from immature developmental stages (i.e., embryonic or postnatal). Here, we describe a protocol for culturing adult mouse DRG neurons on substrate-integrated multiwell microelectrode arrays (MEAs). This approach enables multiplexed measurements of spontaneous as well as stimulus-evoked extracellular action potentials from large populations of cells. The DRG cultures exhibit stable spontaneous activity from 9 to 21 days in vitro. Activity is readily evoked by known chemical and physical agonists of sensory neuron activity such as capsaicin, bradykinin, PGE2, heat, and electrical field stimulation. Most importantly, we demonstrate that both spontaneous and stimulus-evoked activity may be potentiated by incubation with the inflammatory cytokine interleukin-6 (IL-6). Acute responsiveness to IL-6 is inhibited by treatment with a MAPK-interacting kinase 1/2 inhibitor, cercosporamide. In total, these findings suggest that adult mouse DRG neurons on multiwell MEAs are applicable to ongoing efforts to discover peripheral analgesic and their mechanisms of action. NEW & NOTEWORTHY This work describes methodologies for culturing spontaneously active adult mouse dorsal root ganglia (DRG) sensory neurons on microelectrode arrays. We characterize spontaneous and stimulus-evoked adult DRG activity over durations consistent with pharmacological interventions. Furthermore, persistent hyperexcitability could be induced by incubation with inflammatory cytokine IL-6 and attenuated with cercosporamide, an inhibitor of the IL-6 sensitization pathway. This constitutes a more physiologically relevant, moderate-throughput in vitro model for peripheral analgesic screening as well as mechanistic lead discovery.

Intelligent Multimodal Framework for Human Assistive Robotics Based on Computer Vision Algorithms.

Assistive technologies help all persons with disabilities to improve their accessibility in all aspects of their life. The AIDE European project contributes to the improvement of current assistive technologies by developing and testing a modular and adaptive multimodal interface customizable to the individual needs of people with disabilities. This paper describes the computer vision algorithms part of the multimodal interface developed inside the AIDE European project. The main contribution of this computer vision part is the integration with the robotic system and with the other sensory systems (electrooculography (EOG) and electroencephalography (EEG)). The technical achievements solved herein are the algorithm for the selection of objects using the gaze, and especially the state-of-the-art algorithm for the efficient detection and pose estimation of textureless objects. These algorithms were tested in real conditions, and were thoroughly evaluated both qualitatively and quantitatively. The experimental results of the object selection algorithm were excellent (object selection over 90%) in less than 12 s. The detection and pose estimation algorithms evaluated using the LINEMOD database were similar to the state-of-the-art method, and were the most computationally efficient.

Median and ulnar nerve injuries reduce volitional forelimb strength in rats.

INTRODUCTION: Peripheral nerve injuries (PNI) are among the leading causes of physical disability in the United States. The majority of injuries occur in the upper extremities, and functional recovery is often limited. Robust animal models are critical first steps for developing effective therapies to restore function after PNI. METHODS: We developed an automated behavioral assay that provides quantitative measurements of volitional forelimb strength in rats. Multiple forelimb PNI models involving the median and ulnar nerves were used to assess forelimb function for up to 13 weeks postinjury. RESULTS: Despite multiple weeks of task-oriented training following injury, rats exhibit significant reductions in multiple quantitative parameters of forelimb function, including maximal pull force and speed of force generation. DISCUSSION: This study demonstrates that the isometric pull task is an effective method of evaluating forelimb function following PNI and may aid in development of therapeutic interventions to restore function. Muscle Nerve 56: 1149-1154, 2017.

Mycoplasma hyopneumoniae does not affect the interferon-related anti-viral response but predisposes the pig to a higher level of inflammation following swine influenza virus infection.

In pigs, influenza A viruses and Mycoplasma hyopneumoniae (Mhp) are major contributors to the porcine respiratory disease complex. Pre-infection with Mhp was previously shown experimentally to exacerbate the clinical outcomes of H1N1 infection during the first week after virus inoculation. In order to better understand the interactions between these pathogens, we aimed to assess very early responses (at 5, 24 and 48 h) after H1N1 infection in pigs pre-infected or not with Mhp. Clinical signs and macroscopic lung lesions were similar in both infected groups at early times post-H1N1 infection; and Mhp pre-infection affected neither the influenza virus replication nor the IFN-induced antiviral responses in the lung. However, it predisposed the animals to a higher inflammatory response to H1N1 infection, as revealed by the massive infiltration of neutrophils and macrophages into the lungs and the increased production of pro-inflammatory cytokines (IL-6, IL-1ß and TNF-α). Thus, it seems it is this marked inflammatory state that would play a role in exacerbating the clinical signs subsequent to H1N1 infection.

Induction and treatment of anergy in murine leprosy.

Leprosy is a disease consisting of a spectrum of clinical, bacteriological, histopathological and immunological manifestations. Tuberculoid leprosy is frequently recognized as the benign polar form of the disease, while lepromatous leprosy is regarded as the malignant form. The different forms of leprosy depend on the genetic and immunological characteristics of the patient and on the characteristics of the leprosy bacillus. The malignant manifestations of lepromatous leprosy result from the mycobacterial-specific anergy that develops in this form of the disease. Using murine leprosy as a model of anergy in this study, we first induced the development of anergy to Mycobacterium lepraemurium (MLM) in mice and then attempted to reverse it by the administration of dialysable leucocyte extracts (DLE) prepared from healthy (HLT), BCG-inoculated and MLM-inoculated mice. Mice inoculated with either MLM or BCG developed a robust cell-mediated immune response (CMI) that was temporary in the MLM-inoculated group and long-lasting in the BCG-inoculated group. DLE were prepared from the spleens of MLM- and BCG-inoculated mice at the peak of CMI. Independent MLM intradermally-inoculated groups were treated every other day with HLT-DLE, BCG-DLE or MLM-DLE, and the effect was documented for 98 days. DLE administered at a dose of 1.0 U (1 × 10(6) splenocytes) did not affect the evolution of leprosy, while DLE given at a dose of 0.1 U showed beneficial effects regardless of the DLE source. The dose but not the specificity of DLE was the determining factor for reversing anergy.