Firing patterns of spontaneously active motor units in spinal cord-injured subjects

Involuntary motor unit activity at low rates is common in hand muscles paralysed by spinal cord injury. Our aim was to describe these patterns of motor unit behaviour in relation to motoneurone and motor unit properties. Intramuscular electromyographic activity (EMG), surface EMG and force were recorded for 30 min from thenar muscles of nine men with chronic cervical SCI. Motor units fired for sustained periods (>10 min) at regular (coefficient of variation 0.15, n = 14). Regularly firing units started and stopped firing independently suggesting that intrinsic motoneurone properties were important for recruitment and derecruitment. Recruitment (3.6 Hz, SD 1.2), maximal (10.2 Hz, SD 2.3, range: 7.5-15.4 Hz) and derecruitment frequencies were low (3.3 Hz, SD 1.6), as were firing rate increases after recruitment (similar to 20 intervals in 3s). Once active, firing often covaried, promoting the idea that units received common inputs. Half of the regularly firing units showed a very slow decline (> 40 s) in discharge before derecruitment and had interspike intervals longer than their estimated afterhyperpolarisation potential (AHP) duration (estimated by death rate and breakpoint analyses). The other units were derecruited more abruptly and had shorter estimated AHP durations. Overall, regularly firing units had longer estimated AHP durations and were weaker than irregularly firing units, suggesting they were lower threshold units. Sustained firing of units at regular rates may reflect activation of persistent inward currents, visible here in the absence of voluntary drive, whereas irregularly firing units may only respond to synaptic noise

The tax-inducible actin-bundling protein fascin is crucial for release and cell-to-cell transmission of human T-cell leukemia virus type 1 (HTLV-1)

The delta-retrovirus Human T-cell leukemia virus type 1 (HTLV-1) preferentially infects CD4(+) T-cells via cell-to-cell transmission. Viruses are transmitted by polarized budding and by transfer of viral biofilms at the virological synapse (VS). Formation of the VS requires the viral Tax protein and polarization of the host cytoskeleton, however, molecular mechanisms of HTLV-1 cell-to-cell transmission remain incompletely understood. Recently, we could show Tax-dependent upregulation of the actin-bundling protein Fascin (FSCN-1) in HTLV-1-infected T-cells. Here, we report that Fascin contributes to HTLV-1 transmission. Using single-cycle replication-dependent HTLV-1 reporter vectors, we found that repression of endogenous Fascin by short hairpin RNAs and by Fascin-specific nanobodies impaired gag p19 release and cell-to-cell transmission in 293T cells. In Jurkat T-cells, Tax-induced Fascin expression enhanced virus release and Fascin-dependently augmented cell-to-cell transmission to Raji/CD4(+) B-cells. Repression of Fascin in HTLV-1-infected T-cells diminished virus release and gag p19 transfer to co-cultured T-cells. Spotting the mechanism, flow cytometry and automatic image analysis showed that Tax-induced T-cell conjugate formation occurred Fascin-independently. However, adhesion of HTLV-1-infected MT-2 cells in co-culture with Jurkat T-cells was reduced upon knockdown of Fascin, suggesting that Fascin contributes to dissemination of infected T-cells. Imaging of chronically infected MS9 T-cells in co-culture with Jurkat T-cells revealed that Fascin's localization at tight cell-cell contacts is accompanied by gag polarization suggesting that Fascin directly affects the distribution of gag to budding sites, and therefore, indirectly viral transmission. In detail, we found gag clusters that are interspersed with Fascin clusters, suggesting that Fascin makes room for gag in viral biofilms. Moreover, we observed short, Fascin-containing membrane extensions surrounding gag clusters and clutching uninfected T-cells. Finally, we detected Fascin and gag in long-distance cellular protrusions. Taken together, we show for the first time that HTLV-1 usurps the host cell factor Fascin to foster virus release and cell-to-cell transmission

Virtual Patient Technology: Engaging Primary Care in Quality Improvement Innovations

BACKGROUND: Engaging health care staff in new quality improvement programs is challenging. OBJECTIVE: We developed 2 virtual patient (VP) avatars in the context of a clinic-level quality improvement program. We sought to determine differences in preferences for VPs and the perceived influence of interacting with the VP on clinical staff engagement with the quality improvement program. METHODS: Using a participatory design approach, we developed an older male smoker VP and a younger female smoker VP. The older male smoker was described as a patient with cardiovascular disease and was ethnically ambiguous. The female patient was younger and was worried about the impact of smoking on her pregnancy. Clinical staff were allowed to choose the VP they preferred, and the more they engaged with the VP, the more likely the VP was to quit smoking and become healthier. We deployed the VP within the context of a quality improvement program designed to encourage clinical staff to refer their patients who smoke to a patient-centered Web-assisted tobacco intervention. To evaluate the VPs, we used quantitative analyses using multivariate models of provider and practice characteristics and VP characteristic preference and analyses of a brief survey of positive deviants (clinical staff in practices with high rates of encouraging patients to use the quit smoking innovation). RESULTS: A total of 146 clinical staff from 76 primary care practices interacted with the VPs. Clinic staff included medical providers (35/146, 24.0%), nurse professionals (19/146, 13.0%), primary care technicians (5/146, 3.4%), managerial staff (67/146, 45.9%), and receptionists (20/146, 13.7%). Medical staff were mostly male, and other roles were mostly female. Medical providers (OR 0.031; CI 0.003-0.281; P=.002) and younger staff (OR 0.411; CI 0.177-0.952; P=.038) were less likely to choose the younger, female VP when controlling for all other characteristics. VP preference did not influence online patient referrals by staff. In high-performing practices that referred 20 or more smokers to the ePortal (13/76), the majority of clinic staff were motivated by or liked the virtual patient (20/26, 77%). CONCLUSIONS: Medical providers are more likely motivated by VPs that are similar to their patient population, while nurses and other staff may prefer avatars that are more similar to them

Antiparasitic Activity of Tea Tree Oil (TTO) and Its Components against Medically Important Ectoparasites: A Systematic Review

Ectoparasites are pathogens that can infect the skin and cause immense pain, discomfort, and disease. They are typically managed with insecticides. However, the fast-emerging antimicrobial resistance and the slow rate of development of new bio-actives combined with environmental and health concerns over the continued use of neurotoxic insecticides warrant newer and alternative methods of control. Tea tree oil (TTO), as an alternative agent, has shown remarkable promise against ectoparasites in recent studies. To our knowledge, this is the first systematic review to assess preclinical and clinical studies exploring the antiparasitic activity of TTO and its components against clinically significant ectoparasites, such as Demodex mites, scabies mites, house dust mites, lice, fleas, chiggers, and bed bugs. We systematically searched databases, including PubMed, MEDLINE (EBSCOhost), Embase (Scopus), CENTRAL, Cochrane Library, CINAHL, ScienceDirect, Web of Science, SciELO, and LILACS in any language from inception to 4 April 2022. Studies exploring the therapeutic activity of TTO and its components against the ectoparasites were eligible. We used the ToxRTool (Toxicological data reliability assessment) tool, the Joanna Briggs Institute (JBI) critical appraisal tools, and the Jadad scale to assess the methodological qualities of preclinical (in vitro and in vivo) studies, non-randomised controlled trials (including cohort, case series, and case studies), and randomised controlled trials, respectively. Of 497 identified records, 71 studies were included in this systematic review, and most (66%) had high methodological quality. The findings of this review revealed the promising efficacy of TTO and its components against ectoparasites of medical importance. Most importantly, the compelling in vitro activity of TTO against ectoparasites noted in this review seems to have translated well into the clinical environment. The promising outcomes observed in clinical studies provide enough evidence to justify the use of TTO in the pharmacotherapy of ectoparasitic infections

Lexicase selection in Learning Classifier Systems

The lexicase parent selection method selects parents by considering performance on individual data points in random order instead of using a fitness function based on an aggregated data accuracy. While the method has demonstrated promise in genetic programming and more recently in genetic algorithms, its applications in other forms of evolutionary machine learning have not been explored. In this paper, we investigate the use of lexicase parent selection in Learning Classifier Systems (LCS) and study its effect on classification problems in a supervised setting. We further introduce a new variant of lexicase selection, called batch-lexicase selection, which allows for the tuning of selection pressure. We compare the two lexicase selection methods with tournament and fitness proportionate selection methods on binary classification problems. We show that batch-lexicase selection results in the creation of more generic rules which is favorable for generalization on future data. We further show that batch-lexicase selection results in better generalization in situations of partial or missing data.Comment: Genetic and Evolutionary Computation Conference, 201

Motor unit firing rates during spasms in thenar muscles of spinal cord injured subjects

Abstract Involuntary contractions of paralyzed muscles (spasms) commonly disrupt daily activities and rehabilitation after human spinal cord injury. Our aim was to examine the recruitment, firing rate modulation, and derecruitment of motor units that underlie spasms of thenar muscles after cervical spinal cord injury. Intramuscular electromyographic activity (EMG), surface EMG, and force were recorded during thenar muscle spasms that occurred spontaneously or that were triggered by movement of a shoulder or leg. Most spasms were submaximal (mean: 39%, SD: 33 of the force evoked by median nerve stimulation at 50 Hz) with strong relationships between EMG and force (R2>0.69). Unit recruitment occurred over a wide force range (0.2-103% of 50 Hz force). Significant unit rate modulation occurred during spasms (frequency at 25% maximal force: 8.8 Hz, 3.3 SD; at maximal force: 16.1 Hz, 4.1 SD). Mean recruitment frequency (7.1 Hz, 3.2 SD) was significantly higher than derecruitment frequency (5.4 Hz, 2.4 SD). Coactive unit pairs that fired for more than 4 s showed high (R2>0.7, n=4) or low (R2:0.3-0.7, n=12) rate-rate correlations, and derecruitment reversals (21 pairs, 29%). Later recruited units had higher or lower maximal firing rates than lower threshold units. These discrepant data show that coactive motoneurons are driven by both common inputs and by synaptic inputs from different sources during muscle spasms. Further, thenar motoneurons can still fire at high rates in response to various peripheral inputs after spinal cord injury, supporting the idea that low maximal voluntary firing rates and forces in thenar muscles result from reduced descending drive

Increased Ipsilateral M1 Activation after Incomplete Spinal Cord Injury Facilitates Motor Performance

Incomplete spinal cord injury (SCI) may result in muscle weakness and difficulties with force gradation. Although these impairments arise from the injury and subsequent changes at spinal levels, changes have also been demonstrated in the brain. Blood-oxygen-level dependent (BOLD) imaging was used to investigate these changes in brain activation in the context of unimanual contractions with the first dorsal interosseous muscle. BOLD- and force data were obtained in 19 individuals with SCI (AISA Impairment Scale [AIS] C/D, level C4-C8) and 24 able-bodied controls during maximal voluntary contractions (MVCs). To assess force modulation, participants performed 12 submaximal contractions with each hand (at 10, 30, 50, and 70% MVC) by matching their force level to a visual target. MVCs were weaker in the SCI group (both hands p < 0.001), but BOLD activation did not differ between SCI and control groups. For the submaximal contractions, force (as %MVC) was similar across groups. However, SCI participants showed increased activity of the ipsilateral motor cortex and contralateral cerebellum across all contractions, with no differential effect of force level. Activity of ipsilateral M1 was best explained by force of the target hand (vs. the non-target hand). In conclusion, the data suggest that after incomplete cervical SCI, individuals remain capable of producing maximal supraspinal drive and are able to modulate this drive adequately. Activity of the ipsilateral motor network appears to be task related, although it remains uncertain how this activity contributes to task performance and whether this effect could potentially be harnessed to improve motor functioning

Rapid response to pandemic threats: immunogenic epitope detection of pandemic pathogens for diagnostics and vaccine development using peptide microarrays

Emergence and re-emergence of pathogens bearing the risk of becoming a pandemic threat are on the rise. Increased travel and trade, growing population density, changes in urbanization, and climate have a critical impact on infectious disease spread. Currently, the world is confronted with the emergence of a novel coronavirus SARS-CoV-$_{2}$, responsible for yet more than 800 000 deaths globally. Outbreaks caused by viruses, such as SARS-CoV-$_{2}$, HIV, Ebola, influenza, and Zika, have increased over the past decade, underlining the need for a rapid development of diagnostics and vaccines. Hence, the rational identification of biomarkers for diagnostic measures on the one hand, and antigenic targets for vaccine development on the other, are of utmost importance. Peptide microarrays can display large numbers of putative target proteins translated into overlapping linear (and cyclic) peptides for a multiplexed, high-throughput antibody analysis. This enabled for example the identification of discriminant/diagnostic epitopes in Zika or influenza and mapping epitope evolution in natural infections versus vaccinations. In this review, we highlight synthesis platforms that facilitate fast and flexible generation of high-density peptide microarrays. We further outline the multifaceted applications of these peptide array platforms for the development of serological tests and vaccines to quickly encounter pandemic threats

Implementation of recommended trauma system criteria in south-eastern Norway: a cross-sectional hospital survey

<p>Abstract</p> <p>Background</p> <p>Formalized trauma systems have shown beneficial effects on patient survival and have harvested great recognition among health care professionals. In spite of this, the implementation of trauma systems is challenging and often met with resistance.</p> <p>Recommendations for a national trauma system in Norway were published in 2007. We wanted to assess the level of implementation of these recommendations.</p> <p>Methods</p> <p>A survey of all acute care hospitals that receive severely injured patients in the south-eastern health region of Norway was conducted. A structured questionnaire based on the 2007 national recommendations was used in a telephone interview of hospital trauma personnel between January 17 and 21, 2011. Seventeen trauma system criteria were identified from the recommendations.</p> <p>Results</p> <p>Nineteen hospitals were included in the study and these received more than 2000 trauma patients annually via their trauma teams. Out of the 17 criteria that had been identified, the hospitals fulfilled a median of 12 criteria. Neither the size of the hospitals nor the distance between the hospitals and the regional trauma centre affected the level of trauma resources available. The hospitals scored lowest on the criteria for transfer of patients to higher level of care and on the training requirements for members of the trauma teams.</p> <p>Conclusion</p> <p>Our study identifies a major shortcoming in the efforts of regionalizing trauma in our region. The findings indicate that training of personnel and protocols for inter-hospital transfer are the major deficiencies from the national trauma system recommendations. Resources for training of personnel partaking in trauma teams and development of inter-hospital transfer agreements should receive immediate attention.</p

Efficacy of Cognitive and Metacognitive Interventions on Executive Functioning Post Traumatic Brain Injury to Enhance Occupational Performance

Cognitive rehabilitation (CR) is proposed as an effective intervention for individuals post Traumatic Brain Injury (TBI), by addressing cognitive function through remediating skills and practicing new compensatory skills. While there is considerable research, including systematic reviews that explore cognitive interventions post TBI, more research is needed in which occupational performance is the primary outcome of cognitive intervention. This current systematic review aims to synthesize the current body of evidence available on how using CR techniques to address executive functioning impact occupational performance in individuals who sustained a mild or moderate TBI