Age-Specific Effects of Mirror-Muscle Activity on Cross-Limb Adaptations Under Mirror and Non-Mirror Visual Feedback Conditions

Cross-limb transfer (CLT) describes the observation of bilateral performance gains due to unilateral motor practice. Previous research has suggested that CLT may be reduced, or absent, in older adults, possibly due to age-related structural and functional brain changes. Based on research showing increases in CLT due to the provision of mirror visual feedback (MVF) during task execution in young adults, our study aimed to investigate whether MVF can facilitate CLT in older adults, who are known to be more reliant on visual feedback for accurate motor performance. Participants (N = 53) engaged in a short-term training regime (300 movements) involving a ballistic finger task using their dominant hand, while being provided with either visual feedback of their active limb, or a mirror reflection of their active limb (superimposed over the quiescent limb). Performance in both limbs was examined before, during and following the unilateral training. Furthermore, we measured corticospinal excitability (using TMS) at these time points, and assessed muscle activity bilaterally during the task via EMG; these parameters were used to investigate the mechanisms mediating and predicting CLT. Training resulted in significant bilateral performance gains that did not differ as a result of age or visual feedback (both p > 0.1). Training also elicited bilateral increases in corticospinal excitability (p < 0.05). For younger adults, CLT was significantly predicted by performance gains in the trained hand (β = 0.47), whereas for older adults it was significantly predicted by mirror activity in the untrained hand during training (β = 0.60). The present study suggests that older adults are capable of exhibiting CLT to a similar degree to younger adults. The prominent role of mirror activity in the untrained hand for CLT in older adults indicates that bilateral cortical activity during unilateral motor tasks is a compensatory mechanism. In this particular task, MVF did not facilitate the extent of CLT

Acute Microvascular Impairment Post-Reperfused STEMI Is Reversible and Has Additional Clinical Predictive Value: A CMR OxAMI Study

OBJECTIVES: This study sought to investigate the clinical utility and the predictive relevance of absolute rest myocardial blood flow (MBF) by cardiac magnetic resonance (CMR) in acute myocardial infarction. BACKGROUND: Microvascular obstruction (MVO) remains one of the worst prognostic factors in patients with reperfused ST-segment elevation myocardial infarction (STEMI). Clinical trials have focused on cardioprotective strategies to maintain microvascular functionality, but there is a need for a noninvasive test to determine their efficacy. METHODS: A total of 64 STEMI patients post-primary percutaneous coronary intervention underwent 3-T CMR scans acutely and at 6 months (6M). The protocol included cine function, T2-weighted edema imaging, pre-contrast T1 mapping, rest first-pass perfusion, and late gadolinium enhancement imaging. Segmental MBF, corrected for rate pressure product (MBFcor), was quantified in remote, edematous, and infarcted myocardium. RESULTS: Acute MBFcor was significantly reduced in infarcted myocardium compared with remote MBF (MBFinfarct 0.76 ± 0.20 ml/min/g vs. MBFremote 1.02 ± 0.21 ml/min/g, p 45% at 6M increased by 1.38:1 [p 2 or index of myocardial resistance <40, acute MBF was associated with long-term functional recovery and was an independent predictor of infarct size reduction. CONCLUSIONS: Acute MBF by CMR could represent a novel quantitative imaging biomarker of microvascular reversibility, and it could be used to identify patients who may benefit from more intensive or novel therapie

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

The Design Of Compact Planar Antennas For Laptop Applications Based On Metamaterial Concepts

Two laptop antennas are presented using two different designs based on metamaterials. The first design consists of planar monopole loaded with an electric-LC resonator (ELC). This novel topology allows for the realization of a multi-band antenna by using the ELC to add multiple resonances. This structure is analyzed using full-wave simulations. A circuit model is also developed to gain further understanding. This technique is then used to design a Wi-Fi antenna. The second design uses a modified double-tuned matching network to create a single-band match for a planar monopole antenna. The matching network is implemented using a complementary-split-ring-resonator (CSRR). The design is once again analyzed using full-wave simulations and a circuit model is also developed. This technique is then applied to design a WiMax antenna. Both the Wi-Fi and WiMax antennas are fabricated and show good agreement between the simulated and measured results.MAS