Influence of virtual reality soccer game on walking performance in robotic assisted gait training for children

BACKGROUND: Virtual reality (VR) offers powerful therapy options within a functional, purposeful and motivating context. Several studies have shown that patients' motivation plays a crucial role in determining therapy outcome. However, few studies have demonstrated the potential of VR in pediatric rehabilitation. Therefore, we developed a VR-based soccer scenario, which provided interactive elements to engage patients during robotic assisted treadmill training (RAGT). The aim of this study was to compare the immediate effect of different supportive conditions (VR versus non-VR conditions) on motor output in patients and healthy control children during training with the driven gait orthosis Lokomat*. METHODS: A total of 18 children (ten patients with different neurological gait disorders, eight healthy controls) took part in this study. They were instructed to walk on the Lokomat in four different, randomly-presented conditions: (1) walk normally without supporting assistance, (2) with therapists' instructions to promote active participation, (3) with VR as a motivating tool to walk actively and (4) with the VR tool combined with therapists' instructions. The Lokomat gait orthosis is equipped with sensors at hip and knee joint to measure man-machine interaction forces. Additionally, subjects' acceptance of the RAGT with VR was assessed using a questionnaire. RESULTS: The mixed ANOVA revealed significant main effects for the factor CONDITIONS (p < 0.001) and a significant interaction CONDITIONS x GROUP (p = 0.01). Tests of between-subjects effects showed no significant main effect for the GROUP (p = 0.592). Active participation in patients and control children increased significantly when supported and motivated either by therapists' instructions or by a VR scenario compared with the baseline measurement "normal walking" (p < 0.001). CONCLUSIONS: The VR scenario used here induces an immediate effect on motor output to a similar degree as the effect resulting from verbal instructions by the therapists. Further research needs to focus on the implementation of interactive design elements, which keep motivation high across and beyond RAGT sessions, especially in pediatric rehabilitation

Selection analysis identifies unusual clustered mutational changes in Omicron lineage BA.1 that likely impact Spike function.

Among the 30 non-synonymous nucleotide substitutions in the Omicron S-gene are 13 that have only rarely been seen in other SARS-CoV-2 sequences. These mutations cluster within three functionally important regions of the S-gene at sites that will likely impact (i) interactions between subunits of the Spike trimer and the predisposition of subunits to shift from down to up configurations, (ii) interactions of Spike with ACE2 receptors, and (iii) the priming of Spike for membrane fusion. We show here that, based on both the rarity of these 13 mutations in intrapatient sequencing reads and patterns of selection at the codon sites where the mutations occur in SARS-CoV-2 and related sarbecoviruses, prior to the emergence of Omicron the mutations would have been predicted to decrease the fitness of any genomes within which they occurred. We further propose that the mutations in each of the three clusters therefore cooperatively interact to both mitigate their individual fitness costs, and adaptively alter the function of Spike. Given the evident epidemic growth advantages of Omicron over all previously known SARS-CoV-2 lineages, it is crucial to determine both how such complex and highly adaptive mutation constellations were assembled within the Omicron S-gene, and why, despite unprecedented global genomic surveillance efforts, the early stages of this assembly process went completely undetected

The experience of brace treatment in children/adolescents with scoliosis

BACKGROUND: Idiopathic scoliosis is a chronic illness with several different braces used for its treatment. Brace treatment during childhood/adolescence can produce stress. There are studies supporting that it can decrease body-image perception while other studies support that it has no such effect. The purpose of this study was to explore the experience of brace treatment in children/adolescents with scoliosis. The aim was to investigate which feelings are created by the bracing experience in children/adolescents with scoliosis and what are the children/adolescents' with scoliosis opinions of the support provided to them by health-care professionals and by their families. METHODS: We conducted interviews with the help of a semi-structured interview guide in order to address the topic of the experience of brace treatment. A convenient sample of twelve children and adolescents with scoliosis was selected from patients attending follow-up appointments at the Outpatient Scoliosis Clinics of two Greek hospitals. The data was analysed using the method of content analysis. RESULTS: Patients in the sample were 10–16 years old and they were mainly females (71%). Almost all of the participants reported having to deal with stress, denial, fear, anger, and shame. They were satisfied with the information they received regarding their condition and therapy. However, the information was not accompanied by support from the health care professionals. They reported that they were receiving support mainly from their families, friends, and classmates. CONCLUSION: The present study is contributing to the development of a better understanding of significant issues related to the experience of bracing therapy. It is clear that scoliosis children/adolescents have to be provided with support during the long period of bracing. It is apparent that those children/adolescents have unmet needs for care and health professionals and policy makers should try to find a way to address those needs

Phylogeography and Taxonomy of Trypanosoma brucei

Trypanosoma brucei, the parasite causing human African trypanosomiasis (sleeping sickness) across sub-Saharan Africa is traditionally split into three subspecies: T. b. gambiense (Tbg), causing a chronic form of human disease in West and Central Africa; T. b. rhodesiense (Tbr), causing an acute form of human disease in East and Southern Africa; and T. b. brucei (Tbb), which is restricted to animals. Tbg is further split into Tbg group 1 and Tbg group 2. Better understanding the evolutionary relationships between these groups may help to shed light on the epidemiology of sleeping sickness. Here, we used three different types of genetic markers to investigate the phylogeographic relationships among the four groups across a large portion of their range. Our results confirm the distinctiveness of Tbg group 1 while highlighting the extremely close relationships among the other three taxa. In particular, Tbg group 2 was closely related to Tbb, while Tbr appeared to be a variant of Tbb, differing only in its phenotype of human infectivity. The wide geographic distribution of the gene conferring human infectivity (SRA) and the fact that it is readily exchanged among lineages of T. brucei in eastern Africa suggests that human-infective trypanosomes have access to an extensive gene pool with which to respond to selective pressures such as drugs

Evasion by Stealth: Inefficient Immune Activation Underlies Poor T Cell Response and Severe Disease in SARS-CoV-Infected Mice

Severe Acute Respiratory Syndrome caused substantial morbidity and mortality during the 2002–2003 epidemic. Many of the features of the human disease are duplicated in BALB/c mice infected with a mouse-adapted version of the virus (MA15), which develop respiratory disease with high morbidity and mortality. Here, we show that severe disease is correlated with slow kinetics of virus clearance and delayed activation and transit of respiratory dendritic cells (rDC) to the draining lymph nodes (DLN) with a consequent deficient virus-specific T cell response. All of these defects are corrected when mice are treated with liposomes containing clodronate, which deplete alveolar macrophages (AM). Inhibitory AMs are believed to prevent the development of immune responses to environmental antigens and allergic responses by interacting with lung dendritic cells and T cells. The inhibitory effects of AM can also be nullified if mice or AMs are pretreated with poly I:C, which directly activate AMs and rDCs through toll-like receptors 3 (TLR3). Further, adoptive transfer of activated but not resting bone marrow–derived dendritic cells (BMDC) protect mice from lethal MA15 infection. These results may be relevant for SARS in humans, which is also characterized by prolonged virus persistence and delayed development of a SARS-CoV-specific immune response in individuals with severe disease

Increasing Dietary Fat Elicits Similar Changes in Fat Oxidation and Markers of Muscle Oxidative Capacity in Lean and Obese Humans

In lean humans, increasing dietary fat intake causes an increase in whole-body fat oxidation and changes in genes that regulate fat oxidation in skeletal muscle, but whether this occurs in obese humans is not known. We compared changes in whole-body fat oxidation and markers of muscle oxidative capacity differ in lean (LN) and obese (OB) adults exposed to a 2-day high-fat (HF) diet. Ten LN (BMI = 22.5±2.5 kg/m2, age = 30±8 yrs) and nine OB (BMI = 35.9±4.93 kg/m2, 38±5 yrs, Mean±SD) were studied in a room calorimeter for 24hr while consuming isocaloric low-fat (LF, 20% of energy) and HF (50% of energy) diets. A muscle biopsy was obtained the next morning following an overnight fast. 24h respiratory quotient (RQ) did not significantly differ between groups (LN: 0.91±0.01; OB: 0.92±0.01) during LF, and similarly decreased during HF in LN (0.86±0.01) and OB (0.85±0.01). The expression of pyruvate dehydrogenase kinase 4 (PDK4) and the fatty acid transporter CD36 increased in both LN and OB during HF. No other changes in mRNA or protein were observed. However, in both LN and OB, the amounts of acetylated peroxisome proliferator-activated receptor γ coactivator-1-α (PGC1-α) significantly decreased and phosphorylated 5-AMP-activated protein kinase (AMPK) significantly increased. In response to an isoenergetic increase in dietary fat, whole-body fat oxidation similarly increases in LN and OB, in association with a shift towards oxidative metabolism in skeletal muscle, suggesting that the ability to adapt to an acute increase in dietary fat is not impaired in obesity

Use of cancer-specific yeast-secreted in vivo biotinylated recombinant antibodies for serum biomarker discovery

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Quality indicators for multiple sclerosis

Determining whether persons with multiple sclerosis (MS) receive appropriate, comprehensive healthcare requires tools for measuring quality. The objective of this study was to develop quality indicators for the care of persons with MS. We used a modified version of the RAND/UCLA Appropriateness Method in a two-stage process to identify relevant MS care domains and to assess the validity of indicators within high-ranking care domains. Based on a literature review, interviews with persons with MS, and discussions with MS providers, 25 MS symptom domains and 14 general health domains of MS care were identified. A multidisciplinary panel of 15 stakeholders of MS care, including 4 persons with MS, rated these 39 domains in a two-round modified Delphi process. The research team performed an expanded literature review for 26 highly ranked domains to draft 86 MS care indicators. Through another two-round modified Delphi process, a second panel of 18 stakeholders rated these indicators using a nine-point response scale. Indicators with a median rating in the highest tertile were considered valid. Among the most highly rated MS care domains were appropriateness and timeliness of the diagnostic work-up, bladder dysfunction, cognition dysfunction, depression, disease-modifying agent usage, fatigue, integration of care, and spasticity. Of the 86 preliminary indicators, 76 were rated highly enough to meet predetermined thresholds for validity. Following a widely accepted methodology, we developed a comprehensive set of quality indicators for MS care that can be used to assess quality of care and guide the design of interventions to improve care among persons with MS

Understanding Communication Signals during Mycobacterial Latency through Predicted Genome-Wide Protein Interactions and Boolean Modeling

About 90% of the people infected with Mycobacterium tuberculosis carry latent bacteria that are believed to get activated upon immune suppression. One of the fundamental challenges in the control of tuberculosis is therefore to understand molecular mechanisms involved in the onset of latency and/or reactivation. We have attempted to address this problem at the systems level by a combination of predicted functional protein∶protein interactions, integration of functional interactions with large scale gene expression studies, predicted transcription regulatory network and finally simulations with a Boolean model of the network. Initially a prediction for genome-wide protein functional linkages was obtained based on genome-context methods using a Support Vector Machine. This set of protein functional linkages along with gene expression data of the available models of latency was employed to identify proteins involved in mediating switch signals during dormancy. We show that genes that are up and down regulated during dormancy are not only coordinately regulated under dormancy-like conditions but also under a variety of other experimental conditions. Their synchronized regulation indicates that they form a tightly regulated gene cluster and might form a latency-regulon. Conservation of these genes across bacterial species suggests a unique evolutionary history that might be associated with M. tuberculosis dormancy. Finally, simulations with a Boolean model based on the regulatory network with logical relationships derived from gene expression data reveals a bistable switch suggesting alternating latent and actively growing states. Our analysis based on the interaction network therefore reveals a potential model of M. tuberculosis latency