The Throw-and-Catch Model of Human Gait: Evidence from Coupling of Pre-Step Postural Activity and Step Location

Postural activity normally precedes the lift of a foot from the ground when taking a step, but its function is unclear. The throw-and-catch hypothesis of human gait proposes that the pre-step activity is organized to generate momentum for the body to fall ballistically along a specific trajectory during the step. The trajectory is appropriate for the stepping foot to land at its intended location while at the same time being optimally placed to catch the body and regain balance. The hypothesis therefore predicts a strong coupling between the pre-step activity and step location. Here we examine this coupling when stepping to visually-presented targets at different locations. Ten healthy, young subjects were instructed to step as accurately as possible onto targets placed in five locations that required either different step directions or different step lengths. In 75% of trials, the target location remained constant throughout the step. In the remaining 25% of trials, the intended step location was changed by making the target jump to a new location 96 ms ± 43 ms after initiation of the pre-step activity, long before foot lift. As predicted by the throw-and-catch hypothesis, when the target location remained constant, the pre-step activity led to body momentum at foot lift that was coupled to the intended step location. When the target location jumped, the pre-step activity was adjusted (median latency 223 ms) and prolonged (on average by 69 ms), which altered the body’s momentum at foot lift according to where the target had moved. We conclude that whenever possible the coupling between the pre-step activity and the step location is maintained. This provides further support for the throw-and-catch hypothesis of human gait

Vertebrate fauna associates of the Wedge-tailed Shearwater, Puffinus pacificus, colonies of Rottnest Island: influence of an ecosystem engineer

Wedge-tailed Shearwaters, Puffinus pacificus, engineer the ecosystem by digging burrows in which they nest. This has been previously shown to affect the soil and vegetation properties of their colonies. Here we report on field surveys employed to investigate how associated vertebrate fauna respond to physical habitat modification by shearwaters. The study area was species poor, with only one mammal, and three reptile species detected in 1440 Elliott trap and 720 pitfall trap nights across a 13-month period. Nineteen bird species were recorded from 98 survey days. Relative to an area of uncolonised heath, we observed an increase in the abundance of King's Skinks, Egernia kingii, and a decrease in the abundance of House Mice, Mus musculus, and West Coast Ctenotus, Ctenotus fallens, in the shearwater colony. The survival rates of King's Skinks and House Mice were not affected by Wedge-tailed Shearwater presence. Bird species richness was less in the colony (9.2 ±0.5 species month-I) than the heath (11.5 ±0.2 species month-I), and the composition of the two communities was different. We suggest that ecosystem engineering by Wedge-tailed Shearwaters is a major determinant of fauna associates of their colonies and offer direct and indirect mechanisms to explain the patterns of species occurrence observed

Case Report: Acute Onset Fear of Falling and Treatment With "Cognitive Physical Therapy"

Fear of falling (FoF) is prevalent in older adults, especially those with previous falls, and typically starts insidiously. We present a 78-year-old woman with an abrupt onset FoF and no history of falls, balance problems, vertigo, oscillopsia, psychiatric or psychological issues to account for this. These cognitive changes led to a behavioural alteration of her gait that became slow and wide-based, with her gaze fixed on the floor. She began a tailored program of “Cognitive Physical Therapy (CPT)” combining cognitive behavioural therapy (CBT) and physical rehabilitation. 1 month later her 6 m walk time and steps were reduced by a 25 and 35%, respectively, and the stride length increased by 34%, with further improvement 2 months later. We postulate that the abrupt onset of symptoms triggered a central shift toward postural hypervigilance and anxiety, suppression of anticipatory (feed forward) postural adjustments (APA) leading to FoF. CPT improved objective gait parameters related to FoF and reduced postural anxiety suggesting that early diagnosis and prompt treatment may avoid chronic symptoms and social isolation

Altered visual and haptic verticality perception in posterior cortical atrophy and Alzheimer's disease

There is increasing theoretical and empirical support for the brain combining multisensory information to determine the direction of gravity and hence uprightness. A fundamental part of the process is the spatial transformation of sensory signals between reference frames: eye-centred, head-centred, body-centred, etc. The question ‘Am I the right way up?’ posed by a patient with posterior cortical atrophy (PCA) suggests disturbances in upright perception, subsequently investigated in PCA and typical Alzheimer's disease (tAD) based on what looks or feels upright. Participants repeatedly aligned to vertical a rod presented either visually (visual-vertical) or haptically (haptic-vertical). Visual-vertical involved orienting a projected rod presented without or with a visual orientation cue (circle, tilted square (±18°)). Haptic-vertical involved orientating a grasped rod with eyes closed using a combination of side (left, right) and hand (unimanual, bimanual) configurations. Intraindividual uncertainty and bias defined verticality perception. Uncertainty was consistently greater in both patient groups than in control groups, and greater in PCA than tAD. Bias in the frontal plane was strongly directionally affected by visual cue tilt (visual-vertical) and grip side (haptic-vertical). A model was developed that assumed verticality information from multiple sources is combined in a statistically optimal way to produce observed uncertainties and biases. Model results suggest the mechanism that spatially transforms graviceptive information between body parts is disturbed in both patient groups. Despite visual dysfunction being typically considered the primary feature of PCA, disturbances were greater in PCA than tAD particularly for haptic-vertical, and are considered in light of posterior parietal vulnerability

Barriers and motivators to gaining access to smoking cessation services amongst deprived smokers – a qualitative study

BACKGROUND: Smoking is strongly associated with disadvantage and is an important contributor to inequalities in health. Smoking cessation services have been implemented in the UK targeting disadvantaged smokers, but there is little evidence available on how to design services to attract this priority group. METHODS: We conducted focus groups with 39 smokers aged 21–75 from the most socio-economically deprived areas of Nottingham UK who had made an unsuccessful attempt to quit within the last year without using smoking cessation services, to identify specific barriers or motivators to gaining access to these services. RESULTS: Barriers to use of existing services related to fear of being judged, fear of failure, a perceived lack of knowledge about existing services, a perception that available interventions – particularly Nicotine Replacement Therapy – are expensive and ineffective, and negative media publicity about bupropion. Participants expressed a preference for a personalised, non-judgemental approach combining counselling with affordable, accessible and effective pharmacological therapies; convenient and flexible timing of service delivery, and the possibility of subsidised complementary therapies. CONCLUSION: We conclude that smokers from these deprived areas generally had low awareness of the services available to help them, and misconceptions about their availability and effectiveness. A more personalised approach to promoting services that are non-judgemental, and with free pharmacotherapy and flexible support may encourage more deprived smokers to quit smoking

The Retinoic Acid Receptor Agonist Am80 Increases Mucosal Inflammation in an IL-6 Dependent Manner During Trichuris muris Infection

PURPOSE: Vitamin A metabolites, such as all-trans-retinoic acid (RA) that act through the nuclear receptor; retinoic acid receptor (RAR), have been shown to polarise T cells towards Th2, and to be important in resistance to helminth infections. Co-incidentally, people harbouring intestinal parasites are often supplemented with vitamin A, as both vitamin A deficiency and parasite infections often occur in the same regions of the globe. However, the impact of vitamin A supplementation on gut inflammation caused by intestinal parasites is not yet completely understood. METHODS: Here, we use Trichuris muris, a helminth parasite that buries into the large intestine of mice causing mucosal inflammation, as a model of both human Trichuriasis and IBD, treat with an RARα/β agonist (Am80) and quantify the ensuing pathological changes in the gut. RESULTS: Critically, we show, for the first time, that rather than playing an anti-inflammatory role, Am80 actually exacerbates helminth-driven inflammation, demonstrated by an increased colonic crypt length and a significant CD4(+) T cell infiltrate. Further, we established that the Am80-driven crypt hyperplasia and CD4(+) T cell infiltrate were dependent on IL-6, as both were absent in Am80-treated IL-6 knock-out mice. CONCLUSIONS: This study presents novel data showing a pro-inflammatory role of RAR ligands in T. muris infection, and implies an undesirable effect for the administration of vitamin A during chronic helminth infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10875-013-9936-8) contains supplementary material, which is available to authorized users

CD28/B7-Mediated Co-stimulation Is Critical for Early Control of Murine Cytomegalovirus Infection

Abstract Control of acute murine cytomegalovirus (MCMV) infection is dependent upon both innate and adaptive immune responses, relying primarily upon natural killer (NK) and T-cell responses for control. Although CD28/B7 plays a clear role in T-cell responses in many antigen systems including some viral infections, the importance of co-stimulation during MCMV infection is unconfirmed. In addition, recent data suggest that CD28/B7 co-stimulation might also be important to Ly49H+ NK-cell expansion. We therefore hypothesized that CD28/B7 co-stimulation is critical to viral control after MCMV infection, and further that CD28/B7 co-stimulation plays a role in MCMV-specific T- and NK-cell responses. To test these hypotheses, we utilized C57BL/6 mice lacking the co-stimulatory molecules B7-1 and B7-2 or CD28. After primary infection with MCMV, viral titers are significantly elevated in mice lacking CD28 or B7 compared with wild-type mice. Impaired viral control is associated with significant defects in peripheral T-cell responses to MCMV, which appear to be dependent upon CD28/B7 co-stimulation. Abnormal hepatic T-cell responses in CD28/ mice are preceded by impaired MCMV-specific Ly49H+ NK-cell responses. Cytokine evaluations confirm that CD28/B7 co-stimulation is not required for non-specific antiviral responses. We conclude that CD28-mediated co-stimulation is critical for early viral control during acute MCMV infection.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78134/1/vim.2008.0080.pd

Interleukin-17D and Nrf2 mediate initial innate immune cell recruitment and restrict MCMV infection.

Innate immune cells quickly infiltrate the site of pathogen entry and not only stave off infection but also initiate antigen presentation and promote adaptive immunity. The recruitment of innate leukocytes has been well studied in the context of extracellular bacterial and fungal infection but less during viral infections. We have recently shown that the understudied cytokine Interleukin (IL)-17D can mediate neutrophil, natural killer (NK) cell and monocyte infiltration in sterile inflammation and cancer. Herein, we show that early immune cell accumulation at the peritoneal site of infection by mouse cytomegalovirus (MCMV) is mediated by IL-17D. Mice deficient in IL-17D or the transcription factor Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), an inducer of IL-17D, featured an early decreased number of innate immune cells at the point of viral entry and were more susceptible to MCMV infection. Interestingly, we were able to artificially induce innate leukocyte infiltration by applying the Nrf2 activator tert-butylhydroquinone (tBHQ), which rendered mice less susceptible to MCMV infection. Our results implicate the Nrf2/IL-17D axis as a sensor of viral infection and suggest therapeutic benefit in boosting this pathway to promote innate antiviral responses

Patent Human Infections with the Whipworm, Trichuris trichiura, Are Not Associated with Alterations in the Faecal Microbiota

Background: The soil-transmitted helminth (STH), Trichuris trichiura colonises the human large intestine where it may modify inflammatory responses, an effect possibly mediated through alterations in the intestinal microbiota. We hypothesised that patent T. trichiura infections would be associated with altered faecal microbiota and that anthelmintic treatment would induce a microbiota resembling more closely that observed in uninfected individuals. Materials and Methods: School children in Ecuador were screened for STH infections and allocated to 3 groups: uninfected, T. trichiura only, and mixed infections with T. trichiura and Ascaris lumbricoides. A sample of uninfected children and those with T. trichiura infections only were given anthelmintic treatment. Bacterial community profiles in faecal samples were studied by 454 pyrosequencing of 16 S rRNA genes. Results: Microbiota analyses of faeces were done for 97 children: 30 were uninfected, 17 were infected with T. trichiura, and 50 with T. trichiura and A. lumbricoides. Post-treatment samples were analyzed for 14 children initially infected with T. trichiura alone and for 21 uninfected children. Treatment resulted in 100% cure of STH infections. Comparisons of the microbiota at different taxonomic levels showed no statistically significant differences in composition between uninfected children and those with T. trichiura infections. We observed a decreased proportional abundance of a few bacterial genera from the Clostridia class of Firmicutes and a reduced bacterial diversity among children with mixed infections compared to the other two groups, indicating a possible specific effect of A. lumbricoides infection. Anthelmintic treatment of children with T. trichiura did not alter faecal microbiota composition. Discussion: Our data indicate that patent human infections with T. trichiura may have no effect on faecal microbiota but that A. lumbricoides colonisation might be associated with a disturbed microbiota. Our results also catalogue the microbiota of rural Ecuadorians and indicate differences with individuals from more urban industrialised societies

Molecular markers for tolerance of European ash (Fraxinus excelsior) to dieback disease identified using Associative Transcriptomics

Tree disease epidemics are a global problem, impacting food security, biodiversity and national economies. The potential for conservation and breeding in trees is hampered by complex genomes and long lifecycles, with most species lacking genomic resources. The European Ash tree Fraxinus excelsior is being devastated by the fungal pathogen Hymenoscyphus fraxineus, which causes ash dieback disease. Taking this system as an example and utilizing Associative Transcriptomics for the first time in a plant pathology study, we discovered gene sequence and gene expression variants across a genetic diversity panel scored for disease symptoms and identified markers strongly associated with canopy damage in infected trees. Using these markers we predicted phenotypes in a test panel of unrelated trees, successfully identifying individuals with a low level of susceptibility to the disease. Co-expression analysis suggested that pre-priming of defence responses may underlie reduced susceptibility to ash dieback