The role of the dominant versus the non-dominant hemisphere: an fMRI study of Aphasia recovery following stroke

Background: Speech production is one of the most frequently affected cognitive functions following stroke; however, the neural mechanisms underlying the recovery of speech function are still incompletely understood. Aims: The current study aims to address the differential contributions of the dominant and non-dominant hemispheres in recovery from aphasia following stroke by comparing data from four stroke patients and 12 control participants to assess the patterns of activation during speech production tasks during functional magnetic resonance imaging (fMRI) scanning. Methods & Procedures: Four chronic stroke patients (three left-hemisphere lesion and one right-hemisphere lesion) diagnosed with Broca’s aphasia at the acute phase, but now recovered to near normal speech ability, were tested on speech production tasks (phonemic fluency, categorical fluency and picture naming) whilst undergoing fMRI. These patients were compared with 12 healthy controls undergoing the same procedure. Outcomes & Results: Individual subject analysis showed activation peaks in perilesional areas in three out of four patients. This included one patient with right-hemisphere lesion, who also showed predominant perilesional activation. Group analysis of control participants showed predominately left-hemisphere activation, but not exclusively so. Laterality indexes were calculated and showed predominant left-hemisphere lateralisation in the control group (LI = 0.4). Three out of the four patients showed speech lateralised to the same hemisphere as their lesion and the fourth patient showed speech lateralised to the opposite hemisphere to their lesion. Different speech production tasks resulted in varying lateralisation indices (LIs) within participants. Conclusions: The data suggest that perilesional areas support recovery of speech in the chronic phase post-stroke regardless of the site of the lesion. The study has implications for the understanding of functional recovery as well as for the paradigms used in fMRI to localise speech production areas. Specifically, a variety of speech tasks are required to elicit activation that is representative of the range of cortical involvement in speech in healthy adults and that also allows for accurate reporting of the extent of recovery experienced in patients

Development of a Modified Cervical Collar to Eliminate Overheating and Dysphagia Side Effects

Currently, thousands of people each year require the use of a rigid cervical collar. The collars are used in situations of emergency, as well as in situations of precaution, when spinal injury is or may be present. There are many different styles and sizes of cervical collars available on the market today; however, common side effects are noticed when wearing the collars that may reduce the effectiveness to the patient. Often patients complain of general discomfort issues or may suffer from more serious side effects such as pressure sores, increased intracranial pressure, dysphagia, and abnormal distraction within the upper spine. A need exists for the modification of current cervical collars to reduce the painful or uncomfortable side effects associated with wearing them which would, in turn, increase the effectiveness of the therapy that the collar provides to the spine. There are two main components of most cervical collar designs: the rigid outer shell and the inner padding. Both of these components have been considered by our design team in the modification design to improve the efficacy of the cervical collar and to reduce side effects from wearing them. The main goals of this project were to reduce the overall discomfort patients experience that is associated with overheating and dysphagia side effects. As a team, we have researched and tested many materials to determine the best fit for our modified cervical collar. The tests included an end user survey that determined the overall comfortability between the available collars, a cold temperature retention test that showed how long the prospective cooling materials would maintain lower temperatures, and an in-collar temperature test that looked at the temperatures of the materials within the lining of a collar As a team, we have designed a rigid cervical collar that utilizes a slightly flexible, but durable 1/16th inch polyethylene outer shell with padded gel inserts. The outer shell is a two piece design that incorporates the favorable concepts of currently manufactured collars. The two pieces were cut using a scroll saw and molded using an application of heat to the desired positions. There are multiple cut outs in the plastic of both pieces that give flexibility when fitting the collar and the pieces can be connected using velcro straps. The inner “cooling system” is composed of two hydrogels: TheraPearl Technology freezable beads and a pressure activated cooling pad marketed by The Green Pet Shop. The cooling materials will then be wrapped together in polyolefin shrink wrap and placed within specified cutout positions in the antimicrobial padding. Finally the components will be covered in a heat resistant cloth material to ensure direct contact with the skin is compatible and comfortable for the patient. The modifications focus on reducing the hot spots on the cheeks, chin, and neck that are commonly associated with discomfort in patients, will address the discomfort of the chin and neck associated with dysphagia, and will also maintain the rigidity and restriction of motion necessary of the collar. Testing on the efficacy of the design concepts brought forth is still in progress, but we believe the modified cervical collar can increase patient comfort levels and reduce overheating

The relationship between lateralization patterns from sequence based motor tasks and hemispheric speech dominance

Objective: Skilled motor praxis and speech production display marked asymmetries at the individual and the population level, favouring the right hand and the left hemisphere respectively. Theories suggesting a common processing mechanism between praxis and speech are supported by evidence that shared neural architecture underlies both functions. Despite advances in understanding the neurobiology of this left-hemisphere specialisation the cortical networks linking these two functions are rarely investigated on a behavioural level. Method: This study deploys functional Transcranial Doppler (fTCD) ultrasound to directly measure hemispheric activation during skilled manual praxis tasks shown to be correlated to hemispheric speech lateralisation indices. In a new paradigm we test the hypothesis that praxis tasks are highly dependent on the left hemisphere's capacity for processing sequential information will be better correlated with direction and strength of hemispheric speech lateralisation Results: Across two experiments we firstly show that only certain praxis tasks (pegboard and coin-rotation) correlated with direct measurements of speech lateralisation despite shared properties across all tasks tested. Secondly, through novel imaging of hemispheric activation during praxis, results showed that the pegboard differed in the lateralisation pattern created and furthermore that it was significantly related to speech laterality indices, which was not the case for either of the other two tasks. Conclusion: These results are discussed in terms of a lateralised speech-praxis control mechanism and demonstrates that measurements of motor paradigms through the use of fTCD are reliable enough to provide a new insight to the behavioural relationship been speech and handedness

Testing the relationship between lateralization on sequence-based motor tasks and language laterality using an online battery

Studies have highlighted an association between motor laterality and speech production laterality. It is thought that common demands for sequential processing may underlie this association. However, most studies in this area have relied on relatively small samples and have infrequently explored the reliability of the tools used to assess lateralization. We, therefore, established the validity and reliability of an online battery measuring sequence-based motor laterality and language laterality before exploring the associations between laterality indices on language and motor tasks. The online battery was completed by 621 participants, 52 of whom returned to complete the battery a second time. The three motor tasks included in the battery showed good between-session reliability (r ≥ .78) and were lateralized in concordance with hand preference. The novel measure of speech production laterality was left lateralized at population level as predicted, but reliability was less satisfactory (r = .62). We found no evidence of an association between sequence-based motor laterality and language laterality. Those with a left-hand preference were more strongly lateralized on motor tasks requiring midline crossing; this effect was not observed in right-handers. We conclude that there is little evidence of the co-lateralization of language and sequence-based motor skill on this battery

A mixed methods investigation into GP attitudes and experiences of using social prescribing in their practice

AimSocial prescribing (SP) enables clinicians to signpost patients to non-medical services in the community in order to support their psycho-social needs. SP has been promoted as a positive service delivery model for primary and community care; however, there are few data on the views of doctors working in this area on the effectiveness of SP and its implementation.Subject and methodsThis study used a mixed methods approach to examine attitudes and experiences of general practitioners (GPs) on their use of SP. GPs completed an online survey (n  = 102), provided narrative written responses (n  = 55) and took part in semi-structured interviews on the topic (n = 8).ResultsPrincipal component analysis (PCA) showed that 90% of respondents use SP in their practice, with significant factor loadings on six separate components. Thematic analysis revealed three main themes, which were then combined with the PCA components to derive overarching themes that underpin effective implementation of SP: (1) perceptions of effectiveness and efficacy of SP, (2) training and awareness, and (3) structure and operational delivery.ConclusionThis study is one of the first to explore attitudes of doctors to SP. Whilst data shows that most respondents are supportive of SP in principle, the analysis also reveals that there are specific barriers that need to be overcome to enable effective implementation

Testing the relationship between lateralisation on sequence-based motor tasks and language laterality using an online battery

Studies have highlighted an association between motor laterality and speech production laterality. It is thought that common demands for sequential processing may underlie this association. However, most studies in this area have relied on relatively small samples and have infrequently explored the reliability of the tools used to assess lateralisation. We, therefore, established the validity and reliability of an online battery measuring sequence-based motor laterality and language laterality before exploring the associations between laterality indices on language and motor tasks. The online battery was completed by 621 participants, 52 of whom returned to complete the battery a second time. The three motor tasks included in the battery showed good between-session reliability (r ≥ .78) and were lateralised in concordance with hand preference. The novel measure of speech production laterality was left lateralised at population level as predicted, but reliability was less satisfactory (r = .62). We found no evidence of an association between sequence-based motor laterality and language laterality. Those with a left-hand preference were more strongly lateralised on motor tasks requiring midline crossing; this effect was not observed in right-handers. We conclude that there is little evidence of the co-lateralisation of language and sequence-based motor skill on this battery

Why test study protocol: a UK-wide audit using the primary care academic collaborative to explore the reasons for primary care testing

This is the author accepted manuscript. The final version is available on open access from the Royal College of General Practitioners via the DOI in this recordBackground The number of blood tests done in primary care has been increasing over the last 20 years. Some estimates suggest that up to a quarter of these tests may not have been needed. This could lead to a cascade effect of further investigations, appointments, or referrals, as well as anxiety for patients, increased workload and costs to the health service. To better understand the impact and sequelae of blood tests on patients, we need to know why blood tests are requested and what is done with the results. Aims To explore who orders blood tests and why, and how test results are actioned in primary care. Design & Setting Retrospective audit of electronic health records in general practices across the UK. Method The Primary care Academic CollaboraTive (PACT), a UK-wide network of primary care health professionals, will be utilised to collect data from individual practices. PACT members will be asked to review the electronic health records of 50 patients who had recent blood tests in their practice, and manually extract anonymised data on who requested the test, the indication, the result, and subsequent actions. Data will also be collected from PACT members to assess the feasibility of the collaborative model. Conclusion PACT offers a unique opportunity to extract clinical data which cannot otherwise be obtained. Understanding the indications for tests will help identify priority areas for research to optimise testing and patient safety in primary care.Bristol, North Somerset and South Gloucestershire Clinical Commissioning Grou

Vintage venoms: proteomic and pharmacological stability of snake venoms stored for up to eight decades

For over a century, venom samples from wild snakes have been collected and stored around the world. However, the quality of storage conditions for "vintage" venoms has rarely been assessed. The goal of this study was to determine whether such historical venom samples are still biochemically and pharmacologically viable for research purposes, or if new sample efforts are needed. In total, 52 samples spanning 5 genera and 13 species with regional variants of some species (e.g., 14 different populations of Notechis scutatus) were analysed by a combined proteomic and pharmacological approach to determine protein structural stability and bioactivity. When venoms were not exposed to air during storage, the proteomic results were virtually indistinguishable from that of fresh venom and bioactivity was equivalent or only slightly reduced. By contrast, a sample of Acanthophis antarcticus venom that was exposed to air (due to a loss of integrity of the rubber stopper) suffered significant degradation as evidenced by the proteomics profile. Interestingly, the neurotoxicity of this sample was nearly the same as fresh venom, indicating that degradation may have occurred in the free N- or C-terminus chains of the proteins, rather than at the tips of loops where the functional residues are located. These results suggest that these and other vintage venom collections may be of continuing value in toxin research. This is particularly important as many snake species worldwide are declining due to habitat destruction or modification. For some venoms (such as N. scutatus from Babel Island, Flinders Island, King Island and St. Francis Island) these were the first analyses ever conducted and these vintage samples may represent the only venom ever collected from these unique island forms of tiger snakes. Such vintage venoms may therefore represent the last remaining stocks of some local populations and thus are precious resources. These venoms also have significant historical value as the Oxyuranus venoms analysed include samples from the first coastal taipan (Oxyuranus scutellatus) collected for antivenom production (the snake that killed the collector Kevin Budden), as well as samples from the first Oxyuranus microlepidotus specimen collected after the species' rediscovery in 1976. These results demonstrate that with proper storage techniques, venom samples can retain structural and pharmacological stability. This article is part of a Special Issue entitled: Proteomics of non-model organisms. Biological significance: •These results show that with proper storage venoms are useful for decades.•These results have direct implications for the use of rare venoms

Solenodon genome reveals convergent evolution of venom in eulipotyphlan mammals

Venom systems are key adaptations that have evolved throughout the tree of life and typically facilitate predation or defense. Despite venoms being model systems for studying a variety of evolutionary and physiological processes, many taxonomic groups remain understudied, including venomous mammals. Within the order Eulipotyphla, multiple shrew species and solenodons have oral venom systems. Despite morphological variation of their delivery systems, it remains unclear whether venom represents the ancestral state in this group or is the result of multiple independent origins. We investigated the origin and evolution of venom in eulipotyphlans by characterizing the venom system of the endangered Hispaniolan solenodon (Solenodon paradoxus). We constructed a genome to underpin proteomic identifications of solenodon venom toxins, before undertaking evolutionary analyses of those constituents, and functional assessments of the secreted venom. Our findings show that solenodon venom consists of multiple paralogous kallikrein 1 (KLK1) serine proteases, which cause hypotensive effects in vivo, and seem likely to have evolved to facilitate vertebrate prey capture. Comparative analyses provide convincing evidence that the oral venom systems of solenodons and shrews have evolved convergently, with the 4 independent origins of venom in eulipotyphlans outnumbering all other venom origins in mammals. We find that KLK1s have been independently coopted into the venom of shrews and solenodons following their divergence during the late Cretaceous, suggesting that evolutionary constraints may be acting on these genes. Consequently, our findings represent a striking example of convergent molecular evolution and demonstrate that distinct structural backgrounds can yield equivalent functions