FAST-IT: Find A Simple Test - In TIA (transient ischaemic attack): a prospective cohort study to develop a multivariable prediction model for diagnosis of TIA through proteomic discovery and candidate lipid mass spectrometry, neuroimaging and machine learning-study protocol.

INTRODUCTION: Transient ischaemic attack (TIA) may be a warning sign of stroke and difficult to differentiate from minor stroke and TIA-mimics. Urgent evaluation and diagnosis is important as treating TIA early can prevent subsequent strokes. Recent improvements in mass spectrometer technology allow quantification of hundreds of plasma proteins and lipids, yielding large datasets that would benefit from different approaches including machine learning. Using plasma protein, lipid and radiological biomarkers, our study will develop predictive algorithms to distinguish TIA from minor stroke (positive control) and TIA-mimics (negative control). Analysis including machine learning employs more sophisticated modelling, allowing non-linear interactions, adapting to datasets and enabling development of multiple specialised test-panels for identification and differentiation. METHODS AND ANALYSIS: Patients attending the Emergency Department, Stroke Ward or TIA Clinic at the Royal Adelaide Hospital with TIA, minor stroke or TIA-like symptoms will be recruited consecutively by staff-alert for this prospective cohort study. Advanced neuroimaging will be performed for each participant, with images assessed independently by up to three expert neurologists. Venous blood samples will be collected within 48 hours of symptom onset. Plasma proteomic and lipid analysis will use advanced mass spectrometry (MS) techniques. Principal component analysis and hierarchical cluster analysis will be performed using MS software. Output files will be analysed for relative biomarker quantitative differences between the three groups. Differences will be assessed by linear regression, one-way analysis of variance, Kruskal-Wallis H-test, χ2 test or Fisher's exact test. Machine learning methods will also be applied including deep learning using neural networks. ETHICS AND DISSEMINATION: Patients will provide written informed consent to participate in this grant-funded study. The Central Adelaide Local Health Network Human Research Ethics Committee approved this study (HREC/18/CALHN/384; R20180618). Findings will be disseminated through peer-reviewed publication and conferences; data will be managed according to our Data Management Plan (DMP2020-00062).

Correction: Two-year efficacy of varenicline tartrate and counselling for inpatient smoking cessation (STOP study): A randomized controlled clinical trial.

[This corrects the article DOI: 10.1371/journal.pone.0231095.].

Clinical Translation of Cell Therapies in Stroke (CT2S) Checklist-a pragmatic tool to accelerate development of cell therapy products.

BACKGROUND: Cell therapies present an exciting potential but there is a long history of expensive translational failures in stroke research. Researchers engaged in cell therapy research would benefit from a practical framework that can help in planning research and development of investigational cell therapies into viable medical products. METHODS: We developed a checklist using a mixed methodology approach to evaluate the impact of study design, regulatory policy, ethical, and health economic considerations for efficient implementation of early phase cell therapy studies. RESULTS: The checklist comprises a series of questions arranged under four domains: the first concerns study design such as characterization of target study population, trial design, endpoints and operational fit of dosage, time, and route of administration to target populations. A second domain addresses the data package required for regulatory approval relevant to the intended use (allogeneic/autologous; homologous/non-homologous; nature of cell processing). The third domain comprises patient involvement to ensure relevant data is collected via targeted study design. The final domain requires the team to determine the critical data elements that could be built into study design to enable health economic data collection to be started at an early phase of the study. CONCLUSIONS: The CT2S checklist can help to determine areas of expertise gaps and enable research groups to appropriately allocate resources for capacity building. Use of this checklist will allow identification of key areas where trial planning needs to be optimized, as well as helping to identify resources that need to be secured. The CT2S checklist can also serve as a general cell therapy research decision aid to improve research output and accelerate new cell therapy development.

Delayed Treatment with Human Dental Pulp Stem Cells Accelerates Functional Recovery and Modifies Responses of Peri-Infarct Astrocytes Following Photothrombotic Stroke in Rats.

Dental pulp contains multipotent mesenchymal stem cells that improve outcomes when administered early after temporary middle cerebral artery occlusion in rats. To further assess the therapeutic potential of these cells, we tested whether functional recovery following stroke induced by photothrombosis could be modified by a delayed treatment that was initiated after the infarct attained maximal volume. Photothrombosis induces permanent focal ischemia resulting in tissue changes that better reflect key aspects of the many human strokes in which early restoration of blood flow does not occur. Human dental pulp stem cells (approximately 400 × 103 viable cells) or vehicle were injected into the infarct and adjacent brain tissue of Sprague-Dawley rats at 3 days after the induction of unilateral photothrombotic stroke in the sensorimotor cortex. Forepaw function was tested up to 28 days after stroke. Cellular changes in peri-infarct tissue at 28 days were assessed using immunohistochemistry. Rats treated with the stem cells showed faster recovery compared with vehicle-treated animals in a test of forelimb placing in response to vibrissae stimulation and in first attempt success in a skilled forelimb reaching test. Total success in the skilled reaching test and forepaw use during exploration in a Perspex cylinder were not significantly different between the 2 groups. At 28 days after stroke, rats treated with the stem cells showed decreased immunolabeling for glial fibrillary acidic protein in tissue up to 1 mm from the infarct, suggesting decreased reactive astrogliosis. Synaptophysin, a marker of synapses, and collagen IV, a marker of capillaries, were not significantly altered at this time by the stem-cell treatment. These results indicate that dental pulp stem cells can accelerate recovery without modifying initial infarct formation. Decreases in reactive astrogliosis in peri-infarct tissue could have contributed to the change by promoting adaptive responses in neighboring neurons.

Two-year efficacy of varenicline tartrate and counselling for inpatient smoking cessation (STOP study): A randomized controlled clinical trial.

INTRODUCTION: Varenicline tartrate is superior for smoking cessation to other tobacco cessation therapies by 52 weeks, in the outpatient setting. We aimed to evaluate the long-term (104 week) efficacy following a standard course of inpatient-initiated varenicline tartrate plus Quitline-counselling compared to Quitline-counselling alone. METHODS: Adult patients (n = 392, 20-75 years) admitted with a smoking-related illnesses to one of three hospitals, were randomised to receive either 12-weeks of varenicline tartrate (titrated from 0.5mg daily to 1mg twice-daily) plus Quitline-counselling, (n = 196) or Quitline-counselling alone, (n = 196), with continuous abstinence from smoking assessed at 104 weeks. RESULTS: A total of 1959 potential participants were screened for eligibility between August 2008 and December 2011. The proportion of participants who remained continuously abstinent (intention-to-treat) at 104 weeks were significantly greater in the varenicline tartrate plus counselling arm (29.2% n = 56) compared to counselling alone (18.8% n = 36; p = 0.02; odds ratio 1.78; 95%CI 1.10 to 2.86, p = 0.02). Twenty-two deaths occurred during the 104 week study (n = 10 for varenicline tartrate plus counselling and n = 12 for Quitline-counselling alone). All of these participants had known or developed underlying co-morbidities. CONCLUSIONS: This is the first study to examine the efficacy and safety of varenicline tartrate over 104 weeks within any setting. Varenicline tartrate plus Quitline-counselling was found to be an effective opportunistic treatment when initiated for inpatient smokers who had been admitted with tobacco-related disease.

Cognitive Reserve as an Emerging Concept in Stroke Recovery.

Stroke is a leading cause of death and disability. It is a complex and largely heterogeneous condition. Prognosis for variations in impairment and recovery following stroke continues to be challenging and inaccurate, highlighting the need to examine the influence of other currently unknown variables to better predict and understand interindividual differences in stroke impairment and recovery. The concept of "cognitive reserve," a feature of brain function said to moderate the relationship between brain pathology and clinical outcomes, might provide a partial explanation. This review discusses the potential significance of cognitive reserve in the context of stroke, with reference to reduced burden of disability poststroke, health promotion, intervention and secondary prevention of cognitive impairment, ease and challenges of translation into clinical practice, prognosis and prediction of recovery, and clinical decisions and trial stratification. Discussions from the review aim to encourage stroke clinicians and researchers to better consider the role of premorbid, lifestyle-related variables, such as cognitive reserve, in facilitating successful neurological outcomes and recovery following stroke.

Stroke survivor attitudes toward, and motivations for, considering experimental stem cell treatments.

Purpose: Interest in stem cell treatments is increasing among some patient groups, but it is unclear whether this holds true for stroke survivors. This study examined stroke survivor attitudes toward stem cell treatments and identified a number of variables that may increase the likelihood that patients will consider these treatments.Methods: Adult stroke survivors (N = 183) were recruited (stroke advocacy/support groups, outpatient register) for a cross-sectional study. Attitudes to stem cell treatments were surveyed, guided by the Theory of Planned Behavior. Demographic information was collected, and a number of self-report medical, cognitive and psychological measures completed.Results: Twenty-five percent (n = 46) of respondents indicated they were considering undergoing stem cell treatments, although most were unsure about the safety/effectiveness and accessibility/affordability. Stroke survivors with positive attitudes toward stem cell treatments, longer post-stroke intervals, poorer physical functioning, younger age, and greater perceived caregiver burden were more likely to be considered experimental treatments (odds ratios = 1.22, 1.08, 0.95, 0.96, 1.07; respectively).Conclusions: Stroke survivors may consider undergoing experimental stem cell treatments despite uncertainty regarding the risks/benefits. Clinicians should be mindful of the factors that may increase the likelihood of patients considering these treatments and intervene, where appropriate, to clarify any misconceptions regarding the medical/financial risks.IMPLICATION FOR REHABILITATIONStem cell treatments offer a new focus for reducing stroke-related disability, although their safety and effectiveness have yet to be established.Despite uncertainty regarding the medical risks and benefits associated with stem cell injections, stroke survivors may still consider undergoing treatment in private, unregulated clinics.A number of factors, including younger age, longer post-stroke interval, poorer physical functioning, and perceived caregiver burden may place stroke survivors at an increased risk of considering these treatments.Clinicians should endeavor to educate stroke survivors regarding the risks and benefits of these experimental treatments and clarify any misconceptions, in order to reduce the likelihood that they will consider these as-yet unproven treatments.

PERSPECTIVES: Stroke survivors' views on the design of an early-phase cell therapy trial for patients with chronic ischaemic stroke.

BACKGROUND: Stem cell research holds the potential for a paradigm shift in the management of diseases such as stroke. Patient and public involvement in research (PPIR) can bring a focus to issues of clinical relevance and accelerate translation to real-world clinical practice. OBJECTIVE: A qualitative thematic analysis of the perspectives of stroke survivors regarding the conduct and design aspects of a proposed phase I clinical cell therapy study in stroke. DESIGN: Twelve stroke survivors were purposively recruited in July 2016-August 2017 and participated in semi-structured, face-to-face interviews for input into the design of a proposed phase I clinical study of autologous dental pulp stem cells. Concurrent thematic analysis was conducted until data saturation was achieved. DISCUSSION AND CONCLUSIONS: Participants conveyed that the most relevant outcomes to them were regaining participation, decreased dependence on caregivers and improvement in cognition, memory, mood, pain and fatigue. The perception of risk vs. benefit was likely influenced by the time elapsed since stroke, with participants being more willing to accept a higher level of risk early in the post-stroke disease course. They believed that all stroke survivors should be given an opportunity to participate in research, irrespective of their cognitive capacity. A relatively small sample population of 12 stroke survivors was studied as thematic saturation was achieved. PERSPECTIVES study applied principles of PPIR to early-phase cell research. Incorporation of outcomes relevant to patients' need within the study design is critical to generate data that will enable personalized application of regenerative medicine in stroke.

Efficacy of botulinum toxin in modifying spasticity to improve walking and quality of life in post-stroke lower limb spasticity - a randomized double-blind placebo controlled study.

BACKGROUND: Post-stroke lower limb spasticity (PSLLS) has a prevalence of 28-37%. PSLLS can cause difficulty in walking and reduce quality of life (QOL). Post stroke spasticity impairs the ability to intervene to improve walking ability. Botulinum Toxin A (BT) is an effective intervention for focal spasticity, but its use is currently restricted in many countries by their reimbursement system stating that the evidence for improvement in walking and quality of life (QOL) is not robust for treatment in the lower limb. This randomized control trial (RCT) will investigate the effectiveness of BT in modifying spasticity, and improving functioning (mobility, walking, activities of daily living (ADL's) and QOL. METHODS/DESIGN: A double-blind placebo-controlled trial injection will assess the effect of BT compared with a placebo (normal saline) in a sample of n = 94 patients. Following treatment of spasticity measured by Modified Ashworth Scale (MAS), the primary outcome of gait velocity will be measured by i) Gait Rite (Electronic Walkway); ii) walking by 2 Min Walk Test; iii) balance by Berg Balance Scale; mobility by iv) Timed Up and Go (TUG); v) lower limb function by ABILICO; vi) patient related goal by Goal Attainment Scale (GAS); vii) QOL by SF 12 (Rand version); viii) activities of daily living by the Functional Autonomy Measurement System (SMAF). There will be an associated health economic analysis. DISCUSSION: The study methodology is based on our systematic review 2026 studies, which concluded the evidence for improving mobility following use of BT to reduce spasticity was not robust. The results of this study could establish the use of BT in improving gait and lower limb function in PSLLS. This study could provide the evidence needed for reimbursement schemes to consider and changes to its funding policy for BT in PSLLS. TRIAL REGISTRATION: The trial is registered with the Australia New Zealand Clinical Trails Registry (ANZCTR)- ANZCTRN12617001603303 . Registered 07/12/2017.

Using Dental Pulp Stem Cells for Stroke Therapy.

Stroke is a leading cause of permanent disability world-wide, but aside from rehabilitation, there is currently no clinically-proven pharmaceutical or biological agent to improve neurological disability. Cell-based therapies using stem cells, such as dental pulp stem cells, are a promising alternative for treatment of neurological diseases, including stroke. The ischaemic environment in stroke affects multiple cell populations, thus stem cells, which act through cellular and molecular mechanisms, are promising candidates. The most common stem cell population studied in the neurological setting has been mesenchymal stem cells due to their accessibility. However, it is believed that neural stem cells, the resident stem cell of the adult brain, would be most appropriate for brain repair. Using reprogramming strategies, alternative sources of neural stem and progenitor cells have been explored. We postulate that a cell of closer origin to the neural lineage would be a promising candidate for reprogramming and modification towards a neural stem or progenitor cell. One such candidate population is dental pulp stem cells, which reside in the root canal of teeth. This review will focus on the neural potential of dental pulp stem cells and their investigations in the stroke setting to date, and include an overview on the use of different sources of neural stem cells in preclinical studies and clinical trials of stroke.

Economic Evaluation of Stem Cell Therapies in Neurological Diseases: A Systematic Review.

OBJECTIVES: To examine economic evaluation studies of stem cell therapies (SCTs) in neurological disorders and to provide an overview of the quality of the economic evidence available on this topic. METHODS: The review examined studies that performed an economic evaluation of the use of stem cells in adult patients with neurological diseases and that were published in English during the period 2007 to 2017. Data analyzed and reported included study population, disease indication, main analytical approaches for the economic analysis and perspective, key assumptions made or tested in sensitivity analyses, cost outcomes, estimates of incremental cost effectiveness, and approaches to quantifying decision uncertainty. RESULTS: A total of three studies reporting on the findings of the economic evaluation of the use of SCT in stroke, Parkinson disease, and secondary progressive multiple sclerosis, respectively, were identified. All three studies conducted a cost-utility analysis using decision-analytic models and reported an incremental cost per quality-adjusted life-years gained (incremental cost-effectiveness ratio) versus standard care. These studies reported meaningful cost savings in stroke, Parkinson disease, and secondary progressive multiple sclerosis in the base-case scenarios. CONCLUSIONS: Despite significant progress in clinical research in the use of SCT in neurological diseases, economic evaluation of these therapies is still at a nascent stage. Given the early stage of research inputs (clinical and cost outcomes data) into the models per se, further research is urgently needed to enable meaningful assessment of the cost effectiveness of these advanced therapies and to ensure sustainable access for population groups most likely to benefit in clinical practice.

Dental Pulp Stem Cells - Exploration in a Novel Animal Model: the Tasmanian Devil (Sarcophilus harrisii).

Dental pulp stem cells (DPSC) are a heterogeneous population of highly proliferative stem cells located in the soft inner pulp tissue of the tooth. Demonstrated to have an affinity for neural differentiation, DPSC have been reported to generate functional Schwann cells (SC) through in vitro differentiation. Both DPSC and SC have neural crest origins, recently a significant population of DPSC have been reported to derive from peripheral nerve-associated glia. The predisposition DPSC have towards the SC lineage is not only a very useful tool for neural regenerative therapies in the medical field, it also holds great promise in the veterinary field. Devil Facial Tumour (DFT) is a clonally transmissible cancer of SC origin responsible for devastating wild populations of the Tasmanian devil. Very few studies have investigated the healthy Tasmanian devil SC (tdSC) for comparative studies between tdSC and DFT cells, and the development and isolation of a tdSC population is yet to be undertaken. A Tasmanian devil DPSC model offers a promising new outlook for DFT research, and the link between SC and DPSC may provide a potential explanation as to how a cancerous SC initially arose in a single Tasmanian devil to then go on to infect others as a parasitic clonal cell line. In this review we explore the current role of DPSC in human regenerative medicine, provide an overview of the Tasmanian devil and the devastating effect of DFT, and highlight the promising potential DPSC techniques pose for DFT research and our current understanding of DFT.

Safety and effectiveness of stem cell therapies in early-phase clinical trials in stroke: a systematic review and meta-analysis.

Stem cells have demonstrated encouraging potential as reparative therapy for patients suffering from post-stroke disability. Reperfusion interventions in the acute phase of stroke have shown significant benefit but are limited by a narrow window of opportunity in which they are beneficial. Thereafter, rehabilitation is the only intervention available. The current review summarises the current evidence for use of stem cell therapies in stroke from early-phase clinical trials. The safety and feasibility of administering different types of stem cell therapies in stroke seem to be reasonably proven. However, the effectiveness needs still to be established through bigger clinical trials with more pragmatic clinical trial designs that address the challenges raised by the heterogeneous nature of stroke per se, as well those due to unique characteristics of stem cells as therapeutic agents.

miR-744 and miR-224 Downregulate Npas4 and Affect Lineage Differentiation Potential and Neurite Development During Neural Differentiation of Mouse Embryonic Stem Cells.

Neuronal PAS domain protein 4 (Npas4) is a brain-specific transcription factor whose expression is enriched in neurogenic regions of the brain. In addition, it was demonstrated that Npas4 expression is dynamic and highly regulated during neural differentiation of embryonic stem cells (ESCs). While these findings implicate a role for Npas4 in neurogenesis, the underlying mechanisms of regulation remain unknown. Given that growing evidence suggests that microRNAs (miRNAs) play important roles in both embryonic and adult neurogenesis, we reasoned that miRNAs are good candidates for regulating Npas4 expression during neural differentiation of ESCs. In this study, we utilized the small RNA sequencing method to profile miRNA expression during neural differentiation of mouse ESCs. Two differentially expressed miRNAs were identified to be able to significantly reduce reporter gene activity by targeting the Npas4 3'UTR, namely miR-744 and miR-224. More importantly, ectopic expression of these miRNAs during neural differentiation resulted in downregulation of endogenous Npas4 expression. Subsequent functional analysis revealed that overexpression of either miR-744 or miR-224 delayed early neural differentiation, reduced GABAergic neuron production and inhibited neurite outgrowth. Collectively, our findings indicate that Npas4 not only functions at the early stages of neural differentiation but may also, in part, contribute to neuronal subtype specification and neurite development.

The impact of tau hyperphosphorylation at Ser262 on memory and learning after global brain ischaemia in a rat model of reversible cardiac arrest.

An increase in phosphorylated tau (p-tau) is associated with Alzheimer's disease (AD), and brain hypoxia. Investigation of the association of residue-specific tau hyperphosphorylation and changes in cognition, leads to greater understanding of its potential role in the pathology of memory impairment. The aims of this study are to investigate the involvement of the main metabolic kinases, Liver Kinase B1 (LKB1) and Adenosine Monophosphate Kinase Protein Kinase (AMPK), in tau phosphorylation-derived memory impairment, and to study the potential contribution of the other tau kinases and phosphatases including Glycogen Synthase Kinase (GSK-3ß), Protein kinase A (PKA) and Protein Phosphatase 2A (PP2A). Spatial memory and learning were tested in a rat global brain ischemic model of reversible cardiac arrest (CA). The phosphorylation levels of LKB1, AMPK, GSK-3ß, PP2A, PKA and tau-specific phosphorylation were assessed in rats, subjected to ischaemia/reperfusion and in clinically diagnosed AD and normal human brains. LKB1 and AMPK phosphorylation increased 4 weeks after CA as did AMPK related p-tau (Ser262). The animals showed unchanged levels of GSK-3ß specific p-tau (Ser202/Thr205), phospho-PP2A (Tyr307), total GSK-3ß, PP2A, phospho-cAMP response element-binding protein (CREB) which is an indicator of PKA activity, and no memory deficits. AD brains had hyperphosphorylated tau in all the residues of Ser262, Ser202 and Thr205, with increased phosphorylation of both AMPK (Thr172) and GSK-3ß (Ser9), and reduced PP2A levels. Our data suggests a crucial role for a combined activation of tau kinases and phosphatases in adversely affecting memory and that hyperphosphorylation of tau in more than one specific site may be required to create memory deficits.

Stem cell therapy clinical research: A regulatory conundrum for academia.

The encouraging pace of discovery and development in the field of regenerative medicine holds tremendous potential for bringing therapies to the clinic that may offer meaningful benefit to patients, particularly in diseases with no or suboptimal therapeutic options. Academic researchers will continue to play a critical role in developing concepts and therapies, thus determining whether regenerative medicine will be able to live up to this potential that clearly excites clinicians, researchers and patients alike. This review summarises recent developments in regulatory frameworks across different countries that aim to ensure adequate oversight of the development of regenerative medicine products, which are unique in structural and functional complexity when compared to traditional chemical drugs and fully characterised biological drugs. It discusses the implications of these developments for researchers aiming to make the challenging transition from laboratory to clinical development of these therapies and considers possible pragmatic solutions that could accelerate this process that is essential to maintain research credibility and ensure patient safety.

Effectiveness of allied health therapy in the symptomatic management of progressive supranuclear palsy: a systematic review.

BACKGROUND: Progressive supranuclear palsy (PSP) is an adult onset neurodegenerative condition associated with mobility, balance, speech, swallowing, vision and cognitive changes. The condition is diagnosed using the National Institute for Neurological Disorders and Stroke (NINDS) and the Society of Progressive Supranuclear Palsy (SPSP) criteria. Therapeutic interventions for PSP are important, and a healthcare team should include a physiotherapist, occupational therapist and speech therapist. Mobility, speech and swallowing problems are commonly experienced, and aspiration pneumonia is the leading cause of death. A preliminary search of the literature has indicated that beyond small case series, there is very little evidence to guide specific allied health therapies in PSP. Many strategies for optimizing independence and function for PSP predominately rely on data extrapolated from the study of Parkinson's disease. OBJECTIVES: The objective of this review was to examine the effectiveness of physical, occupational and speech therapy interventions in the symptomatic management of PSP. INCLUSION CRITERIA TYPES OF PARTICIPANTS: This review included participants with PSP as per the NINDS and the SPSP criteria, aged over 40 years of age from all community and clinical settings. TYPES OF INTERVENTIONS: This review included studies evaluating any allied health therapy that addressed mobility, vision, swallowing, communication or cognitive/neuropsychiatric difficulties experienced by patients with PSP. Studies examining interventions within the current scope of practice, and emerging interventions (non-invasive brain stimulation therapy) were eligible for inclusion. TYPES OF COMPARATOR: The effectiveness of interventions of interest was compared with usual care and/or baseline measurements. OUTCOMES: Outcomes of interest included the degree of change, or no change, in the symptoms experienced by patients with PSP relevant to allied health. These included difficulties with mobility, vision, swallowing, communication and cognition. TYPES OF STUDIES: All types of quantitative study designs published in English from the time of development of the NINDS and the SPSP criteria in 1996-2014 were considered for inclusion. SEARCH STRATEGY: A broad range of synonyms for PSP and a three-step search strategy was utilized to identify possible published and unpublished studies from 11 different databases. An initial limited search via MEDLINE (PubMed), CINAHL, Health Informit, PsycINFO, PEDRO, OTSeeker and SpeechBite was undertaken followed by analysis of the text words contained in the title and abstract, and of the index terms used to describe the article. A second search using all identified keywords and index terms was then undertaken across all included databases. Third, hand-searching was conducted and the reference list of all identified reports and articles was searched for additional studies. METHODOLOGICAL QUALITY: Critical appraisal was conducted by two independent reviewers using standardized instruments. DATA EXTRACTION: Quantitative data were extracted from articles included in the review using standardized data extraction tools. DATA SYNTHESIS: As the quantitative articles examined different interventions, pooling of data was not appropriate. Instead, the findings were presented in narrative summary and tabular form. RESULTS: Following methodological appraisal, six studies were included in the review. Aside from one small quasi-randomized control study, most studies were small case series and one was a case report. Five of the six studies examined the effectiveness of a range of different physiotherapy rehabilitation programs targeting gait, balance and physical capability, with one study also targeting gaze control. The sixth study examined non-invasive brain stimulation in improving gait and midline symptoms in PSP. No studies examined the effectiveness of occupational therapy or speech therapy interventions in PSP. CONCLUSIONS: Research into the effectiveness of allied health therapeutic interventions for PSP symptoms is in its infancy. This review found preliminary evidence to support the use of various physiotherapy rehabilitation programs to improve balance, gait and gaze control in people affected by PSP. Further research is urgently required to identify effective interventions to manage mobility, vision, swallowing, communication and cognitive/neuropsychiatric symptoms associated with this devastating condition.

Characterization of p75 neurotrophin receptor expression in human dental pulp stem cells.

Human adult dental pulp stem cells (DPSC) are a heterogeneous stem cell population, which are able to differentiate down neural, chondrocyte, osteocyte and adipocyte lineages. We studied the expression pattern of p75 neurotrophin receptors (p75NTR), a marker of neural stem cells, within human DPSC populations from eight donors. p75NTR are expressed at low levels (<10%) in DPSC. Importantly, p75(+) DPSC represent higher expression levels of SOX1 (neural precursor cell marker), SOX2 (cell pluripotency marker) and nestin (neural stem cell marker) in comparison to p75(-) DPSC. Our results suggest that p75(+) hDPSC may denote a subpopulation with greater neurogenic potential.