MUSIC CUED EXERCISES FOR MOTOR AND NON-MOTOR SIGNS IN PEOPLE WITH DEMENTIA: PROTOCOL FOR A SYSTEMATIC REVIEW

Background: Movement disorders and non-motor problems such as cognitive decline, anxiety, depression and behavioural problems, are common in people with dementia and can progress over time. Exercise coupled with music is a promising form of therapy designed to improve both the motor and non-motor manifestations of this debilitating neurological condition. Objectives: To present a protocol for a systematic review and critical analysis of the literature to answer the following questions: (i) Is music-cued exercise more effective than usual care for the treatment of motor and non-motor symptoms of dementia? (ii) What are the outcomes of music-cued exercise for people living with dementia? Methods: We provide the protocol for a systematic review and critical analysis of the literature using the PRISMA guidelines. Studies shall be reviewed that use music cued exercises aimed at improving the management of physical and non-physical problems associated with dementia. Eligibility criteria will be applied to the title and abstract of each citation as a first step followed by full text screening. Data extraction and quality appraisal are to be performed by two reviewers. Data sources: This protocol documents the comprehensive search strategy to be performed using MEDLINE, CINAHL, EMBASE, PSYCHINFO, PUBMED, SCOPUS and web of science databases. Science, technology and engineering databases will also be searched. Eligibility criteria: All study designs incorporating data will be included in this review. The following selection criteria shall be applied: • Participants will be people diagnosed with dementia, including Alzheimer’s disease, of any stage and severity, all ages, any range of co-morbidities, any medications. • Interventions will use rhythmic music with any physical exercise or rehabilitation program. • Outcomes shall include motor impairments such as gait, postural stability and general mobility. Studies considering non-motor signs such as anxiety, depression, behavioural disturbances and cognitive decline will also be included. Results: Evidence will be built from this review regarding the effectiveness of using music-cued exercises to optimise physical abilities and improve non-motor disorders in people with dementia. Conclusions: This protocol paper documents the methods that we shall use for a forthcoming systematic review. The knowledge obtained from the review will provide guidance to people with dementia, caregivers and clinicians by clarifying the strength of the evidence for music-cued movement rehabilitation

MUSIC CUED EXERCISES FOR PEOPLE LIVING WITH DEMENTIA: A SYSTEMATIC REVIEW

Background: Dementia can be associated with motor and non-motor disorders such as cognitive impairment, depression, and behavioral disturbance. The symptoms typically progress gradually over time. Music-cued exercises have been of therapeutic interest in recent years, especially to enable people with chronic neurological diseases to move more easily and to experience greater well-being. Objective: To investigate whether music-cued exercises are more effective than usual care for the management of motor and non-motor symptoms in people living with dementia. Methods: Systematic searching of the international literature was conducted in January 2018. Keywords were searched through electronic databases including MEDLINE, CINAHL, Embase, PsycINFO, PubMed, Scopus, the Web of Science, Science Direct, Wiley online library, and JOVE. The Cochrane collaboration tool was used to assess the risk of bias of the randomized controlled trials (RCTs). The Downs and Black checklist assessed the quality of non-RCTs. Results: Twelve studies met the eligibility criteria, including 4 RCTs. Three investigated the effects of music-cued exercises on motor performance, four examined non-motor outcomes, four quantified the level of exercise participation, and one examined both motor and non-motor outcomes. The included studies were of modest to low quality. Conclusion: There is growing evidence for the beneficial effects of music-cued exercises for people living with dementia. Enjoyable music and physical exercises matched to rhythmical music appear to have benefits for some individuals.The dosage of music-cued exercise is a key determinant of the motor and non-motor outcomes in people living with a variety of forms of dementia

Microneedle/nanoencapsulation-mediated transdermal delivery: Mechanistic insights

A systematic study was undertaken to gain more insight into the mechanism of transdermal delivery of nanoencapsulated model dyes across microneedle (MN)-treated skin, a complex process not yet explored. Rhodamine B (Rh B) and fluorescein isothiocyanate (FITC) as model hydrophilic and hydrophobic small/medium-size molecules, respectively, were encapsulated in poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) and delivered through full thickness porcine skin pretreated with MN array. Permeation through MN-treated skin was affected by physicochemical characteristics of NPs and the encapsulated dyes. Dye flux was enhanced by smaller particle size, hydrophilicity, and negative zeta potential of NPs. Regarding encapsulated dyes, solubility at physiological pH and potential interaction with skin proteins proved to outweigh molecular weight as determinants of skin permeation. Data were verified using confocal laser scanning microscopy imaging. Findings coupled with the literature data are supportive of a mechanism involving influx of NPs, particularly of smaller size, deep into MN-created channels, generating depot dye-rich reservoirs. Molecular diffusion of the released dye across viable skin layers proceeds at a rate determined by its molecular characteristics. Data obtained provide mechanistic information of importance to the development of formulation strategies for more effective intradermal and transdermal MN-mediated delivery of nanoencapsulated therapeutic agents

Effect of microneedle treatment on the skin permeation of a nanoencapsulated dye

OBJECTIVES: The aim of the study was to investigate the effect of microneedle (MN) treatment on the transdermal delivery of a model drug (rhodamine B, Rh B) encapsulated in polylactic-co-glycolic acid (PLGA) nanoparticles (NPs) focusing on the MN characteristics and application variables. METHODS: Gantrez® MNs were fabricated using laser-engineered silicone micro-mould templates. PLGA NPs were prepared using a modified emulsion–diffusion–evaporation method and characterized in vitro. Permeation of encapsulated Rh B through MN treated full thickness porcine skin was performed using Franz diffusion cells using appropriate controls. KEY FINDINGS: In vitro skin permeation of the nanoencapsulated Rh B (6.19 ± 0.77 μg/cm(2)/ h) was significantly higher (P<0.05) compared to the free solution (1.66 ± 0.53 μg/cm(2)/ h). Mechanistic insights were supportive of preferential and rapid deposition of NPs in the MN-created microconduits, resulting in accelerated dye permeation. Variables such as MN array configuration and application mode were shown to affect transdermal delivery of the nanoencapsulated dye. CONCLUSIONS: This dual MN/NPs mediated approach offers potential for both the dermal and transdermal delivery of therapeutic agents with poor passive diffusion

Laser-engineered dissolving microneedles for active transdermal delivery of nadroparin calcium

There is an urgent need to replace the injection currently used for low molecular weight heparin (LMWH) multi-dose therapy with a non-invasive delivery device. In this study, laser-engineered dissolving microneedle (DMN) arrays fabricated from aqueous blends of 15% w/w poly (methylvinylether co maleic anhydride) have been fabricated as a potential device for the active transdermal delivery of nadroparin calcium (NC) as a model LMWH. An array loading of 630 IU of NC was achieved without compromising the array mechanical strength or the drug bioactivity. Application of NC-DMNs to dermatomed human skin (DHS) using the single step “poke and release” approach allowed permeation of approximately 10.6 % of the total NC load over a 48 h-study period. The cumulative amount of NC that permeated DHS at 24 h and 48 h attained 12.28 ± 4.23 IU/cm(2) and 164.84 ± 8.47 IU/cm(2), respectively. Skin permeation of NC could be modulated by controlling the DMN array variables, such as MN length and array density as well as application force to meet various clinical requirements including adjustment for body mass and renal function. NC-loaded DMN offer potentials as a relatively low cost functional delivery system for the transdermal delivery of LMWH and other macromolecules

Flux of ionic dyes across microneedle-treated skin : effect of molecular characteristic

Drug fluxacrossmicroneedle (MN)-treatedskin is influenced by the characteristics of the MN array, formed microconduits and physicochemical properties of the drug molecules in addition to the overall diffusional resistance of microconduits and viable tissue. Relative implication of these factors has not been fully explored. In the present study, the in vitro permeation of a series of six structurally related ionic xanthene dyes with different molecular weights (MW) and chemical substituents, across polymer MN-pretreated porcine skin was investigated in relation of their molecular characteristics. Dyes equilibrium solubility, partition coefficient in both n-octanol or porcine skin/aqueous system, and dissociation constants were determined. Results indicated that for rhodamine dyes, skin permeation of the zwitterionic form which predominates at physiological pH, was significantly reduced by an increase in MW, the skin thickness and by the presence of the chemically reactive isothiocyanate substituent. These factors were generally shown to override the aqueous solubility, an important determinant of drug diffusion in an aqueous milieu. The data obtained provided more insight into the mechanism of drug permeation across MN-treatedskin, which is of importance to both the design of MN-based transdermal drug delivery systems and of relevance to skin permeation research