Role of virtual reality in examining the effect of fear of falling (FOF) on postural stability in individuals without and with Parkinson's disease in Egypt: a mixed-methods feasibility study protocol.

BACKGROUND: Falls are common in older people and individuals with neurological conditions. Parkinson's disease (PD) is known for postural instability causing mobility disabilities, falls and reduced quality of life. The fear of falling (FOF), a natural response to unstable balance, can worsen postural control problems. Evaluating FOF relies largely on affected persons' subjective accounts due to limited objective assessment methods available. The aim of this mixed-methods feasibility study is to develop an assessment method for FOF while in motion and walking within virtual environments. This study will assess a range of FOF-related responses, including cognitive factors, neuromuscular response and postural stability. METHODS AND ANALYSIS: This feasibility study will consist of four phases: the first two phases will include people without PD, while the other two will include people diagnosed with PD. Participants will be assessed for direct and indirect responses to real life, as well as virtual environment walking scenarios that may induce FOF. Data from questionnaires, different neurophysiological assessments, movement and gait parameters, alongside evaluations of usability and acceptability, will be collected. Semistructured interviews involving both participants and research assistants shall take place to elicit their experiences throughout different phases of the assessments undertaken. Demographic data, the scores of assessment scales, as well as feasibility, usability and acceptability of the measurement methods, will be illustrated via descriptive statistics. Movement and gait outcomes, together with neurophysiological data, will be extracted and calculated. Exploring relationships between different factors in the study will be achieved using a regression model. Thematic analysis will be the approach used to manage qualitative data. ETHICS AND DISSEMINATION: This feasibility study was approved by the Ethics Committee of the Faculty of Physical Therapy, Kafr El Sheikh University, Egypt (number: P.T/NEUR/3/2023/46). The results of this study will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT05931692).

Effect of High-intensity Laser Therapy on Carpal Tunnel Syndrome Patients: A Systematic Review and Meta-analysis.

OBJECTIVE: To provide a strong foundation for the use of high-intensity laser therapy (HILT) in carpel tunnel syndrome (CTS,) we conducted a systematic review and meta-analysis to investigate the outcomes of short- and long-term follow-up studies. DESIGN: Systematic review and meta-analysis. RESULTS: Sample sizes of included studies ranged from 16 to 98 patients (total N = 308). Overall, a significant difference between the treatment and control groups were found across majority of the measures. Studies using a four-week follow-up period, however, only found significantly greater benefits for HILT in visual analogue scale (VAS) compared to placebo (p = 0.0191), Transcutaneous electrical nerve stimulation (TENS) (p = 0.0026), and low-intensity laser therapy-20 J/cm2 (p < 0.0002), and exercise (p < 0.0001). For improvement in VAS score over a long treatment period, HILT was also preferred over control group (p < 0.0071). Insufficient evidence exists to determine effect of HILT on nerve conduction examinations. The only statistically significant differences observed in examinations were in relation to sensory nerve action potential (p = 0.0083) and sensory nerve conduction velocity (SNCV) (p = 0.0468). CONCLUSION: Moderate evidence exists regarding efficacy of HILT compared to placebo, HILT + wrist splint, and exercise in a short period of follow-up time but evidence on long-term follow-up is limited.

The Extent of Evidence Supporting the Effectiveness of Extended Reality Telerehabilitation on Different Qualitative and Quantitative Outcomes in Stroke Survivors: A Systematic Review.

Objective: To present the extent of evidence concerning the effectiveness of extended reality telerehabilitation and patients' experiences of using different types of virtual reality exercises at home. Methods: We included studies on virtual reality and augmented reality telerehabilitation published in English. Systematic searches were undertaken in PubMed, Web of Sciences, Medline, Embase, CINAHL, and PEDro, with no date limitations. We included only RCTs and qualitative studies exploring patients' experiences. Methodological quality was assessed using the Cochrane Risk of Bias assessment tool for quantitative papers and the CASP scale for qualitative studies. All results are presented narratively. Results: Thirteen studies, nine quantitative and four qualitative, were included, with one qualitative and seven quantitative having a high risk of bias. All studies reported that extended reality-based telerehabilitation may be effective compared to conventional exercises or other extended reality exercises. Seven quantitative studies focused on upper limb function. Qualitative papers suggested that VR exercises were perceived as feasible by patients. Conclusions: The literature suggests VR home exercises are feasible and potentially effective for patients after a stroke in the upper limb. Further high-quality studies are needed to examine the effectiveness of XR exercises early adoption on different qualitative and quantitative outcomes. Registration number: (CRD42022384356).

Role of drug delivery technologies in the success of COVID-19 vaccines: a perspective.

The triumphant success of mRNA vaccines is a testimony to the important role drug delivery technologies have played in protecting billions of people against SARS-CoV-2 (or the Corona Virus Disease 2019; COVID-19). Several lipid nanoparticle (LNP) mRNA vaccines were developed and have been instrumental in preventing the disease by boosting the immune system against the pathogen, SARS-CoV-2. These vaccines have been built on decades of scientific research in drug delivery of mRNA, vaccines, and other biologicals. In this manuscript, several leading and emerging scientists in the field of drug delivery share their perspective on the role of drug delivery technologies in developing safe and efficacious vaccines, in a roundtable discussion. The authors also discussed their viewpoint on the current challenges, and the key research questions that should drive this important area of research.

Development of a thermostable oxytocin microneedle patch.

Oxytocin is a nonapeptide hormone used in labor to initiate uterine contractions and to prevent and treat postpartum hemorrhage. Oxytocin is currently administered by injection and requires refrigerated transport and storage, which limits access, especially during home birth in developing countries. Here, we propose a thermostable, simple-to-administer microneedle (MN) patch for rapid delivery of oxytocin suitable for use by healthcare workers with limited training, like traditional birth attendants. Oxytocin (10 IU, 16.8 µg) coated onto stainless steel MN arrays was released into skin within 1-5 min after manual insertion. Among tested excipients, polyacrylic acid was best at stabilizing oxytocin stored at 75% relative humidity, with no significant loss for up to 2 months at 40 °C. Under desiccated conditions, MNs coated with formulations containing trehalose in a mixture of citrate buffer and ethanol retained 75% oxytocin potency at 40 °C for 12 months; the commercial oxytocin product Pitocin® was reduced to 35% potency under these conditions. These findings support development of MN patches for oxytocin administration with improved ease of use, extended thermostability and simplified logistics to enable greater access to this life-saving medicine.

Therapeutic Dancing for Frail Older People in Residential Aged Care: A Thematic Analysis of Barriers and Facilitators to Implementation.

BACKGROUND: Adults who live in residential aged care can have reduced participation in physical activities and sit for prolonged periods. Therapeutic dancing aims to optimize movement, creative expression, well-being, and social interaction. OBJECTIVES: To investigate the benefits, challenges, and facilitators to implementing therapeutic dancing in residential aged care. METHODS: Thematic analysis of semistructured interviews of residential aged care staff and therapists. Interviews were digitally audio-recorded and thematically analyzed. Findings: Four main themes were identified: (a) despite frailty, dancing classes afforded motor and nonmotor benefits, (b) music and dance genre selections were key to success, (c) the skills of the dance instructor were associated with successful outcomes, and (d) there were modifiable and nonmodifiable facilitators and barriers to implementation. CONCLUSION: Enablers included support from management, resident supervision, age-appropriate music with a strong rhythmical beat, and a dance instructor skilled in comprehensive care. Barriers included multimorbidity, frailty, severe cognitive impairment, and funding.

Development of a thermostable microneedle patch for polio vaccination.

The aim of this study was to develop a dissolving microneedle (MN) patch for administration of inactivated polio vaccine (IPV) with improved thermal stability when compared with conventional liquid IPV. Excipient screening showed that a combination of maltodextrin and D-sorbitol in histidine buffer best preserved IPV activity during MN patch fabrication and storage. As determined by D-antigen ELISA, all three IPV serotypes maintained > 70% activity after 2 months and > 50% activity after 1-year storage at 5 °C or 25 °C with desiccant. Storage at 40 °C yielded > 40% activity after 2 months and > 20% activity after 1 year. In contrast, commercial liquid IPV types 1 and 2 lost essentially all activity within 1 month at 40 °C and IPV type 3 had < 40% activity. Residual moisture content in MN patches measured by thermogravimetric analysis was 1.2-6.5%, depending on storage conditions. Glass transition temperature measured by differential scanning calorimetry, structural changes measured by X-ray diffraction, and molecular interactions measured by Fourier transform infrared spectroscopy showed changes in MN matrix properties, but they did not correlate with IPV activity changes during storage. We conclude that appropriately formulated MN patches can exhibit thermostability that could enable distribution of IPV with less reliance on cold chain storage.

Intradermal immunization by Ebola virus GP subunit vaccines using microneedle patches protects mice against lethal EBOV challenge.

Development of a safe and efficacious filovirus vaccine is of high importance to public health. In this study, we compared immune responses induced by Ebola virus (EBOV) glycoprotein (GP) subunit vaccines via intradermal immunization with microneedle (MN) patches and the conventional intramuscular (IM) injection in mice, which showed that MN delivery of GP induced higher levels and longer lasting antibody responses against GP than IM injection. Further, we found that EBOV GP in formulation with a saponin-based adjuvant, Matrix-M, can be efficiently loaded onto MN patches. Co-delivery of Matrix-M with GP significantly enhanced induction of antibody responses by MN delivery, as also observed for IM injection. Results from challenge studies showed that all mice that received the GP/adjuvant formulation by MN or IM immunizations were protected from lethal EBOV challenge. Further, 4 out of 5 mice vaccinated by MN delivery of unadjuvanted GP also survived the challenge, whereas only 1 out of 5 mice vaccinated by IM injection of unadjuvanted GP survived the challenge. These results demonstrate that MN patch delivery of EBOV GP subunit vaccines, which is expected to enable improved safety and thermal stability, can confer effective protection against EBOV infection that is superior to IM vaccination.

Intradermal Vaccination With Adjuvanted Ebola Virus Soluble Glycoprotein Subunit Vaccine by Microneedle Patches Protects Mice Against Lethal Ebola Virus Challenge.

In this study, we investigated immune responses induced by purified Ebola virus (EBOV) soluble glycoprotein (sGP) subunit vaccines via intradermal immunization with microneedle (MN) patches in comparison with intramuscular (IM) injection in mice. Our results showed that MN delivery of EBOV sGP was superior to IM injection in eliciting higher levels and longer lasting antibody responses against EBOV sGP and GP antigens. Moreover, sGP-specific immune responses induced by MN or IM immunizations were effectively augmented by formulating sGP with a saponin-based adjuvant, and they were shown to confer complete protection of mice against lethal mouse-adapted EBOV (MA-EBOV) challenge. In comparison, mice that received sGP without adjuvant by MN or IM immunizations succumbed to lethal MA-EBOV challenge. These results show that immunization with EBOV sGP subunit vaccines with adjuvant by MN patches, which have been shown to provide improved safety and thermal stability, is a promising approach to protect against EBOV infection.

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) pretreatment 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 characterised in vitro. Permeation of encapsulated Rh B through MN-treated full thickness porcine skin was performed using Franz diffusion cells with appropriate controls. KEY FINDINGS: In-vitro skin permeation of the nanoencapsulated Rh B (6.19 ± 0.77 µg/cm²/h) was significantly higher (P < 0.05) compared with the free solution (1.66 ± 0.53 µg/cm²/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/NP-mediated approach offers potential for both the dermal and transdermal delivery of therapeutic agents with poor passive diffusion characteristics.

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

Drug flux across microneedle (MN)-treated skin 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-treated skin, which is of importance to both the design of MN-based transdermal drug delivery systems and of relevance to skin permeation research.

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) multidose therapy with a non- or minimally invasive delivery approach. In this study, laser-engineered dissolving microneedle (DMN) arrays fabricated from aqueous blends of 15% w/w poly(methylvinylether-co-maleic anhydride) were used for the first time in active transdermal delivery of the LMWH nadroparin calcium (NC). Importantly, an array loading of 630IU of NC was achieved without compromising the array mechanical strength or 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 24h and 48h attained 12.28±4.23IU/cm(2) and 164.84±8.47IU/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 offers great potential as a relatively low-cost functional delivery system for enhanced transdermal delivery of LMWH and other macromolecules.

Effects of microneedle length, density, insertion time and multiple applications on human skin barrier function: assessments by transepidermal water loss.

Microneedle (MN) arrays have attracted considerable attention in recent years due to their ability to facilitate effective transdermal drug delivery. Despite appreciable research, there is still debate about how different MN dimensions or application modes influence permeabilization. This study aimed to investigate this issue by taking transepidermal water-loss measurements of dermatomed human skin samples following the insertion of solid polymeric MNs. Insertions caused an initial sharp drop in barrier function followed by a slower incomplete recovery - a paradigm consistent with MN-generation of microchannels that subsequently contract due to skin elasticity. While 600 µm-long MNs were more skin-perturbing than 400 µm MNs, insertion of 1000 µm-long MNs caused a smaller initial drop in integrity followed by a degree of long term permeabilization. This is explainable by the longest needles compacting the tissue, which then decompresses over subsequent hours. Multiple insertions had a similar effect as increasing MN length. There was some evidence that increasing MN density suppressed the partial barrier recovery caused by tissue contraction. Leaving MNs embedded in skin seemed to reduce the initial post-insertion drop in barrier function. Our results suggest that this in vitro TEWL approach can be used to rapidly screen MN-effects on skin.

Microbiological assessment of the ultraviolet screening effect of sunscreen preparations.

The purpose of this study was the development of a microbiological method for the assessment of the ultraviolet (UV) screening effect of sunscreen preparations and determination of their sun protection factor. The method is based on the lethal effect of UV radiation on Escherichia coli (E. coli ) and the protective ability of sunscreens. The time of UV exposure required for the reduction of the E. coli viable count by 90% (decimal reduction time, DRT) was used as the photoprotection assessment parameter. The method was tested by assessing the effect of selected experimental variables on the DRT. The suitability of the method as a quality control tool for sunscreen preparations was then checked by assessing the influence of selected formulation variables on the photoprotective effect of a series of o/w emulsion formulations with different compositions. The method proved valid for detecting changes in the photoprotective effect of a market sunscreen product as a result of modifying experimental conditions. It also proved valid for ranking market sunscreen products according to their UV screening effect. Equally important, the method could successfully detect changes in the photoprotective effect of sunscreen test formulations as a function of the concentration and type of the sunscreen agents.