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To investigate the sustainability of Robot-assisted upper limb therapy (RT-UL) as part of routine occupational therapy and physiotherapy clinical practice. Two separate audits, 12 months apart, of RT-UL computer data records were undertaken to determine sustainability in a subacute rehabilitation unit. Records of the two audits were compared in terms of the number of early subacute stroke survivors using RT-UL, the number of RT-UL sessions, duration of RT-UL sessions, and disciplines prescribing RT-UL. During Audit 1 58% (n = 18) of stroke survivors received RT-UL compared to 50% (n = 7) in Audit 2. The total number of RT-UL sessions reduced between audits (148 vs. 36 sessions) reflecting the overall reduction in admission rates for stroke survivors. There was no significant difference between audits in the average number of RT-UL sessions per patient (p = 0.203) nor the length of sessions (p = 0.762). Patients engaged in active therapy more than three-quarters of the time when on the robotic device. Physiotherapists were the primary prescribers of RT-UL when compared to occupational therapists. RT-UL was in continued and regular use with stroke survivors 2 years after initial implementation within an inpatient rehabilitation setting. RT-UL practice was intensive and used routinely with patients. RT-UL is a sustainable and intensive intervention for stroke survivors within an inpatient rehabilitative setting. The cost-benefits of RT-UL should be evaluated from the perspective of the whole rehabilitation service not just at an individual patient level. RT-UL may be considered a "bridging" form of UL practice for those with more limited active UL movement until there is sufficient UL movement and power for more complex real-world task-specific practice. [ABSTRACT FROM AUTHOR]

Robot assisted upper limb (UL) therapy has been identified as an intervention with the potential to help improve the amount of practice performed by stroke survivors. This study aimed to measure the amount of UL practice (i.e., repetitions, duration, intensity) performed by subacute stroke survivors, in particular those with severe UL impairment, pre and post implementation of robot assisted upper limb therapy (RT-UL) into an inpatient rehabilitation setting. Two observational study phases (pre-RT-UL and post-RT-UL) were undertaken of occupational therapy and physiotherapy sessions performed by subacute stroke survivors. Upper limb tasks observed and recorded in therapy were classified as either impairment-related therapy or activity-related. In the pre-RT-UL observational phase, 7 subacute stroke survivors were observed across 11 days involving 25 therapy sessions. Post-RT-UL, 12 subacute stroke survivors were observed across 12 days involving 29 therapy sessions. There were no significant differences in characteristics of patients observed in each phase (p >.05). The mean difference (95% CI) between pre and post RT-UL for repetitions (reps) (569 (1 to 1136) and intensity (7 (4–11)) reps/min of practice increased for all patients, including those with severe UL impairment (337 (37–638)) reps and 8 (2–14) reps/minute, with the duration of therapy unchanged. This is the first study to have observed an increase in UL practice with the inclusion of RT-UL as part of routine clinical practice. This increase in practice is considered to be due to RT-UL providing highly supportive and expeditious semi-supervised practice. Notably, RT-UL was able to be implemented within the existing organisational structures with only basic training of therapy staff. Robotics presents as a viable intervention to increase the amount and intensity of upper limb practice performed by stroke survivors in routine clinical practice Robotics were able to be implemented within the existing organisational structures with only basic training of therapy staff [ABSTRACT FROM AUTHOR]

Erythrocytes have been extensively investigated as drug delivery vehicles. However, many existing methods for loading therapeutic biomolecules into erythrocytes perturb the cell membrane, resulting in a loss of erythrocyte structural integrity and recognition by the host immune system. To overcome this challenge, we developed a novel nanoparticle carrier for transporting proteins into intact erythrocytes. We designed and characterized a nanoparticle where a poly-L-lysine-grafted-poly(ethylene) glycol copolymer was used to encapsulate a model protein, bovine serum albumin. The nanoparticle was functionalized with either an erythrocyte targeting peptide ERY1, the cell-penetrating peptide low molecular weight protamine, or a combination of the two peptides. The three resulting constructs, ENP, LNP, and ELNP, had a core/shell structure and, depending on functionalization, were approximately 30–90 nm in diameter and had negative surface charge. Esterase-like activity of the encapsulated protein was not affected by encapsulation. Under physiological conditions, nanoparticles caused no significant hemolysis and were resistant to dissociation by surfactants. The three nanoparticle constructs were evaluated using confocal microscopy and flow cytometry for their ability to bind and internalize within intact erythrocytes. LNPs showed significant binding and internalization into intact erythrocytes, with ~90% of erythrocytes containing particles after 24 h of co-incubation. Internalization occurred without adversely affecting erythrocyte membrane structure. Together, these results demonstrate that low molecular weight protamine–functionalized nanoparticles may serve as a universal platform to deliver protein therapeutics into erythrocytes. [ABSTRACT FROM AUTHOR]

Advancement of therapeutic protein therapies can be hindered by their poor stability and short in vivo half‐life. There is emerging evidence that biocompatible zwitterionic materials can prevent nonspecific interactions within proteins systems that contribute to protein instability. Here, zwitterionic hydrogel beads are synthesized from poly(sulfobetaine methyl methacrylate), pSB, using an inverse emulsion, free radical polymerization reaction technique. The transport properties within the zwitterionic hydrogels were characterized using 1H NMR diffusometry. Equilibrium water content as high as 0.90 was measured for the synthesized hydrogels. Our study revealed that the pSB hydrogels are nontoxic, ion responsive, and their swelling is temperature dependent. The zwitterionic hydrogel beads were capable of undergoing lyophilization without aggregation. Hydrogel beads were loaded with a model protein, bovine serum albumin (BSA), using a postfabrication loading technique. The protein loading was studied using confocal laser microscopy, indicating homogenous protein dispersion of up to 40 μg BSA/mg hydrogel within the beads. Furthermore, the release rate of the protein from the synthesized hydrogel was studied at different crosslinker to monomer ratios. The protein encapsulated within the zwitterionic hydrogel had slower rates of thermal aggregation compared to nonencapsulated protein in solution. Furthermore, the protein‐loaded inside the zwitterionic hydrogel better maintained its bioactivity. [ABSTRACT FROM AUTHOR]

Therapeutic proteins are utilized in a variety of clinical applications, but side effects and rapid in vivo clearance still present hurdles. An approach that addresses both drawbacks is protein encapsulation within in a polymeric nanoparticle, which is effective but introduces the additional challenge of destabilizing the nanoparticle shell in clinically relevant locations. This study examined the effects of crosslinking self‐assembled poly(l‐lysine)‐grafted‐poly(ethylene glycol) nanoparticles with redox‐responsive 3,3′‐dithiobis(sulfosuccinimidyl propionate) (DTSSP) to achieve nanoparticle destabilization in a reductive environment. The polymer‐protein nanoparticles (DTSSP NPs) were formed through electrostatic self‐assembly and crosslinked with DTSSP, which contains a glutathione‐reducible disulfide. As glutathione is upregulated in various cancers, DTSSP NPs could display destabilization within cancer cells. A library of DTSSP NPs was formed with varying copolymer to protein (C:P) and crosslinker to protein (X:P) mass ratios and characterized by size and encapsulation efficiency. DTSSP NPs with a 7:1 C:P ratio and 2:1 X:P ratio were further characterized by stability in the presence proteases and reducing agents. DTSSP NPs fully encapsulated the model protein and displayed 81% protein release when incubated with 5 mM dithiothreitol for 12 hr. This study contributes to understanding stimulus‐responsive crosslinking of polymeric nanoparticles and could be foundational to clinical administration of therapeutic proteins. [ABSTRACT FROM AUTHOR]

Introduction: Robot‐assisted therapy for the upper limb (RT‐UL) is an emerging form of intervention for stroke survivors with upper limb deficits. However, there is limited knowledge regarding therapists' perceptions of RT‐UL and the factors influencing the implementation of RT‐UL into the clinical setting. This is important when considering that therapists in Australia are primarily responsible for the prescription of RT‐UL in daily practice. This study aimed to explore occupational therapists' and physiotherapists' perceptions of RT‐UL and the perceived barriers and enablers influencing implementation. Methods: Two discipline‐specific focus groups were conducted involving occupational therapists (n = 6) and physiotherapists (n = 6). Participants were members of the same multidisciplinary team working in an Australian public health rehabilitation facility where RT‐UL (i.e. InMotion2) was being introduced for the first time. Focus groups explored therapist perceptions of the new RT‐UL as well as perceived barriers and enablers to implementation. Focus groups were recorded, transcribed and deductively analysed using the Theoretical Domains Framework (TDF). Results: Out of the 14 domains of the TDF, 7 were raised by participants during the focus groups: environmental context and resources, beliefs about consequences, optimism, knowledge, skills, social influences, and social and professional role and identity. Therapists' expressed their optimism towards the introduction of RT‐UL but believed successful implementation would be primarily dependent on the availability of clinical leadership, training and a suitable client mix. Conclusion: Therapists perceived that RT‐UL would provide opportunity for increased upper limb practice particularly for patients with severe upper limb impairment. To facilitate implementation, support of RT‐UL should come from both management and clinical leaders and training include RT‐UL efficacy, device functionality and patient suitability. The availability of a single RT‐UL device in a workplace may create unique interdisciplinary and logistical challenges. [ABSTRACT FROM AUTHOR]

This article examines the perception of the (ing) variants, [ɪŋ] and [ɪn], in three regionally distinct localities in Britain: London in the South of England; Manchester in the North; and Edinburgh in Scotland. Data was gathered in perceptual tests in which respondents from each location rated stimuli doublets, each containing only one of the variants of (ing), on multiple social attribute scales. In London and Manchester, the perception of [ɪŋ] and [ɪn] broadly matches findings made for the United States in that speakers using [ɪŋ] are considered more articulate and hardworking, and less casual than speakers using [ɪn]. In Edinburgh, results are markedly different. We argue that these differences are due to a combination of factors that include the historical development of (ing) in a particular locale, which led to differences in production, variations in language ideology and, as a result, class-specific evaluations that appear to be regionally dependent. [ABSTRACT FROM AUTHOR]

Purpose: Nanoparticle (NP) attachment to biocompatible secondary carriers such as red blood cell (RBC) can prolong blood residence time of drug molecules and help create next-generation nanotherapeutics. However, little is known about the impact of RBC-targeted NPs on erythrocyte function. Methods: The objectives of this study were to develop and characterize in vitro a novel poly-L-lysine (PLL) and polyethylene glycol (PEG) copolymer-based NP containing fluorescent-tagged bovine serum albumin (BSA), and conjugated with ERY1, a 12 amino acid peptide with high affinity for the RBC membrane protein glycophorin A (ENP). Results: Confocal and flow cytometry data suggest that ENPs efficiently and irreversibly bind to RBC, with approximately 70% of erythrocytes bound after 24 h in a physiologic flow loop model compared to 10% binding of NPs without ERY1. Under these conditions, synthesized ENPs were not toxic to the RBCs. The rheological parameters at the applied shear. (0-15 Pa) were not influenced by ENP attachment to the RBCs. However, at high concentration, the strong affinity of ENPs to the glycophorin-A reduced the deformability of the RBC. Conclusions: ENPs can be efficiently attached to the RBCs without adversely affecting cellular function, and this may potentially enhance circulatory half-life of drug molecules. [ABSTRACT FROM AUTHOR]

This study examines the social meanings that speakers associate with variants of the variable (ing) in Manchester, focusing on a comparison of two age groups: a young age group of adolescents and those in very early adulthood, and an older age group. In most English varieties, (ing) has two possible realisations: [In] and [In]. However, in Manchester, a third possibility exists: [Ing]. Social meanings differ between age groups on three scales: articulateness, poshness and reliability. When compared to the youths, those in the older age group consider [In] to sound substantially more articulate than [In], as well as posher and more reliable than [Ing]. In contrast, those in the younger group consider [Ing] more reliable and posher-sounding than the older speakers. This is due, we argue, to developmental constraints during adolescence, but, more importantly, to life-stage experiences, with social meanings on these three scales altering as speakers leave adolescence behind and become increasingly subject to the standardisation pressures of adult communities. [ABSTRACT FROM AUTHOR]