Ternary NiCoTi-layered double hydroxide nanosheets as a pH-responsive nanoagent for photodynamic/chemodynamic synergistic therapy.

Combining photodynamic therapy (PDT) with chemodynamic therapy (CDT) has been proven to be a promising strategy to improve the treatment efficiency of cancer, because of the synergistic therapeutic effect arising between the two modalities. Herein, we report an inorganic nanoagent based on ternary NiCoTi-layered double hydroxide (NiCoTi-LDH) nanosheets to realize highly efficient photodynamic/chemodynamic synergistic therapy. The NiCoTi-LDH nanosheets exhibit oxygen vacancy-promoted electron-hole separation and photogenerated hole-induced O2-independent reactive oxygen species (ROS) generation under acidic circumstances, realizing in situ pH-responsive PDT. Moreover, due to the effective conversion between Co3+ and Co2+ caused by photogenerated electrons, the NiCoTi-LDH nanosheets catalyze the release of hydroxyl radicals (·OH) from H2O2 through Fenton reactions, resulting in CDT. Laser irradiation enhances the catalyzed ability of the NiCoTi-LDH nanosheets to promote the ROS generation, resulting in a better performance than TiO2 nanoparticles at pH 6.5. In vitro and in vivo experimental results show conclusively that NiCoTi-LDH nanosheets plus irradiation lead to efficient cell apoptosis and significant inhibition of tumor growth. This study reports a new pH-responsive inorganic nanoagent with oxygen vacancy-promoted photodynamic/chemodynamic synergistic performance, offering a potentially appealing clinical strategy for selective tumor elimination.

The safety of overdose and repeat administrations of BCG Danish strain 1331 vaccine in calves and pregnant heifers.

Bovine tuberculosis (bTB), caused by Mycobacterium bovis infection, is a zoonotic disease in cattle that represents a significant ongoing challenge to cattle farming productivity and the livelihoods of livestock farmers in the UK. Vaccination of cattle with BCG could directly target the ability of M. bovis to proliferate within vaccinates, restricting bTB pathogenesis and onward disease transmission, and represent a step change in the tools available to help control bTB in farmed cattle. A Marketing Authorisation (MA) is required before a cattle BCG vaccine could be sold and supplied as a veterinary medicine within the UK and this requires comprehensive data supporting vaccine quality, efficacy and, most importantly, its safety. We carried out two independent Good Laboratory Practice (GLP) studies in which the safety of BCG vaccination in cattle was stringently tested through overdose and repeat vaccine administrations in young calves and pregnant heifers. Mild and generally short-lived reactions to vaccinations were observed in some animals, most commonly increases in body temperature and swelling at vaccine injection sites, but these did not have a negative impact on the overall health status of vaccinates. BCG was not shed in the saliva, faeces, milk or urine from vaccinated animals and its dissemination was limited to injection site tissues and associated lymph nodes. Overall, young calves and pregnant heifers vaccinated with BCG remained in good general health, and the vaccinated pregnant heifers had normal pregnancies and gave birth to healthy calves. Obtaining a Marketing Authorisation for a cattle BCG vaccine is a critical milestone in the progress towards the eventual use of BCG vaccination in cattle as an additional bTB control tool within the UK; these pivotal GLP vaccine safety studies generated the detailed and essential target animal safety data needed to support this.

A one-step method for generating antimicrobial nanofibre meshes via coaxial electrospinning.

Respiratory diseases, including influenza, infectious pneumonia, and severe acute respiratory syndrome (SARS), are a leading cause of morbidity and mortality worldwide. The recent COVID-19 pandemic claimed over 6.9 million lives globally. With the possibility of future pandemics, the creation of affordable antimicrobial meshes for protective gear, such as facemasks, is essential. Electrospinning has been a focus for much of this research, but most approaches are complex and expensive, often wasting raw materials by distributing antiviral agents throughout the mesh despite the fact they can only be active if at the fibre surface. Here, we report a low cost and efficient one-step method to produce nanofibre meshes with antimicrobial activity, including against SARS-CoV-2. Cetrimonium bromide (CTAB) was deposited directly onto the surface of polycaprolactone (PCL) fibres by coaxial electrospinning. The CTAB-coated samples have denser meshes with finer nanofibres than non-coated PCL fibres (mean diameter: ∼300 nm versus ∼900 nm, with mean pore size: ∼300 nm versus > 600 nm). The formulations have > 90% coating efficiency and exhibit a burst release of CTAB upon coming into contact with aqueous media. The CTAB-coated materials have strong antibacterial activity against Staphylococcus aureus (ca. 100%) and Pseudomonas aeruginosa (96.5 ± 4.1%) bacteria, as well as potent antiviral activity with over 99.9% efficacy against both respiratory syncytial virus and SARS-CoV-2. The CTAB-coated nanofibre mesh thus has great potential to form a mask material for preventing both bacterial and viral respiratory infections.

Boosting the sonodynamic performance of CoBiMn-layered double hydroxide nanoparticles via tumor microenvironment regulation for ultrasound imaging-guided sonodynamic therapy.

Sonodynamic therapy (SDT), a promising strategy for cancer treatment with the ability for deep tissue penetration, has received widespread attention in recent years. Sonosensitizers with intrinsic characteristics for tumor-specific curative effects, tumor microenvironment (TME) regulation and tumor diagnosis are in high demand. Herein, amorphous CoBiMn-layered double hydroxide (a-CoBiMn-LDH) nanoparticles are presented as multifunctional sonosensitizers to trigger reactive oxygen species (ROS) generation for ultrasound (US) imaging-guided SDT. Hydrothermal-synthesized CoBiMn-LDH nanoparticles are etched via a simple acid treatment to obtain a-CoBiMn-LDH nanoparticles with abundant defects. The a-CoBiMn-LDH nanoparticles give greater ROS generation upon US irradiation, reaching levels ~ 3.3 times and ~ 8.2 times those of the crystalline CoBiMn-LDH nanoparticles and commercial TiO2 sonosensitizer, respectively. This excellent US-triggered ROS generation performance can be attributed to the defect-induced narrow band gap and promoted electrons and holes (e-/h+) separation. More importantly, the presence of Mn4+ enables the a-CoBiMn-LDH nanoparticles to regulate the TME by decomposing H2O2 into O2 for hypoxia relief and US imaging, and consuming glutathione (GSH) for protection against ROS clearance. Biological mechanism analysis shows that a-CoBiMn-LDH nanoparticles modified with polyethylene glycol can serve as a multifunctional sonosensitizer to effectively kill cancer cells in vitro and eliminate tumors in vivo under US irradiation by activating p53, apoptosis, and oxidative phosphorylation-related signaling pathways.

The role of circadian rhythms and sleep in the aetiology of autism spectrum disorder and attention-deficit/hyperactivity disorder: New evidence from bidirectional two-sample Mendelian randomization analysis.

LAY ABSTRACT: Research shows that people with autism spectrum disorder and attention-deficit/hyperactivity disorder often have sleep issues and problems with the body's natural daily rhythms, known as circadian rhythms. By exploring the genetic variants associated with these rhythms and the conditions, this study reveals that these rhythm changes and sleep patterns are directly linked to autism spectrum disorder and attention-deficit/hyperactivity disorder. It found that the timing of one's most active hours can increase the likelihood of having both autism spectrum disorder and attention-deficit/hyperactivity disorder. Importantly, it also shows that good sleep quality might protect against autism spectrum disorder, while disturbed sleep in people with attention-deficit/hyperactivity disorder seems to be a result rather than the cause of the condition. This understanding can help doctors and researchers develop better treatment approaches that focus on the specific ways sleep and body rhythms affect those with autism spectrum disorder and attention-deficit/hyperactivity disorder, considering their unique associations with circadian rhythms and sleep patterns. Understanding these unique links can lead to more effective, personalized care for those affected by these conditions.

Variation in farming damselfish behaviour creates a competitive landscape of risk on coral reefs.

Interspecific interactions are fundamental drivers of animal space use. Yet while non-consumptive effects of predation risk on prey space use are well-known, the risk of aggressive interactions on space use of competitors is largely unknown. We apply the landscape of risk framework to competition-driven space use for the first time, with the hypothesis that less aggressive competitors may alter their behaviour to avoid areas of high competitor density. Specifically, we test how aggressive risk from territorial algal-farming damselfishes can shape the spatial distribution of herbivore fish competitors. We found that only the most aggressive damselfish had fewer competitors in their surrounding area, demonstrating that individual-level behavioural variation can shape spatial distributions. In contradiction to the landscape of risk framework, abundances of farming damselfish and other fishes were positively associated. Our results suggest that reef fishes do not simply avoid areas of high damselfish abundance, but that spatial variation in aggressive behaviour, rather than of individuals, created a competitive landscape of risk. We emphasize the importance of individual-level behaviour in identifying patterns of space use and propose expanding the landscape of risk framework to non-predatory interactions to explore cascading behavioural responses to aggressive risk.

The Potential of Selenium-Based Therapies for Ocular Oxidative Stress.

Oxidative stress plays a critical role in the development of chronic ocular conditions including cataracts, age-related macular degeneration, and diabetic retinopathy. There is a need to explore the potential of topical antioxidants to slow the progression of those conditions by mediating oxidative stress and maintaining ocular health. Selenium has attracted considerable attention because it is a component of selenoproteins and antioxidant enzymes. The application of selenium to a patient can increase selenoprotein expression, counteracting the effect of reactive oxygen species by increasing the presence of antioxidant enzymes, and thus slowing the progression of chronic ocular disorders. Oxidative stress effects at the biomolecular level for prevalent ocular conditions are described in this review along with some of the known defensive mechanisms, with a focus on selenoproteins. The importance of selenium in the eye is described, along with a discussion of selenium studies and uses. Selenium's antioxidant and anti-inflammatory qualities may prevent or delay eye diseases. Recent breakthroughs in drug delivery methods and nanotechnology for selenium-based ocular medication delivery are enumerated. Different types of selenium may be employed in formulations aimed at managing ocular oxidative stress conditions.

Impact of Short-Term Computerized Cognitive Training on Cognition in Older Adults With and Without Genetic Risk of Alzheimer's Disease: Outcomes From the START Randomized Controlled Trial.

OBJECTIVES: To establish the impact of a 3-minute computerized cognitive training program (START) on cognition in older adults with and without genetic risk of Alzheimer's disease. DESIGN: Two-arm randomized controlled trial of the START program. SETTING AND PARTICIPANTS: Remote online trial in adults older than 50 taking part from home. METHODS: The trial compared the START program with placebo in 6544 people older than 50. Primary outcome was executive function measured through Trailmaking B, with other secondary cognitive measures. Genetic risk profile and ApoE4 status were determined by Illumina Array. RESULTS: START conferred benefit to executive function, attention, memory, and a composite measure, including in people with the ApoE4 genotype. CONCLUSIONS AND IMPLICATIONS: The 3-minute START task offers a means of supporting cognitive health in older adults and could be used at scale and within a precision medicine approach to reduce risk of cognitive decline in a targeted way.

Cisplatin-loaded mesoporous polydopamine nanoparticles capped with MnO2 and coated with platelet membrane provide synergistic anti-tumor therapy.

A multifunctional nanoplatform was constructed in this work, with the goal of ameliorating the challenges faced with traditional cancer chemotherapy. Cisplatin (CP) was loaded into mesoporous polydopamine (mPDA) nanoparticles (NPs) with a drug loading of 15.8 ± 0.1 %, and MnO2 used as pore sealing agent. Finally, the NPs were wrapped with platelet membrane (PLTM). P-selectin on the PLTM can bind to CD44, which is highly expressed on the tumor cell membrane, so as to improve the targeting performance of the NPs. In addition, the CD47 on the PLTM can prevent the NPs from being phagocytosed by macrophages, which is conducive to immune escape. The final PLTM-CP@mPDA/MnO2 NPs were found to have a particle size of approximately 198 nm. MnO2 is degraded into Mn2+ in the tumor microenvironment, leading to CP release from the pores in the mPDA. CP both acts as a chemotherapy agent and can also increase the concentration of H2O2 in cells. Mn2+ can catalyze the conversion of H2O2 to OH, resulting in oxidative damage and chemodynamic therapy. In addition, Mn2+ can be used as a contrast agent in magnetic resonance imaging (MRI). In vitro and in vivo experiments were performed to explore the therapeutic effect of the NPs. When the concentration of CP is 30 µg/mL, the NPs cause approximately 50 % cell death. It was found that the PLTM-CP@mPDA/MnO2 NPs are targeted to cancerous cells, and in the tumor site cause extensive apoptosis. Tumor growth is thereby repressed. No negative off-target side effects were noted. MRI could be used to confirm the presence of the NPs in the tumor site. Overall, the nano-platform developed here provides cooperative chemotherapy and chemodynamic therapy, and can potentially be used for effective cancer treatment which could be monitored by MRI.

Layered rare-earth hydroxides as multi-modal medical imaging probes: particle size optimisation and compositional exploration.

Recently, layered rare-earth hydroxides (LRHs) have received growing attention in the field of theranostics. We have previously reported the hydrothermal synthesis of layered terbium hydroxide (LTbH), which exhibited high biocompatibility, reversible uptake of a range of model drugs, and release-sensitive phosphorescence. Despite these favourable properties, LTbH particles produced by the reported method suffered from poor size-uniformity (670 ± 564 nm), and are thus not suitable for therapeutic applications. To ameliorate this issue, we first derive an optimised hydrothermal synthesis method to generate LTbH particles with a high degree of homogeneity and reproducibility, within a size range appropriate for in vivo applications (152 ± 59 nm, n = 6). Subsequently, we apply this optimised method to synthesise a selected range of LRH materials (R = Pr, Nd, Gd, Dy, Er, Yb), four of which produced particles with an average size under 200 nm (Pr, Nd, Gd, and Dy) without the need for further optimisation. Finally, we incorporate Gd and Tb into LRHs in varying molar ratios (1 : 3, 1 : 1, and 3 : 1) and assess the combined magnetic relaxivity and phosphorescence properties of the resultant LRH materials. The lead formulation, LGd1.41Tb0.59H, was demonstrated to significantly shorten the T2 relaxation time of water (r2 = 52.06 mM-1 s-1), in addition to exhibiting a strong phosphorescence signal (over twice that of the other LRH formulations, including previously reported LTbH), therefore holding great promise as a potential multi-modal medical imaging probe.

Regional reef fish assemblage maps provide baseline biogeography for tropicalization monitoring.

The Anthropocene rise in global temperatures is facilitating the expansion of tropical species into historically non-native subtropical locales, including coral reef fish. This redistribution of species, known as tropicalization, has serious consequences for economic development, livelihoods, food security, human health, and culture. Measuring the tropicalization of subtropical reef fish assemblages is difficult due to expansive species ranges, temporal distribution shifts with the movement of isotherms, and many dynamic density-dependent factors affecting occurrence and density. Therefore, in locales where tropical and subtropical species co-occur, detecting tropicalization changes relies on regional analyses of the relative densities and occurrence of species. This study provides a baseline for monitoring reef fish tropicalization by utilizing extensive monitoring data from a pivotal location in southeast Florida along a known transition between tropical and subtropical ecotones to define regional reef fish assemblages and use benthic habitat maps to spatially represent their zoogeography. Assemblages varied significantly by ecoregion, habitat depth, habitat type, and topographic relief. Generally, the southern assemblages had higher occurrences and densities of tropical species, whereas the northern assemblages had a higher occurrence and density of subtropical species. A total of 108 species were exclusive to regions south of the Bahamas Fracture Zone (BFZ) (South Palm Beach, Deerfield, Broward-Miami) and 35 were exclusive to the north (North Palm Beach, Martin), supporting the BFZ as a pivotal location that affects the coastal biogeographic extent of tropical marine species in eastern North America. Future tropicalization of reef fish assemblages are expected to be evident in temporal deviance of percent occurrence and/or relative species densities between baseline assemblages, where the poleward expansion of tropical species is expected to show the homogenization of assemblage regions as adjacent regions become more similar or the regional boundaries expand poleward. Ecoregions, habitat depth, habitat type, and relief should be incorporated into the stratification and analyses of reef fish surveys to statistically determine assemblage differences across the seascape, including those from tropicalization.

Fibre-based fluorescence-lifetime imaging microscopy: a real-time biopsy guidance tool for suspected lung cancer.

Lung cancer is the most common cause of cancer-related deaths worldwide. Early detection improves outcomes, however, existing sampling techniques are associated with suboptimal diagnostic yield and procedure-related complications. Autofluorescence-based fluorescence-lifetime imaging microscopy (FLIM), a technique which measures endogenous fluorophore decay rates, may aid identification of optimal biopsy sites in suspected lung cancer. Our fibre-based fluorescence-lifetime imaging system, utilising 488 nm excitation, which is deliverable via existing diagnostic platforms, enables real-time visualisation and lifetime analysis of distal alveolar lung structure. We evaluated the diagnostic accuracy of the fibre-based fluorescence-lifetime imaging system to detect changes in fluorescence lifetime in freshly resected ex vivo lung cancer and adjacent healthy tissue as a first step towards future translation. The study compares paired non-small cell lung cancer (NSCLC) and non-cancerous tissues with gold standard diagnostic pathology to assess the performance of the technique. Paired NSCLC and non-cancerous lung tissues were obtained from thoracic resection patients (N=21). A clinically compatible 488 nm fluorescence-lifetime endomicroscopy platform was used to acquire simultaneous fluorescence intensity and lifetime images. Fluorescence lifetimes were calculated using a computationally-lightweight, rapid lifetime determination method. Fluorescence lifetime was significantly reduced in ex vivo lung cancer, compared with non-cancerous lung tissue [mean ± standard deviation (SD), 1.79±0.40 vs. 2.15±0.26 ns, P<0.0001], and fluorescence intensity images demonstrated distortion of alveolar elastin autofluorescence structure. Fibre-based fluorescence-lifetime imaging demonstrated good performance characteristics for distinguishing lung cancer, from adjacent non-cancerous tissue, with 81.0% sensitivity and 71.4% specificity. Our novel fibre-based fluorescence-lifetime imaging system, which enables label-free imaging and quantitative lifetime analysis, discriminates ex vivo lung cancer from adjacent healthy tissue. This minimally invasive technique has potential to be translated as a real-time biopsy guidance tool, capable of optimising diagnostic accuracy in lung cancer.

Hydrophilic and hydrophobic drug release from core (polyvinylpyrrolidone)-sheath (ethyl cellulose) pressure-spun fibers.

A core-sheath structure is one of the methods developed to overcome the challenges often faced when using monolithic fibers for drug delivery. In this study, fibers based on polyvinylpyrrolidone (core) and ethyl cellulose (sheath) were successfully produced using a novel core-sheath pressure-spinning process. For comparison, these two polymers were also processed into as blend fibers. All samples were then investigated for their performances in releasing water-soluble ampicillin (AMP) and poorly water-soluble ibuprofen (IBU) model drugs. Scanning electron,digital and confocal microscopy confirmed that fibers with a core-sheath structure were successfully made. Fourier transform infrared spectroscopy showed the success of the pressure-spinning technique in encapsulating AMP/IBU in all fiber samples. Compared to blend fibers, the core-sheath fibers had better performance in encapsulating both water-soluble and poorly water-soluble drugs. Moreover, the core-sheath structure was able to reduce the initial burst release and provided a better sustained release profile than the blend fiber analog. In conclusion, the pressure-spinning method was capable of producing core-sheath and blend fibers that could be used for the loading of either hydrophilic or hydrophobic drugs for controlled drug delivery systems.

A Novel Fit-Flexible Fluorescence Soft Imager: Tri-Sensing of Intensity, Fall-Time, and Life Profile.

Time-resolved fluorescence imaging techniques, like confocal fluorescence lifetime imaging microscopy, are powerful photonic instrumentation tools of modern science with diverse applications, including: biology, medicine, and chemistry. However, complexities of the systems, both at specimen and device levels, cause difficulties in quantifying soft biomarkers. To address the problems, we first aim to understand and model the underlying photophysics of fluorescence decay curves. For this purpose, we provide a set of mathematical functions, called "life models", fittable with the real temporal recordings of histogram of photon counts. For each model, an equivalent electrical circuit, called a "life circuit", is derived for explaining the whole process. In confocal endomicroscopy, the components of excitation laser, specimen, and fluorescence-emission signal as the histogram of photon counts are modelled by a power source, network of resistor-inductor-capacitor circuitry, and multimetre, respectively. We then design a novel pixel-level temporal classification algorithm, called a "fit-flexible approach", where qualities of "intensity", "fall-time", and "life profile" are identified for each point. A model selection mechanism is used at each pixel to flexibly choose the best representative life model based on a proposed Misfit-percent metric. A two-dimensional arrangement of the quantified information detects some kind of structural information. This approach showed a potential of separating microbeads from lung tissue, distinguishing the tri-sensing from conventional methods. We alleviated by 7% the error of the Misfit-percent for recovering the histograms on real samples than the best state-of-the-art competitor. Codes are available online.

Temporal dynamics of the early immune response following Mycobacterium bovis infection of cattle.

Bovine tuberculosis is an infectious disease of global significance that remains endemic in many countries. Mycobacterium bovis infection in cattle is characterized by a cell-mediated immune response (CMI) that precedes humoral responses, however the timing and trajectories of CMI and antibody responses determined by newer generation assays remain undefined. Here we used defined-antigen interferon-gamma release assays (IGRA) and an eleven-antigen multiplex ELISA (Enferplex TB test) alongside traditional tuberculin-based IGRA and IDEXX M. bovis antibody tests to assess immune trajectories following experimental M. bovis infection of cattle. The results show CMI responses developed as early as two-weeks post-infection, with all infected cattle testing positive three weeks post-infection. Interestingly, 6 of 8 infected animals were serologically positive with the Enferplex TB assay as early as 4 weeks post-infection. As expected, application of the tuberculin skin test enhanced subsequent serological reactivity. Infrequent M. bovis faecal shedding was observed but was uncorrelated with observed immune trajectories. Together, the results show that early antibody responses to M. bovis infection are detectable in some individuals and highlight an urgent need to identify biomarkers that better predict infection outcomes, particularly for application in low-and-middle income countries where test-and-slaughter based control methods are largely unfeasible.

The relationship between playing musical instruments and cognitive trajectories: Analysis from a UK ageing cohort.

BACKGROUND: The accumulation of age-associated cognitive deficits can lead to Mild Cognitive Impairment (MCI) and dementia. This is a major public health issue for the modern ageing population, as it impairs health, independence and overall quality of life. Keeping the brain active during life has been associated with an increased cognitive reserve, therefore reducing the risk of cognitive impairment in older age. Previous research has identified a potential relationship between musicality and cognition. OBJECTIVES: Explore the relationship between musicality and cognitive function in a large cohort of older adults. METHODS: This was a nested study within the PROTECT-UK cohort, which collects longitudinal computerised assessments of cognitive function in adults over 40. Participants were invited to complete the validated Edinburgh Lifetime Musical Experience Questionnaire (ELMEQ) to assess their musical experience and lifetime exposure to music. Linear regression analysis was performed using cognitive data from PROTECT-UK. RESULTS: Analysis identified an association between musicality and cognition in this cohort. Playing a musical instrument was associated with significantly better performance in working memory and executive function. Significant associations were also found between singing and executive function, and between overall musical ability and working memory. CONCLUSIONS: Our findings confirm previous literature, highlighting the potential value of education and engagement in musical activities throughout life as a means of harnessing cognitive reserve as part of a protective lifestyle for brain health.

Advanced Formulation Approaches for Emerging Therapeutic Technologies.

In addition to proteins, discussed in the Chapter "Advances in Vaccine Adjuvants: Nanomaterials and Small Molecules", there are a wide range of alternatives to small molecule active ingredients. Cells, extracellular vesicles, and nucleic acids in particular have attracted increasing research attention in recent years. There are now a number of products on the market based on these emerging technologies, the most famous of which are the mRNA-based vaccines against SARS-COV-2. These advanced therapeutic moieties are challenging to formulate however, and there remain significant challenges for their more widespread use. In this chapter, we consider the potential and bottlenecks for developing further medical products based on these systems. Cells, extracellular vesicles, and nucleic acids will be discussed in terms of their mechanism of action, the key requirements for translation, and how advanced formulation approaches can aid their future development. These points will be presented with selected examples from the literature, and with a focus on the formulations which have made the transition to clinical trials and clinical products.

Electrospun aligned tacrolimus-loaded polycaprolactone biomaterials for peripheral nerve repair.

Background: Efficacious repair of peripheral nerve injury is an unmet clinical need. The implantation of biomaterials containing neurotrophic drugs at the injury site could promote nerve regeneration and improve outcomes for patients. Materials & methods: Random and aligned electrospun poly-ε-caprolactone scaffolds containing encapsulated tacrolimus were fabricated, and the gene expression profile of Schwann cells (SCs) cultured on the surface was elucidated. On aligned fibers, the morphology of SCs and primary rat neurons was investigated. Results: Both scaffold types exhibited sustained release of drug, and the gene expression of SCs was modulated by both nanofibrous topography and the presence of tacrolimus. Aligned fibers promoted the alignment of SCs and orientated outgrowth from neurons. Conclusion: Electrospun PCL scaffolds with tacrolimus hold promise for the repair of peripheral nerve injury.

This article reports the production and testing of fibrous materials loaded with tacrolimus, a drug known to improve nerve regeneration, for the surgical repair of peripheral nerve injury. Materials were created with either a randomly orientated structure or an aligned structure that mimics the anatomy of native nerve, and both displayed long-term release of the loaded drug. Schwann cells, which are a critical cell type in nerve regeneration, were grown on the materials and their behaviour was positively influenced by the fibrous surfaces and/or the presence of tacrolimus. Neurons grown on the aligned materials demonstrated directional outgrowth, which may be also beneficial for increasing the rate of regeneration. These materials have the potential to improve outcomes of nerve repair for patients.

Advanced Formulation Approaches for Proteins.

Proteins and peptides are highly desirable as therapeutic agents, being highly potent and specific. However, there are myriad challenges with processing them into patient-friendly formulations: they are often unstable and have a tendency to aggregate or degrade upon storage. As a result, the vast majority of protein actives are delivered parenterally as solutions, which has a number of disadvantages in terms of cost, accessibility, and patient experience. Much work has been undertaken to develop new delivery systems for biologics, but to date this has led to relatively few products on the market. In this chapter, we review the challenges faced when developing biologic formulations, discuss the technologies that have been explored to try to overcome these, and consider the different delivery routes that can be applied. We further present an overview of the currently marketed products and assess the likely direction of travel in the next decade.

Impact of the iWHELD digital person-centered care program on quality of life, agitation and psychotropic medications in people with dementia living in nursing homes during the COVID-19 pandemic: A randomized controlled trial.

INTRODUCTION: iWHELD is a digital person-centered care program for people with dementia in nursing homes adapted for remote delivery during the COVID-19 pandemic. METHODS: A 16-week two-arm cluster-randomized controlled trial in 149 UK nursing homes compared iWHELD with treatment as usual (TAU). Primary outcome was the overall quality of life with secondary outcomes of agitation and psychotropic use. RESULTS: iWHELD conferred benefit to quality of life on the primary (F = 4.3, p = 0.04) and secondary measures of quality of life (F = 6.45, p = 0.01) and reduced psychotropic medication use (χ2  = 4.08, p = 0.04) with no worsening of agitation. Benefit was seen in participants who contracted COVID-19, those with agitation at baseline, and those taking psychotropic medications. DISCUSSION: iWHELD confers benefits to quality of life and key measures of well-being, can be delivered during the challenging conditions of a pandemic, and should be considered for use alongside any emerging pharmacological treatment for neuropsychiatric symptoms. HIGHLIGHTS: iWHELD is the only remote, digital delivery nursing home training programme for dementia care iWHELD improved quality of life in people with dementia and reduced antipsychotic use without worsening of agitation Residents who contracted Covid-19 during the study also experienced benefits from iWHELD iWHELD offers a valuable, pandemic-safe tool for improving dementia care.