The benefits of exercise to human health have long been recognised. However, only in the past decade have researchers started to discover the molecular benefits that exercise confers, especially to ...the central nervous system (CNS). These discoveries include the magnitude of molecular messages that are communicated from skeletal muscle to the CNS. Despite these advances in understanding, very limited studies have been conducted to decipher the molecular benefits of exercise in retinal health and disease. Here, we review the latest work on the effects of exercise on the retina and discuss its effects on the wider CNS, with a focus on demonstrating the potential applicability and comparative molecular mechanisms that may be occurring in the retina. This review covers the key molecular pathways where exercise exerts its effects: oxidative stress and mitochondrial health; inflammation; protein aggregation; neuronal health; and tissue crosstalk via extracellular vesicles. Further research on the benefits of exercise to the retina and its molecular messages within extracellular vesicles is highly topical in this field.
Background Diabetes mellitus (DM) is a growing global health problem. In Singapore, the prevalence of Type 2 DM is rising, but comprehensive information about trends in DM-related complications is ...lacking. Objectives We utilized the Singapore Health Services (SingHealth) diabetes registry (SDR) to assess trends in DM micro and macro-vascular complications at the population level, explore factors influencing these trends. Methods We studied trends for ten DM-related complications: ischemic heart disease (IHD), acute myocardial infarction (AMI), peripheral arterial disease (PAD) and strokes, diabetic eye complications, nephropathy, neuropathy, diabetic foot, major and minor lower extremity amputation (LEA). The complications were determined through clinical coding in hospital (inpatient and outpatient) and primary care settings within the SingHealth cluster. We described event rates for the complications in 4 age-bands. Joinpoint regression was used to identify significant changes in trends. Results Among 222,705 patients studied between 2013 and 2020. 48.6% were female, 70.7% Chinese, 14.7% Malay and 10.6% Indian with a mean (SD) age varying between 64.6 (12.5) years in 2013 and 65.7 (13.2) years in 2020. We observed an increase in event rates in IHD, PAD, stroke, diabetic eye complications nephropathy, and neuropathy. Joinpoints was observed for IHD and PAD between 2016 to 2018, with subsequent plateauing of event rates. Major and minor LEA event rates decreased through the study period. Conclusion We found that DM and its complications represent an important challenge for healthcare in Singapore. Improvements in the trends of DM macrovascular complications were observed. However, trends in DM microvascular complications remain a cause for concern.
Sleep spindles are a hallmark of non-REM sleep and play a fundamental role in memory consolidation. Alterations in these spindles are emerging as sensitive biomarkers for neurodegenerative diseases ...of ageing. Understanding the clinical presentations associated with spindle alterations may help to elucidate the functional role of these distinct electroencephalographic oscillations and the pathophysiology of sleep and neurodegenerative disorders. Here, we use a data-driven approach to examine the sleep, memory and default mode network connectivity phenotypes associated with sleep spindle architecture in older adults (mean age = 66 years). Participants were recruited from a specialist clinic for early diagnosis and intervention for cognitive decline, with a proportion showing mild cognitive deficits on neuropsychological testing. In a sample of 88 people who underwent memory assessment, overnight polysomnography and resting-state fMRI, a k-means cluster analysis was applied to spindle measures of interest: fast spindle density, spindle duration and spindle amplitude. This resulted in three clusters, characterised by preserved spindle architecture with higher fast spindle density and longer spindle duration (Cluster 1), and alterations in spindle architecture (Clusters 2 and 3). These clusters were further characterised by reduced memory (Clusters 2 and 3) and nocturnal hypoxemia, associated with sleep apnea (Cluster 3). Resting-state fMRI analysis confirmed that default mode connectivity was related to spindle architecture, although directionality of this relationship differed across the cluster groups. Together, these results confirm a diversity in spindle architecture in older adults, associated with clinically meaningful phenotypes, including memory function and sleep apnea. They suggest that resting-state default mode connectivity during the awake state can be associated with sleep spindle architecture; however, this is highly dependent on clinical phenotype. Establishing relationships between clinical and neuroimaging features and sleep spindle alterations will advance our understanding of the bidirectional relationships between sleep changes and neurodegenerative diseases of ageing.
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•PdNiO anode catalyst supported on exfoliated graphene oxide (EGO) was chemically prepared for alkaline direct ethanol fuel cell.•PdNiO/EGO catalyst exhibits greater catalytic ...activity and stability towards ethanol oxidation reaction in the alkaline medium compared to PdNiO/C and PdNiO.•PdNiO/EGO catalyst shows the highest open circuit voltage (OCV) and power density as compared to the other PdNiO composites and commercially available Pd/C catalyst.•PdNiO/EGO is a promising anode material for direct ethanol fuel cell application.
A catalyst consisting of palladium – nickel supported on exfoliated graphene oxide (PdNi/EGO) composite was synthesized. The catalytic activity was tested for ethanol oxidation reaction (EOR) in half-cell using cyclic voltammetry (CV) and subsequently it was used as an anode material in a direct ethanol fuel cell (DEFC). Transmission Electron Microscopy showed the catalyst particles are uniformly dispersed on the surface of graphene oxide with the particle size ranging from 3 to 6nm. X-ray Photoelectron Spectroscopy analysis of catalysts revealed that the surface consisting of mostly Pd, PdO, Ni(OH)2, and NiOOH. CV and chronoamperometry measurements demonstrated higher electrocatalytic activity and stability for PdNi/EGO in the alkaline medium than the unsupported PdNi and carbon black-supported PdNi (PdNi/C) catalysts. A single cell anion exchange membrane DEFC constructed with a PdNi/EGO anode catalyst showed a maximum power density of 16.6mWcm−2 at 50°C, which is higher than the unsupported PdNi, PdNi/C, and commercial Pd/C catalyst.
Game theory is used by all behavioral sciences, but its development has long centered around the economic interpretation of equilibrium outcomes in relatively simple games and toy systems. But game ...theory has another potential use: the high-level design of large game compositions that express complex architectures and represent real-world institutions faithfully. Compositional game theory, grounded in the mathematics underlying programming languages, and introduced here as a general computational framework, increases the parsimony of game representations with abstraction and modularity, accelerates search and design, and helps theorists across disciplines express real-world institutional complexity in well-defined ways. Relative to existing approaches in game theory, compositional game theory is especially promising for solving game systems with long-range dependencies, for comparing large numbers of structurally related games, and for nesting games into the larger logical or strategic flows typical of real world policy or institutional systems.
Game theory is used by all behavioral sciences, but its development has long centered around the economic interpretation of equilibrium outcomes in relatively simple games and toy systems. But game ...theory has another potential use: the high-level design of large game compositions that express complex architectures and represent real-world institutions faithfully. Compositional game theory, grounded in the mathematics underlying programming languages, and introduced here as a general computational framework, increases the parsimony of game representations with abstraction and modularity, accelerates search and design, and helps theorists across disciplines express real-world institutional complexity in well-defined ways. Relative to existing approaches in game theory, compositional game theory is especially promising for solving game systems with long-range dependencies, for comparing large numbers of structurally related games, and for nesting games into the larger logical or strategic flows typical of real world policy or institutional systems.
Combinations of monoclonal antibodies (mAbs) against different epitopes on the same antigen synergistically neutralize many viruses. However, there are limited studies assessing whether combining ...human mAbs against distinct regions of the Plasmodium falciparum (Pf) circumsporozoite protein (CSP) enhances in vivo protection against malaria compared to each mAb alone or whether passive transfer of PfCSP mAbs would improve protection following vaccination against PfCSP. Here, we isolated a panel of human mAbs against the subdominant C-terminal domain of PfCSP (C-CSP) from a volunteer immunized with radiation-attenuated Pf sporozoites. These C-CSP-specific mAbs had limited binding to sporozoites in vitro that was increased by combination with neutralizing human "repeat" mAbs against the NPDP/NVDP/NANP tetrapeptides in the central repeat region of PfCSP. Nevertheless, passive transfer of repeat- and C-CSP-specific mAb combinations did not provide enhanced protection against in vivo sporozoite challenge compared to repeat mAbs alone. Furthermore, combining potent repeat-specific mAbs (CIS43, L9, and 317) that respectively target the three tetrapeptides (NPDP/NVDP/NANP) did not provide additional protection against in vivo sporozoite challenge. However, administration of either CIS43, L9, or 317 (but not C-CSP-specific mAbs) to mice that had been immunized with R21, a PfCSP-based virus-like particle vaccine that induces polyclonal antibodies against the repeat region and C-CSP, provided enhanced protection against sporozoite challenge when compared to vaccine or mAbs alone. Collectively, this study shows that while combining mAbs against the repeat and C-terminal regions of PfCSP provide no additional protection in vivo, repeat mAbs do provide increased protection when combined with vaccine-induced polyclonal antibodies. These data should inform the implementation of PfCSP human mAbs alone or following vaccination to prevent malaria infection.
Chemokine signalling is required for the homing of leukocytes during retinal inflammation, and is associated with pathogenesis of diseases such as age-related macular degeneration (AMD). Here, we ...explore the role of interleukin-1β (IL-1β) in modulating AMD-associated chemokines Ccl2, Cxcl1, and Cxcl10 during photo-oxidative retinal damage, and the effect on both the accumulation of outer-retinal macrophages, and death of photoreceptors.
Inhibition of retinal IL-1β expression was performed using either siRNA or antibody neutralisation, which was intravitreally injected in SD rats prior to photo-oxidative damage. Changes in the expression and localisation of Il-1β, Ccl2, Cxcl1 and Cxcl10 genes were assessed using qPCR and in situ hybridisation, while the recruitment of retinal macrophages was detected using immunohistochemistry for IBA1. Levels of photoreceptor cell death were determined using TUNEL.
Photo-oxidative damage elevated the expression of Il-1β and inflammasome-related genes, and IL-1β protein was detected in microglia infiltrating the outer retina. This was associated with increased expression of Ccl2, Cxcl1, and Cxcl10. Intravitreal IL-1β inhibitors suppressed chemokine expression following damage and reduced macrophage accumulation and photoreceptor death. Moreover, in Müller and RPE cell cultures, and in vivo, Ccl2, Cxcl1 and Cxcl10 were variously upregulated when stimulated with IL-1β, with increased macrophage accumulation detected in vivo.
IL-1β is produced by retinal microglia and macrophages and promotes chemokine expression by Müller cells and RPE in retinal degeneration. Targeting IL-1β may prove efficacious in broadly suppressing chemokine-mediated inflammation in retinal dystrophies such as AMD.
The use of novel mRNA platforms for COVID-19 vaccines raised concern about vaccine safety, especially in Asian populations that made up less than 10% of study populations in the pivotal vaccine ...trials used for emergency use authorisation. Vaccine safety issues also remain a concern in assessing the clinical risks and benefits of vaccine boosters, particularly in specific age groups or segments of the population. This study describes a vaccination exercise involving Asian military personnel, and the adverse reactions and safety events observed.
Minor adverse reactions, hospitalisations and adverse events of special interest were monitored as part of the organisation's protocol for safety monitoring of COVID-19 vaccinations. All vaccine recipients were invited to complete an online adverse reaction questionnaire. Medical consults at the military's primary healthcare facilities were monitored for vaccine-related presentations. All hospitalisations involving vaccine recipients were analysed. Adverse reaction rates between doses, vaccines and age groups were compared.
A total of 127,081 mRNA vaccine doses were administered to 64,661 individuals up to 24 July 2021. Common minor adverse reactions included fever/chills, body aches and injection site pain. These were more common after dose 2. Younger individuals experienced minor adverse reactions more frequently. Rare cases of anaphylaxis, Bell's palsy and myocarditis/pericarditis were observed. No deaths occurred.
Minor adverse reactions were less common than reported in other studies, and rates of anaphylaxis, Bell's palsy and myocarditis/pericarditis were comparable. Our study supports the favourable safety profile of mRNA COVID-19 vaccines, which may help guide decisions about booster doses if required.
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