A scoping review of stroke services within the Philippines.

Background: Stroke is a leading cause of mortality and disability. In higher-income countries, mortality and disability have been reduced with advances in stroke care and early access to rehabilitation services. However, access to such services and the subsequent impact on stroke outcomes in the Philippines, which is a lower- and middle-income countries (LMIC), is unclear.

In vivo mitochondria-targeted protection against uterine artery vascular dysfunction and remodelling in rodent hypoxic pregnancy.

Gestational hypoxia adversely affects uterine artery function, increasing complications. However, an effective therapy remains unidentified. Here, we show in rodent uterine arteries that hypoxic pregnancy promotes hypertrophic remodelling, increases constrictor reactivity via protein kinase C signalling, and triggers compensatory dilatation via nitric oxide-dependent mechanisms and stimulation of large conductance Ca -activated K -channels.

measurement of mitochondrial ROS production in mouse models of photoreceptor degeneration.

Retinitis pigmentosa (RP) is a disease characterised by photoreceptor cell death. It can be initiated by mutations in a number of different genes, primarily affecting rods, which will die first, resulting in loss of night vision. The secondary death of cones then leads to loss of visual acuity and blindness.

Rapid and selective generation of HS within mitochondria protects against cardiac ischemia-reperfusion injury.

Mitochondria-targeted HS donors are thought to protect against acute ischemia-reperfusion (IR) injury by releasing HS that decreases oxidative damage. However, the rate of HS release by current donors is too slow to be effective upon administration following reperfusion. To overcome this limitation here we develop a mitochondria-targeted agent, MitoPerSulf that very rapidly releases HS within mitochondria.

Native chemical ligation approach to sensitively probe tissue acyl-CoA pools.

During metabolism, carboxylic acids are often activated by conjugation to the thiol of coenzyme A (CoA). The resulting acyl-CoAs comprise a group of ∼100 thioester-containing metabolites that could modify protein behavior through non-enzymatic N-acylation of lysine residues. However, the importance of many potential acyl modifications remains unclear because antibody-based methods to detect them are unavailable and the in vivo concentrations of their respective acyl-CoAs are poorly characterized.

Telerehabilitation for people with physical disabilities and movement impairment: development and evaluation of an online toolkit for practitioners and patients.

Purpose: Telerehabilitation has increasingly been used since the COVID-19 pandemic but with limited guidance available on undertaking physical assessments using remote methods. We aimed to provide such guidance by developing a Telerehab Toolkit, an online information and training resource for practitioners, patients, and carers on telerehabilitation for people with physical disabilities and movement impairment.

Materials And Methods: Development and evaluation of the toolkit were informed by the Knowledge to Action framework and took place iteratively in two phases-knowledge creation and action.

Telerehabilitation for physical disabilities and movement impairment: A service evaluation in South West England.

Unlabelled: RATIONALE, AIMS AND OBJECTIVES: Telerehabilitation was used to ensure continued provision of care during the COVID-19 pandemic, but there was a lack of guidance on how to use it safely and effectively for people with physical disabilities and movement impairment. In this service evaluation, we aimed to collate information on practitioner and patient experiences, challenges and facilitators, and examples of best practice to inform the development of an online toolkit and training package.

Methods: Guided discussions were carried out with 44 practitioners, 7 patients and 2 carers from five health and social care organisations in South West England, and analysed thematically.

Functional standing frame programme early after severe sub-acute stroke (SPIRES): a randomised controlled feasibility trial.

Background: Early mobilisation (> 24 h post-stroke) is recommended for people with stroke. However, there is a paucity of evidence about how to implement early mobilisation for people who have had a severe stroke. Prolonged standing and task-specific training (sit-to-stand repetitions) have separately been evaluated in the literature; however, these functionally linked tasks have not been evaluated in combination for people with severe sub-acute stroke.

Telerehabilitation for People With Physical Disabilities and Movement Impairment: A Survey of United Kingdom Practitioners.

Background: Telerehabilitation is a feasible and potentially effective alternative to face-to-face rehabilitation. However, specific guidance, training, and support for practitioners who undertake remote assessments in people with physical disabilities and movement impairment are limited.

Objective: The aims of this survey of United Kingdom-based health and social care practitioners were to explore experiences, assess training needs, and collate ideas on best practices in telerehabilitation for physical disabilities and movement impairment.

Technologies to Support Assessment of Movement During Video Consultations: Exploratory Study.

Background: Understanding and assessing patients' body movements is essential for physical rehabilitation but is challenging in video consultations, as clinicians are frequently unable to see the whole patient or observe the patient as they perform specific movements.

Objective: The objective of this exploratory study was to assess the use of readily available technologies that would enable remote assessment of patient movement as part of a video consultation.

Methods: We reviewed the literature and available technologies and chose four technologies (Kubi and Pivo desktop robots, Facebook Portal TV, wide-angle webcam), in addition to help from a friend or a simple mobile phone holder, to assist video consultations.

Scope, context and quality of telerehabilitation guidelines for physical disabilities: a scoping review.

Objective: To identify the available guidance and training to implement telerehabilitation movement assessments for people (adults and children) with a physical disability, including those recovering from COVID-19.

Design: Rapid scoping review.

Included Sources And Articles: PubMed, CINAHL, PsychInfo, Cochrane, Embase, Web of Science, PEDro, UK Health Forum, WHO, National Archives and NHS England were searched using the participant-concept-context framework from 2015 to August 2020.

Outcomes of hepatitis C virus nucleic acid testing positive donors in aviremic recipients with delayed direct-acting antiviral initiation.

The use of allografts from hepatitis C virus (HCV) Nucleic Acid Testing (NAT)+ donors into HCV NAT- recipients has been reported to be efficacious in a handful of studies. However, these studies have not reflected real-world practice where the initiation of direct-acting antivirals (DAA) is dependent on insurance coverage. A single-center, retrospective chart review of HCV NAT- recipients who underwent solid organ transplantation (SOT) from a HCV NAT+ donor between April 1, 2019 and May 27, 2020 was conducted.

Mitochondria antioxidant protection against cardiovascular dysfunction programmed by early-onset gestational hypoxia.

Mitochondria-derived oxidative stress during fetal development increases cardiovascular risk in adult offspring of pregnancies complicated by chronic fetal hypoxia. We investigated the efficacy of the mitochondria-targeted antioxidant MitoQ in preventing cardiovascular dysfunction in adult rat offspring exposed to gestational hypoxia, integrating functional experiments in vivo, with those at the isolated organ and molecular levels. Rats were randomized to normoxic or hypoxic (13%-14% O ) pregnancy ± MitoQ (500 μM day ) in the maternal drinking water.

Early detection of doxorubicin-induced cardiotoxicity in rats by its cardiac metabolic signature assessed with hyperpolarized MRI.

Doxorubicin (DOX) is a widely used chemotherapeutic agent that can cause serious cardiotoxic side effects culminating in congestive heart failure (HF). There are currently no clinical imaging techniques or biomarkers available to detect DOX-cardiotoxicity before functional decline. Mitochondrial dysfunction is thought to be a key factor driving functional decline, though real-time metabolic fluxes have never been assessed in DOX-cardiotoxicity.

Confirmation of the Cardioprotective Effect of MitoGamide in the Diabetic Heart.

Purpose: HFpEF (heart failure with preserved ejection fraction) is a major consequence of diabetic cardiomyopathy with no effective treatments. Here, we have characterized Akita mice as a preclinical model of HFpEF and used it to confirm the therapeutic efficacy of the mitochondria-targeted dicarbonyl scavenger, MitoGamide.

Methods And Results: A longitudinal echocardiographic analysis confirmed that Akita mice develop diastolic dysfunction with reduced E peak velocity, E/A ratio and extended isovolumetric relaxation time (IVRT), while the systolic function remains comparable with wild-type mice.

Targeting succinate dehydrogenase with malonate ester prodrugs decreases renal ischemia reperfusion injury.

Renal ischemia reperfusion (IR) injury leads to significant patient morbidity and mortality, and its amelioration is an urgent unmet clinical need. Succinate accumulates during ischemia and its oxidation by the mitochondrial enzyme succinate dehydrogenase (SDH) drives the ROS production that underlies IR injury. Consequently, compounds that inhibit SDH may have therapeutic potential against renal IR injury.

Effectiveness of non-pharmacological interventions to treat orthostatic hypotension in elderly people and people with a neurological condition: a systematic review.

Objective: The objective of this review was to summarize the best available evidence regarding the effectiveness of non-pharmacological interventions to treat orthostatic hypotension (OH) in elderly people and people with a neurological condition.

Introduction: Orthostatic hypotension is common in elderly people and people with a neurological condition and can interfere with or limit rehabilitation. Non-pharmacological interventions to treat OH could allow for longer and earlier mobilization, which is recommended in national clinical guidelines for rehabilitation in the acute or sub-acute phase following stroke or other neurological conditions.

Ester Prodrugs of Malonate with Enhanced Intracellular Delivery Protect Against Cardiac Ischemia-Reperfusion Injury In Vivo.

Purpose: Mitochondrial reactive oxygen species (ROS) production upon reperfusion of ischemic tissue initiates the ischemia/reperfusion (I/R) injury associated with heart attack. During ischemia, succinate accumulates and its oxidation upon reperfusion by succinate dehydrogenase (SDH) drives ROS production. Inhibition of succinate accumulation and/or oxidation by dimethyl malonate (DMM), a cell permeable prodrug of the SDH inhibitor malonate, can decrease I/R injury.

Isolating adverse effects of glucocorticoids on the embryonic cardiovascular system.

Antenatal glucocorticoid therapy reduces mortality in the preterm infant, but evidence suggests off-target adverse effects on the developing cardiovascular system. Whether deleterious effects are direct on the offspring or secondary to alterations in uteroplacental physiology is unclear. Here, we isolated direct effects of glucocorticoids using the chicken embryo, a model system in which the effects on the developing heart and circulation of therapy can be investigated, independent of effects on the mother and/or the placenta.

Succinate accumulation drives ischaemia-reperfusion injury during organ transplantation.

During heart transplantation, storage in cold preservation solution is thought to protect the organ by slowing metabolism; by providing osmotic support; and by minimising ischaemia-reperfusion (IR) injury upon transplantation into the recipient. Despite its widespread use our understanding of the metabolic changes prevented by cold storage and how warm ischaemia leads to damage is surprisingly poor. Here, we compare the metabolic changes during warm ischaemia (WI) and cold ischaemia (CI) in hearts from mouse, pig, and human.

A sensitive mass spectrometric assay for mitochondrial CoQ pool redox state in vivo.

Coenzyme Q (CoQ) is an essential cofactor, primarily found in the mitochondrial inner membrane where it functions as an electron carrier in the respiratory chain, and as a lipophilic antioxidant. The redox state of the CoQ pool is the ratio of its oxidised (ubiquinone) and reduced (ubiquinol) forms, and is a key indicator of mitochondrial bioenergetic and antioxidant status. However, the role of CoQ redox state in vivo is poorly understood, because determining its value is technically challenging due to redox changes during isolation, extraction and analysis.

Selective Disruption of Mitochondrial Thiol Redox State in Cells and In Vivo.

Mitochondrial glutathione (GSH) and thioredoxin (Trx) systems function independently of the rest of the cell. While maintenance of mitochondrial thiol redox state is thought vital for cell survival, this was not testable due to the difficulty of manipulating the organelle's thiol systems independently of those in other cell compartments. To overcome this constraint we modified the glutathione S-transferase substrate and Trx reductase (TrxR) inhibitor, 1-chloro-2,4-dinitrobenzene (CDNB) by conjugation to the mitochondria-targeting triphenylphosphonium cation.

Myocardial NADPH oxidase-4 regulates the physiological response to acute exercise.

Regular exercise has widespread health benefits. Fundamental to these beneficial effects is the ability of the heart to intermittently and substantially increase its performance without incurring damage, but the underlying homeostatic mechanisms are unclear. We identify the ROS-generating NADPH oxidase-4 (Nox4) as an essential regulator of exercise performance in mice.

Placental Adaptation to Early-Onset Hypoxic Pregnancy and Mitochondria-Targeted Antioxidant Therapy in a Rodent Model.

The placenta responds to adverse environmental conditions by adapting its capacity for substrate transfer to maintain fetal growth and development. Early-onset hypoxia effects on placental morphology and activation of the unfolded protein response (UPR) were determined using an established rat model in which fetal growth restriction is minimized. We further established whether maternal treatment with a mitochondria-targeted antioxidant (MitoQ) confers protection during hypoxic pregnancy.