Heart failure self-care, factors influencing self-care and the relationship with health-related quality of life: A cross-sectional observational study.

Background:Self-care helps maintain health, prevents complications and improves the quality of life of patients living with heart failure (HF). Self-care is critical to HF management but has received limited attention in Nepal. Identification of the sociodemographic and clinical characteristics associated with self-care is crucial to tailoring appropriate self-care programs to improve health outcomes including patients' quality of life. Aims:The aims of this study were to describe self-care including the factors influencing self-care and the relationship between self-care and health-related quality of life in patients living with HF in Kathmandu, Nepal. Methods:We used a cross-sectional observational study design to measure self-care maintenance, self-care management, and self-care confidence using the Nepali Self-Care of Heart Failure Index. To analyze data, we used descriptive statistics, bivariate associations and regression modeling. Results:We recruited 221 patients with HF: mean age 57.5 ± 15.76 years, 62% male. The results in this sample indicated poor self-care maintenance (38.5 ± 11.56), management (45.7 ± 15.14), and confidence (40.9 ± 16.31). Patients with higher education were associated with higher self-care maintenance and management. Living alone and a better New York Heart Association functional classification for HF were related to higher self-care confidence. Higher social support was associated with better self-care. Self-care confidence was an independent predictor of self-care maintenance, management and health-related quality of life on adjusted analyses. Conclusion:Self-care was limited among patients living with HF in Nepal yet was associated with better quality of life. The study identified various sociodemographic and clinical factors related to self-care, which could be crucial while developing self-care interventions

New Insights on the Role of TRP Channels in Calcium Signalling and Immunomodulation: Review of Pathways and Implications for Clinical Practice

Calcium is the most abundant mineral in the human body and is central to many physiological processes, including immune system activation and maintenance. Studies continue to reveal the intricacies of calcium signalling within the immune system. Perhaps the most well-understood mechanism of calcium influx into cells is store-operated calcium entry (SOCE), which occurs via calcium release-activated channels (CRACs). SOCE is central to the activation of immune system cells; however, more recent studies have demonstrated the crucial role of other calcium channels, including transient receptor potential (TRP) channels. In this review, we describe the expression and function of TRP channels within the immune system and outline associations with murine models of disease and human conditions. Therefore, highlighting the importance of TRP channels in disease and reviewing potential. The TRP channel family is significant, and its members have a continually growing number of cellular processes. Within the immune system, TRP channels are involved in a diverse range of functions including T and B cell receptor signalling and activation, antigen presentation by dendritic cells, neutrophil and macrophage bactericidal activity, and mast cell degranulation. Not surprisingly, these channels have been linked to many pathological conditions such as inflammatory bowel disease, chronic fatigue syndrome and myalgic encephalomyelitis, atherosclerosis, hypertension and atopy

Medication Adherence Interventions for Cardiovascular Disease in Low- and Middle-Income Countries: A Systematic Review.

Purpose: The burden of cardiovascular diseases (CVD) is high in low- and middle-income countries (LMICs). Medications are integral to the management and control of CVD; however, suboptimal adherence impacts health outcomes. This systematic review aims to critically examine interventions targeted at improving medication adherence among persons with CVD in LMICs. Methods: In this systematic review, we searched online databases PubMed, Embase, and CINAHL for studies that evaluated a medication adherence intervention for CVD, reported adherence as an outcome measure, were conducted in LMICs and reported the strategy or tool used to measure adherence. We included articles published in English, available in full text, peer-reviewed, and published between 2010 and 2020. Results: We included 45 articles in this review. The majority of the studies implemented counseling and educational interventions led by nurses, pharmacists, or community health workers. Many of the studies delivered medication-taking reminders in the form of phone calls, text messages, short message services (SMS), and in-phone calendars. Multi-component interventions were more effective than unifocal interventions. Interventions involving technology, such as mobile phone calls, electronic pillboxes, and interactive phone SMS reminders, were more effective than generic reminders. The outcomes reported in the studies varied based on the complexity and combination of strategies. When interventions were implemented at both the patient level, such as reminders, and at the provider level, such as team-based care, the effect on medication adherence was larger. Conclusion: In LMICs, medication adherence interventions among persons with CVD included a combination of patient education, reminders, fixed-dose combination therapy and team-based care approach were generally more effective than singular interventions. Among patients who had CVD, the medication adherence interventions were found to be moderately effective. Future studies focusing on improving medication adherence in LMICs should consider non-physician-led interventions and appropriately adapt the interventions to the local context

Signal intensity enhancement of laser ablated volume holograms

Conventional volume holographic gratings (VHGs) fabricated in photosensitive emulsions such as gelatin containing silver salts enable the facile visualisation of the holographic image in ambient lighting. However, for the fabrication of holographic sensors, which require more defined and chemically-functionalised polymer matrices, laser ablation has been introduced to create the VHGs and thereby broaden their applications, although the replay signal can be challenging to detect in ambient lighting. When traditional photochemical bleaching solutions used to reduce light scattering and modulate refractive index within the VHG are applied to laser ablated volume holographic gratings, these procedures decrease the holographic peak intensity. This is postulated to occur because both light and dark fringes contain a proportion of metal particles, which upon solubilisation are converted immediately to silver iodide, yielding no net refractive index modulation. This research advances a hypothesis that the reduced intensity of holographic replay signals is linked to a gradient of different sized metal particles within the emulsion, which reduces the holographic signal and may explain why traditional bleaching processes result in a reduction in intensity. In this report, a novel experimental protocol is provided, along with simulations based on an effective medium periodic 1D stack, that offers a solution to increase peak signal intensity of holographic sensors by greater than 200%. Nitric acid is used to etch the silver nanoparticles within the polymer matrix and is thought to remove the smaller particles to generate more defined metal fringes containing a soluble metal salt. Once the grating efficiency has been increased, this salt can be converted to a silver halide, to modulate the refractive index and increase the intensity of the holographic signal. This new protocol has been tested in a range of polymer chemistries; those containing functional groups that help to stabilise the metal nanoparticles within the matrix yield more intense holographic signals as the integrity of the fringe is more protected with increasing metal solubility.EPSRC Integrated Photonics and Electronic Systems (Grant number: EP/L015455/1) Centre for Doctoral Training

Extracellular histones are a target in myocardial ischaemia reperfusion injury.

Acute myocardial infarction causes lethal cardiomyocyte injury during ischaemia and reperfusion (I/R). Histones have been described as important Danger Associated Molecular Proteins (DAMPs) in sepsis. Aims The objective of this study was to establish whether extracellular histone release contributes to myocardial infarction. Methods and results Isolated, perfused rat hearts were subject to I/R. Nucleosomes and histone H4 release was detected early during reperfusion. Sodium-β-O-Methyl cellobioside sulfate (mCBS), a newly developed histone-neutralising compound, significantly reduced infarct size whilst also reducing the detectable levels of histones. Histones were directly toxic to primary adult rat cardiomyocytes in vitro. This was prevented by mCBS, or HIPe, a recently described, histone-H4 neutralizing peptide, but not by an inhibitor of TLR4, a receptor previously reported to be involved in DAMP-mediated cytotoxicity. Furthermore, TLR4-reporter HEK293 cells revealed that cytotoxicity of histone H4 was independent of TLR4 and NF-κB. In an in vivo rat model of I/R, HIPe significantly reduced infarct size. Conclusion Histones released from the myocardium are cytotoxic to cardiomyocytes, via a TLR4-independent mechanism. The targeting of extracellular histones provides a novel opportunity to limit cardiomyocyte death during I/R injury of the myocardium. Translational perspective Acute myocardial infarction causes lethal cardiomyocyte injury during ischaemia and reperfusion (I/R). New approaches are needed to prevent cardiomyocyte injury and limit final infarct size. We show that histones released from damaged cells, and histone-H4 in particular, causes rapid cardiomyocyte death during I/R. mCBS, a compounds targeting histones non-specifically, was cardioprotective in ex vivo rat hearts, while HIPe, a targeting histone H4 specifically, was cardioprotective in an in vivo rat model. HIPe may have potential as a therapeutic agent in the setting of acute myocardial infarction

Caterpillars and fungal pathogens: two co-occurring parasites of an ant-plant mutualism

In mutualisms, each interacting species obtains resources from its partner that it would obtain less efficiently if alone, and so derives a net fitness benefit. In exchange for shelter (domatia) and food, mutualistic plant-ants protect their host myrmecophytes from herbivores, encroaching vines and fungal pathogens. Although selective filters enable myrmecophytes to host those ant species most favorable to their fitness, some insects can by-pass these filters, exploiting the rewards supplied whilst providing nothing in return. This is the case in French Guiana for Cecropia obtusa (Cecropiaceae) as Pseudocabima guianalis caterpillars (Lepidoptera, Pyralidae) can colonize saplings before the installation of their mutualistic Azteca ants. The caterpillars shelter in the domatia and feed on food bodies (FBs) whose production increases as a result. They delay colonization by ants by weaving a silk shield above the youngest trichilium, where the FBs are produced, blocking access to them. This probable temporal priority effect also allows female moths to lay new eggs on trees that already shelter caterpillars, and so to occupy the niche longer and exploit Cecropia resources before colonization by ants. However, once incipient ant colonies are able to develop, they prevent further colonization by the caterpillars. Although no higher herbivory rates were noted, these caterpillars are ineffective in protecting their host trees from a pathogenic fungus, Fusarium moniliforme (Deuteromycetes), that develops on the trichilium in the absence of mutualistic ants. Therefore, the Cecropia treelets can be parasitized by two often overlooked species: the caterpillars that shelter in the domatia and feed on FBs, delaying colonization by mutualistic ants, and the fungal pathogen that develops on old trichilia. The cost of greater FB production plus the presence of the pathogenic fungus likely affect tree growth

Transphyletic conservation of developmental regulatory state in animal evolution

Specific regulatory states, i.e., sets of expressed transcription factors, define the gene expression capabilities of cells in animal development. Here we explore the functional significance of an unprecedented example of regulatory state conservation from the cnidarian Nematostella to Drosophila, sea urchin, fish, and mammals. Our probe is a deeply conserved cis-regulatory DNA module of the SRY-box B2 (soxB2), recognizable at the sequence level across many phyla. Transphyletic cis-regulatory DNA transfer experiments reveal that the plesiomorphic control function of this module may have been to respond to a regulatory state associated with neuronal differentiation. By introducing expression constructs driven by this module from any phyletic source into the genomes of diverse developing animals, we discover that the regulatory state to which it responds is used at different levels of the neurogenic developmental process, including patterning and development of the vertebrate forebrain and neurogenesis in the Drosophila optic lobe and brain. The regulatory state recognized by the conserved DNA sequence may have been redeployed to different levels of the developmental regulatory program during evolution of complex central nervous systems

How large should whales be?

The evolution and distribution of species body sizes for terrestrial mammals is well-explained by a macroevolutionary tradeoff between short-term selective advantages and long-term extinction risks from increased species body size, unfolding above the 2g minimum size induced by thermoregulation in air. Here, we consider whether this same tradeoff, formalized as a constrained convection-reaction-diffusion system, can also explain the sizes of fully aquatic mammals, which have not previously been considered. By replacing the terrestrial minimum with a pelagic one, at roughly 7000g, the terrestrial mammal tradeoff model accurately predicts, with no tunable parameters, the observed body masses of all extant cetacean species, including the 175,000,000g Blue Whale. This strong agreement between theory and data suggests that a universal macroevolutionary tradeoff governs body size evolution for all mammals, regardless of their habitat. The dramatic sizes of cetaceans can thus be attributed mainly to the increased convective heat loss is water, which shifts the species size distribution upward and pushes its right tail into ranges inaccessible to terrestrial mammals. Under this macroevolutionary tradeoff, the largest expected species occurs where the rate at which smaller-bodied species move up into large-bodied niches approximately equals the rate at which extinction removes them.Comment: 7 pages, 3 figures, 2 data table