Is there an app for that? Mobile phones and secondary prevention of cardiovascular disease.

Purpose of review: Advances in technology coupled with increased penetration of mobile phones and smart devices are rapidly changing healthcare delivery. Mobile phone applications (‘apps’), text messages, and Internet platforms used alone or in combination are now providing interventions targeting people with multiple cardiovascular risk factors. The present article will review the emerging evidence regarding apps and discuss their potential role in providing secondary prevention interventions via mobile phones. Recent findings: Seven recent randomized controlled trials used text messages or apps for six to 12 months, with or without differing combinations of other technology platforms. All studies, involved cardiac and diabetes populations, and demonstrated at least one positive improvement to cardiovascular risk factor profiles. When measured, acceptability of the intervention was high. Summary: Mobile apps and technology can deliver positive outcomes in the management of cardiovascular risk factors. However, because of the complexity of combination interventions, it is difficult to determine the ‘active’ ingredient. A future challenge for researchers and clinicians will be to respond quickly to these rapidly evolving interventions in order to ensure the delivery of effective, evidence-based outcomes

The Dust Emissivity Spectral Index in the Starless Core TMC-1C

In this paper we present a dust emission map of the starless core TMC-1C taken at 2100 microns. Along with maps at 160, 450, 850 and 1200 microns, we study the dust emissivity spectral index from the (sub)millimeter spectral energy distribution, and find that it is close to the typically assumed value of beta = 2. We also map the dust temperature and column density in TMC-1C, and find that at the position of the dust peak (A_V ~ 50), the line-of-sight-averaged temperature is ~7 K. Employing simple Monte Carlo modeling, we show that the data are consistent with a constant value for the emissivity spectral index over the whole map of TMC-1C.Comment: 11 pages, including 5 pages of figures. Accepted to Ap

Gender differences in uptake, adherence and experiences: a longitudinal, mixed methods study of a physical activity referral scheme in Scotland, UK

Physical activity referral schemes (PARS) are implemented internationally to increase physical activity (PA) but evidence of effectiveness for population subgroups is equivocal. We examined gender differences for a Scottish PARS. This mixed-method, concurrent longitudinal study had equal status quantitative and qualitative components. We conducted 348 telephone interviews across three time points (pre-scheme, 12 and 52 weeks). These included validated self-reported PA and exercise self-efficacy measures, and open-ended questions about experiences. We recruited 136 participants, 120 completed 12-week and 92 completed 52-week interviews. PARS uptake was 83.8% (114/136) and 12-week adherence for those who started was 43.0% (49/114). Living in less deprived areas was associated with better uptake (p=0.021) and 12-week adherence (p=0.020), and with male uptake (p=0.024) in gender-stratified analysis. Female adherers significantly increased self-reported PA at 12 weeks (p=0.005) but not 52 weeks. Males significantly increased exercise self-efficacy between baseline and 52 weeks (p=0.009). Three qualitative themes and eight subthemes developed; gender perspectives, personal factors (health, social circumstances, transport and attendance benefits) and scheme factors (communication, social/staff support, individualisation and age appropriateness). Both genders valued the PARS. To increase uptake, adherence and PA, PARS should ensure timely, personalized communication, individualised, affordable PA and include mechanisms to re-engage those who disengage temporarily

The effect of Dnaaf5 gene dosage on primary ciliary dyskinesia phenotypes

DNAAF5 is a dynein motor assembly factor associated with the autosomal heterogenic recessive condition of motile cilia, primary ciliary dyskinesia (PCD). The effects of allele heterozygosity on motile cilia function are unknown. We used CRISPR-Cas9 genome editing in mice to recreate a human missense variant identified in patients with mild PCD and a second, frameshift-null deletion in Dnaaf5. Litters with Dnaaf5 heteroallelic variants showed distinct missense and null gene dosage effects. Homozygosity for the null Dnaaf5 alleles was embryonic lethal. Compound heterozygous animals with the missense and null alleles showed severe disease manifesting as hydrocephalus and early lethality. However, animals homozygous for the missense mutation had improved survival, with partially preserved cilia function and motor assembly observed by ultrastructure analysis. Notably, the same variant alleles exhibited divergent cilia function across different multiciliated tissues. Proteomic analysis of isolated airway cilia from mutant mice revealed reduction in some axonemal regulatory and structural proteins not previously reported in DNAAF5 variants. Transcriptional analysis of mouse and human mutant cells showed increased expression of genes coding for axonemal proteins. These findings suggest allele-specific and tissue-specific molecular requirements for cilia motor assembly that may affect disease phenotypes and clinical trajectory in motile ciliopathies

A method for probing the mutational landscape of amyloid structure

Motivation: Proteins of all kinds can self-assemble into highly ordered β-sheet aggregates known as amyloid fibrils, important both biologically and clinically. However, the specific molecular structure of a fibril can vary dramatically depending on sequence and environmental conditions, and mutations can drastically alter amyloid function and pathogenicity. Experimental structure determination has proven extremely difficult with only a handful of NMR-based models proposed, suggesting a need for computational methods. Results: We present AmyloidMutants, a statistical mechanics approach for de novo prediction and analysis of wild-type and mutant amyloid structures. Based on the premise of protein mutational landscapes, AmyloidMutants energetically quantifies the effects of sequence mutation on fibril conformation and stability. Tested on non-mutant, full-length amyloid structures with known chemical shift data, AmyloidMutants offers roughly 2-fold improvement in prediction accuracy over existing tools. Moreover, AmyloidMutants is the only method to predict complete super-secondary structures, enabling accurate discrimination of topologically dissimilar amyloid conformations that correspond to the same sequence locations. Applied to mutant prediction, AmyloidMutants identifies a global conformational switch between Aβ and its highly-toxic ‘Iowa’ mutant in agreement with a recent experimental model based on partial chemical shift data. Predictions on mutant, yeast-toxic strains of HET-s suggest similar alternate folds. When applied to HET-s and a HET-s mutant with core asparagines replaced by glutamines (both highly amyloidogenic chemically similar residues abundant in many amyloids), AmyloidMutants surprisingly predicts a greatly reduced capacity of the glutamine mutant to form amyloid. We confirm this finding by conducting mutagenesis experiments.National Institutes of Health (U.S.) (grant 1R01GM081871)National Institutes of Health (U.S.) (grant GM25874

Lactobacillus mucosae DPC 6426 as a bile-modifying and immunomodulatory microbe.

BACKGROUND: Lactobacillus mucosae DPC 6426 has previously demonstrated potentially cardio-protective properties, in the form of dyslipidaemia and hypercholesterolemia correction in an apolipoprotein-E deficient mouse model. This study aims to characterise the manner in which this microbe may modulate host bile pool composition and immune response, in the context of cardiovascular disease. Lactobacillus mucosae DPC 6426 was assessed for bile salt hydrolase activity and specificity. The microbe was compared against several other enteric strains of the same species, as well as a confirmed bile salt hydrolase-active strain, Lactobacillus reuteri APC 2587. RESULTS: Quantitative bile salt hydrolase assays revealed that enzymatic extracts from Lactobacillus reuteri APC 2587 and Lactobacillus mucosae DPC 6426 demonstrate the greatest activity in vitro. Bile acid profiling of porcine and murine bile following incubation with Lactobacillus mucosae DPC 6426 confirmed a preference for hydrolysis of glyco-conjugated bile acids. In addition, the purified exopolysaccharide and secretome of Lactobacillus mucosae DPC 6426 were investigated for immunomodulatory capabilities using RAW264.7 macrophages. Gene expression data revealed that both fractions stimulated increases in interleukin-6 and interleukin-10 gene transcription in the murine macrophages, while the entire secretome was necessary to increase CD206 transcription. Moreover, the exopolysaccharide elicited a dose-dependent increase in nitric oxide and interleukin-10 production from RAW264.7 macrophages, concurrent with increased tumour necrosis factor-α secretion at all doses. CONCLUSIONS: This study indicates that Lactobacillus mucosae DPC 6426 modulates both bile pool composition and immune system tone in a manner which may contribute significantly to the previously identified cardio-protective phenotype

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space. While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes, vast areas of the tropics remain understudied. In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity, but it remains among the least known forests in America and is often underrepresented in biodiversity databases. To worsen this situation, human-induced modifications may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge, it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Nectar palatability can selectively filter bird and insect visitors to coral tree flowers

Secondary compounds in nectar may play a decisive role in determining the spectrum of floral visitors on plants. Flowers of the African coral tree Erythrina caffra are visited mainly by generalist passerine nectarivores, such as weavers and bulbuls. As the nectar of this species tastes very bitter to humans, it was hypothesized that secondary compounds may repel sunbirds and honeybees which are common in the same habitats yet seldom consume the nectar. We conducted choice tests using fresh nectar and both sucrose and hexose (glucose/fructose) solutions of the same concentration as the nectar. Whitebellied Sunbirds (Cinnyris talatala) were repelled by nectar of both E. caffra and a related species Erythrina lysistemon, but Dark-capped Bulbuls (Pycnonotus tricolor) did not discriminate between the Erythrina nectar and control sugar solution in terms of amounts consumed. Honeybees (Apis mellifera scutellata) probed exposed droplets of E. caffra nectar and a control sugar solution at the same rate, suggesting that there is no volatile deterrent, but they immediately withdrew their proboscis far more often from the droplets of Erythrina nectar than they did from the sugar solution, suggesting that they find Erythrina nectar distasteful. These results contribute to a growing awareness that non-sugar components of nectar can play important functional roles in plant pollination systems.South African National Research Foundation (NRF)http://link.springer.com/journal/106822016-03-31hb201

Abordagens para Prevenção Secundária do Tromboembolismo Pulmonar (TEP): Uma Revisão de Literatura

This literature review aims to investigate contemporary strategies for the secondary prevention of Pulmonary Embolism (PE). The research encompassed recent studies, focusing on anticoagulation, including novel oral anticoagulants, surgical interventions, and advanced diagnostic methods. Emphasizing the importance of personalized treatment considering individual factors, the review underscores the need for additional studies to validate conclusions and inform more robust clinical guidelines. This review contributes to an in-depth understanding of secondary prevention strategies for PE, highlighting the integrated and personalized approach as crucial for optimizing clinical outcomes and reducing PE recurrence.Esta revisão de literatura explora estratégias contemporâneas para a prevenção secundária do Tromboembolismo Pulmonar (TEP). A pesquisa abrangeu estudos recentes, enfocando anticoagulação, incluindo novos anticoagulantes orais, intervenções cirúrgicas, e métodos de diagnóstico avançados. Destaca-se a importância da personalização do tratamento, considerando fatores individuais, enquanto ressalta a necessidade de estudos adicionais para validar conclusões e informar diretrizes clínicas mais sólidas. Esta revisão contribui para uma compreensão aprofundada das estratégias de prevenção secundária do TEP, enfatizando a abordagem integrada e personalizada como crucial para otimizar desfechos clínicos e reduzir recorrências do TEP

Affinity binding of antibodies to supermacroporous cryogel adsorbents with immobilized protein A for removal of anthrax toxin protective antigen

Polymeric cryogels are efficient carriers for the immobilization of biomolecules because of their unique macroporous structure, permeability, mechanical stability and different surface chemical functionalities. The aim of the study was to demonstrate the potential use of macroporous monolithic cryogels for biotoxin removal using anthrax toxin protective antigen (PA), the central cell-binding component of the anthrax exotoxins, and covalent immobilization of monoclonal antibodies. The affinity ligand (protein A) was chemically coupled to the reactive hydroxyl and epoxy-derivatized monolithic cryogels and the binding efficiencies of protein A, monoclonal antibodies to the cryogel column were determined. Our results show differences in the binding capacity of protein A as well as monoclonal antibodies to the cryogel adsorbents caused by ligand concentrations, physical properties and morphology of surface matrices. The cytotoxicity potential of the cryogels was determined by an in vitro viability assay using V79 lung fibroblast as a model cell and the results reveal that the cryogels are non-cytotoxic. Finally, the adsorptive capacities of PA from phosphate buffered saline (PBS) were evaluated towards a non-glycosylated, plant-derived human monoclonal antibody (PANG) and a glycosylated human monoclonal antibody (Valortim®), both of which were covalently attached via protein A immobilization. Optimal binding capacities of 108 and 117 mg/g of antibody to the adsorbent were observed for PANG attached poly(acrylamide-allyl glycidyl ether) [poly(AAm-AGE)] and Valortim® attached poly(AAm-AGE) cryogels, respectively, This indicated that glycosylation status of Valortim® antibody could significantly increase (8%) its binding capacity relative to the PANG antibody on poly(AAm-AGE)-protien-A column (p < 0.05). The amounts of PA which remained in the solution after passing PA spiked PBS through PANG or Valortim bound poly(AAm-AGE) cryogel were significantly (p < 0.05) decreased relative to the amount of PA remained in the solution after passing through unmodified as well as protein A modified poly(AAm-AGE) cryogel columns, indicates efficient PA removal from spiked PBS over 60 min of circulation. The high adsorption capacity towards anthrax toxin PA of the cryogel adsorbents indicated potential application of these materials for treatment of Bacillus anthracis infection