Prolongation of atrio-ventricular node conduction in a rabbit model of ischaemic cardiomyopathy: Role of fibrosis and connexin remodelling

Conduction abnormalities are frequently associated with cardiac disease, though the mechanisms underlying the commonly associated increases in PQ interval are not known. This study uses a chronic left ventricular (LV) apex myocardial infarction (MI) model in the rabbit to create significant left ventricular dysfunction (LVD) 8weeks post-MI. In vivo studies established that PQ interval increases by approximately 7ms (10%) with no significant change in average heart rate. Optical mapping of isolated Langendorff perfused rabbit hearts recapitulated this result; time to earliest activation of the LV was increased by 14ms (16%) in the LVD group. Intra-atrial and LV transmural conduction times were not altered in the LVD group. Isolated AVN preparations from the LVD group demonstrated a significantly longer conduction time (by approximately 20ms) between atrial and His electrograms than sham controls across a range of pacing cycle lengths. This difference was accompanied by increased effective refractory period and Wenckebach cycle length, suggesting significantly altered AVN electrophysiology post-MI. The AVN origin of abnormality was further highlighted by optical mapping of the isolated AVN. Immunohistochemistry of AVN preparations revealed increased fibrosis and gap junction proteins (connexin43 and 40) remodelling in the AVN of LVD animals compared to sham. A significant increase in myocyte-non-myocyte connexin co-localization was also observed after LVD. These changes may increase the electrotonic load experienced by AVN muscle cells and contribute to slowed conduction velocity within the AVN

The influence of feeding behaviour and temperature on the capacity of mosquitoes to transmit malaria

Insecticide-treated bed nets reduce malaria transmission by limiting contact between mosquito vectors and human hosts when mosquitoes feed during the night. However, malaria vectors can also feed in the early evening and in the morning when people are not protected. Here, we explored how the timing of blood feeding interacts with environmental temperature to influence the capacity of Anopheles mosquitoes to transmit the human malaria parasite Plasmodium falciparum. In laboratory experiments, we found no effect of biting time itself on the proportion of mosquitoes that became infectious (vector competence) at constant temperature. However, when mosquitoes were maintained under more realistic fluctuating temperatures, there was a significant increase in competence for mosquitoes feeding in the evening (18:00), and a significant reduction in competence for those feeding in the morning (06:00), relative to those feeding at midnight (00:00). These effects appear to be due to thermal sensitivity of malaria parasites during the initial stages of parasite development within the mosquito, and the fact that mosquitoes feeding in the evening experience cooling temperatures during the night, whereas mosquitoes feeding in the morning quickly experience warming temperatures that are inhibitory to parasite establishment. A transmission dynamics model illustrates that such differences in competence could have important implications for malaria prevalence, the extent of transmission that persists in the presence of bed nets, and the epidemiological impact of behavioural resistance. These results indicate that the interaction of temperature and feeding behaviour could be a major ecological determinant of the vectorial capacity of malaria mosquitoes

Towards cot-side mapping of the sensorimotor cortex in preterm and term infants with wearable high-density diffuse optical tomography

We are translating wearable HD-DOT to the neonatal clinic to investigate healthy and brain-injured infants and establish a model of the developmental trajectory of the infant sensorimotor system

HAM-5 functions as a MAP kinase scaffold during cell fusion in Neurospora crassa.

Cell fusion in genetically identical Neurospora crassa germlings and in hyphae is a highly regulated process involving the activation of a conserved MAP kinase cascade that includes NRC-1, MEK-2 and MAK-2. During chemotrophic growth in germlings, the MAP kinase cascade members localize to conidial anastomosis tube (CAT) tips every ∼8 minutes, perfectly out of phase with another protein that is recruited to the tip: SOFT, a recently identified scaffold for the MAK-1 MAP kinase pathway in Sordaria macrospora. How the MAK-2 oscillation process is initiated, maintained and what proteins regulate the MAP kinase cascade is currently unclear. A global phosphoproteomics approach using an allele of mak-2 (mak-2Q100G) that can be specifically inhibited by the ATP analog 1NM-PP1 was utilized to identify MAK-2 kinase targets in germlings that were potentially involved in this process. One such putative target was HAM-5, a protein of unknown biochemical function. Previously, Δham-5 mutants were shown to be deficient for hyphal fusion. Here we show that HAM-5-GFP co-localized with NRC-1, MEK-2 and MAK-2 and oscillated with identical dynamics from the cytoplasm to CAT tips during chemotropic interactions. In the Δmak-2 strain, HAM-5-GFP localized to punctate complexes that did not oscillate, but still localized to the germling tip, suggesting that MAK-2 activity influences HAM-5 function/localization. However, MAK-2-GFP showed cytoplasmic and nuclear localization in a Δham-5 strain and did not localize to puncta. Via co-immunoprecipitation experiments, HAM-5 was shown to physically interact with NRC-1, MEK-2 and MAK-2, suggesting that it functions as a scaffold/transport hub for the MAP kinase cascade members for oscillation and chemotropic interactions during germling and hyphal fusion in N. crassa. The identification of HAM-5 as a scaffold-like protein will help to link the activation of MAK-2 cascade to upstream factors and proteins involved in this intriguing process of fungal communication

Malaria control in Bhutan: case study of a country embarking on elimination

<p>Abstract</p> <p>Background</p> <p>Bhutan has achieved a major reduction in malaria incidence amid multiple challenges. This case study seeks to characterize the Bhutan malaria control programme over the last 10 years.</p> <p>Methods</p> <p>A review of the malaria epidemiology, control strategies, and elimination strategies employed in Bhutan was carried out through a literature review of peer-reviewed and grey national and international literature with the addition of reviewing the surveillance and vector control records of the Bhutan Vector-Borne Disease Control Programme (VDCP). Data triangulation was used to identify trends in epidemiology and key strategies and interventions through analysis of the VDCP surveillance and programme records and the literature review. Enabling and challenging factors were identified through analysis of socio-economic and health indicators, corroborated through a review of national and international reports and peer-review articles.</p> <p>Findings</p> <p>Confirmed malaria cases in Bhutan declined by 98.7% from 1994 to 2010. The majority of indigenous cases were due to <it>Plasmodium vivax </it>(59.9%) and adult males are most at-risk of malaria. Imported cases, or those in foreign nationals, varied over the years, reaching 21.8% of all confirmed cases in 2006.</p> <p>Strategies implemented by the VDCP are likely to be related to the decline in cases over the last 10 years. Access to malaria diagnosis in treatment was expanded throughout the country and evidence-based case management, including the introduction of artemisinin-based combination therapy (ACT) for <it>P. falciparum</it>, increasing coverage of high risk areas with Indoor Residual Spraying, insecticide-treated bed nets, and long-lasting insecticidal nets are likely to have contributed to the decline alongside enabling factors such as economic development and increasing access to health services.</p> <p>Conclusion</p> <p>Bhutan has made significant strides towards elimination and has adopted a goal of national elimination. A major challenge in the future will be prevention and management of imported malaria infections from neighbouring Indian states. Bhutan plans to implement screening at border points to prevent importation of malaria and to targeted prevention and surveillance efforts towards at-risk Bhutanese and migrant workers in construction sites.</p

Impacts of household sources on air pollution at village and regional scales in India

Approximately 3 billion people worldwide cook with solid fuels, such as wood, charcoal, and agricultural residues. These fuels, also used for residential heating, are often combusted in inefficient devices, producing carbonaceous emissions. Between 2.6 and 3.8 million premature deaths occur as a result of exposure to fine particulate matter from the resulting household air pollution (Health Effects Institute, 2018a; World Health Organization, 2018). Household air pollution also contributes to ambient air pollution; the magnitude of this contribution is uncertain. Here, we simulate the distribution of the two major health-damaging outdoor air pollutants (PM2:5 and O3) using state-of-thescience emissions databases and atmospheric chemical transport models to estimate the impact of household combustion on ambient air quality in India. The present study focuses on New Delhi and the SOMAARTH Demographic, Development, and Environmental Surveillance Site (DDESS) in the Palwal District of Haryana, located about 80 km south of New Delhi. The DDESS covers an approximate population of 200 000 within 52 villages. The emissions inventory used in the present study was prepared based on a national inventory in India (Sharma et al., 2015, 2016), an updated residential sector inventory prepared at the University of Illinois, updated cookstove emissions factors from Fleming et al. (2018b), and PM2:5 speciation from cooking fires from Jayarathne et al. (2018). Simulation of regional air quality was carried out using the US Environmental Protection Agency Community Multiscale Air Quality modeling system (CMAQ) in conjunction with the Weather Research and Forecasting modeling system (WRF) to simulate the meteorological inputs for CMAQ, and the global chemical transport model GEOS-Chem to generate concentrations on the boundary of the computational domain. Comparisons between observed and simulated O3 and PM2:5 levels are carried out to assess overall airborne levels and to estimate the contribution of household cooking emissions

Evaluating a new generation of wearable high-density diffuse optical tomography (HD-DOT) technology via retinotopic mapping in the adult brain

We investigated the performance of a novel HD-DOT system by replicating a series of classic visual stimulation paradigms. Haemodynamic response functions and cortical activation maps replicated the results obtained with larger fibre-based systems

Evaluating a new generation of wearable high-density diffuse optical tomography (HD-DOT) technology via retinotopic mapping in the adult brain

We investigated the performance of a novel HD-DOT system by replicating a series of classic visual stimulation paradigms. Haemodynamic response functions and cortical activation maps replicated the results obtained with larger fibre-based systems

Effects of Tip Clearance on Stall Inception in a Multistage Compressor

Rotor tip clearance height and the associated tip leakage flow have a significant effect on the performance and stability of compressors. Existing studies considering tip clearance effects on stability have been primarily limited to low-speed compressors, and many of these evaluated single-stage machines, which may not adequately represent stall trends for engine-scale compressors. Furthermore, test campaigns for engine-scale compressors cannot provide instrumentation accessibility required for detailed stage performance and stall investigations. Using results collected from a three-stage intermediate-speed axial compressor with appreciable density rise, this study addresses these needs. In this paper, three rotor tip clearances are tested, ranging from 1.5 to 4% span (1 to 3% chord). Previous studies have primarily shown a transition from short-length-scale spikes to long-length-scale modes as the clearance is increased, whereas the present study shows the opposite: a transition from modes to spikes with increased tip clearance. As a result, these data emphasize that a definitive trend does not exist between the stall inception mechanism and increasing tip clearance. Instead, the clearance effects alter stage matching with speed and change the stall inception mechanism. These results also elicit future research by preliminarily suggesting that stall inception mechanisms may be predictable from steady performance measurements collected in the stalling stage. Read More: https://arc.aiaa.org/doi/10.2514/1.B36364This material is based upon work supported by NASA under the ROA-2010 NRA of the Subsonic Fixed Wing project, with Technical Monitor Mark Celestina, and in part by the National Science Foundation Graduate Research Fellowship Program under grant DGE-1333468

ANIMATE: Wearable, flexible, and ultra-lightweight high-density diffuse optical tomography technologies for functional neuroimaging of newborns

We have developed a series of wearable high-density diffuse optical tomography (HD-DOT) technologies specifically for neonatal applications. These systems provide an ultra-lightweight form factor, a low profile and high mechanical flexibility. This new technology is validated using a novel, anatomically accurate dynamic phantom