Burden of asymptomatic malaria among a tribal population in a forested village of central India: a hidden challenge for malaria control in India.

OBJECTIVE: Chhattisgarh in India is a malaria-endemic state with seven southern districts that contributes approximately 50-60% of the reported malaria cases in the state every year. The problem is further complicated due to asymptomatic malaria cases which are largely responsible for persistent transmission. This study was undertaken in one of the forested villages of the Keshkal subdistrict in Kondagaon district to ascertain the proportion of the population harbouring subclinical malarial infections. STUDY DESIGN: Community-based cross-sectional study. METHODS: Mass blood surveys were undertaken of the entire population of the village in the post-monsoon seasons of 2013 and 2014. Fingerprick blood smears were prepared from individuals of all ages to detect malaria infections in their blood. Individuals with fever at the time of the survey were tested with rapid diagnostic tests, and parasitaemia in thick blood smears was confirmed by microscopy. Malaria-positive cases were treated with anti-malarials in accordance with the national drug policy. RESULTS: Peripheral blood smears of 134 and 159 individuals, including children, were screened for malaria infection in 2013 and 2014, respectively. Overall, the malaria slide positivity rates were 27.6% and 27.7% in 2013 and 2014, respectively, and the prevalence rates of asymptomatic malaria were 20% and 22.8%. This study showed that, for two consecutive years, the prevalence of asymptomatic malaria infection was significantly higher among children aged ?14 years (34.4% and 34.1% for 2013 and 2014, respectively) compared with adults (15.2% and 18.2% for 2013 and 2014, respectively; P = 0.023 and 0.04, respectively). CONCLUSION: The number of asymptomatic malaria cases, especially Plasmodium falciparum, is significant, reinforcing the underlying challenge facing the malaria elimination programme in India

In situ characterisation of surface roughness and its amplification during multilayer single-track laser powder bed fusion additive manufacturing

Surface roughness controls the mechanical performance and durability (e.g., wear and corrosion resistance) of laser powder bed fusion (LPBF) components. The evolution mechanisms of surface roughness during LPBF are not well understood due to a lack of in situ characterisation methods. Here, we quantified key processes and defect dynamics using synchrotron X-ray imaging and ex situ optical imaging and explained the evolution mechanisms of side-skin and top-skin roughness during multi-layer LPBF of Ti-6Al-4V (where down-skin roughness was out of the project scope). We found that the average surface roughness alone is not an accurate representation of surface topology of an LPBF component and that the surface topology is multimodal (e.g., containing both roughness and waviness) and multiscale (e.g., from 25 µm sintered powder features to 250 µm molten pool wavelength). Both roughness and topology are significantly affected by the formation of pre-layer humping, spatter, and rippling defects. We developed a surface topology matrix that accurately describes surface features by combining 8 different metrics: average roughness, root mean square roughness, maximum profile peak height, maximum profile valley height, mean height, mean width, skewness, and melt pool size ratio. This matrix provides a guide to determine the appropriate linear energy density to achieve the optimum surface finish of Ti-6Al-4V thin-wall builds. This work lays a foundation for surface texture control which is critical for build design, metrology, and performance in LPBF

Eurasian Arctic greening reveals teleconnections and the potential for novel ecosystems

Arctic warming has been linked to observed increases in tundra shrub cover and growth in recent decades on the basis of significant relationships between deciduous shrub growth/biomass and temperature. These vegetation trends have been linked to Arctic sea ice decline and thus to the sea ice/albedo feedback known as Arctic amplification. However, the interactions between climate, sea ice and tundra vegetation remain poorly understood. Here we reveal a 50- year growth response over a >100,000 km2 area to a rise in summer temperature for alder (Alnus) and willow (Salix), the most abundant shrub genera respectively at and north of the continental treeline. We demonstrate that whereas plant productivity is related to sea ice in late spring, the growing season peak responds to persistent synoptic-scale air masses over West Siberia associated with Fennoscandian weather systems through the Rossby wave train. Substrate is important for biomass accumulation, yet a strong correlation between growth and temperature encompasses all observed soil types. Vegetation is especially responsive to temperature in early summer. These results have significant implications for modelling present and future Low Arctic vegetation responses to climate change, and emphasize the potential for structurally novel ecosystems to emerge fromwithin the tundra zone.Vertaisarviointia edeltävä käsikirjoitu

Littoral cell angioma of the spleen in a patient with previous pulmonary sarcoidosis: a TNF-α related pathogenesis?

<p>Abstract</p> <p>Background</p> <p>Littoral cell angioma (LCA) is a rare vascular tumor of the spleen. Generally thought to be benign, additional cases of LCA with malignant features have been described. Thus, its malignant potential seems to vary and must be considered uncertain. The etiology remains unclear, but an immune dysregulation for the apparent association with malignancies of visceral organs or immune-mediated diseases has been proposed.</p> <p>Case Presentation</p> <p>We report a case of LCA in a 43-year old male patient who presented with a loss of appetite and intermittent upper abdominal pain. Computed tomography showed multiple hypoattenuating splenic lesions which were hyperechogenic on abdominal ultrasound. Lymphoma was presumed and splenectomy was performed. Pathological evaluation revealed LCA.</p> <p>Conclusions</p> <p>LCA is a rare, primary vascular neoplasm of the spleen that might etiologically be associated with immune dysregulation. In addition, it shows a striking association with synchronous or prior malignancies. With about one-third of the reported cases to date being co-existent with malignancies of visceral organs or immune-mediated diseases, this advocates for close follow-ups in all patients diagnosed with LCA. To our knowledge, this report is the first one of LCA associated with previous pulmonary sarcoidosis and hypothesizes a TNF-α related pathogenesis of this splenic tumor.</p

Exploring the Conformational Transitions of Biomolecular Systems Using a Simple Two-State Anisotropic Network Model

Biomolecular conformational transitions are essential to biological functions. Most experimental methods report on the long-lived functional states of biomolecules, but information about the transition pathways between these stable states is generally scarce. Such transitions involve short-lived conformational states that are difficult to detect experimentally. For this reason, computational methods are needed to produce plausible hypothetical transition pathways that can then be probed experimentally. Here we propose a simple and computationally efficient method, called ANMPathway, for constructing a physically reasonable pathway between two endpoints of a conformational transition. We adopt a coarse-grained representation of the protein and construct a two-state potential by combining two elastic network models (ENMs) representative of the experimental structures resolved for the endpoints. The two-state potential has a cusp hypersurface in the configuration space where the energies from both the ENMs are equal. We first search for the minimum energy structure on the cusp hypersurface and then treat it as the transition state. The continuous pathway is subsequently constructed by following the steepest descent energy minimization trajectories starting from the transition state on each side of the cusp hypersurface. Application to several systems of broad biological interest such as adenylate kinase, ATP-driven calcium pump SERCA, leucine transporter and glutamate transporter shows that ANMPathway yields results in good agreement with those from other similar methods and with data obtained from all-atom molecular dynamics simulations, in support of the utility of this simple and efficient approach. Notably the method provides experimentally testable predictions, including the formation of non-native contacts during the transition which we were able to detect in two of the systems we studied. An open-access web server has been created to deliver ANMPathway results. © 2014 Das et al

Thermal modeling of lesion growth with radiofrequency ablation devices

BACKGROUND: Temperature is a frequently used parameter to describe the predicted size of lesions computed by computational models. In many cases, however, temperature correlates poorly with lesion size. Although many studies have been conducted to characterize the relationship between time-temperature exposure of tissue heating to cell damage, to date these relationships have not been employed in a finite element model. METHODS: We present an axisymmetric two-dimensional finite element model that calculates cell damage in tissues and compare lesion sizes using common tissue damage and iso-temperature contour definitions. The model accounts for both temperature-dependent changes in the electrical conductivity of tissue as well as tissue damage-dependent changes in local tissue perfusion. The data is validated using excised porcine liver tissues. RESULTS: The data demonstrate the size of thermal lesions is grossly overestimated when calculated using traditional temperature isocontours of 42°C and 47°C. The computational model results predicted lesion dimensions that were within 5% of the experimental measurements. CONCLUSION: When modeling radiofrequency ablation problems, temperature isotherms may not be representative of actual tissue damage patterns

Targeting KSHV/HHV-8 Latency with COX-2 Selective Inhibitor Nimesulide: A Potential Chemotherapeutic Modality for Primary Effusion Lymphoma

The significance of inflammation in KSHV biology and tumorigenesis prompted us to examine the role of COX-2 in primary effusion lymphoma (PEL), an aggressive AIDS-linked KSHV-associated non-Hodgkin's lymphoma (NHL) using nimesulide, a well-known COX-2 specific NSAID. We demonstrate that (1) nimesulide is efficacious in inducing proliferation arrest in PEL (KSHV+/EBV-; BCBL-1 and BC-3, KSHV+/EBV+; JSC-1), EBV-infected (KSHV-/EBV+; Raji) and non-infected (KSHV-/EBV-; Akata, Loukes, Ramos, BJAB) high malignancy human Burkitt's lymphoma (BL) as well as KSHV-/EBV+ lymphoblastoid (LCL) cell lines; (2) nimesulide is selectively toxic to KSHV infected endothelial cells (TIVE-LTC) compared to TIVE and primary endothelial cells (HMVEC-d); (3) nimesulide reduced KSHV latent gene expression, disrupted p53-LANA-1 protein complexes, and activated the p53/p21 tumor-suppressor pathway; (4) COX-2 inhibition down-regulated cell survival kinases (p-Akt and p-GSK-3β), an angiogenic factor (VEGF-C), PEL defining genes (syndecan-1, aquaporin-3, and vitamin-D3 receptor) and cell cycle proteins such as cyclins E/A and cdc25C; (5) nimesulide induced sustained cell death and G1 arrest in BCBL-1 cells; (6) nimesulide substantially reduced the colony forming capacity of BCBL-1 cells. Overall, our studies provide a comprehensive molecular framework linking COX-2 with PEL pathogenesis and identify the chemotherapeutic potential of nimesulide in treating PEL

Summer warming explains widespread but not uniform greening in the Arctic tundra biome

Arctic warming can influence tundra ecosystem function with consequences for climate feedbacks, wildlife and human communities. Yet ecological change across the Arctic tundra biome remains poorly quantified due to field measurement limitations and reliance on coarse-resolution satellite data. Here, we assess decadal changes in Arctic tundra greenness using time series from the 30 m resolution Landsat satellites. From 1985 to 2016 tundra greenness increased (greening) at ~37.3% of sampling sites and decreased (browning) at ~4.7% of sampling sites. Greening occurred most often at warm sampling sites with increased summer air temperature, soil temperature, and soil moisture, while browning occurred most often at cold sampling sites that cooled and dried. Tundra greenness was positively correlated with graminoid, shrub, and ecosystem productivity measured at field sites. Our results support the hypothesis that summer warming stimulated plant productivity across much, but not all, of the Arctic tundra biome during recent decades

Illumination of Parainfluenza Virus Infection and Transmission in Living Animals Reveals a Tissue-Specific Dichotomy

The parainfluenza viruses (PIVs) are highly contagious respiratory paramyxoviruses and a leading cause of lower respiratory tract (LRT) disease. Since no vaccines or antivirals exist, non-pharmaceutical interventions are the only means of control for these pathogens. Here we used bioluminescence imaging to visualize the spatial and temporal progression of murine PIV1 (Sendai virus) infection in living mice after intranasal inoculation or exposure by contact. A non-attenuated luciferase reporter virus (rSeV-luc(M-F*)) that expressed high levels of luciferase yet was phenotypically similar to wild-type Sendai virus in vitro and in vivo was generated to allow visualization. After direct intranasal inoculation, we unexpectedly observed that the upper respiratory tract (URT) and trachea supported robust infection under conditions that result in little infection or pathology in the lungs including a low inoculum of virus, an attenuated virus, and strains of mice genetically resistant to lung infection. The high permissivity of the URT and trachea to infection resulted in 100% transmission to naïve contact recipients, even after low-dose (70 PFU) inoculation of genetically resistant BALB/c donor mice. The timing of transmission was consistent with the timing of high viral titers in the URT and trachea of donor animals but was independent of the levels of infection in the lungs of donors. The data therefore reveals a disconnect between transmissibility, which is associated with infection in the URT, and pathogenesis, which arises from infection in the lungs and the immune response. Natural infection after transmission was universally robust in the URT and trachea yet limited in the lungs, inducing protective immunity without weight loss even in genetically susceptible 129/SvJ mice. Overall, these results reveal a dichotomy between PIV infection in the URT and trachea versus the lungs and define a new model for studies of pathogenesis, development of live virus vaccines, and testing of antiviral therapies