Very different performance of the power Doppler modalities of several ultrasound machines ascertained by a microvessel flow phantom

Introduction

In many patients with rheumatoid arthritis (RA) subclinical disease activity can be detected with ultrasound (US), especially using power Doppler US (PDUS). However, PDUS may be highly dependent on the type of machine. This could create problems both in clinical trials and in daily clinical practice. To clarify how the PDUS signal differs between machines we created a microvessel flow phantom.

Methods

The flow phantom contained three microvessels (150, 1000, 2000 microns). A syringe pump was used to generate flows. Five US machines were used. Settings were optimised to assess the lowest detectable flow for each US machine.

Results

The minimal detectable flow velocities showed very large differences between the machines. Only two of the machines may be able to detect the very low flows in the capillaries of inflamed joints. There was no clear relation with price. One of the lower-end machines actually performed best in all three vessel sizes.

Conclusions

We created a flow phantom to test the sensitivity of US machines to very low flows in small vessels. The sensitivity of the power Doppler modalities of 5 different machines was very different. The differences found between the machines are probably caused by fundamental differences in processing of the PD signal or internal settings inaccessible to users. Machines considered for PDUS assessment of RA patients should be tested using a flow phantom similar to ours. Within studies, only a single machine type should be used.     

Separating Drought Effects from Roof Artifacts on Ecosystem Processes in a Grassland Drought Experiment

1

Given the predictions of increased drought probabilities under various climate change scenarios, there have been numerous experimental field studies simulating drought using transparent roofs in different ecosystems and regions. Such roofs may, however, have unknown side effects, called artifacts, on the measured variables potentially confounding the experimental results. A roofed control allows the quantification of potential artifacts, which is lacking in most experiments.

2

We conducted a drought experiment in experimental grasslands to study artifacts of transparent roofs and the resulting effects of artifacts on ecosystems relative to drought on three response variables (aboveground biomass, litter decomposition and plant metabolite profiles). We established three drought treatments, using (1) transparent roofs to exclude rainfall, (2) an unroofed control treatment receiving natural rainfall and (3) a roofed control, nested in the drought treatment but with rain water reapplied according to ambient conditions.

3

Roofs had a slight impact on air (+0.14°C during night) and soil temperatures (−0.45°C on warm days, +0.25°C on cold nights), while photosynthetically active radiation was decreased significantly (−16%). Aboveground plant community biomass was reduced in the drought treatment (−41%), but there was no significant difference between the roofed and unroofed control, i.e., there were no measurable roof artifact effects.

4

Compared to the unroofed control, litter decomposition was decreased significantly both in the drought treatment (−26%) and in the roofed control treatment (−18%), suggesting artifact effects of the transparent roofs. Moreover, aboveground metabolite profiles in the model plant species Medicago x varia were different from the unroofed control in both the drought and roofed control treatments, and roof artifact effects were of comparable magnitude as drought effects.

5

Our results stress the need for roofed control treatments when using transparent roofs for studying drought effects, because roofs can cause significant side effects.     

Metformin Protects Rat Hepatocytes against Bile Acid-Induced Apoptosis

Background

Metformin is used in the treatment of Diabetes Mellitus type II and improves liver function in patients with non-alcoholic fatty liver disease (NAFLD). Metformin activates AMP-activated protein kinase (AMPK), the cellular energy sensor that is sensitive to changes in the AMP/ATP-ratio. AMPK is an inhibitor of mammalian target of rapamycin (mTOR). Both AMPK and mTOR are able to modulate cell death.

Aim

To evaluate the effects of metformin on hepatocyte cell death.

Methods

Apoptotic cell death was induced in primary rat hepatocytes using either the bile acid glycochenodeoxycholic acid (GCDCA) or TNFα in combination with actinomycin D (actD). AMPK, mTOR and phosphoinositide-3 kinase (PI3K)/Akt were inhibited using pharmacological inhibitors. Apoptosis and necrosis were quantified by caspase activation, acridine orange staining and Sytox green staining respectively.

Results

Metformin dose-dependently reduces GCDCA-induced apoptosis, even when added 2 hours after GCDCA, without increasing necrotic cell death. Metformin does not protect against TNFα/ActD-induced apoptosis. The protective effect of metformin is dependent on an intact PI3-kinase/Akt pathway, but does not require AMPK/mTOR-signaling. Metformin does not inhibit NF-κB activation.

Conclusion

Metformin protects against bile acid-induced apoptosis and could be considered in the treatment of chronic liver diseases accompanied by inflammation.     

Using expert knowledge and modeling to define mangrove composition,functioning, and threats and estimate time frame for recovery

Mangroves are threatened worldwide, and their loss or degradation could impact functioning of the ecosystem. Our aim was to investigate three aspects of mangroves at a global scale: (1) their constituents (2) their indispensable ecological functions, and (3) the maintenance of their constituents and functions in degraded mangroves. We focused on answering two questions: “What is a mangrove ecosystem” and “How vulnerable are mangrove ecosystems to different impacts”? We invited 106 mangrove experts globally to participate in a survey based on the Delphi technique and provide inputs on the three aspects. The outputs from the Delphi technique for the third aspect, i.e. maintenance of constituents and functions were incorporated in a modeling approach to simulate the time frame for recovery. Presented here for the first time are the consensus definition of the mangrove ecosystem and the list of mangrove plant species. In this study, experts considered even monospecific (tree) stands to be a mangrove ecosystem as long as there was adequate tidal exchange, propagule dispersal, and faunal interactions. We provide a ranking of the important ecological functions, faunal groups, and impacts on mangroves. Degradation due to development was identified as having the largest impact on mangroves globally in terms of spatial scale, intensity, and time needed for restoration. The results indicate that mangroves are ecologically unique even though they may be species poor (from the vegetation perspective). The consensus list of mangrove species and the ranking of the mangrove ecological functions could be a useful tool for restoration and management of mangroves. While there is ample literature on the destruction of mangroves due to aquaculture in the past decade, this study clearly shows that more attention must go to avoiding and mitigating mangrove loss due to coastal development (such as building of roads, ports, or harbors).     

The Rise and Fall of HIV in High-Prevalence Countries: A Challenge for Mathematical Modeling

Several countries with generalized, high-prevalence HIV epidemics, mostly in sub-Saharan Africa, have experienced rapid declines in transmission. These HIV epidemics, often with rapid onsets, have generally been attributed to a combination of factors related to high-risk sexual behavior. The subsequent declines in these countries began prior to widespread therapy or implementation of any other major biomedical prevention. This change has been construed as evidence of behavior change, often on the basis of mathematical models, but direct evidence for behavior changes that would explain these declines is limited. Here, we look at the structure of current models and argue that the common “fixed risk per sexual contact" assumption favors the conclusion of substantial behavior changes. We argue that this assumption ignores reported non-linearities between exposure and risk. Taking this into account, we propose that some of the decline in HIV transmission may be part of the natural dynamics of the epidemic, and that several factors that have traditionally been ignored by modelers for lack of precise quantitative estimates may well hold the key to understanding epidemiologic trends.     

The influence of tibial component fixation techniques on resorption of supporting bone stock after total knee replacement

Periprosthetic bone resorption after tibial prosthesis implantation remains a concern for long-term fixation performance. The fixation techniques may inherently aggravate the "stress-shielding" effect of the implant, leading to weakened bone foundation. In this study, two cemented tibial fixation cases (fully cemented and hybrid cementing with cement applied under the tibial tray leaving the stem uncemented) and three cementless cases relying on bony ingrowth (no, partial and fully ingrown) were modelled using the finite element method with a strain-adaptive remodelling theory incorporated to predict the change in the bone apparent density after prosthesis implantation. When the models were loaded with physiological knee joint loads, the predicted patterns of bone resorption correlated well with reported densitometry results. The modelling results showed that the firm anchorage fixation formed between the prosthesis and the bone for the fully cemented and fully ingrown cases greatly increased the amount of proximal bone resorption. Bone resorption in tibial fixations with a less secure anchorage (hybrid cementing, partial and no ingrowth) occurred at almost half the rate of the changes around the fixations with a firm anchorage. The results suggested that the hybrid cementing fixation or the cementless fixation with partial bony ingrowth (into the porous-coated prosthesis surface) is preferred for preserving proximal tibial bone stock, which should help to maintain post-operative fixation stability. Specifically, the hybrid cementing fixation induced the least amount of bone resorption.     

Microalgal bacterial floc properties are improved by a balanced inorganic/organic carbon ratio

Microalgal bacterial floc (MaB‐floc) reactors have been suggested as a more sustainable secondary wastewater treatment. We investigated whether MaB‐flocs could be used as tertiary treatment. Tertiary influent has a high inorganic/organic carbon ratio, depending on the efficiency of the secondary treatment. In this study, the effect of this inorganic/organic carbon ratio on the MaB‐flocs performance was determined, using three sequencing batch photobioreactors. The MaB‐flocs were fed with synthetic wastewater containing 84, 42, and 0 mg L⁻¹ C‐KHCO₃ supplemented with 0, 42, 84 mg L⁻¹ C‐sucrose, respectively, representing inorganic versus organic carbon. Bicarbonate significantly decreased the autotrophic index of the MaB‐flocs and resulted in poorly settling flocs. Moreover, sole bicarbonate addition led to a high pH of 9.5 and significant lower nitrogen removal efficiencies. Sucrose without bicarbonate resulted in good settling MaB‐flocs, high nitrogen removal efficiencies and neutral pH levels. Despite the lower chlorophyll a content of the biomass and the lower in situ oxygen concentration, 92–96% of the soluble COD‐sucrose was removed. This study shows that the inorganic/organic carbon ratio of the wastewater is of major importance and that organic carbon is requisite to guarantee a good performance of the MaB‐flocs for wastewater treatment. Biotechnol. Bioeng. 2011; 108:549–558. © 2010 Wiley Periodicals, Inc.     

Influence of atmospheric modes of variability on the limnological characteristics of large lakes south of the Alps: a new emerging paradigm

Winter air and spring surface water temperatures, spring epilimnetic phosphorus, and hypolimnetic oxygen in the deep lakes south of the Alps (Garda, Iseo, Como, Lugano, and Maggiore) showed a high degree of temporal coherence. The common temporal patterns were originating from the effects caused by winter climate, and from corresponding synchronisms in the interannual variations in the extent of the spring water renewal and replenishment of nutrients. In turn, the sequence of linked causal events was triggered by two atmospheric modes of variability relevant for the Mediterranean region, i.e. the East Atlantic pattern (EA) and the Eastern Mediterranean Pattern (EMP). In contrast, there were no significant relationships of air and water temperatures with the North Atlantic Oscillation. In oligotrophic lakes, which were characterised by weak vertical nutrient gradients, the spring replenishment of P was negligible and difficult to detect (Maggiore), or detectable but of minor importance (Garda and Como) compared to that measured in more enriched lakes (Iseo and Lugano). The applicability of EA and EMP in the study of the impact of climate on aquatic ecosystems will require to be tested by expanding the number, typology, and geographical location of water bodies in the Alpine and Mediterranean regions.     

Structure of Transmembrane Domain of Lysosome-associated Membrane Protein Type 2a (LAMP-2A) Reveals Key Features for Substrate Specificity in Chaperone-mediated Autophagy

Chaperone-mediated autophagy (CMA) is a highly regulated cellular process that mediates the degradation of a selective subset of cytosolic proteins in lysosomes. Increasing CMA activity is one way for a cell to respond to stress, and it leads to enhanced turnover of non-critical cytosolic proteins into sources of energy or clearance of unwanted or damaged proteins from the cytosol. The lysosome-associated membrane protein type 2a (LAMP-2A) together with a complex of chaperones and co-chaperones are key regulators of CMA. LAMP-2A is a transmembrane protein component for protein translocation to the lysosome. Here we present a study of the structure and dynamics of the transmembrane domain of human LAMP-2A in n-dodecylphosphocholine micelles by nuclear magnetic resonance (NMR). We showed that LAMP-2A exists as a homotrimer in which the membrane-spanning helices wrap around each other to form a parallel coiled coil conformation, whereas its cytosolic tail is flexible and exposed to the cytosol. This cytosolic tail of LAMP-2A interacts with chaperone Hsc70 and a CMA substrate RNase A with comparable affinity but not with Hsp40 and RNase S peptide. Because the substrates and the chaperone complex can bind at the same time, thus creating a bimodal interaction, we propose that substrate recognition by chaperones and targeting to the lysosomal membrane by LAMP-2A are coupled. This can increase substrate affinity and specificity as well as prevent substrate aggregation, assist in the unfolding of the substrate, and promote the formation of the higher order complex of LAMP-2A required for translocation.