The Impact of a Line Probe Assay Based Diagnostic Algorithm on Time to Treatment Initiation and Treatment Outcomes for Multidrug Resistant TB Patients in Arkhangelsk Region,Russia

BackgroundIn the Arkhangelsk region of Northern Russia, multidrug-resistant (MDR) tuberculosis (TB) rates in new cases are amongst the highest in the world. In 2014, MDR-TB rates reached 31.7% among new cases and 56.9% among retreatment cases. The development of new diagnostic tools allows for faster detection of both TB and MDR-TB and should lead to reduced transmission by earlier initiation of anti-TB therapy.MethodsA culture-based diagnostic algorithm used prior to LPA implementation was compared to an LPA-based algorithm that replaced BacTAlert and Löwenstein Jensen (LJ) for drug sensitivity testing. A total of 295 MDR-TB patients were included in the study, 163 diagnosed with the culture-based algorithm, 132 with the LPA-based algorithm.ResultsAmong smear positive patients, the implementation of the LPA-based algorithm was associated with a median decrease in time to MDR-TB treatment initiation of 50 and 66 days compared to the culture-based algorithm (BacTAlert and LJ respectively, p<0.001). In smear negative patients, the LPA-based algorithm was associated with a median decrease in time to MDR-TB treatment initiation of 78 days when compared to the culture-based algorithm (LJ, p<0.001). However, several weeks were still needed for treatment initiation in LPA-based algorithm, 24 days in smear positive, and 62 days in smear negative patients. Overall treatment outcomes were better in LPA-based algorithm compared to culture-based algorithm (p = 0.003). Treatment success rates at 20 months of treatment were higher in patients diagnosed with the LPA-based algorithm (65.2%) as compared to those diagnosed with the culture-based algorithm (44.8%). Mortality was also lower in the LPA-based algorithm group (7.6%) compared to the culture-based algorithm group (15.9%). There was no statistically significant difference in smear and culture conversion rates between the two algorithms.ConclusionThe results of the study suggest that the introduction of LPA leads to faster time to MDR diagnosis and earlier treatment initiation as well as better treatment outcomes for patients with MDR-TB. These findings also highlight the need for further improvements within the health system to reduce both patient and diagnostic delays to truly optimize the impact of new, rapid diagnostics.     

Influence of Obesity and Metabolic Disease on Carotid Atherosclerosis in Patients with Coronary Artery Disease (CordioPrev Study)

BackgroundRecent data suggest that the presence of associated metabolic abnormalities may be important modifiers of the association of obesity with a poorer prognosis in coronary heart disease. We determined the influence of isolated overweight and obesity on carotid intima media thickness (IMT-CC), and also assessed whether this influence was determined by the presence of metabolic abnormalities.Methods1002 participants from the CordioPrev study were studied at entry. We determined their metabolic phenotypes and performed carotid ultrasound assessment. We evaluated the influence of obesity, overweight and metabolic phenotypes on the IMT-CC.ResultsMetabolically sick participants (defined by the presence of two or more metabolic abnormalities) showed a greater IMT-CC than metabolically healthy individuals (p = 4 * 10⁻⁶). Overweight and normal weight patients who were metabolically healthy showed a lower IMT-CC than the metabolically abnormal groups (all p<0.05). When we evaluated only body weight (without considering metabolic phenotypes), overweight or obese patients did not differ significantly from normal-weight patients in their IMT-CC (p = 0.077). However, obesity was a determinant of IMT-CC when compared to the composite group of normal weight and overweight patients (all not obese).ConclusionsIn coronary patients, a metabolically abnormal phenotype is associated with a greater IMT-CC, and may be linked to a higher risk of suffering new cardiovascular events. The protection conferred in the IMT-CC by the absence of metabolic abnormality may be blunted by the presence of obesity.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00924937","term_id":"NCT00924937"}}NCT00924937     

Transgenic mice recapitulate the phenotypic heterogeneity of genetic prion diseases without developing prion infectivity: Role of intracellular PrP retention in neurotoxicity

Genetic prion diseases are degenerative brain disorders caused by mutations in the gene encoding the prion protein (PrP). Different PrP mutations cause different diseases, including Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker (GSS) syndrome and fatal familial insomnia (FFI). The reason for this variability is not known. It has been suggested that prion strains with unique self-replicating and neurotoxic properties emerge spontaneously in individuals carrying PrP mutations, dictating the phenotypic expression of disease. We generated transgenic mice expressing the FFI mutation, and found that they developed a fatal neurological illness highly reminiscent of FFI, and different from those of similarly generated mice modeling genetic CJD and GSS. Thus transgenic mice recapitulate the phenotypic differences seen in humans. The mutant PrPs expressed in these mice are misfolded but unable to self-replicate. They accumulate in different compartments of the neuronal secretory pathway, impairing the membrane delivery of ion channels essential for neuronal function. Our results indicate that conversion of mutant PrP into an infectious isoform is not required for pathogenesis, and suggest that the phenotypic variability may be due to different effects of mutant PrP on intracellular transport.     

Estimation of the diversity between DNA calorimetric profiles,differential melting curves and corresponding melting temperatures

The Poland–Fixman–Freire formalism was adapted for modeling of calorimetric DNA melting profiles, and applied to plasmid pBR 322 and long random sequences. We studied the influence of the difference (H_GC?H_AT) between the helix‐coil transition enthalpies of AT and GC base pairs on the calorimetric melting profile and on normalized calorimetric melting profile. A strong alteration of DNA calorimetrical profile with H_GC?H_AT was demonstrated. In contrast, there is a relatively slight change in the normalized profiles and in corresponding ordinary (optical) normalized differential melting curves (DMCs). For fixed H_GC?H_AT, the average relative deviation (S) between DMC and normalized calorimetric profile, and the difference between their melting temperatures (T_cal?T_m) are weakly dependent on peculiarities of the multipeak fine structure of DMCs. At the same time, both the deviation S and difference (T_cal?T_m) enlarge with the temperature melting range of the helix‐coil transition. It is shown that the local deviation between DMC and normalized calorimetric profile increases in regions of narrow peaks distant from the melting temperature.     

Novel materials based on DNA‐CTMA and lanthanide (Ce3+, Pr3+)

New, deoxyribonucleic acid (DNA) based compounds, functionalized with hexadecyltrimethylammonium chloride (CTMA) and lanthanide hydroxide nanoparticles were synthesized. The spectral measurements suggest that between the DNA‐CTMA complex and the lanthanide (III) ions a chemical interaction takes place. The obtained materials exhibit an improved fluorescence efficiency, showing a potential interest for application in photonics, and more particularly, in light emitting devices. © 2016 Wiley Periodicals, Inc. Biopolymers 105: 613–617, 2016.     

Decaying in different clays: implications for soft‐tissue preservation

Lagerstätten, places where soft‐bodied organisms became mineralized, provide a substantial bulk of palaeobiological information, but the detailed mechanisms of how soft‐tissue preservation takes place remain debatable. An experimental taphonomy approach, which allows for direct study of decay and mineralization, offers a means to study the preservational potential of different soft‐bodied organisms under controlled conditions. Here we compare the preservational capacity of two types of clay (kaolinite and montmorillonite) through a long‐term (24 month) experiment involving the burial and decay of small crustaceans. Our experimental design is innovative in that it models catastrophic sedimentation in fine‐grained colloidal suspension, which is believed to form Lagerstätten deposits. We demonstrated better preservation of buried organisms in clays compared to water, and in kaolinite compared to montmorillonite. As aluminium cations were present in high concentrations in kaolinite sediment but not in montmorillonite, the better preservation in kaolinite is attributed to the tanning properties of aluminium, which catalyses cross‐linking in proteins, protecting them from bacterial degradation. Anaerobic environments and acidification also slow down decay, but they are less effective than tanning. Kaolinite and montmorillonite replaced the crustacean integuments differently: in the remains buried in kaolinite, Al and Si were detected in equal proportions, while in those buried in montmorillonite, the Si content appeared to be much higher even in comparison with the initial sample of the clay. These variations probably arose from the different dynamics of acidic hydrolysis in the two clays associated with anaerobic decomposition of organic matter. Our results show that the preservation mechanism includes multi‐component interactions between the solution, mineral, sediment and organic remains; taken separately, any single component explains little. The specific conditions that occur within the colloidal clay sediments can facilitate conservation and start fast mineralization according to chemical properties and elemental content.     

Transcriptional profiling of epigenetic regulators in somatic embryos during temperature induced formation of an epigenetic memory in Norway spruce

Planta - A significant number of epigenetic regulators were differentially expressed during embryogenesis at different epitype-inducing conditions. Our results support that methylation of DNA and...     

Microhabitat preference of sympatric Hydraena Kugelann, 1794 species (Coleoptera: Hydraenidae) in a low-order forest stream

Aim of this study was to investigate the presence and distribution of Hydraenidae in relation to selected abiotic parameters in a single, uniform riffle of the Caramagna Stream (northwestern Italy). Six species belonging to the genus of Hydraena Kugelann, 1794 were found (H. andreinii D'Orchymont, 1934, H. subimpressa Rey, 1885, H. assimilis Rey, 1885, H. heterogyna Bedel, 1898, H. truncata Rey, 1884 and H. devillei Ganglbauer, 1901), with evident niche preferences. Our study provided interesting information about ecological requirements of minute moss beetles at small-scale and evidenced that maintaining elevate habitat diversity is essential to preserve high species abundance at local scale.