Micron resolution, high-fidelity three-dimensional vascular optical imaging phantoms

Microscopic and mesoscale optical imaging techniques allow for three-dimensional (3-D) imaging of biological tissue across millimeter-scale regions, and imaging phantom models are invaluable for system characterization and clinical training. Phantom models that replicate complex 3-D geometries with both structural and molecular contrast, with resolution and lateral dimensions equivalent to those of imaging techniques (<20  μm), have proven elusive. We present a method for fabricating phantom models using a combination of two-photon polymerization (2PP) to print scaffolds, and microinjection of tailored tissue-mimicking materials to simulate healthy and diseased tissue. We provide a first demonstration of the capabilities of this method with intravascular optical coherence tomography, an imaging technique widely used in clinical practice. We describe the design, fabrication, and validation of three types of phantom models: a first with subresolution wires (5- to 34-μm diameter) arranged circumferentially, a second with a vessel side-branch, and a third containing a lipid inclusion within a vessel. Silicone hybrid materials and lipids, microinjected within a resin framework created with 2PP, served as tissue-mimicking materials that provided realistic optical scattering and absorption. We demonstrate that optical phantom models made with 2PP and microinjected tissue-mimicking materials can simulate complex anatomy and pathology with exquisite detail

Armed conflicts have an impact on the spread of tuberculosis: the case of the Somali Regional State of Ethiopia

<p>Abstract</p> <p/> <p>A pessimistic view of the impact of armed conflicts on the control of infectious diseases has generated great interest in the role of conflicts on the global TB epidemic. Nowhere in the world is such interest more palpable than in the Horn of Africa Region, comprising Ethiopia, Somalia, Eritrea, Djibouti, Kenya and Sudan. An expanding literature has demonstrated that armed conflicts stall disease control programs through distraction of health system, interruption of patients' ability to seek health care, and the diversion of economic resources to military ends rather than health needs. Nonetheless, until very recently, no research has been done to address the impact of armed conflict on TB epidemics in the Somali Regional State (SRS) of Ethiopia.</p> <p>Methods</p> <p>This study is based on the cross-sectional data collected in 2007, utilizing structured questionnaires filled-out by a sample of 226 TB patients in the SRS of Ethiopia. Data was obtained on the delay patients experienced in receiving a diagnosis of TB, on the biomedical knowledge of TB that patients had, and the level of self-treatment by patients. The outcome variables in this study are the delay in the diagnosis of TB experienced by patients, and extent of self-treatment utilized by patients. Our main explanatory variable was place of residence, which was dichotomized as being in 'conflict zones' and in 'non-conflict zones'. Demographic data was collected for statistical control. Chi-square and Mann-Whitney tests were used on calculations of group differences. Logistic regression analysis was used to determine the association between outcome and predictor variables.</p> <p>Results</p> <p>Two hundred and twenty six TB patients were interviewed. The median delay in the diagnosis of TB was 120 days and 60 days for patients from conflict zones and from non-conflict zones, respectively. Moreover, 74% of the patients residing in conflict zones undertook self-treatment prior to their diagnosis. The corresponding proportion from non-conflict zones was 45%. Fully adjusted logistic regression analysis shows that patients from conflict zones had significantly greater odds of delay (OR = 3.06; 95% CI: 1.47-6.36) and higher self treatment utilization (OR = 3.34; 95% CI: 1.56-7.12) compared to those from non-conflict zones.</p> <p>Conclusion</p> <p>Patients from conflict zones have a longer delay in receiving a diagnosis of TB and have higher levels of self treatment utilization. This suggests that access to TB care should be improved by the expansion of user friendly directly observed therapy short-course (DOTS) in the conflict zones of the region.</p

Fenretinide induces mitochondrial ROS and inhibits the mitochondrial respiratory chain in neuroblastoma

Fenretinide induces apoptosis in neuroblastoma by induction of reactive oxygen species (ROS). In this study, we investigated the role of mitochondria in fenretinide-induced cytotoxicity and ROS production in six neuroblastoma cell lines. ROS induction by fenretinide was of mitochondrial origin, demonstrated by detection of superoxide with MitoSOX, the scavenging effect of the mitochondrial antioxidant MitoQ and reduced ROS production in cells without a functional mitochondrial respiratory chain (Rho zero cells). In digitonin-permeabilized cells, a fenretinide concentration-dependent decrease in ATP synthesis and substrate oxidation was observed, reflecting inhibition of the mitochondrial respiratory chain. However, inhibition of the mitochondrial respiratory chain was not required for ROS production. Co-incubation of fenretinide with inhibitors of different complexes of the respiratory chain suggested that fenretinide-induced ROS production occurred via complex II. The cytotoxicity of fenretinide was exerted through the generation of mitochondrial ROS and, at higher concentrations, also through inhibition of the mitochondrial respiratory chain

The Cryptic African Wolf: Canis aureus lupaster Is Not a Golden Jackal and Is Not Endemic to Egypt

The Egyptian jackal (Canis aureus lupaster) has hitherto been considered a large, rare subspecies of the golden jackal (C. aureus). It has maintained its taxonomical status to date, despite studies demonstrating morphological similarities to the grey wolf (C. lupus). We have analyzed 2055 bp of mitochondrial DNA from C. a. lupaster and investigated the similarity to C. aureus and C. lupus. Through phylogenetic comparison with all wild wolf-like canids (based on 726 bp of the Cytochrome b gene) we conclusively (100% bootstrap support) place the Egyptian jackal within the grey wolf species complex, together with the Holarctic wolf, the Indian wolf and the Himalayan wolf. Like the two latter taxa, C. a. lupaster seems to represent an ancient wolf lineage which most likely colonized Africa prior to the northern hemisphere radiation. We thus refer to C. a. lupaster as the African wolf. Furthermore, we have detected C. a. lupaster individuals at two localities in the Ethiopian highlands, extending the distribution by at least 2,500 km southeast. The only grey wolf species to inhabit the African continent is a cryptic species for which the conservation status urgently needs assessment

Interaction between M-Like Protein and Macrophage Thioredoxin Facilitates Antiphagocytosis for Streptococcus equi ssp. zooepidemicus

Streptococcus equi ssp. zooepidemicus (S. zooepidemicus, S.z) is one of the common pathogens that can cause septicemia, meningitis, and mammitis in domesticated species. M-like protein (SzP) is an important virulence factor of S. zooepidemicus and contributes to bacterial infection and antiphagocytosis. The interaction between SzP of S. zooepidemicus and porcine thioredoxin (TRX) was identified by the yeast two-hybrid and further confirmed by co-immunoprecipitation. SzP interacted with both reduced and the oxidized forms of TRX without inhibiting TRX activity. Membrane anchored SzP was able to recruit TRX to the surface, which would facilitate the antiphagocytosis of the bacteria. Further experiments revealed that TRX regulated the alternative complement pathway by inhibiting C3 convertase activity and associating with factor H (FH). TRX alone inhibited C3 cleavage and C3a production, and the inhibitory effect was additive when FH was also present. TRX inhibited C3 deposition on the bacterial surface when it was recruited by SzP. These new findings indicated that S. zooepidemicus used SzP to recruit TRX and regulated the alternative complement pathways to evade the host immune phagocytosis

Measurement of B(t->Wb)/B(t->Wq) at the Collider Detector at Fermilab

We present a measurement of the ratio of top-quark branching fractions R= B(t -> Wb)/B(t -> Wq), where q can be a b, s or a d quark, using lepton-plus-jets and dilepton data sets with integrated luminosity of ~162 pb^{-1} collected with the Collider Detector at Fermilab during Run II of the Tevatron. The measurement is derived from the relative numbers of t-tbar events with different multiplicity of identified secondary vertices. We set a lower limit of R > 0.61 at 95% confidence level.Comment: 7 pages, 2 figures, published in Physical Review Letters; changes made to be consistent with published versio

Search for ZZ and ZW Production in ppbar Collisions at sqrt(s) = 1.96 TeV

We present a search for ZZ and ZW vector boson pair production in ppbar collisions at sqrt(s) = 1.96 TeV using the leptonic decay channels ZZ --> ll nu nu, ZZ --> l l l' l' and ZW --> l l l' nu. In a data sample corresponding to an integrated luminosity of 194 pb-1 collected with the Collider Detector at Fermilab, 3 candidate events are found with an expected background of 1.0 +/- 0.2 events. We set a 95% confidence level upper limit of 15.2 pb on the cross section for ZZ plus ZW production, compared to the standard model prediction of 5.0 +/- 0.4 pb.Comment: 7 pages, 2 figures. This version is accepted for publication by Phys. Rev. D Rapid Communication

Measurement of the Cross Section for Prompt Diphoton Production in p-pbar Collisions at sqrt(s) = 1.96 TeV

We report a measurement of the rate of prompt diphoton production in $p\bar{p}$ collisions at $\sqrt{s}=1.96 ~\hbox{TeV}$ using a data sample of 207 pb$^{-1}$ collected with the upgraded Collider Detector at Fermilab (CDF II). The background from non-prompt sources is determined using a statistical method based on differences in the electromagnetic showers. The cross section is measured as a function of the diphoton mass, the transverse momentum of the diphoton system, and the azimuthal angle between the two photons and is found to be consistent with perturbative QCD predictions.Comment: 7 pages, 3 figures,revtex4. Version accepted by PRL, but with cross section tables i

MtSNPscore: a combined evidence approach for assessing cumulative impact of mitochondrial variations in disease

Human mitochondrial DNA (mtDNA) variations have been implicated in a broad spectrum of diseases. With over 3000 mtDNA variations reported across databases, establishing pathogenicity of variations in mtDNA is a major challenge. We have designed and developed a comprehensive weighted scoring system (MtSNPscore) for identification of mtDNA variations that can impact pathogenicity and would likely be associated with disease. The criteria for pathogenicity include information available in the literature, predictions made by various in silico tools and frequency of variation in normal and patient datasets. The scoring scheme also assigns scores to patients and normal individuals to estimate the cumulative impact of variations. The method has been implemented in an automated pipeline and has been tested on Indian ataxia dataset (92 individuals), sequenced in this study, and other publicly available mtSNP dataset comprising of 576 mitochondrial genomes of Japanese individuals from six different groups, namely, patients with Parkinson's disease, patients with Alzheimer's disease, young obese males, young non-obese males, and type-2 diabetes patients with or without severe vascular involvement. MtSNPscore, for analysis can extract information from variation data or from mitochondrial DNA sequences. It has a web-interface http://bioinformatics.ccmb.res.in/cgi-bin/snpscore/Mtsnpscore.pl webcite that provides flexibility to update/modify the parameters for estimating pathogenicity

Bioaccumulation and ecotoxicity of carbon nanotubes

Carbon nanotubes (CNT) have numerous industrial applications and may be released to the environment. In the aquatic environment, pristine or functionalized CNT have different dispersion behavior, potentially leading to different risks of exposure along the water column. Data included in this review indicate that CNT do not cross biological barriers readily. When internalized, only a minimal fraction of CNT translocate into organism body compartments. The reported CNT toxicity depends on exposure conditions, model organism, CNT-type, dispersion state and concentration. In the ecotoxicological tests, the aquatic organisms were generally found to be more sensitive than terrestrial organisms. Invertebrates were more sensitive than vertebrates. Single-walled CNT were found to be more toxic than double-/multi-walled CNT. Generally, the effect concentrations documented in literature were above current modeled average environmental concentrations. Measurement data are needed for estimation of environmental no-effect concentrations. Future studies with benchmark materials are needed to generate comparable results. Studies have to include better characterization of the starting materials, of the dispersions and of the biological fate, to obtain better knowledge of the exposure/effect relationships