Investigating spillover of multidrug-resistant tuberculosis from a prison: a spatial and molecular epidemiological analysis.

BACKGROUND: Congregate settings may serve as institutional amplifiers of tuberculosis (TB) and multidrug-resistant tuberculosis (MDR-TB). We analyze spatial, epidemiological, and pathogen genetic data prospectively collected from neighborhoods surrounding a prison in Lima, Peru, where inmates experience a high risk of MDR-TB, to investigate the risk of spillover into the surrounding community. METHODS: Using hierarchical Bayesian statistical modeling, we address three questions regarding the MDR-TB risk: (i) Does the excess risk observed among prisoners also extend outside the prison? (ii) If so, what is the magnitude, shape, and spatial range of this spillover effect? (iii) Is there evidence of additional transmission across the region? RESULTS: The region of spillover risk extends for 5.47 km outside of the prison (95% credible interval: 1.38, 9.63 km). Within this spillover region, we find that nine of the 467 non-inmate patients (35 with MDR-TB) have MDR-TB strains that are genetic matches to strains collected from current inmates with MDR-TB, compared to seven out of 1080 patients (89 with MDR-TB) outside the spillover region (p values: 0.022 and 0.008). We also identify eight spatially aggregated genetic clusters of MDR-TB, four within the spillover region, consistent with local transmission among individuals living close to the prison. CONCLUSIONS: We demonstrate a clear prison spillover effect in this population, which suggests that interventions in the prison may have benefits that extend to the surrounding community

Morphological characterization of Mycobacterium tuberculosis in a MODS culture for an automatic diagnostics through pattern recognition.

Tuberculosis control efforts are hampered by a mismatch in diagnostic technology: modern optimal diagnostic tests are least available in poor areas where they are needed most. Lack of adequate early diagnostics and MDR detection is a critical problem in control efforts. The Microscopic Observation Drug Susceptibility (MODS) assay uses visual recognition of cording patterns from Mycobacterium tuberculosis (MTB) to diagnose tuberculosis infection and drug susceptibility directly from a sputum sample in 7-10 days with a low cost. An important limitation that laboratories in the developing world face in MODS implementation is the presence of permanent technical staff with expertise in reading MODS. We developed a pattern recognition algorithm to automatically interpret MODS results from digital images. The algorithm using image processing, feature extraction and pattern recognition determined geometrical and illumination features used in an object-model and a photo-model to classify TB-positive images. 765 MODS digital photos were processed. The single-object model identified MTB (96.9% sensitivity and 96.3% specificity) and was able to discriminate non-tuberculous mycobacteria with a high specificity (97.1% M. avium, 99.1% M. chelonae, and 93.8% M. kansasii). The photo model identified TB-positive samples with 99.1% sensitivity and 99.7% specificity. This algorithm is a valuable tool that will enable automatic remote diagnosis using Internet or cellphone telephony. The use of this algorithm and its further implementation in a telediagnostics platform will contribute to both faster TB detection and MDR TB determination leading to an earlier initiation of appropriate treatment

The value of spreader grafts in rhinoplasty: a critical review

The value of spreader grafts in rhinoplasty cannot be underestimated. Various studies have demonstrated that they play a valuable role in the restoration of nasal dorsum aesthetics, provide support for the nasal valve and maintain the straightened position of the corrected deviated cartilaginous septal dorsum. However, there is still controversy on the extent of its value in nasal patency. This study reviews the literature and describes the values and limitations of spreader grafts in rhinoplasty and the alternatives to classic spreader grafts

Very Bright Green Fluorescent Proteins from the Pontellid Copepod Pontella mimocerami

Marguerite E. Hunt is with UT Austin; Michael P. Scherrer is with UT Austin; Frank D. Ferrari is with the National Museum of Natural History at the Smithsonian Institution; Mikhail V. Matz is with UT Austin.Background -- Fluorescent proteins (FP) homologous to the green fluorescent protein (GFP) from the jellyfish Aequorea victoria have revolutionized biomedical research due to their usefulness as genetically encoded fluorescent labels. Fluorescent proteins from copepods are particularly promising due to their high brightness and rapid fluorescence development. Results -- Here we report two novel FPs from Pontella mimocerami (Copepoda, Calanoida, Pontellidae), which were identified via fluorescence screening of a bacterial cDNA expression library prepared from the whole-body total RNA of the animal. The proteins are very similar in sequence and spectroscopic properties. They possess high molar extinction coefficients (79,000 M−1 cm−) and quantum yields (0.92), which make them more than two-fold brighter than the most common FP marker, EGFP. Both proteins form oligomers, which we were able to counteract to some extent by mutagenesis of the N-terminal region; however, this particular modification resulted in substantial drop in brightness. Conclusions -- The spectroscopic characteristics of the two P. mimocerami proteins place them among the brightest green FPs ever described. These proteins may therefore become valuable additions to the in vivo imaging toolkit.This work was supported by the Ocean Exploration program of the National Oceanic and Atmospheric Administration (“Operation Deep Scope 2007”), and the National Institutes of Health grant R01 GM078247 to M. V. M. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Biological Sciences, School o

Filamins Regulate Cell Spreading and Initiation of Cell Migration

Mammalian filamins (FLNs) are a family of three large actin-binding proteins. FLNa, the founding member of the family, was implicated in migration by cell biological analyses and the identification of FLNA mutations in the neuronal migration disorder periventricular heterotopia. However, recent knockout studies have questioned the relevance of FLNa to cell migration. Here we have used shRNA-mediated knockdown of FLNa, FLNb or FLNa and FLNb, or, alternatively, acute proteasomal degradation of all three FLNs, to generate FLN-deficient cells and assess their ability to migrate. We report that loss of FLNa or FLNb has little effect on migration but that knockdown of FLNa and FLNb, or proteolysis of all three FLNs, impairs migration. The observed defect is primarily a deficiency in initiation of motility rather than a problem with maintenance of locomotion speed. FLN-deficient cells are also impaired in spreading. Re-expression of full length FLNa, but not re-expression of a mutated FLNa lacking immunoglobulin domains 19 to 21, reverts both the spreading and the inhibition of initiation of migration

Segmental Duplications Arise from Pol32-Dependent Repair of Broken Forks through Two Alternative Replication-Based Mechanisms

The propensity of segmental duplications (SDs) to promote genomic instability is of increasing interest since their involvement in numerous human genomic diseases and cancers was revealed. However, the mechanism(s) responsible for their appearance remain mostly speculative. Here, we show that in budding yeast, replication accidents, which are most likely transformed into broken forks, play a causal role in the formation of SDs. The Pol32 subunit of the major replicative polymerase Polδ is required for all SD formation, demonstrating that SDs result from untimely DNA synthesis rather than from unequal crossing-over. Although Pol32 is known to be required for classical (Rad52-dependant) break-induced replication, only half of the SDs can be attributed to this mechanism. The remaining SDs are generated through a Rad52-independent mechanism of template switching between microsatellites or microhomologous sequences. This new mechanism, named microhomology/microsatellite-induced replication (MMIR), differs from all known DNA double-strand break repair pathways, as MMIR-mediated duplications still occur in the combined absence of homologous recombination, microhomology-mediated, and nonhomologous end joining machineries. The interplay between these two replication-based pathways explains important features of higher eukaryotic genomes, such as the strong, but not strict, association between SDs and transposable elements, as well as the frequent formation of oncogenic fusion genes generating protein innovations at SD junctions

Organ preservation surgery for laryngeal cancer

The principles of management of the laryngeal cancer have evolved over the recent past with emphasis on organ preservation. These developments have paralleled technological advancements as well as refinement in the surgical technique. The surgeons are able to maintain physiological functions of larynx namely speech, respiration and swallowing without compromising the loco-regional control of cancer in comparison to the more radical treatment modalities. A large number of organ preservation surgeries are available to the surgeon; however, careful assessment of the stage of the cancer and selection of the patient is paramount to a successful outcome. A comprehensive review of various organ preservation techniques in vogue for the management of laryngeal cancer is presented

IL28B SNP rs12979860 Is a Critical Predictor for On-Treatment and Sustained Virologic Response in Patients with Hepatitis C Virus Genotype-1 Infection

Single nucleotide polymorphisms (SNPs) of interleukin-28B (IL28B) have received considerable interest for their association with sustained virological response (SVR) when treating patients of genotype-1 hepatitis C virus (GT1-HCV) chronic infection with pegylated interferon and ribavirin (PegIFN/RBV). This study was to investigate the predictive power of IL28B SNPs for on-treatment responses and SVR in treatment-naïve patients with GT1-HCV chronic infection.We analyzed ten SNPs of IL28B in 191 treatment-naïve patients with GT1-HCV chronic infection who received PegIFN/RBV. In these patients, rapid virological response (RVR), early virological response (EVR) and SVR were achieved in 69.6%, 95.8% and 68.6% of the patients, respectively. Multivariate analysis (odds ratio; 95% confidence interval; P value) indicated age (0.96; 0.93-0.99; 0.012), low baseline viral load (4.65; 2.23-9.66; <0.001) and CC genotype of rs12979860 (7.74; 2.55-23.53; <0.001) but no other SNPs were independent predictors for SVR. In addition, none of the ten SNPs examined were associated with baseline viral load and stages of liver fibrosis. Regarding RVR, low baseline viral load (2.83; 1.40-5.73; 0.004) and CC genotype of rs12979860 (10.52; 3.45-32.04; <0.001) were two critical predictors. As for EVR, only CC genotype of rs12979860 (36.21; 6.68-196.38; <0.001) was the predictor. Similarly, for end of treatment response (ETR), CC genotype of rs12979860 (15.42; 4.62-51.18; <0.001) was the only predictor. For patients with RVR, only low baseline viral load (3.90; 1.57-9.68; 0.003) could predict the SVR. For patients without RVR, only rs12979860 (4.60; 1.13-18.65; 0.033) was the predictor for SVR.rs12979860 is the critical predictor for RVR, EVR, ETR and SVR in treatment-naïve patients of GT1-HCV chronic infection. Furthermore, this SNP is the only predictor for SVR in patients without RVR. These results have provided evidence that rs12979860 is the ideal IL28B SNP for genetic testing in treating patients of GT1-HCV chronic infection