Outbreak of Mycobacterium Abscessus Infection After Soft Tissue Augmentation

BACKGROUND: Illicit soft-tissue augmentation performed in New York City resulted in an outbreak of Mycobacterium abscessus infection in 2002. OBJECTIVE: To report two cases of women who developed tender, subcutaneous nodules of the face and buttocks after illicit soft-tissue augmentation with a hyaluronic acid derivative. METHODS: Two case reports are presented, and the literature is reviewed. RESULTS: Empiric treatment with clarithromycin (for M. abscessus infection) and prednisone (for foreign body reaction) resulted in clearance of lesions. CONCLUSION: Contaminated or impure material used for soft-tissue augmentation can result in a clustered outbreak of infection or foreign body reaction.     

Screening for Meares–Irlen sensitivity in adults: can assessment methods predict changes in reading speed?

Two methods of assessing candidates for coloured overlays were compared with the aim of determining which method had the most practical utility. A total of 58 adults were assessed as potential candidates for coloured overlays, using two methods; a questionnaire, which identified self-reported previous symptoms, and a measure of perceptual distortions immediately prior to testing. Participants were classified as normal, Meares-Irlen sensitive, and borderline sensitive. Reading speed was measured with and without coloured overlays, using the Wilkins Rate of Reading Test and the change in speed was calculated. Participants classified as normal did not show any significant benefit from reading with an overlay. In contrast, a significant reading advantage was found for the borderline and Meares-Irlen participants. Current symptom rating was found to be a significant predictor of the change in reading speed, however the previous symptom rating was not found to be a reliable predictor. These data indicate that the assessment of perceptual distortions immediately prior to measuring colour preference and reading speed is the most meaningful method of assessing pattern glare and determining the utility of coloured overlays.     

Prospective technical validation and assessment of intra-tumour heterogeneity of a low density array hypoxia gene profile in head and neck squamous cell carcinoma

Background and purposeTumour hypoxia is associated with a poor prognosis in head and neck squamous cell carcinoma (HNSCC), however there is no accepted method for assessing hypoxia clinically. We aimed to conduct a technical validation of a hypoxia gene expression signature using the TaqMan Low Density Array (TLDA) platform to investigate if this approach reliably identified hypoxic tumours.Materials and methodsTumour samples (n = 201) from 80 HNSCC patients were collected prospectively from two centres. Fifty-three patients received pimonidazole prior to surgery. TaqMan Low Density Array-Hypoxia Scores (TLDA-HS) were obtained by quantitative real-time PCR (qPCR) using a 25-gene signature and customised TLDA cards. Assay performance was assessed as coefficient of variation (CoV).ResultsThe assay was sensitive with linear reaction efficiencies across a 4log₁₀ range of inputted cDNA (0.001–10 ng/μl). Intra- (CoV = 6.9%) and inter- (CoV = 2.0%) assay reproducibility were excellent. Intra-tumour heterogeneity was lower for TLDA-HS (23.2%) than for pimonidazole (67.2%) or single gene measurements of CA9 (62.2%), VEGFA (45.0%) or HIG2 (39.4%). TLDA-HS in HNSCC cell lines increased with decreasing pO₂. TLDA-HS correlated with Affymetrix U133 Plus 2.0 microarray HS (p < 0.01) and positive pimonidazole scores (p = 0.005).ConclusionsGene expression measurements of hypoxia using a 25-gene signature and TLDA cards are sensitive, reproducible and associated with lower intra-tumour heterogeneity than assaying individual genes or pimonidazole binding. The approach is suitable for further assessment of prognostic and predictive capability in clinical trial material.     

Working memory as a moderator of impulsivity and alcohol involvement: Testing the cognitive-motivational theory of alcohol use with prospective and working memory updating data

Research consistently shows that individuals high in impulsivity are at increased risk for excessive alcohol use and alcohol-related problems including alcohol use disorders (AUDs). Recent theorizing posits that working memory (WM) ability might moderate this association, but extant studies have suffered from methodological shortcomings, particularly mischaracterizing WM as a single, unitary construct and using only cross-sectional designs. This paper reports two studies that attempted to replicate and extend previous investigations of the relationship between WM, impulsivity, and alcohol involvement using two independent samples. Study 1 used a large (N = 489 at baseline), prospective cohort of college students at high and low risk for AUD to investigate interactions between WM capacity and impulsivity on cross-sectional and prospective alcohol involvement. Study 2 used a large (N = 420), cross-sectional sample of participants in an alcohol challenge study to investigate similar interactions between WM updating and impulsivity on recent alcohol involvement. Whereas Study 1 found that WM capacity moderates the relationship between some measures of impulsivity and alcohol involvement, with effects prospectively predicting alcohol involvement for up to three years, Study 2 did not find similar moderation effects when using measures of WM updating. These findings highlight the multifaceted nature of WM, which is often overlooked in the alcohol and impulsivity literature.     

Functional significance of evolving protein sequence in dihydrofolate reductase from bacteria to humans

With the rapidly growing wealth of genomic data, experimental inquiries on the functional significance of important divergence sites in protein evolution are becoming more accessible. Here we trace the evolution of dihydrofolate reductase (DHFR) and identify multiple key divergence sites among 233 species between humans and bacteria. We connect these sites, experimentally and computationally, to changes in the enzyme’s binding properties and catalytic efficiency. One of the identified evolutionarily important sites is the N23PP modification (∼mid-Devonian, 415–385 Mya), which alters the conformational states of the active site loop in Escherichia coli dihydrofolate reductase and negatively impacts catalysis. This enzyme activity was restored with the inclusion of an evolutionarily significant lid domain (G51PEKN in E. coli enzyme; ∼2.4 Gya). Guided by this evolutionary genomic analysis, we generated a human-like E. coli dihydrofolate reductase variant through three simple mutations despite only 26% sequence identity between native human and E. coli DHFRs. Molecular dynamics simulations indicate that the overall conformational motions of the protein within a common scaffold are retained throughout evolution, although subtle changes to the equilibrium conformational sampling altered the free energy barrier of the enzymatic reaction in some cases. The data presented here provide a glimpse into the evolutionary trajectory of functional DHFR through its protein sequence space that lead to the diverged binding and catalytic properties of the E. coli and human enzymes.     

From the Cover: Rice yields in tropical/subtropical Asia exhibit large but opposing sensitivities to minimum and maximum temperatures

Data from farmer-managed fields have not been used previously to disentangle the impacts of daily minimum and maximum temperatures and solar radiation on rice yields in tropical/subtropical Asia. We used a multiple regression model to analyze data from 227 intensively managed irrigated rice farms in six important rice-producing countries. The farm-level detail, observed over multiple growing seasons, enabled us to construct farm-specific weather variables, control for unobserved factors that either were unique to each farm but did not vary over time or were common to all farms at a given site but varied by season and year, and obtain more precise estimates by including farm- and site-specific economic variables. Temperature and radiation had statistically significant impacts during both the vegetative and ripening phases of the rice plant. Higher minimum temperature reduced yield, whereas higher maximum temperature raised it; radiation impact varied by growth phase. Combined, these effects imply that yield at most sites would have grown more rapidly during the high-yielding season but less rapidly during the low-yielding season if observed temperature and radiation trends at the end of the 20th century had not occurred, with temperature trends being more influential. Looking ahead, they imply a net negative impact on yield from moderate warming in coming decades. Beyond that, the impact would likely become more negative, because prior research indicates that the impact of maximum temperature becomes negative at higher levels. Diurnal temperature variation must be considered when investigating the impacts of climate change on irrigated rice in Asia.