Accuracy of ultrasonography (US) and magnetic resonance imaging (MRI) in detection of rotator cuff tears in district general hospital

Background: Rotator cuff tears (RCTs) represent a significant proportion of shoulder diseases, hence they are a frequent cause of patient visits in shoulder clinics. However, the diagnosis of rotator cuff tears is controversial. Investigation of cuff tears is based on ultrasonography (US) and magnetic resonance imaging (MRI). Both modalities have been in use for decades, and their advantages and limitations are known. A recent Cochrane review of the subject suggested that US and MRI both performed well with respect to full thickness rotator cuff tears (FTT). However, they were less accurate with respect to partial thickness tears (PTT). The aim of this study is to assess the accuracy of US and MRI in diagnosing rotator cuff tears. Material/Methods: This is a retrospective analysis of a cohort of 255 patients who underwent shoulder arthroscopy. Of them, 125 patients had preoperative US, and 130 had preoperative MRI. The imaging results were compared with arthroscopic findings for patient. Results: After calculating sensitivity, specificity, positive prediction value (PPV), and negative prediction value, we found no statistically significant difference between US and MRI in detection of rotator cuff tears of any type (RCT) or FTT. However, US is more specific in detecting PTT compared to MRI (P=0.00008) but with no significant difference in other parameters. Conclusions: We concluded that US and MRI both have similar accuracy in diagnosing RCT of any sort and FTT. However, US is more specific than MRI in detecting PTT. In our institute, we now recommend US as the investigation of choice for diagnosing rotator cuff tears

Estimate of the Spontaneous Mutation Rate in Chlamydomonas reinhardtii

The nature of spontaneous mutations, including their rate, distribution across the genome, and fitness consequences, is of central importance to biology. However, the low rate of mutation has made it difficult to study spontaneous mutagenesis, and few studies have directly addressed these questions. Here, we present a direct estimate of the mutation rate and a description of the properties of new spontaneous mutations in the unicellular green alga Chlamydomonas reinhardtii. We conducted a mutation accumulation experiment for ∼350 generations followed by whole-genome resequencing of two replicate lines. Our analysis identified a total of 14 mutations, including 5 short indels and 9 single base mutations, and no evidence of larger structural mutations. From this, we estimate a total mutation rate of 3.23 × 10(−10)/site/generation (95% C.I. 1.82 × 10(−10) to 5.23 × 10(−10)) and a single base mutation rate of 2.08 × 10(−10)/site/generation (95% C.I., 1.09 × 10(−10) to 3.74 × 10(−10)). We observed no mutations from A/T → G/C, suggesting a strong mutational bias toward A/T, although paradoxically, the GC content of the C. reinhardtii genome is very high. Our estimate is only the second direct estimate of the mutation rate from plants and among the lowest spontaneous base-substitution rates known in eukaryotes

Structural determination of the complement inhibitory domain of Borrelia burgdorferi BBK32 provides insight into classical pathway complement evasion by Lyme disease spirochetes

The carboxy-terminal domain of the BBK32 protein from Borrelia burgdorferi sensu stricto, termed BBK32-C, binds and inhibits the initiating serine protease of the human classical complement pathway, C1r. In this study we investigated the function of BBK32 orthologues of the Lyme-associated Borrelia burgdorferi sensu lato complex, designated BAD16 from B. afzelii strain PGau and BGD19 from B. garinii strain IP90. Our data show that B. afzelii BAD16-C exhibits BBK32-C-like activities in all assays tested, including high-affinity binding to purified C1r protease and C1 complex, and potent inhibition of the classical complement pathway. Recombinant B. garinii BGD19-C also bound C1 and C1r with high-affinity yet exhibited significantly reduced in vitro complement inhibitory activities relative to BBK32-C or BAD16-C. Interestingly, natively produced BGD19 weakly recognized C1r relative to BBK32 and BAD16 and, unlike these proteins, BGD19 did not confer significant protection from serum killing. Site-directed mutagenesis was performed to convert BBK32-C to resemble BGD19-C at three residue positions that are identical between BBK32 and BAD16 but different in BGD19. The resulting chimeric protein was designated BXK32-C and this BBK32-C variant mimicked the properties observed for BGD19-C. To query the disparate complement inhibitory activities of BBK32 orthologues, the crystal structure of BBK32-C was solved to 1.7Ã… limiting resolution. BBK32-C adopts an anti-parallel four-helix bundle fold with a fifth alpha-helix protruding from the helical core. The structure revealed that the three residues targeted in the BXK32-C chimera are surface-exposed, further supporting their potential relevance in C1r binding and inhibition. Additional binding assays showed that BBK32-C only recognized C1r fragments containing the serine protease domain. The structure-function studies reported here improve our understanding of how BBK32 recognizes and inhibits C1r and provide new insight into complement evasion mechanisms of Lyme-associated spirochetes of the B. burgdorferi sensu lato complex

Extensive de novo mutation rate variation between individuals and across the genome of <i>Chlamydomonas reinhardtii</i>

Describing the process of spontaneous mutation is fundamental for understanding the genetic basis of disease, the threat posed by declining population size in conservation biology, and much of evolutionary biology. Directly studying spontaneous mutation has been difficult, however, because new mutations are rare. Mutation accumulation (MA) experiments overcome this by allowing mutations to build up over many generations in the near absence of natural selection. Here, we sequenced the genomes of 85 MA lines derived from six genetically diverse strains of the green alga Chlamydomonas reinhardtii. We identified 6843 new mutations, more than any other study of spontaneous mutation. We observed sevenfold variation in the mutation rate among strains and that mutator genotypes arose, increasing the mutation rate approximately eightfold in some replicates. We also found evidence for fine-scale heterogeneity in the mutation rate, with certain sequence motifs mutating at much higher rates, and clusters of multiple mutations occurring at closely linked sites. There was little evidence, however, for mutation rate heterogeneity between chromosomes or over large genomic regions of 200 kbp. We generated a predictive model of the mutability of sites based on their genomic properties, including local GC content, gene expression level, and local sequence context. Our model accurately predicted the average mutation rate and natural levels of genetic diversity of sites across the genome. Notably, trinucleotides vary 17-fold in rate between the most and least mutable sites. Our results uncover a rich heterogeneity in the process of spontaneous mutation both among individuals and across the genome

Proteome changes in a human retinal pigment epithelial cell line during oxidative stress and following antioxidant treatment

Age related macular degeneration (AMD) is the most common cause of blindness in the elderly. Oxidative stress contributes to retinal pigment epithelium (RPE) dysfunction and cell death thereby leading to AMD. Using improved RPE cell model systems, such as human telomerase transcriptase-overexpressing (hTERT) RPE cells (hTERT-RPE), pathophysiological changes in RPE during oxidative stress can be better understood. Using this model system, we identified changes in the expression of proteins involved in the cellular antioxidant responses after induction of oxidative stress. Some antioxidants such as vitamin E (tocopherols and tocotrienols) are powerful antioxidants that can reduce oxidative damage in cells. Alpha-tocopherol (α-Toc or αT) and gamma-tocopherol (γ-Toc or γT) are well-studied tocopherols, but signaling mechanisms underlying their respective cytoprotective properties may be distinct. Here, we determined what effect oxidative stress, induced by extracellularly applied tBHP in the presence and absence of αT and/or γT, has on the expression of antioxidant proteins and related signaling networks. Using proteomics approaches, we identified differential protein expression in cellular antioxidant response pathways during oxidative stress and after tocopherol treatment. We identified three groups of proteins based on biochemical function: glutathione metabolism/transfer, peroxidases and redox-sensitive proteins involved in cytoprotective signaling. We found that oxidative stress and tocopherol treatment resulted in unique changes in these three groups of antioxidant proteins indicate that αT and γT independently and by themselves can induce the expression of antioxidant proteins in RPE cells. These results provide novel rationales for potential therapeutic strategies to protect RPE cells from oxidative stress

From bare peat desert to nature reserve within ten years: a review of restoration practice on Little Woolden Moss, Manchester, UK

Peat-harvesting results in significant carbon emissions and complete eradication of specialised flora and fauna on lowland peatlands; recovery can be lengthy, difficult and not always successful. This review documents the techniques and procedures used to transform a bare peat-milled site into a functioning nature reserve within a decade. Site preparation, planting regimes, and methods of measuring progress are discussed, and evaluation of the site’s natural capital include three descriptive essays from an initial project officer, an experienced species recorder and a long-term volunteer. The aim of the review is both to celebrate the success of the venture and to offer experience gained to other lowland bog restoration managers

Association between Sex-Biased Gene Expression and Mutations with Sex-Specific Phenotypic Consequences in Drosophila

Genome-wide mRNA transcription profiles reveal widespread molecular sexual dimorphism or “sex-biased” gene expression, yet the relationship between molecular and phenotypic sexual dimorphism remains unclear. A major unresolved question is whether sex-biased genes typically perform male- and female-specific functions (whether these genes have sex-biased phenotypic or fitness consequences) or have similar functional importance for both sexes. To elucidate the relationship between sex-biased transcription and sex-biased fitness consequences, we analyzed a large data set of lethal, visible, and sterile mutations that have been mapped to the Drosophila melanogaster genome. The data permitted us to classify genes according to their sex-specific mutational effects and to infer the relationship between sex-biased transcription level and sex-specific fitness consequences. We find that mutations in female-biased genes are (on average) more deleterious to females than to males and that mutations in male-biased genes tend to be more deleterious to males than to females. Nevertheless, mutations in most sex-biased genes have similar phenotypic consequences for both sexes, which suggests that sex-biased transcription is not necessarily associated with functional genetic differentiation between males and females. These results have interesting implications for the evolution of sexual dimorphism and sex-specific adaptation

A comparison in a youth population between those with and without a history of concussion using biomechanical reconstruction

OBJECTIVE: Concussion is a common topic of research as a result of the short- and long-term effects it can have on the affected individual. Of particular interest is whether previous concussions can lead to a biomechanical susceptibility, or vulnerability, to incurring further head injuries, particularly for youth populations. The purpose of this research was to compare the impact biomechanics of a concussive event in terms of acceleration and brain strains of 2 groups of youths: those who had incurred a previous concussion and those who had not. It was hypothesized that the youths with a history of concussion would have lower-magnitude biomechanical impact measures than those who had never suffered a previous concussion. METHODS: Youths who had suffered a concussion were recruited from emergency departments across Canada. This pool of patients was then separated into 2 categories based on their history of concussion: those who had incurred 1 or more previous concussions, and those who had never suffered a concussion. The impact event that resulted in the brain injury was reconstructed biomechanically using computational, physical, and finite element modeling techniques. The output of the events was measured in biomechanical parameters such as energy, force, acceleration, and brain tissue strain to determine if those patients who had a previous concussion sustained a brain injury at lower magnitudes than those who had no previously reported concussion. RESULTS: The results demonstrated that there was no biomechanical variable that could distinguish between the concussion groups with a history of concussion versus no history of concussion. CONCLUSIONS: The results suggest that there is no measureable biomechanical vulnerability to head impact related to a history of concussions in this youth population. This may be a reflection of the long time between the previous concussion and the one reconstructed in the laboratory, where such a long period has been associated with recovery from injury