Isolated displaced non-union of a triquetral body fracture: a case report

<p>Abstract</p> <p>Introduction</p> <p>Fractures of the body of the triquetral bone are the second most common carpal fractures, and these fractures can be missed on plain X-ray. Although non-union of triquetral body fractures is very rare, such cases are associated with considerable morbidity and reduction in functional activity.</p> <p>Case presentation</p> <p>We report the case of a 29-year-old Caucasian British man who sustained an isolated displaced triquetral body fracture that resulted in non-union, who was treated surgically. We describe an original operative management for this debilitating injury. An open reduction and internal fixation using double headed compression screws was performed, without bone grafting, and with early immobilization of the wrist.</p> <p>Conclusions</p> <p>We propose this novel approach and advocate early clinical suspicion of triquetral body fractures in patients with a history of fall on an outstretched hand and ulnar sided wrist pain. We recommend evaluation using computed tomography or magnetic resonance imaging scanning.</p

Dissecting Nucleosome Free Regions by a Segmental Semi-Markov Model

BACKGROUND: Nucleosome free regions (NFRs) play important roles in diverse biological processes including gene regulation. A genome-wide quantitative portrait of each individual NFR, with their starting and ending positions, lengths, and degrees of nucleosome depletion is critical for revealing the heterogeneity of gene regulation and chromatin organization. By averaging nucleosome occupancy levels, previous studies have identified the presence of NFRs in the promoter regions across many genes. However, evaluation of the quantitative characteristics of individual NFRs requires an NFR calling method. METHODOLOGY: In this study, we propose a statistical method to identify the patterns of NFRs from a genome-wide measurement of nucleosome occupancy. This method is based on an appropriately designed segmental semi-Markov model, which can capture each NFR pattern and output its quantitative characterizations. Our results show that the majority of the NFRs are located in intergenic regions or promoters with a length of about 400-600bp and varying degrees of nucleosome depletion. Our quantitative NFR mapping allows for an investigation of the relative impacts of transcription machinery and DNA sequence in evicting histones from NFRs. We show that while both factors have significant overall effects, their specific contributions vary across different subtypes of NFRs. CONCLUSION: The emphasis of our approach on the variation rather than the consensus of nucleosome free regions sets the tone for enabling the exploration of many subtler dynamic aspects of chromatin biology

An Active Site Aromatic Triad in Escherichia coli DNA Pol IV Coordinates Cell Survival and Mutagenesis in Different DNA Damaging Agents

DinB (DNA Pol IV) is a translesion (TLS) DNA polymerase, which inserts a nucleotide opposite an otherwise replication-stalling N2-dG lesion in vitro, and confers resistance to nitrofurazone (NFZ), a compound that forms these lesions in vivo. DinB is also known to be part of the cellular response to alkylation DNA damage. Yet it is not known if DinB active site residues, in addition to aminoacids involved in DNA synthesis, are critical in alkylation lesion bypass. It is also unclear which active site aminoacids, if any, might modulate DinB's bypass fidelity of distinct lesions. Here we report that along with the classical catalytic residues, an active site “aromatic triad”, namely residues F12, F13, and Y79, is critical for cell survival in the presence of the alkylating agent methyl methanesulfonate (MMS). Strains expressing dinB alleles with single point mutations in the aromatic triad survive poorly in MMS. Remarkably, these strains show fewer MMS- than NFZ-induced mutants, suggesting that the aromatic triad, in addition to its role in TLS, modulates DinB's accuracy in bypassing distinct lesions. The high bypass fidelity of prevalent alkylation lesions is evident even when the DinB active site performs error-prone NFZ-induced lesion bypass. The analyses carried out with the active site aromatic triad suggest that the DinB active site residues are poised to proficiently bypass distinctive DNA lesions, yet they are also malleable so that the accuracy of the bypass is lesion-dependent

The NS1 Glycoprotein Can Generate Dramatic Antibody-Enhanced Dengue Viral Replication in Normal Out-Bred Mice Resulting in Lethal Multi-Organ Disease

Antibody-enhanced replication (AER) of dengue type-2 virus (DENV-2) strains and production of antibody-enhanced disease (AED) was tested in out-bred mice. Polyclonal antibodies (PAbs) generated against the nonstructural-1 (NS1) glycoprotein candidate vaccine of the New Guinea-C (NG-C) or NSx strains reacted strongly and weakly with these antigens, respectively. These PAbs contained the IgG2a subclass, which cross-reacted with the virion-associated envelope (E) glycoprotein of the DENV-2 NSx strain, suggesting that they could generate its AER via all mouse Fcγ-receptor classes. Indeed, when these mice were challenged with a low dose (<0.5 LD50) of the DENV-2 NSx strain, but not the NG-C strain, they all generated dramatic and lethal DENV-2 AER/AED. These AER/AED mice developed life-threatening acute respiratory distress syndrome (ARDS), displayed by diffuse alveolar damage (DAD) resulting from i) dramatic interstitial alveolar septa-thickening with mononuclear cells, ii) some hyperplasia of alveolar type-II pneumocytes, iii) copious intra-alveolar protein secretion, iv) some hyaline membrane-covered alveolar walls, and v) DENV-2 antigen-positive alveolar macrophages. These mice also developed meningo-encephalitis, with greater than 90,000-fold DENV-2 AER titers in microglial cells located throughout their brain parenchyma, some of which formed nodules around dead neurons. Their spleens contained infiltrated megakaryocytes with DENV-2 antigen-positive red-pulp macrophages, while their livers displayed extensive necrosis, apoptosis and macro- and micro-steatosis, with DENV-2 antigen-positive Kuppfer cells and hepatocytes. Their infections were confirmed by DENV-2 isolations from their lungs, spleens and livers. These findings accord with those reported in fatal human “severe dengue” cases. This DENV-2 AER/AED was blocked by high concentrations of only the NG-C NS1 glycoprotein. These results imply a potential hazard of DENV NS1 glycoprotein-based vaccines, particularly against DENV strains that contain multiple mutations or genetic recombination within or between their DENV E and NS1 glycoprotein-encoding genes. The model provides potential for assessing DENV strain pathogenicity and anti-DENV therapies in normal mice

Data-analysis strategies for image-based cell profiling

Image-based cell profiling is a high-throughput strategy for the quantification of phenotypic differences among a variety of cell populations. It paves the way to studying biological systems on a large scale by using chemical and genetic perturbations. The general workflow for this technology involves image acquisition with high-throughput microscopy systems and subsequent image processing and analysis. Here, we introduce the steps required to create high-quality image-based (i.e., morphological) profiles from a collection of microscopy images. We recommend techniques that have proven useful in each stage of the data analysis process, on the basis of the experience of 20 laboratories worldwide that are refining their image-based cell-profiling methodologies in pursuit of biological discovery. The recommended techniques cover alternatives that may suit various biological goals, experimental designs, and laboratories' preferences.Peer reviewe

Coping strategies, vision-related quality of life, and emotional health in managing retinitis pigmentosa: a survey study.

Background Retinitis pigmentosa is a group of genetic progressive retinal dystrophies that may adversely affect daily life. Those with RP should develop adaptive coping strategies to manage their condition. This study investigates the relationship between engaging (ECS) and disengaging coping strategies (DCS), vision-related quality of life (VRQoL), and emotional health, in adults living at home with retinitis pigmentosa. Method One hundred and five participants (70 female; meanage of 46.98, SD age  = 13.77) completed a cross-sectional survey. The questionnaire booklet consisted of the Coping Strategies Inventory – Short Form (32 items), the National Eye Institute Visual Functioning Questionnaire 25 (25 items), Marylands Trait Depression Scale (18 items), the Warwick-Edinburgh Mental Well-being Scale (14 items), and the Subjective Happiness Scale (4 items). Results Data was analysed with a two-block hierarchical multiple regression, with the first block controlling for the demographic data (age, sex, years since retinitis pigmentosa diagnosis, number of comorbidities, participant-perceived retinitis pigmentosa severity, and knowing RP type) and the second block consisting of primary measures (type of coping strategy, VRQoL, and Emotional Health). Type of coping strategy was found to impact psychosocial variables of VRQoL, not overall VRQoL. These psychosocial VRQoL variables had a positive association with ECS and a negative association with DCS. Emotional Health increased with ECS and decreased with DCS. There was a larger impact of DCS on VRQoL and Emotional Health compared to ECS, that is, VRQoL and Emotional Health decreased more with increasing DCS than VRQoL, and Emotional Health increased with increasing ECS. Conclusion In concordance with previous research, ECS increased with increasing VRQoL and DCS decreased with increasing VRQoL. However, the findings also indicated that DCS had a greater impact than ECS on VRQoL and Emotional Health. This suggests that diminishing DCS should be prioritised over developing ECS to positively influence VRQoL and Emotional Health. Further research should investigate the impact of reducing DCS compared to increasing ECS, and how this may influence VRQoL and Emotional Health.N/