Functional outcome following external fixator (JESS) application for proximal humeral fractures

Background: Proximal humeral fractures account for 5% of all fractures. Observed frequently in older osteoporotic patients but found in young patients with high-energy trauma.About 80% of these fractures are undisplaced or minimally displaced. Non-operative method requiring immobilization of shoulder often leads to a stiff shoulder, whereas surgical procedures such as plating need excessive soft tissue dissection. It was overcome in this study by less soft tissue dissection by use of external fixator application and early mobilization.Methods: Total of 18 patients mean age 40.5 years, predominantly male (16/18) treated with external fixator - JESS (Joshi’s external immobilization system) for Neer’s two, three and four part proximal humeral fractures. Vehicular accidents were the most common mode of injury followed by fall. There were 8 cases each of Neer's two and three part fractures. Shoulder mobilization started within a week as postoperativelyas pain allowed. Patients followed up at 3, 6, 12 and 18 weeks for pain, function, range of motion and anatomy with check X-ray. After radiological union at 8-10 weeks JESS was removed. Cases were evaluated for functional result by constant scoring system.Results: Average score on constant scoring system was 72 after a mean follow-up of 6 months. All fractures united in mean duration of 9.33 weeks. The complications included shoulder stiffness in one case and pin tract infection in two cases.Conclusions: Early shoulder mobilization a prerequisite for good results can be achieved without compromising fracture union. Less soft tissue dissection required and significant cost effective

Gcn5 and Sirtuins Regulate Acetylation of the Ribosomal Protein Transcription Factor Ifh1

SummaryBackgroundIn eukaryotes, ribosome biosynthesis involves the coordination of ribosomal RNA and ribosomal protein (RP) production. In S. cerevisiae, the regulation of ribosome biosynthesis occurs largely at the level of transcription. The transcription factor Ifh1 binds at RP genes and promotes their transcription when growth conditions are favorable. Although Ifh1 recruitment to RP genes has been characterized, little is known about the regulation of promoter-bound Ifh1.ResultsWe used a novel whole-cell-extract screening approach to identify Spt7, a member of the SAGA transcription complex, and the RP transactivator Ifh1 as highly acetylated nonhistone species. We report that Ifh1 is modified by acetylation specifically in an N-terminal domain. These acetylations require the Gcn5 histone acetyltransferase and are reversed by the sirtuin deacetylases Hst1 and Sir2. Ifh1 acetylation is regulated by rapamycin treatment and stress and limits the ability of Ifh1 to act as a transactivator at RP genes.ConclusionsOur data suggest a novel mechanism of regulation whereby Gcn5 functions to titrate the activity of Ifh1 following its recruitment to RP promoters to provide more than an all-or-nothing mode of transcriptional regulation. We provide insights into how the action of histone acetylation machineries converges with nutrient-sensing pathways to regulate important aspects of cell growth

PatientExploreR: an extensible application for dynamic visualization of patient clinical history from electronic health records in the OMOP common data model.

MotivationElectronic health records (EHRs) are quickly becoming omnipresent in healthcare, but interoperability issues and technical demands limit their use for biomedical and clinical research. Interactive and flexible software that interfaces directly with EHR data structured around a common data model (CDM) could accelerate more EHR-based research by making the data more accessible to researchers who lack computational expertise and/or domain knowledge.ResultsWe present PatientExploreR, an extensible application built on the R/Shiny framework that interfaces with a relational database of EHR data in the Observational Medical Outcomes Partnership CDM format. PatientExploreR produces patient-level interactive and dynamic reports and facilitates visualization of clinical data without any programming required. It allows researchers to easily construct and export patient cohorts from the EHR for analysis with other software. This application could enable easier exploration of patient-level data for physicians and researchers. PatientExploreR can incorporate EHR data from any institution that employs the CDM for users with approved access. The software code is free and open source under the MIT license, enabling institutions to install and users to expand and modify the application for their own purposes.Availability and implementationPatientExploreR can be freely obtained from GitHub: https://github.com/BenGlicksberg/PatientExploreR. We provide instructions for how researchers with approved access to their institutional EHR can use this package. We also release an open sandbox server of synthesized patient data for users without EHR access to explore: http://patientexplorer.ucsf.edu.Supplementary informationSupplementary data are available at Bioinformatics online

Engineering nucleotide specificity of succinyl-CoA synthetase in blastocystis: the emerging role of gatekeeper residues

Charged, solvent-exposed residues at the entrance to the substrate binding site (gatekeeper residues) produce electrostatic dipole interactions with approaching substrates, and control their access by a novel mechanism called "electrostatic gatekeeper effect". This proof-of-concept study demonstrates that the nucleotide specificity can be engineered by altering the electrostatic properties of the gatekeeper residues outside the binding site. Using Blastocystis succinyl-CoA synthetase (SCS, EC 6.2.1.5), we demonstrated that the gatekeeper mutant (ED) resulted in ATP-specific SCS to show high GTP specificity. Moreover, nucleotide binding site mutant (LF) had no effect on GTP specificity and remained ATP-specific. However, via combination of the gatekeeper mutant with the nucleotide binding site mutant (ED+LF), a complete reversal of nucleotide specificity was obtained with GTP, but no detectable activity was obtained with ATP. This striking result of the combined mutant (ED+LF) was due to two changes; negatively charged gatekeeper residues (ED) favored GTP access, and nucleotide binding site residues (LF) altered ATP binding, which was consistent with the hypothesis of the "electrostatic gatekeeper effect". These results were further supported by molecular modeling and simulation studies. Hence, it is imperative to extend the strategy of the gatekeeper effect in a different range of crucial enzymes (synthetases, kinases, and transferases) to engineer substrate specificity for various industrial applications and substrate-based drug design

An approach for the identification of targets specific to bone metastasis using cancer genes interactome and gene ontology analysis

Metastasis is one of the most enigmatic aspects of cancer pathogenesis and is a major cause of cancer-associated mortality. Secondary bone cancer (SBC) is a complex disease caused by metastasis of tumor cells from their primary site and is characterized by intricate interplay of molecular interactions. Identification of targets for multifactorial diseases such as SBC, the most frequent complication of breast and prostate cancers, is a challenge. Towards achieving our aim of identification of targets specific to SBC, we constructed a 'Cancer Genes Network', a representative protein interactome of cancer genes. Using graph theoretical methods, we obtained a set of key genes that are relevant for generic mechanisms of cancers and have a role in biological essentiality. We also compiled a curated dataset of 391 SBC genes from published literature which serves as a basis of ontological correlates of secondary bone cancer. Building on these results, we implement a strategy based on generic cancer genes, SBC genes and gene ontology enrichment method, to obtain a set of targets that are specific to bone metastasis. Through this study, we present an approach for probing one of the major complications in cancers, namely, metastasis. The results on genes that play generic roles in cancer phenotype, obtained by network analysis of 'Cancer Genes Network', have broader implications in understanding the role of molecular regulators in mechanisms of cancers. Specifically, our study provides a set of potential targets that are of ontological and regulatory relevance to secondary bone cancer.Comment: 54 pages (19 pages main text; 11 Figures; 26 pages of supplementary information). Revised after critical reviews. Accepted for Publication in PLoS ON

The use of complementary and alternative medicine by women experiencing menopausal symptoms in Bologna

<p>Abstract</p> <p>Background</p> <p>The present study describes Complementary and Alternative Medicine (CAM) use amongst Italian women transitioning through menopause. Popularity and perceived effectiveness of CAM treatments, use of pharmaceutical medications, characteristics of CAM users, the extent of communication between medical practitioners and women about their use of CAM, and variables associated with CAM use were also investigated.</p> <p>Methods</p> <p>Women, aged 45-65 years attending Family Planning and Women's Health clinics or Menopause Centres in Bologna were invited to complete a voluntary, anonymous, self administered questionnaire, which was used in a previous study in Sydney. The questionnaire was translated and adapted for use amongst Italian women. Data on general demographic and health characteristics, menopause related symptoms and the use of CAM and pharmaceutical treatments during the previous 12 months were collected.</p> <p>Results</p> <p>In total, 1,203 women completed the survey, of which 1,106 were included in the final sample. Of women who had symptoms linked with menopause and/or used remedies to alleviate symptoms, 33.5% reported to have used CAM. Among these, 23.5% had consulted one or more practitioners and 24% had used at least one CAM product.</p> <p>Approximately nine out of ten respondents reported medical practitioners did not seek information about their use of CAM; while one third of CAM users did not disclose the use of CAM to their physician. Nevertheless, medical practitioners were the most popular source of information. From the multivariate analysis, variables associated with CAM use were: professional employment, time since the last natural menses, use of CAM for conditions other than menopause, and presence of some severe symptoms.</p> <p>Conclusions</p> <p>The relatively high prevalence of CAM use by women transitioning through menopause should encourage research initiatives into determining which CAM treatments are the safest and effective. The increasing and likely concomitant use of CAM with HRT and other pharmaceuticals underlines the need for the implementation of a surveillance system to report and monitor possible drug-herb adverse events. The discrepancy between women preferring to seek information about CAM from their medical doctor and the difficulties noted in communication between doctor and patient should encourage educational initiatives on CAM by health-care agencies and institutions.</p

Key role of SMN/SYNCRIP and RNA-Motif 7 in spinal muscular atrophy: RNA-Seq and motif analysis of human motor neurons

Spinal muscular atrophy is a motor neuron disorder caused by mutations in SMN1. The reasons for the selective vulnerability of motor neurons linked to SMN (encoded by SMN1) reduction remain unclear. Therefore, we performed deep RNA sequencing on human spinal muscular atrophy motor neurons to detect specific altered gene splicing/expression and to identify the presence of a common sequence motif in these genes. Many deregulated genes, such as the neurexin and synaptotagmin families, are implicated in critical motor neuron functions. Motif-enrichment analyses of differentially expressed/spliced genes, including neurexin2 (NRXN2), revealed a common motif, motif 7, which is a target of SYNCRIP. Interestingly, SYNCRIP interacts only with full-length SMN, binding and modulating several motor neuron transcripts, including SMN itself. SYNCRIP overexpression rescued spinal muscular atrophy motor neurons, due to the subsequent increase in SMN and their downstream target NRXN2 through a positive loop mechanism and ameliorated SMN-loss-related pathological phenotypes in Caenorhabditis elegans and mouse models. SMN/SYNCRIP complex through motif 7 may account for selective motor neuron degeneration and represent a potential therapeutic target