Functional outcome of medial distal tibial locking compression plate fixation in distal tibial fractures: A prospective study

INTRODUCTION: Fractures of the distal tibia can be challenging to treat because of limited soft tissue, the subcutaneous location and poor vascularity. Fractures of distal tibia remain a controversial subject despite advances in both nonoperative and operative care. The goal in expect care is to realign the fracture, realign limb length and early functional recovery. Fractures of distal tibia remains one of the most challenging for treatment because of high complication rates both from initial injury and also from treatment. All these fractures are severe injuries. They are increased in frequency because of higher incidences of Road Traffic Accidents. Accounts to 1% of all lower extremity fractures, 10% of tibial fractures and bilateral in 0-8% and compartment syndrome in 0-5%. AIM: To Study and analyze the functional outcome of Distal Tibial fractures Treated by Medial Distal Tibial Locking Compression Plate in our Institute of Orthopaedics and Traumatology, Madras Medical College and Rajiv Gandhi Government General Hospital Chennai over a period of May 2011 to November 2012. MATERIALS AND METHODS: This prospective study analyses the functional outcome of Medial distal tibial LCP for treatment of distal tibial fracture depending on the type of fracture and to find out their prognosis. The study included patients who were treated in Rajiv Gandhi Government General Hospital with Medial distal tibial Locking compression plate for distal tibial fractures. The period of study was from may2011 to December 2012 with a total duration of 20 months. In this period patients admitted for distal tibial fractures with or without intra-articular extension were considered for this study. The mean duration from hospital admission to definitive surgery was around 10 days to 14days in cases of closed fractures. Inclusion Criteria • Patients willing to participate in this study. • Skeletally mature patients. • Ruedi and Allgower type – I, II, III fractures. • Only closed fractures. • Minimum follow up of 6 months. Exclusion Criteria - • Age less than 16 years and above 60. • Compound fractures. • Associated calcaneum fractures and talus fractures. • Severely mangled extremity. • Associated spinal and abdominal injuries. The total number of patients in this study was 30. RESULTS: Distal tibial fractures though amenable to open reduction and internal fixation carries a high risk of complication and a potential for redo surgery. The outcome of an injury is best judged by how much it affects the patients, deformity, impairment or loss of function. Ovoida and Beals considered “an excellent result to be pain free patient who has returned to all activities without limp”. A number of factors affect the outcome of distal tibial fractures. The single most important factor is the severity of the initial injury, which is indicated primarily by the amount of damage to the plafond and the impaction, comminution and the displacement of the fragments and the extent to which soft tissue damage have occured. Another is the extent to which reduction was achieved and also the postoperative complications. CONCLUSION: A short series of result of our study were analyzed and the overall results have encouraged us in preferring the surgical management of distal tibial fractures over conservative methods. Distal tibial fractures are to be internally fixed either within 24 hrs of the injury before the edema sets in or a delay of 8 to 12 days for the edema to settle down and the wrinkle sign appears. Respect the soft tissues: do not operate too early or through compromised skin, instead wait till the soft tissues is amenable for surgery. Restoration of the articular surface and reestablishing its relationship to the tibial shaft is the primary goal of treatment. Good functional result depends on reasonable anatomic reduction of the articular surface either by direct or indirect methods

Efficiency enhancement of natural cocktail dyes in a TiO2-based dye-sensitized solar cell and performance of electron kinetics on the TiO2 surface

In this study, natural dye extracts were prepared from the dried leaves of Andrographis paniculata and Psidium guajava (APPG). The study’s objective was to increase the light harvesting phenomenon from solar energy utilizing natural dye from APPG, and the problem statement was to harvest the optimum solar radiation and convert it into electrical energy. Acetone and ethanol were used as solvents during the preparation process. Based on this research, the crystallite size of TiO2 nanoparticles was assessed, the impact of acetone and ethanol on APPG dye was compared, and the absorption, FTIR, and UV-Vis spectra of the solar cell fabrication process using solvents were experimentally explored. APPG leaf extract functions as a dye sensitizer. Cells are precisely sandwiched with a photoanode, TiO2 nanoparticles, an electrolyte (I/I3−), and a cathode. The JV properties of dye extracts utilizing acetone and ethanol were measured using a solar simulator equipped with a 100 mW/cm2 Xenon light and a Keithley 2400 Graphical Series SMU. An experimental DSSC with dye extraction and utilizing acetone solvent yielded a maximum photo-conversion efficiency of 0.6914%, while ethanol yielded a photo-conversion efficiency of 0.5630%. Furthermore, an energy-level diagram was used to explain the electron kinetics of DSSC, and the time required for transfer electron injection in the TiO2 surface from a dye-excited state was 150 ps

Estimation and testing for the effect of a genetic pathway on a disease outcome using logistic kernel machine regression via logistic mixed models

<p>Abstract</p> <p>Background</p> <p>Growing interest on biological pathways has called for new statistical methods for modeling and testing a genetic pathway effect on a health outcome. The fact that genes within a pathway tend to interact with each other and relate to the outcome in a complicated way makes nonparametric methods more desirable. The kernel machine method provides a convenient, powerful and unified method for multi-dimensional parametric and nonparametric modeling of the pathway effect.</p> <p>Results</p> <p>In this paper we propose a logistic kernel machine regression model for binary outcomes. This model relates the disease risk to covariates parametrically, and to genes within a genetic pathway parametrically or nonparametrically using kernel machines. The nonparametric genetic pathway effect allows for possible interactions among the genes within the same pathway and a complicated relationship of the genetic pathway and the outcome. We show that kernel machine estimation of the model components can be formulated using a logistic mixed model. Estimation hence can proceed within a mixed model framework using standard statistical software. A score test based on a Gaussian process approximation is developed to test for the genetic pathway effect. The methods are illustrated using a prostate cancer data set and evaluated using simulations. An extension to continuous and discrete outcomes using generalized kernel machine models and its connection with generalized linear mixed models is discussed.</p> <p>Conclusion</p> <p>Logistic kernel machine regression and its extension generalized kernel machine regression provide a novel and flexible statistical tool for modeling pathway effects on discrete and continuous outcomes. Their close connection to mixed models and attractive performance make them have promising wide applications in bioinformatics and other biomedical areas.</p

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

The polycomb group protein EZH2 is involved in progression of prostate cancer

Prostate cancer is a leading cause of cancer-related death in males and is second only to lung cancer. Although effective surgical and radiation treatments exist for clinically localized prostate cancer, metastatic prostate cancer remains essentially incurable. Here we show, through gene expression profiling(1), that the polycomb group protein enhancer of zeste homolog 2 (EZH2)(2,3) is overexpressed in hormone-refractory, metastatic prostate cancer. Small interfering RNA (siRNA) duplexes(4) targeted against EZH2 reduce the amounts of EZH2 protein present in prostate cells and also inhibit cell proliferation in vitro. Ectopic expression of EZH2 in prostate cells induces transcriptional repression of a specific cohort of genes. Gene silencing mediated by EZH2 requires the SET domain and is attenuated by inhibiting histone deacetylase activity. Amounts of both EZH2 messenger RNA and EZH2 protein are increased in metastatic prostate cancer; in addition, clinically localized prostate cancers that express higher concentrations of EZH2 show a poorer prognosis. Thus, dysregulated expression of EZH2 may be involved in the progression of prostate cancer, as well as being a marker that distinguishes indolent prostate cancer from those at risk of lethal progression.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62896/1/nature01075.pd

Five Challenges in the Field of Viral Diversity and Evolution

Viral diversity and evolution play a central role in processes such as disease emergence, vaccine failure, drug resistance, and virulence. However, significant challenges remain to better understand and manage these processes. Here, we discuss five of these challenges. These include improving our ability to predict viral evolution, developing more relevant experimental evolutionary systems, integrating viral dynamics and evolution at different scales, more thoroughly characterizing the virosphere, and deepening our understanding of virus-virus interactions. Intensifying future research on these areas should improve our ability to combat viral diseases, as well as to more efficiently use viral diversity and evolution for biotechnological purposes

Doxorubicin and vinorelbine act independently via p53 expression and p38 activation respectively in breast cancer cell lines

In the treatment of breast cancer, combination chemotherapy is used to overcome drug resistance. Combining doxorubicin and vinorelbine in the treatment of patients with metastatic breast cancer has shown high response rates; even single-agent vinorelbine in patients previously exposed to anthracyclines results in significant remission. Alterations in protein kinase-mediated signal transduction and p53 mutations may play a role in drug resistance with cross-talk between signal transduction and p53 pathways. The aim of this study was to establish the effects of doxorubicin and vinorelbine, as single agents, in combination, and as sequential treatments, on signal transduction and p53 in the breast cancer cell lines MCF-7 and MDA-MB-468. In both cell lines, increased p38 activity was demonstrated following vinorelbine but not doxorubicin treatment, whether vinorelbine was given prior to or simultaneously with doxorubicin. Mitogen-activated protein kinase (MAPK) activity and p53 expression remained unchanged following vinorelbine treatment. Doxorubicin treatment resulted in increased p53 expression, without changes in MAPK or p38 activity. These findings suggest that the effect of doxorubicin and vinorelbine used in combination may be achieved at least in part through distinct mechanisms. This additivism, where doxorubicin acts via p53 expression and vinorelbine through p38 activation, may contribute to the high clinical response rate when the two drugs are used together in the treatment of breast cancer

GOLPH2 protein expression as a novel tissue biomarker for prostate cancer: implications for tissue-based diagnostics

GOLPH2 is coding the 73-kDa type II Golgi membrane antigen GOLPH2/GP73. Upregulation of GOLPH2 mRNA has been recently reported in expression array analyses of prostate cancer. As GOLPH2 protein expression in prostate tissues is currently unknown, this study aimed at a comprehensive analysis of GOLPH2 protein in benign and malignant prostate lesions. Immunohistochemically detected GOLPH2 protein expression was compared with the basal cell marker p63 and the prostate cancer marker α-methylacyl-CoA racemase (AMACR) in 614 radical prostatectomy specimens. GOLPH2 exhibited a perinuclear Golgi-type staining pattern and was preferentially seen in prostatic gland epithelia. Using a semiquantitative staining intensity score, GOLPH2 expression was significantly higher in prostate cancer glands compared with normal glands (P<0.001). GOLPH2 protein was upregulated in 567 of 614 tumours (92.3%) and AMACR in 583 of 614 tumours (95%) (correlation coefficient 0.113, P=0.005). Importantly, GOLPH2 immunohistochemistry exhibited a lower level of intratumoral heterogeneity (25 vs 45%). Further, GOLPH2 upregulation was detected in 26 of 31 (84%) AMACR-negative prostate cancer cases. These data clearly suggest GOLPH2 as an additional ancillary positive marker for tissue-based diagnosis of prostate cancer

Expression analysis onto microarrays of randomly selected cDNA clones highlights HOXB13 as a marker of human prostate cancer

In a strategy aimed at identifying novel markers of human prostate cancer, we performed expression analysis using microarrays of clones randomly selected from a cDNA library prepared from the LNCaP prostate cancer cell line. Comparisons of expression profiles in primary human prostate cancer, adjacent normal prostate tissue, and a selection of other (nonprostate) normal human tissues, led to the identification of a set of clones that were judged as the best candidate markers of normal and/or malignant prostate tissue. DNA sequencing of the selected clones revealed that they included 10 genes that had previously been established as prostate markers: NKX3.1, KLK2, KLK3 (PSA), FOLH1 (PSMA), STEAP2, PSGR, PRAC, RDH11, Prostein and FASN. Following analysis of the expression patterns of all selected and sequenced genes through interrogation of SAGE databases, a further three genes from our clone set, HOXB13, SPON2 and NCAM2, emerged as additional candidate markers of human prostate cancer. Quantitative RT–PCR demonstrated the specificity of expression of HOXB13 in prostate tissue and revealed its ubiquitous expression in a series of 37 primary prostate cancers and 20 normal prostates. These results demonstrate the utility of this expression-microarray approach in hunting for new markers of individual human cancer types