Autologous minced cartilage implantation along with MPFC advancement for recurrent dislocation of the patella with chondral defect of the medial patellar facet- A novel technique

Recurrent patellar dislocation often requires surgical intervention. It is often associated with chondral defects of the Patella. Even a small cartilage lesion of the patella of 1 cm2 dimension will lead to rapid onset of arthrosis. Minced cartilage has a strong biologic potential since autologous, activated non- dedifferentiated cartilage cells are utilized . MPFC advancement is an isometric procedure. Good knowledge of the layers of the knee on the medial side helps in proper advancement of the layer. It can be combined with the cartilaginous procedures on the patella

Towards pain-free diagnosis of skin diseases through multiplexed microneedles: biomarker extraction and detection using a highly sensitive blotting method

Immunodiagnostic microneedles provide a novel way to extract protein biomarkers from the skin in a minimally invasive manner for analysis in vitro. The technology could overcome challenges in biomarker analysis specifically in solid tissue, which currently often involves invasive biopsies. This study describes the development of a multiplex immunodiagnostic device incorporating mechanisms to detect multiple antigens simultaneously, as well as internal assay controls for result validation. A novel detection method is also proposed. It enables signal detection specifically at microneedle tips and therefore may aid the construction of depth profiles of skin biomarkers. The detection method can be coupled with computerised densitometry for signal quantitation. The antigen specificity, sensitivity and functional stability of the device were assessed against a number of model biomarkers. Detection and analysis of endogenous antigens (interleukins 1α and 6) from the skin using the device was demonstrated. The results were verified using conventional enzyme-linked immunosorbent assays. The detection limit of the microneedle device, at ≤10 pg/mL, was at least comparable to conventional plate-based solid-phase enzyme immunoassays

Comparison of the sensitivity of the UKCAT and A levels to sociodemographic characteristics: a national study

Background: The UK Clinical Aptitude Test (UKCAT) was introduced to facilitate widening participation in medical and dental education in the UK by providing universities with a continuous variable to aid selection; one that might be less sensitive to the sociodemographic background of candidates compared to traditional measures of educational attainment. Initial research suggested that males, candidates from more advantaged socioeconomic backgrounds and those who attended independent or grammar schools performed better on the test. The introduction of the A* grade at A level permits more detailed analysis of the relationship between UKCAT scores, secondary educational attainment and sociodemographic variables. Thus, our aim was to further assess whether the UKCAT is likely to add incremental value over A level (predicted or actual) attainment in the selection process. Methods: Data relating to UKCAT and A level performance from 8,180 candidates applying to medicine in 2009 who had complete information relating to six key sociodemographic variables were analysed. A series of regression analyses were conducted in order to evaluate the ability of sociodemographic status to predict performance on two outcome measures: A level ‘best of three’ tariff score; and the UKCAT scores. Results: In this sample A level attainment was independently and positively predicted by four sociodemographic variables (independent/grammar schooling, White ethnicity, age and professional social class background). These variables also independently and positively predicted UKCAT scores. There was a suggestion that UKCAT scores were less sensitive to educational background compared to A level attainment. In contrast to A level attainment, UKCAT score was independently and positively predicted by having English as a first language and male sex. Conclusions: Our findings are consistent with a previous report; most of the sociodemographic factors that predict A level attainment also predict UKCAT performance. However, compared to A levels, males and those speaking English as a first language perform better on UKCAT. Our findings suggest that UKCAT scores may be more influenced by sex and less sensitive to school type compared to A levels. These factors must be considered by institutions utilising the UKCAT as a component of the medical and dental school selection process

First Neutrino Observations from the Sudbury Neutrino Observatory

The first neutrino observations from the Sudbury Neutrino Observatory are presented from preliminary analyses. Based on energy, direction and location, the data in the region of interest appear to be dominated by 8B solar neutrinos, detected by the charged current reaction on deuterium and elastic scattering from electrons, with very little background. Measurements of radioactive backgrounds indicate that the measurement of all active neutrino types via the neutral current reaction on deuterium will be possible with small systematic uncertainties. Quantitative results for the fluxes observed with these reactions will be provided when further calibrations have been completed.Comment: Latex, 7 pages, 10 figures, Invited paper at Neutrino 2000 Conference, Sudbury, Canada, June 16-21, 2000 to be published in the Proceeding

The association between misperceptions around weight status and quality of life in adults in Australia

Objective: Limited evidence supports a possible association between a person’s perception of their weight status and their quality of life (QoL). This study evaluates whether misperception around weight status is associated with QoL and the impact of gender on this association. Methods: A cross-sectional survey of Australian adults (n=1,905 analysed) collected selfreported height and weight (used to estimate BMI), gender and QoL (described using the AQoL-8D). Participants reported whether they perceived their weight status to be ‘underweight’, ‘healthy weight’, ‘overweight’ or ‘obese’. Misperception around weight status was categorised based on perceived weight status and self-reported BMI. Ordinary least squares regression was used to test associations between self-reported overall, physical and psychosocial QoL, misperception of weight status, and gender, across different BMI categories, after controlling for income, education, relationship status and health conditions. Results: Compared to accurate perception, underestimation of weight status was associated with higher overall QoL for obese males and females and for overweight males. Overestimation of weight status was associated with higher overall QoL for underweight females and lower overall QoL for healthy weight males and females. The same pattern was seen for psychosocial QoL. Physical QoL was less sensitive to misperception than psychosocial QoL. Conclusions: Self-reported misperception around weight status is associated with overall, psychosocial and to a lesser extent physical QoL in Australian adults, although its role depends on BMI category and gender. Generally misperception in the direction of “healthy weight” is associated with higher QoL and overestimation of weight status by those who are of healthy weight is associated with lower QoL. Findings should be confirmed in datasets that contain measured as opposed to self-report height and weight

Evaluation of molecular descriptors for antitumor drugs with respect to noncovalent binding to DNA and antiproliferative activity

34 pages, 6 additional files, 5 tables, 4 figures.[Background ] Small molecules that bind reversibly to DNA are among the antitumor drugs currently used in chemotherapy. In the pursuit of a more rational approach to cancer chemotherapy based upon these molecules, it is necessary to exploit the interdependency between DNA-binding affinity, sequence selectivity and cytotoxicity. For drugs binding noncovalently to DNA, it is worth exploring whether molecular descriptors, such as their molecular weight or the number of potential hydrogen acceptors/donors, can account for their DNA-binding affinity and cytotoxicity.[Results] Fifteen antitumor agents, which are in clinical use or being evaluated as part of the National Cancer Institute’s drug screening effort, were analyzed in silico to assess the contribution of various molecular descriptors to their DNA-binding affinity, and the capacity of the descriptors and DNA-binding constants for predicting cell cytotoxicity. Equations to predict drug-DNA binding constants and growth-inhibitory concentrations were obtained by multiple regression following rigorous statistical procedures.[Conclusions] For drugs binding reversibly to DNA, both their strength of binding and their cytoxicity are fairly predicted from molecular descriptors by using multiple regression methods. The equations derived may be useful for rational drug design. The results obtained agree with that compounds more active across the National Cancer Institute’s 60-cell line data set tend to have common structural features.Supported by a grant from the former Spanish Ministry of Education and Science (BFU2007-60998) and the FEDER program of the European Community.Peer reviewe

Evaluation of gut modulatory and bronchodilator activities of Amaranthus spinosus Linn.

Background The aqueous-methanolic extract of Amaranthus spinosus (A. spinosus Linn.,) whole plant, was studied for its laxative, spasmolytic and bronchodilator activities to validate some of its medicinal uses. Methods The crude extract of A. spinosus was studied in-vivo for bronchodilator and laxative activities and in-vitro using isolated tissue preparations which were mounted in tissue baths assembly containing physiological salt solutions, maintained at 37°C and aerated with carbogen, to assess the spasmolytic effect and to find out the possible underlying mechanisms. Results In the in-vivo experiments in mice, the administration of A. spinosus increased fecal output at doses of 100 and 300 mg/kg showing laxative activity. It also inhibited carbachol-induced bronchospasm in anesthetized rats at 1, 3, 10 and 30 mg/kg indicative of bronchodilator activity. When tested on isolated gut preparations, the plant extract showed a concentration-dependent (0.01-10.0 mg/ml) spasmogenic effect in spontaneously contracting rabbit jejunum and guinea-pig ileum. The spasmogenic effect was partially blocked in tissues pretreated with atropine (0.1 μM). When tested on K+ (80 mM)-induced sustained contractions in isolated rabbit jejunum, the plant extract caused complete relaxation and also produced a shift in the Ca++ concentration-response curves (CRCs) towards right, similar to diltiazem. In rabbit trachea, the plant extract completely inhibited K+ (80 mM) and carbachol (CCh, 1 μM)-induced contractions at 1 mg/ml but pretreatment of tissue with propranolol (1 μM), caused around 10 fold shift in the inhibitory CRCs of the plant extract constructed against CCh-induced contraction. The plant extract (up to 0.3 mg/ml) also increased both force and rate of spontaneous contractions of isolated guinea-pig atria, followed by relaxation at higher concentration (1.0-5.0 mg/ml). The cardio-stimulant effect was abolished in the presence of propranolol, similar to that of isoprenaline. Activity-directed fractionation revealed that the spasmolytic component(s) was separated in the organic fraction, whereas the spasmogenic component was concentrated in the aqueous fraction. Conclusion These results indicate that A. spinosus possesses laxative activity partially mediated through cholinergic action. The spasmolytic effect was mediated through calcium channel blocking (CCB), while bronchodilator activity through a combination of β-adrenergic and CCB pathways, which may explain the traditional uses of A. spinosus in gut and airways disorders

Is the inflammasome a potential therapeutic target in renal disease?

The inflammasome is a large, multiprotein complex that drives proinflammatory cytokine production in response to infection and tissue injury. Pattern recognition receptors that are either membrane bound or cytoplasmic trigger inflammasome assembly. These receptors sense danger signals including damage-associated molecular patterns and pathogen-associated molecular patterns (DAMPS and PAMPS respectively). The best-characterized inflammasome is the NLRP3 inflammasome. On assembly of the NLRP3 inflammasome, post-translational processing and secretion of pro-inflammatory cytokines IL-1β and IL-18 occurs; in addition, cell death may be mediated via caspase-1. Intrinsic renal cells express components of the inflammasome pathway. This is most prominent in tubular epithelial cells and, to a lesser degree, in glomeruli. Several primary renal diseases and systemic diseases affecting the kidney are associated with NLRP3 inflammasome/IL-1β/IL-18 axis activation. Most of the disorders studied have been acute inflammatory diseases. The disease spectrum includes ureteric obstruction, ischaemia reperfusion injury, glomerulonephritis, sepsis, hypoxia, glycerol-induced renal failure, and crystal nephropathy. In addition to mediating renal disease, the IL-1/ IL-18 axis may also be responsible for development of CKD itself and its related complications, including vascular calcification and sepsis. Experimental models using genetic deletions and/or receptor antagonists/antiserum against the NLRP3 inflammasome pathway have shown decreased severity of disease. As such, the inflammasome is an attractive potential therapeutic target in a variety of renal diseases

Integrated Analysis of Residue Coevolution and Protein Structure in ABC Transporters

Intraprotein side chain contacts can couple the evolutionary process of amino acid substitution at one position to that at another. This coupling, known as residue coevolution, may vary in strength. Conserved contacts thus not only define 3-dimensional protein structure, but also indicate which residue-residue interactions are crucial to a protein’s function. Therefore, prediction of strongly coevolving residue-pairs helps clarify molecular mechanisms underlying function. Previously, various coevolution detectors have been employed separately to predict these pairs purely from multiple sequence alignments, while disregarding available structural information. This study introduces an integrative framework that improves the accuracy of such predictions, relative to previous approaches, by combining multiple coevolution detectors and incorporating structural contact information. This framework is applied to the ABC-B and ABC-C transporter families, which include the drug exporter P-glycoprotein involved in multidrug resistance of cancer cells, as well as the CFTR chloride channel linked to cystic fibrosis disease. The predicted coevolving pairs are further analyzed based on conformational changes inferred from outward- and inward-facing transporter structures. The analysis suggests that some pairs coevolved to directly regulate conformational changes of the alternating-access transport mechanism, while others to stabilize rigid-body-like components of the protein structure. Moreover, some identified pairs correspond to residues previously implicated in cystic fibrosis