A multicenter prospective trial evaluating fetal bovine dermal graft (Xenform® Matrix) for pelvic reconstructive surgery

<p>Abstract</p> <p>Background</p> <p>A prospective multicenter clinical study was performed to evaluate the safety and efficacy of a bovine dermal graft (Xenform^®Matrix, Boston Scientific, Natick, MA, USA) during vaginal reconstructive surgery.</p> <p>Methods</p> <p>Forty-five women with ICS stage 2 or higher pelvic organ prolapse (POP) were enrolled at 4 centers. POP-Q, pelvic floor function (PFDI-20), sexual function (PISQ-12), and patient satisfaction tools were used to assess subjects at baseline, and at 2 and 6 weeks, and 3, 6 and 12 months post surgery. The significance of symptom score changes at 6 months and 1 year were determined by the t-test for paired data. Forty-three of the 45 patients completed the 12 month study.</p> <p>Results</p> <p>The majority of the subjects had cystocele (98%) and/or rectocele (84%) defects at study entry. At 12 months, 74% of the defects had improved to a stage 0 or 1. Mean PFDI-20 scores improved by 72% (p < 0.001) at 12 months, and PISQ-12 scores were maintained during the follow-up period indicating no decline in sexual function. Three subjects experienced one serious adverse event each; one of the adverse events (constipation) was deemed by the study physician to be unrelated to Xenform^®. One subject had severe pyelonephritis resulting in dialysis. This subject had a previous history of pyelonephritis, sepsis and acute renal failure. The third subject had a reported recurrent cystocele of moderate severity, possibly related to the device. No graft related erosions or pain lasting more than 30 days were reported. No subjects withdrew due to an adverse event.</p> <p>Conclusion</p> <p>This study is the first to investigate the use of Xenform^®Matrix in vaginal reconstructive surgery among patients with POP. Significant improvement was maintained at 12 months utilizing both objective and subjective assessment tools, confirming the safety and efficacy of this material in vaginal surgery.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT01244165</p

Potential conservation of circadian clock proteins in the phylum Nematoda as revealed by bioinformatic searches

Although several circadian rhythms have been described in C. elegans, its molecular clock remains elusive. In this work we employed a novel bioinformatic approach, applying probabilistic methodologies, to search for circadian clock proteins of several of the best studied circadian model organisms of different taxa (Mus musculus, Drosophila melanogaster, Neurospora crassa, Arabidopsis thaliana and Synechoccocus elongatus) in the proteomes of C. elegans and other members of the phylum Nematoda. With this approach we found that the Nematoda contain proteins most related to the core and accessory proteins of the insect and mammalian clocks, which provide new insights into the nematode clock and the evolution of the circadian system.Fil: Romanowski, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; ArgentinaFil: Garavaglia, Matías Javier. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Ing.genética y Biolog.molecular y Celular. Area Virus de Insectos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Goya, María Eugenia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ghiringhelli, Pablo Daniel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Ing.genética y Biolog.molecular y Celular. Area Virus de Insectos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Golombek, Diego Andres. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Chronic non-specific low back pain - sub-groups or a single mechanism?

Copyright 2008 Wand and O'Connell; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Low back pain is a substantial health problem and has subsequently attracted a considerable amount of research. Clinical trials evaluating the efficacy of a variety of interventions for chronic non-specific low back pain indicate limited effectiveness for most commonly applied interventions and approaches. Discussion: Many clinicians challenge the results of clinical trials as they feel that this lack of effectiveness is at odds with their clinical experience of managing patients with back pain. A common explanation for this discrepancy is the perceived heterogeneity of patients with chronic non-specific low back pain. It is felt that the effects of treatment may be diluted by the application of a single intervention to a complex, heterogeneous group with diverse treatment needs. This argument presupposes that current treatment is effective when applied to the correct patient. An alternative perspective is that the clinical trials are correct and current treatments have limited efficacy. Preoccupation with sub-grouping may stifle engagement with this view and it is important that the sub-grouping paradigm is closely examined. This paper argues that there are numerous problems with the sub-grouping approach and that it may not be an important reason for the disappointing results of clinical trials. We propose instead that current treatment may be ineffective because it has been misdirected. Recent evidence that demonstrates changes within the brain in chronic low back pain sufferers raises the possibility that persistent back pain may be a problem of cortical reorganisation and degeneration. This perspective offers interesting insights into the chronic low back pain experience and suggests alternative models of intervention. Summary: The disappointing results of clinical research are commonly explained by the failure of researchers to adequately attend to sub-grouping of the chronic non-specific low back pain population. Alternatively, current approaches may be ineffective and clinicians and researchers may need to radically rethink the nature of the problem and how it should best be managed

Comparison of two self-reported measures of physical work demands in hospital personnel: A cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Low back pain (LBP) is a frequent health complaint among health care personnel. Several work tasks and working postures are associated with an increased risk of LBP. The aim of this study was to compare two self-reported measures of physical demands and their association with LBP (the daily number of patient handling tasks and Hollmann's physical load index).</p> <p>Methods</p> <p>A questionnaire was distributed to 535 hospital employees in a psychiatric and an orthopedic ward in a Danish hospital. Of these 411 (77%) filled in and returned the questionnaire. Only the 373 respondents who had non-missing values on both measures of physical demands were included in the analyses. The distribution of physical demands in different job groups and wards are presented, variance analysis models are employed, and logistic regression analysis is used to analyze the association between measures of physical demands and LBP.</p> <p>Results</p> <p>In combination, hospital ward and job category explained 56.6% and 23.3% of the variance in the self-reported physical demands measured as the daily number of patient handling tasks and as the score on the physical load index, respectively. When comparing the 6% with the highest exposure the prevalence odds ratio (POR) for LBP was 5.38 (95% CI 2.03–14.29) in the group performing more than 10 patient handling tasks per day and 2.29 (95% CI 0.93–5.66) in the group with the highest score on the physical load index.</p> <p>Conclusion</p> <p>In specialized hospital wards the daily number of patient handling tasks seems to be a more feasible measure of exposure when assessing the risk of LBP compared to more advanced measures of physical load on the lower lumbar spine.</p

Multidimensional Proteomics Analysis of Amniotic Fluid to Provide Insight into the Mechanisms of Idiopathic Preterm Birth

Though recent advancement in proteomics has provided a novel perspective on several distinct pathogenetic mechanisms leading to preterm birth (inflammation, bleeding), the etiology of most preterm births still remains elusive. We conducted a multidimensional proteomic analysis of the amniotic fluid to identify pathways related to preterm birth in the absence of inflammation or bleeding.A proteomic fingerprint was generated from fresh amniotic fluid using surface-enhanced laser desorbtion ionization time of flight (SELDI-TOF) mass spectrometry in a total of 286 consecutive samples retrieved from women who presented with signs or symptoms of preterm labor or preterm premature rupture of the membranes. Inflammation and/or bleeding proteomic patterns were detected in 32% (92/286) of the SELDI tracings. In the remaining tracings, a hierarchical algorithm was applied based on descriptors quantifying similarity/dissimilarity among proteomic fingerprints. This allowed identification of a novel profile (Q-profile) based on the presence of 5 SELDI peaks in the 10-12.5 kDa mass area. Women displaying the Q-profile (mean+/-SD, gestational age: 25+/-4 weeks, n = 40) were more likely to deliver preterm despite expectant management in the context of intact membranes and normal amniotic fluid clinical results. Utilizing identification-centered proteomics techniques (fluorescence two-dimensional differential gel electrophoresis, robotic tryptic digestion and mass spectrometry) coupled with Protein ANalysis THrough Evolutionary Relationships (PANTHER) ontological classifications, we determined that in amniotic fluids with Q-profile the differentially expressed proteins are primarily involved in non-inflammatory biological processes such as protein metabolism, signal transduction and transport.Proteomic profiling of amniotic fluid coupled with non-hierarchical bioinformatics algorithms identified a subgroup of patients at risk for preterm birth in the absence of intra-amniotic inflammation or bleeding, suggesting a novel pathogenetic pathway leading to preterm birth. The altered proteins may offer opportunities for therapeutical intervention and future drug development to prevent prematurity

Wind anisotropies and GRB progenitors

We study the effect of wind anisotropies on the stellar evolution leading to collapsars. Rotating models of a 60 M$_\odot$ star with $\Omega/\Omega_{\rm crit}=0.75$ on the ZAMS, accounting for shellular rotation and a magnetic field, with and without wind anisotropies, are computed at $Z$=0.002 until the end of the core He-burning phase. Only the models accounting for the effects of the wind anisotropies retain enough angular momentum in their core to produce a Gamma Ray Burst (GRB). The chemical composition is such that a type Ic supernova event occurs. Wind anisotropies appear to be a key physical ingredient in the scenario leading to long GRBs.Comment: 5 pages, 4 figures, accepted for publication in A&A Lette

Mass Spectrometry Analysis of Hepcidin Peptides in Experimental Mouse Models

The mouse is a valuable model for unravelling the role of hepcidin in iron homeostasis, however, such studies still report hepcidin mRNA levels as a surrogate marker for bioactive hepcidin in its pivotal function to block ferroportin-mediated iron transport. Here, we aimed to assess bioactive mouse Hepcidin-1 (Hep-1) and its paralogue Hepcidin-2 (Hep-2) at the peptide level. To this purpose, fourier transform ion cyclotron resonance (FTICR) and tandem-MS was used for hepcidin identification, after which a time-of-flight (TOF) MS-based methodology was exploited to routinely determine Hep-1 and -2 levels in mouse serum and urine. This method was biologically validated by hepcidin assessment in: i) 3 mouse strains (C57Bl/6; DBA/2 and BABL/c) upon stimulation with intravenous iron and LPS, ii) homozygous Hfe knock out, homozygous transferrin receptor 2 (Y245X) mutated mice and double affected mice, and iii) mice treated with a sublethal hepatotoxic dose of paracetamol. The results showed that detection of Hep-1 was restricted to serum, whereas Hep-2 and its presumed isoforms were predominantly present in urine. Elevations in serum Hep-1 and urine Hep-2 upon intravenous iron or LPS were only moderate and varied considerably between mouse strains. Serum Hep-1 was decreased in all three hemochromatosis models, being lowest in the double affected mice. Serum Hep-1 levels correlated with liver hepcidin-1 gene expression, while acute liver damage by paracetamol depleted Hep-1 from serum. Furthermore, serum Hep-1 appeared to be an excellent indicator of splenic iron accumulation. In conclusion, Hep-1 and Hep-2 peptide responses in experimental mouse agree with the known biology of hepcidin mRNA regulators, and their measurement can now be implemented in experimental mouse models to provide novel insights in post-transcriptional regulation, hepcidin function, and kinetics

Genome-Wide Association Study Identifies Genetic Loci Associated with Iron Deficiency

The existence of multiple inherited disorders of iron metabolism in man, rodents and other vertebrates suggests genetic contributions to iron deficiency. To identify new genomic locations associated with iron deficiency, a genome-wide association study (GWAS) was performed using DNA collected from white men aged ≥25 y and women ≥50 y in the Hemochromatosis and Iron Overload Screening (HEIRS) Study with serum ferritin (SF) ≤ 12 µg/L (cases) and iron replete controls (SF>100 µg/L in men, SF>50 µg/L in women). Regression analysis was used to examine the association between case-control status (336 cases, 343 controls) and quantitative serum iron measures and 331,060 single nucleotide polymorphism (SNP) genotypes, with replication analyses performed in a sample of 71 cases and 161 controls from a population of white male and female veterans screened at a US Veterans Affairs (VA) medical center. Five SNPs identified in the GWAS met genome-wide statistical significance for association with at least one iron measure, rs2698530 on chr. 2p14; rs3811647 on chr. 3q22, a known SNP in the transferrin (TF) gene region; rs1800562 on chr. 6p22, the C282Y mutation in the HFE gene; rs7787204 on chr. 7p21; and rs987710 on chr. 22q11 (GWAS observed P<1.51×10−7 for all). An association between total iron binding capacity and SNP rs3811647 in the TF gene (GWAS observed P = 7.0×10−9, corrected P = 0.012) was replicated within the VA samples (observed P = 0.012). Associations with the C282Y mutation in the HFE gene also were replicated. The joint analysis of the HEIRS and VA samples revealed strong associations between rs2698530 on chr. 2p14 and iron status outcomes. These results confirm a previously-described TF polymorphism and implicate one potential new locus as a target for gene identification

Lumbar segmental mobility disorders: comparison of two methods of defining abnormal displacement kinematics in a cohort of patients with non-specific mechanical low back pain

BACKGROUND: Lumbar segmental rigidity (LSR) and lumbar segmental instability (LSI) are believed to be associated with low back pain (LBP), and identification of these disorders is believed to be useful for directing intervention choices. Previous studies have focussed on lumbar segmental rotation and translation, but have used widely varying methodologies. Cut-off points for the diagnosis of LSR & LSI are largely arbitrary. Prevalence of these lumbar segmental mobility disorders (LSMDs) in a non-surgical, primary care LBP population has not been established. METHODS: A cohort of 138 consecutive patients with recurrent or chronic low back pain (RCLBP) were recruited in this prospective, pragmatic, multi-centre study. Consenting patients completed pain and disability rating instruments, and were referred for flexion-extension radiographs. Sagittal angular rotation and sagittal translation of each lumbar spinal motion segment was measured from the radiographs, and compared to a reference range derived from a study of 30 asymptomatic volunteers. In order to define reference intervals for normal motion, and define LSR and LSI, we approached the kinematic data using two different models. The first model used a conventional Gaussian definition, with motion beyond two standard deviations (2sd) from the reference mean at each segment considered diagnostic of rotational LSMD and translational LSMD. The second model used a novel normalised within-subjects approach, based on mean normalised contribution-to-total-lumbar-motion. An LSMD was then defined as present in any segment that contributed motion beyond 2sd from the reference mean contribution-to-normalised-total-lumbar-motion. We described reference intervals for normal segmental mobility, prevalence of LSMDs under each model, and the association of LSMDs with pain and disability. RESULTS: With the exception of the conventional Gaussian definition of rotational LSI, LSMDs were found in statistically significant prevalences in patients with RCLBP. Prevalences at both the segmental and patient level were generally higher using the normalised within-subjects model (2.8 to 16.8% of segments; 23.3 to 35.5% of individuals) compared to the conventional Gaussian model (0 to 15.8%; 4.7 to 19.6%). LSMDs are associated with presence of LBP, however LSMDs do not appear to be strongly associated with higher levels of pain or disability compared to other forms of non-specific LBP. CONCLUSION: LSMDs are a valid means of defining sub-groups within non-specific LBP, in a conservative care population of patients with RCLBP. Prevalence was higher using the normalised within-subjects contribution-to-total-lumbar-motion approach

Sensory Perception of Food and Insulin-Like Signals Influence Seizure Susceptibility

Food deprivation is known to affect physiology and behavior. Changes that occur could be the result of the organism's monitoring of internal and external nutrient availability. In C. elegans, male mating is dependent on food availability; food-deprived males mate with lower efficiency compared to their well-fed counterparts, suggesting that the mating circuit is repressed in low-food environments. This behavioral response could be mediated by sensory neurons exposed to the environment or by internal metabolic cues. We demonstrated that food-deprivation negatively regulates sex-muscle excitability through the activity of chemosensory neurons and insulin-like signaling. Specifically, we found that the repressive effects of food deprivation on the mating circuit can be partially blocked by placing males on inedible food, E. coli that can be sensed but not eaten. We determined that the olfactory AWC neurons actively suppress sex-muscle excitability in response to food deprivation. In addition, we demonstrated that loss of insulin-like receptor (DAF-2) signaling in the sex muscles blocks the ability of food deprivation to suppress the mating circuit. During low-food conditions, we propose that increased activity by specific olfactory neurons (AWCs) leads to the release of neuroendocrine signals, including insulin-like ligands. Insulin-like receptor signaling in the sex muscles then reduces cell excitability via activation of downstream molecules, including PLC-γ and CaMKII