Silent soft tissue pathology is common with a modern metal-on-metal hip arthroplasty: Early detection with routine metal artifact-reduction MRI scanning

Adverse reactions to metal debris have been reported to be a cause of pain in metal-on-metal hip arthroplasty. We assessed the incidence of both symptomatic and asymptomatic adverse reactions in a consecutive series of patients with a modern large-head metal-on-metal hip arthroplasty

A double-blind, placebo-controlled study of the short term effects of a spring water supplemented with magnesium bicarbonate on acid/base balance, bone metabolism and cardiovascular risk factors in postmenopausal women

<p>Abstract</p> <p>Background</p> <p>A number of health benefits including improvements in acid/base balance, bone metabolism, and cardiovascular risk factors have been attributed to the intake of magnesium rich alkaline mineral water. This study was designed to investigate the effects of the regular consumption of magnesium bicarbonate supplemented spring water on pH, biochemical parameters of bone metabolism, lipid profile and blood pressure in postmenopausal women.</p> <p>Findings</p> <p>In this double-blind, placebo-controlled, parallel-group, study, 67 postmenopausal women were randomised to receive between 1500 mL and 1800 mL daily of magnesium bicarbonate supplemented spring water (650 mg/L bicarbonate, 120 mg/L magnesium, pH 8.3-8.5) (supplemented water group) or spring water without supplements (control water group) over 84 days. Over this period biomarkers of bone turnover (serum parathyroid hormone (PTH), 1,25-dihydroxyvitamin D, osteocalcin, urinary telopeptides and hydroxyproline), serum lipids (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides), venous and urinary pH were measured together with measurements of standard biochemistry, haematology and urine examinations.</p> <p>Serum magnesium concentrations and urinary pH in subjects consuming the magnesium bicarbonate supplemented water increased significantly at Day 84 compared to subjects consuming the spring water control (magnesium - p = 0.03; pH - p = 0.018). The consumption of spring water led to a trend for an increase in parathyroid hormone (PTH) concentrations while the PTH concentrations remained stable with the intake of the supplemented spring water. However there were no significant effects of magnesium bicarbonate supplementation in changes to biomarkers of bone mineral metabolism (n-telopeptides, hydroxyproline, osteocalcin and 1,25-dihydroxyvitamin D) or serum lipids or blood pressure in postmenopausal women from Day 0 to Day 84.</p> <p>Conclusions</p> <p>Short term regular ingestion of magnesium bicarbonate supplemented water provides a source of orally available magnesium. Long term clinical studies are required to investigate any health benefits.</p> <p>Trial registration</p> <p>ACTRN12609000863235</p

Comparing two intramedullary devices for treating trochanteric fractures: A prospective study

<p>Abstract</p> <p>Background</p> <p>Intertrochanteric fractures are surgically treated by using different methods and implants. The optional type of surgical stabilization is still under debate. However, between devices with the same philosophy, different design characteristics may substantially influence fracture healing. This is a prospective study comparing the complication and final functional outcome of two intramedullary devices, the intramedullary hip screw (IMHS) and the ENDOVIS nail.</p> <p>Materials and methods</p> <p>Two hundred fifteen patients were randomized on admission in two treatment groups. Epidemiology features and functional status was similar between two treatment groups. Fracture stability was assessed according to the Evan's classification. One hundred ten patients were treated with IMHS and 105 with ENDOVIS nail.</p> <p>Results</p> <p>There were no significant statistical differences between the two groups regarding blood loss, transfusion requirements and mortality rate. In contrast, the number of total complications was significantly higher in the ENDOVIS nail group. Moreover, the overall functional and walking competence was superior in the patients treated with the IMHS nail.</p> <p>Conclusions</p> <p>These results indicate that the choice of the proper implant plays probably an important role in the final outcome of surgical treatment of intertrochanteric fractures. IMHS nail allows for accurate surgical technique, for both static and dynamic compression and high rotational stability. IMHS nail proved more reliable in our study regarding nail insertion and overall uncomplicated outcome.</p

Schizophrenia-associated HapICE haplotype is associated with increased NRG1 type III expression and high nucleotide diversity

Excitement and controversy have followed neuregulin (NRG1) since its discovery as a putative schizophrenia susceptibility gene; however, the mechanism of action of the associated risk haplotype (HapICE) has not been identified, and specific genetic variations, which may increase risk to schizophrenia have remained elusive. Using a postmortem brain cohort from 37 schizophrenia cases and 37 controls, we resequenced upstream of the type I–IV promoters, and the HapICE repeat regions in intron 1. Relative abundance of seven NRG1 mRNA transcripts in the prefrontal cortex were determined and compared across diagnostic and genotypic groups. We identified 26 novel DNA variants and showed an increased novel variant load in cases compared with controls (χ2=7.815; P=0.05). The average nucleotide diversity (θ=10.0 × 10−4) was approximately twofold higher than that previously reported for BDNF, indicating that NRG1 may be particularly prone to genetic change. A greater nucleotide diversity was observed in the HapICE linkage disequilibrium block in schizophrenia cases (θ(case)=13.2 × 10−4; θ(control)=10.0 × 10−4). The specific HapICE risk haplotype was associated with increased type III mRNA (F=3.76, P=0.028), which in turn, was correlated with an earlier age of onset (r=−0.343, P=0.038). We found a novel intronic five-SNP haplotype ∼730 kb upstream of the type I promoter and determined that this region functions as transcriptional enhancer that is suppressed by SRY. We propose that the HapICE risk haplotype increases expression of the most brain-abundant form of NRG1, which in turn, elicits an earlier clinical presentation, thus providing a novel mechanism through which this genetic association may increase risk of schizophrenia

The potential of the solitary parasitoid Microctonus brassicae for the biological control of the adult cabbage stem flea beetle, Psylliodes chrysocephala

The cabbage stem flea beetle (CSFB), Psylliodes chrysocephala L. (Coleoptera: Chrysomelidae), is a major pest of oilseed rape, Brassica napus L. (Brassicaceae), within the UK and continental Europe. Following the withdrawal of many broad‐spectrum pesticides, most importantly neonicotinoids, and with increased incidence of pyrethroid resistance, few chemical control options remain, resulting in the need for alternative pest management strategies. We identified the parasitoid wasp Microctonus brassicae (Haeselbarth) (Hymenoptera: Braconidae) within CSFB collected from three independent sites in Norfolk, UK. Parasitism of adult CSFB was confirmed, and wasp oviposition behaviour was described. Moreover, we show that within captive colonies parasitism rates are sufficient to generate significant biological control of CSFB populations. A sequence of the M. brassicae mitochondrial cytochrome oxidase 1 (MT‐CO1) gene was generated for rapid future identification. Moroccan specimens of Microctonus aethiopoides (Loan), possessing 90% sequence similarity, were the closest identified sequenced species. This study represents the first description published in English of this parasitoid of the adult cabbage stem flea beetle.© 2020 The Authors. Entomologia Experimentalis et Applicata published by John Wiley & Sons Ltd on behalf of Netherlands Entomological Society This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. The attached file is the published pdf

Characterization of the effects of cross-linking of macrophage CD44 associated with increased phagocytosis of apoptotic PMN

Control of macrophage capacity for apoptotic cell clearance by soluble mediators such as cytokines, prostaglandins and lipoxins, serum proteins, and glucocorticoids may critically determine the rate at which inflammation resolves. Previous studies suggested that macrophage capacity for clearance of apoptotic neutrophils was profoundly altered following binding of CD44 antibodies. We have used a number of different approaches to further define the mechanism by which CD44 rapidly and specifically augment phagocytosis of apoptotic neutrophils. Use of Fab ’ fragments unequivocally demonstrated a requirement for cross-linking of macrophage surface CD44. The molecular mechanism of CD44-augmented phagocytosis was shown to be opsonin-independent and to be distinct from the Mer/protein S pathway induced by glucocorticoids and was not functional for clearance of apoptotic eosinophils. CD44-cross-linking also altered macrophage migration and induced cytoskeletal re-organisation together with phosphorylation of paxillin and activation of Rac2. Investigation of signal transduction pathways that might be critical for CD44 augmentation of phagocytosis revealed that Ca 2+ signalling, PI-3 kinase pathways and altered cAMP signalling were not involved, but did implicate a key role for tyrosine phosphorylation events. Finally, although CD44 antibodies were able to augment phagocytosis of apoptotic neutrophils by murine peritoneal and bone marrow-derived macrophages, we did not observe a difference in the clearance of neutrophils following induction of peritonitis with thioglycollate in CD44-deficient animals. Together, these data demonstrate that CD4

Insulin-like growth factor binding protein 5 enhances survival of LX2 human hepatic stellate cells

ABSTRACT: BACKGROUND: Expression of insulin-like growth factor binding protein 5 (IGFBP5) is strongly induced upon activation of hepatic stellate cells and their transdifferentiation into myofibroblasts in vitro. This was confirmed in vivo in an animal model of liver fibrosis. Since IGFBP5 has been shown to promote fibrosis in other tissues, the aim of this study was to investigate its role in the progression of liver fibrosis. METHODS: The effect of IGFBP5 was studied in LX2 cells, a model for partially activated hepatic stellate cells, and in human primary liver myofibroblasts. IGFBP5 signalling was modulated by the addition of recombinant protein, by lentiviral overexpression, and by siRNA mediated silencing. Furthermore, the addition of IGF1 and silencing of the IGF1R was used to investigate the role of the IGF-axis in IGFBP5 mediated effects. RESULTS: IGFBP5 enhanced the survival of LX2 cells and myofibroblasts via a >50% suppression of apoptosis. This effect of IGFBP5 was not modulated by the addition of IGF1, nor by silencing of the IGF1R. Additionally, IGFBP5 was able to enhance the expression of established pro-fibrotic markers, such as collagen Ialpha1, TIMP1 and MMP1. CONCLUSION: IGFBP5 enhances the survival of (partially) activated hepatic stellate cells and myofibroblasts by lowering apoptosis via an IGF1-independent mechanism, and enhances the expression of profibrotic genes. Its lowered expression may, therefore, reduce the progression of liver fibrosi

Suramin Alleviates Glomerular Injury and Inflammation in the Remnant Kidney

Background: Recently, we demonstrated that suramin, a compound that inhibits the interaction of multiple cytokines/ growth factors with their receptors, inhibits activation and proliferation of renal interstitial fibroblasts, and attenuates the development of renal interstitial fibrosis in the murine model of unilateral ureteral obstruction (UUO). However, it remains unclear whether suramin can alleviate glomerular and vascular lesions, which are not typical pathological changes in the UUO model. So we tested the efficacy of suramin in the remnant kidney after 5/6 nephrectomy, a model characterized by the slow development of glomerulosclerosis, vascular sclerosis, tubulointerstitial fibrosis and renal inflammation, mimicking human disease. Methods/Findings: 5/6 of normal renal mass was surgically ablated in male rats. On the second week after surgery, rats were randomly divided into suramin treatment and non-treatment groups. Suramin was given at 10 mg/kg once per week for two weeks. In the remnant kidney of mice receiving suramin, glomerulosclerosis and vascular sclerosis as well as inflammation were ameliorated. Suramin also attenuated tubular expression of two chemokines, monocyte chemoattractant protein-1 and regulated upon expression normal T cell expressed and secreted (RANTES). After renal mass ablation, several intracellular molecules associated with renal fibrosis, including NF-kappaB p65, Smad-3, signal transducer and activator of transcription-3 and extracellular regulated kinase 1/2, are phosphorylated; suramin treatment inhibited thei

Genome-wide RNA-Sequencing analysis reveals a distinct fibrosis gene signature in the conjunctiva after glaucoma surgery

Fibrosis-related events play a part in most blinding diseases worldwide. However, little is known about the mechanisms driving this complex multifactorial disease. Here we have carried out the first genome-wide RNA-Sequencing study in human conjunctival fibrosis. We isolated 10 primary fibrotic and 7 non-fibrotic conjunctival fibroblast cell lines from patients with and without previous glaucoma surgery, respectively. The patients were matched for ethnicity and age. We identified 246 genes that were differentially expressed by over two-fold and p < 0.05, of which 46 genes were upregulated and 200 genes were downregulated in the fibrotic cell lines compared to the non-fibrotic cell lines. We also carried out detailed gene ontology, KEGG, disease association, pathway commons, WikiPathways and protein network analyses, and identified distinct pathways linked to smooth muscle contraction, inflammatory cytokines, immune mediators, extracellular matrix proteins and oncogene expression. We further validated 11 genes that were highly upregulated or downregulated using real-time quantitative PCR and found a strong correlation between the RNA-Seq and qPCR results. Our study demonstrates that there is a distinct fibrosis gene signature in the conjunctiva after glaucoma surgery and provides new insights into the mechanistic pathways driving the complex fibrotic process in the eye and other tissues