Phylogenomic reconstruction of Cryptosporidium spp. captured directly from clinical samples reveals extensive genetic diversity.

Cryptosporidium is a leading cause of severe diarrhea and mortality in young children and infants in Africa and southern Asia. More than twenty Cryptosporidium species infect humans, of which C. parvum and C. hominis are the major agents causing moderate to severe diarrhea. Relatively few genetic markers are typically applied to genotype and/or diagnose Cryptosporidium. Most infections produce limited oocysts making it difficult to perform whole genome sequencing (WGS) directly from stool samples. Hence, there is an immediate need to apply WGS strategies to 1) develop high-resolution genetic markers to genotype these parasites more precisely, 2) to investigate endemic regions and detect the prevalence of different genotypes, and the role of mixed infections in generating genetic diversity, and 3) to investigate zoonotic transmission and evolution. To understand Cryptosporidium global population genetic structure, we applied Capture Enrichment Sequencing (CES-Seq) using 74,973 RNA-based 120 nucleotide baits that cover ~92% of the genome of C. parvum. CES-Seq is sensitive and successfully sequenced Cryptosporidium genomic DNA diluted up to 0.005% in human stool DNA. It also resolved mixed strain infections and captured new species of Cryptosporidium directly from clinical/field samples to promote genome-wide phylogenomic analyses and prospective GWAS studies.

Radiomic Phenotypes Distinguish Atypical Teratoid/Rhabdoid Tumors from Medulloblastoma.

BACKGROUND AND PURPOSE: Atypical teratoid/rhabdoid tumors and medulloblastomas have similar imaging and histologic features but distinctly different outcomes. We hypothesized that they could be distinguished by MR imaging-based radiomic phenotypes. MATERIALS AND METHODS: We retrospectively assembled T2-weighted and gadolinium-enhanced T1-weighted images of 48 posterior fossa atypical teratoid/rhabdoid tumors and 96 match-paired medulloblastomas from 7 institutions. Using a holdout test set, we measured the performance of 6 candidate classifier models using 6 imaging features derived by sparse regression of 900 T2WI and 900 T1WI Imaging Biomarker Standardization Initiative-based radiomics features. RESULTS: From the originally extracted 1800 total Imaging Biomarker Standardization Initiative-based features, sparse regression consistently reduced the feature set to 1 from T1WI and 5 from T2WI. Among classifier models, logistic regression performed with the highest AUC of 0.86, with sensitivity, specificity, accuracy, and F1 scores of 0.80, 0.82, 0.81, and 0.85, respectively. The top 3 important Imaging Biomarker Standardization Initiative features, by decreasing order of relative contribution, included voxel intensity at the 90th percentile, inverse difference moment normalized, and kurtosis-all from T2WI. CONCLUSIONS: Six quantitative signatures of image intensity, texture, and morphology distinguish atypical teratoid/rhabdoid tumors from medulloblastomas with high prediction performance across different machine learning strategies. Use of this technique for preoperative diagnosis of atypical teratoid/rhabdoid tumors could significantly inform therapeutic strategies and patient care discussions.

Insect antimicrobial peptides: potential weapons to counteract the antibiotic resistance.

Misuse and overuse of antibiotics have contributed in the last decades to a phenomenon known as antibiotic resistance which is currently considered one of the principal threats to global public health by the World Health Organization. The aim to find alternative drugs has been demonstrated as a real challenge. Thanks to their biodiversity, insects represent the largest class of organisms in the animal kingdom. The humoral immune response includes the production of antimicrobial peptides (AMPs) that are released into the insect hemolymph after microbial infection. In this review, we have focused on insect immune responses, particularly on AMP characteristics, their mechanism of action and applications, especially in the biomedical field. Furthermore, we discuss the Toll, Imd, and JAK-STAT pathways that activate genes encoding for the expression of AMPs. Moreover, we focused on strategies to improve insect peptides stability against proteolytic susceptibility such as D-amino acid substitutions, N-terminus modification, cyclization and dimerization.

Deep Learning for Pediatric Posterior Fossa Tumor Detection and Classification: A Multi-Institutional Study.

BACKGROUND AND PURPOSE: Posterior fossa tumors are the most common pediatric brain tumors. MR imaging is key to tumor detection, diagnosis, and therapy guidance. We sought to develop an MR imaging-based deep learning model for posterior fossa tumor detection and tumor pathology classification. MATERIALS AND METHODS: The study cohort comprised 617 children (median age, 92 months; 56% males) from 5 pediatric institutions with posterior fossa tumors: diffuse midline glioma of the pons (n = 122), medulloblastoma (n = 272), pilocytic astrocytoma (n = 135), and ependymoma (n = 88). There were 199 controls. Tumor histology served as ground truth except for diffuse midline glioma of the pons, which was primarily diagnosed by MR imaging. A modified ResNeXt-50-32x4d architecture served as the backbone for a multitask classifier model, using T2-weighted MRIs as input to detect the presence of tumor and predict tumor class. Deep learning model performance was compared against that of 4 radiologists. RESULTS: Model tumor detection accuracy exceeded an AUROC of 0.99 and was similar to that of 4 radiologists. Model tumor classification accuracy was 92% with an F1 score of 0.80. The model was most accurate at predicting diffuse midline glioma of the pons, followed by pilocytic astrocytoma and medulloblastoma. Ependymoma prediction was the least accurate. Tumor type classification accuracy and F1 score were higher than those of 2 of the 4 radiologists. CONCLUSIONS: We present a multi-institutional deep learning model for pediatric posterior fossa tumor detection and classification with the potential to augment and improve the accuracy of radiologic diagnosis.

Silencing of the DNA methyltransferase 1 associated protein 1 (DMAP1) gene in the invasive ladybird Harmonia axyridis implies a role of the DNA methyltransferase 1-DMAP1 complex in female fecundity.

The invasive harlequin ladybird Harmonia axyridis is a textbook example of polymorphism and polyphenism as the temperature during egg development determines the frequency of melanic morphs and the number and size of black spots in nonmelanic morphs. Recent concepts in evolutionary biology suggest that epigenetic mechanisms can translate environmental stimuli into heritable phenotypic changes. To investigate whether epigenetic mechanisms influence the penetrance and expressivity of colour morphs in H. axyridis, we used RNA interference to silence key enzymes required for DNA methylation and histone modification. We found that neither of these epigenetic mechanisms affected the frequency of different morphs, but there was a significant impact on life-history traits such as longevity and fecundity. Strikingly, we found that silencing the gene encoding for DNA methyltransferase 1 associated protein 1 (DMAP1) severely reduced female fecundity, which correlated with an abundance of degenerated ovaries in DMAP1-knockdown female beetles. Finally, we observed significant differences in DMAP1 expression when we compared native and invasive H. axyridis populations with a biocontrol strain differing in egg-laying capacity, suggesting that the DNA methyltransferase 1-DMAP1 complex may influence the invasive performance of this ladybird.

Early diagenetic behavior of arsenic in the sediment of the hypersaline Maharlu Lake, southern Iran.

Arsenic (As) is a toxic element can experience phase and speciation changes during the early diagenesis of sediments across the sediment-water interface, affecting its mobility and toxicity. Maharlu Lake is a hypersaline lake in Southern Iran that today receives significant inflow from urban, industrial and agricultural wastewater. A 1-m core was sampled from the lake sediment in an area far away from the major inflows. We performed a semi-quantitative analysis of the elemental composition, and a quantitative analysis of the total As concentration, pH, loss on ignition, water content, salt content, and grain size distribution to characterize changes in sediment composition with depth and their influence on the variability of As partitioning and speciation. Nine characterized lithologies were selected for a sequential As extraction analysis to study the vertical variations in phase and speciation of As in the heterogenic lithologies. Total As concentrations range from 1.0 µg g-1 to 13.6 µg g-1. As is present mostly in HNO3 and HCl extractable fractions with As5+ being the predominant species. As3+ was mostly found in phosphate and NH2OH·HCl extractable fractions. The concentration of mobile As fractions generally decrease with depth. It seems that the As stored in volatile sulfides and very poorly crystalline Fe and Al hydr-oxides in the shallow sediment transforms to sulfides phases during burring. Our findings show that the mobility and toxicity of As decreases during early diagenetic processes in Maharlu lake. However, the As can be remobilized either via changes in the redox conditions in the lake.

Capacity of Abbott RealTime MTB RIF/INH to detect rifampicin- and isoniazid-resistant tuberculosis.

Abbott RealTime MTB RIF/INH Resistance (RT RIF/INH) is a new assay for the detection of resistance to rifampicin (RIF) and isoniazid (INH) in tuberculosis (TB) patients. To evaluate the capacity of RT RIF/INH to detect resistance-associated mutations in target genes. A total of 311 Mycobacterium tuberculosis strains that had been pre-characterised using genotypic methods (GenoType® MTBDRplus, Sanger sequencing) and phenotypic drug susceptibility testing were subjected to DNA extraction on Abbott m2000sp and analysed using RT RIF/INH. Detection of heteroresistant mutations was studied with artificial mixtures of wild-type and mutant DNA. Overall sensitivity and specificity values of RT RIF/INH to detect resistance were respectively 87.2% and 98.4% for RIF and respectively 90.1% and 99.2% for INH. The capacity of RT RIF/INH to detect specific mutations was 100% for katG, inhA and frequent rpoB mutations, and 76% for rare rpoB mutations. Among the latter, two rare mutations were not consistently detected. With heteroresistant samples, RT RIF/INH reported resistance if samples contained at least 75-90% of mutant DNA. RT RIF/INH is a reliable high-throughput assay for the detection of RIF and INH resistance markers. The ability to detect INH resistance also may be of benefit in areas with high rates of INH-resistant, non-multidrug-resistant TB. .

[Video-assisted patient education in anesthesia : How do medical users assess the procedure?] / Videoassistierte anästhesiologische Patientenaufklärung : Wie bewerten ärztliche Anwender das Verfahren?

BACKGROUND: Video-assisted patient education (VaPE) has in the past been a subject of many studies. Compared to conventional methods, most authors reported a better transfer of information, some found increased patient satisfaction and a time-sparing effect. There was no increase in anxiety caused by VaPE. Some authors even found a reduction of anxiety levels before anesthesia. All publications to date have focused on the patient's point of view. There have been no reports on how anesthetists as users assess VaPE. METHODS: In this study 22 anesthesia departments using VaPE were contacted. A total of 122 anesthetists were sent questionnaires of which 81 (66%) were completed and returned. The anesthetists were first questioned about the characteristics of the workplace, the frequency of preanesthesia patient contacts, the content of the videos, the technique of video presentation and their own professional experience. After this the anesthetists were asked to assess five statements concerning: usefulness of VaPE, economy of time, transfer of knowledge, induction of anxiety and influence on the quality of the consent interview. In each category there were 4 choices: fully agree, partly agree, partly disagree and fully disagree. The first two choices were evaluated as positive and the second two as negative answers. The anesthetists were also asked to state the most valued characteristics of VaPE. Out of eight given options they were to select the most favored three. A final question was whether in their opinion VaPE could be recommended to non-users. RESULTS: Of the anesthetists 97.5% stated that disclosure interviews predominantly took place in the preoperative anesthetic clinic and 73% performed 15 or more patient interviews per day. Videos about general anesthesia were applied by 70%, about non-obstetric regional anesthesia by 56% and about obstetric epidural anesthesia by 59%. The videos were presented to groups of patients via large screens by 27%, individually with CD players or tablet computers by 51% or with both methods (22%). Of the anesthetists 69% had 5 years or more professional experience, 97.5% found VaPE useful for patients education, 92.5% observed a time-saving effect for the following interview and 96% stated that after watching the video patients were better informed. An increase of anxiety caused by VaPE was noted by 46% whereas 54% found no such effect. As to the quality of interview 50% reported an advantage in focusing on the patient's individual risk profile and the other 50% reported no advantage. The ranking of the main advantages was 1) better patient information, 2) time-saving effect, 3) helpful for patient education, followed by 4) increased patient satisfaction, 5) better understanding of anesthesiology, 6) individualization of the interview and 7) helpful in questions of legal liability. The answer option "no advantage" was not chosen at all. Of the participants 82.5% would recommend VaPE unconditionally (fully agree), 17.5% would give a conditional recommendation to colleagues and no one would not recommend VaPE. CONCLUSION: This survey among anesthetists confirmed most results obtained from patient-based studies: medical users attributed to VaPE a better information transfer and a time-sparing effect. Furthermore, users regarded VaPE as helpful for the preanesthesia interview. As compared to the patient-based results, however, many anesthetists seem to overrate the anxiety, caused by disclosure videos. From the users' point of view, VaPE is a highly appreciated method for patient education which can be recommended to colleagues.

Prospective study of device-related complications in intensive care unit detected by virtual autopsy.

BACKGROUND: There has been increasing use of invasive techniques, such as extracorporeal organ support, in intensive care units (ICU), and declining autopsy rates. Thus, new measures are needed to maintain high-quality standards. We investigated the potential of computed tomography (CT)-based virtual autopsy to substitute for medical autopsy in this setting. METHODS: We investigated the potential of virtual autopsy by post-mortem CT to identify complications associated with medical devices in a prospective study of patients who had died in the ICU. Clinical records were reviewed to determine the number and types of medical devices used, and findings from medical and virtual autopsies, related and unrelated to the medical devices, were compared. RESULTS: Medical and virtual autopsies could be performed in 61 patients (Group M/V), and virtual autopsy only in 101 patients (Group V). In Group M/V, 41 device-related complications and 30 device malpositions were identified, but only with a low inter-method agreement. Major findings unrelated to a device were identified in about 25% of patients with a high level of agreement between methods. In Group V, 8 device complications and 36 device malpositions were identified. CONCLUSIONS: Device-related complications are frequent in ICU patients. Virtual and medical autopsies showed clear differences in the detection of complications and device malpositions. Both methods should supplement each other rather than one alone for quality control of medical devices in the ICU. Further studies should focus on the identification of special patient populations in which virtual autopsy might be of particular benefit. CLINICAL TRIAL REGISTRATION: NCT01541982.

[Application for Inpatient Psychosomatic Rehabilitation: Frequency, Quality, and Approval Rates]. / Anträge auf psychosomatische Rehabilitation ­ Häufigkeit, Qualität und Befürwortungsrate.

BACKGROUND: There has been a steady increase in psychiatric primary diagnoses in medical rehabilitation services carried out by the statutory pension insurance (DRV). To date, no data are available regarding frequency, quality, and approval rates of applications for psychosomatic rehabilitation. Pension insurance physicians reviewing the application require sufficient information on rehabilitation-related needs, motivation, abilities, and prognosis of an insured person. Medical reports accompanying application for rehabilitation are often provided by a family physician. Psychiatric disorders are often misdiagnosed by general practitioners. METHOD: In a 2-week period, all decisions made by pension insurance physicians evaluating applications for rehabilitation were recorded. For each incoming application, the following data were documented: psychiatric and somatic primary diagnosis; availability of medical reports; information on prior treatment/therapy; request for further information; decision made by the physician. RESULTS: 1,366 applications (with 81% first-time applications) were included in the analysis. 16.2% of all applications were from insurants with psychiatric primary diagnoses. 44.0% of these applications included a medical report from the family physician only. The proportion of rejected applications (34.7%) and undecided applications (27.2%) was higher in the group of applicants with psychiatric primary diagnosis vs. somatic primary diagnosis (19.6% rejected; 12.7% undecided; χ2=79.8(4), p=0.001). Applications from patients with psychiatric primary diagnosis that lacked a medical report from a psychiatrist/psychotherapist were more likely to be rejected (45.3 vs. 32.3%) or to remain undecided (28.0 vs. 18.3%; χ2=10.2(2), p=0.006). In contrast, among applicants with a history of psychiatric/psychotherapeutic treatment, there was a higher proportion of undecided applications accompanied by a medical report from the family physician (35.7 vs. 18.2%). CONCLUSION: It might be useful to have medical reports generally provided by medical specialists. This may help both to increase the informative value of applications for psychosomatic rehabilitation and enable quicker decisions and better diagnosis.

Genomic innovations, transcriptional plasticity and gene loss underlying the evolution and divergence of two highly polyphagous and invasive Helicoverpa pest species.

BACKGROUND: Helicoverpa armigera and Helicoverpa zea are major caterpillar pests of Old and New World agriculture, respectively. Both, particularly H. armigera, are extremely polyphagous, and H. armigera has developed resistance to many insecticides. Here we use comparative genomics, transcriptomics and resequencing to elucidate the genetic basis for their properties as pests. RESULTS: We find that, prior to their divergence about 1.5 Mya, the H. armigera/H. zea lineage had accumulated up to more than 100 more members of specific detoxification and digestion gene families and more than 100 extra gustatory receptor genes, compared to other lepidopterans with narrower host ranges. The two genomes remain very similar in gene content and order, but H. armigera is more polymorphic overall, and H. zea has lost several detoxification genes, as well as about 50 gustatory receptor genes. It also lacks certain genes and alleles conferring insecticide resistance found in H. armigera. Non-synonymous sites in the expanded gene families above are rapidly diverging, both between paralogues and between orthologues in the two species. Whole genome transcriptomic analyses of H. armigera larvae show widely divergent responses to different host plants, including responses among many of the duplicated detoxification and digestion genes. CONCLUSIONS: The extreme polyphagy of the two heliothines is associated with extensive amplification and neofunctionalisation of genes involved in host finding and use, coupled with versatile transcriptional responses on different hosts. H. armigera's invasion of the Americas in recent years means that hybridisation could generate populations that are both locally adapted and insecticide resistant.

A DNA methylation site within the KLF13 gene is associated with orexigenic processes based on neural responses and ghrelin levels.

We investigated five methylation markers recently linked to body mass index, for their role in the neuropathology of obesity. In neuroimaging experiments, our analysis involving 23 participants showed that methylation levels for the cg07814318 site, which lies within the KLF13 gene, correlated with brain activity in the claustrum, putamen, cingulate gyrus and frontal gyri, some of which have been previously associated to food signaling, obesity or reward. Methylation levels at cg07814318 also positively correlated with ghrelin levels. Moreover, expression of KLF13 was augmented in the brains of obese and starved mice. Our results suggest the cg07814318 site could be involved in orexigenic processes, and also implicate KLF13 in obesity. Our findings are the first to associate methylation levels in blood with brain activity in obesity-related regions, and further support previous findings between ghrelin, brain activity and genetic differences.

Data set for diet specific differential gene expression analysis in three Spodoptera moths.

Examination of closely related species pairs is suggested for evolutionary comparisons of different degrees of polyphagy, which we did here with three taxa of lepidopteran herbivores, Spodoptera spp (S. littoralis, S. frugiperda maize (C) and rice (R) strains) for a RNAseq analysis of the midguts from the 3rd instar insect larvae for differential metabolic responses after feeding on pinto bean based artificial diet vs maize leaves. Paired-end (2×100 bp) Illumina HiSeq2500 sequencing resulted in a total of 24, 23, 24, and 21 million reads for the SF-C-Maize, SF-C-Pinto, SF-R-Maize, SF-R Pinto, and a total of 35 and 36 million reads for the SL-Maize and SL-Pinto samples, respectively. After quality control measures, a total of 62.2 million reads from SL and 71.7 million reads from SF were used for transcriptome assembly (TA). The resulting final de novo reference TA (backbone) for the SF taxa contained 37,985 contigs with a N50 contig size of 1030 bp and a maximum contig length of 17,093 bp, while for SL, 28,329 contigs were generated with a N50 contig size of 1980 bp and a maximum contig length of 18,267 bp. The data presented herein contains supporting information related to our research article Roy et al. (2016) http://dx.doi.org/10.1016/j.ibmb.2016.02.006[1].

Exploring complex pheromone biosynthetic processes in the bumblebee male labial gland by RNA sequencing.

Male marking pheromones (MPs) are used by the majority of bumblebee species (Hymenoptera: Apidae), including a commercially important greenhouse pollinator, the buff-tailed bumblebee (Bombus terrestris), to attract conspecific females. MP biosynthetic processes in the cephalic part of the bumblebee male labial gland (LG) are of extraordinary complexity, involving enzymes of fatty acid and isoprenoid biosynthesis, which jointly produce more than 50 compounds. We employed a differential transcriptomic approach to identify candidate genes involved in MP biosynthesis by sequencing Bombus terrestris LG and fat body (FB) transcriptomes. We identified 12 454 abundantly expressed gene products (reads per kilobase of exon model per million mapped reads value > 1) that had significant hits in the GenBank nonredundant database. Of these, 876 were upregulated in the LG (> 4-fold difference). We identified more than 140 candidate genes potentially involved in MP biosynthesis, including esterases, fatty acid reductases, lipases, enzymes involved in limited fatty acid chain shortening, neuropeptide receptors and enzymes involved in biosynthesis of triacylglycerols, isoprenoids and fatty acids. For selected candidates, we confirmed their abundant expression in LG using quantitative real-time reverse transcription-PCR (qRT-PCR). Our study shows that the Bombus terrestris LG transcriptome reflects both fatty acid and isoprenoid MP biosynthetic processes and identifies rational gene targets for future studies to disentangle the molecular basis of MP biosynthesis. Additionally, LG and FB transcriptomes enrich the available transcriptomic resources for Bombus terrestris.

Failure of primary atovaquone prophylaxis for prevention of toxoplasmosis in hematopoietic cell transplant recipients.

The efficacy of primary prophylaxis with atovaquone in preventing Toxoplasma reactivation and disease in hematopoietic cell transplant (HCT) recipients is unknown. We describe 2 cases of atovaquone prophylaxis failure in pre-HCT Toxoplasma-seropositive (pre-HCTSP) recipients who underwent allogeneic HCT (allo-HCT) and review the literature on atovaquone prophylaxis in HCT recipients.

Diet dependent metabolic responses in three generalist insect herbivores Spodoptera spp.

Adaption to dietary changes is critical in the evolution of host plant ranges in polyphagous insects. We compared three taxa of lepidopteran herbivores from the predominantly generalist genus Spodoptera showing different degrees of polyphagy: Spodoptera littoralis, with a broad host range including both mono- and dicotyledonous plants, and two Spodoptera frugiperda strains [Corn (i.e. maize) (C) and Rice (R)] adapted primarily to different grass species. When feeding on maize we show a lower performance in the broad generalist taxon compared to the grass adapted taxa. Among these taxa, the maize adapted S. frugiperda C-strain generally performed better than the R-strain on maize leaves. On artificial pinto diet, all taxa performed well. Our RNA-Seq analysis of midgut transcriptomes from 3rd instar larvae feeding on maize showed broader transcriptional readjustments in the generalist S. littoralis compared to grass adapted S. frugiperda strains. Substantial alteration in the expression levels of midgut physiological function related transcripts, such as digestive and detoxifying enzymes, transporters, immunity, and peritrophic membrane associated transcripts, existed in all taxa. We found high background expression of UDP-glucosyl transferases, which are known to neutralize maize leaf toxins, in the maize adapted S. frugiperda C-strain, contributing to its fitness on maize compared to the R-strain. Our findings provide evidence for divergent diet specific response of digestive physiology within these Spodoptera taxa. Unexpectedly, the C- and R-strains of S. frugiperda fed on the same diet showed large differences in expression patterns between these two closely related taxa.

Expression and characterization of a recombinant i-type lysozyme from the harlequin ladybird beetle Harmonia axyridis.

Lysozymes are enzymes that destroy bacterial cell walls by hydrolysing the polysaccharide component of peptidoglycan. In insects, there are two classes of lysozymes, the c-type with muramidase activity and the i-type whose prototypical members from annelids and molluscs possess both muramidase and isopeptidase activities. Many insect genes encoding c-type and i-type lysozymes have been identified during genome and transcriptome analyses, but only c-type lysozymes have been functionally characterized at the protein level. Here we produced one of five i-type lysozymes represented in the immunity-related transcriptome of the invasive harlequin ladybird beetle Harmonia axyridis as recombinant protein. This was the only one containing the serine and histidine residues that are thought to be required for isopeptidase activity. This i-type lysozyme was recombinantly expressed in the yeast Pichia pastoris, but the purified protein was inactive in both muramidase and isopeptidase assays. Transcription and immunofluorescence analysis revealed that this i-type lysozyme is produced in the fat body but is not inducible by immune challenge. These data suggest that i-type lysozymes in insects may have acquired novel and as yet undetermined functions in the course of evolution.

Lubricin/Proteoglycan 4 binds to and regulates the activity of Toll-Like Receptors In Vitro.

Proteoglycan 4 (PRG4/lubricin) is secreted by cells that reside in articular cartilage and line the synovial joint. Lubricin may play a role in modulating inflammatory responses through interaction with CD44. This led us to examine if lubricin could be playing a larger role in the modulation of inflammation/immunity through interaction with Toll-like receptors (TLRs). Human Embryonic Kidney (HEK) cells overexpressing TLRs 2, 4 or 5 and surface plasmon resonance were employed to determine if full length recombinant human lubricin was able to bind to and activate TLRs. Primary human synovial fibroblasts were also examined using flow cytometry and Luminex multiplex ELISA. A rat destabilization model of osteoarthritis (OA) was used to determine if lubricin injections were able to regulate pain and/or inflammation in vivo. Lubricin can bind to and regulate the activity of TLRs, leading to downstream changes in inflammatory signalling independent of HA. We confirmed these findings in vivo through intra-articular injections of lubricin in a rat OA model where the inhibition of systemic inflammatory signaling and reduction in pain were observed. Lubricin plays an important role in regulating the inflammatory environment under both homeostatic and tissue injury states.

[Quality Assurance in Sociomedical Evaluation by Peer Review: A Pilot Project of the German Statutory Pension Insurance]. / Qualitätssicherung in der Sozialmedizinischen Begutachtung durch Peer Review - ein Pilotprojekt der Deutschen Rentenversicherung.

BACKGROUND: The sociomedical evaluation by the German Pension Insurance serves the purpose of determining entitlement to disability pensions. A quality assurance concept for the sociomedical evaluation was developed, which is based on a peer Review process. Peer review is an established process of external quality assurance in health care. The review is based on a hierarchically constructed manual that was evaluated in this pilot project. METHODS: The database consists of 260 medical reports for disability pension of 12 pension insurance agencies. 771 reviews from 19 peers were included in the evaluation of the inter-rater reliability. Kendall's coefficient of concordance W for more than 2 raters is used as primary measure of inter-rater reliability. RESULTS: Reliability appeared to be heterogeneous. Kendalls W varies for the particular criteria from 0.09 to 0.88 and reached for primary criterion reproducibility a value of 0.37. CONCLUSION: The reliability of the manual seemed acceptable in the context of existing research data and is in line with existing peer review research outcomes. Nevertheless, the concordance is limited and requires optimisation. Starting points for improvement can be seen in a systematic training and regular user meetings of the peers involved.