A novel corpus of molecular to higher-order events that facilitates the understanding of the pathogenic mechanisms of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a severe and progressive chronic fibrosing interstitial lung disease with causes that have remained unclear to date. Development of effective treatments will require elucidation of the detailed pathogenetic mechanisms of IPF at both the molecular and cellular levels. With a biomedical corpus that includes IPF-related entities and events, text-mining systems can efficiently extract such mechanism-related information from huge amounts of literature on the disease. A novel corpus consisting of 150 abstracts with 9297 entities intended for training a text-mining system was constructed to clarify IPF-related pathogenetic mechanisms. For this corpus, entity information was annotated, as were relation and event information. To construct IPF-related networks, we also conducted entity normalization with IDs assigned to entities. Thereby, we extracted the same entities, which are expressed differently. Moreover, IPF-related events have been defined in this corpus, in contrast to existing corpora. This corpus will be useful to extract IPF-related information from scientific texts. Because many entities and events are related to lung diseases, this freely available corpus can also be used to extract information related to other lung diseases such as lung cancer and interstitial pneumonia caused by COVID-19.

A systematic review of meta-analyses in orthopaedic surgery between 2000 and 2016.

AIMS: The aims of this systematic review were to describe the quantity and methodological quality of meta-analyses in orthopaedic surgery published during the last 17 years. MATERIALS AND METHODS: MEDLINE, EMBASE, and PubMed, between 1 January 2000 and 31 December 2016, were searched for meta-analyses in orthopaedic surgery dealing with at least one surgical intervention. Meta-analyses were included if the interventions involved a human muscle, ligament, bone or joint. RESULTS: A total of 392 meta-analyses met eligibility criteria, for which the mean AMSTAR quality score was 7.1/11. There was a positive correlation between the year of publication and the quality of the meta-analysis (r = 0.238, p < 0.001). Between 2000 and 2011, the mean AMSTAR score corresponded to that of a medium quality review. However, between 2012 and 2016, the mean scores have been consistently equivalent to those of a high-quality review. The number of meta-analyses published increased 10-fold between 2005 and 2014. CONCLUSION: The quantity and quality of meta-analyses in orthopaedic surgery which have been published has increased, reaching a plateau in 2012. Methodological flaws remain to be addressed in future meta-analyses in order to continue increasing the quality of the orthopaedic literature. Cite this article: Bone Joint J 2018;100-B:1270-4.

Twenty-year analysis of implant treatment in an Australian public dental clinic.

BACKGROUND: This retrospective cohort study reviewed dental implant treatment completed at the Adelaide Dental Hospital over a 20-year period. METHODS: The database of implant treatment completed between 1996 and 2015 was analysed for patient, implant, prosthesis and operator specifics together with known implant status. RESULTS: Three hundred and twenty patients (mean age, 51.50 years) were treated with 527 implants. One hundred and eighty-four female patients received 296 implants and 136 males received 231 implants. Three hundred implants were restored with single crowns, 147 implants were restored with 63 mandibular implant overdentures, five implants were restored with two maxillary implant overdentures and 67 implants were restored with 20 full-arch fixed prostheses. The overall known implant survival rate was 87.67%. Mandibular implant overdentures had a risk of implant failure four times that of single implant-retained crowns that was statistically significant (P = 0.0100). CONCLUSIONS: Implant treatment completed in this public sector clinic using finite resources and a defined system of patient and restorative selection criteria demonstrated a high known implant survival rate. Utilizing a structured and maintained patient recall protocol, it would be ideal to investigate further parameters of interest, particularly those that could improve treatment delivery and longevity.

Surgical treatment of femoroacetabular impingement following slipped capital femoral epiphysis: A systematic review.

OBJECTIVES: The purpose of this study was to evaluate the existing literature from 2005 to 2016 reporting on the efficacy of surgical management of patients with femoroacetabular impingement (FAI) secondary to slipped capital femoral epiphysis (SCFE). METHODS: The electronic databases MEDLINE, EMBASE, and PubMed were searched and screened in duplicate. Data such as patient demographics, surgical technique, surgical outcomes and complications were retrieved from eligible studies. RESULTS: Fifteen eligible level IV studies were included in this review comprising 261 patients (266 hips). Treatment groups included arthroscopic osteochondroplasty, surgical hip dislocation, and traditional open osteotomy. The mean alpha angle corrections were 32.14° (standard deviation (sd) 7.02°), 41.45° (sd 10.5°) and 6.0° (sd 5.21°), for arthroscopy, surgical hip dislocation, and open osteotomy groups, respectively (p < 0.05). Each group demonstrated satisfactory clinical outcomes across their respective scoring systems. Major complication rates were 1.6%, 10.7%, and 6.7%, for arthroscopy, surgical dislocation and osteotomy treatments, respectively. CONCLUSION: In the context of SCFE-related FAI, surgical hip dislocation demonstrated improved correction of the alpha angle, albeit at higher complication and revision rates than both arthroscopic and open osteotomy treatments. Further investigation, including high-quality trials with standardised radiological and clinical outcome measures for young patients, is warranted to clarify treatment approaches and safety.Cite this article: K. O. Oduwole, D. de Sa, J. Kay, F. Findakli, A. Duong, N. Simunovic, Y. Yi-Meng, O. R. Ayeni. Surgical treatment of femoroacetabular impingement following slipped capital femoral epiphysis: A systematic review. Bone Joint Res 2017;6:472-480. DOI: 10.1302/2046-3758.68.BJR-2017-0018.R1.

Authorship in the field of femoroacetabular impingement: an analysis of journal publications.

PURPOSE: This review provides a bibliometric analysis of the contributors to the field of FAI research. METHODS: A comprehensive search of three databases (MEDLINE, EMBASE, and PubMed) was performed to identify all clinical research articles on the topic of FAI (from inception to 2015). Cadaveric and animal studies were excluded. Study characteristics including authors, residing country of corresponding author, and journal were abstracted from the respective databases. RESULTS: In total, 1073 articles were included in this review. There were a total of 5471 different authors who contributed to the field of FAI research, 28.3 % of whom were only published in one article. The top 20 authors were associated with over half of all publications, and research studies were typically performed in their countries of residence. The greatest proportion of FAI-related articles was published in the Journal of Arthroscopy and Clinical Orthopaedics and Related Research. CONCLUSIONS: The number of authors contributing to FAI research is increasing, suggesting not only increasing prevalence of FAI treatment among orthopaedic surgeons but also increasing interest among hip arthroscopists in furthering understanding regarding the diagnosis and management of the condition. The number of publications produced by the top 20 authors (and their affiliated countries: USA, Switzerland, Canada, and the UK) is expected to contribute to a majority of future publications. Current trends suggest that the quality of evidence will continue to improve in the near future, as large-scale, collaborative studies are currently underway. LEVEL OF EVIDENCE: Retrospective study, Level IV.

Tissue recovery practices and bioburden: a systematic review.

For successful transplantation, allografts should be free of microorganisms that may cause harm to the allograft recipient. Before or during recovery and subsequent processing, tissues can become contaminated. Effective tissue recovery methods, such as minimizing recovery times (<24 h after death) and the number of experienced personnel performing recovery, are examples of factors that can affect the rate of tissue contamination at recovery. Additional factors, such as minimizing the time after asystole to recovery and the total time it takes to perform recovery, the type of recovery site, the efficacy of the skin prep performed immediately prior to recovery of tissue, and certain technical recovery procedures may also result in control of the rate of contamination. Due to the heterogeneity of reported recovery practices and experiences, it cannot be concluded if the use of other barriers and/or hygienic precautions to avoid contamination have had an effect on bioburden detected after tissue recovery. Qualified studies are lacking which indicates a need exists for evidence-based data to support methods that reduce or control bioburden.

Disinfection of human musculoskeletal allografts in tissue banking: a systematic review.

Musculoskeletal allografts are typically disinfected using antibiotics, irradiation or chemical methods but protocols vary significantly between tissue banks. It is likely that different disinfection protocols will not have the same level of microorganism kill; they may also have varying effects on the structural integrity of the tissue, which could lead to significant differences in terms of clinical outcome in recipients. Ideally, a disinfection protocol should achieve the greatest bioburden reduction with the lowest possible impact on tissue integrity. A systematic review of three databases found 68 laboratory and clinical studies that analyzed the microbial bioburden or contamination rates of musculoskeletal allografts. The use of peracetic acid-ethanol or ionizing radiation was found to be most effective for disinfection of tissues. The use of irradiation is the most frequently published method for the terminal sterilization of musculoskeletal allografts; it is widely used and its efficacy is well documented in the literature. However, effective disinfection results were still observed using the BioCleanse™ Tissue Sterilization process, pulsatile lavage with antibiotics, ethylene oxide, and chlorhexidine. The variety of effective methods to reduce contamination rate or bioburden, in conjunction with limited high quality evidence provides little support for the recommendation of a single bioburden reduction method.

Five-year publication rate of clinical presentations at the open and closed American shoulder and elbow surgeons annual meeting from 2005-2010.

BACKGROUND: The purpose of this study was to evaluate the five-year publication rate of papers presented at both the open and closed American Shoulder and Elbow Surgeons' (ASES) annual meetings from 2005 to 2010. METHODS: Online abstracts of the presentations at the open and closed ASES annual meetings were independently screened for clinical studies and graded for quality using level of evidence. The databases PubMed (MEDLINE), Ovid (MEDLINE), and EMBASE were comprehensively searched for full-text publications corresponding to these presentations and any paper published within five years of the presentation date was counted. RESULTS: Overall, 131/266 papers corresponding to the meeting presentations were identified for a five-year publication rate of 49.2 %. Sixty two (48 %) of the papers were published in The Journal of Shoulder and Elbow Surgeons, 23 (18 %) were published in The American Journal of Sports Medicine, and 20 (16 %) were published in The Journal of Bone and Joint Surgery. The mean patient sample size included in presentations with a subsequent full-text publication was higher (154; standard error =27) than the presentations not published (93; standard error = 13) (p = 0.039). There was no correlation (p = 0.248) between the publication rate and the level of evidence of the presentations. CONCLUSIONS: The publication rate of presentations at ASES meetings from 2005 to 2010 is similar to that reported from other orthopaedic meetings. Studies with large sample sizes should continue to be encouraged, and high quality presentations must consistently be followed up with full-text manuscript preparation in order to maximize the future clinical impact.

Disinfection of human skin allografts in tissue banking: a systematic review report.

The use of skin allografts to temporarily replace lost or damaged skin is practiced worldwide. Naturally occurring contamination can be present on skin or can be introduced at recovery or during processing. This contamination can pose a threat to allograft recipients. Bacterial culture and disinfection of allografts are mandated, but the specific practices and methodologies are not dictated by standards. A systematic review of literature from three databases found 12 research articles that evaluated bioburden reduction processes of skin grafts. The use of broad spectrum antibiotics and antifungal agents was the most frequently identified disinfection method reported demonstrating reductions in contamination rates. It was determined that the greatest reduction in the skin allograft contamination rates utilized 0.1 % peracetic acid or 25 kGy of gamma irradiation at lower temperatures.

Disinfection of human cardiac valve allografts in tissue banking: systematic review report.

Cardiovascular allografts are usually disinfected using antibiotics, but protocols vary significantly between tissue banks. It is likely that different disinfection protocols will not have the same level of efficacy; they may also have varying effects on the structural integrity of the tissue, which could lead to significant differences in terms of clinical outcome in recipients. Ideally, a disinfection protocol should achieve the greatest bioburden reduction with the lowest possible impact on tissue integrity. We conducted a systematic review of methods applied to disinfect cardiovascular tissues. The use of multiple broad spectrum antibiotics in conjunction with an antifungal agent resulted in the greatest reduction in bioburden. Antibiotic incubation periods were limited to less than 24 h, and most protocols incubated tissues at 4 °C, however one study demonstrated a greater reduction of microbial load at 37 °C. None of the reviewed studies looked at the impact of these disinfection protocols on the risk of infection or any other clinical outcome in recipients.

Domain-specific cognitive effects of tramiprosate in patients with mild to moderate Alzheimer's disease: ADAS-cog subscale results from the Alphase Study.

OBJECTIVES: Tramiprosate (homotaurine, ALZHEMEDTM) was recently investigated for its efficacy, safety and disease-modification effects in a Phase III clinical study in mild to moderate Alzheimer's disease (AD) patients (the Alphase study). The primary cognitive endpoint measure of that study was the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog). To characterize potential cognitive benefits of tramiprosate, the present study describes exploratory analyses performed on scores obtained from the specific ADAS-cog subscales in order to determine whether specific domains of cognition may be differentially affected by tramiprosate, which would not have been evident from the measure's total score. DESIGN: Multi-center, double-blind, randomized, placebo-controlled study. SETTING: 67 investigative sites in the United States and Canada. PARTICIPANTS: A total of 1,052 patients were randomized. INTERVENTIONS: Patients were randomized to receive twice a day Placebo (n=353), tramiprosate 100 mg (n=352) and tramiprosate 150 mg (n=347). MEASUREMENTS: ADAS-cog assessments were conducted every three months over the 78-week study period. Exploratory analyses were performed by comparing ADAS-cog subscale scores between Placebo and each active treatment arm at each visit. RESULTS: The findings of this analysis revealed statistically significant differences or statistical trends in favour of tramiprosate on six ADAS-cog subscales, namely Following Commands, Language Comprehension, Ideational Praxis, Object Naming, Remembering Test Instructions, and Spoken Language Ability. Differences in favor of Placebo were only observed on the Constructional Praxis subscale. CONCLUSION: This exploratory analysis suggests that tramiprosate may have some benefit on memory, language and praxis skills in mild to moderate AD individuals. Future clinical studies of tramiprosate should include specialized neuropsychological tests to validate its effects within these cognitive domains.

Effect of tramiprosate in patients with mild-to-moderate Alzheimer's disease: exploratory analyses of the MRI sub-group of the Alphase study.

OBJECTIVES: The efficacy, safety and disease-modification of tramiprosate (homotaurine)were investigated in a recently completed large-scale Phase III clinical study in patients with mild to moderate Alzheimer's disease (AD), the Alphase study. Disease-modification was assessed using longitudinal volumetric MRI (vMRI) measurements of the hippocampus in a subgroup of patients. The present study describes the vMRI, cognitive and clinical results obtained in this subgroup. DESIGN: Multi-center, double-blind, randomized, placebo-controlled study in a subset of the 1052 patients of the Alphase study. SETTING: 51 vMRI investigative sites in the United States and Canada. PARTICIPANTS: A total of 508 patients underwent vMRI scanning. Of these, 312 provided scan pairs for assessing hippocampus volume changes and were included in the analyses. INTERVENTIONS: Patients were randomized to receive Placebo BID (n = 109), tramiprosate 100 mg BID (n = 103), or tramiprosate 150 mg BID (n = 100) for 78 weeks. MEASUREMENTS: Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and Clinical Dementia Rating-Sum-of-boxes CDR-SB assessments were conducted at Baseline and at Weeks 13, 26, 39, 52, 65 and 78. Exploratory analyses were performed using similar First and Final mixed-effects repeated-measures models that were used for the analysis of the entire patient dataset. RESULTS: Psychometric score results showed numerical trends in favour of tramiprosate that did not reach statistical significance. While there were no statistically significant group differences in hippocampus volume using the First modeling approach, a significant dose-response reduction in hippocampus volume change was found in the Final models. Moreover, there was a marginally significant overall treatment main effect and a significant slope difference in favour of tramiprosate according to the Final model analysis of the ADAS-cog scores. ADAS-cog scores analyzed according to this model also revealed differences in favor of the tramiprosate 150 mg group at weeks 26 and 52, with marginally significant differences at Weeks 13 and 39. Slope analyses of ADAS-cog score changes showed significant differences in favor of the 150 mg BID group, and when both active groups were combined, in comparison to the placebo group. No between-group differences with respect to changes to each visit in the CDR-SB were observed with either modeling approach. Although there was a similar dose-response relationship observed in the hippocampus volume and ADAS-cog Final model analyses, the overall changes in psychometric scores and hippocampus volume were not significantly correlated. CONCLUSION: Exploratory analysis of the vMRI subgroup suggests that tramiprosate slows hippocampal atrophy, and reveals some evidence of a beneficial effect on cognition. The clinical validity of the vMRI biomarker is discussed.

Production of narratives: picture sequence facilitates organizational but not conceptual processing in less educated subjects.

Fifty-three healthy older adults were produced stories induced by two types of picture stimuli (single picture and picture sequence). Discourse samples were analyzed for: (1) percentage of expected main ideas (which reflect conceptual processing) and (2) number of transitional markers (which reflect organizational processing). Results indicate that the older group (75 to 84 years) produced a lower percentage of main ideas and less transitional markers than the younger group (65 to 74 years). Both groups also showed better performance in response to the picture sequence than to the single picture. For the percentage of expected main ideas, however, a superior performance in response to the picture sequence was observed only among older subjects with higher (11 to 18 years) but not lower (4 to 10 years) levels of formal education. The role of education and the importance of stimulus type in discourse-specific tasks are discussed.

In vivo induction of massive proliferation, directed migration, and differentiation of neural cells in the adult mammalian brain.

The development of an in vivo procedure for the induction of massive proliferation, directed migration, and neurodifferentiation (PMD) in the damaged adult central nervous system would hold promise for the treatment of human neurodegenerative disorders such as Parkinson's disease. We investigated the in vivo induction of PMD in the forebrain of the adult rat by using a combination of 6-hydroxydopamine lesion of the substantia nigra dopaminergic neurons and infusions of transforming growth factor alpha (TGFalpha) into forebrain structures. Only in animals with both lesion and infusion of TGFalpha was there a rapid proliferation of forebrain stem cells followed by a timed migration of a ridge of neuronal and glial progenitors directed toward the region of the TGFalpha infusion site. Subsequently, increasing numbers of differentiated neurons were observed in the striatum. In behavioral experiments, there was a significant reduction of apomorphine-induced rotations in animals receiving the TGFalpha infusions. These results show that the brain contains stem cells capable of PMD in response to an exogenously administered growth factor. This finding has significant implications with respect to the development of treatments for both acute neural trauma and neurodegenerative diseases.

Interpretation of sham feeding data: curve-shift studies.

We explored the possibility that quantitative analysis of the relationship between sucrose concentration and sham intake differentiated how various treatments affected the intake of sweet solutions. Rats were sham fed sucrose solutions varying in concentration from 0.03125 to 1.5 M. Under different treatment conditions, intake concentration functions were generated that plotted amount sham fed against sucrose concentration. Sucrose concentration that yielded 50% maximal sham intake were calculated to indicate the position of the concentration-intake function on the x-axis. Quinine adulteration of sucrose solutions and injection of 0.5 mg/kg i.p. of the dopamine antagonist pimozide reduced sham intake and shifted the concentration-intake function to the right. Lithium chloride (60 mg/kg i.p.) injected 30 min before sham feeding, a reduction of food deprivation from 18 to 6 h before sham feeding, and 6 micrograms/kg cholecystokinin octapeptide reduced sham intake equivalent amounts but did not shift the concentration-intake functions along the x-axis. The data indicate that of several factors that reduce sham feeding, only some also shift the position of concentration-intake curves, and these curve shifts may identify intake changes mediated by alterations in the processing of the taste input.

Two forms of the prolactin receptor messenger ribonucleic acid are Present in ovine fetal liver and adult ovary.

Previous binding studies indicated that there is little to no specific prolactin binding in ovine fetal liver and adult ovary. Therefore, we sought to determine if ovine prolactin receptor (PRLR) mRNA is present in those tissues. Primers were designed from the bovine PRLR cDNA sequence for use in reverse transcriptase-polymerase chain reaction (RT-PCR). RT-PCR analysis of ovine fetal liver total cellular RNA (tcRNA) isolated from days 60, 90, 105, 120 and 135 of gestation, and luteal tcRNA isolated from days 3, 7, 10, 13 and 16 of the estrous cycle revealed that PRLR mRNA was present in these tissues. However, two RT-PCR products were generated from both tissues. The two RT-PCR products did not differ between the two tissue sources in sequence, and were designated oPRLR-1 and oPRLR-2. Ovine PRLR-1 is 513 bp in length and is 96.4% identical to the bovine cDNA. Ovine PRLR-2 is identical to oPRLR-1 until nucleotide (nt) 420 at which point a 39 bp insertion occurs. This insertion occurs between Homology Boxes 1 and 2 within the cytoplasmic domain of the receptor, resulting in an 11 amino acid divergent sequence, followed by two stop codons. Ribonuclease-protection assay revealed that oPRLR-1 mRNA is the most abundant in these tissues. Our data indicate that two forms of oPRLR mRNA are Present in fetal liver and adult ovary, and that one form (oPRLR-2) is predicted to encode a truncated PRLR.

Dopamine antagonists act on central, but not peripheral, receptors to inhibit sham and real feeding.

We examined the relative contribution of dopamine (DA) receptors in the brain and periphery in the control of sham and real feeding of sucrose solutions. Intraperitoneal (IP) administration of pimozide, an antagonist of peripheral and brain DA receptors, suppressed both sham and real feeding in a dose-related manner. In contrast, IP injections of domperidone, a DA antagonist restricted to peripheral receptors, had no effect on either sham or real feeding. The inability of domperidone to influence sucrose intake did not result from a lack of biological activity of the drug because the identical doses of domperidone that failed to alter eating significantly inhibited gastric acid secretion. The results implicate central, but not peripheral, DA receptors in the control of the ingestion of palatable foods and also suggest that sham feeding is more sensitive to DA antagonism than real feeding.

Immunohistological localization of cell adhesion proteins and integrins in the periodontium.

The distribution of the cell adhesion proteins vitronectin, fibronectin, tenascin, and laminin as well as several integrin subunits, alpha 2, alpha 5, and alpha v, was studied in primate periodontal tissues. Full baboon mandibular sections were analyzed by immunohistochemical methods in order to localize the molecules studied in both soft and hard tissues. Vitronectin was associated with the connective tissue of the marginal gingiva, the periodontal ligament, as well as the endosteum and periosteum. A notable finding was the particularly high staining intensity of vitronectin in the periodontal ligament. Fibronectin was widely distributed in the periodontal connective tissue and was also localized to the pericellular matrix of osteocytes and blood vascular elements. Epithelial basement membranes stained positively for both fibronectin and tenascin. These proteins were also expressed in the periosteal and endosteal connective tissues and the periodontal ligament. The staining intensity for tenascin was higher in zones along the cementum and bone surfaces. Laminin was, characteristically, limited to basement membranes of epithelium and endothelium. The distribution of fibronectin, tenascin, and laminin is related to previous findings in other species. The localization of the several integrin alpha-subunits is also described in full baboon mandibular sections. The vitronectin receptor (alpha v) had a uniquely strong expression in osteoclasts of the alveolar bone and was found, at lesser intensity, on periodontal ligament fibroblasts. The fibronectin receptor alpha subunit, alpha 5, was also observed on osteoclasts, and, in addition, was widely distributed on fibroblasts, cementoblasts, and osteoblasts.(ABSTRACT TRUNCATED AT 250 WORDS)