Macarena Aguilar-Luque

Systematic reviews and meta‐analyses on psoriasis: role of funding sources, conflict of interest and bibliometric indices as predictors of methodological quality

The quality of systematic reviews and meta‐analyses on psoriasis, a chronic inflammatory skin disease that severely impairs quality of life and is associated with high costs, remains unknown.

Lipopolysaccharide Binding Protein and Oxidative Stress in a Multiple Sclerosis Model

Recent findings in experimental autoimmune encephalomyelitis (EAE) suggest that altering certain bacterial populations present in the gut may lead to a proinflammatory condition, that could result in the development of multiple sclerosis (MS). Also, Reactive Oxygen Species seem to be involved in the course of MS. In this study, it has been aimed to relate all these variables starting from an analysis of the lipopolysaccharide (LPS) and LPS-binding protein (LBP) with the determination of parameters related to oxidative stress in the blood, brain and spinal cord. For this purpose, samples obtained from EAE rats and relapsing-remitting (RRMS) MS patients were used. In addition, EAE rats were treated with Natalizumab, N-acetyl-cysteine and dimethyl fumarate. Natalizumab was also employed in RRMS. The results of this study revealed an improvement in the clinical symptoms of the EAE and MS with the treatments, as well as a reduction in the oxidative stress parameters and in LBP. Correlations between the clinical variables of the disease, i.e. oxidative damage and LBP, were established. Although the conclusions of this research are indeed relevant, further investigation would be necessary to establish the intrinsic mechanisms of the MS-oxidative stress-microbiota relationship.

Transcranial magnetic stimulation modifies astrocytosis, cell density and lipopolysaccharide levels in experimental autoimmune encephalomyelitis.

Aims: Experimental autoimmune encephalomyelitis (EAE) is considered a valid experimental model for multiple sclerosis, a chronic neuroinflammatory condition of the central nervous system. Additionally, some evidence has shown that some microbial products such as the bacterial lipopolysaccharide could lead to the activation of reactive immune cells, triggering neuroinflammation. Several studies have found that transcranial magnetic stimulation (TMS) may exert a neuroprotective effect. Therefore, we aimed to assess the effect of TMS on the neuroinflammation occurring in EAE. Materials and methods: A total of 44 male Dark Agouti rats were used. EAE induction was performed administering subcutaneously at the dorsal base of the tail a single dose of myelin oligodendrocyte glycoprotein. Clinical evaluation of motor symptoms was performed. Brain and spinal cord were collected and analyzed for nitric oxide, bacterial lipopolysaccharide and lipopolysaccharide‐binding protein. We also carried out a histologic exam, which included an astrocyte immunostaining and Nissl staining for the assessment of brain cell density and pyknotic nuclei. Key findings: TMS effectively ameliorated motor impairment secondary to EAE. This form of magnetic field was capable of decreasing the proliferation of astrocytes as a response to the autoimmune attack, reducing the content of nitric oxide, bacterial lipopolysaccharide and lipopolysaccharide‐binding protein in central nervous system. Moreover, in treated animals, brain cell density was improved and the number of pyknotic nuclei was decreased. Significance: Transcranial magnetic stimulation modifies astrocytosis, cell density and lipopolysaccharide levels in EAE. These results suggest that TMS could be a promising treatment for neuroinflammatory conditions such as multiple sclerosis.

Author-paper affiliation network architecture influences the methodological quality of systematic reviews and meta-analyses of psoriasis

Moderate-to-severe psoriasis is associated with significant comorbidity, an impaired quality of life, and increased medical costs, including those associated with treatments. Systematic reviews (SRs) and meta-analyses (MAs) of randomized clinical trials are considered two of the best approaches to the summarization of high-quality evidence. However, methodological bias can reduce the validity of conclusions from these types of studies and subsequently impair the quality of decision making. As co-authorship is among the most well-documented forms of research collaboration, the present study aimed to explore whether authors’ collaboration methods might influence the methodological quality of SRs and MAs of psoriasis. Methodological quality was assessed by two raters who extracted information from full articles. After calculating total and per-item Assessment of Multiple Systematic Reviews (AMSTAR) scores, reviews were classified as low (0-4), medium (5-8), or high (9-11) quality. Article metadata and journal-related bibliometric indices were also obtained. A total of 741 authors from 520 different institutions and 32 countries published 220 reviews that were classified as high (17.2%), moderate (55%), or low (27.7%) methodological quality. The high methodological quality subnetwork was larger but had a lower connection density than the low and moderate methodological quality subnetworks; specifically, the former contained relatively fewer nodes (authors and reviews), reviews by authors, and collaborators per author. Furthermore, the high methodological quality subnetwork was highly compartmentalized, with several modules representing few poorly interconnected communities. In conclusion, structural differences in author-paper affiliation network may influence the methodological quality of SRs and MAs on psoriasis. As the author-paper affiliation network structure affects study quality in this research field, authors who maintain an appropriate balance between scientific quality and productivity are more likely to develop higher quality reviews.

Effects of transcranial magnetic stimulation on oxidative stress in experimental autoimmune encephalomyelitis

Abstract Experimental autoimmune encephalomyelitis (EAE) reproduces a multiple sclerosis (MS)-like experimental model. The main objective was to evaluate the effect of extremely low-frequency electromagnetic fields (EL-EMF) application, like a paradigm of transcranial magnetic stimulation (TMS) in the development of EAE. Rats were injected with a single dose of 150 μg of myelin oligodendrocyte glycoprotein (MOG, fragment 35–55) to produce experimental MS. To assess the effect of TMS application in EAE, the rats were treated with TMS (60 Hz and 0.7 mT) for 2 h in the morning, once a day, 5 days a week, during 3 weeks. TMS was applied to the head. The effect of TMS on EAE was evaluated as motor symptoms and, oxidative and cell damage. The data showed that MOG induced motor symptoms as tail paralysis and limb paresis/paralysis, oxidative stress and cell death similar to MS when compared with control animals. Importantly, TMS application attenuated motor symptoms, oxidative and cell damage, whereas it increased antioxidant system. Our findings suggest that: (i) MOG reproduces an experimental model of MS characterised by oxidative and cell damage; and (ii) TMS application decreases oxidative stress and cell death induced by MOG.

Skeletal muscle findings in experimental autoimmune encephalomyelitis.

INTRODUCTION Skeletal muscle is a target organ in multiple sclerosis, a chronic debilitating disease of the central nervous system caused by demyelination and axonal deterioration. Since the experimental autoimmune encephalomyelitis model reproduces the relapsing-remitting course found in most multiple sclerosis patients, this model was used to compare the histological features of skeletal muscle at onset with those observed at the start of the second relapse. MATERIAL AND METHODS Histological, histochemical and ultrastructural changes, as well as biochemical oxidative damage and antioxidant-system markers, were examined in the soleus and extensor digitorum longus muscles of Dark Agouti rats in which experimental autoimmune encephalomyelitis had been induced by active immunization using myelin oligodendrocyte glycoprotein. RESULTS Histological examination at disease onset revealed ragged-red fibers and ultrastructural evidence of mitochondrial degeneration. At the second relapse, neurogenic changes included a wide range of cytoarchitectural lesions, skeletal muscle atrophy and the appearance of intermediate fibers; however, differences were observed between soleus and extensor digitorum longus lesions. Biochemical tests disclosed an increase in oxidative stress markers at onset, which was more pronounced at the second relapse. CONCLUSIONS Microscopic findings suggest that two patterns can be distinguished at disease onset: an initial phase characterized by muscle mitochondrial alterations, and a second phase dominated by a histological muscle pattern of clearly neurogenic origin.

The differential impact of scientific quality, bibliometric factors, and social media activity on the influence of systematic reviews and meta-analyses about psoriasis

Researchers are increasingly using on line social networks to promote their work. Some authors have suggested that measuring social media activity can predict the impact of a primary study (i.e., whether or not an article will be highly cited). However, the influence of variables such as scientific quality, research disclosures, and journal characteristics on systematic reviews and meta-analyses has not yet been assessed. The present study aims to describe the effect of complex interactions between bibliometric factors and social media activity on the impact of systematic reviews and meta-analyses about psoriasis (PROSPERO 2016: CRD42016053181). Methodological quality was assessed using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) tool. Altmetrics, which consider Twitter, Facebook, and Google+ mention counts as well as Mendeley and SCOPUS readers, and corresponding article citation counts from Google Scholar were obtained for each article. Metadata and journal-related bibliometric indices were also obtained. One-hundred and sixty-four reviews with available altmetrics information were included in the final multifactorial analysis, which showed that social media and impact factor have less effect than Mendeley and SCOPUS readers on the number of cites that appear in Google Scholar. Although a journal’s impact factor predicted the number of tweets (OR, 1.202; 95% CI, 1.087–1.049), the years of publication and the number of Mendeley readers predicted the number of citations in Google Scholar (OR, 1.033; 95% CI, 1.018–1.329). Finally, methodological quality was related neither with bibliometric influence nor social media activity for systematic reviews. In conclusion, there seems to be a lack of connectivity between scientific quality, social media activity, and article usage, thus predicting scientific success based on these variables may be inappropriate in the particular case of systematic reviews.

Dose-dependent S-allyl cysteine ameliorates multiple sclerosis disease-related pathology by reducing oxidative stress and biomarkers of dysbiosis in experimental autoimmune encephalomyelitis

Abstract Garlic is a component of the Mediterranean diet. S‐allyl cysteine (SAC), the most common organosulphur present in garlic, possesses neuroprotective properties. This investigation was performed to evaluate the dose‐dependent protective action of SAC on oxidative damage, inflammation and gut microbiota alterations biomarkers. Experimental autoimmune encephalomyelitis (EAE) as a model of multiple sclerosis (MS) was induced by the myelin oligodendrocyte glycoprotein (MOG), whose effects were quantified by examining the changes in: clinical score, lipid peroxidation products, carbonylated proteins, glutathione system, tumor necrosis factor alpha (TNF&agr;), and lipopolysaccharide membrane bacteria (LPS). Our results reveal that MOG induces paralysis, oxidative damage and increases in LPS binding protein (LBP) and LPS levels. In this work, two doses of SAC were compared with two dose of N‐acetyl cysteine (NAC). SAC was more effective than NAC and it prevented the harmful effects induced by MOG more effectively at the dose of 50 mg/kg than that of 18 mg/kg. Surprisingly, NAC increases LBP levels while SAC had not such negative effect. In conclusion the data show the ability of SAC to modify EAE evolution.

Evaluating characteristics of PROSPERO records as predictors of eventual publication of non-Cochrane systematic reviews: a meta-epidemiological study protocol

BackgroundEpidemiology and the reporting characteristics of systematic reviews (SRs) and meta-analyses (MAs) are well known. However, no study has analyzed the influence of protocol features on the probability that a study’s results will be finally reported, thereby indirectly assessing the reporting bias of International Prospective Register of Systematic Reviews (PROSPERO) registration records.ObjectiveThe objective of this study is to explore which factors are associated with a higher probability that results derived from a non-Cochrane PROSPERO registration record for a systematic review will be finally reported as an original article in a scientific journal.Methods/designThe PROSPERO repository will be web scraped to automatically and iteratively obtain all completed non-Cochrane registration records stored from February 2011 to December 2017. Downloaded records will be screened, and those with less than 90% fulfilled or are duplicated (i.e., those sharing titles and reviewers) will be excluded. Manual and human-supervised automatic methods will be used for data extraction, depending on the data source (fields of PROSPERO registration records, bibliometric databases, etc.). Records will be classified into published, discontinued, and abandoned review subgroups. All articles derived from published reviews will be obtained through multiple parallel searches using the full protocol “title” and/or “list reviewers” in MEDLINE/PubMed databases and Google Scholar. Reviewer, author, article, and journal metadata will be obtained using different sources. R and Python programming and analysis languages will be used to describe the datasets; perform text mining, machine learning, and deep learning analyses; and visualize the data. We will report the study according to the recommendations for meta-epidemiological studies adapted from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for SRs and MAs.DiscussionThis meta-epidemiological study will explore, for the first time, characteristics of PROSPERO records that may be associated with the publication of a completed systematic review. The evidence may help to improve review workflow performance in terms of research topic selection, decision-making regarding team selection, planning relationships with funding sources, implementing literature search strategies, and efficient data extraction and analysis. We expect to make our results, datasets, and R and Python code scripts publicly available during the third quarter of 2018.

A Scoping Review Protocol to Explore the Use of Interleukin-1-Targeting Drugs for the Treatment of Dermatological Diseases: Indications, Mechanism of Action, Efficacy, and Safety

IntroductionThe interleukin (IL)-1 pathway has been identified as being involved in inflammatory and neoplastic skin diseases such as psoriasis, atopic dermatitis, neutrophilic dermatosis, melanoma, and squamous cell carcinoma. Drugs developed to target the IL-1 pathway are currently used to treat these pathologies, and although they are becoming more selective, they are not exempt from adverse events and high costs. Integrating the best research evidence with clinical experience and patient needs has been shown to improve care, health, and cost outcomes. This is because evidence-based guidelines rank interventions according to cost-effectiveness. However, evidence on this topic is scarce for several reasons. First, although randomized clinical trials currently provide the best evidence, they are not always available. Second, there are no secondary scientific studies that summarize the use of IL-1-targeting agents in dermatology. We therefore sought to develop an a priori protocol for broadly reviewing the available evidence on the use of IL-1-targeting drugs in the treatment of dermatological diseases.MethodsWe used the latest methodology to perform a scoping review as described in the Joanna Briggs Institute manual.Results/DiscussionDeveloping and applying a methodology for evidence synthesis promotes reproducibility and increases the validity of secondary scientific investigations, making it the optimal strategy for scientifically synthesizing a broad field such as the indications for and the mechanisms of action, efficacies, safety, and costs of IL-1-targeting drugs in the treatment of dermatological diseases. Quantitative synthesis facilitates the detection of knowledge gaps and the identification of new questions that can be addressed through systematic reviews. We present an a priori protocol for exploring the available evidence on this topic.