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ID PMID Title PublicationDate abstract
31445443 Surface water extracts impair gene profiles and differentiation in human mesenchymal stem 2019 Nov Low concentrations of pollutants in surface water challenge the assessment of chronic effects on human health. Human bone mesenchymal stem cells (hBMSCs) were employed as a sensitive and relevant in vitro model to evaluate the potential biological effects caused by mixtures of pollutants in surface water. Organic extracts of surface water collected from Hun River inhibited cell viability in a dose-dependent manner. Surface water extracts at noncytotoxic concentrations induced 533 to 1055 differentially expressed genes (DEGs) in hBMSCs after 48 h of exposure. Total of 370 genes were commonly affected by surface water from different sites and accounted for 35-69% of DEGs impaired by individual sample. Pathways related to human diseases, genetic information processing and organismal systems were enriched based on DEGs. Interleukins (IL1B, IL6 and IL8) were affected and involved in most human diseases related pathways. The significantly downregulation of COL1A1 and the variation of rheumatoid arthritis pathway suggested that surface water potentially inhibited osteogenic differentiation of hBMSCs. Clustering analysis and principle component analysis with DEGs distinguish the surface water from tributary and mainstream. The crossing-species comparison of transcriptomic changes identified 923 and 2715 differentially expressed orthologs in hBMSCs and zebrafish, respectively. After the exposure ceased, the followed osteogenic and adipogenic differentiation in hBMSCs for 14 days were inhibited by the treatment of surface water during undifferentiated period, whereas the non-polar fraction exhibited stronger potency in affecting differentiation than the mid to polar fractions. hBMSCs, combining unsupervised transcriptomic technique and specific endpoints test, are promising in screening the health effects of environmental mixtures in surface water.
31318655 Case 268: Bilateral Adrenal Hemorrhage in the Context of Sepsis. 2019 Aug History A 65-year-old man presented to the emergency department with a 1-week history of constipation, which was associated with increasing abdominal distention and not passing flatus. Four weeks prior to the current admission he had been diagnosed with metastatic primary adenocarcinoma of the appendix. One week ago, he had been hospitalized with small-bowel obstruction, for which he required laparotomy and loop ileostomy. His medical history included basal cell carcinoma, rheumatoid arthritis, and Barrett esophagus. Physical examination revealed a distended abdomen with tenderness at palpation within the right upper quadrant and lower abdomen and reduced bowel sounds at auscultation. Initial plain-film radiography of the abdomen at admission revealed dilated gas-filled small-bowel loops, suggestive of obstruction. His small-bowel obstruction was managed conservatively on this occasion. Nine days after admission, the patient became unwell and reported a productive cough. He became tachycardic, tachypneic, and hypotensive. Relevant blood tests at this stage revealed a C-reactive protein level of 206 mg/L (normal range, 0-10 mg/L), a white blood cell count of 24.5 × 10(9)/L (normal range, [4.0-11.0] × 10(9)/L), a red blood cell count of 3.39 × 10(12)/L (normal range, [4.5-5.5] × 10(12)/L), a hemoglobin level of 93 g/L (normal range, 130-170 g/L), and a hematocrit level of 0.27 (normal range, 0.4-0.5). CT of the abdomen and pelvis with intravenous contrast material (100 mL Omnipaque 350; GE Healthcare, Oslo, Norway) was performed.
31129308 Traditional uses, secondary metabolites, and pharmacology of Celastrus species - a review. 2019 Sep 15 ETHNOPHARMACOLOGICAL RELEVANCE: Plants of genus Celastrus (Celastraceae) have been widely used in traditional Chinese medicine (TCM) and Indian medicine to treat cognitive dysfunction, epilepsy, insomnia, rheumatism, gout, and dyspepsia for thousands of years. AIM OF STUDY: We critically summarized the current evidence on the botanic characterization and distribution, ethnopharmacology, secondary metabolites, pharmacological activities, qualitative and quantitative analysis, and toxicology of Celastrus species to provide perspectives for developing more attractive pharmaceuticals of plant origin. MATERIALS AND METHODS: The relevant information on Celastrus species was gathered from worldwide accepted scientific databases via electronic search (Web of Science, SciFinder, PubMed, Elsevier, SpringerLink, Wiley Online, China Knowledge Resource Integrated, and Google Scholar). Information was also obtained from the literature and books as well as PhD and MSc dissertations. Plant names were validated by "The Plant List" (www.theplantlist.org). RESULTS: Comprehensive analysis of the above mentioned databases and other sources confirmed that ethnomedical uses of plants of Celastrus genus had been recorded in China, India, and other countries in Southern Asia. The phytochemical investigation revealed the presence of β-dihydroagarofuranoids, diterpenoids, triterpenoids, tetraterpenes, phenylpropanoids, alkaloids, flavonoids, lignans, and others. The crude extracts and isolated constituents have exhibited a wide range of in vitro and in vivo pharmacological effects, including antitumor, cytotoxic, insecticidal, antimicrobial, anti-rheumatoid arthritis (RA), anti-inflammatory, anti-ageing and antioxidative, and neuroprotective activities. CONCLUSION: Plants of genus Celastrus have been confirmed to show a strong potential for therapeutic and health-maintaining effects, in light of their long traditional use and the phytochemical and pharmacological studies summarized here. Currently, pharmacological studies of this genus mainly focus on Celastrus paniculatus Willd. and Celastrus orbiculatus Thunb. Therefore, more pharmacological investigations should be implemented to support traditional uses of other medicinal plants of the genus Celastrus. Moreover, studies on the toxicity, bioavailability, and pharmacokinetics, in addition to clinical trials, are indispensable for assessing the safety and efficacy of the secondary metabolites or extracts obtained from plants belonging to this genus.
31885481 Oxidative free radicals scavenging activity (in vitro and in vivo assay) of standardized f 2019 Dec TRADITIONAL PERTINENCE: Argyreia speciosa Sweet (Linn.), belongs to the family convolvulaceae, a traditional Indian medicinal herb, has been used to treat acute/chronic ulcers, gonorrhea, rheumatoid arthritis and several nervous disorders having a long history. AIM OF THE STUDY: A broad spectrum approach of this work was to find out the antioxidant activity of Argyreia speciosa seeds, in vitro and in vivo antioxidant assay were performed. MATERIAL AND METHODS: Total phenolic content (TPC), reducing power (RP), antioxidant activity (AOA), O2·- (superoxide anion), DPPḢ (1,1-diphenyl-2-picrylhydrazyl) and ˙OH (hydroxyl) radicals scavenging activities, GSH (glutathione), CAT (catalase), SOD (superoxide dismutase) and LPO (lipid peroxidase) are the major parameters which were studied for determining in vitro and in vivo antioxidant property of seed extract & their six fractions obtained from A. speciosa. Carbon tetrachloride (CCl(4)) induced rat model was used to determine in vivo antioxidant assay of extract and its fractions. RESULTS: Butanol fraction (AS-BF) showed strong antioxidant property and protected oxidative DNA damage. AS-BF was found best as compared to all other fraction for determining antioxidant property of seeds with the reduction in lipid peroxide formation and increment in GSH, CAT and SOD. AS-BF showed the presence of phenolic compounds viz. gallic acid, chlorogenic acid, and ellagic acid. CONCLUSION: From these results, it was proved that A. speciosa seeds prevent tissue damage due to oxidative stress with strong antioxidant activity.
31694754 Algorithm for antinuclear antibodies in subjects with clinical suspicion of autoimmune dis 2020 Jul OBJECTIVES: Antinuclear antibodies (ANA) are fundamental in the diagnosis of systemic autoimmune rheumatic diseases (SARDs). Different assays for ANA screening are available, such as indirect immunofluorescence (IIF) on HEp-2 cells and Multiplex fluorescent immunoassay (MFI). This study aimed to clarify the importance of ANA detected only by IIF in the future development of SARDs and to recommend a laboratory algorithm that integrates the available diagnostic approaches to optimise the diagnosis of ANA IIF+MFI- subjects. METHODS: A total of 9,291 subjects with clinical suspicion of SARDs were evaluated for ANA by IIF and MFI. One hundred and ninety-eight subjects (2.1%) were ANA IIF+MFI-, who were followed up for 2 years. ANA were evaluated using IIF on HEp-2 cells and MFI on the BioPlex 2200. RESULTS: The ANA IIF+MFI- cohort included 106 subjects with SARDs, 26 subject with other autoimmune diseases (not-SARDs) and 66 subjects with minor symptoms or ANA requested in check-ups. Only 94 subjects underwent re-evaluation. After a 2-year follow-up, most re-evaluated subjects (51 patients) became ANA negative for both assays (mainly rheumatoid arthritis, polymyalgia and inflammatory bowel disease patients) and 35 subjects remained ANA IIF+MFI- (principally systemic sclerosis and systemic lupus erythematosus patients). A new algorithm for ANA evaluation was suggested. CONCLUSIONS: According to the proposed algorithm, ANA IIF+MFI- subjects should be screened by an alternative solid-phase assay such as line-immunoassay or ELISA.
31663542 Tannic acid-based nanogel as an efficient anti-inflammatory agent. 2020 Feb 21 Biologically produced reactive oxygen species (ROS) are important signaling molecules in the human body. Despite their importance under normal conditions, abnormal overproduction of ROS under unbalanced or irregular homeostasis can cause severe inflammatory diseases. Various antioxidants have been developed in the biomedical field to resolve high levels of ROS; however, high doses of natural antioxidants such as polyphenol can induce side effects on health. Further, synthetic antioxidants are still controversial in regards to their safety and their complicated synthesis. Inspired from our previous work, a nitric oxide-scavenging nanogel designed for treating rheumatoid arthritis, we report herein a biocompatible tannic acid (TA)-based nanogel as an effective ROS scavenger. A polymeric phenylboronic acid-tannic acid nanogel (PTNG) was prepared by simply mixing through to the formation of phenylboronic ester bonds between polymeric phenylboronate and TA. We focused on the reaction of phenylboronic ester with H(2)O(2), which readily consumes H(2)O(2) molecules, and applied it as an antioxidant. In addition, TA is a well-known antioxidant, specifically a free radical scavenger; thus, we expected combinatory ROS scavenging effects for PTNG. Various ROS scavenging assays revealed the significant antioxidant effects of PTNG. Under an induced inflammation model in vitro, our PTNG showed high biocompatibility as well as strong anti-inflammatory effects. Furthermore, in the zymosan-induced peritonitis mouse model, a representative acute inflammation model in vivo, PTNG reduced significant neutrophil recruitment and pro-inflammatory cytokines, indicating successful alleviation of inflammation. On the basis of these results, we suggest that PTNG has great potential as an antioxidant and should find application in the treatment of further ROS-overproducing inflammatory diseases.
31477883 Lysosomes as a therapeutic target. 2019 Dec Lysosomes are membrane-bound organelles with roles in processes involved in degrading and recycling cellular waste, cellular signalling and energy metabolism. Defects in genes encoding lysosomal proteins cause lysosomal storage disorders, in which enzyme replacement therapy has proved successful. Growing evidence also implicates roles for lysosomal dysfunction in more common diseases including inflammatory and autoimmune disorders, neurodegenerative diseases, cancer and metabolic disorders. With a focus on lysosomal dysfunction in autoimmune disorders and neurodegenerative diseases - including lupus, rheumatoid arthritis, multiple sclerosis, Alzheimer disease and Parkinson disease - this Review critically analyses progress and opportunities for therapeutically targeting lysosomal proteins and processes, particularly with small molecules and peptide drugs.
31432093 Hydroxytyrosol promotes autophagy by regulating SIRT1 against advanced oxidation protein p 2019 Oct Advanced oxidation protein products (AOPPs) can trigger NADPH oxidase (NOX) and lead to the production of reactive oxygen species (ROS) in the pathophysiology of rheumatoid arthritis (RA). Hydroxytyrosol (HT) is a phenolic composite in olive oil that has antioxidant and anti‑inflammatory effects and enhances autophagy. Early research has revealed that HT can activate the silent information regulator 1 (SIRT1) pathway to induce autophagy and alleviate the cartilage inflammatory response caused by H2O2. However, whether HT can attenuate AOPP‑induced NOX and inflammatory responses remains to be elucidated. The present study aimed to investigate how HT can alleviate the damage caused by AOPPs. In cell experiments, chondrocytes were pre‑stimulated with HT and then exposed to AOPPs. First, it was found that HT promoted autophagy through the SIRT1 pathway, increased the expression of autophagy‑related proteins including microtubule‑associated protein 1 light chain 3, autophagy related (ATG)5 and ATG7, and decreased the expression of P62. Furthermore, HT reduced the expression of NOX, which was affected by AOPPs in chondrocytes through the SIRT1 pathway. Finally, the expression of inflammatory cytokines caused by AOPPs was downregulated following HT treatment. In conclusion, it was found that HT reduced the expression of NOX and inhibited the inflammatory response caused by AOPPs in chondrocytes through the SIRT1 pathway.
31066629 FMS-like Tyrosine Kinase 3/FLT3: From Basic Science to Clinical Implications. 2019 Jul 1 FMS-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase that is expressed almost exclusively in the hematopoietic compartment. Its ligand, FLT3 ligand (FL), induces dimerization and activation of its intrinsic tyrosine kinase activity. Activation of FLT3 leads to its autophosphorylation and initiation of several signal transduction cascades. Signaling is initiated by the recruitment of signal transduction molecules to activated FLT3 through binding to specific phosphorylated tyrosine residues in the intracellular region of FLT3. Activation of FLT3 mediates cell survival, cell proliferation, and differentiation of hematopoietic progenitor cells. It acts in synergy with several other cytokines to promote its biological effects. Deregulated FLT3 activity has been implicated in several diseases, most prominently in acute myeloid leukemia where around one-third of patients carry an activating mutant of FLT3 which drives the disease and is correlated with poor prognosis. Overactivity of FLT3 has also been implicated in autoimmune diseases, such as rheumatoid arthritis. The observation that gain-of-function mutations of FLT3 can promote leukemogenesis has stimulated the development of inhibitors that target this receptor. Many of these are in clinical trials, and some have been approved for clinical use. However, problems with acquired resistance to these inhibitors are common and, furthermore, only a fraction of patients respond to these selective treatments. This review provides a summary of our current knowledge regarding structural and functional aspects of FLT3 signaling, both under normal and pathological conditions, and discusses challenges for the future regarding the use of targeted inhibition of these pathways for the treatment of patients.
31021403 Identification of a novel salivary biomarker miR-143-3p for periodontal diagnosis: A proof 2019 Oct BACKGROUND: Though the use of salivary miRNAs as potential biomarkers has been reported in few diseases/conditions such as rheumatoid arthritis and oral cancer, there are no reported studies on their utility in periodontal diagnostics. Thus, the aim of the present study was to profile salivary miRNAs and identify the most suitable salivary miRNA biomarker in chronic periodontitis. METHODS: In this study, we have explored the potential application of next generation sequencing (NGS) technology for profiling miRNAs in two unstimulated saliva samples collected by passive drool method from a patient diagnosed with generalized chronic periodontitis and a healthy control. Subsequently, the validation of most highly expressed known miRNA in periodontitis was performed in saliva samples collected from an independent set of 16 chronic periodontitis patients and 16 periodontally healthy controls using quantitative real-time PCR (qRT-PCR). Target gene prediction and pathway mapping were performed using bioinformatic tools. RESULTS: NGS analysis identified 40 upregulated and 40 downregulated known miRNAs in chronic periodontitis compared to healthy controls, of which miR-143-3p was the most highly expressed miRNA in periodontitis (Read count - 227630; fold change - 5.82). Validation using qRT-PCR showed significant upregulation of miR-143-3p expression in the test group compared with controls (P < 0.05). K-RAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene) gene was predicted as the target gene for miR-143-3p in humans. KEGG (Kyoto Encyclopedia of genes and genomes) pathway mapping revealed the involvement of K-RAS in mitogen-activated protein kinases (MAPK) pathway. CONCLUSIONS: The application of NGS for miRNA expression profiling can be considered a valuable tool in detection of novel biomarkers in periodontal diagnostics. Also, the results of the study points to the potential utility of miR143-3p as a novel salivary biomarker for chronic periodontitis.
30909660 Bacterial sialoglycosidases in Virulence and Pathogenesis. 2019 Mar 24 Human oral microbiome and dysbiotic infections have been recently evidently identified. One of the major reasons for such dysbiosis is impairment of the immune system. Periodontitis is a chronic inflammatory disease affecting the tissues that surround and support the teeth. In the United States., approximately 65 million people are affected by this condition. Its occurrence is also associated with many important systemic diseases such as cardiovascular disease, rheumatoid arthritis, and Alzheimer's disease. Among the most important etiologies of periodontitis is Porphyromonas gingivalis, a keystone bacterial pathogen. Keystone pathogens can orchestrate inflammatory disease by remodeling a normally benign microbiota causing imbalance between normal and pathogenic microbiota (dysbiosis). The important characteristics of P. gingivalis causing dysbiosis are its virulence factors which cause effective subversion of host defenses to its advantage allowing other pathogens to grow. Some of the mechanisms involved in these processes are still not well-understood. However, various microbial strategies target host sialoglycoproteins for immune dysregulation. In addition, the enzymes that break down sialoglycoproteins and sialoglycans are the "sialoglycoproteases", resulting in exposed terminal sialic acid. This process could lead to pathogen-toll like receptor (TLR) interactions mediated through sialic acid receptor ligand mechanisms. Assessing the function of P. gingivalis sialoglycoproteases, could pave the way to designing carbohydrate analogues and sialic acid mimetics to serve as drug targets.
30813943 Intralymphatic histiocytosis in a patient with lung adenocarcinoma treated with pembrolizu 2019 Feb 27 BACKGROUND: Pembrolizumab, an anti-programmed cell death-1 protein monoclonal antibody, is effective for patients with advanced non-small-cell lung cancer. However, immune checkpoint inhibitors such as pembrolizumab induce various immune-related adverse events, involving the lung, liver, gastrointestinal, endocrine system, and skin. Intralymphatic histiocytosis (ILH) is a rare, chronic cutaneous disorder with a reactive inflammatory component, which often occurs in patients with rheumatoid arthritis. CASE PRESENTATION: We present a 67-year-old man with lung adenocarcinoma who developed ILH associated with pembrolizumab treatment. He was treated with palliative thoracic radiotherapy for superior vena cava syndrome. Subsequently, he received four cycles of pembrolizumab. Approximately 2.5 months after the initiation of pembrolizumab, he developed erythema on the trunk of his body. Based on findings of skin biopsies, he was diagnosed with pembrolizumab-induced ILH. Moreover, the upregulation of tumor necrosis factor-α was observed during pembrolizumab therapy. CONCLUSIONS: This is the first report of ILH induced by pembrolizumab in a patient with lung adenocarcinoma.
30590021 17-β-estradiol enhances neutrophil extracellular trap formation by interaction with estro 2019 Mar 15 Cell death-associated neutrophil extracellular trap formation (NETosis) occurs during various autoimmune diseases including systemic lupus erythematosus and rheumatoid arthritis, as well as during gestation. Although increasing estrogen concentrations associated with pregnancy might induce NETosis via nuclear estrogen receptor (ERα/ERβ), little is known about the mechanisms associated with estrogen-induced NETosis. Here, we investigated the effects of estrogen (17-β-estradiol; E2) on NETosis, focusing on mechanisms associated with estrogen membrane receptor (GPR30) in neutrophil-like HL-60 cells. Our results show that E2 and the GPR30 agonist G-1 increases level of NETosis and NET formation. Moreover, NETosis-associated intracellular and extracellular histone citrullination and peptidyl arginine deiminase 4 (PAD4) expression were also increased by E2 or G-1 treatment. Furthermore, GPR30 antagonist pre-treatment inhibited increases in NETosis and PAD4 expression mediated by G-1 and partially inhibited these effects mediated by E2. These results demonstrate that E2 treatment induces NETosis via not only ERα/ERβ but also GPR30 in neutrophil-like HL-60 cells.
30572710 Impact of Yoga on Inflammatory Biomarkers: A Systematic Review. 2019 Mar BACKGROUND: Many chronic conditions, including heart disease, cancer, and rheumatoid arthritis, are associated with underlying chronic inflammatory processes. Literature reviews have analyzed a variety of integrative therapies and their relationships with chronic inflammation. This systematic review is unique in reporting solely on yoga's relationship with inflammation. Its purpose was to synthesize current literature examining the impact of yoga interventions on inflammatory biomarkers in adults with chronic inflammatory-related disorders. METHOD: Searches of several electronic databases were conducted. Inclusion criteria were (a) English language, (b) sample age >18 years old, (c) yoga interventions involving postures with or without yoga breathing and/or meditation, and (d) measured inflammatory biomarkers. RESULTS: The final review included 15 primary studies. Of these, seven were rated as excellent and eight as average or fair. There was considerable variability in yoga types, components, frequency, session length, intervention duration, and intensity. The most common biomarkers measured were interleukin-6 ( n = 11), C-reactive protein ( n = 10), and tumor necrosis factor ( n = 8). Most studies reported positive effects on inflammatory biomarkers ( n = 11) from baseline to post yoga intervention. Analysis of the dose showed higher total dose (>1,000 min) resulted in greater improvements in inflammation. CONCLUSION: This review suggests that yoga can be a viable intervention to reduce inflammation across a multitude of chronic conditions. Future studies with detailed descriptions of yoga interventions, measurement of new and well-established inflammatory biomarkers, and larger sample sizes are warranted to advance the science and corroborate results.
30502718 A role for Th1-like Th17 cells in the pathogenesis of inflammatory and autoimmune disorder 2019 Jan The T helper 17 (Th17) cells contain a dynamic subset of CD4+ T-cells that are able to develop into other different lineage subsets, including the Th1-like Th17 cells. These cells co-express retinoic acid-related orphan receptor gamma t (RORγt) and transcription factor T-box-expressed-in-T-cells (T-bet) and produce both interleukin (IL)-17 and interferon (IFN)-γ. Recent reports have shown that Th1-like Th17 cells play crucial roles in the pathogenesis of autoimmune diseases such as inflammatory bowel disease, multiple sclerosis and rheumatoid arthritis, as well as, some primary immunodeficiency with autoimmune features. Here, the actual mechanisms for Th17 cells plasticity to Th1-like Th17 cells are discussed and reviewed in association to the role that Th1-like Th17 cells have on inflammatory and autoimmune disorders.
30045682 Case series of unique adverse events related to the use of ibrutinib in patients with B-ce 2019 Jul BACKGROUND: Ibrutinib, a Bruton's tyrosine kinase inhibitor has reformed the treatment of various B-cell malignancies including chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom's macroglobulinemia. Although generally well tolerated, here we describe our institutional experience of unique adverse effects encountered with the use of ibrutinib in patients with B-cell lymphomas. METHODS: This is a retrospective observational study done at a tertiary care facility, to evaluate adverse events in patients with B-cell malignancies on treatment with ibrutinib between 2014 and 2018. Further details including type of malignancy, cytogenetics, interventions for treatment of the side effect, and outcomes were obtained through electronic health record. CASE SERIES: We found 10 patients with unique adverse events related to ibrutinib. Among those, six had chronic lymphocytic leukemia, two had Waldenstrom's macroglobulinemia, and two had mantle cell lymphoma. The events included palindromic rheumatoid arthritis, diffuse spongiotic dermatitis, bullous pemphigoid, recurrent hemorrhagic stroke, peripheral neuropathy, recurrent paronychia, intramedullary fibrosis, recurrent joint pains, pulmonary aspergillosis, dyspnea with exacerbation of atrial fibrillation, and resolution of autoimmune hemolytic anemia. CONCLUSION: Our case series illustrates the wide variety of unique events recognized in patients treated with ibrutinib, some of which required cessation and most had dose reduction of the treatment. Thus, stressing the importance of early identification and intervention for the events to avoid worsening of toxicity and inability to continue treatment in such patients.
29292028 Effectiveness of interventions to improve therapy adherence in people with upper limb cond 2019 Apr STUDY DESIGN: Systematic review. INTRODUCTION: Patient adherence to orthosis wear and/or prescribed exercises improves functional outcome after acute injury and can prevent deformities, contractures, and reinjury of tissues. This is the first systematic review to review the evidence of the effectiveness of interventions to improve treatment adherence in children and adults with acute or chronic upper limb injuries or conditions. PURPOSE OF THE STUDY: The purpose of this study is to establish the effectiveness of interventions to improve hand therapy adherence in people with upper limb conditions and to report on outcome measures used when reporting adherence. METHODS: A literature search of MEDLINE (OVID), Embase (OVID), CENTRAL (OVID), CINAHL (EBSCO), and EmCare (OVID) (from inception to March 2017) was undertaken. Studies were selected if they met the following inclusion criteria: clinical trials; in adults or children with any injury or condition affecting the upper limb including acute trauma and injury; chronic and acquired musculoskeletal conditions; and neurological conditions. Two independent assessors rated the study quality and risk of bias using the Cochrane Collaboration tool for assessing the risk of bias. RESULTS: Eight studies met the inclusion criteria. Study quality ranged from 3 to 6 out of 7 points on the Cochrane risk of bias tool. There were 4 categories of intervention for improving adherence: orthosis/cast material/design; orthosis wear schedule; patient education mode for home exercise programs; and behavioral approaches. Due to heterogeneity of condition acuity, interventions, and outcomes reported, it was not possible to pool the results from all studies. Therefore, a narrative best evidence synthesis was undertaken. There is weak evidence from a very small number of trials that orthosis/cast material has no influence on treatment adherence in acute or chronic conditions and mode of patient education (audio-visual vs written) has no effect in acute conditions. There is low-to-moderate quality of evidence in support of behavioral interventions for achieving treatment adherence in chronic rheumatoid arthritis. CONCLUSION: Behavioral approaches that encourage self-efficacy are likely to be useful in achieving treatment adherence in populations with chronic upper limb conditions. There is insufficient evidence for other interventions aimed at improving adherence in acute upper limb injuries and conditions.
34288615 2019 Mar Tofacitinib (Xeljanz) is an orally administered Janus kinase inhibitor indicated for the treatment of patients with moderately to severely active ulcerative colitis (UC) who have had an inadequate response, loss of response, or intolerance to either conventional UC therapy or a biologic agent. The recommended dosage for tofacitinib is one 10 mg tablet administered twice daily during an induction period lasting at least eight weeks, followed by one 5 mg tablet administered twice daily thereafter during the maintenance phase of treatment once response to treatment has been achieved. Tofacitinib 10 mg twice daily in the maintenance phase may be prescribed to some patients. The product monograph states that tofacitinib should be discontinued if no evidence of benefit is achieved by week 16. At the manufacturer-submitted price of $23.96 per 5 mg tablet and $42.34 per 10 mg tablet, the annual cost of tofacitinib is $19,501 in the first year and $17,442 every year thereafter, based on the recommended dosage for induction and 5 mg twice daily in the maintenance phase. This cost could increase significantly, up to $30,181 per year, in certain populations requiring tofacitinib 10 mg twice daily in the maintenance phase. Tofacitinib 5 mg was previously considered by CADTH Canadian Drug Expert Committee for the treatment of rheumatoid arthritis in 2015 and was recommended to be listed with clinical criteria, with the condition that the drug plan cost for tofacitinib not exceed the drug plan costs for the biologic disease-modifying antirheumatic drugs. The manufacturer submitted a cost-utility analysis comparing tofacitinib plus conventional therapy (a mix of 5-aminosalicylates, corticosteroids, and immunomodulators) with biologic treatments (vedolizumab, infliximab, infliximab biosimilar, adalimumab, and golimumab) plus conventional therapy (same as tofacitinib), as well as continuing conventional therapy (the same mix of 5-aminosalicylates, steroids, and immunomodulators) in patients (≥ 18 years of age) with moderately to severely active UC and an inadequate response to conventional therapy or biological agents. The analysis was conducted over a lifetime time horizon from a Canadian public health care payer perspective. The manufacturer submitted a cohort-level state-transition (Markov) model, in which patients entered the model in an active UC state and started an eight-week induction period with tofacitinib or a biologic comparator plus conventional therapy or continued on conventional therapy alone. At any time in the model, patients could experience a response or clinical remission, or remain in an active UC state (nonresponders), and patients in a clinical remission or response state could lose their response and regress to active UC. Patients in the active UC state could undergo a colectomy at any point; the risk of colectomy differed based on time since UC diagnosis.
29130124 Systemic autoimmune diseases complicated with hydrocephalus: pathogenesis and management. 2019 Jun Systemic autoimmune diseases (SAIDs) represent a group of syndromes involving at least two organ systems. Classical SAIDs include connective tissue diseases, vasculitis, and granulomatous diseases, many of which involve the nervous system and result in different neurological manifestations. Hydrocephalus can be a rare but lethal complication of various SAIDs, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), sarcoidosis, and primary vasculitis. However, the pathogenesis of SAIDs complicated with different types of hydrocephalus is varied and difficult to determine using the existing published data, and various manifestations and expressive forms of the conditions bring a substantial challenge to a timely clinical diagnosis and treatment. The commonly used medical management programs based on the etiology of hydrocephalus are anti-inflammatory or anti-infectious therapies, while surgical management such as ventriculoperitoneal shunts is effective most of the time. Further research should be directed toward improving our understanding of the pathogenesis of these conditions and determining the most effective method for treating this life-threatening condition.
32881511 Epitope Identification and Affinity Determination of an Inhibiting Human Antibody to Inter 2020 Jan 2 The polypeptide chemokine Interleukin-8 (IL8) plays a crucial role in inflammatory processes in humans. IL8 is involved in chronic inflammatory lung diseases, rheumatoid arthritis, and cancer. Previous studies have shown that the interaction of IL8 with its natural receptors CXCR1 and CXCR2 is critical in these diseases. Antibodies have been used to study the receptor interaction of IL8; however, the binding epitopes were hitherto unknown. Identification of the antibody epitope(s) could lead to a molecular understanding of the inhibiting mechanism and development of improved inhibitors. Here, we report the epitope identification and the affinity characterization of IL8 to a monoclonal anti-human IL8 antibody inhibiting the receptor binding by a combination of surface plasmon resonance (SPR) biosensor analysis and MALDI-mass spectrometry. SPR determination of IL8 with the immobilized antibody revealed high affinity (K(D), 82.2 nM). Epitope identification of IL-8 was obtained by proteolytic epitope-extraction mass spectrometry of the peptide fragments upon high pressure trypsin digestion, using an affinity microcolumn with immobilized anti-IL-8 antibody. MALDI-MS of the affinity-bound peptide elution fraction revealed an assembled (discontinuous) epitope comprising two specific peptides, IL8 [12-20] and IL8 [55-60]. Identical epitope peptides were identified by direct MALDI-MS of the eluted epitope fraction from the immobilized anti-IL8 antibody on the SPR chip. SPR determination of the synthetic epitope peptides provided high affinities confirming their binding specificity. The previously reported finding that the anti-Il8 antibody is inhibiting the IL8-CXCR1 interaction is well consistent with the overlapping region of epitope interactions identified in the present study.