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ID PMID Title PublicationDate abstract
30016852 Skeletal muscle-gut axis: emerging mechanisms of sarcopenia for intestinal and extra intes 2018 Dec In recent years, there has been an increasing interest on muscle wasting, considering the reduction of quality of life and the increase of morbidity and mortality associated. Sarcopenia and cachexia represent two conditions of reduction of muscle mass, sharing several elements involved in their pathogenesis, such as systemic inflammation, impaired muscle protein synthesis, increased muscle apoptosis, mitochondrial dysfunction in skeletal muscle tissue and insulin resistance. These features often characterize cancer, inactivity or denervation, but also inflammatory diseases, such as chronic obstructive pulmonary disease, renal failure, cardiac failure, rheumatoid arthritis, inflammatory bowel disease and aging in general. The gastrointestinal tract and gut microbiota are thought to be deeply associated with muscle function and metabolism, although the exact mechanisms that link gut with skeletal muscle are still not well known. This review summarized the potential pathways linking gut with muscle, in particular in conditions as sarcopenia and cachexia. The main emerging pathways implicated in the skeletal muscle-gut axis are: the myostatin/activin signaling pathway, the IGF1/PI3K/AKT/mTOR signaling pathway, which results suppressed, the NF-kB signaling pathway and the FOXO signaling pathway. Further researches in this field are necessary to better explain the linkage between gut microbiota and muscle wasting and the possible emerging therapies associated.
29891877 Trans-eQTLs identified in whole blood have limited influence on complex disease biology. 2018 Sep Trans-eQTLs have been implicated in complex traits and common diseases, but many were initially identified on the basis of having an effect in cis, and there has been no assessment of the significance of the overlap in relation to chance expectations. Here, we investigated whether trans-expression quantitative trait loci (eQTL) associations identified in whole blood contribute to variance in complex traits by determining (1) whether genome-wide significant (GWS) single-nucleotide polymorphisms (SNPs) were enriched for trans-eQTL (including trans-only eQTL), and (2) whether the genomic regions surrounding associated trans-genes were enriched for statistical associations in the relevant GWAS. On average for a given phenotype, we identify 4.8% of GWS SNPs overlapping with trans-eQTL present in blood, and show that for the majority of these phenotypes, this observation does not exceed that expected by chance. Likewise, we observe no enrichment for genetic associations with the GWAS phenotype in the regions surrounding the linked trans-genes, with the exception of rheumatoid arthritis. Interestingly, the GWS SNPs for each phenotype were consistently more enriched for unique trans-eQTL SNPs than trans-eQTL SNP-probe pairs (p = 4 × 10(-)(7)), with schizophrenia the only exception. This relative enrichment for trans-eQTL SNPs over trans-eQTL SNP-probe pairs implies that trait-associated trans-eQTL SNPs in whole blood are less likely to be 'master regulators' than random trans-eQTL SNPs. Taken together, these results suggest little evidence for the role of blood-based trans-eQTL in complex traits and disease, although this may reflect the finite size of currently available data sets and our findings may not hold for trans-eQTLs in more trait-relevant tissues. All software is publically available at https://github.com/IMB-Computational-Genomics-Lab/eqtlOverlapper .
29802059 Conservative surgical treatment of medication related osteonecrosis of the jaw (MRONJ) les 2018 Jul The purpose of the study was to evaluate the efficacy of conservative surgical treatment of medication related osteonecrosis of the jaw (MRONJ) in patients affected by osteoporosis and exposed to oral bisphosphonates (BPs). Subjects diagnosed with MRONJ and osteoporosis under oral BPs that had undergone conservative surgery and had at least 24 months follow-up were included. All patients received medical-antibiotic therapy and then underwent conservative surgical treatment consisting of sequestrectomy, soft tissue debridement and bone curettage with limited or no extension. A total of 53 patients, mean age of 71.9 ± 10.2 years (range 41-87), were enrolled. Two years after conservative surgical therapy 45 patients (91.8%) showed complete healing. The presence of rheumatoid arthritis (p = 0.003) and a more severe initial MRONJ stage (p = 0.023) were associated with a negative surgical outcome while the presence of bone sequestrum was strongly associated with a positive outcome (p = 0.036). Conservative surgical treatment of MRONJ lesions in patients affected by osteoporosis and receiving only oral BPs may represent a valid therapeutic approach determining a high number of complete healing cases. Conservative surgery should be encouraged at early MRONJ stages and after medical therapy failure.
29568300 Tailoring Immune Responses toward Autoimmunity: Transcriptional Regulators That Drive the 2018 T-dependent humoral immune responses to infection involve a collaboration between B and CD4 T cell activation, migration, and co-stimulation, thereby culminating in the formation of germinal centers (GCs) and eventual differentiation into memory cells and long-lived plasma cells (PCs). CD4 T cell-derived signals drive the formation of a tailored B cell response. Downstream of these signals are transcriptional regulators that are the critical enactors of immune cell programs. In particular, a core group of transcription factors regulate both B and T cell differentiation, identity, and function. The timing and expression levels of these transcription factors are tightly controlled, with dysregulated expression correlated to immune cell dysfunction in autoimmunity and lymphomagenesis. Recent studies have significantly advanced our understanding of both extrinsic and intrinsic regulators of autoreactive B cells and antibody-secreting PCs in systemic lupus erythematosus, rheumatoid arthritis, and other autoimmune conditions. Yet, there are still gaps in our understanding of the causative role these regulators play, as well as the link between lymphoid responses and peripheral damage. This review will focus on the genesis of immunopathogenic CD4 helper and GC B cells. In particular, we will detail the transcriptional regulation of cytokine and chemokine receptor signaling during the pathogenesis of GC-derived autoimmune conditions in both murine models and human patients.
29454012 Immunologic effects of chronic administration of tofacitinib, a Janus kinase inhibitor, in 2018 Apr Tofacitinib, an oral Janus kinase (JAK) inhibitor for treatment of rheumatoid arthritis, targets JAK1, JAK3, and to a lesser extent JAK2 and TYK2. JAK1/3 inhibition impairs gamma common chain cytokine receptor signaling, important in lymphocyte development, homeostasis and function. Adult and juvenile cynomolgus monkey and rat studies were conducted and the impact of tofacitinib on immune parameters (lymphoid tissues and lymphocyte subsets) and function (T-dependent antibody response (TDAR), mitogen-induced T cell proliferation) assessed. Tofacitinib administration decreased circulating T cells and NK cells in juvenile and adult animals of both species. B cell decreases were observed only in rats. These changes and decreased lymphoid tissue cellularity are consistent with the expected pharmacology of tofacitinib. No differences were observed between juvenile and adult animals, either in terms of doses at which effects were observed or differential effects on immune endpoints. Lymphomas were observed in three adult monkeys. Tofacitinib impaired the primary TDAR in juvenile monkeys, although a recall response was generated. Complete or partial reversal of the effects on the immune system was observed.
27334466 Small Molecules as SIRT Modulators. 2018 Sirtuins are a family of NAD+-dependent deacetylases (class III histone deacetylases). Seven mammalian sirtuins, SIRT1-7, are identified, as the functions and locations differ greatly. SIRT1 and SIRT2 locate in nucleus and cytoplasm, while SIRT3-5 in mitochondria. Sirtuins are not only involved in many important biological processes such as apoptosis, cellular senescence, endocrine signaling, glucose homeostasis, aging, and longevity, it can also control circadian clocks and mitochondrial biogenesis. Small molecules that can modulate the sirtuins activity have been shown to have potentials for treating many human diseases such as type II diabetes, cancer, rheumatoid arthritis, cardiovascular and other age-relating diseases. Some polyphenolic natural products such as Resveratrol, Fisetin, and Quercetin have demonstrated health benefits due to their SIRT1 activation effects. Some structurally diverse synthetic compounds, such as SRT1720, SRT1460, Selisistat (EX 527), and AGK2 were used as small molecular SIRT modulators (IC50 = 0.04-100 μM) to treat ischemic stroke, myocardial infarction, neurodegenerative diseases, cancer, aging, and obesity. In order to get better understanding of how the small molecules interact with the sirtuin, the small molecules that having SIRT inhibitory or activation effect, found by HTS or other modern medicinal chemistry techniques, are reviewed in this article.
30765202 IL-17 and limits of success. 2019 May Interleukin-17 (IL-17) is a potent proinflammatory cytokine that protects a host against fungal and extracellular bacterial infections. On the other hand, excessive or dysregulated production of IL-17 underlines susceptibility to autoimmune disease. Consequently, blocking IL-17 has become an effective strategy for modulating several autoimmune diseases, including multiple sclerosis (MS), psoriasis, and rheumatoid arthritis (RA). Notably, however, IL-17 blockade remains ineffective or even pathogenic against important autoimmune diseases such as inflammatory bowel disease (IBD). Furthermore, the efficacy of IL-17 blockade against other autoimmune diseases, including type 1 diabetes (T1D) is currently unknown and waiting results of ongoing clinical trials. Coming years will determine whether the efficacy of IL-17 blockade is limited to certain autoimmune diseases or can be expanded to other autoimmune diseases. These efforts include new clinical trials aimed at testing second-generation agents with the goal of increasing the efficiency, spectrum, and ameliorating side effects of IL-17 blockade. Here we briefly review the roles of IL-17 in the pathogenesis of selected autoimmune diseases and provide updates on ongoing and recently completed trials of IL-17 based immunotherapies.
30584505 Chronic Recurrent Multifocal Osteomyelitis - A Rare Clinical Presentation and Review of Li 2018 May INTRODUCTION: Chronic recurrent multifocal osteomyelitis (CRMO) is an idiopathic inflammatory disorder of bone seen primarily in children and adolescents. It is part of the clinical picture of non-bacterial osteomyelitis and typically presents a relapsing course with both remissions and spontaneous exacerbations. CRMO is typically seen in the metaphysis of long bones. Usually, the clinical symptoms include painful swellings of the affected regions. It is being reported with increasing frequency but many cases of this disease go unreported. No infective agent has been identified and antibiotics do not affect the course of the disease. CASE REPORT: A 12-year-old girl presented with complaints of pain and swelling over both clavicles for 6 months duration. It was of insidious onset and it started bilaterally on the same day. It was not associated with fever. There was no history of trauma or any other swellings. On clinical examination, both clavicles were enlarged on medial half, non-tender on palpation and there was no local rise of temperature. The swellings were hard in consistency with smooth surface and margins were ill-defined. On examination, both shoulders range of motion were normal. There was no distal neurovascular deficits. Systemic examination was unremarkable. Blood investigations revealed erythrocyte sedimentation rate - 90, C-reactive protein - 0.6, total count - 8000. Rheumatoid arthritis factor, anti-cyclic citrullinated peptide, and anti-streptolysin O titer were negative. Hemoglobin electrophoresis was normal. Peripheral smear was normal. Sickling test was negative. Mantoux test and sputum acid-fast bacillus were also negative. Liver function tests and renal function tests, were within normal limits. No abnormalities were noted in ultrasonography abdomen. MRI of bilateral clavicle showed expansile lesions in bilateral clavicles -(medial aspect) possibility of CRMO. Histopathological examination showed mainly ossifying bone with foci of hemorrhage. Culture from the lesion showed no growth. CONCLUSION: CRMO is a rare benign condition. A detailed history, thorough clinical examination and rationale investigations are required. Furthermore, multidisciplinary approach including pathologist, radiologist, and pediatrician is a must. Although CRMO is rare mainly because most of the cases go undiagnosed, prognosis is good without permanent skeletal abnormalities. CRMO is essentially a diagnosis of exclusion, and hence, it is paramount importance to rule out all other fatal causes before making diagnosis of CRMO.
30543919 The loss of tolerance to CHI3L1 - A putative role in inflammatory bowel disease? 2019 Feb The incidence of inflammatory bowel disease (IBD) is steadily increasing. IBD is characterized by chronic inflammation of the gastrointestinal tract and is divided into the two main entities Crohn's disease (CD) and ulcerative colitis (UC). Genetic predispositions, environmental factors and a dysregulated immune response are known to be involved at the beginning of IBD. However, their etiopathogenesis is not yet fully understood. Over the last ten years, there has been increasing evidence of the involvement of the member of the 18-glycosylhydrolase family chitinase-3-like protein 1 (CHI3L1) in IBD. CHI3L1 is associated with various diseases such as cancer and chronic inflammatory diseases including rheumatoid arthritis or IBD as well as neurological diseases where it can act as a chemoattractant, mitogen or growth factor. This review will focus on the role of autoimmunity to CHI3L1 in IBD in the context of its expression in inflamed colonic epithelia and interaction with intestinal microbiota. Further, it will provide insights into the interaction of CHI3L1 with different mechanisms of the innate and adaptive immune response in IBD.
30387008 Internet-delivered cognitive behaviour therapy for chronic health conditions: a systematic 2019 Apr This systematic review and meta-analysis aims to evaluate the effectiveness of internet-delivered cognitive behavioural therapy (ICBT) on anxiety and depression among persons with chronic health conditions. A systematic database search was conducted of MEDLINE, CINAHL, PsycInfo, EMBASE, and Cochrane for relevant studies published from 1990 to September 2018. A study was included if the following criteria were met: (1) randomized controlled trial involving an ICBT intervention; (2) participants experienced a chronic health condition; (3) participants ≥ 18 years of age; and (4) effects of ICBT on anxiety and/or depression were reported. The Cochrane Risk of Bias tool was used to assess the risk of bias on the included studies. Pooled analysis was conducted on the primary and condition specific secondary outcomes. Twenty-five studies met inclusion criteria and investigated the following chronic health conditions: tinnitus (n = 6), fibromyalgia (n = 3), pain (n = 7), rheumatoid arthritis (n = 3), cardiovascular disease (n = 2), diabetes (n = 1), cancer (n = 1), heterogeneous chronic disease population (n = 1), and spinal cord injury (n = 1). Pooled analysis demonstrated small effects of ICBT in improving anxiety and depression. Moderate effects of therapist-guided approach were seen for depression and anxiety outcomes; while, self-guided approaches resulted in small effects for depression and moderate effects in anxiety outcomes. ICBT shows promise as an alternative to traditional face-to-face interventions among persons with chronic health conditions. Future research on long-term effects of ICBT for individuals with chronic health conditions is needed.Trial Registration PROSPERO registration number: CRD42018087292.
30255029 Common DNA Variants Accurately Rank an Individual of Extreme Height. 2018 Polygenic scores (or genetic risk scores) quantify the aggregate of small effects from many common genetic loci that have been associated with a trait through genome-wide association. Polygenic scores were first used successfully in schizophrenia and have since been applied to multiple phenotypes including multiple sclerosis, rheumatoid arthritis, and height. Because human height is an easily-measured and complex polygenic trait, polygenic height scores provide exciting insights into the predictability of aggregate common variant effect on the phenotype. Shawn Bradley is an extremely tall former professional basketball player from Brigham Young University and the National Basketball Association (NBA), measuring 2.29 meters (7'6(″), 99.99999th percentile for height) tall, with no known medical conditions. Here, we present a case where a rare combination of common SNPs in one individual results in an extremely high polygenic height score that is correlated with an extreme phenotype. While polygenic scores are not clinically significant in the average case, our findings suggest that for extreme phenotypes, polygenic scores may be more successful for the prediction of individuals.
30233139 Are laboratory parameter (biomarker) values similar to the healthy volunteer reference ran 2018 BACKGROUND: Liver biomarkers alanine aminotransferase (ALT) and bilirubin in patients with hepatitis are above the healthy volunteer reference range (HVRR) at baseline (prior to receiving the clinical trial medication). Discussions continue as how to best distinguish drug-induced liver injury in patients with abnormal baseline values participating in clinical trials. This study investigated if other baseline routine clinical safety biomarkers (lab parameters) are different from the HVRR. MATERIALS AND METHODS: Clinical trial data (TransCelerate dataset) from placebo and standard of care treated patients were compared to the HVRR using a 10% threshold above or below the HVRR to classify a lab parameter in a patient population as potentially different from the HVRR at baseline. The TransCelerate dataset, batch 4, contained data from patients with Alzheimer's, asthma, COPD, cardiovascular disease, diabetes, hidradenitis, hypercholesterolemia, rheumatoid arthritis, schizophrenia, stroke, and ulcerative colitis. A subset of the 200 biomarkers in Trans-Celerate were evaluated in this pilot: glucose, platelet count, neutrophil count, ALT, aspartate aminotransferase (AST), and bilirubin. RESULTS: Glucose was potentially higher than the HVRR in patients with diabetes, COPD, cardiovascular disease, hypercholesterolemia, and schizophrenia. At least one or more of the hematology and hepatic biomarkers were different from the HVRR in at least one patient population, except bilirubin. All the patient populations, except Alzheimer's and asthma, had at least one biomarker that was higher than the HVRR. SUMMARY: The routine biomarkers evaluated in this pilot study demonstrated that not all lab parameters in patient populations are similar to the HVRR. Further efforts are needed to determine which biomarkers are different from the HVRR and how to evaluate the biomarkers in patient populations for detecting drug-induced altered lab values in clinical trials.
29953725 A Small Library of 1,2,3-Triazole Analogs of CAP-55: Synthesis and Binding Affinity at Nic 2018 Sep Alpha7 nicotinic acetylcholine receptor is emerging as a central regulator in inflammatory processes, as documented by increasing studies reported in the literature. For instance, the activation of this nicotinic receptor subtype in resident macrophages inhibits the production of pro-inflammatory cytokines, thereby attenuating local inflammatory responses, and may open a new window in the treatment of chronic inflammatory disease, such as Crohn's disease, rheumatoid arthritis, psoriasis, and asthma. In continuation of our ongoing research for the development of new cholinergic drug candidates, we selected the nicotine derivative CAP55, which was previously shown to exert anti-inflammatory effects via nicotinic stimulation, as a suitable compound for lead optimization. Through the isosteric replacement of its 3,5-disubstituted 4,5-dihydroisoxazole core with a 1,4-disubstituted 1,2,3-triazole ring, we could rapidly generate a small library of CAP55-related analogs via a one-pot copper(I)-catalyzed azide-alkyne cycloaddition. Receptor binding assays at nAChRs led to the identification of two promising derivatives, compounds 4 and 10, worthy of further pharmacological studies.
29512901 Regulation of autoimmune and anti-tumour T-cell responses by PTPN22. 2018 Jul A number of polymorphisms in immune-regulatory genes have been identified as risk factors for the development of autoimmune disease. PTPN22 (that encodes a tyrosine phosphatase) has been associated with the development of several autoimmune diseases, including type 1 diabetes, rheumatoid arthritis and systemic lupus erythematosus. PTPN22 regulates the activity and effector functions of multiple important immune cell types, including lymphocytes, granulocytes and myeloid cells. In this review, we describe the role of PTPN22 in regulating T-cell activation and effector responses. We discuss progress in our understanding of the impact of PTPN22 in autoimmune disease in humans and mouse models, as well as recent evidence suggesting that genetic manipulation of PTPN22 expression might enhance the efficacy of anti-tumour T-cell responses.
29372043 Mast cells and pro-inflammatory cytokines roles in assessment of grape seeds extract anti- 2018 Jan OBJECTIVES: Reactive oxygen species (ROS)-produced oxidative disorders were involved at the pathophysiology of many inflammatory processes via the generation of pro-inflammatory cytokines and antioxidant defense system suppression. Although herbal antioxidants as mono-therapy relief many inflammatory diseases including, autoimmunity rheumatoid arthritis, but as combination therapy with other proven anti-inflammatory drugs in order to decreasing their toxic impacts has not yet been studied clearly, especially against chemical substances that's induced local inflammation with characteristic edema. MATERIALS AND METHODS: Grape seeds extract (GSE) at a concentration of 40 mg/kg B. wt alone or in combination with indomethacin (Indo.) at a dose of 5 mg/Kg B. wt orally given for 10 days prior (gps VI, VII, VIII) or as a single dose after edema induction (gps IX, X, XI) in rat's left hind paw by sub-planter single injection of 0.1 carrageenan: saline solution (1%) (gp. V) to assess the prophylactic and therapeutic anti-inflammatory activities of both through the estimation of selective inflammatory mediators and oxidative damage-related biomarkers as well as tissue mast cell scoring. Furthermore, both substances were given alone (gps II, III, IV) for their blood, liver and kidney safety evaluation comparing with negative control rats (gp. I) which kept without medication. RESULTS: A marked reduction on the inflammatory mediators, edema volume and oxidative byproducts in edema bearing rats' prophylactic and treated with grape seeds extract and indomethacin was observed. Indomethacin found to induce some toxicological impacts which minimized when administered together with GSE. CONCLUSION: GSE is a safe antioxidant agent with anti-inflammatory property.
29358708 Selective autophagy of the adaptor TRIF regulates innate inflammatory signaling. 2018 Mar Defective autophagy is linked to diseases such as rheumatoid arthritis, lupus and inflammatory bowel disease (IBD). However, the mechanisms by which autophagy limits inflammation remain poorly understood. Here we found that loss of the autophagy-related gene Atg16l1 promoted accumulation of the adaptor TRIF and downstream signaling in macrophages. Multiplex proteomic profiling identified SQSTM1 and Tax1BP1 as selective autophagy-related receptors that mediated the turnover of TRIF. Knockdown of Tax1bp1 increased production of the cytokines IFN-β and IL-1β. Mice lacking Atg16l1 in myeloid cells succumbed to lipopolysaccharide-mediated sepsis but enhanced their clearance of intestinal Salmonella typhimurium in an interferon receptor-dependent manner. Human macrophages with the Crohn's disease-associated Atg16l1 variant T300A exhibited more production of IFN-β and IL-1β. An elevated interferon-response gene signature was observed in patients with IBD who were resistant to treatment with an antibody to the cytokine TNF. These findings identify selective autophagy as a key regulator of signaling via the innate immune system.
29267164 A new ELISA for autoantibodies to steroid 21-hydroxylase. 2018 May 24 BACKGROUND: A new ELISA for autoantibodies to steroid 21-hydroxylase (21-OH Ab) is described. METHODS: In the assay test sample autoantibodies form a bridge between 21-OH coated onto the plate well and liquid phase 21-OH-biotin. Bound 21-OH-biotin is detected by the addition of streptavidin peroxidase and colorogenic peroxidase substrate. RESULTS: Of 100 samples from patients with autoimmune Addison's disease, 86 (86%) were positive for 21-OH Ab ELISA whereas 84 (84%) were positive in an immunoprecipitation assay based on 125I-labeled 21-OH. Six (0.6%) of 928 healthy adult blood donors and 1 (2.0%) of 49 adult patients with type 1 diabetes mellitus (T1DM) were positive by ELISA. No samples from adult patients with Graves' disease (GD; n=50), celiac disease (n=29), systemic lupus erythematosis (n=9) or rheumatoid arthritis (n=20) were positive by ELISA. However, 2/51 (3.9%) children with GD, 3/69 (4.3%) children with Hashimoto's thyroiditis (HT) and 3/119 (2.5%) children with T1DM alone or associated with autoimmune thyroid disorders were ELISA positive. CONCLUSIONS: The new assay should be useful for screening patients known to be at increased risk of developing clinical autoimmune Addison's disease, in particular children with HT, GD and/or T1DM.
29193331 Host modulation therapy with anti-inflammatory agents. 2018 Feb Host modulation therapy refers to a treatment concept in which drug therapies are used as an adjunct to conventional periodontal treatment to ameliorate destructive aspects of the host inflammatory response. This strategy is not new in the treatment of periodontitis. Previously, nonsteroidal anti-inflammatory drugs have been investigated in this regard, with evidence of reductions in alveolar bone resorption when these drugs are used for prolonged periods of time. However, the risk of significant unwanted effects precludes the use of both nonselective nonsteroidal anti-inflammatory drugs and the selective cyclooxygenase-2 inhibitors as adjunctive treatments for periodontitis. Currently, the only available adjunctive host response modulator that is licensed for the treatment of periodontitis is subantimicrobial dose doxycycline, which functions as an inhibitor of matrix metalloproteinases. Although clinical benefits have been shown in carefully conducted randomized controlled trials, the efficacy of subantimicrobial dose doxycycline in routine clinical practice has yet to be determined. Anti-cytokine therapies have been developed for use in the treatment of rheumatoid arthritis, the pathogenesis of which bears many similarities to that of periodontitis; however, the significant risk of unwanted effects (as well as cost and lack of human trials in the treatment of periodontal diseases) precludes the use of any of the currently available anti-cytokine therapies in the treatment of periodontitis. The identification of pro-resolving lipid mediators as well as small molecule biologicals that influence inflammatory responses offers the best potential, at the present time, for the development of novel host response modulators in periodontal therapy, but much research remains to be done to confirm safety and efficacy.
28945457 Preferences for Medical Marijuana over Prescription Medications Among Persons Living with 2018 Feb OBJECTIVES: Despite expanded legalization and utilization of medical cannabis (MC) internationally, there is a lack of patient-centered data on how MC is used by persons living with chronic conditions in tandem with or instead of prescription medications. This study describes approaches to use of MC vis-à-vis prescription medications in the treatment of selected chronic conditions. DESIGN: Participants completed semistructured telephone interviews with open-ended questions. Content analysis of qualitative data identified themes and subthemes relating to patient approaches to using MC products. PARTICIPANTS: Thirty persons (mean age = 44.6 years) living with a range of chronic conditions (e.g., rheumatoid arthritis, Crohn's disease, spinal cord injury/disease, and cancer) who had qualified for and used MC in Illinois. RESULTS: Participants described a range of approaches to using MC, including (1) as alternatives to using prescription or over-the-counter medications; (2) complementary use with prescription medications; and (3) as a means for tapering off prescription medications. Motives reported for reducing or eliminating prescription medications included concerns regarding toxicity, dependence, and tolerance, and perceptions that MC improves management of certain symptoms and has quicker action and longer lasting effects. CONCLUSIONS: MC appears to serve as both a complementary method for symptom management and treatment of medication side-effects associated with certain chronic conditions, and as an alternative method for treatment of pain, seizures, and inflammation in this population. Additional patient-centered research is needed to identify specific dosing patterns of MC products associated with symptom alleviation and produce longitudinal data assessing chronic disease outcomes with MC use.
30075555 Retinitis associated with double infection of Epstein-Barr virus and varicella-zoster viru 2018 Aug RATIONALE: Chronic uveitis with immunosuppressive agents could develop chronic herpetic retinitis with varicella-zoster virus (VZV) or herpes simplex virus (HSV). Ocular Epstein-Barr virus (EBV) infection develops uveitis and vitritis, but the clinical feature of EBV retinitis is not typical as a viral retinitis. EBV retinitis is rare, and only a few cases of EBV retinitis have been reported. Herein, we describe a case of retinitis with EBV and VZV which were the primary viruses verified by multiplex polymerase chain reaction (PCR). PATIENT CONCERNS: A 75-year-old woman suffered from sudden visual loss in the left eye. She had been diagnosed with rheumatoid arthritis. At presentation, visual acuity (VA) was 20/400 in the left eye. Slit lamp examination disclosed fine white keratic precipitates with infiltrating cells and dense vitreous opacities in the anterior segment and vitreous. Fundus photographs showed multifocal chorioretinal scars in macula and peripheral retina, and granular lesions surrounding arcade vessels. DIAGNOSES: Ocular toxoplasmosis was primarily suspected. INTERVENTIONS: However, serological test showed negative of toxoplasmosis. Therefore, a diagnostic and therapeutic vitrectomy was performed. Vitreous fluid sample was used for multiplex PCR for detection of human herpesvirus (HHV) -1 to -8, toxoplasmosis and toxocariasis. OUTCOMES: Multiplex PCR detected 5.8 × 10 copies/mL of EBV-deoxyribonucleic acid (DNA), and 3.6 × 10 copies/mL of VZV-DNA in the sample. Therefore, we could diagnose the unidentified panuveitis a retinitis associated with double infection of EBV and VZV. At 85 days after the vitrectomy, VA of the left eye recovered to be 20/16. LESSONS: Elderly patients under immunosuppression may be susceptible to develop retinitis associated with infection of multiple HHVs, and multiplex PCR is an excellent tool to diagnose an unidentified panuveitis resembling this case.