Miracle-dz/UniFAR-FTUs huggingface dataset:
Is atherosclerosis accelerated in systemic sclerosis? Novel insights

Purpose of reviewDuring the last few decades, the death rate due to cardiovascular disease in systemic sclerosis (SSc) patients has substantially increased. Whether this is because of accelerated atherosclerosis, similar to what has been demonstrated in rheumatoid arthritis and systemic lupus erythematosus, remains to be established. In this review, the main recent evidence about potential pathogenic mechanisms of accelerated atherosclerosis, microvascular disease and macrovascular disease in SSc, and the results from the surrogate measures for detecting and quantifying subclinical atherosclerosis in SSc patients are reviewed. Recent findingsSignificantly higher risk of coronary heart disease in SSc patients compared with the general population has been found in the largest cohort studies. However, no difference in either atherosclerotic plaque occurrence or intima-media thickness was detected. The diagnostic utility of other techniques, such as cardiac MRI, in order to improve detection and characterization of SSc heart disease remains to be determined. SummaryAlthough microvascular disease is a hallmark of SSc, mechanistic insights explaining the presence of accelerated atherosclerosis, and the presence and extent of macrovascular disease in SSc patients are lacking. Future challenges will be to unravel the genetic, environmental and ethnic determinants of such processes.
New insights into the measurement of disease activity in rheumatoid arthritis

Purpose of reviewDisease activity assessment in rheumatoid arthritis (RA) is a rapidly evolving field. Not only are new measures suggested or introduced in the field, but also we continuously learn about the better use of existing ones in the context of managing disease. On that background, we reviewed the literature on disease activity in RA of 2014 and selected interesting or relevant studies for further discussion. Recent findingsEULAR Management Criteria suggest that stringent disease activity targets should be used to guide treatment adaptation. Several studies support this, some even claim to change cutpoints for existing composite indices to match this stringency requirement, while others suggest seeking additional guidance by musculoskeletal ultrasound. One study suggests substantial modifications of existing composite measures in order to make them more objective, although the evident patient contribution to treatment decisions from another study would claim the opposite, namely to give more emphasis on the patient's perspective. New measures of disease activity include modification of core set parameters or existing MRI scores, but range up to currently less feasible whole-body MRI scans or sophisticated nuclear medicine methods. SummaryHere, we review several new studies on disease activity assessment in the management of RA. On the basis of the studies in 2014, we expect that this specific field will continue to attract scientific attention.
Subchondral bone and osteoarthritis

Purpose of reviewIncreasing evidence show that bone is a key factor in the development of osteoarthritis. This article reviews the latest results of basic and clinical research on the role of the subchondral bone in osteoarthritis. Recent findingsEarly changes in the subchondral bone can predict subsequent symptoms or disease structural progression. New tools may help clinicians to stratify different osteoarthritis phenotypes with regards to bone remodeling status. SummaryThe involvement of bone in osteoarthritis has long been thought to be secondary to cartilage damage as an adaptation of the joint. Recent clinical studies with MRI have demonstrated that bone changes could be observed in early stages of the disease, even preceding cartilage lesions. Moreover, there is clear evidence of an association between subchondral bone mineral density and osteoarthritis. The level of bone remodeling plays a critical role under mechanical loading conditions as demonstrated by consistent experimental studies. Yet new clinical biomarkers are being developed to assess the bone phenotype of osteoarthritic patients. This stratification strategy is likely to better identify groups of patients who would benefit from bone-acting drugs to decrease disease progression and improve pain and disability.
The role of neutrophils in the pathogenesis of systemic lupus erythematosus

Purpose of reviewRecent discoveries implicate neutrophils as important regulators of innate and adaptive immunity and in the development of organ damage in systemic autoimmune diseases, including systemic lupus erythematosus (SLE). Recent findingsVarious putative SLE biomarkers are neutrophil-related, including neutrophil granular proteins and histones undergoing post-translational modifications during neutrophil extracellular trap (NET) formation. In the bone marrow, lupus neutrophils can drive B and T cell abnormalities, at least in part, by their enhanced production of type-I interferons, tumor necrosis factor-alpha (TNF&agr;) and the B-cell stimulating factors B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL). Lupus neutrophils and, in particular, lupus low-density granulocytes (a distinct pathogenic subset) display epigenetic modifications and genomic alterations that may be relevant to their deleterious roles in SLE. Proteins and enzymes externalized by lupus NETs can affect vascular health by inducing endothelial apoptosis and oxidizing lipoproteins. Hampering NET formation through peptidylarginine deiminase inhibitors abrogates lupus phenotype and atherosclerosis in murine studies. SummaryRecent discoveries support the notion that neutrophils, low-density granulocytes and aberrant NET formation and clearance play important roles in lupus pathogenesis. Future studies should focus on how to selectively target these immunostimulatory pathways in this disease.
Local Biologies, Leaky Things, and the Chemical Infrastructure of Global Health

ABSTRACT This article examines how two chemical substances are woven into the infrastructure of global health as well as into the social lives of health workers in urban Nicaragua. One chemical is temephos, an organophosphate used to control mosquitoes. The other is chlorine-based products, which are used to disinfect surfaces and water. While global health projects tend to treat these substances as stable objects, there are three ways in which they might be understood as leaky things, implicated in fluid social interactions. First, global health chemicals are tracked through rigid accounting, but because of numerical leakages, they become vehicles for fashioning new forms of concern. Second, chemicals leak structurally: They can be dissolved and reproduced at a molecular level, although that dissolution is never absolute, and that reproduction is not everywhere the same. Third, chemicals leak in a sensory fashion. Sensory interactions with chemicals produce an entanglement of knowledge about bodies and environments.
Update on cardiovascular disease in lupus

Purpose of reviewAtherosclerotic cardiovascular disease confers significant morbidity and mortality in patients with systemic lupus erythematosus (SLE) and cannot be fully explained by traditional cardiovascular risk factors. Recent immunologic discoveries have outlined putative pathways in SLE that may also accelerate the development of atherosclerosis. Recent findingsAberrant innate and adaptive immune responses implicated in lupus pathogenesis may also contribute to the development of accelerated atherosclerosis in these patients. Defective apoptosis, abnormal lipoprotein function, autoantibodies, aberrant neutrophil responses, and a dysregulated type I interferon pathway likely contribute to endothelial dysfunction. SLE macrophages have an inflammatory phenotype that may drive progression of plaque. SummaryRecent discoveries have placed increased emphasis on the immunology of atherosclerotic cardiovascular disease. Understanding the factors that drive the increased risk for cardiovascular disease in SLE patients may provide selective therapeutic targets for reducing inflammation and improving outcomes in atherosclerosis.
Reasons for Prosthetic Rejection by Children With Unilateral Congenital Transverse Forearm Total Deficiency

As many as half of children with unilateral congenital transverse forearm total deficiency (UCTFTD) choose not to wear a prosthesis. In a multicenter study, 489 children and young adults aged 2 to 20 years with UCTFTD and their parents were tested for satisfaction, quality of life, and function. One hundred sixty-eight (34%) of those tested had chosen not to wear a prosthesis. Subjects and parents were asked the open-ended question “What are the reasons for not wearing a prosthesis? ” and were allowed to give more than one response. Of the 135 subjects who had chosen not to wear a prosthesis and who responded to the question, the reason most frequently (53%) given was that the prosthesis did not help function. Forty-nine percent reported they stopped wearing it because the prosthesis was uncomfortable. Currently, upper-extremity prosthetic management for children with UCTFTD is a matter of controversy, with some clinicians advocating the need for prostheses to accomplish bilateral hand tasks, particularly in the scheme of normal development. Responses from children who do not wear a prosthesis may aid practitioners in re-evaluating the prosthetic role and potentially improve prosthetic options.
Luminescent thermometer based on Eu3+ /Tb3+ -organic-functionalized mesoporous silica.

In this work we investigate a mesoporous silica (MS) decorated with dipyridyl-pyridazine (dppz) ligands and further grafted with a mixture of Eu3+ /Tb3+ ions (28.45%:71.55%), which was investigated as a potential thermometer in the 10-360 K temperature range. The MS material was prepared employing a hetero Diels-Alder reaction: 3,6-di(2-pyridyl)-1,2,4,5-tetrazine was reacted with the double bonds of vinyl-silica (vSilica) followed by an oxidation procedure. We explore using the dppz-vSilica material to obtain visible emitting luminescent materials and for obtaining a luminescent thermometer when grafted with Eu3+ /Tb3+ ions. For the dppz-vSilica@Eu,Tb material absolute sensitivity Sa of 0.011 K-1 (210 K) and relative sensitivity Sr of 1.32 %K-1 (260 K) were calculated showing good sensing capability of the material. Upon temperature change from 10 K to 360 K the emission color of the material changed gradually from yellow to red.
Chromosomal aberrations, sister chromatid exchanges, and micronuclei in lymphocytes of oncology department personnel handling anti-neoplastic drugs

Abstract Objective: Concern exists regarding the possible hazards to the personnel handling anti-neoplastic drugs. The purpose of the present study was to assess the genotoxicity induced by anti-neoplastic agents in oncology department personnel. Materials and methods: To do this, the frequency of chromosomal aberrations (CAs) induced in peripheral blood lymphocytes was assessed at G0 phase of the cell cycle using metaphase analysis, cytokinesis block-micronucleus (MN) assay and sister chromatid exchange (SCE) assay. These cytogenetic end points were measured among 71 nurses in oncology department and 10 drugstore personnel handling and preparing anti-neoplastic drugs. The results were compared to those of 74 matched nurses for age and sex not exposed to any anti-neoplastic agents. Results: There was no significant difference between the age of study subjects and control group (p > 0.05). The results showed that the mean frequency of cytogenetic damages in terms of CAs [chromatid breaks (p = 0.01), chromosome breaks (p = 0.005), total CAs (p = 0.001)], MN formation (p = 0.001), and SCE (p = 0.004) in lymphocytes of personnel handling anti-neoplastic drugs were significantly higher than those in control unexposed group. Conclusion: Results of the present study demonstrate the cytogenetic damage in peripheral blood lymphocytes of oncology department personnel. Suitable training and proper knowledge when handling anti-neoplastic drugs are emphasized to avoid potential health hazards caused by cytostatic agents.
Combined repeated-dose and reproductive/developmental toxicity screening test of 1-tert-butoxy-4-chlorobenzene in rats

Abstract We have carried out animal toxicity tests of chemicals for a chemical safety program implemented by the Ministry of Economy, Trade, and Industry of Japan. Here, we tested 1-tert-butoxy-4-chlorobenzene in a combined repeat-dose and developmental and reproductive toxicity test. The test chemical was administered daily by gavage to 9-week-old Crl:CD (SD) rats at doses of 0, 20, 100, and 500 mg/kg/d. Males were treated for 42 d beginning 14 d before mating. Females were treated from 14 d before mating to day 4 of lactation. Decreased spontaneous locomotion, decreased respiratory rate, and incomplete eyelid opening were observed at 500 mg/kg/d (both sexes), but resolved within 30 min of administration, suggesting central nervous system depression. No notable changes were observed in body weight, food consumption, functional battery tests, or blood test. Increased liver weight with centrilobular or diffuse hepatocyte hypertrophy was observed at 100 and 500 mg/kg/d (both sexes). There were no biochemical or histopathological changes related to hepatotoxicity. Increased kidney weight with basophilic tubules, tubule dilatation, and increased hyaline droplets were observed in males dosed at 100 and 500 mg/kg/d. Immunohistochemical staining indicated α2u-globulin nephropathy, a male rat-specific toxicity. Although kidney weight was also increased in females dosed at 500 mg/kg/d, it was not considered to be an adverse effect because there were no histopathological changes. Pup weights on postnatal day 0 were decreased at 500 mg/kg/d and still decreased on postnatal day 4. Our data indicated the no-observed-adverse-effect-level for repeated-dose and reproductive/developmental toxicity for 1-tert-butoxy-4-chlorobenzene was 100 mg/kg/d.
New approaches of B-cell-directed therapy: beyond rituximab

Purpose of reviewThis study reviews therapeutic approaches of direct and indirect B-cell targeting in autoimmune diseases and their impact on protective immunity. Recent findingsBeyond recent clinical experiences with rituximab as B-cell-depleting agent, other biologicals targeting CD20, such as ocrelizumab, ofatumumab, hA20, and TRU-015 mainly deplete B cells and are under clinical investigation in different entities. Moreover, anti-CD22 targeting as another approach that has been studied in clinical trials showed a modest depletion, but inhibition of B-cell activation. More indirect innovative B-cell-affecting therapies comprise blockade of cytokines, such as B-cell-activating factor (BAFF/BLyS), APRIL, and their receptors as well as blockade of costimulation. Although decreases of immunoglobulin levels were seen, so far no major increases in infections were reported. SummaryThe value of certain B-cell-depletion therapies as well as other therapies modulating B-cell functions needs to be further delineated, especially in the therapeutic regimen of rheumatoid arthritis, specific collagen vascular diseases and vasculitis. Long-term observations of protective immunity are also needed to further evaluate the rate of infections.
Curcumin in various cancers

Curcumin (diferuloylmethane), an active constituent of turmeric, is a well‐described phytochemical, which has been used since ancient times for the treatment of various diseases. The dysregulation of cell signaling pathways by the gradual alteration of regulatory proteins is the root cause of cancers. Curcumin modulates regulatory proteins through various molecular mechanisms. Several research studies have provided in‐depth analysis of multiple targets through which curcumin induces protective effects against cancers including gastrointestinal, genitourinary, gynecological, hematological, pulmonary, thymic, brain, breast, and bone. The molecular mechanisms of action of curcumin in treating different types of cancers remain under investigation. The multifaceted role of this dietary agent is mediated through its inhibition of several cell signaling pathways at multiple levels. Curcumin has the ability to inhibit carcinogenicity through the modulation of the cell cycle by binding directly and indirectly to molecular targets including transcription factors (NF‐kB, STAT3, β‐catenin, and AP‐1), growth factors (EGF, PDGF, and VEGF), enzymes (COX‐2, iNOS, and MMPs), kinases (cyclin D1, CDKs, Akt, PKC, and AMPK), inflammatory cytokines (TNF, MCP, IL‐1, and IL‐6), upregulation of proapoptotic (Bax, Bad, and Bak) and downregulation of antiapoptotic proteins (Bcl2 and Bcl‐xL). A variety of animal models and human studies have proven that curcumin is safe and well tolerated even at very high doses. This study elaborates the current understanding of the chemopreventive effects of curcumin through its multiple molecular pathways and highlights its therapeutic value in the treatment and prevention of a wide range of cancers. © 2013 BioFactors, 39(1):56–68, 2013
Relationship between Clinical Complications and Disability in Colombians with Spinal Cord Injury: Results from WHO-DAS II

Introduction: Clinical complications in persons with spinal cord injury are associated with increased morbidity and mortality, aggravated disability and prolonged rehabilitation processes. Recognizing these difficulties is important to developing strategies for prevention and early detection to mitigate their impact on disability and to improve the quality of life for this population. Objective: The study was intended to identify the relationship between clinical complications and the degree of disability among Colombians with spinal cord injury. Materials and methods: The frequency of clinical complications in the last year was determined and the relationship between these complications and the degree of disability was identified, evaluated with WHO-DAS II, through the Student’s t-test and an exploration of simple linear regression models. The participants included 363 persons over 18 years of age with a spinal cord injury sustained more than six months before. The participants were from eight Colombian cities. Results: There were seven clinical complications per patient, on average. The most frequent complications were urinary tract infections, spasticity, hyperesthesia, psychological stress and chronic pain. The complications that best explain the disability, using simple regression models, are depression and psychological stress, followed by respiratory complications, intestinal problems, pressure ulcers, malnutrition and spasticity (p <0.01). Conclusions: The clinical complications associated with spinal cord injury are still frequent in Colombia, despite the improvement in processes for care and rehabilitation. Many of these complications are associated fundamentally with the generation of disability.
Chromosomal damage at bone-marrow cells is induced by exposure of rats to waterpipe water filtrate

Abstract Waterpipe smoking is continuing to spread globally. The aim of this study is to investigate the effect of waterpipe water filtrate on chromosomal integrity in the bone-marrow cells of rats. Chromosomal damage was examined using in vivo chromosomal aberrations (CAs) and SCEs assays. Young Wistar male rats were exposed to WWF via drinking water. Chromosomal damage was measured in bone marrow cells after 6 weeks of treatment using fluorescent-plus-Giemsa staining. Treatment of rats with waterpipe water filtrate for 6 weeks did not affect food/liquid consumption and gain in body weight. The results showed that waterpipe water filtrate increased the frequencies of chromosomal breaks and exchanges by more than 30% (p < 0.01). In addition, waterpipe water filtrate significantly increased SCEs in the bone-marrow cells of rats. In conclusion, waterpipe water filtrate contains genotoxic compounds providing additional evidence for genotoxicity of waterpipe smoke.
Exercise and Circadian Rhythm-Induced Variations in Plasma Cortisol Differentially Regulate Interleukin-1β (IL-1β), IL-6, and Tumor Necrosis Factor-α (TNFα) Production in Humans: High Sensitivity of TNFα and Resistance of IL-6

Although we have previously shown that the integrity of inflammatory mediator-induced activation of the hypothalamic-pituitary-adrenal axis is essential for conferring resistance to inflammatory disease in susceptible Lewis rats, the role of endogenous glucocorticoid secretion in human immune function in either health or disease is less clear. To further understand the relevance of physiological variations in plasma cortisol on immune function in humans, we evaluated ex vivo lipopolysaccharide-induced interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNFα) production in the whole blood of healthy volunteers studied under conditions chosen to approximate either physiological or pharmacological glucocorticoid levels. Administration of a pharmacological dose of hydrocortisone suppressed the production of all three cytokines, whereas administration of a physiological dose of hydrocortisone suppressed only TNFα production. Stress-induced levels of glucocorticoids, achieved during exercise at 100% maxi.
Iodine deficiency in Australia: be alarmed

Iodine deficiency, the leading preventable cause of intellectual impairment in the world (World Health Organization, 1999), has reappeared in Australia. Recently, we identified the re-emergence of iodine deficiency in Sydney (Gunton, Hams, Fiegert & McElduff, 1999). This has been confirmed locally (Li, Ma, Boyages & Eastman, 2001) and interstate (Guttikonda et al., 2002), most recently in a study of Melbourne schoolchildren (McDonnell, Harris & Zacharin, 2003). We also provided evidence that iodine deficiency influences neonatal thyroid function (McElduff, McElduff, Gunton, Hams & Wiley, 2002). Evidence has been presented from other developed countries that iodine deficiency is re-emerging as a major potential health problem (Hollowell et al., 1998). The reasons for this are not clear, but a loss of awareness of the potential of iodine deficiency in the developed world and a decreased use of iodised salt appear to be major contributors (Gunton et al., 1999). Iodine deficiency impairs brain development through foetal hypothyroidism and in particular hypothyroidism in the early stages of pregnancy (Glinoer et al., 1992; Hetzel, 2000). Endemic cretinism, which is characterised by intellectual impairment, spastic diplegia and deafness, is due to severe iodine deficiency during pregnancy (Hetzel, Chavadej & Potter, 1988). It has been suggested that severe brain impairment easily identified as cretinism is merely one end of a continuous spectrum of neuro-psychological impairment induced by iodine deficiency (Boyages, 1994). Maternal iodine supplementation in populations with high levels of endemic cretinism results in a reduced incidence of cretinism without significant adverse effects (Mahomed & Gulmezoglu, 2000). In populations with less severe iodine deficiency and without cretinism the benefit of iodine
Lupus nephritis. How latest insights into its pathogenesis promote novel therapies

Purpose of reviewLupus nephritis is a complex autoimmune disease that develops its own dynamic upon damaging the renal ultrastructure. Here, we summarize the latest pathophysiological concepts of lupus nephritis and how these translate into novel therapeutic options. Recent findingsMultidisciplinary research activities form a better understanding about how lupus develops from an unfortunate combination of gene variants that promote the loss of tolerance, that impair the clearance of dying cells, that regulate the immune interpretation of autoantigens as well as the peripheral control of autoreactive lymphocytes. As a new entry, nuclear particles also act as autoadjuvants mimicking viral particles and triggering interferon-alpha-dependent antiviral immune responses that cause symptoms similar to viral infection. SummaryA set of novel drugs have the potential to more specifically interfere with these pathomechanisms and raise hope to more efficiently treat lupus nephritis with fewer side-effects in the near future.