Miracle-dz/UniFAR-FTUs huggingface dataset:
Frequency and determinants of flare and persistently active disease in systemic lupus erythematosus.

OBJECTIVE Selection of flare as the primary outcome variable in systemic lupus erythematosus (SLE) clinical trials fails to capture patients with persistently active disease (PAD). We sought to elucidate the frequency and determinants of flare and PAD. METHODS Prospectively collected data from the Toronto Lupus Cohort were used to determine the incidence of flare and PAD in 2004 and 2005. Flare was defined as an increase in SLE Disease Activity Index 2000 update (SLEDAI-2K) score of >/=4 from the previous visit. PAD was defined as a SLEDAI-2K score of >/=4, excluding serology alone, on >/=2 consecutive visits. Data from 1, 2, and 3 years prior were used to model flare and PAD in 2004. Model properties were tested for prediction of flare and PAD in 2005. RESULTS One-third of the patients had >/=1 flare, whereas nearly half experienced PAD in a given year. Nearly 60% of the patients had episodes of flare or PAD per year. At least 25% of patients had PAD without achieving the definition of flare. In the best-fitting model, predictors of PAD in 2004 were SLEDAI-2K score at the start of the outcome interval and prior cutaneous or musculoskeletal disease activity. This model gave 79% correct prediction of PAD in 2005. In contrast, flare prediction models performed poorly. CONCLUSION Persistent activity is a common disease state in SLE and should be an outcome variable in SLE clinical trials. Our PAD prediction model may aid prognostication and selection of patients for inclusion in clinical trials.
Cautionary tales from the neonatal intensive care unit: Diapers may mislead urinary output estimation in extremely low birthweight infants

Objective: To examine the validity of the weighing of modern polyacrylate diapers to determine urine output in the extremely low birth weight infant nursed in a humidified incubator. Design: Observational study with repeated measures using high-absorbency cellulose/polyacrylate diapers and a humidified incubator in a modeled clinical scenario. Setting: A tertiary referral neonatal intensive care unit. Interventions: Six dry diapers were placed into eight levels of humidity, between 55% and 90% inclusive, in an incubator set at 37°C. Hourly weight increments were recorded. The study was repeated with 5 mL of normal saline added to the diaper to mimic prior urine output. Results were compared by Kruskal-Wallis nonparametric analysis of variance. Measurements and Main Results: Dry diapers increased in weight for each humidity level after 1 hr (p < .05). This was significantly greater at higher humidity. The maximum increase was a median of 3.06 g (range, 2.47–3.31 g) at 85% humidity after 6 hrs. When 5 mL of 0.9% saline had been added, the diaper weight changes depended on environmental relative humidity. At ≥80% humidity, the diapers continued to gain weight; at 70% or 75% humidity, they did not change weight; and at ≤65% humidity, the diapers lost weight. Maximal evaporative loss was median 1.11 g (range, 0.8–1.24 g) at 6 hrs in 55% relative humidity. Conclusions: The use of diaper weighing in high-humidity infant environments may not be an accurate measure of actual urine output in the extremely low birth weight infant. This study demonstrates the need for caution when interpreting this measure, and we discuss some possible clinical approaches to ameliorate this difficulty.
Fcgamma receptor-dependent expansion of a hyperactive monocyte subset in lupus-prone mice.

OBJECTIVE Lupus-prone BXSB mice develop monocytosis characterized by selective accumulation of the Gr-1- monocyte subset. The aim of this study was to explore the possible role of activating IgG Fc receptors (FcgammaR) in the development of monocytosis and to characterize the functional phenotype of the Gr-1- subset that accumulates in lupus-prone mice bearing the NZB-type defective Fcgr2b allele for the inhibitory FcgammaRIIB. METHODS The development of monocytosis was analyzed in BXSB and anti-IgG2a rheumatoid factor-transgenic C57BL/6 mice deficient in activating FcgammaR. Moreover, we assessed the expression levels of activating FcgammaR and inhibitory FcgammaRIIB on Gr-1+ and Gr-1- monocyte subsets in C57BL/6 mice bearing the C57BL/6-type or the NZB-type Fcgr2b allele. RESULTS We observed monocytosis with expansion of the Gr-1- subset in anti-IgG2a-transgenic C57BL/6 mice expressing IgG2a, but not in those lacking IgG2a. Moreover, monocytosis barely developed in BXSB and anti-IgG2a-transgenic C57BL/6 mice deficient in activating FcgammaR. The Gr-1- subset that accumulated in lupus-prone mice displayed a unique hyperactive phenotype. It expressed very low levels of inhibitory FcgammaRIIB, due to the presence of the NZB-type Fcgr2b allele, but high levels of activating FcgammaRIV. This was in contrast to high levels of FcgammaRIIB expression and no FcgammaRIV expression on the Gr-1+ subset. CONCLUSION Our results demonstrated a critical role of activating FcgammaR in the development of monocytosis and in the expansion of a Gr-1-FcgammaRIIB(low)FcgammaRIV+ hyperactive monocyte subset in lupus-prone mice. Our findings further highlight the importance of the NZB-type Fcgr2b susceptibility allele in murine lupus, the presence of which induces increased production of hyperactive monocytes as well as dysregulated activation of autoreactive B cells.
Changes in serum albumin levels and neutrophil–lymphocyte ratio in patients with convulsive status epilepticus

Aim: Inflammation may be involved in the ictogenesis and development of some partial epilepsies. Serum albumin levels and the neutrophil–lymphocyte ratio (NLR) are markers of inflammation. The aim of this study was to investigate the ability of serum albumin levels and NLR to predict inflammation in patients with convulsive status epilepticus (CSE). Methods: This retrospective study was conducted on 58 patients who were diagnosed with CSE and control group comprised of 58 healthy individuals. Albumin levels and NLR were evaluated during both the acute and subacute periods of CSE. Results: The average serum albumin levels were 3.27 ± 0.62 g/dL during the acute period and 3.4 ± 0.67 g/dL in the subacute period in the patient group and 3.92 ± 0.52 g/dL in the control group. Neutrophil counts were higher in patients in the acute phase of CSE, but lymphocyte counts were lower compared to the control group and the subacute phase. The average NLR values were 4.83 ± 5.1 in the acute period, 3.07 ± 3.02 during the subacute period and 1.98 ± 0.42 in the control group. Serum albumin and NLR levels were significantly different between the patients in the subacute and acute periods of CSE and the control group (p < 0.05). There were significant negative correlational relationships between serum albumin and NLR levels (p < 0.05). Conclusion: We found serum albumin levels were significantly lower and the NLR was significantly higher in the acute period of CSE. Neutrophil-mediated inflammation may be important in the aetiopathogenesis of CSE.
Student′s attitudes toward effective factors in lecturing didactic dental courses

Introduction: Effective communication between educators and students is essential in the learning process. Knowledge of student attitudes toward effective teaching methodologies can be used for future development of dental faculty. The purpose of this study was to investigate dental student attitudes toward effective factors affecting quality of well-delivered didactic dental courses in classrooms. Materials and Methods: This descriptive cross-sectional study was performed between 130 dental students at clinical stage (4-6 years) in academic year 2012-2013 in Babol University of Medical Sciences. The questionnaires were consisted of 36 items and further categorized into four dimensions: (1) Educators, (2) Academic Administration, (3) Course content and (4) Classrooms physical environment. After confirmation of content validity and reliability, they were filled by students. Students ′agreement with each item in the questionnaire was measured using 5-point Likert scale. Descriptive statistics of the data and statistical analysis, t-test and Pearson correlation coefficient, were used. P<0.05 was considered significant. Results: Ninety-eight students responded with response rate of 75 percent. Oral presentation skills and integrated logical order of content in relation to educators, early detailed course plan and visual aids such as instructional videos in relation to course content, were the most important factors recognized by student to influence quality of didactic dental course presentations in the classrooms. Future dental faculty development requires investments, trainings, and support. Conclusion: Dental educators should analyze predominant learning styles of students and change dental curriculum in a way to provide an optimal learning experience.
The use of drotrecogin alfa (activated) in solid organ transplant patients: a case series

Background. Drotrecogin alfa (activated) (DAA), a recombinant human activated protein C, is indicated for the reduction of mortality in patients with severe sepsis who have a high risk of death. In the initial trial, DAA demonstrated a significant reduction in mortality at 28 days for patients treated with DAA in comparison with standard supportive treatment (placebo). However, solid organ transplant recipients were excluded from the study. Transplant recipients are at an increased risk for sepsis and there is minimal literature describing the safety and efficacy of DAA in the transplant population.
Successful salvage therapy with daptomycin after linezolid and vancomycin failure in a liver transplant recipient with methicillin‐resistant Staphylococcus aureus endocarditis

Abstract: Infective endocarditis is a rare complication affecting solid organ transplant recipients. Staphylococcus aureus is a common cause of infective endocarditis accounting for about 30% of cases. We present a case of nosocomial methicillin‐resistant S. aureus endocarditis with persistent bacteremia, in a patient following orthotopic liver transplantation. We were unable to eradicate this infection with primary linezolid therapy or with secondary treatment with combined vancomycin and rifampicin, but successfully treated it with daptomycin, in addition to tricuspid and aortic valve replacement.
Interferon-alpha mediates suppression of C-reactive protein: explanation for muted C-reactive protein response in lupus flares?

OBJECTIVE C-reactive protein (CRP) is synthesized by hepatocytes in response to interleukin-6 (IL-6) during inflammation. Despite raised IL-6 levels and extensive systemic inflammation, serum CRP levels remain low during most viral infections and disease flares of systemic lupus erythematosus (SLE). Because both viral infections and SLE are characterized by high levels of interferon-alpha (IFNalpha), the aim of this study was to determine whether this cytokine can inhibit the induction of CRP. METHODS The interference of all 12 IFNalpha subtypes with CRP promoter activity induced by IL-6 and IL-1beta was studied in a CRP promoter- and luciferase reporter-transfected human hepatoma cell line, Hep-G2. CRP secretion by primary human hepatocytes was analyzed by enzyme-linked immunosorbent assay. RESULTS CRP promoter activity was inhibited by all single IFNalpha subtypes, as well as by 2 different mixtures of biologically relevant IFNalpha subtypes. The most prominent effect was seen using a leukocyte-produced mixture of IFNalpha (56% inhibition at 1,000 IU/ml). The inhibitory effect of IFNalpha was confirmed in primary human hepatocytes. CRP promoter inhibition was dose dependent and mediated via the type I IFN receptor. Transferrin production and Hep-G2 proliferation/viability were not affected by IFNalpha. CONCLUSION The current study demonstrates that IFNalpha is an inhibitor of CRP promoter activity and CRP secretion. This finding concords with previous observations of up-regulated IFNalpha and a muted CRP response during SLE disease flares. Given the fundamental role of both IFNalpha and CRP in the immune response, our results are of importance for understanding the pathogenesis of SLE and may also contribute to understanding the differences in the CRP response between viral and bacterial infections.
Mercurius solubilis attenuates scopolamine-induced memory deficits and enhances the motor coordination in mice

ABSTRACT Aim: The present study was designed to investigate the effect of mercurius solubilis (merc sol) on scopolamine induced memory deficits and motor coordination in mice. Materials and methods: Three different formulations of merc sol (30X, 200M, 1M) were screened for their in vitro antioxidant potential through DPPH (2, 2-diphenyl-1-picrylhydrazyl) and nitric oxide scavenging activity using response surface methodology. Memory impairment was induced by the administration of scopolamine (1mg/kg i.p.) for 3 days to mice and assessment of memory acquisition and retention was done using Morris water maze test, passive avoidance test, elevated plus maze test, light and dark box test, motor coordination was evaluated using rotarod test and inclined plan test. The involvement of ion channels and nitric oxide pathway in the observed effect of merc sol was elucidated by administration of veratrine (0.125 μg/kg, i.p.), A23187 (20 μg/kg, i.p.), L- arginine (40 mg/kg, i.p.), aminoguanidine (50 mg/kg, i.p.) 30 min prior to merc sol. Acute toxicity studies were performed in accordance with the OECD (Organisation for Economic Co-operation and Development) guidelines. Results: In vitro studies have revealed merc sol 30 X to have maximum free radical and nitric oxide scavenging activity. Administration of merc sol 30 X to mice significantly reduced scopolamine induced memory deficits and motor incoordination in all the performance tasks. The calcium ionophore, A23187 significantly altered the effect of merc sol in mice. No major signs of toxicity were observed. Conclusion: Merc sol has antiamnesic effect in scopolamine induced deficits and motor coordination in mice.
Oxyhemoglobin changes in the prefrontal cortex in response to cognitive tasks: a systematic review

Abstract Purpose of the study: the aim of this study was to synthesize PFC fNIRS outcomes on the effects of cognitive tasks compared to resting/baseline tasks in healthy adults from studies utilizing a pre/post design. Material and methods: original research studies were searched from seven databases (MEDLINE, EMBASE, CENTRAL, CINAHL, SCOPUS, PEDro and PubMed). Subsequently, two independent reviewers screened the titles and abstracts followed by full-text reviews to assess the studies' eligibility. Results: eleven studies met the inclusion criteria and had data abstracted and quality assessed. Methodology varied considerably and yet cognitive tasks resulted in the ΔO2Hb increasing in 8 of the 11 and ΔHHb decreasing in 8 of 8 studies that reported this outcome. The cognitive tasks from 10 of the 11 studies were classified as “Working Memory” and “Verbal Fluency Tasks”. Conclusions: although, the data comparison was challenging provided the heterogeneity in methodology, the results across studies were similar.
Cutaneous infection by Phomopsis longicolla in a renal transplant recipient from Guinea: first report of human infection by this fungus

A. Garcia‐Reyne, F. López‐Medrano, J.M. Morales, C. García Esteban, I. Martín, I. Eraña, Y. Meije, A. Lalueza, A. Alastruey‐Izquierdo, J.L. Rodríguez‐Tudela, J.M. Aguado. Cutaneous infection by Phomopsis longicolla in a renal transplant recipient from Guinea: first report of human infection by this fungus. Transpl Infect Dis 2011: 13: 204–207. All rights reserved
Persistence of influenza vaccine‐induced antibodies in lung transplant patients between seasons

J.J.M. Moran, W.E. Rose, A.J. Darga, K.A. Rohde, M.S. Hayney. Persistence of influenza vaccine‐induced antibodies in lung transplant patients between seasons. Transpl Infect Dis 2011: 13: 466–470. xx: 000–000. All rights reserved
Disruption of tight junction structure in salivary glands from Sjögren's syndrome patients is linked to proinflammatory cytokine exposure.

OBJECTIVE Disorganization of acinar cell apical microvilli and the presence of stromal collagen in the acinar lumen suggest that the labial salivary gland (LSG) barrier function is impaired in patients with Sjögren's syndrome. Tight junctions define cell polarity and regulate the paracellular flow of ions and water, crucial functions of acinar cells. This study was undertaken to evaluate the expression and localization of tight junction proteins in LSGs from patients with SS and to determine in vitro the effects of tumor necrosis factor alpha (TNFalpha) and interferon-gamma (IFNgamma) on tight junction integrity of isolated acini from control subjects. METHODS Twenty-two patients and 15 controls were studied. The messenger RNA and protein levels of tight junction components (claudin-1, claudin-3, claudin-4, occludin, and ZO-1) were determined by semiquantitative reverse transcriptase-polymerase chain reaction and Western blotting. Tight junction protein localization was determined by immunohistochemistry. Tight junction ultrastructure was examined by transmission electron microscopy. Isolated acini from control subjects were treated with TNFalpha and IFNgamma. RESULTS Significant differences in tight junction protein levels were detected in patients with SS. ZO-1 and occludin were strongly down-regulated, while claudin-1 and claudin-4 were overexpressed. Tight junction proteins localized exclusively to apical domains in acini and ducts of LSGs from controls. In SS patients, the ZO-1 and occludin the apical domain presence of decreased, while claudin-3 and claudin-4 was redistributed to the basolateral plasma membrane. Exposure of isolated control acini to TNFalpha and IFNgamma reproduced these alterations in vitro. Ultrastructural analysis associated tight junction disorganization with the presence of endocytic vesicles containing electron-dense material that may represent tight junction components. CONCLUSION Our findings indicate that local cytokine production in LSGs from SS patients may contribute to the secretory gland dysfunction observed in SS patients by altering tight junction integrity of epithelial cells, thereby decreasing the quality and quantity of saliva.
Selective blockade of BAFF for the prevention and treatment of systemic lupus erythematosus nephritis in NZM2410 mice.

OBJECTIVE To determine whether BAFF or combined BAFF/APRIL blockade is effective in a mouse model of systemic lupus erythematosus (SLE) nephritis characterized by rapidly progressive glomerulosclerosis. METHODS NZM2410 mice at early and late stages of SLE nephritis were treated with a short course of BAFF-R-Ig or TACI-Ig fusion protein. Proteinuria and serologic profile were evaluated every 2 weeks. Immunohistochemical, flow cytometric, and enzyme-linked immunospot analyses of the spleen, kidney, and bone marrow were performed after 8 weeks and after 33 weeks. RESULTS A short course of selective blockade of BAFF alone was sufficient to prevent and treat SLE nephritis in NZM2410 mice, despite the formation of pathogenic autoantibodies. Decreases in spleen size and B cell depletion persisted for more than 33 weeks after treatment and resulted in secondary decreases in CD4 memory T cell formation and activation of splenic and peripheral monocytes. Immune complex deposition in the kidneys was dissociated from renal damage and from activation of renal endothelial and resident dendritic cells. CONCLUSION Selective blockade of BAFF alone, which resulted in B cell depletion and splenic collapse, was sufficient to prevent and treat the disease in this model of noninflammatory SLE nephritis. This shows that the inflammatory microenvironment may be a determinant of the outcome of B cell modulation strategies.
Cognitive Function In Systemic Lupus Erythematosus, Rheumatoid Arthritis And Multiple Sclerosis Assessed By Computerized Neuropsychological Tests

Objective—Computerized neuropsychological testing may facilitate screening for cognitive impairment in SLE. We used the Automated Neuropsychological Assessment Metrics (ANAM), to compare patients with SLE, rheumatoid arthritis (RA) and multiple sclerosis (MS) with healthy controls. Methods—Patients with SLE (68), RA (33), and MS (20), were compared to 29 healthy controls. Efficiency of cognitive performance on eight ANAM subtests was examined using throughput (Tp), inverse efficiency (IE) and adjusted IE scores. The latter is more sensitive to higher cognitive functions because it adjusts for the impact of simple reaction time on performance. The results were analyzed using O’Brien’s generalized least squares test. Results—Control subjects were the most efficient in cognitive performance. MS patients were least efficient overall (Tp and IE scores) and were less efficient than both SLE (p=0.01) and RA (p<0.01) patients, who did not differ. Adjusted IE scores were similar between SLE, RA patients and controls reflecting the impact of simple reaction time on cognitive performance. Thus, 50% of SLE patients, 61% of RA patients and 75% of MS patients were impaired on at least one ANAM subtest. Only 9% of RA patients and 11% of SLE patients were impaired on 4 or more subtests, whereas this was true for 20% of MS patients. Address Correspondence and Reprints to: Dr. John G Hanly, Division of Rheumatology, Nova Scotia Rehabilitation Centre (2nd Floor), 1341 Summer Street, Halifax, Nova Scotia, Canada, B3H 4K4. Telephone: (902) 473 3818; Fax: (902) 473 7019; john.hanly@cdha.nshealth. ca. Arthritis Rheum. Author manuscript; available in PMC 2015 November 23. Published in final edited form as: Arthritis Rheum. 2010 May ; 62(5): 1478–1486. doi:10.1002/art.27404. C IH R A uhor M anscript C IH R A uhor M anscript C IH R A uhor M anscript Conclusion—ANAM is sensitive to cognitive impairment. While such computerized testing may be a valuable screening tool, our results emphasize the lack of specificity of slowed performance as a reliable indicator of impairment of higher cognitive function in SLE patients.
Glycan profiling of anti-citrullinated protein antibodies isolated from human serum and synovial fluid.

OBJECTIVE Anti-citrullinated protein antibodies (ACPA) exhibit unique specificity for rheumatoid arthritis. However, it is incompletely understood whether and how ACPA contribute to disease pathogenesis. The Fc part of human IgG carries 2 N-linked glycan moieties that are crucial for the structural stability of the antibody and that modulate both its binding affinity to Fcgamma receptors and its ability to activate complement. We undertook this study to analyze Fc glycosylation of IgG1 ACPA in serum and synovial fluid (SF) in order to further characterize the immune response to citrullinated antigens. METHODS ACPA were isolated by affinity purification using cyclic citrullinated peptides as antigen. IgG1 Fc glycosylation was analyzed by mass spectrometry. ACPA IgG1 glycan profiles were compared with glycan profiles of total serum IgG1 obtained from 85 well-characterized patients. Glycan profiles of paired SF and serum samples were available from 11 additional patients. RESULTS Compared with the pool of serum IgG1, ACPA IgG1 lacked terminal sialic acid residues. In SF, ACPA were highly agalactosylated and lacked sialic acid residues, a feature that was not detected for total SF IgG1. Moreover, differential ACPA glycan profiles were detected in rheumatoid factor (RF)-positive and RF-negative patients. CONCLUSION ACPA IgG1 exhibit a specific Fc-linked glycan profile that is distinct from that of total serum IgG1. Moreover, Fc glycosylation of ACPA differs markedly between SF and serum. Since Fc glycosylation directly affects the recruitment of Fc-mediated effector mechanisms, these data could further our understanding of the contribution of ACPA to disease pathogenesis.