Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of anti-interleukin-6 receptor blockade on circulating T and B cell subsets in patients with systemic lupus erythematosus

Background Circulating plasmablasts/plasma cells and activated B and T cells are increased in systemic lupus erythematosus (SLE). Interleukin (IL)-6 induces differentiation of B cells into antibody-forming cells and of T cells into effector cells. Objective To examine the hypothesis that blocking IL-6 would reverse some of the immune abnormalities present in SLE. Methods Fifteen patients with SLE with mild-to moderate disease activity were treated with biweekly infusions of tocilizumab, a humanised anti-IL-6 receptor monoclonal antibody for 12 weeks. Lymphocyte subsets (analysed by flow cytometry) and serum immunoglobulin levels were compared at baseline and at weeks 6 and 12. Results Tocilizumab decreased activated T and B cells, the frequency of CD27highCD38highIgD− plasmablasts/plasma cells and IgD−CD27+ post-switched memory B cells as well as IgG+ memory B cell, whereas it increased the frequency of IgD+CD27− antigen-inexperienced B cells. Among antigen-inexperienced IgD+CD27− B cells, CD38low mature naïve B cells increased significantly and CD38IntermediateCD5+ pre-naïve B cells showed a decreasing trend, whereas CD38highCD5+ transitional type 1 B cells did not change. Most of the changes occurred in patients who had abnormal values at baseline. IgG, IgA, IgG1 and IgG3 serum levels decreased albeit within the normal range. The frequency of CD4+CD45RA+CCR7+ naïve T cells increased. Conclusions In vivo blockade of the IL-6 receptor decreases lymphocyte activation and restores B and T cell homoeostasis by either blocking differentiation and/or trafficking in patients with SLE and leads to normalisation of the abnormal B and T cell subsets seen at baseline.
Respiratory Function in Speech and Song

The authors of this publication address themselves to the diagnosis and management of a wide range of relatively common problems associated with the renal tract. Occasional contributors have attempted to be too comprehensive and have allowed themselves to discuss problems which could hardly be termed 'emergencies'. This is particularly true in the chapter devoted to hypertension, which is often confusing rather than helpful. However, the chapters on infection of the renal tract and that devoted to urological sepsis, are extremely clearly presented and well structured, providing a balanced view relating to the pathophysiology and management of the various problems under discussion. Although chapters 4 and 5, which examine the problems associated with electrolyte and acid base disorders, might be considered a little lengthy, they nevertheless contain a very carefully argued and clearly expressed physiological basis for the various disturbances discussed, with a logical approach to treatment. However, they both suggest applying 'formulae' for the correction of biochemical disorders: this must be applied with caution by the reader. Chapter 1 advises on the evaluation of patients with azotaemia and/or oliguria, providing a comprehensive catalogue of causes responsible for this relatively common condition. In discussing the diagnostic approach, it fails, however, to stress the importance of the early exclusion of obstructive uropathies. Likewise, it contains one or two 'throw-away' statements relating to management, which must be viewed with caution. This applies particularly to the use of bicarbonate. Complications relating to dialysis and transplantation and the early management of retention are also comprehensively covered. This is an excellent and timely publication, based on a sound pathophysiological approach to the diagnosis and management ofmany renal disorders. Although it is styled in some respects to meet the needs of emergency medicine as practised in North America, this does not detract from its value to both general physicians and/or trainee nephrologists who are exposed to decision making in the diagnosis and acute management of patients with major disturbances of renal function in the United Kingdom.
Fetal and neonatal iron deficiency causes volume loss and alters the neurochemical profile of the adult rat hippocampus

Abstract Objective Perinatal iron deficiency results in persistent hippocampus-based cognitive deficits in adulthood despite iron supplementation. The objective of the present study was to determine the long-term effects of perinatal iron deficiency and its treatment on hippocampal anatomy and neurochemistry in formerly iron-deficient young adult rats. Methods Perinatal iron deficiency was induced using a low-iron diet during gestation and the first postnatal week in male rats. Hippocampal size was determined using volumetric magnetic resonance imaging at 8 weeks of age. Hippocampal neurochemical profile, consisting of 17 metabolites indexing neuronal and glial integrity, energy reserves, amino acids, and myelination, was quantified using high-field in vivo 1H NMR spectroscopy at 9.4 T (N = 11) and compared with iron-sufficient control group (N = 10). Results The brain iron concentration was 56% lower than the control group at 7 days of age in the iron-deficient group, but had recovered completely at 8 weeks. The cross-sectional area of the hippocampus was decreased by 12% in the formerly iron-deficient group (P = 0.0002). The hippocampal neurochemical profile was altered: relative to the control group, creatine, lactate, N-acetylaspartylglutamate, and taurine concentrations were 6–29% lower, and glutamine concentration 18% higher in the formerly iron-deficient hippocampus (P < 0.05). Discussion Perinatal iron deficiency was associated with reduced hippocampal size and altered neurochemistry in adulthood, despite correction of brain iron deficiency. The neurochemical changes suggest suppressed energy metabolism, neuronal activity, and plasticity in the formerly iron-deficient hippocampus. These anatomic and neurochemical changes are consistent with previous structural and behavioral studies demonstrating long-term hippocampal dysfunction following perinatal iron deficiency.
The Treatment of Hypertensive Patients with a Calcium Antagonist or Moxonidine: A Comparison

Moxonidine represents a new generation of centrally acting antihypertensive drugs. Clinical experience shows that blood pressure normalized in 50 and 80% of patients treated with 0.2 and 0.4 mg moxonidine, respectivaly in a dose-dependent manner. The antihypertensive potencies and tolerability of nifedipine and moxonidine were studied in 229 patients with primary hypertension (world Health Organization class I or II)
Prevalence of bacterial vaginosis in women with vaginal symptoms in South Province, Rwanda.

This is a prospective study of 297 Consecutive High Vaginal Swab (HVS) specimen from patients with vaginal symptoms at the laboratory of Butare University Teaching Hospital, South Province, Rwanda. The aim of the study was to evaluate the prevalence of bacterial vaginosis and the role of some micro-organisms and laboratory indices associated with it. The age range was 16-57 years with a mean of 30.8 years. The overall prevalence of bacterial vaginosis was 17.8% and the highest percentage of 52.8 % (28) found in the age group of 21-30 years compared with the lowest percentage of 1.9% (1) in the age group less than 20 years. Almost half of patients with trichomoniasis were found to have bacterial vaginosis (P infection with bacterial vaginosis ( p> 0.05, positive predictive value 26.0%). Bacterial vaginosis is common among women with vaginal symptoms in Rwanda as showed by gram stain examination. Further research into this pathology in other Rwandan women populations is needed.
Autoantibodies to small ubiquitin-like modifier activating enzymes in Japanese patients with dermatomyositis: comparison with a UK Caucasian cohort

Dermatomyositis (DM) is a heterogeneous disease with varying degrees and time courses of skin eruptions, myositis and internal organ involvement.1 Increasing evidence has demonstrated that myositis-specific autoantibodies (MSAs) are closely associated with distinct clinical subsets.2 Recently, Betteridge et al 3 ,4 reported a novel MSA against small ubiquitin-like modifier activating enzyme (SAE) in DM patients. In this study, we detected this autoantibody in a Japanese DM cohort and assessed its clinical correlations. We screened 456 consecutive Japanese patients with DM (11 children, 445 adults); 373 fulfilled the criteria of Bohan and Peter5 ,6 and the remaining 83 fulfilled Sontheimer's criteria for clinically amyopathic DM (CADM). 7 Controls included 62 patients with polymyositis, 108 with systemic lupus erythematosus, 433 with systemic sclerosis and 124 with interstitial lung disease (ILD) alone. The institutional review board approved the study protocol. Immunoprecipitation assays were performed as described.8 Protein A-agarose beads preincubated with sera were incubated with 35S-methionine-labelled or unlabelled K562 cell extracts. Immunoprecipitants were fractionated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis, followed by autoradiography or …
Serum urate association with hypertension in young adults: analysis from the Coronary Artery Risk Development in Young Adults cohort

Objective To determine if serum urate concentration is associated with development of hypertension in young adults. Methods Retrospective cohort analysis from 4752 participants with available serum urate and without hypertension at baseline from the Coronary Artery Risk Development in Young Adults (CARDIA) study; a mixed race (African-American and White) cohort established in 1985 with 20 years of follow-up data for this analysis. Associations between baseline serum urate concentration and incident hypertension (defined as a blood pressure greater or equal to 140/90 or being on antihypertensive drugs) were investigated in sex-stratified bivariate and multivariable Cox-proportional analyses. Results Mean age (SD) at baseline was 24.8 (3.6) years for men and 24.9 (3.7) years for women. Compared with the referent category, we found a greater hazard of developing hypertension starting at 345 µmol/l (5.8 mg/dl) of serum urate for men and 214 µmol/l (3.6 mg/dl) for women. There was a 25% increase in the hazard of developing hypertension in men (HR1.25 (95% CI 1.15 to 1.36)) per each mg/dl increase in serum urate but no significant increase in women (HR 1.06 (95%CI 0.97 to 1.16)). Conclusions We found a significant independent association between higher serum urate concentrations and the subsequent hazard of incident hypertension, even at concentrations below the conventional hyperuricaemia threshold of 404 µmol/l (6.8 mg/dl).
Physical Activity Levels Among Participants in the Robert Wood Johnson Foundation Diabetes Initiative

Abstract Objective. The purposes of this study were to describe physical activity habits of individuals with type 2 diabetes participating in a self-management initiative conducted in real-world settings that was sponsored by the Robert Wood Johnson Foundation (RWJF); to assess changes in physical activity over time; and to identify factors associated with physical activity levels. Research design and methods. Clinical and community-based programs participating in the RWJF-funded Diabetes Initiative implemented comprehensive models for self-management, including supports to increase physical activity. A cohort of 622 largely lower-income and ethnic minority program participants (72% female, 85% overweight or obese) completed telephone surveys assessing self-reported physical activity levels at two times that were about 8 months apart. Results. Approximately 70% of participants who reported being inactive at Time 1 reported at least some physical activity at Time 2. Approximately 29% of participants who reported insufficient activity at Time 1 increased their activity enough to meet current public health guidelines at Time 2, whereas 28% of those who were sufficiently active no longer met the guidelines. Sufficient physical activity was associated with greater intervention intensity; being male, younger, and speaking English; and having greater self-efficacy, a lower BMI, and a health care provider who assisted in finding physical activity resources. Conclusions. Personal, behavioral, and program factors were related to physical activity levels among participants in these comprehensive self-management programs.
A 2-year randomised, double-blind, placebo-controlled, multicentre study of oral selective iNOS inhibitor, cindunistat (SD-6010), in patients with symptomatic osteoarthritis of the knee

Objective To determine if inhibition of inducible nitric oxide synthase (iNOS) with cindunistat hydrochloride maleate slows progression of osteoarthritis (OA) Methods This 2-year, multinational, double-blind, placebo-controlled trial enrolled patients with symptomatic knee OA (Kellgren and Lawrence Grade (KLG) 2 or 3). Standard OA therapies were permitted throughout. Patients were randomly assigned to cindunistat (50 or 200 mg/day) or placebo. Randomisation was stratified by KLG. Radiographs to assess joint space narrowing (JSN) were acquired using the modified Lyon-schuss protocol at baseline, week 48 and 96. Results Of 1457 patients (50 mg/day, n=485; 200 mg/day, n=486; placebo, n=486), 1048 (71.9%) completed the study. Patients were predominantly women; 56% had KLG3. The primary analysis did not demonstrate superiority of cindunistat versus placebo for rate of change in JSN. In KLG2 patients, JSN after 48 weeks was lower with cindunistat 50 mg/day versus placebo (p=0.032). Least-squares mean±SE JSN with cindunistat 50 mg/day ( −0.048±0.028 mm) and 200 mg/day (−0.062±0.028 mm) were 59.9% (95% CI 6.8% to 106.9%) and 48.7% (95% CI -8.4% to 93.9%) of placebo, improvement was not maintained at 96 weeks. No improvement was observed for KLG3 patients at either time-point. Cindunistat did not improve joint pain or function, but was generally well tolerated. Conclusions Cindunistat (50 or 200 mg/day) did not slow the rate of JSN versus placebo. After 48-weeks, KLG2 patients showed less JSN; however, the improvement was not sustained at 96-weeks. iNOS inhibition did not slow OA progression in KLG3 patients. Clinical trial listing NCT00565812
Risk of mortality in patients with psoriatic arthritis, rheumatoid arthritis and psoriasis: a longitudinal cohort study

Background There are conflicting reports in the literature of the mortality risk among patients with psoriatic arthritis (PsA). The objective of this study was to examine the risk of mortality in patients with PsA compared with matched controls, patients with psoriasis and those with rheumatoid arthritis (RA). Methods A longitudinal cohort study was performed in a large UK medical record database, The Health Improvement Network, among patients with PsA, rheumatoid arthritis (RA) or psoriasis with data from 1994 to 2010. Unexposed controls were matched on practice and start date within the practice for each patient with PsA. Cox proportional hazards models were used to calculate the relative hazards for death. Results Patients with PsA (N=8706), RA (N=41 752), psoriasis (N=138 424) and unexposed controls (N=82 258) were identified; 1 442 357 person-years were observed during which 21 825 deaths occurred. Compared with population controls, patients with PsA did not have an increased risk of mortality after adjusting for age and sex (disease-modifying antirheumatic drug (DMARD) users: HR 0.94, 95% CI 0.80 to 1.10; DMARD non-users: HR 1.06, 95% CI 0.94 to 1.19) whereas patients with RA had increased mortality (DMARD users: HR 1.59, 95% CI 1.52 to 1.66; DMARD non-users: HR 1.54, 95% CI 1.47 to 1.60). Patients with psoriasis who had not been prescribed a DMARD had a small increased risk of mortality (HR 1.08, 95% CI 1.04 to 1.12) while those who had been prescribed a DMARD, indicating severe psoriasis, were at increased risk (HR 1.75, 95% CI 1.56 to 1.95). Conclusions Patients with RA and psoriasis have increased mortality compared with the general population but patients with PsA do not have a significantly increased risk of mortality.
Statins do not influence clinical response and B cell depletion after rituximab treatment in rheumatoid arthritis

B cell depletion by rituximab requires cross linking of CD20, which induces redistribution of CD20 to lipid rafts. This redistribution is correlated with efficiency of complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) in previous studies. The integrity of the lipid rafts may also be important in induction of apoptosis. In vitro , statins interfere with the formation of cholesterol-rich micro domains within the plasma membrane- the lipid rafts, which impairs lymphoma cell killing by ADCC and CDC by rituximab.1 We previously demonstrated that pre- and post-treatment numbers of plasmablasts were associated with clinical response to rituximab.2 Statins were recently reported to inhibit rituximab's clinical efficacy in rheumatoid arthritis (RA). 3 We therefore tested for an association of statin use and both …
Differential skeletal impact of tenofovir disoproxil fumarate in young versus old HIV-infected adults

Abstract Background: Lower peak bone mass in early adulthood predicts subsequent fragility fractures. Antiretroviral toxicity could contribute to young HIV-infected individuals not achieving adequate peak bone mass. Objective: To determine if tenofovir disoproxil fumarate's (TDF) effect on bone mineral density (BMD) differs by age. Methods: We examined BMD data at the lumbar spine and hip from AIDS Clinical Trials Group (ACTG) A5224s and ASSERT and randomized treatment-naive studies comparing TDF/emtricitabine versus abacavir/lamivudine (with efavirenz or atazanavir/ritonavir). In this post hoc analysis, we defined the TDF effect as the difference between mean 48-week BMD per cent changes for lumbar spine and hip in individuals randomized to TDF versus abacavir. We used multivariable linear regression to compare the TDF effect in individuals younger and older than 30 years. If TDF effect by age did not differ significantly between studies, we pooled study populations. Otherwise, analyses were conducted separately within each study population. Results: Among 652 subjects, 21% were below age 30 years. The relationship between age and TDF effect significantly differed between A5224s and ASSERT (P = 0.008 for lumbar spine; P = 0.007 for hip). In A5224s, there was more bone loss with TDF at lumbar spine and hip in subjects under 30 years old versus in older subjects ( − 4.5% vs − 1.4%; P = 0.045; − 4.3% vs − 1.6%; P = 0.026, respectively). There was no significant evidence for this age-associated TDF effect in ASSERT. Conclusions: There was heterogeneity in the observed effect of TDF on bone density in young adults compared to older adults, suggesting that further investigation is required to understand the impact of age on BMD decline with TDF.
EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) is sensitive to show efficacy of rituximab treatment in a randomised controlled trial

Rituximab therapy is a promising treatment for primary Sjogren's syndrome (pSS). 1 ,2 So far, treatment studies performed in patients with pSS lacked the use of a uniform outcome measure to monitor disease activity. Recently, the European League Against Rheumatism (EULAR) developed the EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI). 3 ESSDAI was shown to be able to monitor disease activity in patient profile and open-label studies.4 ,5 To further study the utility of ESSDAI for clinical studies, we assessed the responsiveness of ESSDAI after rituximab treatment in a randomised controlled trial (RCT) of patients with pSS.6 As the principal investigator (HB) was involved in the development of ESSDAI, the database of a single-centre, randomised, double-blind, placebo-controlled trial (see ref. 6 for details) was prospectively completed with regard to all ESSDAI domains, namely the cutaneous, respiratory, renal, articular, muscular, peripheral and central nervous system, haematological, glandular, constitutional, …
Movement-aware action control — Integrating symbolic and control-theoretic action execution

In this paper we propose a bridge between a symbolic reasoning system and a task function based controller. We suggest to use modular position- and force constraints, which are represented as action-object-object triples on the symbolic side and as task function parameters on the controller side. This description is a considerably more fine-grained interface than what has been seen in high-level robot control systems before. It can preserve the 'null space' of the task and make it available to the control level. We demonstrate how a symbolic description can be translated to a control-level description that is executable on the robot. We describe the relation to existing robot knowledge bases and indicate information sources for generating constraints on the symbolic side. On the control side we then show how our approach outperforms a traditional controller, by exploiting the task's null space, leading to a significantly extended work space.
Education is the key to protecting children against smoking: What parents think and do

The purpose of this study was to examine parents’ communication with their children about the topic of smoking. A qualitative descriptive design was used. Twenty-nine parents who lived in rural communities and who had children in kindergarten to Grade 6 were interviewed. The data were analyzed for themes. A large majority of parents communicated with their children about smoking through verbal interaction, using any one of three approaches: discussing smoking with their children, telling their children about smoking, or acknowledging their children’s understanding of smoking. Those parents also had shown disapproval of smoking, which took different forms and varied from explicit messages in their verbal communication to implicit messages in their behaviours. Three parents had not verbally communicated at all with their children about smoking. Overall, the parents’ communication patterns with their children varied in terms of quality and coherence with recommendations in the literature.
Differential expression of adipokines in infrapatellar fat pad (IPFP) and synovium of osteoarthritis patients and healthy individuals

Osteoarthritis (OA) is the most common form of arthritis and a major cause of pain and disability in elders. It is characterised by cartilage loss and structural changes in the whole joint. Although some mechanisms involved in the pathogenesis of OA are more and more understood, several factors involved in the onset and progression of the disease remain elusive. Together with aging and genetic factors, obesity is an important risk factor for OA.1 Recent data suggest a clear role of systemic inflammatory mediators, produced by fat mass, called adipokines, in OA.2–4 Actually, experimental evidences confirm the critical role of adipokines with an emphasis on old members, such as leptin and visfatin,3–5 but also on new members such as chemerin.2 To this regard, several lines of evidence indicate that these factors exert pro-inflammatory and pro-catabolic actions at cartilage level.2 ,4 ,5 For instance, leptin, chemerin and visfatin trigger the expression of nitric oxide, MMPs and PGE2 in chondrocytes.2 ,4 ,5 Leptin, chemerin and visfatin have been detected in synovial fluid obtained from OA patients.6–8 Moreover, the levels of these adipokines have …