Miracle-dz/UniFAR-FTUs huggingface dataset:
Presence of significant synovitis in rheumatoid arthritis patients with disease-modifying antirheumatic drug-induced clinical remission: evidence from an imaging study may explain structural progression.

OBJECTIVE More timely and effective therapy for rheumatoid arthritis (RA) has contributed to increasing rates of clinical remission. However, progression of structural damage may still occur in patients who have satisfied remission criteria, which suggests that there is ongoing disease activity. This questions the validity of current methods of assessing remission in RA. The purpose of this study was to test the hypothesis that modern joint imaging improves the accuracy of remission measurement in RA. METHODS We studied 107 RA patients receiving disease-modifying antirheumatic drug therapy who were judged by their consultant rheumatologist to be in remission and 17 normal control subjects. Patients underwent clinical, laboratory, functional, and quality of life assessments. The Disease Activity Score 28-joint assessment and the American College of Rheumatology remission criteria, together with strict clinical definitions of remission, were applied. Imaging of the hands and wrists using standardized acquisition and scoring techniques with conventional 1.5T magnetic resonance imaging (MRI) and ultrasonography (US) were performed. RESULTS Irrespective of which clinical criteria were applied to determine remission, the majority of patients continued to have evidence of active inflammation, as shown by findings on the imaging assessments. Even in asymptomatic patients with clinically normal joints, MRI showed that 96% had synovitis and 46% had bone marrow edema, and US showed that 73% had gray-scale synovial hypertrophy and 43% had increased power Doppler signal. Only mild synovial thickening was seen in 3 of the control subjects (18%), but no bone marrow edema. CONCLUSION Most RA patients who satisfied the remission criteria with normal findings on clinical and laboratory studies had imaging-detected synovitis. This subclinical inflammation may explain the observed discrepancy between disease activity and outcome in RA. Imaging assessment may be necessary for the accurate evaluation of disease status and, in particular, for the definition of true remission.
Quenching of Singlet Oxygen by Pyocyanin and Related Phenazines †

Pseudomonas aeruginosa is a human pathogen, which causes infections of various organs, including lung, skin and eye, particularly in individuals who are immunocompromised. Pyocyanin (1‐hydroxy‐5‐methylphenazine), a cytotoxic pigment secreted by the bacterium, is among the factors that contribute to virulence of this pathogen. We have previously shown that rose bengal and riboflavin photosensitize oxidation of pyocyanin to a product(s) with diminished reactivity and toxicity. Singlet oxygen was suggested as the major oxidant, based on the inhibitory effect of sodium azide. In the present study, we used the time resolved technique to investigate direct interaction of pyocyanin and related phenazines (1‐hydroxyphenazine [1‐OH‐Phen], 1‐methoxy‐5‐methylphenazine [1‐MeO‐PCN] and phenazine methosulfate [PMS]) with 1O2. The rate constants for the 1O2 quenching (physical + chemical) by pyocyanin and 1‐OH‐Phen in D2O buffer (pD ∼7.2) have been determined to be 4.8 × 108 and 6.8 × 108 M−1 s−1, respectively. 1‐MeO‐PCN and PMS were markedly less efficient 1O2 quenchers. Among the phenazines studied only phenazine methosulfate photogenerated 1O2 (Φ(1O2) = 0.56 in acetonitrile). Interaction of 1O2 with pyocyanin and other related phenazines produced by the bacteria may be important in determining the potential utility of photochemical/pharmacological approaches to eradicate P. aeruginosa from infected tissues.
Neurally mediated vasoconstriction is capable of decreasing skin blood flow during orthostasis in the heat‐stressed human

Given the large increase in cutaneous vascular conductance (CVC) during whole‐body heat stress, this vascular bed is important in the regulation of blood pressure during orthostatic stress. In this thermal state, changes in CVC are reported to be due to withdrawal of active vasodilator activity. The purpose of this study was to identify, contrary to the current line of thinking, whether cutaneous vasoconstrictor neural activity is enhanced and capable of contributing to reductions in CVC during an orthostatic challenge of heat‐stressed individuals. Healthy normotensive subjects were pretreated, subcutaneously, with botulinum toxin A (BTX‐A) to inhibit the release of neurotransmitters from cutaneous active vasodilator nerves. On the experimental day, microdialysis probes were placed in the BTX‐A‐treated site and in an adjacent untreated site. In protocol 1, internal temperature was elevated ∼0.7°C, followed by the application of lower body negative pressure (LBNP; −30 mmHg). LBNP reduced CVC at the BTX‐A‐treated sites (Δ4.2 ± 2.9%max), as well as at the control site (Δ9.8 ± 4.1%max). In protocol 2, after confirming the absence of cutaneous vasodilatation at the BTX‐A‐treated site during whole‐body heating, CVC at this site was elevated to a similar level relative to the control site (55.4 ± 13.4 versus 60.7 ± 10.4%max, respectively) via intradermal administration of isoproterenol prior to LBNP. Similarly, when flow was matched between sites, LBNP reduced CVC at both the BTX‐A‐treated (Δ15.3 ± 4.6%max) and the control sites (Δ8.8 ± 5.6%max). These data suggest that the cutaneous vasoconstrictor system is engaged and is capable of decreasing CVC during an orthostatic challenge in heat‐stressed individuals.
Biomarkers increase detection of active smoking and secondhand smoke exposure in critically ill patients*

Objectives:The association between tobacco smoke exposure and critical illness is not well studied, largely because obtaining an accurate smoking history from critically ill patients is difficult. Biomarkers can provide quantitative data on active and secondhand cigarette smoke exposure. We sought to compare cigarette smoke exposure as measured by biomarkers to exposure by self-report in a cohort of critically ill patients and to determine how well biomarkers of cigarette smoke exposure correlate with each other in this population. Design, Setting, and Patients:Serum and urine cotinine and trans-3′-hydroxycotinine, urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol, and hair and nail nicotine levels were measured in 60 subjects enrolled in an observational cohort of critically ill subjects at a tertiary academic medical center in Tennessee. Smoking history was obtained from patients, their surrogates, or the medical chart. Cigarette smoke exposure as measured by biomarkers was compared to exposure by history. Measurements and Main Results:By smoking history, 29 subjects were identified as smokers, 28 were identified as nonsmokers, and 3 were identified as unknown. The combination of serum cotinine and urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol identified 27 of the 28 nonsmokers by history either as active smokers (n = 6, 21%) or as exposed to secondhand smoke (n = 21, 75%). All biomarker levels were strongly correlated with each other (r = .69–.95, p < .0001). Conclusions:The combination of serum cotinine and urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol identified considerably more active smokers than did smoking history and detected a high prevalence of secondhand smoke exposure in a critically ill population. These markers will be important for future studies investigating the relationship between active smoking and secondhand smoke exposure and critical illness.
Acute myeloid and T‐cell acute lymphoblastic leukaemia with aberrant antigen expression exhibit similar TCRδ gene rearrangements

TCRδ gene recombination patterns were analysed by Southern blot, polymerase chain reaction and nucleotide sequencing in acute myeloid leukaemias with coexpression of lymphoid antigens (Ly+ AML, n = 10) as well as in early T‐cell acute lymphoblastic leukaemias with (My+ T‐ALL, n = 10) and without coexpression of myeloid antigens (My− T‐ALL, n = 9). These 29 acute leukaemias exhibiting TCRδ gene rearrangements were selected from 66 Ly+ AML, 14 My+ T‐ ALL and 12 My− T‐ALL cases.
Interventions for vaginismus.

BACKGROUND Vaginismus is involuntary vaginal muscle contraction which makes sexual intercourse difficult or impossible. It is one of the more common female psychosexual problems. Various therapeutic strategies for vaginismus, such as sex therapy and desensitization, have been considered in uncontrolled studies. OBJECTIVES The aim of this review is to determine the clinical effectiveness of treatments for vaginismus and also to examine the role of partner participation in the effectiveness of the treatment. SEARCH STRATEGY The Cochrane Collaboration Depression, Anxiety & Neurosis Controlled Trials Register (Issue 3, 2000), the Cochrane Controlled Trials Register (Cochrane Library, Issue 2, 2000), MEDLINE (1966 to Apr 2000), EMBASE (1980 to Apr 2000), PsycINFO (1967 to April 2000) and CINAHL (1982 to Mar 2000) were searched. The Journal of Sex Research (1974 to 1999), Sexual & Marital Therapy (1986 to 1999), Sexual Dysfunction (1998 to 1999) and the Journal of Sex and Marital Therapy (1974 to 1999) were handsearched. Reference lists and conference abstracts were searched. Experts in the field were contacted regarding unpublished material. SELECTION CRITERIA Controlled trials comparing treatments for vaginismus with another treatment, a placebo treatment, treatment as usual or waiting list control. DATA COLLECTION AND ANALYSIS The reviewers extracted data which were verified with the trial investigator. MAIN RESULTS Two controlled trials were identified although data were only available from one trial. The second trial compared two forms of systematic desensitization and reported no discernible differences between them. REVIEWER'S CONCLUSIONS In spite of encouraging results reported from uncontrolled series of patients there is very limited evidence from controlled trials concerning the effectiveness treatments for vaginismus. Further trials are need to compare therapies with waiting list control and with other therapies.
Waist circumference and visceral fat in CKD: a cross-sectional study.

BACKGROUND In the general population, waist circumference was noted to be a reliable predictor of visceral fat. In addition, increased waist circumference was strongly associated with risk factors for cardiovascular disease. In patients with chronic kidney disease (CKD), the association of waist circumference with visceral fat was never tested. STUDY DESIGN Cross-sectional study. SETTING & PARTICIPANTS 122 patients with CKD not yet on dialysis therapy (75 men; diabetes mellitus, 30%; age, 55.3 +/- 11.3 years; body mass index, 27.1 +/- 5.2 kg/m(2); estimated glomerular filtration rate, 35.4 +/- 15.2 mL/min/1.73 m(2)) were studied. PREDICTOR Waist circumference. OUTCOMES & MEASUREMENTS Anthropometry, abdominal visceral fat measured by means of computed tomography, and cardiovascular disease risk factors. RESULTS Waist circumference strongly correlated with visceral fat (r = 0.75 for men, r = 0.81 for women; P < 0.01). kappa Statistic was 0.56, indicating relatively good agreement between methods. Body mass index showed a lower correlation coefficient (r = 0.68 for men, r = 0.76 for women; P < 0.01) and poor agreement (0.36) with visceral fat in comparison to waist circumference. In men, waist circumference and visceral fat similarly correlated with high-density lipoprotein cholesterol level, triacylglycerol level, and Homeostasis Model Assessment Index (P < 0.05). In women, waist circumference correlated with age, C-reactive protein level, and Homeostasis Model Assessment Index, whereas visceral fat also correlated with low-density lipoprotein cholesterol and triacylglycerol levels (P < 0.05). LIMITATIONS Findings are restricted to patients with CKD not yet on dialysis therapy from a single center. CONCLUSIONS Waist circumference was strongly associated with visceral fat in patients with CKD. Associations between waist circumference and cardiovascular disease risk factors were similar to those observed for visceral fat, particularly in men. These findings suggest that waist circumference may be a simple and inexpensive tool to be used in epidemiological studies.
Diet and colon cancer: integration of the descriptive, analytic, and metabolic epidemiology.

Case-control studies of diet and colon cancer have produced inconsistent findings. Data from descriptive and metabolic epidemiologic studies suggest that colon carcinogenesis varies by sex-age status, particularly when considered in relation to anatomic subsite. Thus stratification of data analysis by these criteria may elucidate dietary etiology. Consideration should also be given to the limited and nonlinear variation in colon cancer risk likely to exist in relation to the range of dietary "exposure" within Western study populations. In our community-based case-control study of colon cancer, comprising 220 patients and 440 individually matched controls, the dietary data have been analyzed by both tertile and quintile of individual consumption level. For total dietary energy intake, the tertile approach indicates a weak (men) to moderate (women) dose-response relationship; however, the quintile approach revealed in women a fourfold step-up in risk between the lowest and next-to-lowest quintile. For dietary protein, the quintile approach doubled the step-up in risk between the 2 lowest consuming categories for men compared with the tertile approach. Applying this quintile approach to data analyses stratified by sex, age, and colon subsite, we found: 1) In women, the risk of colon cancer for the upper four quintiles of consumption of calories and other major nutrients was greatest at young ages, whereas for men it was greatest at older ages. 2) The diet-associated risks tend to be maximal in the left (distal) colon for men and in the right (proximal) colon for women. (ABSTRACT TRUNCATED AT 250 WORDS)
Increased prevalence of chronic rhinosinusitis in carriers of a cystic fibrosis mutation.

OBJECTIVE To explore whether there is an increased prevalence of chronic rhinosinusitis (CRS) in known cystic fibrosis (CF) carriers. Self-reported CRS affects 13% to 14% of the US population and clusters in families, which suggests that genetic factors may play an etiologic role. Cystic fibrosis is an inherited recessive disorder that invariably affects the sinuses. The frequency of CF mutations has been reported to be higher in patients with CRS than in unaffected controls. PATIENTS Obligate CF carriers (parents of patients with CF) were recruited from the Johns Hopkins CF clinic. The presence of signs and symptoms of CRS was assessed by a sinus disease questionnaire. A subgroup of participants was evaluated by a physician experienced in the diagnosis of CRS. RESULTS Fifty-three (36%) of 147 obligate CF carriers who returned a completed questionnaire had self-reported CRS. Twenty-three CF carriers (14 with and 9 without CRS based on self-reporting in the questionnaire) were clinically evaluated. Seven were diagnosed as having CRS (all 7 with self-reported CRS), while another 6 had allergic rhinitis or recurrent acute rhinosinusitis (all 6 with self-reported CRS), and 10 had no evidence of active sinus disease (1 with self-reported CRS). The sensitivity (100%) and specificity (56%) of the questionnaire for physician-diagnosed CRS was similar to that of other survey instruments used to estimate the prevalence of self-reported CRS in the general population. CONCLUSION Carriers of a single CF mutation have a higher prevalence of CRS than the general population.
The use of wild edible plants in western and central Anatolia (Turkey)

In this study, 121 wild edible plants used as food in Anatolia were surveyed to determine the plant parts used and their detailed preparation methods. The results of this study show that the plants may be boiled, fried in fat, and eaten raw or as rolled vegetables. They may also be consumed as pickles, fruits, sweets and spices, and drunk as cold and hot drinks. Thirty species (8 genera) were identified as belonging to the Lamiaceae family, 15 species (15 genera) belong to the Asteraceae family, 13 species (5 genera) belong to the Rosaceae family, 8 species (7 genera) belong to the Brassicaceae family, 6 species (3 genera) belong to the Orchidaceae family and 5 species (5 genera) belong to the Apiaceae family. The genera represented by the highest number of species in the study are as follows:Sideritis L. is represented by 13 species, Origanum L. by 7 species,Rubus L. by 5 species,Thymus L. by 4 species andRumex L. by 4 species.
Estimation of Improvement in Indian Summer Monsoon Circulation by Assimilation of Satellite Retrieved Temperature Profiles in WRF Model

This study estimates the improvement in the simulation of Indian summer monsoon (ISM) circulation in the weather research and forecasting (WRF) model by assimilating temperature profiles from atmospheric infrared sounder. Two experiments are carried out from 1st May to 1st October during 2003-2011. In the first experiment control (CTRL), National Centers for Environmental Prediction final analysis forcing is used; whereas the second one (WRFAIRS) is same as CTRL but temperature profiles are assimilated. The improvements in the simulation are quantified using different statistical scores. Overall, the assimilation has improved the spatial and temporal distribution of various fields associated with ISM. Some of the major improvements are 1) elimination of asymmetric (north-south) SLP bias; 2) larger error reduction in winds; 3) reduction in the temperature biases at boundary layer and midtroposphere; 4) improvement in the vertical wind shear; 5) reduction in the water vapor mixing ratio errors by 0.3-0.6 g · Kg-1; and 6) improved simulation of monsoon circulation indices. Further improvements are noticed in dynamic and thermodynamic fields over different convective regions. This study advocates that accurate representation of the thermal structure in WRF is crucial for the simulation of realistic monsoon circulation. It may further pave way for developing/improving convective parameterization schemes for the model.
Improved diagnosis of porcine proliferative enteropathy caused by Lawsonia intracellularis using polymerase chain reaction-enzyme-linked oligosorbent assay (PCR-ELOSA).

Proliferative enteropathy (PE) caused by Lawsonia intracellularis is a major diarrheal disease affecting swine worldwide. Routine laboratory diagnosis of PE is done by amplification of L. intracellularis -specific DNA sequences by PCR followed by agarose gel electrophoresis and staining of PCR products with ethidium bromide. We report the development of an enzyme-linked oligosorbent assay (ELOSA) for specific identification of chromosomal L. intracellularis 328-bp PCR amplified products. The ELOSA involved determination of optical density value at 450 nm (OD(450)) after hybridization of biotin-labelled PCR products with an amine-modified internal oligonucleotide capture probe immobilized in microwell plates, and avidin-biotin-peroxidase complex. A positive ELOSA cut-off value of > or =0.375 was established using the mean OD(450)of negative control specimens plus three times the standard deviation. Using this value, the detection limit of PCR amplified L. intracellularis -specific products by ethidium bromide-stained agarose gel electrophoresis, Southern blot, and ELOSA were estimated to be 6.1 ng, between 0.8 and 3.0 ng, and 0.8 ng of DNA, respectively. Comparison of ethidium bromide-stained agarose gel analysis with ELOSA for detection of L. intracellularis -specific PCR products from 315 clinical specimens revealed 78% sensitivity, 100% specificity and 94% accuracy. The ELOSA produced a spectrophotometric signal that confirmed the authenticity of PCR products without subjective interpretation of ethidium bromide-stained PCR products after agarose gel electrophoresis.
Specific Role of Phosphodiesterase 4B in Lipopolysaccharide-Induced Signaling in Mouse Macrophages 1

Cyclic nucleotide signaling functions as a negative modulator of inflammatory cell responses, and type 4 phosphodiesterases (PDE4) are important regulators of this pathway. In this study, we provide evidence that only one of the three PDE4 genes expressed in mouse peritoneal macrophages is involved in the control of TLR signaling. In these cells, LPS stimulation of TLR caused a major up-regulation of PDE4B but not the paralogs PDE4A or PDE4D. Only ablation of PDE4B impacted LPS signaling and TNF-α production. TNF-α mRNA and protein were decreased by >50% in PDE4B−/−, but not in PDE4A−/− or PDE4D−/− macrophages. The PDE4 selective inhibitors rolipram and roflumilast had no additional inhibitory effect in macrophages deficient in PDE4B, but suppressed the TNF-α response in the other PDE4 null cells. The inhibition of TNF-α production that follows either genetic ablation or acute inhibition of PDE4B is cAMP-dependent and requires protein kinase A activity. However, no global changes in cAMP concentration were observed in the PDE4B−/− macrophages. Moreover, ablation of PDE4B protected mice from LPS-induced shock, suggesting that altered TLR signaling is retained in vivo. These findings demonstrate the highly specialized function of PDE4B in macrophages and its critical role in LPS signaling. Moreover, they provide proof of concept that a PDE4 inhibitor with subtype selectivity retains useful pharmacological effects.
GM‐CSF‐ and M‐CSF‐dependent macrophage phenotypes display differential dependence on Type I interferon signaling

M‐CSF and GM‐CSF are mediators involved in regulating the numbers and function of macrophage lineage populations and have been shown to contribute to macrophage heterogeneity. Type I IFN is an important mediator produced by macrophages and can have profound regulatory effects on their properties. In this study, we compared bone marrow‐derived macrophages (BMM) and GM‐CSF‐induced BMM (GM‐BMM) from wild‐type and IFNAR1−/− mice to assess the contribution of endogenous type I IFN to the phenotypic differences between BMM and GM‐BMM. BMM were capable of higher constitutive IFN‐β production, which contributed significantly to their basal transcriptome. Microarray analysis found that of the endogenous type I IFN‐regulated genes specific to either BMM or GM‐BMM, 488 of these gene alterations were unique to BMM, while only 50 were unique to GM‐BMM. Moreover, BMM displayed enhanced basal mRNA levels, relative to GM‐BMM, of a number of genes identified as being dependent on type I IFN signaling, including Stat1, Stat2, Irf7, Ccl5, Ccl12, and Cxcl10. As a result of prior type I IFN “priming,” upon LPS stimulation BMM displayed increased activation of the MyD88‐independent IRF‐3/STAT1 pathways compared with GM‐BMM, which correlated with the distinct cytokine/chemokine profiles of the two macrophage subsets. Furthermore, the autocrine type I IFN signaling loop regulated the production of the M1 and M2 signature cytokines, IL‐12p70 and IL‐10. Collectively, these findings demonstrate that constitutive and LPS‐induced type I IFN play significant roles in regulating the differences in phenotype and function between BMM and GM‐BMM.