Miracle-dz/UniFAR-FTUs huggingface dataset:
Nrf2 is essential for cholesterol crystal‐induced inflammasome activation and exacerbation of atherosclerosis

Oxidative stress and inflammation — two components of the natural host response to injury — constitute important etiologic factors in atherogenesis. The pro‐inflammatory cytokine interleukin (IL)‐1 significantly enhances atherosclerosis, however, the molecular mechanisms of IL‐1 induction within the artery wall remain poorly understood. Here we have identified the oxidative stress‐responsive transcription factor NF‐E2‐related 2 (Nrf2) as an essential positive regulator of inflammasome activation and IL‐1‐mediated vascular inflammation. We show that cholesterol crystals, which accumulate in atherosclerotic plaques, represent an endogenous danger signal that activates Nrf2 and the NLRP3 inflammasome. The resulting vigorous IL‐1 response critically depended on expression of Nrf2, and Nrf2‐deficient apolipoprotein E (Apoe)−/− mice were highly protected against diet‐induced atherogenesis. Importantly, therapeutic neutralization of IL‐1α and IL‐1β reduced atherosclerosis in Nrf2+/−Apoe−/− but not in Nrf2−/−Apoe−/− mice, suggesting that the pro‐atherogenic effect of Nrf2‐signaling was primarily mediated by its permissive role in IL‐1 production. Our studies demonstrate a role for Nrf2 in inflammasome activation, and identify cholesterol crystals as disease‐relevant triggers of the NLRP3 inflammasome and potent pro‐atherogenic cytokine responses. These findings suggest a common pathway through which oxidative stress and metabolic danger signals converge and mutually perpetuate the chronic vascular inflammation that drives atherosclerosis.
Prevalence and reasons for non-adherence to hyperlipidemia treatment

AimTo assess the prevalence of medication non-adherence, and to assess the effect of selected patient-, doctor-, and therapyrelated factors on patient adherence to hyperlipidemia treatment.MethodsOpen-label questionnaire study in the primary care patients diagnosed with hyperlipidemia.ResultsA total of 255 outpatients aged 60.2 +/− 10.3 (mean +/− SD) were enrolled. Only 61.6% of patients claimed to be fully adherent during the last week. The major source of motivation to take medication was expectation to lower cholesterol level, and only extremely infrequently (2.7%) — to prolong life. Patients often pointed at economic constrains as a reason for low adherence. Getting information from doctor about the purpose of therapy (OR=3.04, 95%CI 1.36–6.80, P<0.01), understanding the purpose of therapy (OR=5.09, 95%CI 1.30–19,90, P<0.05), reading the patient information leaflet (OR=3.37, 95%CI 1.78–6.36, P<0.001), positive opinion about the effectiveness of the treatment (OR=2.45, 95%CI 1.24–4.81, P<0.01), and visiting primary care once a month (OR=2.22, 95%CI 1.05–4.69, P<0.05) were associated with adherence to the treatment.ConclusionsNon-adherence to lipid-lowering medication is a frequent problem. This study suggests that effective doctor-patient communication may play an important role in rising patients’ motivation to systematic treatment. Better adherence might be also obtained with prescribing more affordable drugs.
Lack of transfer of skills after virtual reality simulator training with haptic feedback

Abstract Background and objective: Virtual reality (VR) simulators enrich surgical training and offer training possibilities outside of the operating room (OR). In this study, we created a criterion-based training program on a VR simulator with haptic feedback and tested it by comparing the performances of a simulator group against a control group. Material and methods: Medical students with no experience in laparoscopy were randomly assigned to a simulator group or a control group. In the simulator group, the candidates trained until they reached predefined criteria on the LapSim® VR simulator (Surgical Science AB, Göteborg, Sweden) with haptic feedback (XitactTM IHP, Mentice AB, Göteborg, Sweden). All candidates performed a cholecystectomy on a porcine organ model in a box trainer (the clinical setting). The performances were video rated by two surgeons blinded to subject training status. Results: In total, 30 students performed the cholecystectomy and had their videos rated (N = 16 simulator group, N = 14 control group). The control group achieved better video rating scores than the simulator group (p < .05). Conclusions: The criterion-based training program did not transfer skills to the clinical setting. Poor mechanical performance of the simulated haptic feedback is believed to have resulted in a negative training effect.
Calcifying Fibrous Tumor

Abstract Calcifying fibrous tumor (CFT) is a benign lesion characterized by its specific histological findings and is found as solitary or multiple lesions in several locations of the human body. The aim of the present systematic review is to give a detailed account of all reported cases of CFT in the literature and to analyze the available data, to completely characterize the entity from epidemiological, medical, and surgical aspects. A bibliographic research was performed from 1988 until 2015. A database with the patients’ characteristics was made, including sex, age, location of the tumor, symptoms, symptoms duration, size of the tumor, diagnostic methods, treatment, metastasis, and follow-up. A total of 104 articles were identified, reporting 157 cases of CFT. Mean age of patients was 33.58 years and the ratio between men and women was 1:1.27. The most common locations of CFT were stomach (18%), small intestine (8.7%), pleura (9.9%), mesentery (5%), and peritoneum (6.8%). Mean diameter of the tumor was estimated 4.6 cm. The correlations proceeded showed that as age increases, size decreases (P = 0.001) and that the tumor is larger in females (P = 0.027). Kruskal-Wallis test showed that the larger tumors appear in the neck and adrenal gland (P = 0.001). The percentage of asymptomatic patients was 30.57%. Computed tomography and biopsy were the most common tests for the diagnosis of CFT. Open surgical procedure was performed in the majority of cases. The median hospitalization was 6.06 days and the mean follow-up period was 29.97 months. Recurrences were mentioned in 10 of 96 patients with available data. No deaths owing to CFT were mentioned in the literature. CFT should be included in the differential diagnosis of enlarging mass revealed by clinical or imaging examination either incidentally or after specific acute or chronic symptomatology.
Recovery 3 and 12 months after hysterectomy

AbstractChronic postsurgical pain (CPSP) is 1 important aspect of surgical recovery. To improve perioperative care and postoperative recovery knowledge on predictors of impaired recovery is essential. The aim of this study is to assess predictors and epidemiological data of CPSP, physical functioning (SF-36PF, 0–100), and global surgical recovery (global surgical recovery index, 0–100%) 3 and 12 months after hysterectomy for benign indication.A prospective multicenter cohort study was performed. Sociodemographic, somatic, and psychosocial data were assessed in the week before surgery, postoperatively up to day 4, and at 3- and 12-month follow-up. Generalized linear model (CPSP) and linear-mixed model analyses (SF-36PF and global surgical recovery index) were used. Baseline data of 468 patients were collected, 412 (88%) patients provided data for 3-month evaluation and 376 (80%) patients for 12-month evaluation.After 3 and 12 months, prevalence of CPSP (numeric rating scale ≥ 4, scale 0–10) was 10.2% and 9.0%, respectively, SF-36PF means (SD) were 83.5 (20.0) and 85.9 (20.2), global surgical recovery index 88.1% (15.6) and 93.3% (13.4). Neuropathic pain was reported by 20 (5.0%) patients at 3 months and 14 (3.9%) patients at 12 months. Preoperative pain, surgery-related worries, acute postsurgical pain on day 4, and surgery-related infection were significant predictors of CPSP. Baseline level, participating center, general psychological robustness, indication, acute postsurgical pain, and surgery-related infection were significant predictors of SF-36PF. Predictors of global surgical recovery were baseline expectations, surgery-related worries, American Society of Anesthesiologists classification, type of anesthesia, acute postsurgical pain, and surgery-related infection.Several predictors were identified for CPSP, physical functioning, and global surgical recovery. Some of the identified factors are modifiable and optimization of patients’ preoperative pain status and psychological condition as well as reduction of acute postsurgical pain and surgery-related infection may lead to improvement of outcome.
Effects of postexercise ice-water and room-temperature water immersion on the sensory organization of balance control and lower limb proprioception in amateur rugby players

Background: This single-blinded, three-armed randomized controlled trial aimed to compare the effects of postexercise ice-water immersion (IWI), room-temperature water immersion (RWI), and no water immersion on the balance performance and knee joint proprioception of amateur rugby players. Methods: Fifty-three eligible amateur rugby players (mean age ± standard deviation: 21.6 ± 2.9 years) were randomly assigned to the IWI group (5.3 °C), RWI group (25.0 °C), or the no immersion control group. The participants in each group underwent the same fatigue protocol followed by their allocated recovery intervention, which lasted for 1 minute. Measurements were taken before and after the fatigue-recovery intervention. The primary outcomes were the sensory organization test (SOT) composite equilibrium score (ES) and the condition-specific ES, which were measured using a computerized dynamic posturography machine. The secondary outcome was the knee joint repositioning error. Two-way repeated measures analysis of variance was used to test the effect of water immersion on each outcome variable. Results: There were no significant within- and between-group differences in the SOT composite ESs or the condition-specific ESs. However, there was a group-by-time interaction effect on the knee joint repositioning error. It seems that participants in the RWI group had lower errors over time, but those in the IWI and control groups had increased errors over time. The RWI group had significantly lower error score than the IWI group at postintervention. Conclusion: One minute of postexercise IWI or RWI did not impair rugby players’ sensory organization of balance control. RWI had a less detrimental effect on knee joint proprioception to IWI at postintervention.
The CD20 homolog Ms4a8a integrates pro‐ and anti‐inflammatory signals in novel M2‐like macrophages and is expressed in parasite infection

Recently, we identified the CD20 homolog Ms4a8a as a novel molecule expressed by tumor‐associated macrophages that directly enhances tumor growth. Here, we analyzed Ms4a8a+ macrophages in M2‐associated infectious pathologies. In late‐stage Trypanosoma congolense and Taenia crassiceps infections, Ms4a8a expression was detected in hepatic and peritoneal macrophages respectively. Innate immunity in these infections is modulated by Toll‐like receptor (TLR) signaling and TLR2/4/7 agonists strongly induced Ms4a8a expression in bone marrow derived macrophages (BMDMs) treated with M2 mediators (glucocorticoids/IL‐4). LPS/dexamethasone/IL‐4‐induced Ms4a8a+ BMDMs were characterized by strong expression of mRNA of mannose receptor (Mmr), arginase 1, and CD163, and by decreased iNOS expression. Coinduction of Ms4a8a by M2 mediators and TLR agonists involved the classical TLR signaling cascade via activation of MyD88/TRIF and NF‐κB. Forced overexpression of Ms4a8a modulated the TLR4 response of RAW264.7 cells as shown by gene expression profiling. Upregulation of Hdc, Tcfec, and Sla was confirmed both in primary LPS/dexamethasone/IL‐4‐stimulated Ms4a8a+ BMDMs and in peritoneal macrophages from late‐stage Taenia crassiceps infection. In conclusion, we show that TLR signaling skews the typical alternative macrophage activation program to induce a special M2‐like macrophage subset in vitro that also occurs in immunomodulatory immune reactions in vivo, a process directly involving the CD20 homolog Ms4a8a.
Respiratory syncytial virus infection augments NOD2 signaling in an IFN‐β‐dependent manner in human primary cells

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in infants, with remarkable variability in disease severity. An exaggerated proinflammatory response and influx of leukocytes is part of the pathogenesis of severe RSV disease. Here, we show an increase in proinflammatory cytokine production by human immune cells after stimulation with RSV and muramyl dipeptide (MDP), which is recognized by nucleotide‐binding oligomerization domain containing 2 (NOD2). PBMCs from Crohn's disease patients homozygous for the 3020insC mutation in the NOD2 gene did not show a synergistic response to stimulation with RSV and MDP, suggesting that NOD2 is essential for the observed synergy. Further experiments aimed at identifying the viral ligand indicated that viral RNA plays an essential role in the recognition of RSV. Stimulation with RSV or Poly(I:C) induced IFN‐β expression, which resulted in an increased expression of the viral receptors TLR3 and RIG‐I, as well as an increased NOD2 expression. Our data indicate that IFN‐β induction by viral RNA is an essential first step in the increased proinflammatory response to MDP. We hypothesize that the enhanced proinflammatory response to MDP following RSV infection may be an important factor in determining the outcome of the severity of disease.
Fatty Acid Metabolism in Patients with PPAR Mutations

Oxford Centre for Diabetes, Endocrinology, and Metabolism (G.D.T., B.A.F., J.C., L.H., S.M.H., K.N.F., F.K.) and National Institute for Health and Research (NIHR) Oxford Biomedical Research Centre (F.K.), University of Oxford, Churchill Hospital, Oxford OX3 7LJ, United Kingdom; and Departments of Medicine and Clinical Biochemistry (D.B.S., S.O., K.C.), Addenbrooke’s Hospital, Cambridge CB2 2QQ, United Kingdom
Competition between T cells maintains clonal dominance during memory inflation induced by MCMV

Both human cytomegalovirus (HCMV) and murine cytomegalovirus (MCMV) establish persistent infections that induce the accumulation of virus‐specific T cells over time in a process called memory inflation. It has been proposed that T cells expressing T‐cell receptors (TCRs) with high affinity for HCMV‐derived peptides are preferentially selected after acute HCMV infection. To test this in the murine model, small numbers of OT‐I transgenic T cells, which express a TCR with high affinity for the SIINFEKL peptide, were transferred into congenic mice and recipients were challenged with recombinant MCMV expressing SIINFEKL. OT‐I T cells were selectively enriched during the first 3 weeks of infection. Similarly, in the absence of OT‐I T cells, the functional avidity of SIINFEKL‐specific T cells increased from early to late times postinfection. However, even when exceedingly small numbers of OT‐I T cells were transferred, their inflation limited the inflation of host‐derived T cells specific for SIINFEKL. Importantly, subtle minor histocompatibility differences led to late rejection of the transferred OT‐I T cells in some mice, which allowed host‐derived T cells to inflate substantially. Thus, T cells with a high functional avidity are selected shortly after MCMV infection and continuously sustain their clonal dominance in a competitive manner.
Modulation of Noradrenaline Release by Peripheral Presynaptic α2‐Adrenoceptors in Humans

The existence of a functional presynaptic a2-adrenoceptor that modulates noradrenaline release was studied in 15 volunteers. Noradrenaline spillover was measured in the forearm under basal conditions, during single intraarterial infusions of the tx-adrenoceptor antagonists yohimbine (α2, 1.0 μg/kg/min) and doxazosin (α2, 0.1 μg/kg/min), and during intraarterial infusion of tyra-mine (1.25 μg/kg/min) alone and in combination with either and both a-adrenoceptor antagonists. Forearm blood flow (FBF) was measured by plethysmography. Noradrenaline spillover was calculated as the product of FBF and the difference in arterial and venous plasma noradrenaline. The various infusions did not induce systemic hemodynamic effects. Tyramine induced a dose-dependent decrease in FBF (p < 0.001) which was reduced by yohimbine (p < 0.01), as well as by doxazosin (p << 0.01), and abolished by the combination of both a-adrenoceptor antagonists (p < 0.001). During basal conditions noradrenaline spillover was virtually zero, and this was not changed by yohimbine or doxazosin. Local infusion of tyramine increased noradrenaline spillover (p < 0.05). This tyramine-induced noradrenaline spillover was further increased by yohimbine (p < 0.01) and by the combination of yohimbine and doxazosin (p < 0.001). The single infusion of doxazosin only enhanced the tyramine-induced noradrenaline spillover significantly when it was preceded by yohimbine. The present investigation supports the concept of a presynaptic α2-adrenoceptor modulating noradrenaline release from sympathetic nerve endings via a negative feedback mechanism in humans. Stimulation of noradrenaline release might help to reveal this mechanism
The combination effect of curcumin with different antibiotics against Staphylococcus aureus

The different investigation has been carried out on the biological activities of curcumin but the effect of this natural product on the antibacterial activity of different antibiotics has not been demonstrated. In this study the enhancement effect of curcumin on the antibacterial activity of different antibiotics was evaluated against Staphylococcus aureus. Disk diffusion method was used to determine the antibacterial activity of these antibiotics in the absence and presence of sub inhibitory concentration of curcumin. A clinical isolate of S. aureus was used as test strain. In the presence of sub-inhibitory concentration of curcumin (500 μg/disc) the antibacterial activities of cefixime, cephotaxime, vancomycin and tetracycline have been increased against test strain. The highest fold increase in area was observed for cefixime against S. aureus (a 52.6 % increase in inhibition zone surface area). Also the increases in inhibition zone areas (%) for cephotaxime, vancomycin and tetracycline were 24.9%, 26.5% and 24.4%, respectively. No enhancing effect on the antibacterial activities of others antibiotics was detected against S. aureus at content of 500μg/disc. Conversely, in case of nalidixic acid, curcumin showed an antagonistic effect on the antibacterial activity of this antibiotic against test strain. These results signify that the curcumin potentiates the antimicrobial action of cefixime, cephotaxime, vancomycin and tetracycline suggesting a possible utilization of this edible compound in combination therapy against S. aureus. Key words: Antibacterial activity, combination effect, Staphylococcus aureus, curcumin
Validation of the factorial structure of the Positive and Negative Syndrome Scale in use by untrained psychiatrists in routine care

Background. The Positive and Negative Syndrome Scale (PANSS) can be called the standard for the assessment of schizophrenic disorders. It is well-known and routinely used. In scientific studies and clinical practice extensive training of raters in the use of the scale can often not be provided. The question is whether under such conditions psychometric properties of the scale can be guaranteed. Method. In a 2-year drug utilization study on risperidone, 1895 schizophrenic outpatients were assessed by their treating psychiatrists, who were working under conditions of routine care, using a modified version of the Positive and Negative Symptom Scale (PANSS/m). Physicians could not be trained in the use of the scale. The results of these ratings were analysed, comparing means and internal consistency with the original Kay et al. results (Kay et al. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987;13:261), and by factor analysis for the total sample and split halves. Results. Means for the positive subscale were similar (6.5 and 6.4, respectively) and means for the negative subscale (11.9 and 8.0, respectively) slightly higher than the original Kay et al. results. Internal consistency of the positive and negative subscales (0.80 and 0.87, and 0.73 and 0.83, respectively) were similar to Kay et al. The same clear factorial solution was found for the total sample and the subsamples. Discussion. Scores for the subscales reflect the predominance of negative symptoms in schizophrenic outpatients. The factorial solution supports the positive and negative subscales of the PANSS. The PANSS/m was easy to use under conditions of routine treatment and is a good and robust scale.
Anxiety and depression and their influence on the quality of life after total hip replacement: preliminary report

Objective. The study investigated health-related quality of life in relation to mental status (anxiety and depression) and demographic factors in patients before and after total hip replacement due to osteoarthrosis. Methods. The SF-36, HADS, socio-demographic data questionnaire was delivered to a group of 184 subjects (108 females, 76 males) at the mean age at the time of surgery of 59 years. Questionnaires were delivered to the subjects 2 weeks before the surgery and 6 months after the operation (by mail). Results. Patients after hip replacement showed significant improvement in health-related quality of life in most domains of SF-36 score and summary scale of PCS (Physical Component Summary Scale) and MCS (Mental Component Summary Scale). They also showed improvement in mental status. Elderly patients were more likely to show worse score in MCS and PCS before and after surgery. BMI (body mass index) was correlated only with preoperative PCS. Mental status was associated with postoperative PCS and MCS. Patients who were satisfied with the results of the surgery showed higher PCS and MCS score. Conclusion. Hip replacement surgery brings significant improvement to the quality of life. Age and mental status of those patients influence markedly their postoperative performance.
Diagnostic performance of magnetic resonance technology in detecting steatosis or fibrosis in patients with nonalcoholic fatty liver disease

Background: The aim of this study was to evaluate the diagnostic accuracy of magnetic resonance (MR) imaging-based methods for detecting steatosis and fibrosis in nonalcoholic fatty liver disease (NAFLD). Methods: Data were extracted from research articles obtained after a literature search from multiple electronic databases. Random-effects meta-analyses were performed to obtain overall effect size of the area of operator receiver curve (AUROC), sensitivity and specificity of MR imaging, MR elastography, and MR spectroscopy in detecting or grading steatosis/fibrosis. Meta-analysis of correlation coefficients was performed to have an overall effect size of correlation between MR-based diagnosis and histological diagnosis. Results: Twenty-one studies (1658 subjects; 45.32 years [95% CI: 35.94, 54.71] of age, 53.67% [45.39, 61.95] males, and 29.98 kg/m2 [21.93, 38.04] BMI) were included in the meta-analysis. Pooled analyses of the AUROC, specificity, and sensitivity values reported in the individual studies revealed an overall effect sizes of 0.90 (0.88, 0.92), 82.27% (77.74, 86.80), and 86.94% (84.18, 95.28) in the use of any MR-based technique for the diagnosis of NAFLD or its severity. The correlation coefficient between MR-based detection of liver steatosis and histologically measured steatosis was 0.748 (0.706, 0.789) (P < .00001). Conclusion: MRI-based diagnostic methods are valuable additions in detecting NAFLD or determining the severity of the NAFLD.