Objective
Recognition of a new type of rheumatoid arthritis (RA)–specific autoantibody, the anti–carbamylated protein antibodies (anti‐CarP), has provided an opportunity to improve the management and ...understanding of RA. The current study was undertaken to assess the relationship between anti‐CarP antibodies and HLA–DRB1 alleles in RA.
Methods
Serum samples were obtained from 3 different collections, comprising a total of 1,126 RA patients. Serum reactivity against in vitro carbamylated fetal calf serum proteins was determined by enzyme‐linked immunosorbent assay. HLA–DRB1 alleles were determined using either hybridization techniques or imputation from HLA‐dense genotypes. Results of these analyses were combined in a meta‐analysis with data from 3 previously reported cohorts. The carrier frequencies of the common HLA–DRB1 alleles were compared between the antibody‐positive RA subgroups and the double‐negative subgroup of RA patients stratified by anti–citrullinated protein antibody (ACPA)/anti‐CarP antibody status, and also between the 4 RA patient strata and healthy controls.
Results
Meta‐analysis was conducted with 3,709 RA patients and 2,305 healthy control subjects. Results revealed a significant increase in frequency of HLA–DRB1*03 carriers in the ACPA−/anti‐CarP+ subgroup as compared to ACPA−/anti‐CarP− RA patients and healthy controls; this was consistently found across the 6 sample collections. This association of HLA–DRB1*03 with ACPA−/anti‐CarP+ RA was independent of the presence of the shared allele (SE) and any other confounders analyzed. No other allele was specifically associated with the ACPA−/anti‐CarP+ RA patient subgroup. In contrast, frequency of the SE was significantly increased in the ACPA+/anti‐CarP− and ACPA+/anti‐CarP+ RA patient subgroups, without a significant distinction between them. Furthermore, some alleles (including HLA–DRB1*03) were associated with protection from ACPA+ RA.
Conclusion
These findings indicate a specific association of HLA–DRB1*03 with ACPA−/anti‐CarP+ RA, suggesting that preferential presentation of carbamylated peptides could be a new mechanism underlying the contribution of HLA alleles to RA susceptibility.
Fatty acids cause endothelial dysfunction involving increased ROS (reactive oxygen species) and reduced NO (nitric oxide) bioavailability. We show that in MAECs (mouse aortic endothelial cells), the ...PPARβ/δ (peroxisome- proliferator-activated receptor β/δ) agonist GW0742 prevented the decreased A23187-stimulated NO production, phosphorylation of eNOS (endothelial nitric oxide synthase) at Ser1177 and increased intracellular ROS levels caused by exposure to palmitate in vitro. The impaired endothelium-dependent relaxation to acetylcholine in mouse aorta induced by palmitate was restored by GW0742. In vivo, GW0742 treatment prevented the reduced aortic relaxation, phosphorylation of eNOS at Ser1177, and increased ROS production and NADPH oxidase in mice fed on a high-fat diet. The PPARβ/δ antagonist GSK0660 abolished all of these protective effects induced by GW0742. This agonist enhanced the expression of CPT (carnitine palmitoyltransferase)-1. The effects of GW0742 on acetylcholine- induced relaxation in aorta and on NO and ROS production in MAECs exposed to palmitate were abolished by the CPT-1 inhibitor etomoxir or by siRNA targeting CPT-1. GW0742 also inhibited the increase in DAG (diacylglycerol), PKCα/βII (protein kinase Cα/βII) activation, and phosphorylation of eNOS at Thr495 induced by palmitate in MAECs, which were abolished by etomoxir. In conclusion, PPARβ/δ activation restored the lipid-induced endothelial dysfunction by up-regulation of CPT-1, thus reducing DAG accumulation and the subsequent PKC-mediated ROS production and eNOS inhibition.
data regarding the association between Wernicke encephalopathy (WE) and alcoholic liver disease (ALD) are scarce in spite of alcohol consumption being the main risk factor for WE.
to describe the ...frequency of ALD in a cohort of patients diagnosed with WE and alcohol use disorders (AUDs) and to compare the characteristics of WE patients with and without ALD.
we conducted an observational study in 21 centers through a nationwide registry of the Spanish Society of Internal Medicine. WE Caine criteria were applied and demographic, clinical, and outcome variables were analyzed.
434 patients were included in the study, of which 372 were men (85.7%), and the mean age was 55 ± 11.8 years. ALD was present in 162 (37.3%) patients and we found a higher percentage of cases with tremor, flapping and hallucinations in the ALD group. A total of 22 patients (5.0%) died during admission (7.4% with ALD vs 3.7% without ALD; P = 0.087). Among the ALD patients, a relationship between mortality and the presence of anemia (Odds ratio OR=4.6 Confidence interval CI95% 1.1–18.8; P = 0.034), low level of consciousness (OR=4.9 CI95% 1.1–21.2; P = 0.031) and previous diagnosis of cancer (OR=10.3 CI95% 1.8–59.5; P = 0.009) was detected. Complete recovery was achieved by 27 patients with ALD (17.8%) and 71 (27.8%) without ALD (P = 0.030).
the association of WE and ALD in patients with AUDs is frequent and potentially linked to differences in clinical presentation and to poorer prognosis, as compared to alcoholic patients with WE without ALD.
•The association of Wernicke encephalopathy and alcoholic liver disease in patients with alcohol use disorders is frequent.•Diagnosis of Wernicke encephalopathy in patients with alcoholic liver disease can be harder due to clinical differences.•Patients with alcoholic liver disease and wernicke encephalopathy have worse prognosis.•The presence of Wernicke encephalopathy should prompt the assessment of alcoholic liver disease.
Previous studies have shown beneficial associations between fruit and vegetable (FV) consumption and cardiometabolic risk factors. However, variety in FV, which may play an important role on ...cardiovascular health due to the different nutrient and phytochemical content among the different groups and subgroups of FV has been poorly investigated. We longitudinally investigated associations between 1-year changes in variety and quantity of FV and concurrent changes in cardiometabolic risk factors in elderly subjects with overweight/obesity and metabolic syndrome.
a one-year data longitudinal analysis of 6647 PREDIMED-plus study participants (48% women) was conducted. Data were collected at baseline, six months and 1-year of follow-up. Variety and quantity of FV were estimated using a food frequency questionnaire and continuous scores for variety were created based on items/month of FV. Linear mixed-models adjusted for potential confounders were performed to estimate associations (β-coefficients and 95% confidence interval) between 1-year changes in FV variety and/or quantity and concurrent changes in cardiometabolic risk factors.
Two points increment in the FV variety score over one year was associated with a concurrent decrease in glucose (-0.33 mg/dL (0.58, -0.07)), body weight (-0.07 kg (-0.13, -0.02)) and waist circumference (WC) (-0.08 cm (-0.16, -10.01)). An increment of 100 g/d of FV over one year was associated with a concurrent decrease in triglycerides (-0.50 mg/dL (-0.93, -0.08)), glucose (-0.21 mg/dL (-0.32, -0.11)), body weight (-0.11 kg (-0.15, -0.07)) and WC (-0.10 cm (-0.14, -0.06)) over 1-year. Changes in FV consumption which led to higher quantity and variety over one year were associated with downward changes in glucose (-1.26 mg/dL (-2.09, -0.43)), body weight (-0.40 kg (-0.58, -0.23)) and WC (-0.50 cm (-0.73, -0.28)).
Greater variety, in combination with higher quantity of FV was significantly associated with a decrease in several cardiometabolic risk factors among elderly subjects at high cardiovascular risk.
Mechanisms linking occupational heat exposure with chronic diseases have been proposed. However, evidence on occupational heat exposure and cancer risk is limited.
We evaluated occupational heat ...exposure and female breast cancer risk in a large Spanish case-control study. We enrolled 1,738 breast cancer cases and 1,910 frequency-matched population controls. A Spanish job-exposure matrix, MatEmEsp, was used to assign estimates of the proportion of workers exposed (
≥ 25% for at least 1 year) and work time with heat stress (wet bulb globe temperature ISO 7243) for each occupation. We used three exposure indices: ever versus never exposed, lifetime cumulative exposure, and duration of exposure (years). We estimated ORs and 95% confidence intervals (CI), applying a lag period of 5 years and adjusting for potential confounders.
Ever occupational heat exposure was associated with a moderate but statistically significant higher risk of breast cancer (OR 1.22; 95% CI, 1.01-1.46), with significant trends across categories of lifetime cumulative exposure and duration (
= 0.01 and 0.03, respectively). Stronger associations were found for hormone receptor-positive disease (OR ever exposure = 1.38; 95% CI, 1.12-1.67). We found no confounding effects from multiple other common occupational exposures; however, results attenuated with adjustment for occupational detergent exposure.
This study provides some evidence of an association between occupational heat exposure and female breast cancer risk.
Our results contribute substantially to the scientific literature. Further investigations are needed considering multiple occupational exposures.
Abstract Background Rasmussen encephalitis is a devastating pediatric syndrome of unknown etiology that is characterized by progressive loss of neurological function and intractable focal epilepsy. ...Cytotoxic T lymphocytes have an active role in the pathogenic process of Rasmussen encephalitis. We studied the implication of CXCL10-CXCR3, a chemotactic axis involved in the pathogenesis of several cases of immune encephalitis. Methods We analyzed surgical specimens of children with Rasmussen encephalitis, and performed functional in vitro assays to test the implications of the pathological findings. Results We found that cytotoxic T lymphocytes infiltrating the damaged areas of primary biopsies expressed CXCR3, whereas neurons and astrocytes in the same areas expressed CXCL10. The in vitro assays demonstrated we found that astrocytes upregulated the expression of CXCL10 messenger RNA and the release of CXCL10 to the supernatants on stimulation with polyinosinic-polycyticylic acid, a synthetic double-stranded RNA that mimics infections with either RNA or DNA viruses. Activated T lymphocytes responded to the production of CXCL10 by astrocytes by increasing their migration in a transwell assay. Finally, the chemotaxis induced by the stimulated astrocytes was completely abrogated in the presence of a small molecule antagonist of CXCR3. Conclusions Our results suggest that the CXCR3-CXCL10 axis has a role in recruiting pathogenic T lymphocytes into the brains of patients with Rasmussen encephalitis. This chemotactic mechanism may be targeted pharmacologically.
Background
Previous studies have investigated weight loss caused by exercise following bariatric surgery. However, in most cases, the training program is poorly reported; the exercise type, volume, ...and intensity are briefly mentioned; and the sample size, selection criteria, and follow-up time vary greatly across studies.
Purpose
The EFIBAR study aims to investigate over 1 year the effects of a 16-week supervised exercise program, initiated immediately after bariatric surgery, on weight loss (primary outcome), body composition, cardiometabolic risk, physical fitness, and quality of life in patients with severe/extreme obesity.
Material and Methods
The EFIBAR study is a parallel-group, superiority, randomized controlled trial (RCT), comprising 80 surgery patients. Half of the participants, randomly selected, perform a 16-week supervised exercise program, including both strength and aerobic training, starting immediately after the surgery (7–14 days). For each participant, all primary and secondary outcomes are measured at three different time points: (i) before the surgery, (ii) after the intervention (≈4 months), and (iii) 1 year after the surgery.
Conclusion
The EFIBAR study will provide new insights into the multidimensional benefits of exercise in adults with severe/extreme obesity following bariatric surgery.
Trial Registration
EFIBAR randomized controlled trial was prospectively registered at
Clinicaltrials.gov
(NCT03497546) on April 13, 2018.
Graphical abstract
Acute subdural hematomas (ASDH) are found frequently following traumatic brain injury (TBI) and they are considered the most lethal type of mass lesions. The decision to perform a procedure to ...evacuate ASDH and the approach, either via craniotomy or decompressive craniectomy (DC), remains controversial.
We reviewed a prospectively collected series of 343 moderate to severe TBI patients in whom ASDH was the main lesion (ASDH volumes ≥10 cc). Patients with early comfort measures (early mortality prediction >50% and not ICP monitored), bilateral ASDH or the presence of another intracranial hematoma with volumes exceeding two times the volume of the ASDH were excluded. Among them, 112 were managed conservatively, 65 underwent ASDH evacuation by craniotomy and 166 by DC (103 pre-emptive DC, 63 obligatory DC). We calculated the average treatment effect by propensity score (PS) analysis using the following covariates: age, year, hypoxia, shock, pupils, major extracranial injury, motor score, midline shift, ASDH volume, swelling, intraventricular and subarachnoid hemorrhage presence. Then, multivariable binary regression and ordinal logistic regression analysis were performed to estimate associations between predictors and mortality and 12 months-GOS respectively. The patients' inverse probability weights were included as an independent variable in both regression models.
The main variables associated with outcome were year, age, falls from patient´s own height, hypoxia, early deterioration, pupillary abnormalities, basal cistern effacement, compliance to ICP monitoring guidelines and type of surgical approach (craniotomy and pre-emptive DC).
According to sliding dichotomy analysis, we found that patients in the intermediate or worst bands of unfavorable outcome prognosis seemed to achieve better than expected outcome if they underwent pre-emptive DC rather than craniotomy.
This paper focuses on the development of patterned graphene/substrate by means of green nanosecond pulse laser irradiation. Monolayer graphene samples supported on a Si/SiO2 substrate were patterned ...using 532 nm laser irradiation under fluence conditions ranging from 31 mJ cm−2 to 4240 mJ cm−2. Raman spectroscopy was used to investigate the effect of laser irradiation on the graphene. It was found that at 356 mJ cm−2 selective ablation of the graphene occurs. However, at fluence values above 1030 mJ cm−2 (when damage to the substrate is observed) no ablation of the graphene takes place. In contrast, its graphenic structure was found to have been modified. Only at fluence values where the ablation of the substrate occurs, is graphene eliminated in an area almost equivalent to that of the ablated substrate. In this case, additional damage to the graphene sheet edges is produced. The increment in the number of oxygenated functional groups in these regions, as measured by x-ray photoelectron spectroscopy (XPS), suggests that this damage is probably caused by thermal phenomena during the ablation of the substrate.
: The aim was to examine the mediating role of basic psychological needs and job satisfaction in the relationship between the gender effect on health problems and psychological well-being for health ...professionals in Europe in 2015.
: Two multiple partial mediation analyses were conducted in order to test the partial mediation of both basic needs and job satisfaction, with gender as the independent variable and health problems or well-being, respectively, as the dependent variables, with a sample of health professionals.
: Women reported lower psychological well-being and more health problems than men. The total effect of gender on both well-being and health problems was found to be significant. Regarding multiple mediation analyses: (a) the effect of gender on well-being was fully mediated by global basic need satisfaction and job satisfaction, such that gender did not present a significant direct effect and (b) the effect of gender on health problems was partially mediated by global basic need satisfaction and job satisfaction, such that the direct effect remained significant.
: The fulfillment of basic needs for autonomy, competence, and relatedness, as postulated within self-determination theory, was hypothesized to play a mediating role in the relationship between gender and well-being. Since significant gender differences in basic need satisfaction were observed, such a mediator should be controlled in order to achieve a significant relationship between gender and well-being when basic needs comes into play. The current study adds to the research emphasizing the need for satisfaction as a promising mechanism underlying for female health professionals' well-being.
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