No known cohort study has investigated whether the Mediterranean diet can reduce incident coronary heart disease (CHD) events in a Mediterranean population. This study examined the relation between ...Mediterranean diet adherence and risk of incident CHD events in the 5 Spanish centers of the European Prospective Investigation into Cancer and Nutrition. Analysis included 41,078 participants aged 29–69 years, recruited in 1992–1996 and followed up until December 2004 (mean follow-up:10.4 years). Confirmed incident fatal and nonfatal CHD events were analyzed according to Mediterranean diet adherence, measured by using an 18-unit relative Mediterranean diet score. A total of 609 participants (79% male) had a fatal or nonfatal confirmed acute myocardial infarction (n = 468) or unstable angina requiring revascularization (n = 141). After stratification by center and age and adjustment for recognized CHD risk factors, high compared with low relative Mediterranean diet score was associated with a significant reduction in CHD risk (hazard ratio = 0.60, 95% confidence interval: 0.47, 0.77). A 1-unit increase in relative Mediterranean diet score was associated with a 6% reduced risk of CHD (95% confidence interval: 0.91, 0.97), with similar risk reductions by sex. Mediterranean diet adherence was associated with a significantly reduced CHD risk in this Mediterranean country, supporting its role in primary prevention of CHD in healthy populations.
Treatment of patients with allergic asthma using low doses of peptides containing T cell epitopes from Fel d 1, the major cat allergen, reduces allergic sensitization and improves surrogate markers ...of disease. Here, we demonstrate a key immunological mechanism, linked epitope suppression, associated with this therapeutic effect. Treatment with selected epitopes from a single allergen resulted in suppression of responses to other ("linked") epitopes within the same molecule. This phenomenon was induced after peptide immunotherapy in human asthmatic subjects and in a novel HLA-DR1 transgenic mouse model of asthma. Tracking of allergen-specific T cells using DR1 tetramers determined that suppression was associated with the induction of interleukin (IL)-10(+) T cells that were more abundant than T cells specific for the single-treatment peptide and was reversed by anti-IL-10 receptor administration. Resolution of airway pathophysiology in this model was associated with reduced recruitment, proliferation, and effector function of allergen-specific Th2 cells. Our results provide, for the first time, in vivo evidence of linked epitope suppression and IL-10 induction in both human allergic disease and a mouse model designed to closely mimic peptide therapy in humans.
Of the 24 Greenland interstadials in the Last Glacial-interglacial cycle (LGIC) only five are conventionally recognised in Britain. This paper aims to improve understanding of the LGIC in Britain ...from a site at Arclid, Cheshire. Sediments were characterised and luminescence used to establish a chronology. This found that the Chelford Sand Formation spans 77-47 ka with sand deposited initially by aeolian but later by fluvial transportation. Coleoptera and Diptera from the basal peat lens provided a reconstruction for a heather-rich heathland environment grazed by large herbivores, with summer temperatures between 13 and 18 °C, and winter temperatures between −14 and 1 °C. Flies included the earliest records of the blood-sucking horsefly Haematopota pluvialis, and the soldierfly Chloromyia formosa. The overlying Stockport Sand Formation was deposited fluvioglacially between 47-41 ka with the upper Stockport Till formed by the advance of the last British icesheet after ∼33 ka. Stenothermic beetle analysis from Arclid indicate similarities with results from other British mid LGIC sites, some of which are at or beyond the limit of radiocarbon dating and may be of a similar age to Arclid. Basal organic sediments found at Arclid along with other reassigned sites are proposed as a new Arclid Interstadial. A revised British LGIC chronostratigraphy has the Wretton, Chelford and Brimpton Interstadials and the previously suggested but not widely recognised Cassington Interstadial. The Arclid Interstadial occurred after these, but prior to the Upton Warren Interstadial complex. This closes the previous gap in interstadials between the Brimpton Interstadial and the Upton Warren Interstadial complex within the British chronostratigraphy.
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•Arclid spans 77-33 ka and was an braided floodplain with heathland during interstadials.•Earliest records of fossil insects Haematopota pluvialis and Chloromyia Formosa found.•Arclid basal peat along with other reassigned sites are proposed as a new Arclid Interstadial.•A revised British chronostratigraphy for the Last Glacial Interglacial cycle is proposed. This is the Wretton, Chelford, Brimpton, Cassington and Arclid Interstadials then the Upton Warren Interstadial complex.
Background Mutations in TNFRSF13B , the gene encoding transmembrane activator and calcium modulator cyclophilin ligand interactor (TACI), are found in 10% of patients with common variable ...immunodeficiency. However, the most commonly detected mutation is the heterozygous change C104R, which is also found in 0.5% to 1% of healthy subjects. The contribution of the C104R mutation to the B-cell defects observed in patients with common variable immunodeficiency therefore remains unclear. Objective We sought to define the functional consequences of the C104R mutation on B-cell function. Methods We performed in vitro studies of TACI C104R expression and signaling. A knock-in mouse with the equivalent mutation murine TACI (mTACI) C76R was generated as a physiologically relevant model of human disease. We examined homozygous and heterozygous C76R mutant mice alongside wild-type littermates and studied specific B-cell lineages and antibody responses to T cell–independent and T cell–dependent challenge. Results C104R expression and ligand binding are significantly diminished when the mutant protein is expressed in 293T cells or in patients’ cell lines. This leads to defective nuclear factor κB activation, which is proportionally restored by reintroduction of wild-type TACI. Mice heterozygous and homozygous for mTACI C76R exhibit significant B-cell dysfunction with splenomegaly, marginal zone B-cell expansion, diminished immunoglobulin production and serological responses to T cell–independent antigen, and abnormal immunoglobulin synthesis. Conclusions These data show that the C104R mutation and its murine equivalent, C76R, can significantly disrupt TACI function, probably through haploinsufficiency. Furthermore, the heterozygous C76R mutation alone is sufficient to disturb B-cell function with lymphoproliferation and immunoglobulin production defects.
Patient education materials (pems) are frequently used to help patients make cancer screening decisions. However, because pems are typically developed by experts, they might inadequately address ...patient barriers to screening. We co-created, with patients, a prostate cancer (pca) screening pem, and we compared how the co-created pem and a pem developed by experts affected decisional conflict and screening intention in patients.
We identified and used patient barriers to pca screening to co-create a pca screening pem with patients, clinicians, and researchers. We then conducted a parallel-group randomized controlled trial with men 40 years of age and older in Ontario to compare decisional conflict and intention about pca screening after those men had viewed the co-created pem (intervention) or an expert-created pem (control). Participants were randomized using dynamic block randomization, and the study team was blinded to the allocation.
Of 287 participants randomized to exposure to the co-created pem, 230 were analyzed, and of 287 randomized to exposure to the expert-created pem, 223 were analyzed. After pem exposure, intervention and control participants did not differ significantly in Decisional Conflict Scale scores mean difference: 0.37 ± 1.23; 95% confidence interval (ci): -2.05 to 2.79; in sure (Sure of myself, Understand information, Risk-benefit ratio, or Encouragement) scores (odds ratio: 0.75; 95% ci: 0.52 to 1.08); or in screening intention (mean difference: 0.09 ± 0.08; 95% ci: -0.06 to 0.24).
The effectiveness of the co-created pem did not differ from that of the pem developed by experts. Thus, pem developers should choose the method that best fits their goals and resources.
Dermatologists can benefit from adopting environmental sustainability in the management of their practices. We can also use opportunities to share best practices in environmental stewardship concepts ...with our colleagues, patients, and communities. Herein, we review easy steps for any health care professional, and dermatologists in particular, to adopt environmental sustainability and become more active in the fight against climate change.
This study included a select literature review, an identification of resources, and an overview of MyGreenDoctor.org.
Many simple, cost effective, energy saving resources were identified. A reference list of climate change resources for health are organizations to help with lower their carbon footprints, educating their staff and patients, and advocacy for better environmental stewardship is presented.
Going green is an easy process that can save money, boost morale, and help educate patients while reducing the carbon footprint of any size medical practice.
The association between alcohol consumption and coronary heart disease (CHD) has been widely studied. Most of these studies have concluded that moderate alcohol intake reduces the risk of CHD. There ...are numerous discussions regarding whether this association is causal or biased. The objective of this paper is to analyse the association between alcohol intake and CHD risk in the Spanish cohort of the European Prospective Investigation into Cancer (EPIC).
Participants from the EPIC Spanish cohort were included (15 630 men and 25 808 women). The median follow-up period was 10 years. Ethanol intake was calculated using a validated dietary history questionnaire. Participants with a definite CHD event were considered cases. A Cox regression model adjusted for relevant co-variables and stratified by age was produced. Separate models were carried out for men and women.
The crude CHD incidence rate was 300.6/100 000 person-years for men and 47.9/100 000 person-years for women. Moderate, high and very high consumption was associated with a reduced risk of CHD in men: hazard ratio 0.90 (95% CI 0.56 to 1.44) for former drinkers, 0.65 (95% CI 0.41 to 1.04) for low, 0.49 (95% CI 0.32 to 0.76) for moderate, 0.46 (95% CI 0.30 to 0.71) for high and 0.50 (95% CI 0.29 to 0.85) for very high consumers. A negative association was found in women, with p values above 0.05 in all categories.
Alcohol intake in men aged 29-69 years was associated with a more than 30% lower CHD incidence. This study is based on a large prospective cohort study and is free of the abstainer error.
Changes in spinopelvic and lower extremity alignment between standing and relaxed sitting have important clinical implications with regard to stability of total hip arthroplasty. This study aimed to ...analyze the effect of body mass index (BMI) on lumbopelvic alignment and motion at the hip joint.
A retrospective review of patients who underwent full-body stereoradiographs in standing and relaxed sitting for total hip arthroplasty planning was conducted. Spinopelvic parameters measured included spinopelvic tilt (SPT), pelvic incidence (PI), lumbar lordosis (LL), PI minus LL (PI-LL), proximal femoral shaft angle (PFSA), and standing-to-sitting hip range of motion. Propensity score matching controlled for age, gender, PI, and hip ostoarthritis grade. Patients were stratified into normal (NORMAL; BMI, 18.5-24.9), overweight (OW; 25.0-29.9), and obese (OB; 30.0-34.9) groups. Alignment parameters were compared using one-way analysis of variance.
There were 84 patients in each group after propensity score matching. Standing alignment between BMI groups was similar for all parameters (P > .05) except for PFSA (P < .001). Significant differences were noted for sitting alignment between patients who are NORMAL, OW, and OB in: SPT (P = .007), PI-LL (P = .018), and LL (P = .029). PFSA between groups was not significantly different (P > .05). Significant differences were found for sitting-to-standing alignment across groups in PFSA change (P < .001), SPT change (P = .006), PI-LL change (P = .005), LL change (P = .037), and hip flexion (P < .001).
Significant differences in sitting and standing-to-sitting change in lumbopelvic alignment based on BMI suggest obese patients recruit more posterior spinopelvic tilt when sitting to compensate for soft-tissue impingement that occurs anterior to the hip joint and limiting hip flexion.
Objective
Despite long‐standing safe and effective use of immunoglobulin replacement therapy (IgRT) in primary immunodeficiency, clinical data on IgRT in patients with secondary immunodeficiency ...(SID) due to B‐cell lymphoproliferative diseases are limited. Here, we examine the correlation between approved IgRT indications, treatment recommendations, and clinical practice in SID.
Methods
An international online survey of 230 physicians responsible for the diagnosis of SID and the prescription of IgRT in patients with hematological malignancies was conducted.
Results
Serum immunoglobulin was measured in 83% of patients with multiple myeloma, 76% with chronic lymphocytic leukemia, and 69% with non‐Hodgkin lymphoma. Most physicians (85%) prescribed IgRT after ≥2 severe infections. In Italy, Germany, Spain, and the United States, immunoglobulin use was above average in patients with hypogammaglobulinemia, while in the UK considerably fewer patients received IgRT. The use of subcutaneous immunoglobulin was highest in France (34%) and lowest in Spain (19%). Immunologists measured specific antibody responses, performed test immunization, implemented IgRT, and used subcutaneous immunoglobulin more frequently than physicians overall.
Conclusions
The management of SID in hematological malignancies varied regionally. Clinical practice did not reflect treatment guidelines, highlighting the need for robust clinical studies on IgRT in this population and harmonization between countries and disciplines.
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