Correction to: Intramuscular clodronate in erosive osteoarthritis of the hand is effective on pain and reduces serum COMP: a randomized pilot trial–The ER.O.D.E. study (ERosive Osteoarthritis and Disodium-clodronate Evaluation)

Clinical Rheumatology - One of the author names on this article was incorrectly tagged during the article mark-up; Luca Dalle Carbonare’s name has now been correctly tagged, with first name...     

A simple healthy lifestyle index as a proxy of wellness: a proof of concept

The evidence supporting the importance of a healthy lifestyle (active life, healthy diet, not smoking, and low stress) as a part of programs for primary and secondary prevention of cardiometabolic diseases is strong, compelling, and continuously growing. In this study, we test whether a simple web-based healthy lifestyle index, using self-reports, is related to indices of cardiovascular health and metabolic syndrome and could be employed in large wellness programs intended to promote healthy lifestyle. We studied 411 workers in an Italian multinational factory who were enrolled in a voluntary program consisting of a health checkup and an online questionnaire on lifestyle. These domains were combined into a single simple index. Participants were subdivided into three healthy lifestyle index (HI) groups (red, yellow, and green) ranging from poor to good HI quality (HI from red to green: 41.8 ± 14.6; 75.7 ± 8.5; 93.8 ± 2.2; p < 0.05). The groups differed in indicators of cardiovascular and metabolic health (waist circumference females: 82.1 ± 9.56, 78.9 ± 9.3, 72.7 ± 6.6; males: 95.2 ± 11.7, 90.0 ± 9.5, 85.7 ± 6.1 cm; group difference p < 0.05). Moreover, they differed significantly in the likelihood of having more components of the metabolic syndrome and, conversely, fewer components of the ideal cardiovascular health profile (with red having the worst profile). The red group was also characterized by the highest absenteeism. We report for the first time that a web-based self-reported poor health behavior was significantly associated with clinical and laboratory (partial correlation between HI and high-density cholesterol 0.192; body mass index ?0.288; systolic blood pressure ?0.130; all p < 0.05) results indicating a negative cardiometabolic profile.     

Bcl-6 gene mutations in primary cutaneous B-cell lymphomas

We analyzed mutations in the 5' non-coding region of the BCL-6 gene in 46 cases of primary cutaneous B-cell lymphomas (PCBCL), using a polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) method. The results indicate that PCBCL display a low frequency of mutations and support a marginal zone B-cell origin for most of these neoplasms.     

Maternal complications and procedures in pregnancy and at birth and wheezing phenotypes in children

RATIONALE: There is increasing interest in the potential influence of fetal and early life conditions on childhood wheezing. OBJECTIVES: To investigate the associations between maternal complications and procedures in pregnancy and at birth and the risk of various wheezing phenotypes in young children. METHODS: We studied 15,609 children, aged 6-7 yr, enrolled in a population-based study. Standardized questionnaires were completed by the children's mothers. RESULTS: Of the children, 9.5% (1,478) had transient early wheezing, 5.4% (884) had persistent wheezing, and 6.1% (948) had late-onset wheezing. Maternal hypertension or preeclampsia was associated with an increased risk of all three wheezing phenotypes (for transient early wheezing: odds ratio [OR], 1.40; 95% confidence interval [95% CI], 1.08-1.82; for persistent wheezing: OR, 1.59; 95% CI, 1.15-2.19; and for late-onset wheezing: OR, 1.47; 95% CI, 1.06-2.01). Use of antibiotics for urinary tract infections was associated with transient early wheezing (OR, 1.52; 95% CI, 1.16-2.00), whereas antibiotic administration at delivery was associated with both transient early wheezing (OR, 1.21; 95% CI, 1.01-1.46) and persistent wheezing (OR, 1.39; 95% CI, 1.10-1.75). Children who had a mother with diabetes were also more likely to have persistent wheezing (OR, 1.72; 95% CI, 0.99-3.00). Neither amniocentesis/chorionic villus sampling, nor weight gain in pregnancy, nor cesarean section was associated with the subsequent development of wheezing. Maternal asthma or atopy was not an effect modifier of the associations found. CONCLUSIONS: Some maternal complications during pregnancy and at delivery may increase the risk of developing different phenotypes of wheezing in childhood.     

Signaling events involved in cytokine and chemokine production induced by secretory phospholipase A2 in human lung macrophages

Secretory phospholipases A(2) (sPLA(2)) are enzymes released during inflammatory reactions. These molecules activate immune cells by mechanisms either related or unrelated to their enzymatic activity. We examined the signaling events activated by group IA (GIA) and group IB (GIB) sPLA(2) in human lung macrophages leading to cytokine/chemokine production. sPLA(2) induced the production of cytokines (TNF-alpha, IL-6 and IL-10) and chemokines (CCL2, CCL3, CCL4 and CXCL8), whereas no effect was observed on IL-12, CCL1, CCL5 and CCL22. sPLA(2) induced the phosphorylation of the MAPK p38 and ERK1/2, and inhibition of these kinases by SB203580 and PD98059, respectively, reduced TNF-alpha and CXCL8 release. Suppression of sPLA(2) enzymatic activity by a site-directed inhibitor influenced neither cytokine/chemokine production nor activation of MAPK, whereas alteration of sPLA(2) secondary structure suppressed both responses. GIA activated the phosphatidylinositol 3-kinase (PI3 K)/Akt system and a specific inhibitor of PI3 K (LY294002) reduced sPLA(2)-induced release of TNF-alpha and CXCL8. GIA promoted phosphorylation and degradation of IkappaB and inhibition of NF-kappaB by MG-132 and 6-amino-4-phenoxyphenylethylamino-quinazoline suppressed the production of TNF-alpha and CXCL8. These results indicate that sPLA(2) induce the production of cytokines and chemokines in human macrophages by a non-enzymatic mechanism involving the PI3 K/Akt system, the MAPK p38 and ERK1/2 and NF-kappaB.     

Delivering cytokines at tumor site: The immunocytokine-conjugated anti-EDB-fibronectin antibody case

Although considerable efforts have been made in the discovery of new agents for cancer treatment, several promising therapeutics cannot be applied systemically because of their severe side effects. This is the case for various recombinant pro-inflammatory cytokines that, despite their potent anti-cancer activity, can not find their way to clinical exploitation due to their devastating toxicity shown during dose escalation to therapeutically active concentrations. To circumvent these problems, an elegant and efficient way to accumulate therapeutic agents at the tumor site, thus reducing systemic side effects, is their conjugation to tumor-specific antibodies. Here, we review preclinical data about immunocytokines conjugated to a promising single-chain human antibody that selectively targets tumor-associated stroma and blood vessels by binding with high affinity and specificity to the extra domain-B (EDB) of fibronectin.