Dietary exposures and allergy prevention in high-risk infants: A joint statement with the Canadian Society of Allergy and Clinical Immunology

Allergic conditions in children are a prevalent health concern in Canada. The burden of disease and the societal costs of proper diagnosis and management are considerable, making the primary prevention of allergic conditions a desirable health care objective. This position statement reviews current evidence on dietary exposures and allergy prevention in infants at high risk for developing allergic conditions. It revisits previous dietary recommendations for pregnancy, breastfeeding and formula feeding, and provides an approach for introducing solid foods to high-risk infants. While there is no evidence that delaying the introduction of any specific food beyond six months of age helps to prevent allergy, the protective effect of early introduction of potentially allergenic foods (at four to six months of age) remains under investigation. Recent research appears to suggest that regularly ingesting a new, potentially allergenic food may be as important as when that food is first introduced.     

Antipodean forensics: a comment on ANZFSS’s response to PCAST

Recently, one of the world’s leading scientific and technical advisory groups, the U.S. President’s Council of Advisors on Science and Technology (or PCAST), published an assessment of the research supporting several forensic science procedures in regular use. PCAST was particularly interested in pattern recognition or comparison procedures, specifically: simple and mixed DNA profiles; bite marks; latent fingerprints; firearms; footwear; and hair analysis. In its report and recommendations PCAST emphasised the primacy of validation. In response, the Council of the Australian and New Zealand Forensic Science Society produced a short statement suggesting that the PCAST report has limited application to forensic science in Australia and New Zealand. This short commentary offers an alternative perspective.     

Dynamic force spectroscopy of parallel individual Mucin1-antibody bonds

We used atomic force microscopy to measure the binding forces between Mucin1 (MUC1) peptide and a single-chain variable fragment (scFv) antibody selected from a scFv library screened against MUC1. This binding interaction is central to the design of molecules used for targeted delivery of radioimmunotherapeutic agents for prostate and breast cancer treatment. Our experiments separated the specific binding interaction from nonspecific interactions by tethering the antibody and MUC1 molecules to the atomic force microscope tip and sample surface with flexible polymer spacers. Rupture force magnitude and elastic characteristics of the spacers allowed identification of the rupture events corresponding to different numbers of interacting proteins. We used dynamic force spectroscopy to estimate the intermolecular potential widths and equivalent thermodynamic off rates for monovalent, bivalent, and trivalent interactions. Measured interaction potential parameters agree with the results of molecular docking simulation. Our results demonstrate that an increase of the interaction valency leads to a precipitous decline in the dissociation rate. Binding forces measured for monovalent and multivalent interactions match the predictions of a Markovian model for the strength of multiple uncorrelated bonds in a parallel configuration. Our approach is promising for comparison of the specific effects of molecular modifications as well as for determination of the best configuration of antibody-based multivalent targeting agents.     

Cardiovascular reactivity score for the assessment of dysautonomia in familial Mediterranean fever

Objective The aim of this study was to assess the presence of dysautonomia, as manifested in abnormal cardiovascular reactivity, in patients with familial Mediterranean fever (FMF).Methods Fifty-five consecutive patients with FMF and 23 age- and sex-matched healthy controls were evaluated. Cardiovascular reactivity was studied: (1) using recordings of blood pressure (BP) and heart rate (HR) during 10 min of recumbence and 30 min of head-up tilt test to identify clinical endpoints and (2) during tilt-test, identifying parameters acting as independent predictors of FMF reactivity and enabling computation of a cardiovascular reactivity score (CVRS).Results Clinically, vasovagal reaction, postural tachycardia syndrome, and/or orthostatic hypotension were observed in ten patients (18.1%). Utilizing a derived equation, the group average CVRS in FMF was 5.83±1.78 (healthy group –7.60±5.41) (P=<0.0001). A CVRS of >3.25 was associated with FMF, with 98% sensitivity and 100% specificity.Conclusion A very high percentage of FMF patients exhibit abnormal cardiovascular reactivity which is clinically occult but can be detected on autonomic challenge and application of the CVRS.     

Polydiacetylene Nanotubes in Heterogeneous Catalysis: Application to the Gold‐Mediated Oxidation of Silanes

A layer‐by‐layer approach is used to anchor small gold nanoparticles onto organic nanotubes resulting from the self‐assembly and polymerization of diacetylene‐containing nitrilotriacetic amphiphiles. The obtained nanotube–gold hybrid is used as a catalyst for the aerobic oxidation of various silanes. With minimal gold loading (0.05 mol%), all substrates are converted into the corresponding silanols with hydrogen gas as the only by‐product. The catalyst operates under mild conditions and can be easily recycled, losing neither activity nor selectivity.

     

Quinacrine added to ongoing therapeutic regimens attenuates anticardiolipin antibody production in SLE

The benefit of combining quinacrine (Qn) with hydroxychloroquine (HCQ) in the treatment of systemic lupus erythematosus (SLE) was previously re-evaluated by us. In our current study we observed that, in 11 active SLE patients (SLEDAI score 5-12), the addition of Qn (100 mg/day) to their existing ongoing therapeutic regimens resulted in a significant attenuation of their previously persistent anticardiolipin antibody (aCL) response. This was in comparison with a matched non-Qn treated control group composed of 14 randomly chosen aCL-positive SLE patients with a similar SLEDAI score 6-10. Prior to Qn treatment the therapeutic regimens of 12 months' duration, included in all cases HCQ (400 mg/day), in many cases prednisone (P, 10-20 mg/day) and in some additional cases immunosuppressive drugs. SLEDAI scores and aCL levels were monitored during the entire follow-up period which totaled 24 months in the study group and 15-18 months in the controls. Along with the beneficial effect of the added Qn on SLEDAI scores, aCL disappearance was documented in eight of 11 patients and remained negative during 8-12 months of follow-up (P = 0.004), compared with such a change in only three of 14 non-Qn treated aCL-positive patients (P = 0.18). We conclude that the added Qn treatment to former established therapeutic protocols may eliminate aCL response in SLE patients. Whether this agent's effect is permanent needs further elucidation.     

Daytime hypercapnia in adult patients with obstructive sleep apnea syndrome in France, before initiating nocturnal nasal continuous positive airway pressure therapy

CONTEXT: Daytime hypercapnia in patients with obstructive sleep apnea syndrome (OSAS) has a highly variable prevalence in the published studies, and is usually thought to be the consequence of an associated disease, COPD, or severe obesity. STUDY OBJECTIVES: To assess the prevalence of daytime hypercapnia in a very large population of adult patients with OSAS, free of associated COPD, and with a wide range of body mass index (BMI), and to evaluate the relationship between daytime hypercapnia and the severity of obesity and obesity-related impairment in lung function. DESIGN: Retrospective analysis of prospectively collected data. METHODS: The database of the observatory of a national nonprofit network for home treatment of patients with chronic respiratory insufficiency (Association Nationale pour le Traitement a Domicile de l'Insuffisance Respiratoire Chronique) was used. Collected data at treatment initiation were age, apnea-hypopnea index, BMI, FEV(1), vital capacity (VC), and arterial blood gases. The study included 1,141 adult patients with OSAS treated in France with nocturnal nasal continuous positive airway pressure (CPAP), FEV(1) >/= 80% predicted, FEV(1)/VC >/= 70%, and absence of restrictive respiratory disease other than related to obesity. RESULTS: The prevalence of daytime hypercapnia (Paco(2) >/= 45 mm Hg) before initiating CPAP therapy was 11% in the whole study population. The prevalence of daytime hypercapnia was 7.2% (27 of 377 patients) with BMI < 30, 9.8% (58 of 590 patients) with BMI from 30 to 40, and 23.6% (41 of 174 patients) with BMI > 40. Patients with daytime hypercapnia had significantly higher BMI values and significantly lower VC, FEV(1), and Pao(2) values than the normocapnic patients. Stepwise multiple regression showed that Pao(2), BMI, and either VC or FEV(1) were the best predictors of hypercapnia, but these variables explained only 9% of the variance in Paco(2) levels. CONCLUSION: Daytime hypercapnia was observed in > 1 of 10 patients with OSAS needing CPAP therapy and free of COPD, and was related to the severity of obesity and obesity-related impairment in lung function. However, other mechanisms than obesity are probably involved in the pathogenesis of daytime hypercapnia in OSAS.