Low-dose endotoxin in allergic asthmatics: effect on bronchial and inflammatory response to cat allergen

BACKGROUND: Endotoxin was proposed to increase the severity of asthma. Endotoxin levels greatly differ according to settings. In domestic environments, airborne concentrations may be dramatically low compared with levels reported in occupational settings. OBJECTIVE: Our first objective was therefore to assess the effect of inhalation of low-level lipopolysaccharide (LPS) on the immediate and late-phase asthmatic bronchial response. Our second objective was to evaluate the effect of exposure to LPS on the local and systemic inflammatory response. METHODS: Nineteen asthmatics sensitized to cat underwent on two separate occasions a bronchial challenge test to cat allergen (cat BCT) preceded randomly by a pre-exposure to either saline or LPS (2 microg). Methacholine challenge test was performed 24 h before exposure to LPS or saline. The Borg scale for dyspnoea and lung function were recorded before and after exposure to LPS or saline, and before and after cat BCT. Induced sputum and blood samples were collected before and after cat BCT, and analysed for cell counts and eosinophil cationic protein (ECP) levels. RESULTS: Inhalation of 2 microg LPS did not induce any changes in forced expiratory volume in 1 s (FEV1), peak expiratory flow (PEF), FEF 25-75 and Borg scale of dyspnoea. It neither modified Fel d 1 PD20 (45.03 ng as compared with 87.03; P=0.42). As well, there was no significant difference in late-phase reaction. Pre-exposure to LPS did not influence eosinophil counts or ECP levels in blood and sputum. CONCLUSION: Our study demonstrated that pre-exposure to LPS at low levels, which may be encountered in domestic environment, had no significant effect on the immediate and late-phase bronchial response to cat allergen. It neither modified local and systemic eosinophilic inflammation.     

The music of speech: music training facilitates pitch processing in both music and language

The main aim of the present experiment was to determine whether extensive musical training facilitates pitch contour processing not only in music but also in language. We used a parametric manipulation of final notes' or words' fundamental frequency (F0), and we recorded behavioral and electrophysiological data to examine the precise time course of pitch processing. We compared professional musicians and nonmusicians. Results revealed that within both domains, musicians detected weak F0 manipulations better than nonmusicians. Moreover, F0 manipulations within both music and language elicited similar variations in brain electrical potentials, with overall shorter onset latency for musicians than for nonmusicians. Finally, the scalp distribution of an early negativity in the linguistic task varied with musical expertise, being largest over temporal sites bilaterally for musicians and largest centrally and over left temporal sites for nonmusicians. These results are taken as evidence that extensive musical training influences the perception of pitch contour in spoken language.     

Energy cost of running during a specific transition in duathlon]

The aim of the present study was to investigate the variability of the energy cost of running (Cr) during a simulated duathlon performed in outdoor conditions by elite duathletes. This duathlon consisted of 5 km of running, 30 km of cycling, and 5 km of running. The main result was the lack of significant difference in Cr between the two running bouts (210 +/- 10 mL d'O2.km-1.kg-1 vs. 217 +/- 10 mL d'O2.km-1.kg-1). This result is different from those observed during a triathlon, where an increase of energy cost of running bout has been reported. Furthermore, during a short-distance duathlon performed by well-trained subjects, none of the physiological (ventilation alteration, metabolic changes, or dehydration) or biomechanical factors that are classically evoked in triathlon research to explain Cr variability seem to be affected by the run-cycle-run transition. These results seem to minimize the negative effect of the cycle-to-run transition during a short-duration event in well-trained subjects.     

COVID-19 mortality in the UK Biobank cohort: revisiting and evaluating risk factors

European Journal of Epidemiology - Most studies of severe/fatal COVID-19 risk have used routine/hospitalisation data without detailed pre-morbid characterisation. Using the community-based UK...     

Iatrogenic Thyrotoxicosis: Causal Circumstances, Pathophysiology, and Principles of Treatment—Review of the Literature

Thyrotoxicosis is the clinical syndrome that results when tissues are exposed to high levels of circulating thyroid hormones. In most instances thyrotoxicosis is due to hyperthyroidism, a term reserved for disorders characterized by overproduction of thyroid hormones by the thyroid gland. Nevertheless, thyrotoxicosis may also result from a variety of conditions other than thyroid hyperfunction. The present report focuses on the etiologies, pathophysiology, and treatment of iatrogenic thyrotoxicosis. Iatrogenic thyrotoxicosis may be caused by (1) subacute thyroiditis (a result of lymphocytic infiltration, cellular injury, trauma, irradiation) with release of preformed hormones into circulation; (2) excessive ingestion of thyroid hormones (“thyrotoxicosis factitia”); (3) iodine-induced hyperthyroidism (radiologic contrast agents, topical antiseptics, other medications). Among these causes of iatrogenic thyrotoxicosis, that induced by the iodine overload and cytotoxicity associated with amiodarone represents a significant challenge. Successful management of amiodarone-induced thyrotoxicosis requires close cooperation between endocrinologists and endocrine surgeons. Surgical treatment may have a leading yet often underestimated role in view of the potential life-threatening severity of this disease, whereas others kinds of iatrogenic thyrotoxicosis are usually treated conservatively.     

A comparison of prevalence and risk factor profiles of prolonged grief disorder among French and Togolese bereaved adults

Social Psychiatry and Psychiatric Epidemiology - With the introduction of the prolonged grief disorder (PGD) in the ICD-11 and most likely in the future DSM-5-TR, there is clinical need to examine...     

Endothelial lipase promotes the catabolism of ApoB-containing lipoproteins

Endothelial lipase (EL) has been found to be a key enzyme in high-density lipoprotein (HDL) metabolism in mice, leading to the concept that inhibition of EL could be a novel strategy for raising HDL cholesterol levels. However, mice are "HDL animals" and the effect of EL on atherogenic apoB-containing lipoproteins has not been elucidated. We previously found that EL is capable of hydrolyzing very low-density lipoprotein (VLDL) and LDL lipids ex vivo. To investigate the role of EL in the metabolism of apoB-containing lipoproteins in vivo, we expressed human EL in three mouse models of elevated apoB-containing lipoproteins: apoE-deficient, LDL receptor-deficient, and human apoB transgenic mice. Unexpectedly, hepatic expression of EL resulted in markedly decreased levels of VLDL/LDL cholesterol, phospholipid, and apoB accompanied by significantly increased LDL apolipoprotein and phospholipid catabolism. To determine whether lipolytic activity is required for this effect, we also expressed a catalytically inactive form of human EL (ELS149A); unexpectedly, expression of ELS149A did not lower and in fact increased plasma lipids. Coexpression and coimmunoprecipitation studies suggested that catalytically inactive ELS149A inhibits endogenous mouse EL, accounting for the increased lipid levels. We conclude that (1) in addition to its known effects on HDL metabolism, EL influences the metabolism of apoB-containing particles; (2) catalytic activity of EL is required for its effects on apoB-containing lipoproteins; and (3) overexpressed catalytically inactive EL inhibits endogenous mouse EL, resulting in increased levels of plasma lipids. In light of these results, inhibition of EL has the potential to raise levels of atherogenic lipoproteins in addition to HDL-C levels.     

Substitute Consent for Research Involving the Elderly: A Comparison Between Quebec and France

The authors first describe the rules enacted in Quebec and France to protect adults with decisional impairment who may be approached by investigators to participate in research protocols. They then present two consecutive postal surveys conducted among Quebec and French researchers in aging and designed to (1) assess their knowledge of the legal provisions implemented to protect decisionally incapable adults, (2) elicit their opinions regarding the person best suited to provide substitute consent for research participation, and (3) document their conduct related to obtaining consent for prospective subjects with impaired decisional capacity. Knowledge of the legislation governing substitute consent was poor, even more so among French than Quebec researchers (p < 0.001). In both samples, the majority of respondents felt that the substitute decision-maker does not have to be legally appointed when the study poses little risk to the participant. Practice data revealed a certain discrepancy between the conduct of researchers in aging and the legal provisions regarding consent for research purposes that prevail in their jurisdictions. These findings underscore the need to better educate clinical investigators about existing measures to protect prospective subjects who lack decisional capacity. They also provide some support for allowing close relatives to consent to research participation on behalf of older adults who are unable to consent by themselves and have not been appointed a legal representative.