Effects of cosmonaut vestibular training on vestibular function prior to spaceflight

The purpose of this study was to quantify the effects of repetitive Coriolis and cross-coupled stimulations, similar to the vestibular training the cosmonauts are exposed to prior to their spaceflight, on vestibular function in control subjects on Earth. Ten volunteers were passively rotated in yaw on a rotating chair while executing standardized pitch head-and-trunk movements. The chair stopped to change direction after 12 head-and-trunk movements were made. The runs were grouped in sessions of ten,which were repeated daily for 10 days. The severity of motion sickness was assessed by subjective judgment and measurements of skin pallor and salivary total protein concentration, and nystagmus was recorded. The severity of motion sickness and nystagmus decreased during cosmonaut vestibular training (CVT). One month after the end of CVT, nystagmus responses were still about 20–30% lower than control values. These results indicate that CVT induces a habituation of vestibular responses. One important implication of this experiment concerns space studies on cosmonauts who are exposed to such vestibular training prior to their spaceflight. Electronic Publication     

Enhanced MHC class II-restricted presentation of measles virus (MV) hemagglutinin in transgenic mice expressing human MV receptor CD46

This study analyzes the role of the measles virus (MV) receptor, i.e. the human CD46 molecule, in the MHC class II-restricted presentation of MV hemagglutinin (H). We generated transgenic mice ubiquitously expressing CD46, with a similar level of transgene expression on the surface of antigen-presenting cells (APC), i.e. B cells, dendritic cells (DC) and macrophages. APC isolated from transgenic mice and nontransgenic controls were tested for their ability to present MV H to H-specific CD4⁺ I-E ^d -restricted T cell hybridomas. All three populations of APC were capable of presenting MV to T cell hybridomas, DC being the most efficient. Expression of CD46 on B lymphocytes increased MHC class II-dependent presentation of MV H up to 100-fold, while CD46-transgenic DC stimulated H-specific T cell hybridomas up to 10-fold better than nontransgenic DC. Interestingly, expression of CD46 did not change the presentation efficiency of transgenic macrophages, indicating that CD46-dependent enhancement of antigen presentation depends on the nature of the APC. Furthermore, a single injection of UV-inactivated MV particles into CD46-transgenic mice, but not nontransgenic controls, induced generation of MV-specific T lymphocytes and production of anti-H antibodies, suggesting a role for CD46 in the efficient capture of MV in vivo. These results show for the first time that one ubiquitously expressed cell surface receptor, like CD46, could function in receptor-mediated antigen presentation both in vitro and in vivo and its performance depends on the type of APC which expresses it.     

Immunolocalization of the cleavage of the aggrecan core protein at the Asn341–Phe342 bond,as an indicator of the location of the metalloproteinases active in the lysis of the rat growth plate

In view of the extensive lysis of hyaline cartilage known to take place during endochondral bone formation, the current study was designed to test the hypothesis that metalloproteinases are the agents that mediate this lysis. Since these enzymes have been shown in vitro to cleave the core protein of the major proteoglycan of cartilage, aggrecan, at the Asn³⁴¹–Phe³⁴² bond, an immunohistochemical method has been developed to find out whether or not there are sites in the growth plate of the rat tibia where cleavage of this bond takes place. The cleavage of aggrecan by metalloproteinases is followed by the retention of the fragment known as G1, for it includes the G1 domain. Since the G1 fragment terminates in the amino acid residues ...FVDIPEN, we prepared an antiserum against FVDIPEN, confirmed its specificity, then applied it to the growth plate of 21-day-old rat tibia in the hope of localizing the G1 fragments. The antiserum specificity was shown by its recognition of the ...FVDIPEN sequence at the C-terminus of peptides and of G1 fragments produced by aggrecan cleavage. When the antiserum was applied to Western blots of guanidinium chloride extracts prepared from epiphyseal growth plate, it recognized two species (56 and 52 kDa), which differed only in the degree of glycosylation. These fragments were comparable in size to the G1 fragments generated by the action of recombinant metalloproteinase in vitro, thus confirming antiserum specificity for these fragments. Applying the antiserum to cryosections of 21-day-old rat tibiae revealed immunostaining at two intensities within the growth plate matrix: a strong staining was observed in a 1–5 μm-wide layer designated “peripheral” matrix, which borders the epiphyseal and metaphyseal marrow spaces as well as the perichondrium, while a weak staining was found in the rest of the plate, designated “central” matrix. The abundance of G1 fragments terminating in ...FVDIPEN in the peripheral matrix indicates that this is where the growth plate is lysed to achieve longitudinal and latitudinal bone growth. The site where metalloproteinases exert their main lytic activity is a thin layer of matrix separating central from peripheral matrix. Anat. Rec. 252:117–132, 1998. © 1998 Wiley-Liss, Inc.     

Simultaneous determination of five systemic azoles in plasma by high-performance liquid chromatography with ultraviolet detection

A simple, specific and automatable HPLC assay was developed for a simultaneous determination of systemic azoles (fluconazole, posaconazole, voriconazole, itraconazole and its metabolite hydroxyl-itraconazole, and ketoconazole) in plasma. The major advantage of this assay was sample preparation by a fully automatable solid phase extraction with Varian Plexa cartridges. C6-phenyl column was used for chromatographic separation, and UV detection was set at a wavelength of 260 nm. Linezolid was used as an internal standard. The assay was specific and linear over the concentration range of 0.05 to 40 μg/ml excepted for fluconazole which was between 0.05 and 100 μg/ml, and itraconazole between 0.1 and 40 μg/ml. Validation data for accuracy and precision for intra- and inter-day were good and satisfied FDA's guidance: CV between 0.24% and 11.66% and accuracy between 93.8% and 108.7% for all molecules. This assay was applied to therapeutic drug monitoring on patients hospitalized in intensive care and onco-hematologic units.     

Impact of Blueberry Consumption on the Human Fecal Bileacidome: A Pilot Study of Bile Acid Modulation by Freeze-Dried Blueberry

Cholesterol-derived bile acids (BAs) affect numerous physiological functions such as glucose homeostasis, lipid metabolism and absorption, intestinal inflammation and immunity, as well as intestinal microbiota diversity. Diet influences the composition of the BA pool. In the present study, we analyzed the impact of a dietary supplementation with a freeze-dried blueberry powder (BBP) on the fecal BA pool composition. The diet of 11 men and 13 women at risk of metabolic syndrome was supplemented with 50 g/day of BBP for 8 weeks, and feces were harvested before (pre) and after (post) BBP consumption. BAs were profiled using liquid chromatography coupled with tandem mass spectrometry. No significant changes in total BAs were detected when comparing pre- vs. post-BBP consumption samples. However, post-BBP consumption samples exhibited significant accumulations of glycine-conjugated BAs (p = 0.04), glycochenodeoxycholic (p = 0.01), and glycoursodeoxycholic (p = 0.01) acids, as well as a significant reduction (p = 0.03) in the secondary BA levels compared with pre-BBP feces. In conclusion, the fecal bileacidome is significantly altered after the consumption of BBP for 8 weeks. While additional studies are needed to fully understand the underlying mechanisms and physiological implications of these changes, our data suggest that the consumption of blueberries can modulate toxic BA elimination.     

Asthma phenotypes based on health services use for allergic diseases in a province-wide birth cohort

Background

Many previous studies on asthma phenotypes were conducted in selected clinical populations and overlooked changes throughout the life course.

Management of human resources of a pharmacy department during the COVID-19 pandemic: Take-aways from the first wave

The coronavirus disease 2019 (COVID-19) is the biggest public health threat the world has seen in many years and poses new challenges and opportunities to healthcare systems. The new reality imposed by the pandemic requires a modification of practices to ensure the health and safety of patients and medical teams. The purpose of this article is to share the experiences of the pharmacy department of the Centre hospitalier de l’Université de Montréal (CHUM) in response to the COVID-19 pandemic. Seven of the most important issues will be addressed: crisis management, internal communications, employee stress, reorganisation of workspaces, reorganisation of pharmacist workforce, telework and schedule management. Some of the changes made in human resources deployment will likely remain even post-pandemic.