Muscle blood flow during isometric activity and its relation to muscle fatigue

The effect of isometric exercise on blood flow, blood pressure, intramuscular pressure as well as lactate and potassium efflux from exercising muscle was examined. The contractions performed were continuous or intermittent (5 s on, 5 s off) and varied between 5% and 50% maximal voluntary contraction (MVC). A knee-extensor and a hand-grip protocol were used. Evidence is presented that blood flow through the muscle is sufficient during low-level sustained contractions (less than 10% MVC). Despite this muscle fatigue occurs during prolonged contractions. One mechanism for this fatigue may be the disturbance of the potassium homeostasis. Such changes may also play a role in the development of fatigue during intermittent isometric contractions and even more so in the recovery from such exercise. In addition the role of impaired transport of substances within the muscle, due to long-lasting daily oedema formation, is discussed in relation to fatigue in highly repetitive, monotonous jobs.     

Waterfowl-wetland relationships in the Aspen Parkland of British Columbia: comparison of analytical methods

We explored the relationships between aquatic bird abundance and various pond features (physical and chemical) using data from 112 ponds located in the Aspen Parkland of British Columbia. As expected, pond size was the most important factor influencing the number of aquatic birds present. Total dissolved nitrogen, conductivity and calcium were positively associated with the abundance of several species whereas chloride tended to be negatively associated. The abundance of dabbling ducks was positively associated with turbidity and total dissolved nitrogen and negatively with percent of forested shoreline, percent of marsh and chloride. The abundance of diving ducks was associated positively with pond depth, conductivity and total dissolved nitrogen and negatively with percent of marsh and phosphorus levels. Pond area influenced more the abundance of diving ducks than dabbling ducks. Relationships between bird density and pond features were affected significantly by the area unit used to calculate density. For example, the density of Bufehead (Bucephala albeola) was correlated positively with pH and conductivity when expressed per area of water 0–2 m deep but negatively when expressed per total area of pond. Results highlight the problems associated with interpreting correlative type studies especially the difficulties in assessing the biological significance of the observed correlations. It underscores the urgent need for experimental approaches to bird-habitat studies.     

SARS-CoV-2 seroprevalence in health care workers from 10 hospitals in Quebec,Canada: a cross-sectional study

Background:The COVID-19 pandemic has disproportionately affected health care workers. We sought to estimate SARS-CoV-2 seroprevalence among hospital health care workers in Quebec, Canada, after the first wave of the pandemic and to explore factors associated with SARS-CoV-2 seropositivity.Methods:Between July 6 and Sept. 24, 2020, we enrolled health care workers from 10 hospitals, including 8 from a region with a high incidence of COVID-19 (the Montréal area) and 2 from low-incidence regions of Quebec. Eligible health care workers were physicians, nurses, orderlies and cleaning staff working in 4 types of care units (emergency department, intensive care unit, COVID-19 inpatient unit and non-COVID-19 inpatient unit). Participants completed a questionnaire and underwent SARS-CoV-2 serology testing. We identified factors independently associated with higher seroprevalence.Results:Among 2056 enrolled health care workers, 241 (11.7%) had positive SARS-CoV-2 serology. Of these, 171 (71.0%) had been previously diagnosed with COVID-19. Seroprevalence varied among hospitals, from 2.4% to 3.7% in low-incidence regions to 17.9% to 32.0% in hospitals with outbreaks involving 5 or more health care workers. Higher seroprevalence was associated with working in a hospital where outbreaks occurred (adjusted prevalence ratio 4.16, 95% confidence interval [CI] 2.63–6.57), being a nurse or nursing assistant (adjusted prevalence ratio 1.34, 95% CI 1.03–1.74) or an orderly (adjusted prevalence ratio 1.49, 95% CI 1.12–1.97), and Black or Hispanic ethnicity (adjusted prevalence ratio 1.41, 95% CI 1.13–1.76). Lower seroprevalence was associated with working in the intensive care unit (adjusted prevalence ratio 0.47, 95% CI 0.30–0.71) or the emergency department (adjusted prevalence ratio 0.61, 95% CI 0.39–0.98).Interpretation:Health care workers in Quebec hospitals were at high risk of SARS-CoV-2 infection, particularly in outbreak settings. More work is needed to better understand SARS-CoV-2 transmission dynamics in health care settings.

The COVID-19 pandemic has disproportionately affected health care workers. In France, Spain, Italy, Germany and the United States, at least 10% of cases reported in spring 2020 were in health care workers.¹ In Quebec, 25% (14 177 of 56 565) of all cases declared during the first wave of the pandemic, from March to July 2020, were in health care workers,² about one-third of whom were working in acute care hospitals.¹ The Montréal area was the most affected region in Quebec and Canada during the first wave, reaching a COVID-19 incidence rate of 1336 per 100 000 population.²The number of COVID-19 cases reported among health care workers underestimated the number of those infected with SARS-CoV-2 during that period, given limited testing leading to undiagnosed asymptomatic or paucisymptomatic infections.³ Seroprevalence studies are an important tool to determine the proportion of people infected with SARS-CoV-2, both in the general population and among health care workers.⁴ After the first wave in Quebec, SARS-CoV-2 seroprevalence in adults aged 18–69 years was found to be low (3.1% in Montréal and 1.3% in less affected regions), but this proportion could be much higher among health care workers who had to work despite the general shutdown of social and economic activities, especially if they were exposed to major outbreaks.⁵Only 2 other Canadian studies provide SARS-CoV-2 seroprevalence estimates among health care workers, and both studies were from a single centre.^6,7 Outside Canada, most seroprevalence studies among health care workers include a single site and do not provide a representative estimate for a defined region.⁸ Several studies have reported a higher seroprevalence among health care workers from units treating patients with COVID-19 (COVID-19 units) compared with other units (non–COVID-19 units), emergency departments or intensive care units.^9,10 Other studies have not identified such associations.^11,12 In this study, we aimed to assess the seroprevalence of SARS-CoV-2 antibody among hospital health care workers from a variety of settings after the first pandemic wave in Quebec, and to explore factors associated with SARS-CoV-2 seropositivity.     

Murine gallbladder epithelial cells can differentiate into hepatocyte-like cells in vitro

We determined whether extrahepatic biliary epithelial cells can differentiate into cells with phenotypic features of hepatocytes. Gallbladders were removed from transgenic mice expressing hepatocyte-specific beta-galactosidase (beta-Gal) and cultured under standard conditions and under experimental conditions designed to induce differentiation into a hepatocyte-like phenotype. Gallbladder epithelial cells (GBEC) cultured under standard conditions exhibited no beta-Gal activity. beta-Gal expression was prominent in 50% of cells cultured under experimental conditions. Similar morphological changes were observed in GBEC from green fluorescent protein transgenic mice cultured under experimental conditions. These cells showed higher levels of mRNA for genes expressed in hepatocytes, but not in GBEC, including aldolase B, albumin, hepatocyte nuclear factor-4alpha, aldehyde dehydrogenase 1, and glutamine synthetase, and they synthesized bile acids. Additional functional evidence of a hepatocyte-like phenotype included LDL uptake and enhanced benzodiazepine metabolism. Connexin-32 expression was evident in murine hepatocytes and in cells cultured under experimental conditions, but not in cells cultured under standard conditions. Notch 1, 2, and 3 and Notch ligand Jagged 1 mRNAs were downregulated in these cells compared with cells cultured under standard conditions. CD34, alpha-fetoprotein, and Sca-1 mRNA were not expressed in cells cultured under standard conditions, suggesting that the hepatocyte-like cells did not arise from hematopoietic stem cells or oval cells. These results point to future avenues for investigation into the potential use of GBEC in the treatment of liver disease.     

Murine immunomodulation of IL-10 and IL-12 induced by new isolates from avian type 2 Lactobacillus acidophilus

Several bacterial and immunogenic factors are involved in the host response to probiotic strains of Lactobacillus. Here, we report the isolation of new intestinal lactobacilli from chicken, with different immunomodulating properties on lymphoid cells from SJL and C57BL/6 mice. Analysis of biochemical markers in the Lactobacillus acidophilus CBA4P, CBA3P, and TPA3P isolates reveal that these bacterial isolates belong to the type 2 prototype, although they differ from each other. The effect of conditioned media (CM) from SJL- and C57BL/6-derived peritoneal macrophages incubated with the 3 sonicated bacterial isolates from chicken, as well as with Lactobacillus rhamnosus 9595, Escherichia coli lipopolysaccharide, or Staphylococcus aureus peptidoglycan were compared. Our results show that the CM of macrophages from C57BL/6 and SJL mice treated with the CBA4P isolate stimulated syngeneic splenic lymphocytes at a level similar to the one induced with CM from peptidoglycan-stimulated macrophages. In contrast, the CM from TPA3P- and CBA3P-treated macrophages promoted low or no stimulation of lymphoid cells. Incubation of splenic cells with CM from macrophages treated with L. rhamnosus or TPA3P led to a relative decrease in the percentages of splenic CD4+ T cells, whereas the relative percentages of B cells increased. The CBA4P and CBA3P isolates induced higher levels of gamma interferon when compared with the TPA3P isolate. The effects of the lactobacilli isolates differed according to the mouse strain used but correlated with the production of macrophagic tumor necrosis factor alpha and interleukins 6, 10, and 12 and with the modulation of the p38 mitogen-activated protein kinase (MAPK). Taken together, these results indicate that the immunomodulating properties of the new L. acidophilus isolates depend on their capacity to induce production of interleukins 10 and 12 by macrophages, which is under genetic control and depends on the p38 MAPK pathway.     

Induction of selective blood-tumor barrier permeability and macromolecular transport by a biostable kinin B1 receptor agonist in a glioma rat model

Treatment of malignant glioma with chemotherapy is limited mostly because of delivery impediment related to the blood-brain tumor barrier (BTB). B1 receptors (B1R), inducible prototypical G-protein coupled receptors (GPCR) can regulate permeability of vessels including possibly that of brain tumors. Here, we determine the extent of BTB permeability induced by the natural and synthetic peptide B1R agonists, LysdesArg(9)BK (LDBK) and SarLys[dPhe(8)]desArg(9)BK (NG29), in syngeneic F98 glioma-implanted Fischer rats. Ten days after tumor inoculation, we detected the presence of B1R on tumor cells and associated vasculature. NG29 infusion increased brain distribution volume and uptake profiles of paramagnetic probes (Magnevist and Gadomer) at tumoral sites (T(1)-weighted imaging). These effects were blocked by B1R antagonist and non-selective cyclooxygenase inhibitors, but not by B2R antagonist and non-selective nitric oxide synthase inhibitors. Consistent with MRI data, systemic co-administration of NG29 improved brain tumor delivery of Carboplatin chemotherapy (ICP-Mass spectrometry). We also detected elevated B1R expression in clinical samples of high-grade glioma. Our results documented a novel GPCR-signaling mechanism for promoting transient BTB disruption, involving activation of B1R and ensuing production of COX metabolites. They also underlined the potential value of synthetic biostable B1R agonists as selective BTB modulators for local delivery of different sized-therapeutics at (peri)tumoral sites.     

Partial meniscectomy changes fluid pressurization in articular cartilage in human knees

Partial meniscectomy is believed to change the biomechanics of the knee joint through alterations in the contact of articular cartilages and menisci. Although fluid pressure plays an important role in the load support mechanism of the knee, the fluid pressurization in the cartilages and menisci has been ignored in the finite element studies of the mechanics of meniscectomy. In the present study, a 3D fibril-reinforced poromechanical model of the knee joint was used to explore the fluid flow dependent changes in articular cartilage following partial medial and lateral meniscectomies. Six partial longitudinal meniscectomies were considered under relaxation, simple creep, and combined creep loading conditions. In comparison to the intact knee, partial meniscectomy not only caused a substantial increase in the maximum fluid pressure but also shifted the location of this pressure in the femoral cartilage. Furthermore, these changes were positively correlated to the size of meniscal resection. While in the intact joint, the location of the maximum fluid pressure was dependent on the loading conditions, in the meniscectomized joint the location was predominantly determined by the site of meniscal resection. The partial meniscectomy also reduced the rate of the pressure dissipation, resulting in even larger difference between creep and relaxation times as compared to the case of the intact knee. The knee joint became stiffer after meniscectomy because of higher fluid pressure at knee compression followed by slower pressure dissipation. The present study indicated the role of fluid pressurization in the altered mechanics of meniscectomized knees.