The management of personal protective equipment during the COVID-19 pandemic: The case of the province of Quebec.

Like other Canadian provinces, Quebec managed shortages of Personal Protective Equipment (PPE) in the early weeks of the COVID-19 pandemic. Two years later, with hindsight, what lessons can we learn from this logistics crisis? It is precisely to better understand the decisions made by the supply chain players in the province of Quebec that this paper was written. To fully understand the events, this paper first describes the Quebec healthcare system. Then it retraces the series of events and actions during the first wave, at a time when it was most challenging to procure PPE. It also specifies the main characteristics of the supply chain in the Quebec healthcare sector. Finally, it analyzed these data to come up with recommendations to help public decision makers adopt better supply chain management practices.

Fostering Innovation through Procurement in the Healthcare Sector: The Danish Experience.

Healthcare institutions have been searching for ways to increase the value they deliver to patients and to society. Innovation is an effective way to boost this value, and procurement strategies are key to bringing innovation into healthcare organizations. However, hospitals are one of the most challenging organizations to implement innovations. Thus, this research highlights some lessons learned and the best practices of a healthcare organization in Denmark that has successfully implemented the value-based procurement approach.

miRNA contents of cerebrospinal fluid extracellular vesicles in glioblastoma patients.

Analysis of extracellular vesicles (EVs) derived from plasma or cerebrospinal fluid (CSF) has emerged as a promising biomarker platform for therapeutic monitoring in glioblastoma patients. However, the contents of the various subpopulations of EVs in these clinical specimens remain poorly defined. Here we characterize the relative abundance of miRNA species in EVs derived from the serum and cerebrospinal fluid of glioblastoma patients. EVs were isolated from glioblastoma cell lines as well as the plasma and CSF of glioblastoma patients. The microvesicle subpopulation was isolated by pelleting at 10,000×g for 30 min after cellular debris was cleared by a 2000×g (20 min) spin. The exosome subpopulation was isolated by pelleting the microvesicle supernatant at 120,000×g (120 min). qRT-PCR was performed to examine the distribution of miR-21, miR-103, miR-24, and miR-125. Global miRNA profiling was performed in select glioblastoma CSF samples. In plasma and cell line derived EVs, the relative abundance of miRNAs in exosome and microvesicles were highly variable. In some specimens, the majority of the miRNA species were found in exosomes while in other, they were found in microvesicles. In contrast, CSF exosomes were enriched for miRNAs relative to CSF microvesicles. In CSF, there is an average of one molecule of miRNA per 150-25,000 EVs. Most EVs derived from clinical biofluids are devoid of miRNA content. The relative distribution of miRNA species in plasma exosomes or microvesicles is unpredictable. In contrast, CSF exosomes are the major EV compartment that harbor miRNAs.

Lessons learned from the pandemic: expanding the collaboration between clinical and logistics activities in a hospital.

PURPOSE: The Covid-19 pandemic generated significant changes in the operating methods of hospital logistics departments. The objective of this research is to understand how these changes took place, what collaboration mechanisms were developed with clinical authorities and, to what extent, logistics and clinical care activities should be decoupled to maximize each area's contribution? DESIGN/METHODOLOGY/APPROACH: The case study is selected to investigate practices implemented during the COVID-19 pandemic in hospitals in Canada. The pandemic presented an opportunity to contrast practices implemented in response to this crisis with those historically used in this environment. FINDINGS: The strategy of decoupling logistical tasks of an operational nature from clinical activities is well-founded and helps free clinical staff from tasks for which they are not trained. However, the decoupling of operational tasks should be combined with an integration of the clinical information flow to the logistics hub players. With this clinical information, the logistics hub can generate its full potential enabling better inventory management decisions to be made. ORIGINALITY/VALUE: The concept of decoupling is studied to identify configurations that offer the best benefits for clinical staff.

Impact of hemochromatosis gene (HFE) mutations on epithelial ovarian cancer risk and prognosis.

Cancer cells require large amounts of micronutrients, particularly iron, for their rapid growth and frequent divisions. Cellular iron uptake is regulated by the transferrin receptor and the hemochromatosis protein (HFE) system. Two frequent mutations in the HFE gene, H63D and C282Y, are associated with hemochromatosis type I, an inherited iron overload disease and, possibly, with cancer. In this study, we evaluated the frequency of the H63D and C282Y mutations in a cohort of 677 consecutive cases of woman with gynecological pathologies. Cases included 80 women with tumor-free pathologies normal ovary (NOV), 124 with benign ovarian tumors (BOV), 96 with epithelial ovarian cancer (EOC) tumors of low malignant potential (LPM), 264 with invasive tumors of the ovary (TOV) and 113 with endometrial cancer. We found that the C282Y allele frequency in EOC patients was higher than that in the control NOV group (5.8% vs. 1.3%, p < 0.001) and was associated with an increased risk of ovarian cancer (OR = 4.88; 95% CI 1.15-20.61; p = 0.018). The effect of the two HFE mutations on patient survival was also analyzed. Kaplan-Meier analyses did not find any significant association between the H63D allele and patient survival. However, EOC patients with at least one C282Y allele had a decreased overall survival compared to those with no C282Y allele (p = 0.001). These results indicate that the C282Y mutation may increase the risk of developing ovarian cancer and may be further associated with poor outcomes.

Description of two new ABCB11 mutations responsible for type 2 benign recurrent intrahepatic cholestasis in a French-Canadian family.

Benign recurrent intrahepatic cholestasis is a rare clinical entity that is caused by mutations in the canalicular transport genes. The present report describes two individuals from the same family whose symptoms were typical of the clinical characteristics of type 2 benign recurrent intrahepatic cholestasis. Sequencing of the ABCB11 gene revealed two previously unreported mutations that predict the absence of expression of the protein. The clinical presentation of the current cases are discussed, as are the differential diagnosis and genetic characteristics of the hereditary cholestatic disorders, overemphasizing the possibility of making a definite genetic diagnosis.

Evolution of high-sensitivity troponin-T and echocardiography parameters in patients undergoing high efficiency on-line hemodiafiltration versus conventional low-flux hemodialysis.

BACKGROUND AND OBJECTIVES: On-line hemodiafiltration (HDF) has been associated with better inflammatory markers profile and survival than low-flux hemodialysis (HD). This study aimed at determining the effect of HDF vs HD on hs-TnT and echocardiography parameters evolution at one year follow-up. METHOD: Patients were randomized from 2007 to 2013 to HD or HDF in accordance with the CONvective TRAnsport STudy protocol initially as part of the Montreal cohort and subsequently as part of a local cohort. Pre-dialysis hs-TnT were analyzed at baseline and 1-year follow-up. RESULTS: A total of 54 HDF patients and 59 HD patients were included. At baseline, median hs-TnT value was 49 ng/L (IQR 31-89) in the HDF group vs. 60 ng/L (36-96) in the HD group (p = 0.370). At one year follow-up, median hs-TnT remained stable in the HDF group (p = 0.707 vs. baseline), but significantly increased to 62 ng/L (40-104) in the HD group (p = 0.021 vs. baseline). The median variation (delta) in hs-TnT values was -3 ng/L (IQR -7-+8) in the HDF group vs. +8 ng/L (-5 -+25) in the HD group (p = 0.042). In the HDF group, LVEF increased from 60.0% (IQR 55.0-65.0) at baseline to 65.0% (60.0-65.5) at 1-year follow-up (p = 0.040) whereas it remained stable in the HD group (LVEF of 60.0% [IQR 55.0-65.0] at baseline and 65.0% [55.0-65.0] at 1-year follow-up [p = 0.312]). CONCLUSIONS: High-efficiency HDF is associated with stability in hs-TnT values, whereas low-flux HD is associated with significant increase in hs-TnT levels.

Use of phosphoproteomics to study tyrosine kinase activity in capacitating boar sperm. Kinase activity and capacitation.

It is generally accepted that sperm capacitation is associated with the protein kinase A-mediated appearance of tyrosine phosphoproteins, although the substrates and kinase(s) involved have not been identified. We described a Mr 32,000 tyrosine phosphoprotein, "p32", appearing in porcine sperm coincident with capacitation. We also discovered a tyrosine kinase-like enzyme in boar sperm of Mr 32,000 ("TK-32") with enhanced activity during capacitation. The present work was conducted to further characterize and to identify these capacitation-related protein(s). Fresh porcine sperm were incubated to induce capacitation then immunoprecipitation, immunoblotting and proteomic analysis revealed seven tyrosine-phosphorylated proteins aligned in the range of Mr 30,000 with different isoelectric pH values (pI). Therefore, p32 may be composed of several tyrosine phosphoproteins. Three were identified as acrosin-binding sp32 (pI 6.5), and two triosephosphate isomerase isoforms (pI 7.1 and 7.9). At present, however, proteonomic analysis has not revealed any kinase at Mr 32,000. Immunoprecipitation experiments show that p32 and TK-32 are different molecules, as TK-32 activity remains in the supernatant of the antiphosphotyrosine precipitates. Finally, in-gel renaturation and immunoblotting suggest that TK-32 is a mitogen-activated protein kinase (MAPK). The discovery of p32 and the MAPK-like TK-32 provides new insight regarding the mechanisms underlying capacitation in the pig.

Role of seaweed laminaran from Saccharina longicruris on matrix deposition during dermal tissue-engineered production.

Our laboratory has developed a technique to reconstruct in vitro tissue from human cells using the self-assembly tissue-engineering method, which utilizes the ability of fibroblasts to deposit the matrix they secrete. The time necessary for tissue construction, several weeks, is a drawback for many clinical uses. We hypothesized that the addition of laminaran can increase the deposition of matrix, speeding up the production of the tissue. Laminaran was isolated from the brown seaweed Saccharina longicruris harvested in Canada and its structure was evaluated. Laminaran is a small molecular weight polysaccharide composed of linear glucose chains. Monolayer-cultured human skin fibroblasts were cultured in the presence of laminaran with ascorbate for 7 or 35 days to produce a dermis. Treatment did not induce any variation in the growth rate or alpha smooth muscle actin content but it did increase the deposition of collagen I in a dose-dependent manner. After 35 days, the reconstructed dermal thickness was increased when laminaran was added, and collagen I deposition and MMP activity were also significantly increased. Thus, laminaran can be used to increase the rate of production of reconstructed self-assembled dermis and can also potentially be used in cosmetic or therapeutic creams to stimulate matrix production.

Boar sperm storage capacity of BTS and Androhep Plus: viability, motility, capacitation, and tyrosine phosphorylation.

Androhep Plus, a long-term extender (up to 7 days) and Beltsville Thawing Solution (BTS), a short-term extender (up to 3 days), are commonly used for liquid storage of porcine semen. To test the hypothesis that modifications in sperm viability, motility, chlortetracycline (CTC) fluorescence patterns, and protein tyrosine phosphorylation occur during semen storage in extenders, we compared these end points at different periods of storage in either Androhep Plus or BTS. Sperm from five boars were assessed daily over 12 days of storage (n = 5 ejaculates from different boars). Viability was not different (P < 0.05 between extenders, except on Day 2, when Androhep Plus maintained better viability. Differences in the percentage of motile (total) sperm due to extender were evident on Days 2, 4, 5, and 6, when Androhep Plus was superior to BTS (P < 0.05). The percentages of progressively motile sperm also differed, with Androhep Plus supporting higher rates on Days 2, 4, 5, 7, 8, 9, 10, and 11 (P < 0.05). The CTC fluorescence pattern distribution differed due to extender as early as Day 2; storage in Androhep Plus induced higher levels of pattern B sperm (P < 0.05) than storage in BTS. A tyrosine-phosphorylated protein of Mr 21,000 appeared after 10 days in sperm incubated in BTS, and was identified as a phospholipid hydroperoxide glutathione peroxidase. Therefore, modifications in viability, motility, CTC fluorescence patterns, and sperm protein tyrosine phosphorylation were apparent during sperm storage in extenders; these may affect the fertilizing capacity of the semen.

The immunopotentiating effects of shark-derived protein hydrolysate.

OBJECTIVE: Peptides derived from natural sources can act as immunomodulating agents and prevent infections. The aim of this study was to investigate the immunopotentiating and protective effects of a shark-derived protein hydrolysate (SPH) against an enterotoxigenic Escherichia coli H10407 infection in a murine model. METHODS: Mice were fed an aqueous solution of SPH for 7 days before being inoculated with an experimental enterotoxigenic Escherichia coli H10407 infection. After euthanasia, small intestines were removed for histological study and the number of IgA and IgG producing cells was determined by direct immunofluorescence. Cytokines were measured in the serum and the intestinal fluid. RESULTS: The oral administration of SPH enhanced the gut barrier function via up-regulation of immunoglobulin A-producing cells and intestinal cytokines production, including interleukin-6 and tumor necrosis factor-α. The increase of transforming growth factor-ß and interleukin-10 contribute to the down-regulation of uncontrolled-inflammatory reaction induced by E. coli infection. From these results, the anti-inflammatory properties of SPH may be caused by regulation and priming mechanisms of the immune system. CONCLUSION: Enzymatic protein degradation confers immunomodulating and protective potentials to shark proteins and the resulted peptides could be used as an alternative therapy to reduce the risk of bacterial infections and inflammatory-related diseases.

Structural characterization of laminaran and galactofucan extracted from the brown seaweed Saccharina longicruris.

Brown seaweed contains several polysaccharides like laminaran, fucoidan and alginate. Laminaran is a beta-glucan that has shown anti-apoptotic and anti-tumoral activities, while galactofucan (fucoidan) is a sulfated polysaccharide that has displayed anticoagulant, anti-tumor, anti-thrombosis, anti-inflammatory and antiviral properties. In this study, crude laminaran and galactofucan (fucoidan) were extracted from the brown seaweed Saccharina longicruris at four harvest periods (M05, A05, N05 and J06). The galactofucan M05 and N05 fractions were depolymerized (RDP) over 2 or 4h to give 4 RDP fractions (M05 RDP 2H, M05 RDP 4H, N05 RDP 2H and N05 RDP 4H) whose molecular weights, monosaccharide compositions and glycosidic linkages were determined by GC-MS. The laminaran fraction gave a molecular weight range from 2900 to 3300 Da and contained between 50.6% and 68.6% d-glucose and an average of 1.3% D-mannitol. The presence of a beta-(1,3) linkage between D-glucose in the main chain was observed, with branching at positions 6 and 2. The M05 fraction contained less branching than other laminaran fractions, which might have influenced its conformation in solution and thus its activity. The crude galactofucan fractions displayed a molecular weight range from 638 to 1529 kDa, whereas the RDP fractions had molecular weights <30 kDa. The structure of the galactofucan fractions remained complex after depolymerization, with these also being more sulfated (30-39%) than the crude fractions (13-20%). The crude and RDP fractions contained 3-linked fucopyranose 4-sulfate and 6-linked galactopyranose 3-sulfate moieties, although the galactofucans isolated from M05 and J06 contained less 6-linked galactopyranose 3-sulfate than the A05 and N05 fractions.

Analytical performance of a qRT-PCR assay to detect guanylyl cyclase C in FFPE lymph nodes of patients with colon cancer.

Up to 30% of patients with stage II (pN0) colon cancer develop recurrences, suggesting that the presence of lymph node (LN) metastases escaped detection at histopathologic staging. A simple way to overcome this limitation and to improve staging accuracy is to use reverse transcription-polymerase chain reaction (RT-PCR) to examine a larger fraction or an entire specimen. The Guanylyl cyclase C (GCC) gene is uniquely expressed in apical cells of the gastrointestinal tract. Its expression in colon cancer cells and metastases is conserved. Therefore, detection of GCC mRNA in LNs has been shown to be indicative of the presence of colon cancer metastases. As the current processing of LNs involves formalin fixation and paraffin embedding, we developed a method for extracting RNA from formalin-fixed paraffin-embedded LN specimens and detecting GCC mRNA by quantitative RT-PCR. The assay has a dynamic range of 5 logs, an average amplification efficiency of 98.4% (95% confidence interval, 96.6-100.3), a reaction linearity of 0.998 (95% confidence interval, 0.997-0.999), and also intraplate and interplate CVs of <1% and <5%, respectively. The test specificity was 98% with LNs collected from patients affected by conditions other than colon cancer (n=380). Sensitivity was 97% for patients with stage III colon cancer (n=34), whereas 35% of patients with stages I and II disease (n=51) had at least 1 GCC mRNA-positive LN. The high specificity of GCC mRNA suggests that routine utilization of the quantitative RT-PCR test has the potential to improve the detection of colon cancer metastases in LNs.

Effect of season on the composition of bioactive polysaccharides from the brown seaweed Saccharina longicruris.

The structural features of laminarans and galactofucans extracted from the brown seaweed Saccharina longicruris were determined for four harvest periods (M05, A05, N05 and J06). Crude laminarans were purified and crude galactofucans were fractionated using DEAE Sepharose anion exchange chromatography with increasing levels of NaCl (0.5, 1 and 2 M). The results showed differences in terms of their monosaccharide compositions. Purified laminaran contained a high proportion of D-glucose, between 45.1% and 69.1%, with a higher amount in M05 and A05, while the amount of D-mannitol remained constant (less than 1.7%). Crude galactofucans from M05, A05, and N05 contained 19.9-21.5% of sulphates, where J06 had only 14.3%. The 2 M fractionated galactofucans contained a higher proportion of sulphate groups, from 27.1% to 36.9%, for each harvest period, while the 1 M fraction contained 9.2% to 15.9% of sulphates. An important variation in the amount of L-fucose and D-galactose was observed for crude and fractionated galactofucans. In M05, a higher content of L-fucose was observed for crude galactofucans compared to that observed for D-galactose (21.5% vs. 11.1%), whereas the opposite was found for A05 (18.5% vs. 36.6%), N05 (20.9% vs. 36.8%), and J06 (12.8% vs. 19.6%). Also, the 0.5 and 2 M fractions were similar to the crude galactofucans. A05, N05, and J06 contained lower amounts of L-fucose than D-galactose, while the M05 fractions showed the opposite behaviour. However, the 1 M fraction showed a higher amount of L-fucose than D-galactose for each harvest period. The next step will be to study the biological activity of the fractions and to attempt to relate this activity to the structure of the galactofucan and laminaran fractions.