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The same heterozygous T [approaches] C transition at nt 8567 of the von Willebrand factor (vWF) transcript was found in two unrelated patients with type IID von Willebrand disease, with no other apparent abnormality. In one family, both alleles were normal in the parents and one sister; thus, the mutation originated de novo in the proposita. The second patient also had asymptomatic parents who, however, were not available for study. The structural consequences of the identified mutation, resulting in the Cys2010 [approaches] Arg substitution, were evaluated by expression of the vWF carboxyl-terminal domain containing residues 1366-2050. Insect cells infected with recombinant baculovirus expressing normal vWF sequence secreted a disulfide linked dimeric molecule with an apparent molecular mass of 150 kDa before reduction, yielding a single band of 80 kDa after disulfide bond reduction. In contrast, cells expressing the mutant fragment secreted a monomeric molecule of apparent molecular mass of 80 kDa, which remained unchanged after reduction. We conclude that Cys2010 is essential for normal dimerization of vWF subunits through disulfide bonding of carboxyl-terminal domains and that a heterozygous mutation in the corresponding codon is responsible for defective multimer formation in type IID von Willebrand disease.

Aims The aim of this study was to compare the performance of four RT-q PCR assays for the detection of human and bovine group A rotaviruses and to characterize the positive samples by sequence analysis of VP4 and VP7 genes. Methods and Results RNA extracted from eight human rotavirus strains, and a panel of 33 human and 25 bovine faecal samples was subjected to different RT-q PCR detection systems. Among these assays, only RT-q PCR primers and probe systems B and C were able to detect all human rotavirus strains from cell culture solutions and faecal samples. However, the results showed that the system C was generally more sensitive by one or two logs than the other RT-q PCR assays tested. With the bovine faecal samples, the most efficient RT-q PCR systems were B and A with the detection in 100 and 92% of samples tested, respectively. Human group A rotavirus G1 P[8] and bovine G6 P[11] were the most frequently used strains identified in this study. A G3 P[9] strain, closely related to a feline rotavirus isolated in the USA, was also discovered in a human rotavirus infection. Conclusion The RT-q PCR system B was the only Taq Man assay evaluated in this study able to detect rotavirus RNA in all positive human and bovine faecal samples. Significance and Impact of the Study Utilization of only one RT-q PCR for the detection of human and bovine group A rotaviruses and the possibility of human infection by a feline rotavirus strain. [ABSTRACT FROM AUTHOR]

Objective: To document the use of psychotropic drugs in Quebec older adult population with a depressive or anxiety disorder.Method: Data from the Enquête sur la Santé des Aînés (ESA) study conducted between 2005 and 2008 using a representative sample (n = 1869) of community-dwelling adults aged 65 years and older were used to examine the use of psychotropic drugs in the Quebec older adult population.Results: Our results indicate that only 46.9% of the older adults with a diagnosis of depression or anxiety during the 24-month period studied according to the Régie de l'assurance maladie du Quebec (RAMQ) register used antidepressants (AD) for 400 days (12.9 months) on average during this period. Also, 59% of the RAMQ's mental health disorder patients used a mean daily dose of 5 mg of a diazepam equivalent for 338 days (10.9 months) on average during the same period. However, 10.0% of the older adults without any symptoms (ESA) at T1 and at T2 and any RAMQ depression and anxiety diagnosis between T0 and T2 were AD users during the 24-month period studied. They represent 26.2% of the AD users and consumed them for 494 days (15.9 months) on average during the 24-month period studied. Finally, the number of days of AD and benzodiazepine use was not associated with partial or total remission.Conclusions: This result questions the population effectiveness of these drugs in this population. [ABSTRACT FROM AUTHOR]

Objective: To document the remission and persistence of psychiatric disorders in Quebec's older adult population.Method: Data came from the Enquête sur la santé des aînés (ESA) study conducted in 2005-2008 using a representative sample (n = 2784) of community-dwelling older adults.Results: The ESA study results indicate that 12% of respondents met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for depression, mania, anxiety disorders, or benzodiazepine drug dependency at the baseline interview. The results also indicate that the 12-month rate of patients with a persistent psychiatric condition was 19.4%. Sixty-seven percent of the patients in remission experienced a total recovery of their symptoms during the following year. The probability of presenting a persistent psychiatric condition or a partial remission after 1 year of follow-up, compared with those in total remission, did not vary according to sociodemographic characteristics. The results also showed that social support and the number of chronic health problems did not influence mental health at follow-up. However, results indicated that the use of health services (OR 7.4; 95% CI 3.72 to 14.55) and the change in the number of chronic health problems reported between baseline and the second interview (OR 1.2; 95% CI 1.06 to 1.34) increased the probability of patients with prevalent disorders at Time 1 having persistent disorders at Time 2.Conclusion: Results suggest that a deterioration of physical health status was associated with the persistence of DSM-IV disorders in the elderly. These results also suggest that the use of mental health services is associated with severity of the mental illness. [ABSTRACT FROM AUTHOR]

Objective: To examine the incidence of psychiatric disorders in the Quebec older adult population.Method: Data from the Enquête sur la Santé des Aînés (ESA) study conducted in 2005 to 2008 using a representative sample (n = 2784) of community-dwelling adults aged 65 years and older were used.Results: The ESA study's results indicate that 12.0% of the respondents met the Diagnostic and Statistical Manual of Mental Disorders (DSM), Fourth Edition, criteria for depression, mania, anxiety disorders, or benzodiazepine drug dependency at the baseline interview. Our results also indicate that the 12-month rate of incident cases of DSM-IV disorders was 6.2%. The proportion of incident cases was higher for the depression group (3.4%) than for the anxiety disorders group (2.3%). The results showed that the probability to develop an incident psychiatric condition after 1 year of follow-up, compared with the noncases group, varied according to sex (OR 2.18; 95% CI 1.39 to 3.44). Our results also showed that the number of chronic health problems (OR 1.20; 95% CI 1.09 to 1.33) and the change in the number of chronic health problems reported between the baseline and the second interview (OR 1.14; 95% CI 1.01 to 1.30) increased the probability to be an incident case at Time 2. The results indicated that social support did not influence the probability to develop a psychiatric disorder.Conclusion: These results indicate that sex and physical health status have an impact on the incidence of DSM-IV disorders in the elderly. This finding underscores the need for improved recognition and treatment of psychiatric disorders associated with physical illness in the older population. [ABSTRACT FROM AUTHOR]

We assessed the effect of greenhouse gas-induced climate change, as well as the direct fertilization effect of CO2, on crop yields in Québec, Canada. Our methodology coupled the transient diagnostics of 2 Atmosphere-Ocean General Circulation Models (CGCM1 and HadCM3) to the DSSAT 3.5 crop simulation system to simulate current (1961-1990) and future (2040-2069) crop yields for spring wheat, maize, soybean and potato grown in 8 agricultural regions of Québec. For the future (2040-2069), we predict significant yield increases for soybean, lesser increases for wheat, no significant change for maize, and yield decreases for potato. These yields, especially for soybean, are further increased when incorporating the CO2 fertilization effect, but vary according to the crop, climate scenario and agricultural region. Similar trends have been found in comparable agricultural regions in the Northeastern USA and in Southern Finland. These results are useful for designing appropriate crop and farm management adaptation strategies in response to future climate change. [ABSTRACT FROM AUTHOR]

During winter moose (Alces alces L.) aerial surveys, a crew aboard a fixed-wing aircraft flew plots initially to delineate track networks visible in the snow; immediately following, a crew in a helicopter made counts of annals associated with each track network. Two models that predict helicopter counts of moose, based on observations made only from fixed-wing aircraft, were computed by using eighty-five 60-krn2 plots covered in I980-84 by both types of aircraft. The crude model used the overall ratio aeroplane counts :helicopter counts (0.29) 1:o predict helicopter counts. The elaborate model was composed of three linear regressions that used aeroplane counts and percentage area covered by track networks to predict helicopter counts; the regression differed when aeroplane counts equalled 0, 1-2, or more. The elaborate model produced better predictions than the crude model: using cross-validation for seven recent aerial surveys, mean helicopter counts predicted by the elaborate model departed at worst by 23% from observed mean counts. Visibility bias was estimated with the help of radio-collared moose; 88% (n= 59) of the animals occupied track networks visible from fixed-wing aircraft while 83% of moose within track networks were observed during helicopter searches. Therefore, 73% of the moose were seen during early winter helicopter ,counts over mixed forests of Quebec. All recent surveys produced imprecise density estimates because of inadequate sample size and poor stratification. Double sampling with regression, using elaborate models, is proposed in order Co improve precision of estimates without increasing costs. [ABSTRACT FROM AUTHOR]

Background: The abundance and diversity of intestinal commensal bacteria influence systemic immunity with impact on disease susceptibility and severity. For example, loss of short chain fatty acid (SCFA)-fermenting bacteria in early life (humans and mice) is associated with enhanced type 2 immune responses in peripheral tissues including the lung., Objective: Our goal was to reveal the microbiome-dependent cellular and molecular mechanisms driving enhanced susceptibility to type 2 allergic lung disease., Methods: We used low-dose vancomycin to selectively deplete SCFA-fermenting bacteria in wild-type mice. We then examined the frequency and activation status of innate and adaptive immune cell lineages with and without SCFA supplementation. Finally, we used ILC2-deficient and signal transducer and activator of transcription 6 (STAT6)-deficient transgenic mouse strains to delineate the cellular and cytokine pathways leading to enhanced allergic disease susceptibility., Results: Mice with vancomycin-induced dysbiosis exhibited a 2-fold increase in lung ILC2 primed to produce elevated levels of IL-2, -5, and -13. In addition, upon IL-33 inhalation, mouse lung ILC2 displayed a novel ability to produce high levels of IL-4. These expanded and primed ILC2s drove B1 cell expansion and IL-4-dependent production of IgE that in turn led to exacerbated allergic inflammation. Importantly, these enhanced lung inflammatory phenotypes in mice with vancomycin-induced dysbiosis were reversed by administration of dietary SCFA (specifically butyrate)., Conclusion: SCFAs regulate an ILC2-B1 cell-IgE axis. Early-life administration of vancomycin, an antibiotic known to deplete SCFA-fermenting gut bacteria, primes and amplifies this axis and leads to lifelong enhanced susceptibility to type 2 allergic lung disease., Competing Interests: Disclosure statement Supported by the Canadian AllerGenNetwork Centre of Excellence, Canadian Microbiome Initiative 2 (CMI2) grants MRT-168044 and MRT-168048, and Project Grant PJT-173240 from the Canadian Institutes of Health Research (CIHR) to K.M.M. A.K. was supported by a Natural Sciences and Engineering Research Council of Canada Vanier scholarship. N.N. was supported by a Stem Cell Network summer studentship award. S.C. was supported by a CIHR Vanier scholarship. J.B. was supported by a postdoctoral award from the Michael Smith Foundation of Health Research. Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Therapeutic angiogenesis represents a promising avenue to revascularize the ischemic heart. Its limited success is partly due to our poor understanding of the cardiac stroma, specifically mural cells, and their response to ischemic injury. Here, we combine single-cell and positional transcriptomics to assess the behavior of mural cells within the healing heart. In response to myocardial infarction, mural cells adopt an altered state closely associated with the infarct and retain a distinct lineage from fibroblasts. This response is concurrent with vascular rarefaction and reduced vascular coverage by mural cells. Positional transcriptomics reveals that the infarcted heart is governed by regional-dependent and temporally regulated programs. While the remote zone acts as an important source of pro-angiogenic signals, the infarct zone is accentuated by chronic activation of anti-angiogenic, pro-fibrotic, and inflammatory cues. Together, our work unveils the spatiotemporal programs underlying cardiac repair and establishes an association between vascular deterioration and mural cell dysfunction., (© 2023. The Author(s).)

Introduction: Targeted-immunotherapies such as antibody-drug conjugates (ADC), chimeric antigen receptor (CAR) T cells or bispecific T-cell engagers (eg, BiTE ® ) all aim to improve cancer treatment by directly targeting cancer cells while sparing healthy tissues. Success of these therapies requires tumor antigens that are abundantly expressed and, ideally, tumor specific. The CD34-related stem cell sialomucin, podocalyxin (PODXL), is a promising target as it is overexpressed on a variety of tumor types and its expression is consistently linked to poor prognosis. However, PODXL is also expressed in healthy tissues including kidney podocytes and endothelia. To circumvent this potential pitfall, we developed an antibody, named PODO447, that selectively targets a tumor-associated glycoform of PODXL. This tumor glycoepitope is expressed by 65% of high-grade serous ovarian carcinoma (HGSOC) tumors., Methods: In this study we characterize these PODO447-expressing tumors as a distinct subset of HGSOC using four different patient cohorts that include pre-chemotherapy, post-neoadjuvant chemotherapy (NACT) and relapsing tumors as well as tumors from various peritoneal locations., Results: We find that the PODO447 epitope expression is similar across tumor locations and negligibly impacted by chemotherapy. Invariably, tumors with high levels of the PODO447 epitope lack infiltrating CD8 + T cells and CD20 + B cells/plasma cells, an immune phenotype consistently associated with poor outcome., Discussion: We conclude that the PODO447 glycoepitope is an excellent biomarker of immune "cold" tumors and a candidate for the development of targeted-therapies for these hard-to-treat cancers., Competing Interests: Authors MH, PD, KM and CR hold patents for the PODXL antibodies described in this manuscript including issued US Patents US11090383B2, US11390673B2. KM and CR hold a patent claiming methods for detecting and treating cancer related to podocalyxin US9309323B2. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Brassard, Hughes, Dean, Hernaez, Thornton, Banville, Smazynski, Warren, Zhang, Milne, Gilks, Mes-Masson, Huntsman, Nelson, Roskelley and McNagny.)

There are limited biosecurity measures directed at preventing airborne transmission of viruses in swine. The effectiveness of dust mitigation strategies such as oil sprinkling, to decrease risk of airborne virus transmission are unknown. Metagenomics and qPCR for common fecal viruses were used to hunt for a ubiquitous virus to serve as a proxy when evaluating the efficiency of mitigation strategies against airborne viral infectious agents. Air particles were collected from swine buildings using high-volume air samplers. Extracted DNA and RNA were used to perform specific RT-qPCR and qPCR and analyzed by high-throughput sequencing. Porcine astroviruses group 2 were common (from 10 2 to 10 5 genomic copies per cubic meter of air or gc/m 3 , 93% positivity) while no norovirus genogroup II was recovered from air samples. Porcine torque teno sus virus were detected by qPCR in low concentrations (from 10 1 to 10 2 gc/m 3 , 47% positivity). Among the identified viral families by metagenomics analysis, Herelleviridae, Microviridae, Myoviridae, Podoviridae, and Siphoviridae were dominant. The phage vB_AviM_AVP of Aerococcus was present in all air samples and a newly designed qPCR revealed between 10 1 and 10 5 gc/m 3 among the samples taken for the present study (97% positivity) and banked samples from 5- and 15-year old studies (89% positivity). According to the present study, both the porcine astrovirus group 2 and the phage vB_AviM_AVP of Aerococcus could be proxy for airborne viruses of swine buildings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)