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Chronic myelomonocytic leukemia (CMML) is a severe myeloid malignancy with limited therapeutic options. Single-cell analysis of clonal architecture demonstrates early clonal dominance with few residual WT hematopoietic stem cells. Circulating myeloid cells of the leukemic clone and the cytokines they produce generate a deleterious inflammatory climate. Our hypothesis is that therapeutic control of the inflammatory component in CMML could contribute to stepping down disease progression. The present study explored the contribution of immature granulocytes (iGRANs) to CMML progression. iGRANs were detected and quantified in the peripheral blood of patients by spectral and conventional flow cytometry. Their accumulation was a potent and independent poor prognostic factor. These cells belong to the leukemic clone and behaved as myeloid-derived suppressor cells. Bulk and single-cell RNA-Seq revealed a proinflammatory status of iGRAN that secreted multiple cytokines of which CXCL8 was at the highest level. This cytokine inhibited the proliferation of WT but not CMML hematopoietic stem and progenitor cells (HSPCs) in which CXCL8 receptors were downregulated. CXCL8 receptor inhibitors and CXCL8 blockade restored WT HSPC proliferation, suggesting that relieving CXCL8 selective pressure on WT HSPCs is a potential strategy to slow CMML progression and restore some healthy hematopoiesis., Introduction Chronic myelomonocytic leukemia (CMML) is a myeloid malignancy defined by overlapping features of both myeloproliferative and myelodysplastic neoplasms (1). CMML diagnosis is based on sustained absolute and relative peripheral [...]

Some studies suggest that narcissism, either grandiose, vulnerable, or normal, is empirically associated with healthy or pathological concern towards others. These relationships remain poorly documented, and existing research only offers theoretical rationales as to the nature of the narcissism-concern association. The present study aims to assess the relationships between the various types of narcissism and concern while including the mediating role of explicit motives. French-speaking adults (n = 213) completed self-report questionnaires measuring these constructs. Results of mediation analyses suggest that specific motives mediate the positive associations observed between vulnerable or grandiose narcissism and pathological concern as well as the negative associations observed between grandiose or normal narcissism and healthy concern. Thus, it seems that pathological concern could be used as a maladaptive self-regulation mechanism by both forms of pathological narcissism. Fear motives mediate both relationships, suggesting avoidance as the main drive behind pathological concern in pathological narcissism. Also, the negative association between normal narcissism and healthy concern is coherent with the antagonistic interpersonal style of this form of narcissism. Results add to the practical knowledge of narcissism through a better understanding of the factors involved in self-regulation mechanisms., Author(s): Arnaud Lapierre-Bédard [sup.1] , Zachary Rancourt-Tremblay [sup.1] , Jacob-Alexandre Marineau Painchaud [sup.1] , Maxime Allard [sup.1] , Jean Descôteaux [sup.1] Author Affiliations: (1) grid.86715.3d, 0000 0000 9064 6198, Department [...]

In the 18th century, Carolus Linnaeus created a formalized system of classification of living organisms based on their anatomic relationships, which we know as taxonomic nomenclature. Historically, the genus Cannabis has been described three ways under this system: Cannabis sativa by C. Linnaeus in 1753, Cannabis indica by J.B. Lamarck in 1785, and Cannabis ruderalis by D.E. Janischewsky in 1924, with these taxonomic classifications having been derived from physical, morphological, chemical, and geographical data. Today, this confusing taxonomy has led to an ongoing debate about whether the genus Cannabis consists of a single species or multiple distinct species or subspecies. Recently, genome sequencing and bioinformatics have provided greater resolution of taxonomic assignments at the species level. As a result, some previously discussed classification frameworks have been brought into question. The aim of this review is to provide a historical context for the confusion surrounding the taxonomy of the genus Cannabis and highlight recent research on genomics-based taxonomical approaches to clarify the question of Cannabis taxonomy. We suggest that the latest evidence shifts away from the previous multiple species framework and points towards the genus Cannabis consisting of a highly diverse monotypic species. Key words: cannabis, taxonomy, genomics, phylogeny, population structure, 1. Introduction Cannabis sativa L. has a long history of human use for a variety of applications, including fiber, food, medicine, and for its psychoactive properties (Kalant 2001). Cannabis was [...]

In 2020, the World Health Organization estimated that in Madagascar there were 238 cases of Mycobacterium tuberculosis complex infection per 100,000 persons, but fewer than half of infected persons were [...]

Melanomas reprogram their metabolism to rapidly adapt to therapy-induced stress conditions, allowing them to persist and ultimately develop resistance. We report that a subpopulation of melanoma cells tolerate MAPK pathway inhibitors (MAPKis) through a concerted metabolic reprogramming mediated by peroxisomes and UDP-glucose ceramide glycosyltransferase (UGCG). Compromising peroxisome biogenesis, by repressing PEX3 expression, potentiated the proapoptotic effects of MAPKis via an induction of ceramides, an effect limited by UGCG-mediated ceramide metabolism. Cotargeting PEX3 and UGCG selectively eliminated a subset of metabolically active, drug-tolerant [CD36.sup.+] melanoma persister cells, thereby sensitizing melanoma to MAPKis and delaying resistance. Increased levels of peroxisomal genes and UGCG were found in patient-derived MAPKi-relapsed melanomas, and simultaneously inhibiting PEX3 and UGCG restored MAPKi sensitivity in multiple models of therapy resistance. Finally, combination therapy consisting of a newly identified inhibitor of the PEX3PEX19 interaction, a UGCG inhibitor, and MAPKis demonstrated potent antitumor activity in preclinical melanoma models, thus representing a promising approach for melanoma treatment., Introduction Melanoma is the deadliest form of skin cancer. Current treatments for patients with metastatic melanoma include therapies that target the MAPK pathway (BRAF and MEK inhibitors) and immunotherapies targeting [...]

The Mycobacterium tuberculosis complex (MTBC) comprises multiple species, divided into humanadapted (M. tuberculosis and M. africanum) and animal-adapted (M. bovis, M. orygis, M. caprae, and others) tuberculosis (TB) lineages (1); [...]

The purpose of this paper is to present the results of a study that draws upon a collaborative research strategy and has two main objectives: 1) Translating and adapting into French the Measure of Victim Empowerment Related to Safety (MOVERS scale) (Goodman et al. Psychology of Violence, 5(4), 355-366, 2015a (See CR21)); 2) Validating the French version of the MOVERS scale in a population of French-Canadian women receiving shelter services. The French-Canadian MOVERS (FCM) was administered to 189 women receiving shelter services in the province of Québec (Canada). The factorial structure, reliability and validity of the FCM were tested. This paper highlights that the FCM replicates the three dimensions found in the original version (Goodman et al. Psychology of Violence, 5(4), 355-366, 2015a (See CR21)), displays significant correlations with measures of depression, anxiety and stress, self-esteem, perceived social support, satisfaction with life and self-efficacy, and has overall good reliability estimates. The FCM is a valid and reliable scale to assess safety-related empowerment among women receiving shelter services. Furthermore, the scale provides interesting opportunities to shelter workers, which will be discussed in the paper., Author(s): Isabelle Côté [sup.1] , Joël Gagnon [sup.2] , Simon Lapierre [sup.3] , Dominique Damant [sup.4] , Stéphanie Louis Jean Esprival [sup.1] , Lisa A. Goodman [sup.5] Author Affiliations: (1) [...]

Context: Providing context-specific information and fostering reflective practice is essential to support a learning health system. Regional health boards in Quebec, Canada, have the responsibility to ensure implementation of the Quebec Alzheimer's Plan (QAP) in primary, secondary, and tertiary care services but need support. As such, we have developed and disseminated regional portraits on dementia care. Objective: To describe the lesson learned and next steps on the development and presentations of regional portraits. Design: A multi-methods study with a participatory approach. Setting: Quebec, Canada. Population: Stakeholders (ministerial decision-maker and project managers, managers and clinicians from the 23 regional health board, and researchers/scientific advisors). Methods: We selected, with stakeholders, 9 indicators (prevalence, regular physician visits, emergency visits, and hospitalizations) and measured them in 2019-20. Also, we thematically analysed the last 3 years of ongoing QAP implementation evaluation reports and meetings. We combined these results to formulate, with stakeholders, key messages for each regional health board. Along with ministerial decision-maker and project managers, we presented these portraits to regional managers and clinicians. Real-time notes were taken using structured observation guide. A thematic analysis was performed. Results: The development of the portraits was facilitated by a strong and ongoing alliance between the stakeholders. Researchers and scientific advisors identified the most relevant data available; project managers ensured the formulated messages were meaningful to regional managers and clinicians; and policymakers ensured the collected data was useful to support the implementation of QAP. The regional managers and clinicians proposed ways to improve the portraits (i.e., adding indicators), and to regularly update and integrate these portraits into steering committees. Monitoring the indicators as precisely presents challenges, including regularly obtaining current data. Conclusion: This innovative project supports a learning health system for the care of persons with dementia. Specifically, it stimulates the emergence of regional and provincial innovations in dementia care to accomplish the implementation of the QAP, ensure its local appropriation and perpetuates sustainable transformed practices. Proposed solutions will guide the preparation of next iteration of regional portraits., Presenters Genevieve Arsenault-Lapierre, PhD, Maxime Guillette, Alexandra Lemay-Compagnat, Louis Rochette, MSc, Victoria Massamba, MPH, Yves Couturier, PhD, Eric Maubert, Christine Fournier, Caroline Morin, Caroline Boudreau, Isabelle Vedel, MD, [...]

Rabies has been endemic to the eastern United States in raccoons (Procyon lotor) since 1960 and endemic to New York, USA, since the 1990s (1). The spread of rabies virus [...]

Paucity of the survival motor neuron (SMN) protein triggers the oft-fatal infantile-onset motor neuron disorder, spinal muscular atrophy (SMA). Augmenting the protein is one means of treating SMA and recently led to FDA approval of an intrathecally delivered SMN-enhancing oligonucleotide currently in use. Notwithstanding the advent of this and other therapies for SMA, it is unclear whether the paralysis associated with the disease derives solely from dysfunctional motor neurons that may be efficiently targeted by restricted delivery of SMN-enhancing agents to the nervous system, or stems from broader defects of the motor unit, arguing for systemic SMN repletion. We investigated the disease-contributing effects of low SMN in one relevant peripheral organ--skeletal muscle--by selectively depleting the protein in only this tissue. We found that muscle deprived of SMN was profoundly damaged. Although a disease phenotype was not immediately obvious, persistent low levels of the protein eventually resulted in muscle fiber defects, neuromuscular junction abnormalities, compromised motor performance, and premature death. Importantly, restoring SMN after the onset of muscle pathology reversed disease. Our results provide the most compelling evidence yet for a direct contributing role of muscle in SMA and argue that an optimal therapy for the disease must be designed to treat this aspect of the dysfunctional motor unit., Introduction Homozygous mutations in the survival of motor neuron 1 (SMN1) gene result in reduced levels of the SMN protein and trigger the infantile-onset neuromuscular disease, spinal muscular atrophy (SMA) [...]

Background High consumption of low- and non-fat dairy products improves vascular dysfunction associated with elevated arterial blood pressure (BP). Currently, it is unknown if conventional full-fat dairy products improve vascular functions. Objectives To determine if adding whole milk and full-fat dairy products to the normal routine diet improves vascular function in adults with elevated BP. Design Sixty adults (age [plus or minus] SEM; 58 [plus or minus] 2 years) with elevated BP (systolic/diastolic; 120-159/ < 99 mmHg) were randomized into a controlled crossover intervention trial consisting of two 4-week dietary periods. The high dairy condition consisted of adding four daily servings of whole milk or full-fat dairy products to the normal diet and eliminated all dairy intake during the control (no dairy) condition. A 2-week washout period separated the dietary conditions. Results Carotid-femoral pulse wave velocity (cfPWV) did not differ significantly between high dairy (11.3 [plus or minus] 0.3 versus 10.9 [plus or minus] 0.3 m/sec) and no dairy conditions (11.2 [plus or minus] 0.3 versus 11.0 [plus or minus] 0.3 m/sec). The results were consistent when ultrasound-derived vascular distension measures (arterial compliance, beta-stiffness index, and elastic modulus) were evaluated. Cardiovagal baroreceptor sensitivity (via Valsalva maneuver) demonstrated no significant difference for either dietary condition. Brachial arterial flow-mediated dilation (FMD) did not differ significantly during the high dairy (5.7 [plus or minus] 0.5 versus 5.4 [plus or minus] 0.6%) and no dairy conditions (6.5 [plus or minus] 0.5 versus 5.6 [plus or minus] 0.6%). Conclusions The solitary addition of whole milk and full-fat dairy products has no effect on subclinical vascular function in adults with elevated BP., Author(s): Stephen J. Roy [sup.1] , Brandon G. Fico [sup.1] , Brett D. Baker [sup.1] , Stephanie S. Lapierre [sup.1] , Jay A. Shah [sup.1] , Drew D. Gourley [sup.1] [...]

Interactions between parasite species may influence their distribution and abundance within communities. Experimental single-species infections of Diplostomum spp. in the gut of the definitive host, the Ringed-billed Gull (Larus delawarensis Ord, 1815), were compared with mixed-species infections to explore interactions among parasites. Three species of Diplostomum von Nordmann, 1832 (Digenea), designated as Diplostomum sp. 1, Diplostomum sp. 4, and Diplostomum baeri Dubois, 1937, were examined for intestinal distribution and fecundity in single and mixed infections. In single-species infections, most specimens of Diplostomum sp. 1 and D. baeri were recovered from the mid-region of the intestine, whereas Diplostomum sp. 4 were mainly present in the anterior region. Significant spatial displacement was observed only for D. baeri when Diplostomum sp. 1 was also present. Intensity was directly correlated to the number of occupied intestinal segments, and there was no significant difference in mean linear span for each species between single-species and mixed-species infections. Diplostomum sp. 4 had the highest mean number of eggs per worm in utero in single-species infections. In mixed-species infections, the fecundity of Diplostomum sp. 4 declined dramatically in the presence of Diplostomum sp. 1, whereas fecundity of Diplostomum sp. 1 increased in the presence of D. baeri. These results highlight interspecific interactions that may play a role in population dynamics of Diplostomum spp. and community structure. Key words: Diplostomum, Ring-billed Gull, Larus delawarensis, fecundity, intestinal distribution, mixed infections, linear span. Les interactions entre especes de parasites peuvent influencer leur repartition et leur abondance au sein de communautes. Des infections experimentales a une seule espece de Diplostomum spp. dans le tube digestif d'hotes definitifs, des goelands a bec cercle (Larus delawarensis Ord, 1815), ont ete comparees a des infections mixtes a plus d'une espece afin d'explorer les interactions de parasites. Trois especes de Diplostomum von Nordmann, 1832 (digeniens), designees Diplostomum sp. 1, Diplostomum sp.4et Diplostomum baeri Dubois, 1937, ont ete examinees pour determiner les perturbations intestinales qu'elles causent et leur fecondite dans des infections a une seule espece et des infections mixtes. Dans les infections a une seule espece, la plupart des specimens de Diplostomum sp.1etD. baeri ont ete recuperes de la region moyenne de l'intestin, alors que les Diplostomum sp. 4 etaient principalement presents dans la region anterieure. Un deplacement spatial significatif n'a ete observe que pour D. baeri quand Diplostomum sp. 1 etait egalement present. L'intensite etait directement correlee au nombre de segments intestinaux occupes, et il n'y avait pas de difference significative de l'etendue lineaire moyenne de chaque espece entre les infections a une seule espece et les infections mixtes. Diplostomum sp. 4 presentait le nombre moyen d'ceufs in utero par ver le plus eleve dans les infections a une seule espece. Dans les infections mixtes, Diplostomum sp. 4 montrait une baisse drastique de fecondite en presence de Diplostomum sp. 1, alors que la fecondite de Diplostomum sp. 1 augmentait dans les infections mixtes avec D. baeri. Ces resultats font ressortir des interactions entre especes qui pourraient jouer un role dans la dynamique des populations de Diplostomum spp. et la structure de leurs communautes. [Traduit par la Redaction] Mots-cles: Diplostomum, goeland a bec cercle, Larus delawarensis, fecondite, repartition intestinale, infections mixtes, etendue lineaire., Introduction A parasite's niche, its physical distribution and ecological role, is dependent on many different factors such as the presence of other species of parasites and potential interactions among them. [...]

Tuberculosis (TB) is an ancient disease affecting a plethora of domestic and wild animals, including humans. In primates, TB can cause severe multisystemic disease. The prevalence of TB in lemurs [...]