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Recent findings suggest important roles for nuclear organization in gene expression. In contrast, little is known about how nuclear organization contributes to genome stability. Epistasis analysis (E-MAP) using DNA repair factors in yeast indicated a functional relationship between a nuclear pore subcomplex and Slx5/Slx8, a small ubiquitin-like modifier (SUMO)-dependent ubiquitin ligase, which we show physically interact. Real-time imaging and chromatin immunoprecipitation confirmed stable recruitment of damaged DNA to nuclear pores. Relocation required the Nup84 complex and Mec1/Tel1 kinases. Spontaneous gene conversion can be enhanced in a Slx8- and Nup84-dependent manner by tethering donor sites at the nuclear periphery. This suggests that strand breaks are shunted to nuclear pores for a repair pathway controlled by a conserved SUMO-dependent E3 ligase.

Malnutrition and poor health are common among recently resettled refugees and may be differentially associated with pre-migration exposure to refugee camp versus non-camp dwelling. We aimed to investigate the associations of iron deficiency (ID), anemia, and ID anemia (IDA) with pre-migration refugee camp exposure among recently arrived refugees to Canada. To this end, we conducted a retrospective cohort study of 1032 adult refugees who received care between January 1, 2011, and December 31, 2015, within a specialized refugee health clinic in Calgary, Canada. We evaluated the prevalence, severity, and predictors of ID, anemia, and IDA, stratified by sex. Using multivariable logistic regression, we estimated the association of refugee camp exposure with these outcomes, adjusting for age, months in Canada prior to investigations, global region of origin, and parity. Among female refugees, the prevalence of ID, anemia, and IDA was 25% (134/534), 21% (110/534), and 14% (76/534), respectively; among males, 0.8% (4/494), 1.8% (9/494), and 0% (0/494), respectively. Anemia was mild, moderate, and severe in 55% (60/110), 44% (48/110) and 1.8% (2/110) of anemic females. Refugee camp exposure was not associated with ID, anemia, or IDA while age by year (ID OR = 0.96, 95% CI 0.93–0.98; anemia OR = 0.98, 95% CI 0.96–1.00; IDA OR = 0.96, 95% CI 0.94–0.99) and months in Canada prior to investigations (ID OR = 0.85, 95% CI 0.72–1.01; anemia OR = 0.81, 95% CI 0.67–0.97; IDA OR = 0.80, 95% CI 0.64–1.00) were inversely correlated with these outcomes. ID, anemia, and IDA are common among recently arrived refugee women irrespective of refugee camp exposure. Our findings suggest these outcomes likely improve after resettlement; however, given proportionally few refugees are resettled globally, likely millions of refugee women and girls are affected.

The integrity of the genome depends on diverse pathways that regulate DNA metabolism. Defects in these pathways result in genome instability, a hallmark of cancer. Deletion of ELG1 in budding yeast, when combined with hypomorphic alleles of PCNA results in spontaneous DNA damage during S phase that elicits upregulation of ribonucleotide reductase (RNR) activity. Increased RNR activity leads to a dramatic expansion of deoxyribonucleotide (dNTP) pools in G1 that allows cells to synthesize significant fractions of the genome in the presence of hydroxyurea in the subsequent S phase. Consistent with the recognized correlation between dNTP levels and spontaneous mutation, compromising ELG1 and PCNA results in a significant increase in mutation rates. Deletion of distinct genome stability genes RAD54 , RAD55 , and TSA1 also results in increased dNTP levels and mutagenesis, suggesting that this is a general phenomenon. Together, our data point to a vicious circle in which mutations in gatekeeper genes give rise to genomic instability during S phase, inducing expansion of the dNTP pool, which in turn results in high levels of spontaneous mutagenesis. Mild DNA damage checkpoint activation in yeast is sufficient to cause increased nucleotide pools and subsequent mutagenesis, revealing basal levels of replication stress as potential source of genomic instability.

Myeloproliferative neoplasms (MPNs) are a group of chronic hematologic malignancies that lead to morbidity and early mortality due to thrombotic complications and progression to acute leukemia. Clinical and mutational risk factors have been demonstrated to predict outcomes in patients with MPNs and are used commonly to guide therapeutic decisions, including allogenic stem cell transplant, in myelofibrosis. Adolescents and young adults (AYA, age ≤45 years) comprise less than 10% of all MPN patients and have unique clinical and therapeutic considerations. The prevalence and clinical impact of somatic mutations implicated in myeloid disease has not been extensively examined in this population. We conducted a retrospective review of patients evaluated at eight Canadian centers for MPN patients diagnosed at ≤45 years of age. In total, 609 patients were included in the study, with median overall survival of 36.8 years. Diagnosis of prefibrotic or overt PMF is associated with the lowest OS and highest risk of AP/BP transformation. Thrombotic complications (24%), including splanchnic circulation thrombosis (9%), were frequent in the cohort. Mutations in addition to those in JAK2/MPL/CALR are uncommon in the initial disease phase in our AYA population (12%); but our data indicate they may be predictive of transformation to post-ET/PV myelofibrosis.

Myeloproliferative neoplasms (MPNs) are a group of rare clonal disorders of hematopoietic progenitor cells associated with disease-related symptoms, thrombotic events, and risk of transformation to acute myeloid leukemia (Tefferi, 2021). The relative rarity and complexity of care led to the establishment of the MPN program at the Princess Margaret (PM) Cancer Centre. The MPN program utilizes a shared-care model wherein partnering with local hematologists (shared-care partners) ensures that patients have access to an MPN specialist while continuing to receive care close to home (Cheung et al., 2021). The clinical nurse specialist (CNS) role was implemented in late 2016 to support not only the shared-care model, but also to triage new patient referrals, and support consultation and follow-up. Although the CNS roles have been part of the healthcare system since the 1940s, the role and its impact remain unclear at times to the inter-disciplinary team. This paper will describe the process and results from evaluating the CNS role's impact in the MPN program using a multimethod approach. This is part one of two papers; herein the quantitative findings are presented, and part two will discuss the qualitative findings.

Myeloproliferative neoplasms (MPN) are a group of rare clonal disorders of hematopoietic progenitor cells associated with disease- related symptoms, thrombotic events, and risk of transformation to acute myeloid leukemia (Tefferi, 2021). Their relative rarity and complexity of care led to the establishment of the MPN program at the Princess Margaret (PM) Cancer Centre, Toronto, Canada. The MPN program utilizes a shared-care model wherein partnering with local hematologists (shared-care partners) ensures that patients have access to a MPN specialist while continuing to receive care close to home. The clinical nurse specialist (CNS) role was implemented in late 2016 to support not only the shared-care model, but also to triage new patient referrals, and support consultation and follow-up. Although the CNS role has been part of the healthcare system since the 1940s, the role and its impact remain unclear at times to the inter-disciplinary team. This paper describes the process and results in evaluating the CNS role's impact in the MPN program through using a multi-method approach. In this Part II of a series, the focus is on discussing the team and patient care experience with having a CNS as part of the care team.

Les néoplasies myéloprolifératives forment un groupe de troubles clonaux rares des cellules progénitrices hématopoïétiques; elles sont associées à des symptômes propres à la maladie, à des événements thrombotiques et à un risque d’évolution vers la leucémie myéloblastique aiguë (Tefferi, 2021). La relative rareté de cette pathologie ainsi que la complexité des soins ont mené à la création du programme des néoplasies myéloprolifératives du Centre de cancérologie Princess Margaret. Le programme applique un modèle de soins partagés avec des hématologues de la région (qui deviennent partenaires des soins partagés) pour assurer aux patients l’accès à un spécialiste des néoplasies myéloprolifératives tout en continuant de recevoir des soins près de chez eux (Cheung et al., 2021). En place depuis 2016, le rôle d’infirmière clinicienne spécialisée (ICS) a fait son apparition non seulement pour appuyer le modèle de soins partagés, mais aussi pour faciliter le triage des patients nouvellement aiguillés vers le centre, et faciliter les consultations et le suivi. Bien que ce rôle fasse partie du système de santé depuis les années 1940, sa définition et ses avantages demeurent parfois flous pour l’équipe interdisciplinaire. La série d’articles décrit, à l’aide d’une approche multiméthode, le processus et les résultats quantitatifs de l’évaluation des effets du rôle d’ICS sur le programme des néoplasies myéloprolifératives. Cette seconde partie traite de l’expérience des soins que font les patients et les soignants de la présence de l’ICS au sein de l’équipe de professionnels.

Les néoplasies myéloprolifératives forment un groupe de troubles clonaux rares des cellules progénitrices hématopoïétiques; elles sont associées à des symptômes propres à la maladie, à des événements thrombotiques et à un risque d’évolution vers la leucémie myéloblastique aiguë (Tefferi, 2021). La relative rareté de cette pathologie ainsi que la complexité des soins ont mené à la création du programme des néoplasies myéloprolifératives du Centre de cancérologie Princess Margaret. Le programme applique un modèle de soins partagés avec des hématologues de la région (qui deviennent partenaires des soins partagés) pour assurer aux patients l’accès à un spécialiste des néoplasies myéloprolifératives tout en continuant de recevoir des soins près de chez eux (Cheung et al., 2021). En place depuis 2016, le rôle d’infirmière clinicienne spécialisée (ICS) a fait son apparition non seulement pour appuyer le modèle de soins partagés, mais aussi pour faciliter le triage des patients nouvellement aiguillés vers le centre, et faciliter les consultations et le suivi. Bien que ce rôle fasse partie du système de santé depuis les années 1940, sa définition et ses avantages demeurent parfois flous pour l’équipe interdisciplinaire. Le présent article (premier d’une série de deux) décrit, à l’aide d’une approche multiméthode, le processus et les résultats quantitatifs de l’évaluation des effets du rôle d’ICS sur le programme des néoplasies myéloprolifératives. Le second article de la série détaillera les résultats qualitatifs.