Search

Individuals living with and beyond cancer face physical impairment and inactivity in survivorship. Neuro-oncology populations have especially high rates of sedentary behaviour and functional deficits, including impaired balance, motor skills, and cognition. Our purpose was to assess the rehabilitation and exercise needs of patients with brain tumours while examining the feasibility of a rehabilitation triage clinic as a part of the Alberta Cancer Exercise–Neuro-Oncology study, where patients were referred to a triage clinic, where health, neurologic, and functional status was assessed, followed by a referral to one or multiple resources, including exercise, physiotherapy, occupational therapy, or physiatry. Qualitative perception of the triage clinic was collected. Overall, the triage clinic was feasible and safe for participants, facilitating referral into rehabilitation and exercise resources. Pre-determined enrollment and attendance rates were met, but referral rates to the triage clinic were not met. Oncology clinic staff reported forgetting to refer patients or uncertainty of who was appropriate for rehabilitation as barriers. Oncology clinic-based screening may improve the identification of patients who are sedentary or have a physical impairment. A proposed screening tool, the Cancer Rehabilitation and Exercise Screening Tool (CREST), is presented within our Cancer Rehabilitation and Exercise Pathways Model. The CREST can identify patients who are sedentary or have a functional impairment, facilitating referral to appropriate rehabilitation resources and ultimately improving patient recovery and functioning.

Not available.

Severe congenital neutropenia (SCN) is caused by germline mutations, most commonly in ELANE, impacting neutrophil maturation and leading to high risk of life-threatening infections. Most patients with ELANE-mutant SCN can achieve safe neutrophil counts with chronic Granulocyte-Colony Stimulating Factor (G-CSF). However, up to 10% of patients have neutropenia refractory to G-CSF and require allogeneic stem cell transplant. Traditional conditioning for these patients includes busulfan and cyclophosphamide which is associated with significant toxicities. We present five patients with SCN without myeloid malignancy transplanted using a reduced toxicity regimen of busulfan, fludarabine and thymoglobulin. 5 pediatric patients with SCN underwent matched sibling donor bone marrow transplant (MSD-BMT) between 2014-2022 on or per CHP14BT057 (NCT02928991), a prospective, single center trial testing elimination of cyclophosphamide from conditioning in pediatric patients with single lineage inherited BMF syndromes. All patients had MSDs and no evidence of MDS. Conditioning consisted of PK-adjusted busulfan, fludarabine, and thymoglobulin, with calcineurin inhibitor and mycophenolate mofetil GVHD prophylaxis. With median follow-up of 48.4 months, overall and event-free survival were 100%. There was no acute GVHD and one instance of chronic limited GVHD. Patients exhibited >95% donor myeloid chimerism at 5 years post-BMT. Two patients experienced CMV reactivation without end-organ disease, and no other viral reactivation or significant infections occurred. MSD-BMT with reduced toxicity myeloablation for SCN provides excellent outcomes while minimizing toxicity. These data suggest that busulfan, fludarabine, and ATG can be considered an efficacious, low-toxicity standard of care regimen for patients with SCN undergoing MSD-BMT.

Alkaloids are important bioactive molecules throughout the natural world, and in many animals they serve as a source of chemical defense against predation. Dendrobatid poison frogs bioaccumulate alkaloids from their diet to make themselves toxic or unpalatable to predators. Despite the proposed roles of plasma proteins as mediators of alkaloid trafficking and bioavailability, the responsible proteins have not been identified. We use chemical approaches to show that a ~50 kDa plasma protein is the principal alkaloid-binding molecule in blood of poison frogs. Proteomic and biochemical studies establish this plasma protein to be a liver-derived alkaloid-binding globulin (ABG) that is a member of the serine-protease inhibitor (serpin) family. In addition to alkaloid-binding activity, ABG sequesters and regulates the bioavailability of ‘free’ plasma alkaloids in vitro. Unexpectedly, ABG is not related to saxiphilin, albumin, or other known vitamin carriers, but instead exhibits sequence and structural homology to mammalian hormone carriers and amphibian biliverdin-binding proteins. ABG represents a new small molecule binding functionality in serpin proteins, a novel mechanism of plasma alkaloid transport in poison frogs, and more broadly points toward serpins acting as tunable scaffolds for small molecule binding and transport across different organisms.

Assessing teaching styles with a valid and reliable instrument would assist in the measurement of an important variable that affects children's socio-emotional and cognitive development. Evaluation of teaching style in the early childhood classroom is difficult, as collecting data from the early childhood classroom often lies in the reliance on second-party reports (typically students or administrators) or lengthy, in-person observations. The purpose of the current study was to develop a self-report questionnaire for teachers in preschool through 3rd grade for use when systematic observations of teachers are unfeasible, students may be too young for a student report measure, or researchers wish to use multiple measures of teaching styles. A convenience sampling approach was used to recruit in-service (certified) and pre-service teachers (college students preparing to become teachers) in the Central Plains region. The researchers developed the initial items used to create the Teaching Styles Questionnaire (TSQ) as a modification of the 60 most relevant items from the Parenting Styles and Dimensions Questionnaire (PSDQ; Robinson et. al, 1995). We used factor analyses to explore potential subscales and test the convergent validity of the Teaching Styles Questionnaire subscales. By using factor analyses, long and short versions of the Teaching Styles Questionnaire were developed, consisting of 27 and 16 items respectively. The model fit indices indicated both versions of the Teaching Styles Questionnaire have a good model fit. Criterion-related validity was supported by correlations with the Teachers' Sense of Efficacy Scale (Tschannen-Moran & Hoy, 2001). Limitations to this study are discussed.

Abstract Introduction Infectious diseases (ID) consultations have been demonstrated to improve patient outcomes in the treatment of severe infections. However, ID consultation is often unavailable to patients that live in rural communities. Little is known regarding the treatment of infections in rural hospitals with no coverage from an ID specialist. We characterized the outcomes of patients cared for in hospitals without coverage from an ID physician. Methods Patients aged 18 years or older admitted to eight community hospitals without access to ID consultation during a 6.5-month period were assessed. All patients had received at least three days of continuous antimicrobial therapy. The primary outcome was the need for transfer to a tertiary facility for ID services. The secondary outcome was the characterization of antimicrobials received. Antimicrobial courses were evaluated independently by two board-certified ID physicians. Results 3706 encounters were evaluated. Transfers for ID consultation occurred in 0.01% of patients. The ID physician would have made modifications in 68.5% of patients. Areas for improvement included treatment of chronic obstructive pulmonary disease exacerbations, broad-spectrum treatment of skin and soft tissue infection, long courses of azithromycin, and management of Staphylococcus aureus bacteremia, including choice and length of therapy, as well as obtaining echocardiography. Patients evaluated received 22,807 days of antimicrobial therapy. Conclusions Patients hospitalized in community hospitals are rarely transferred for ID consultation. Our work demonstrates a need for ID consultation in community hospitals, identifying opportunities to enhance patient care by modifying antimicrobial regimens to improve antimicrobial stewardship and avoid inappropriate antimicrobials. Efforts to expand the ID workforce to include coverage at rural hospitals will likely improve antibiotic utilization.

Abstract Immunization with the Amastigote Surface Protein-2 (ASP-2) and Trans-sialidase (TS) antigens either in the form of recombinant protein, encoded in plasmids or human adenovirus 5 (hAd5) confers robust protection against various lineages of Trypanosoma cruzi. Herein we generated a chimeric protein containing the most immunogenic regions for T and B cells from TS and ASP-2 (TRASP) and evaluated its immunogenicity in comparison with our standard protocol of heterologous prime-boost using plasmids and hAd5. Mice immunized with TRASP protein associated to Poly-ICLC (Hiltonol) were highly resistant to challenge with T. cruzi, showing a large decrease in tissue parasitism, parasitemia and no lethality. This protection lasted for at least 3 months after the last boost of immunization, being equivalent to the protection induced by DNA/hAd5 protocol. TRASP induced high levels of T. cruzi-specific antibodies and IFNγ-producing T cells and protection was primarily mediated by CD8+ T cells and IFN-γ. We also evaluated the toxicity, immunogenicity, and efficacy of TRASP and DNA/hAd5 formulations in dogs. Mild collateral effects were detected at the site of vaccine inoculation. While the chimeric protein associated with Poly-ICLC induced high levels of antibodies and CD4+ T cell responses, the DNA/hAd5 induced no antibodies, but a strong CD8+ T cell response. Immunization with either vaccine protected dogs against challenge with T. cruzi. Despite the similar efficacy, we conclude that moving ahead with TRASP together with Hiltonol is advantageous over the DNA/hAd5 vaccine due to pre-existing immunity to the adenovirus vector, as well as the cost-benefit for development and large-scale production.

Abstract Purpose The primary objective was to investigate the feasibility of a synchronous, online-delivered, group-based, supervised, exercise oncology maintenance program supported with health coaching. Methods Participants had previously completed a 12-week group-based exercise program. All participants received synchronous online delivered exercise maintenance classes, and half were block randomized to receive additional weekly health coaching calls. A class attendance rate of ≥ 70%, a health coaching completion rate of ≥ 80%, and an assessment completion rate of ≥ 70% were set as markers of feasibility. Additionally, recruitment rate, safety, and fidelity of the classes and health coaching calls were reported. Post-intervention interviews were performed to further understand the quantitative feasibility data. Two waves were conducted — as a result of initial COVID-19 delays, the first wave was 8 weeks long, and the second wave was 12 weeks long, as intended. Results Forty participants (n 8WK = 25; n 12WK = 15) enrolled in the study with 19 randomized to the health coaching group and 21 to the exercise only group. The recruitment rate (42.6%), attrition (2.5%), safety (no adverse events), and feasibility were confirmed for health coaching attendance (97%), health coaching fidelity (96.7%), class attendance (91.2%), class fidelity (92.6%), and assessment completion (questionnaire = 98.8%; physical functioning = 97.5%; Garmin wear-time = 83.4%). Interviews highlighted that convenience contributed to participant attendance, while the diminished ability to connect with other participants was voiced as a drawback compared to in-person delivery. Conclusion The synchronous online delivery and assessment of an exercise oncology maintenance class with health coaching support was feasible for individuals living with and beyond cancer. Providing feasible, safe, and effective exercise online to individuals living with cancer may support increased accessibility. For example, online may provide an accessible alternative for those living in rural/remote locations as well as for those who may be immunocompromised and cannot attend in-person classes. Health coaching may additionally support individuals’ behavior change to a healthier lifestyle. Trial registration The trial was retrospectively registered (NCT04751305) due to the rapidly evolving COVID-19 situation that precipitated the rapid switch to online programming.

ObjectiveTo determine the frequency and predictors of antibiotic escalation in response to the inpatient sepsis screen at our institution.DesignRetrospective cohort study.SettingTwo affiliated academic medical centers in Los Angeles, California.PatientsHospitalized patients aged 18 years and older who had their first positive sepsis screen between January 1, 2019, and December 31, 2019, on acute-care wards.MethodsWe described the rate and etiology of antibiotic escalation, and we conducted multivariable regression analyses of predictors of antibiotic escalation.ResultsOf the 576 cases with a positive sepsis screen, antibiotic escalation occurred in 131 cases (22.7%). New infection was the most documented etiology of escalation, with 76 cases (13.2%), followed by known pre-existing infection, with 26 cases (4.5%). Antibiotics were continued past 3 days in 17 cases (3.0%) in which new or existing infection was not apparent. Abnormal temperature (adjusted odds ratio [aOR], 3.00; 95% confidence interval [CI], 1.91-4.70) and abnormal lactate (aOR, 2.04; 95% CI, 1.28-3.27) were significant predictors of antibiotic escalation. The patient already being on antibiotics (aOR, 0.54; 95% CI, 0.34-0.89) and the positive screen occurred during a nursing shift change (aOR, 0.36; 95% CI, 0.22-0.57) were negative predictors. Pneumonia was the most documented new infection, but only 19 (50%) of 38 pneumonia cases met full clinical diagnostic criteria.ConclusionsInpatient sepsis screening led to a new infectious diagnosis in 13.2% of all positive sepsis screens, and the risk of prolonged antibiotic exposure without a clear infectious source was low. Pneumonia diagnostics and lactate testing are potential targets for future stewardship efforts.

The National Association for the Education of Young Children (NAEYC) states that building bridges between home and school benefits students' development. With online teaching, this translates into informal conversations before class starts or at the end of class as a teacher waits for a virtual classroom to fill up or empty out. Much of teaching language learners relies on fostering relationships with students. The ability to build those relationships can be compromised by the challenges of remote learning. When schools were closed due to the COVID-19 pandemic, many teachers were struggling with questions about how to deliver lessons and engage second language learners online. This article highlights one teacher's experiences and offers some advice based on those experiences and the literature.

Lake Winnipeg in Manitoba, Canada is heavily impacted by harmful algal blooms that contain non-protein amino acids (NPAAs) produced by cyanobacteria: N-(2-aminoethyl)glycine (AEG), β-aminomethyl-L-alanine (BAMA), β-N-methylamino-L-alanine (BMAA), and 2,4-diaminobutyric acid (DAB). Our objective was to investigate the impact of microbial diversity on NPAA production by cyanobacteria using semi-purified crude cyanobacterial cultures established from field samples collected by the Lake Winnipeg Research Consortium between 2016 and 2021. NPAAs were detected and quantified by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) using validated analytical methods, while Shannon and Simpson alpha diversity scores were determined from 16S rRNA metagenomic sequences. Alpha diversity in isolate cultures was significantly decreased compared to crude cyanobacterial cultures (p < 0.001), indicating successful semi-purification. BMAA and AEG concentrations were higher in crude compared to isolate cultures (p < 0.0001), and AEG concentrations were correlated to the alpha diversity in cultures (r = 0.554; p < 0.0001). BAMA concentrations were increased in isolate cultures (p < 0.05), while DAB concentrations were similar in crude and isolate cultures. These results demonstrate that microbial community complexity impacts NPAA production by cyanobacteria and related organisms.

This study investigates the resistance against alkali-silica reaction (ASR) of two alternative binder systems, alkali-activated slag (AAS) and Celitement (Celite). Experimental studies on expansion and mechanical strength are carried out. Coupled kinetic and equilibrium thermodynamic modeling is used to clarify the role of binder chemistry on ASR. It was observed that under accelerated conditions OPC based mortars were more susceptible to ASR compared to AAS and Celite-based mortars. Based on experimental and modeling results, a correlation is shown between the dissolution of silica and the degree of expansion, but no correlation was found between the predicted amount of ASR products and the measured degree of expansion. Finally, the expansion degree could only be correlated with the reduction in compressive and flexural tensile strength for ASR-exposed samples.