Development and feasibility of a sedentary behavior intervention for stroke: a case series

Background and Objective: High levels of sedentary behavior are prevalent among people with stroke and contribute to elevated risk for recurrent stroke. Few interventions reduce sedentary behavior post-stroke. The ABLE intervention aims to reduce sedentary behavior using activity monitoring, activity scheduling, problem-solving, and self-assessment to promote engagement in meaningful daily activities. The purpose of this study was to assess the feasibility (tolerability, acceptability, reliability, safety) of the ABLE intervention after stroke and describe trends in sedentary behavior at baseline and 4 weeks.

Clinical Presentation: Participants (n = 5) who were 6 months to 2 years post-stroke, ambulatory, and reported ≥6 h of daily sitting time.

Intervention: Twelve ABLE intervention sessions (3x/week for 4 weeks) conducted in participants’ homes. The ABLE intervention includes activity monitoring, activity scheduling, self-assessment, and collaborative problem-solving.

Results: All feasibility benchmarks were met for three participants. Two participants met tolerability and safety benchmarks but did not meet acceptability and reliability benchmarks. Variability in feasibility and sedentary behavior outcomes may be related to baseline levels of sedentary behavior and social support.

Conclusions: The ABLE intervention was tolerable and safe. The intervention protocol was refined to enhance reliability and acceptability. Future studies should estimate the effects of the ABLE intervention.     

Accelerated ferumoxytol‐enhanced 4D multiphase,steady‐state imaging with contrast enhancement (MUSIC) cardiovascular MRI: validation in pediatric congenital heart disease

The purpose of this work was to validate a parallel imaging (PI) and compressed sensing (CS) combined reconstruction method for a recently proposed 4D non‐breath‐held, multiphase, steady‐state imaging technique (MUSIC) cardiovascular MRI in a cohort of pediatric congenital heart disease patients. We implemented a graphics processing unit accelerated CS‐PI combined reconstruction method and applied it in 13 pediatric patients who underwent cardiovascular MRI after ferumoxytol administration. Conventional breath‐held contrast‐enhanced magnetic resonance angiography (CE‐MRA) was first performed during the first pass of ferumoxytol injection, followed by the original MUSIC and the proposed CS‐PI MUSIC during the steady‐state distribution phase of ferumoxytol. Qualities of acquired images were then evaluated using a four‐point scale. Left ventricular volumes and ejection fractions calculated from the original MUSIC and the CS‐PI MUSIC were also compared with conventional multi‐slice 2D cardiac cine MRI. The proposed CS‐PI MUSIC reduced the imaging time of the MUSIC acquisition to 4.6 ± 0.4 min from 8.9 ± 1.2 min. Computationally intensive image reconstruction was completed within 5 min without interruption of sequential clinical scans. The proposed method (mean 3.3–4.0) provided image quality comparable to that of the original MUSIC (3.2–4.0) (all P ≥ 0.42), and better than conventional breath‐held first‐pass CE‐MRA (1.1–3.3) for 13 anatomical structures (all P ≤ 0.0014) with good inter‐observer agreement (κ > 0.46). The calculated ventricular volumes and ejection fractions from both original MUSIC (r > 0.90) and CS‐PI MUSIC (r > 0.85) correlated well with 2D cine imaging. In conclusion, PI and CS were successfully incorporated into the 4D MUSIC acquisition to further reduce scan time by approximately 50% while maintaining highly comparable image quality in a clinically practical reconstruction time.     

Genotype-phenotype correlation and molecular heterogeneity in pyruvate kinase deficiency

Pyruvate kinase (PK) deficiency is a rare recessive congenital hemolytic anemia caused by mutations in the PKLR gene. This study reports the molecular features of 257 patients enrolled in the PKD Natural History Study. Of the 127 different pathogenic variants detected, 84 were missense and 43 non-missense, including 20 stop-gain, 11 affecting splicing, five large deletions, four in-frame indels, and three promoter variants. Within the 177 unrelated patients, 35 were homozygous and 142 compound heterozygous (77 for two missense, 48 for one missense and one non-missense, and 17 for two non-missense variants); the two most frequent mutations were p.R510Q in 23% and p.R486W in 9% of mutated alleles. Fifty-five (21%) patients were found to have at least one previously unreported variant with 45 newly described mutations. Patients with two non-missense mutations had lower hemoglobin levels, higher numbers of lifetime transfusions, and higher rates of complications including iron overload, extramedullary hematopoiesis, and pulmonary hypertension. Rare severe complications, including lower extremity ulcerations and hepatic failure, were seen more frequently in patients with non-missense mutations or with missense mutations characterized by severe protein instability. The PKLR genotype did not correlate with the frequency of complications in utero or in the newborn period. With ICCs ranging from 0.4 to 0.61, about the same degree of clinical similarity exists within siblings as it does between siblings, in terms of hemoglobin, total bilirubin, splenectomy status, and cholecystectomy status. Pregnancy outcomes were similar across genotypes in PK deficient women. This report confirms the wide genetic heterogeneity of PK deficiency.     

Attitudes toward tobacco cessation and lung cancer screening in two South African communities

ABSTRACT

Among men in South Africa, the prevalence of tobacco smoking is as high as 33%. Although smoking is responsible for most lung cancer in South Africa, occupational and environmental exposures contribute greatly to risk. We conducted a tobacco and lung cancer screening needs assessment and administered surveys to adults who smoked >100 cigarettes in their lifetime in Johannesburg (urban) and Kimberley (rural). We compared tobacco use, risk exposure, attitudes toward and knowledge of, and receptivity to cessation and screening, by site. Of 324 smokers, nearly 85% of current smokers had a <30 pack-year history of smoking; 58.7% had tried to stop smoking ≥1 time, and 78.9% wanted to quit. Kimberley smokers more often reported being advised by a healthcare provider to stop smoking (56.5% vs. 37.3%, p=0.001) than smokers in Johannesburg but smokers in Johannesburg were more willing to stop smoking if advised by their doctor (72.9% vs. 41.7%, p<0.001). Findings indicate that tobacco smokers in two geographic areas of South Africa are motivated to stop smoking but receive no healthcare support to do so. Developing high risk criteria for lung cancer screening and creating tobacco cessation infrastructure may reduce tobacco use and decrease lung cancer mortality in South Africa.     

Effects of a novel Nodal-targeting monoclonal antibody in melanoma

Nodal is highly expressed in various human malignancies, thus supporting the rationale for exploring Nodal as a therapeutic target. Here, we describe the effects of a novel monoclonal antibody (mAb), 3D1, raised against human Nodal. In vitro treatment of C8161 human melanoma cells with 3D1 mAb shows reductions in anchorage-independent growth and vasculogenic network formation. 3D1 treated cells also show decreases of Nodal and downstream signaling molecules, P-Smad2 and P-ERK and of P-H3 and CyclinB1, with an increase in p27. Similar effects were previously reported in human breast cancer cells where Nodal expression was generally down-regulated; following 3D1 mAb treatment, both Nodal and P-H3 levels are reduced. Noteworthy is the reduced growth of human melanoma xenografts in Nude mice treated with 3D1 mAb, where immunostaining of representative tumor sections show diminished P-Smad2 expression. Similar effects both in vitro and in vivo were observed in 3D1 treated A375SM melanoma cells harboring the active BRAF(V600E) mutation compared to treatments with IgG control or a BRAF inhibitor, dabrafenib. Finally, we describe a 3D1-based ELISA for the detection of Nodal in serum samples from cancer patients. These data suggest the potential of 3D1 mAb for selecting and targeting Nodal expressing cancers.