Effectiveness of Problem-Based Learning Prior to Lectures on Learning and Retention

In the mandatory tutorial sections of an introductory probability and statistics course of just over 70 students in the Arts and Science undergraduate program, students were randomly assigned to small groups to work on accessible problems from upcoming material without any prior instruction on how to solve them. Solutions were ungraded, and marks were assigned for participation only. A multiyear study was conducted to test students for their level of retention one year later, comparing them to a previous control group. The test question concerned Bayes’ Theorem. Results suggest that the strategy improves student reasoning and retention of concepts while, as expected, a formula is long forgotten. However, low participation rates in the survey post-test produced a p-value of 20%, precluding a claim of statistical significance. Nonetheless, qualitative student feedback on surveys during the course showed a very strong positive response to the approach. Students reported the approach helped their thinking and reasoning, and assisted in their learning. They appreciated the informal, low-pressure environment of the problem-based learning (PBL) sessions, and reported that the sessions were beneficial for developing their own understanding of the concepts before going to lecture. Notwithstanding their positive feedback on PBL activities, students still expressed a preference for traditional instructional approaches where the teaching assistant leads them through solution procedures

Incorporating systems-level stakeholder perspectives into the clinical trial design of school-supervised asthma therapy

RATIONALE: Few evidence-based public health interventions are adopted in practice, in part due to a disconnect between the outcomes measured in clinical trials and the outcomes important to stakeholders that determine implementation in real-world practice. AsthmaLink is a school-supervised asthma therapy program which partners pediatric providers, school nurses, and families. To inform the design of a cluster randomized controlled trial of AsthmaLink, we elicited systems-level stakeholder input. METHODS: Maximum variation sampling was used to recruit 18 stakeholders to participate in semi-structured interviews that were recorded, transcribed, and open coded: Department of Public Health officials (n = 4), school officials (n = 4), pediatric practice managers (n = 3), health insurance officials (n = 4), and legislators (n = 3). Thematic analysis was used to identify common themes related to stakeholder priorities for clinical trial design and perceived barriers to AsthmaLink adoption. RESULTS: Stakeholder groups identified common priorities for the clinical trial design, including examination of the extent to which AsthmaLink (1) reduces health care utilization, (2) is cost effective (2) addresses health disparities, (3) reduces school absenteeism, and (4) educates families about asthma. Stakeholder groups reported potential barriers to AsthmaLink adoption, including challenges pertaining to (1) securing resources, staffing, and reimbursement, (2) variability across school districts, and (3) standing out amidst multiple programs vying for resources. CONCLUSIONS: Systems-level stakeholder input informed refinements to the clinical trial design of a school-supervised therapy program including outcome and implementation measures and choice of study population. Incorporating systems-level stakeholder perspectives into clinical trial design is critical to achieve adoption of evidence-based interventions into practice

A response to COVID-19 school closures: The feasibility of a school-linked text message intervention as an adaptation to school-supervised asthma therapy

BACKGROUND: School-supervised asthma therapy improves asthma medication adherence and morbidity, particularly among low-income and underrepresented minority (URM) children. However, COVID-19-related school closures abruptly suspended this therapy. In response, we developed a school-linked text message intervention. OBJECTIVE: The purpose of the study is to investigate the feasibility and acceptability of a school-linked text message intervention. METHODS: In December 2020, children previously enrolled in school-supervised asthma therapy in Central Massachusetts were recruited into this school-linked text message intervention. We sent two-way, automated, daily text reminders in English or Spanish to caregivers of these children, asking if they had given their child their daily preventive asthma medicine. Our study team notified the school nurse if the caregiver did not consistently respond to text messages. School nurses performed weekly remote check-ins with all families. The primary outcome of the study was feasibility: recruitment, retention, and intervention fidelity. Secondarily we examined intervention acceptability and asthma health outcomes. RESULTS: Twenty-six children (54% male, 69% Hispanic, 8% Black, 23% White, 93% Medicaid insured) and their caregivers were enrolled in the intervention with 96% participant retention at 6 months. Caregiver response rate to daily text messages was 81% over the study period. Children experienced significant improvements in asthma health outcomes. The intervention was well accepted by nurses and caregivers. CONCLUSION: A school-linked text messaging intervention for pediatric asthma is feasible and acceptable. This simple, accessible intervention may improve health outcomes for low-income and URM children with asthma. It merits further study as a potential strategy to advance health equity

Interactions between the discoidin domain receptor 1 and 1 integrin regulate attachment to collagen

Collagen degradation by phagocytosis is essential for physiological collagen turnover and connective tissue homeostasis. The rate limiting step of phagocytosis is the binding of specific adhesion receptors, which include the integrins and discoidin domain receptors (DDR), to fibrillar collagen. While previous data suggest that these two receptors interact, the functional nature of these interactions is not defined. In mouse and human fibroblasts we examined the effects of DDR1 knockdown and over-expression on β1 integrin subunit function. DDR1 expression levels were positively associated with enhanced contraction of floating and attached collagen gels, increased collagen binding and increased collagen remodeling. In DDR1 over-expressing cells compared with control cells, there were increased numbers, area and length of focal adhesions immunostained for talin, paxillin, vinculin and activated β1 integrin. After treatment with the integrin-cleaving protease jararhagin, in comparison to controls, DDR1 over-expressing cells exhibited increased β1 integrin cleavage at the cell membrane, indicating that DDR1 over-expression affected the access and susceptibility of cell-surface β1 integrin to the protease. DDR1 over-expression was associated with increased glycosylation of the β1 integrin subunit, which when blocked by deoxymannojirimycin, reduced collagen binding. Collectively these data indicate that DDR1 regulates β1 integrin interactions with fibrillar collagen, which positively impacts the binding step of collagen phagocytosis and collagen remodeling

Interactions between the discoidin domain receptor 1 and b1 integrin regulate attachment to collagen

The following is a link to the original publication http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3828761/Collagen degradation by phagocytosis is essential for physiological collagen turnover and connective tissue homeostasis. The rate limiting step of phagocytosis is the binding of specific adhesion receptors, which include the integrins and discoidin domain receptors (DDR), to fibrillar collagen. While previous data suggest that these two receptors interact, the functional nature of these interactions is not defined. In mouse and human fibroblasts we examined the effects of DDR1 knockdown and over-expression on β1 integrin subunit function. DDR1 expression levels were positively associated with enhanced contraction of floating and attached collagen gels, increased collagen binding and increased collagen remodeling. In DDR1 over-expressing cells compared with control cells, there were increased numbers, area and length of focal adhesions immunostained for talin, paxillin, vinculin and activated β1 integrin. After treatment with the integrin-cleaving protease jararhagin, in comparison to controls, DDR1 over-expressing cells exhibited increased β1 integrin cleavage at the cell membrane, indicating that DDR1 over-expression affected the access and susceptibility of cell-surface β1 integrin to the protease. DDR1 over-expression was associated with increased glycosylation of the β1 integrin subunit, which when blocked by deoxymannojirimycin, reduced collagen binding. Collectively these data indicate that DDR1 regulates β1 integrin interactions with fibrillar collagen, which positively impacts the binding step of collagen phagocytosis and collagen remodeling.Research was funded by a CIHR operating grant to C.A.M. [MOP418228], whose salary is supported by a Canada Research Chair (Tier 1)

School-supervised Asthma Therapy is Associated with Improved Long-Term Asthma Outcomes for Underrepresented Minority Children

Asthma morbidity disproportionately impacts children from low-income and racial/ethnic minority communities. School-supervised asthma therapy improves asthma outcomes for up to 15 months for underrepresented minority children, but little is known about whether these benefits are sustained over time. We examined the frequency of emergency department (ED) visits and hospital admissions for 83 children enrolled in Asthma Link, a school nurse-supervised asthma therapy program serving predominantly underrepresented minority children. We compared outcomes between the year preceding enrollment and years one-four post-enrollment. Compared with the year prior to enrollment, asthma-related ED visits decreased by 67.9% at one year, 59.5% at two years, 70.2% at three years, and 50% at four years post-enrollment (all p-values \u3c 0.005). There were also significant declines in mean numbers of total ED visits, asthma-related hospital admissions, and total hospital admissions. Our results indicate that school nurse-supervised asthma therapy could potentially mitigate racial/ethnic and socioeconomic inequities in childhood asthma

Dissecting the interface between apicomplexan parasite and host cell: Insights from a divergent AMA–RON2 pair

Plasmodium falciparum and Toxoplasma gondii are widely studied parasites in phylum Apicomplexa and the etiological agents of severe human malaria and toxoplasmosis, respectively. These intracellular pathogens have evolved a sophisticated invasion strategy that relies on delivery of proteins into the host cell, where parasite-derived rhoptry neck protein 2 (RON2) family members localize to the host outer membrane and serve as ligands for apical membrane antigen (AMA) family surface proteins displayed on the parasite. Recently, we showed that T. gondii harbors a novel AMA designated as TgAMA4 that shows extreme sequence divergence from all characterized AMA family members. Here we show that sporozoite-expressed TgAMA4 clusters in a distinct phylogenetic clade with Plasmodium merozoite apical erythrocyte-binding ligand (MAEBL) proteins and forms a high-affinity, functional complex with its coevolved partner, TgRON2(L1). High-resolution crystal structures of TgAMA4 in the apo and TgRON2(L1)-bound forms complemented with alanine scanning mutagenesis data reveal an unexpected architecture and assembly mechanism relative to previously characterized AMA–RON2 complexes. Principally, TgAMA4 lacks both a deep surface groove and a key surface loop that have been established to govern RON2 ligand binding selectivity in other AMAs. Our study reveals a previously underappreciated level of molecular diversity at the parasite–host-cell interface and offers intriguing insight into the adaptation strategies underlying sporozoite invasion. Moreover, our data offer the potential for improved design of neutralizing therapeutics targeting a broad range of AMA–RON2 pairs and apicomplexan invasive stages