Association between sagittal alignment and loads at the adjacent segment in the fused spine: a combined clinical and musculoskeletal modeling study of 205 patients with adult spinal deformity.

PURPOSE: Sagittal malalignment is a risk factor for mechanical complications after surgery for adult spinal deformity (ASD). Spinal loads, modulated by sagittal alignment, may explain this relationship. The aims of this study were to investigate the relationships between: (1) postoperative changes in loads at the proximal segment and realignment, and (2) absolute postoperative loads and postoperative alignment measures. METHODS: A previously validated musculoskeletal model of the whole spine was applied to study a clinical sample of 205 patients with ASD. Based on clinical and radiographic data, pre-and postoperative patient-specific alignments were simulated to predict loads at the proximal segment adjacent to the spinal fusion. RESULTS: Weak-to-moderate associations were found between pre-to-postop changes in lumbar lordosis, LL (r = - 0.23, r = - 0.43; p < 0.001), global tilt, GT (r = 0.26, r = 0.38; p < 0.001) and the Global Alignment and Proportion score, GAP (r = 0.26, r = 0.37; p < 0.001), and changes in compressive and shear forces at the proximal segment. GAP score parameters, thoracic kyphosis measurements and the slope of upper instrumented vertebra were associated with changes in shear. In patients with T10-pelvis fusion, moderate-to-strong associations were found between postoperative sagittal alignment measures and compressive and shear loads, with GT showing the strongest correlations (r = 0.75, r = 0.73, p < 0.001). CONCLUSIONS: Spinal loads were estimated for patient-specific full spinal alignment profiles in a large cohort of patients with ASD pre-and postoperatively. Loads on the proximal segments were greater in association with sagittal malalignment and malorientation of proximal vertebra. Future work should explore whether they provide a causative mechanism explaining the associated risk of proximal junction complications.

Heart 2 Heart: Pilot Study of a Church-Based Community Health Worker Intervention for African Americans with Hypertension.

African Americans (AAs) have higher prevalence of uncontrolled hypertension than Whites, which leads to reduced life expectancy. Barriers to achieving blood pressure control in AAs include mistrust of healthcare and poor adherence to medication and dietary recommendations. We conducted a pilot study of a church-based community health worker (CHW) intervention to reduce blood pressure among AAs by providing support and strategies to improve diet and medication adherence. To increase trust and cultural concordance, we hired and trained church members to serve as CHWs. AA adults (n = 79) with poorly controlled blood pressure were recruited from churches in a low-income, segregated neighborhood of Chicago. Participants had an average of 7.5 visits with CHWs over 6 months. Mean change in systolic blood pressure across participants was - 5 mm/Hg (p = 0.029). Change was greater among participants (n = 45) with higher baseline blood pressure (- 9.2, p = 0.009). Medication adherence increased at follow-up, largely due to improved timeliness of medication refills, but adherence to the DASH diet decreased slightly. Intervention fidelity was poor. Recordings of CHW visits revealed that CHWs did not adhere closely to the intervention protocol, especially with regard to assisting participants with action plans for behavior change. Participants gave the intervention high ratings for acceptability and appropriateness, and slightly lower ratings for feasibility of achieving intervention behavioral targets. Participants valued having the intervention delivered at their church and preferred a church-based intervention to an intervention conducted in a clinical setting. A church-based CHW intervention may be effective at reducing blood pressure in AAs.

A new MMP-mediated prodomain cleavage mechanism to activate bone morphogenetic proteins from the extracellular matrix.

Since their discovery as pluripotent cytokines extractable from bone matrix, it has been speculated how bone morphogenetic proteins (BMPs) become released and activated from the extracellular matrix (ECM). In contrast to TGF-ßs, most investigated BMPs are secreted as bioactive prodomain (PD)-growth factor (GF) complexes (CPLXs). Recently, we demonstrated that PD-dependent targeting of BMP-7 CPLXs to the extracellular fibrillin microfibril (FMF) components fibrillin-1 and -2 represents a BMP sequestration mechanism by rendering the GF latent. Understanding how BMPs become activated from ECM scaffolds such as FMF is crucial to elucidate pathomechanisms characterized by aberrant BMP activation and ECM destruction. Here, we describe a new MMP-dependent BMP-7 activation mechanism from ECM-targeted pools via specific PD degradation. Using Edman sequencing and mutagenesis, we identified a new and conserved MMP-13 cleavage site within the BMP-7 PD. A degradation screen with different BMP family PDs and representative MMP family members suggested utilization of the identified site in a general MMP-driven BMP activation mechanism. Furthermore, sandwich ELISA and solid phase cleavage studies in combination with bioactivity assays, single particle TEM, and in silico molecular docking experiments provided evidence that PD cleavage by MMP-13 leads to BMP-7 CPLX disintegration and bioactive GF release.

Enhancing spatial skills of preschoolers from under-resourced backgrounds: A comparison of digital app vs. concrete materials.

Spatial skills support STEM learning and achievement. However, children from low-socioeconomic (SES) backgrounds typically lag behind their middle- and high-SES peers. We asked whether a digital educational app-designed to mirror an already successful, spatial assembly training program using concrete materials-would be as effective for facilitating spatial skills in under-resourced preschoolers as the concrete materials. Three-year-olds (N = 61) from under-resourced backgrounds were randomly assigned to a business-as-usual control group or to receive 5 weeks of spatial training using either concrete, tangible materials or a digital app on a tablet. The spatial puzzles used were an extension of items from the Test of Spatial Assembly (TOSA). Preschoolers were pretested and posttested on new two-dimensional (2D) TOSA trials. Results indicate that both concrete and digital spatial training increased performance on the 2D-TOSA compared to the control group. The two trainings did not statistically differ from one another suggesting that educational spatial apps may be one route to providing early foundational skills to children from under-resourced backgrounds.

Empowering Health Care Workers on Social Media to Bolster Trust in Science and Vaccination During the Pandemic: Making IMPACT Using a Place-Based Approach.

BACKGROUND: Given the widespread and concerted efforts to propagate health misinformation on social media, particularly centered around vaccination during the pandemic, many groups of clinicians and scientists were organized on social media to tackle misinformation and promote vaccination, using a national or international lens. Although documenting the impact of such social media efforts, particularly at the community level, can be challenging, a more hyperlocal or "place-based approach" for social media campaigns could be effective in tackling misinformation and improving public health outcomes at a community level. OBJECTIVE: We aimed to describe and document the effectiveness of a place-based strategy for a coordinated group of Chicago health care workers on social media to tackle misinformation and improve vaccination rates in the communities they serve. METHODS: The Illinois Medical Professionals Action Collaborative Team (IMPACT) was founded in March 2020 in response to the COVID-19 pandemic, with representatives from major academic teaching hospitals in Chicago (eg, University of Chicago, Northwestern University, University of Illinois, and Rush University) and community-based organizations. Through crowdsourcing on multiple social media platforms (eg, Facebook, Twitter, and Instagram) with a place-based approach, IMPACT engaged grassroots networks of thousands of Illinois health care workers and the public to identify gaps, needs, and viewpoints to improve local health care delivery during the pandemic. RESULTS: To address vaccine misinformation, IMPACT created 8 "myth debunking" infographics and a "vaccine information series" of 14 infographics that have generated >340,000 impressions and informed the development of vaccine education for the Chicago Public Libraries. IMPACT delivered 13 policy letters focusing on different topics, such as health care worker personal protective equipment, universal masking, and vaccination, with >4000 health care workers signatures collected through social media and delivered to policy makers; it published over 50 op-eds on COVID-19 topics in high-impact news outlets and contributed to >200 local and national news features. Using the crowdsourcing approach on IMPACT social media channels, IMPACT mobilized health care and lay volunteers to staff >400 vaccine events for >120,000 individuals, many in Chicago's hardest-hit neighborhoods. The group's recommendations have influenced public health awareness campaigns and initiatives, as well as research, advocacy, and policy recommendations, and they have been recognized with local and national awards. CONCLUSIONS: A coordinated group of health care workers on social media, using a hyperlocal place-based approach, can not only work together to address misinformation but also collaborate to boost vaccination rates in their surrounding communities.

A coordinated strategy to develop and distribute infographics addressing COVID-19 vaccine hesitancy and misinformation.

BACKGROUND: Visual communication strategies are becoming increasingly prevalent for conveying information to health professionals as well as to the general public. The potential of social media for rapid knowledge dissemination using infographics was recognized early in the coronavirus disease (COVID-19) pandemic by health professionals. OBJECTIVE: The purpose of this study was to describe a coalition of health professionals' approach to developing infographics about COVID-19 vaccines and the reach and engagement of those infographics when shared through social media. METHODS: Infographics were created by a core team within the coalition following a stepwise approach. Each underwent a multistep review process, readability evaluation, and translation into Spanish. Infographics were then shared through multiple social media platforms. They were grouped into 1 of 3 categories for this analysis: COVID-19 vaccine series, myth debunkers, or other. RESULTS: All infographics had greater outreach, impressions, and engagement on Twitter than they did on other platforms. When comparing the 3 groups, no 1 infographic type was consistently performing higher than the others. CONCLUSION: Each infographic reached thousands to tens of thousands of people. We do not know whether those who viewed these infographics changed their perspective on vaccination, so we are unable to draw a conclusion about their impact on vaccine hesitancy based on this study alone.

Pre-arrayed Pan-AAV Peptide Display Libraries for Rapid Single-Round Screening.

Display of short peptides on the surface of adeno-associated viruses (AAVs) is a powerful technology for the generation of gene therapy vectors with altered cell specificities and/or transduction efficiencies. Following its extensive prior use in the best characterized AAV serotype 2 (AAV2), recent reports also indicate the potential of other AAV isolates as scaffolds for peptide display. In this study, we systematically explored the respective capacities of 13 different AAV capsid variants to tolerate 27 peptides inserted on the surface followed by production of reporter-encoding vectors. Single-round screening in pre-arrayed 96-well plates permitted rapid and simple identification of superior vectors in >90 cell types, including T cells and primary cells. Notably, vector performance depended not only on the combination of capsid, peptide, and cell type, but also on the position of the inserted peptide and the nature of flanking residues. For optimal data availability and accessibility, all results were assembled in a searchable online database offering multiple output styles. Finally, we established a reverse-transduction pipeline based on vector pre-spotting in 96- or 384-well plates that facilitates high-throughput library panning. Our comprehensive illustration of the vast potential of alternative AAV capsids for peptide display should accelerate their in vivo screening and application as unique gene therapy vectors.

Optimizing imitation: Examining cognitive factors leading to imitation, overimitation, and goal emulation in preschoolers.

Humans imitate patently irrelevant actions known as overimitation, and rather than decreasing with age, overimitation increases with age. Whereas most overimitation research has focused on social factors associated with overimitation, comparatively little is known about the cognitive- and task-specific features that influence overimitation. Specifically, developmental contrasts between imitation and overimitation are confounded by the addition of irrelevant actions to causally necessary actions, increasing sequence length, cognitive load, and processing costs-variables known to be age dependent. We constructed a novel puzzle box task such that a four-step imitation, four-step overimitation, and two-step efficient sequence could be demonstrated using the same apparatus on video. In Experiments 1 and 2, 2.5- to 5-year-olds randomly assigned to imitation and overimitation groups performed significantly more target actions than baseline control groups. Rates of imitation and overimitation increased as a function of age, with older preschoolers outperforming younger preschoolers in both conditions. In Experiment 3, preschoolers were shown a video of an efficient two-step demonstration prior to testing. After they responded, they were shown a four-step overimitation video and were tested on the same puzzle box. Children imitated the efficient demonstration, but after watching the overimitation video, they also overimitated the irrelevant actions. Once again, older children overimitated more than younger children. Together, results show that preschoolers are faithful, flexible, and persistent overimitators. The fidelity and flexibility of overimitation are constrained not only by social factors but also by basic cognitive processes that vary across age groups. As these constraints diminish, overimitation and flexible (optimal) imitation increases.

Applying computational modeling to assess age-, sex-, and strategy-related differences in Spin the Pots, a working memory task for 2- to 4-year-olds.

Working memory (WM) develops rapidly during early childhood. In the present study, visual WM (VSM) was measured using the well-established Spin the Pots task (Hughes & Ensor, 2005), a complex non-verbal eight-location object occlusion task. A self-ordered hiding procedure was adopted to allow for an examination of children's strategy use during a VWM task. Participants (N = 640) between the ages of 2 and 4 years were tested under semi-naturalistic conditions, in the home or in a museum. Computational modeling was used to estimate an expected value for the total trials to complete Spin the Pots via a random search and child performance was compared to expected values. Based on this approach, we determined that children who found six stickers retrieved them in significantly fewer trials than the expected value, excluding chance performance and implicating VWM. Results also showed age-related and sex-related changes in VWM. Between 2 and 4 years of age, 4-year-olds performed significantly better than younger children and girls out-performed the boys. Spontaneous use of a color matching hiding strategy was associated with a higher success rate on the task. Implications of these findings for early development of VWM are discussed.

Only domain-specific imitation practice makes imitation perfect.

Does imitation involve specialized mechanisms or general-unspecialized-learning processes? To address this question, preschoolers (3- and 4-year-olds) were assigned to one of four "practice" groups. Before and after the practice phases, each group was tested on a novel Spatial Imitation sequence. During the practice phase, children in the Spatial Imitation group practiced jointly attending, vicariously encoding, and copying the novel spatial sequences. In the Item Imitation group, children practiced jointly attending, vicariously encoding, and copying novel item sequences. In the Trial-and-Error group, children practiced encoding and recalling a series of novel spatial sequences entirely through individual (operant) learning. In the Free Play (no practice) control group, children played a touchscreen drawing game that controlled for practice time on the touchscreen and mirrored some of the same actions and responses used in the experimental conditions. Results of the difference between pre- and post-practice effects on novel spatial imitation sequences showed that only the Spatial Imitation practice group significantly improved relative to the Free Play group. Individual Spatial Trial-and-Error practice did not significantly improve spatial imitation. The effect of Item Imitation practice was intermediate. These results are inconsistent with the hypothesis that general processes alone--or primarily--support imitation learning and is more consistent with a mosaic model that posits an additive-interaction-effect on imitation performance where a more general social cognitive mechanism (i.e., natural pedagogy) gathers the relevant information from the demonstration and another more specialized mechanism (i.e., imitation specific) transforms that information into a matching response.

Effects of Geometric Toy Design on Parent-Child Interactions and Spatial Language.

Geometric forms have formal definitions. While knowing shape names is considered important for school-readiness, many children do not understand the defining features of shapes until well into elementary school (Satlow & Newcombe, 1998). One reason is likely that they do not encounter enough variety in the shapes they see (citation removed). The present study observed 60 parents and their 3-year-old children during play with geometric toys, exploring how spatial language varied with the nature of the shape-toy set (canonical shapes versus a mix of canonical and unusual or less-canonical variants) and whether geometric shapes were presented as tangible, traditional toys or shown on a touchscreen tablet app. Although children in the app condition heard more shape names than the other conditions due to the language produced by the app itself, children used more overall words and more spatial language with tangible toys that included varied shapes. In addition, parents used more shape names with sons than with daughters and tended to adjust their use of spatial language more in response to varied shape sets with boys, although these findings need replication to evaluate generality. These data suggest that including non-canonical shapes in tangible shape toys may provide a low-cost, high-impact way of refining adult-child interactions that might facilitate children's early geometric knowledge.

The Ghost in the Touchscreen: Social Scaffolds Promote Learning by Toddlers.

This study examined the effect of a "ghost" demonstration on toddlers' imitation. In the ghost condition, virtual pieces moved to make a fish or boat puzzle. Fifty-two 2.5- and 3-year-olds were tested on a touchscreen (no transfer) or with 3D pieces (transfer); children tested with 3D pieces scored above a no demonstration baseline, but children tested on the touchscreen did not. Practice on the touchscreen (n = 23) by 2.5- and 3-year-olds prior to the ghost demonstration did not improve performance. Finally, children who learned the puzzle task via a social demonstration and were tested on the touchscreen (n = 26) performed better than the ghost conditions. Taken together, these studies demonstrate that social demonstrations enhance learning from novel touchscreen tools during early childhood.

Mentalization Mediates the Relationship between Early Maltreatment and Potential for Violence in Adolescence.

AIM: The present study investigates the role of attachment representation and mentalization as possibly protective factors in the relationship between early maltreatment and potential for violence in adolescence. METHODS: For the current study, 161 adolescents, aged 14-21 years, were recruited from high schools and youth psychiatry. Early maltreatment was assessed by the Childhood Experiences of Care and Abuse Questionnaire, attachment was assessed using the Adult Attachment Projective Picture System, and mentalization was coded with the Reflective Functioning Scale from Adult Attachment Interviews. Potential for violence was operationalized using the Reactive-Proactive Aggression Questionnaire, and the presence of conduct disorder was assessed by the Structured Clinical Interview. Using structural equation modeling, reflective functioning and attachment were tested as mediators on the direct effect of early maltreatment on potential for violence. RESULTS: There was a direct effect of early maltreatment on potential for violence. Furthermore, this direct effect was partially mediated by reflective functioning but not by attachment representations. DISCUSSION: The results contribute to the idea that mentalization serves as a protective factor that may suspend the pathway from early maltreatment to violence in adolescence. Because of the transformation of attachment patterns into generalized cognitive models of attachment, attachment in adolescence may have a less pronounced effect on violence in this specific developmental phase. Future studies should test for further group differences in community and clinical groups, which was not possible in the present study due to the limited sample size.

The impact of memory load and perceptual cues on puzzle learning by 24-month olds.

Early childhood is characterized by memory capacity limitations and rapid perceptual and motor development [Rovee-Collier (1996). Infant Behavior & Development, 19, 385-400]. The present study examined 2-year olds' reproduction of a sliding action to complete an abstract fish puzzle under different levels of memory load and perceptual feature support. Experimental groups were compared to baseline controls to assess spontaneous rates of production of the target actions; baseline production was low across all experiments. Memory load was manipulated in Exp. 1 by adding pieces to the puzzle, increasing sequence length from 2 to 3 items, and to 3 items plus a distractor. Although memory load did not influence how toddlers learned to manipulate the puzzle pieces, it did influence toddlers' achievement of the goal-constructing the fish. Overall, girls were better at constructing the puzzle than boys. In Exp. 2, the perceptual features of the puzzle were altered by changing shape boundaries to create a two-piece horizontally cut puzzle (displaying bilateral symmetry), and by adding a semantically supportive context to the vertically cut puzzle (iconic). Toddlers were able to achieve the goal of building the fish equally well across the 2-item puzzle types (bilateral symmetry, vertical, iconic), but how they learned to manipulate the puzzle pieces varied as a function of the perceptual features. Here, as in Exp. 1, girls showed a different pattern of performance from the boys. This study demonstrates that changes in memory capacity and perceptual processing influence both goal-directed imitation learning and motoric performance.

They can interact, but can they learn? Toddlers' transfer learning from touchscreens and television.

Despite the ubiquity of touchscreen applications and television programs for young children, developmental research suggests that learning in this context is degraded relative to face-to-face interactions. Most previous research has been limited to transfer of learning from videos, making it difficult to isolate the relative perceptual and social influences for transfer difficulty, and has not examined whether the transfer deficit persists across early childhood when task complexity increases. The current study examined whether the transfer deficit persists in older children using a complex puzzle imitation task constructed to investigate transfer from video demonstrations. The current test adapted this task to permit bidirectional transfer from touchscreens as well. To test for bidirectional transfer deficits, 2.5- and 3-year-olds were shown how to assemble a three-piece puzzle on either a three-dimensional magnetic board or a two-dimensional touchscreen (Experiment 1). Unidirectional transfer from video was also tested (Experiment 2). Results indicate that a bidirectional transfer deficit persists through 3 years, with younger children showing a greater transfer deficit; despite high perceptual similarities and social engagement, children learned less in transfer tasks, supporting the memory flexibility account of the transfer deficit. Implications of these findings for use of screen media (e.g., video, tablets) in early education are discussed.

Digital Strategies for Screen Time Reduction: A Randomized Field Experiment.

Many consumers nowadays wish to reduce their smartphone usage in the hope of improving productivity and well-being. We conducted a pre-registered field experiment (N = 112) over a period of several weeks to test the effectiveness of two widely available digital strategies for screen time reduction. The effectiveness of a design friction intervention (i.e., activating grayscale mode) was compared with a goal-setting intervention (i.e., self-commitment to time limits) and a control condition (i.e., self-monitoring). The design friction intervention led to an immediate, significant reduction of objectively measured screen time compared with the control condition. Conversely, the goal-setting intervention led to a smaller and more gradual screen time reduction. In contrast to the popular belief that reducing screen time has broad benefits, we found no immediate causal effect of reducing usage on subjective well-being and academic performance.

Rationale and design of the Heart-to-Heart study: A church-based intervention to reduce blood pressure in African Americans.

Heart-to-Heart (H2H) is a church-based behavioral cluster randomized trial to measure the effectiveness of a lifestyle education program for reducing blood pressure (BP) in African American adults with uncontrolled BP. Design and implementation of this study were informed by our ALIVE pilot study conducted with church pastors and leaders using a community-based participatory research methodology. The current study employs a cross-over design in which all participants receive two 6-month programs in different orders: the intervention arm receives the H2H program first, followed by a financial education program, and the comparator arm receives the programs in the reverse order. Approximately 34 churches will be randomized with the aim of including at least 272 participants across churches. The H2H program consists of 24 weekly dietitian-led diet and lifestyle virtual education sessions, 12 Bible studies taught by the church pastor reinforcing positive dietary behaviors from a biblical perspective, daily self-monitoring of BP, and, as needed, one-on-one support from a community health worker to assist with medication adherence. The Money Smart program consists of 14 financial education sessions and 12 Bible studies teaching the biblical basis of good financial management over a 6-month period. The primary outcome measure is systolic BP at 6 months with a follow-up at 12 months. Secondary outcome measures include medication adherence, Dietary Approaches to Stop Hypertension (DASH) diet adherence, self-efficacy for hypertension self-care, social support for eating a healthy diet, hypertension and nutrition knowledge, beliefs about medicines, barriers to medication use, depression, and financial knowledge and behaviors.

Optimized peptide nanofibrils as efficient transduction enhancers for in vitro and ex vivo gene transfer.

Chimeric antigen receptor (CAR)-T cell therapy is a groundbreaking immunotherapy for cancer. However, the intricate and costly manufacturing process remains a hurdle. Improving the transduction rate is a potential avenue to cut down costs and boost therapeutic efficiency. Peptide nanofibrils (PNFs) serve as one such class of transduction enhancers. PNFs bind to negatively charged virions, facilitating their active engagement by cellular protrusions, which enhances virion attachment to cells, leading to increased cellular entry and gene transfer rates. While first-generation PNFs had issues with aggregate formation and potential immunogenicity, our study utilized in silico screening to identify short, endogenous, and non-immunogenic peptides capable of enhancing transduction. This led to the discovery of an 8-mer peptide, RM-8, which forms PNFs that effectively boost T cell transduction rates by various retroviral vectors. A subsequent structure-activity relationship (SAR) analysis refined RM-8, resulting in the D4 derivative. D4 peptide is stable and assembles into smaller PNFs, avoiding large aggregate formation, and demonstrates superior transduction rates in primary T and NK cells. In essence, D4 PNFs present an economical and straightforward nanotechnological tool, ideal for refining ex vivo gene transfer in CAR-T cell production and potentially other advanced therapeutic applications.

Not just for your health alone: Regular exercisers' decision-making in unrelated domains.

Do regularly physically active individuals differ in their decision-making from people who are not regularly physically active? Across five studies, we document a novel benefit of being regularly physically active for decisions that require the appropriate weighing of goal-relevant versus goal-irrelevant information. Usually, when faced with a mix of relevant and irrelevant attribute information, decision makers find it difficult to ignore the irrelevant information, and as such, "dilute" their judgments (i.e., judgments become less extreme). Such a dilution effect has been amply documented in past research. In contrast, we find that people who engage in regular leisure physical activity are less susceptible to dilution effects. Beyond the dilution effect, we also find similar benefits of being regularly physically active for decisions involving desirability-feasibility trade-offs. The results hold across multiple replicates, diverse samples, and different measures of regular physical activity. We also rule out several potential alternative accounts (e.g., demographics, personality traits). The results cannot be explained by physical effort alone as these benefits are observed only for regular leisure physical activity and not for occupational physical activity. (PsycInfo Database Record (c) 2022 APA, all rights reserved).