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ObjectiveAdministrative data are used to describe the pancreatic cancer (pcc) population. The analysis examines demographic details, incidence, site, survival, and factors influencing mortality in a cohort of individuals diagnosed with pcc.MethodsIncident cases of pcc diagnosed in Ontario between 1 January 2004 and 31 December 2011 were extracted from the Ontario Cancer Registry. They were linked by encrypted health card number to several administrative databases to obtain demographic and mortality information. Descriptive, bivariate, and survival analyses were conducted.ResultsDuring the period of interest, 9221 new cases of pcc (4548 in men, 4673 in women) were diagnosed, for an age-adjusted standardized annual incidence in the range of 8.6-9.5 per 100,000 population. Mean age at diagnosis was 70.3 ± 12.5 years (standard deviation). Five-year survival was 7.2% (12.8% for those 80 years of age). Survival varied by sex, older age, rural residence, lower income, site of involvement in the pancreas, and presence of comorbidity.ConclusionsThe mortality rate in pcc is exceptionally high. With an increasing incidence and a mortality positively associated with age, additional support will be needed for this highly fatal disease as demographics in Ontario continue to trend toward a higher proportion of older individuals.

ObjectiveThe objective of the present analysis was to determine the publicly funded health care costs associated with the care of breast cancer (bca) patients by disease stage.MethodsIncident cases of female invasive bca (2005-2009) were extracted from the Ontario Cancer Registry and linked to administrative datasets from the publicly funded system. The type and use of health care services were stratified by disease stage over the first 2 years after diagnosis. Mean costs and costs by type of clinical resource used in the care of bca patients were compared with costs for a matched control group. The attributable cost for the 2-year time horizon was determined in 2008 Canadian dollars.ResultsThis cohort study involved 39,655 patients with bca and 190,520 control subjects. The average age in those groups was 61.1 and 60.9 years respectively. Most bca patients were classified as either stage i (34.4%) or stage ii (31.8%). Of the bca cohort, 8% died within the first 2 years after diagnosis. The overall mean cost per bca case from a public payer perspective in the first 2 years after diagnosis was $41,686. Over the 2-year time horizon, the mean cost increased by stage: i, $29,938; ii, $46,893; iii, $65,369; and iv, $66,627. The attributable cost of bca was $31,732. Cost drivers were cancer clinic visits, physician billings, and hospitalizations.ConclusionsCosts of care increased by stage of bca. Cost drivers were cancer clinic visits, physician billings, and hospitalizations. These data will assist planning and decision-making for the use of limited health care resources.

Presently, there are no guidelines to help predict which patients are more likely to have successful laparoscopic adhesiolysis. We attempt to define which preoperative characteristics of trauma patients who later develop small bowel obstruction are most amenable to a laparoscopic operation. We did a retrospective review of all patients with small bowel obstruction after previous laparotomy for trauma. For the patients that received an operation to relieve the obstruction, the location of transition zone via CT scan and location of the previous abdominal scar were recorded. A previous upper abdominal surgical incision and a transition zone outside of the pelvis on CT scan were preoperative predictors of a successful laparoscopic adhesiolysis. The laparoscopic group had a shorter length of stay. Laparoscopic surgery as the initial operative approach in the management of SBO after previous laparotomy for trauma is safe and effective. Characteristics that make the laparoscopic approach most favorable are CT transition point above the pelvis and previous midline incision above umbilicus. [ABSTRACT FROM AUTHOR]

Antiviral immunity compromises the efficacy of adeno-associated virus (AAV) vectors used for gene therapy. This is well understood for the adaptive immune response. However, innate immune effectors like alpha-defensin antimicrobial peptides also block AAV infection, although their mechanisms of action are unknown. To address this gap in knowledge, we investigated AAV2 neutralization by human neutrophil peptide 1 (HNP1), a myeloid alpha-defensin, and human defensin 5 (HD5), an enteric alpha-defensin. We found that both defensins bind to AAV2 and inhibit infection at low micromolar concentrations. While HD5 prevents AAV2 from binding to cells, HNP1 does not. However, AAV2 exposed to HD5 after binding to cells is still neutralized, indicating an additional block to infection. Accordingly, both HD5 and HNP1 inhibit externalization of the VP1 unique domain, which contains a phospholipase A 2 enzyme required for endosome escape and nuclear localization signals required for nuclear entry. Consequently, both defensins prevent AAV2 from reaching the nucleus. Disruption of intracellular trafficking of the viral genome to the nucleus is reminiscent of how alpha-defensins neutralize other non-enveloped viruses, suggesting a common mechanism of inhibition. These results will inform the development of vectors capable of overcoming these hurdles to improve the efficiency of gene therapy., Author Summary: AAVs are commonly used as gene therapy vectors due to their broad tropism and lack of disease association; however, host innate immune factors, such as human alpha-defensin antimicrobial peptides, can hinder gene delivery. Although it is becoming increasingly evident that human alpha-defensins can block infection by a wide range of nonenveloped viruses, including AAVs, their mechanism of action remains poorly understood. In this study, we describe for the first time how two types of abundant human alpha-defensins neutralize a specific AAV serotype, AAV2. We found that one defensin prevents AAV2 from binding to cells, the first step in infection, while both defensins block a critical later step in AAV2 entry. Our findings support the emerging idea that defensins use a common strategy to block infection by DNA viruses that replicate in the nucleus. Through understanding how innate immune effectors interact with and impede AAV infection, vectors can be developed to bypass these interventions and allow more efficient gene delivery.

Background: Complete macroscopic resection is a key factor associated with prolonged survival in ovarian cancer. However, most evidence derives from high-grade serous ovarian carcinoma, and the benefit of complete macroscopic resection in other histotypes is poorly characterized. We sought to determine which histotypes derive the greatest benefit from complete macroscopic resection to better inform future decisions on radical cytoreductive efforts., Methods: We performed multivariable analysis of disease-specific survival across 2 independent patient cohorts to determine the magnitude of benefit associated with complete macroscopic resection within each histotype., Results: Across both cohorts (Scottish: n = 1622; Surveillance, Epidemiology, and End Results [SEER]: n = 18 947), complete macroscopic resection was associated with prolonged disease-specific survival; this was more marked in the Scottish cohort (multivariable hazard ratio [HR] = 0.44, 95% confidence interval [CI] = 0.37 to 0.52 vs HR = 0.59, 95% CI = 0.57 to 0.62 in SEER). In both cohorts, clear cell ovarian carcinoma was among the histotypes to benefit most from complete macroscopic resection (multivariable HR = 0.23 and HR = 0.50 in Scottish and SEER cohorts, respectively); high-grade serous ovarian carcinoma patients demonstrated highly statistically significant and clinically meaningful survival benefit, but this was of lower magnitude than in clear cell ovarian carcinoma and endometrioid ovarian carcinoma across both cohorts. The benefit derived in low-grade serous ovarian carcinoma is also high (multivariable HR = 0.27 in Scottish cohort). Complete macroscopic resection was associated with prolonged survival in mucinous ovarian carcinoma patients in the SEER cohort (multivariable HR = 0.65), but the association failed to reach statistical significance in the Scottish cohort., Conclusions: The overall ovarian cancer patient population demonstrates clinically significant survival benefit associated with complete macroscopic resection; however, the magnitude of benefit differs between histotypes., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Low grade serous ovarian carcinoma (LGSOC) is a distinct histotype of ovarian cancer characterised high levels of intrinsic chemoresistance, highlighting the urgent need for new treatments. High throughput screening in clinically-informative cell-based models represents an attractive strategy for identifying candidate treatment options for prioritisation in clinical studies., Methods: We performed a high throughput drug screen of 1610 agents across a panel of 6 LGSOC cell lines (3 RAS/RAF-mutant, 3 RAS/RAF-wildtype) to identify novel candidate therapeutic approaches. Validation comprised dose-response analysis across 9 LGSOC models and 5 high grade serous comparator lines., Results: 16 hits of 1610 screened compounds were prioritised for validation based on >50% reduction in nuclei counts in over half of screened cell lines at 1000 nM concentration. 11 compounds passed validation, and the four agents of greatest interest (dasatinib, tyrosine kinase inhibitor; disulfiram, aldehyde dehydrogenase inhibitor; carfilzomib, proteasome inhibitor; romidepsin, histone deacetylase inhibitor) underwent synergy profiling with the recently approved MEK inhibitor trametinib. Disulfiram demonstrated excellent selectivity for LGSOC versus high grade serous ovarian carcinoma comparator lines (P = 0.003 for IC50 comparison), while the tyrosine kinase inhibitor dasatinib demonstrated favourable synergy with trametinib across multiple LGSOC models (maximum zero interaction potency synergy score 46.9). The novel, highly selective Src family kinase (SFK) inhibitor NXP900 demonstrated a similar trametinib synergy profile to dasatinib, suggesting that SFK inhibition is the likely driver of synergy., Conclusion: Dasatinib and other SFK inhibitors represent novel candidate treatments for LGSOC and demonstrate synergy with trametinib. Disulfiram represents an additional treatment strategy worthy of investigation., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: RLH: consultancy fees from GlaxoSmithKline and DeciBio. RE: none. JCD: none. NI: none. RM: none. LJS: none. AJO: research funding from AstraZeneca (jointly funded Clinical Research Training Fellowship with Cancer Research UK) outside the scope of this work. HK: none. MLF: none. MC: none. JMP: none. PR: translational research grants from GSK, Atrios; funds to institution for clinical trials delivery from AstraZeneca, Atrios, Clovis, Forma, GSK, Tesaro, Imuntep, Incyte, Iovance, Mersana, Nucana, PsiOxus, Replimune, Sierra, Starpharma; personal fees from AstraZeneca, GSK, Starpharma. AUB: patents (EP3298015B1, JP6684831B2, US10294227B2, CN107849050B, CA3021550A1) pertaining to the discovery of eCF506/NXP900 that have been licensed to Nuvectis Pharma Inc.; research grants from Nuvectis Pharma. DG: grant from Novartis; consultancy fees from Verastem; royalties from Elsevier, UpToDate; personal fees for Advisory Boards from Verastem, Aadi, Beigene/Springworks, Onconova; stock equity in Johnson & Johnson, Bristol Myers Squibb, Procter and Gamble, all outside the scope of this work. CSH: none. MSC: grants from Ovarian Cancer Canada; consulting fees from Verastem. NOC: patents (EP3298015B1, JP6684831B2, US10294227B2, CN107849050B, CA3021550A1) pertaining to the discovery of eCF506/NXP900 that have been licensed to Nuvectis Pharma Inc.; research grants from Nuvectis Pharma. CG: grants from AstraZeneca, MSD, BMS, GSK, Clovis, Novartis, BerGenBio, Medannex, Roche, Verastem, Artios; personal fees from AstraZeneca, MSD, GSK, Clovis, Verastem, Eisai, Roche, Takeda, Peervoice and Cor2Ed outside the scope of this work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Mammalian α-defensins are a family of abundant effector peptides of the mucosal innate immune system. Although primarily considered to be antimicrobial, α-defensins can increase rather than block infection by certain prominent bacterial and viral pathogens in cell culture and in vivo. We have shown previously that exposure of mouse and human adenoviruses (HAdVs) to α-defensins is able to overcome competitive inhibitors that block cell binding, leading us to hypothesize a defensin-mediated binding mechanism that is independent of known viral receptors. To test this hypothesis, we used genetic approaches to demonstrate that none of several primary receptors nor integrin co-receptors are needed for human α-defensin-mediated binding of HAdV to cells; however, infection remains integrin dependent. Thus, our studies have revealed a novel pathway for HAdV binding to cells that bypasses viral primary receptors. We speculate that this pathway functions in parallel with receptor-mediated entry and contributes to α-defensin-enhanced infection of susceptible cells. Remarkably, we also found that in the presence of α-defensins, HAdV tropism is expanded to non-susceptible cells, even when viruses are exposed to a mixture of both susceptible and non-susceptible cells. Therefore, we propose that in the presence of sufficient concentrations of α-defensins, such as in the lung or gut, integrin expression rather than primary receptor expression will dictate HAdV tropism in vivo. In summary, α-defensins may contribute to tissue tropism not only through the neutralization of susceptible viruses but also by allowing certain defensin-resistant viruses to bind to cells independently of previously described mechanisms., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Ovarian carcinosarcoma (OCS) is an unusual ovarian cancer type characterized by distinct carcinomatous and sarcomatous components. OCS has been excluded from many of the pan-histotype studies of ovarian carcinoma, limiting our understanding of its behavior., Methods: We performed a multi-cohort cross-sectional study of characteristics and outcomes in ovarian cancer patients from Scotland (n=2082) and the Surveillance, Epidemiology and End Results Program (SEER, n=44946) diagnosed with OCS or one of the other major histotypes: high grade serous (HGSOC), endometrioid (EnOC), clear cell (CCOC), mucinous (MOC) or low grade serous ovarian carcinoma (LGSOC). Differences in overall survival were quantified using Cox regression models to calculate hazard ratios (HR)., Results: Across both cohorts, OCS patients were significantly older at diagnosis compared to all other histotypes (median age at diagnosis 69 and 67 in Scottish and SEER cohorts) and demonstrated the shortest survival time upon univariable analysis. Within the Scottish cohort, 59.3% and 16.9% of OCS patients presented with FIGO stage III and IV disease, respectively; this was significantly higher than in EnOC, CCOC or MOC (P<0.0001 for all), but lower than in HGSOC (P=0.004). Multivariable analysis accounting for other prognostic factors identified OCS as independently associated with significantly shorter survival time compared to HGSOC, EnOC, LGSOC and MOC in both the Scottish (multivariable HR vs OCS: HGSOC 0.45, EnOC 0.39, LGSOC 0.26, MOC 0.43) and SEER cohorts (multivariable HR vs OCS: HGSOC 0.59, EnOC 0.34, LGSOC 0.30, MOC 0.81). Within the SEER cohort, OCS also demonstrated shorter survival compared to CCOC (multivariable HR 0.63, 95% CI 0.58-0.68), but this was not replicated within the Scottish cohort (multivariable HR for CCOC: 1.05, 95% CI 0.74-1.51). Within early-stage disease specifically (FIGO I-II or SEER localized stage), OCS was associated with the poorest survival of all histotypes across both cohorts. In the context of late-stage disease (FIGO III-IV or SEER distant stage), OCS, MOC and CCOC represented the histotypes with poorest survival., Conclusion: OCS is a unique ovarian cancer type that affects older women and is associated with exceptionally poor outcome, even when diagnosed at earlier stage. New therapeutic options are urgently required to improve outcomes., Competing Interests: RH: consultancy fees from GlaxoSmithKline and DeciBio. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 McFarlane, Porter, Brownsell, Ghaoui, Connolly, Herrington and Hollis.)

The contextual interference (CI) approach has proposed that a random order of practice for motor skills is superior in facilitating learning compared to a blocked arrangement of practice trials. Two groups of physical education students learned sprint hurdles, employing either an increasing CI practice schedule (n = 23) or a blocked practice schedule (n = 23). In both the practice schedules, the same exercises were used in a different trial order during each learning session. Eleven practice sessions were conducted over a period of six weeks, with two days of practice per week. Ten and 40 days after the acquisition phase, a retention and transfer test were conducted. The results showed no differences between the two practice schedules during the retention tests. However, students practicing with an increasing CI arrangement performed better on the delayed transfer test compared to students which practiced with a blocked schedule. Specifically, the increasing CI group more effectively (p < 0.05) cleared the hurdles due to a lower take-off step angle and longer step length than the blocked practice group. Although utilizing an increase in CI during the learning phase of sprint hurdling produced more persistent learning effects relative to a traditional blocked practice schedule for adult novice learners, further research is warranted to explore the CI effect across a broader range of sport skills., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Makaruk et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In vitro drug screening for type 1 diabetes therapies has largely been conducted on human organ donor islets for proof of efficacy. While native islets are the ultimate target of these drugs (either in situ or for transplantation), significant benefit can be difficult to ascertain due to the highly heterogeneous nature of individual donors and the overall scarcity of human islets for research. We present an in vitro coculture model based on immortalized insulin-producing beta-cell lines with human endothelial cells in 3D spheroids that aims to recapitulate the islet morphology in an effort towards developing a standardized cell model for in vitro diabetes research. Human insulin-producing immortalized EndoC- β H5 cells are cocultured with human endothelial cells in varying ratios to evaluate 3D cell culture models for type 1 diabetes research. Insulin secretion, metabolic activity, live cell fluorescence staining, and gene expression assays were used to compare the viability and functionality of spheroids composed of 100% beta-cells, 1 : 1 beta-cell/endothelial, and 1 : 3 beta-cell/endothelial. Monoculture and β H5/HUVEC cocultures formed compact spheroids within 7 days, with average diameter ~140  μ m. This pilot study indicated that stimulated insulin release from 0 to 20 mM glucose increased from ~8-fold for monoculture and 1 : 1 coculture spheroids to over 20-fold for 1 : 3 EndoC- β H5/HUVEC spheroids. Metabolic activity was also ~12% higher in the 1 : 3 EndoC- β H5/HUVEC group compared to other groups. Stimulating monoculture beta-cell spheroids with 20 mM glucose +1  μ g/mL glycine-modified INGAP-P increased the insulin stimulation index ~2-fold compared to glucose alone. Considering their availability and consistent phenotype, EndoC- β H5-based spheroids present a useful 3D cell model for in vitro testing and drug screening applications., Competing Interests: The authors declare that they have no conflicts of interest regarding this manuscript., (Copyright © 2023 James M. Porter et al.)

Prior research has questioned the appropriateness of internal focus instructions or the juxtaposition to external and control conditions. Moreover, there has been a lack of research conducted to test a variety of internal conditions on motor performance. The purpose of the present study was to address those critiques and add to the attentional focus literature by varying the location of an internal focus while performing a standing long jump. Participants performed a standing long jump during five separate conditions (internal focus: toes, knees, hips, arms; and control). The analysis revealed that all internal focus conditions performed worse than the control condition. Furthermore, the only difference between internal conditions was found between arms and knees, where the knee condition resulted in a significantly shorter jump distance relative to the arms. Regardless of the location specified, all internal focus conditions led to detriments in jump performance when compared to the control condition. These findings add to a large body of work demonstrating the importance of instructional content on motor performance., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Strick et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Public health data modernization efforts frequently overlook the far-reaching effects of structural racism across the data life cycle. Modernizing data requires creating data ecosystems grounded in six principles: dismantling structural racism and building community power explicitly; centering justice in all stages of data collection and analysis; ensuring communities can govern their data; driving positive population-level change; engaging nonprofit organizations; and obtaining commitments from governments to make changes in policy and practice. As government agencies spearhead and finance data modernization initiatives, it is imperative that they address structural racism head-on and integrate these principles into all aspects of their work., Competing Interests: None of the authors declares any conflicts of interest., (© Jamila M. Porter et al., 2023; Published by Mary Ann Liebert, Inc.)

Background and Aims: Few studies of angiosperms have focused on androecial evolution in conjunction with evolutionary shifts in corolla morphology and pollinator relationships. The Western Hemisphere clade of Justiciinae (Acanthaceae) presents the rare opportunity to examine remarkable diversity in staminal morphology. We took a phylogenetically informed approach to examine staminal diversity in this hypervariable group and asked whether differences in anther thecae separation is associated with phylogenetically informed patterns of variation in corolla morphology. We further discuss evidence for associations between anther diversity and pollinators in this lineage., Methods: For the Dianthera/Sarotheca/Plagiacanthus (DSP) clade of Western Hemisphere Justiciinae, we characterized floral diversity based on a series of corolla measurements and using a model-based clustering approach. We then tested for correlations between anther thecae separation and corolla traits, and for shifts in trait evolution, including evidence for convergence., Key Results: There is evolutionary vagility in corolla and anther traits across the DSP clade with little signal of phylogenetic constraint. Floral morphology clusters into four distinct groups that are, in turn, strongly associated with anther thecae separation, a novel result in Acanthaceae and, to our knowledge, across flowering plants. These cluster groups are marked by floral traits that strongly point to associations with pollinating animals. Specifically, species that are known or likely to be hummingbird pollinated have stamens with parallel thecae, whereas those that are likely bee or fly pollinated have stamens with offset, divergent thecae., Conclusions: Our results suggest that anther thecae separation is likely under selection in concert with other corolla characters. Significant morphological shifts detected by our analyses corresponded to putative shifts from insect to hummingbird pollination. Results from this study support the hypothesis that floral structures function in an integrated manner and are likely subject to selection as a suite. Further, these changes can be hypothesized to represent adaptive evolution., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The evolution of virtual reality (VR) has created the opportunity for a relatively low-cost and accessible method to practice motor skills. Previous studies have demonstrated how motor skill practice in non-immersive virtual environments transfers to physical environments. Though minimal research has investigated motor learning and transfer within immersive VR, multiple experiments provide empirical evidence of positive transfer effects. Most studies have used software engines and modified hardware to enhance the similarities between virtual and physical environments. However, many learners and practitioners currently use commercially available VR intending to enhance real-world performance, though there is very little evidence to support the notion of positive transfer for these systems. Therefore, this experiment aimed to investigate how motor skill practice using a commercially available VR system improved real-world performance and how that compared to physical practice. Participants (n = 68) were randomly selected into one of two groups: virtual reality (VR) practice (n = 33) or real-world (RW) practice (n = 35). The experiment occurred over two consecutive days, with a pretest, posttest, and practice phase occurring each day. The pre- and post-testing phases were identical for both groups and consisted of putting a golf ball 10 times on a carpeted surface towards the center of a target. The practice phases consisted of 60 total putts per day in the respective environment (VR or RW). Participants continuously alternated golf putting holes from three different distances until they accrued 60 total putts. Participants in the RW group performed golf putts to three targets. Participants in the VR group also performed golf putts on three different miniature golf putting holes, using the commercially available Oculus Rift and the Cloudlands VR Minigolf game. The VR putting targets were designed to replicate the putting holes in the physical environment. Separate 2 (group) x 4 (test) repeated measures ANOVAs were used to assess accuracy and club head kinematics. The results revealed a significant main effect for test, but not for group. Post hoc analyses revealed that both groups significantly improved their putting accuracy and club head kinematics at similar rates. The results from this study indicate that the transfer of learning that occurred as a result of practicing in a commercially available VR environment was similarly effective when compared to RW practice., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Markwell et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Fundamental motor skills (FMS) are essential for enjoyable, confident and skillful participation in physical activity across the lifespan. Due to the alarming low level of FMS proficiency in children and adolescents worldwide, the development of motor competency is an urgent issue for physical education. The promotion and implementation of a systematic process of teaching and learning FMS should be a physical education priority. Accordingly, effective assessment tools for evaluating FMS should be adopted or developed. Because FMS assessment for both children and adolescents need further effective solutions, the primary aim of this study was to develop the new age-related test of FMS (Fundamental Motor Skills in Sport test, in Polish: Test Fundamentalnych Umiejętności Ruchowych w Sporcie, FUS). The secondary aim of this study was to establish validity and inter-rater, intra-rater, test-retest reliabilities and internal consistency of the FUS test. The FUS test involves six sport skill-based tasks: hurdling, jumping rope, forward roll, ball bouncing, throwing and catching a ball, and kicking and stopping a ball. Two hundred sixty-four Polish students in grades 1-3 (7-9 yrs; n = 81), 4-6 (10-12 yrs; n = 89) and 7-8 (13-14 yrs; n = 94), including 139 girls and 125 boys completed the FUS test. The content validity index for all items was notably high. Both inter-rater and intra-rater reliability showed substantial to almost perfect agreement, with observed agreements for FUS skills between 78.5 and 93.1%. Ball bouncing had a moderate correlation with the forward roll and throwing and catching, while other correlations were low or insignificant. ICC values, ranging from 0.95 to 0.97, confirmed excellent test-retest reliability. The results of our study provide evidence that the FUS test is valid, reliable, and feasible to administer in school settings. Therefore, this tool test has the potential to support deliberate practice and improve motor competence by providing a standardized and structured approach to measuring FMS among school-aged children and adolescents., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Whole blood use in trauma has historically been limited to military use, but in recent years, there has been increasing data for use in civilian trauma. Emerging clinical data demonstrate an associated survival benefit, while some authors have also identified decreased use of an overall number of blood products and decreased complications. Use of whole blood is gradually moving toward becoming the standard of care in the hemorrhaging trauma patient., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Whole blood (WB) resuscitation has been associated with a mortality benefit in trauma patients. Several small series report the safe use of WB in the pediatric trauma population. We performed a subgroup analysis of the pediatric patients from a large prospective multicenter trial comparing patients receiving WB or blood component therapy (BCT) during trauma resuscitation. We hypothesized that WB resuscitation would be safe compared to BCT resuscitation in pediatric trauma patients., Methods: This study included pediatric trauma patients (0-17 y), from ten level-I trauma centers, who received any blood transfusion during initial resuscitation. Patients were included in the WB group if they received at least one unit of WB during their resuscitation, and the BCT group was composed of patients receiving traditional blood product resuscitation. The primary outcome was in-hospital mortality with secondary outcomes being complications. Multivariate logistic regression was performed to assess for mortality and complications in those treated with WB vs BCT., Results: Ninety patients, with both penetrating and blunt mechanisms of injury (MOI), were enrolled in the study (WB: 62 (69%), BCT: 28 (21%)). Whole blood patients were more likely to be male. There were no differences in age, MOI, shock index, or injury severity score between groups. On logistic regression, there was no difference in complications. Mortality was not different between the groups ( P = .983)., Conclusion: Our data suggest WB resuscitation is safe when compared to BCT resuscitation in the care of critically injured pediatric trauma patients.

Background: Injuries and violence share many of the same risk and protective factors, which are rooted in the social determinants of health (SDOH) and the social determinants of equity. Addressing shared risk and protective factors (SRPFs)-common factors that make it more or less likely that a population will experience injuries or violence-is critical prevention efforts. The Safe States Alliance created the Connections Lab-a suite of web-based resources to help injury and violence prevention public health practitioners and their partners understand, describe, implement and evaluate SRPF approaches., Design: A mixed-methods approach using the Diffusion of Innovation Theory assessed how the Connections Lab influenced users' knowledge, abilities and work related to SRPF approaches. A web-based survey was administered to 234 participants in April-May 2021. Semistructured virtual group discussions were conducted with a subset of 15 survey respondents who volunteered to participate., Results: The case study revealed three key findings. The Connections Lab: was diffused among practitioners across sectors within and outside of public health; it increased practitioners' perceived proficiency across 10 skill sets related to describing, planning, implementing and evaluating SRPF approaches; and it increased understanding of the importance of upstream and structural drivers of injuries and violence., Conclusion: The Connections Lab was a critical first step to expand the definition of SRPF approaches, connect SRPFs to concepts of equity and the SDOH, and provide strategies for engaging partners in public health and across other sectors in SRPF approaches., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Changes in the workrate and seat position have been linked to changes in internal knee extension moment. However, there is limited research on effects of those changes on knee kinetics in recumbent bike. The purpose of this study was to examine the effects of different seat positions and workrates on KAbM, knee extension moment and perceived effort during stationary recumbent cycling. Fifteen cyclists cycled on a recumbent ergometer in 6 test conditions of pedalling in far, medium and close seat positions in each of the two workrates of 60 and 100 W at the cadence of 80 RPM. A three-dimensional motion analysis system and a pair of instrumented pedals collected kinematic and kinetic data. A 3 ×2 repeated measures ANOVA was used to examine the effect of seat positions and workrates on selected variables of interest. Different seat positions did not change either peak KAbM (p = 0.592) or knee extension moment (p = 0.132). Increased workrates significantly increased peak KAbM (p <0.001 and η p 2 =0.794) and knee extension moment (p <0.001 and η p 2 =0.722). This study showed that the far or close seat position did not increase frontal-plane or overall knee joint loading and provided evidence for prescribing recumbent bike for healthy population.

Objectives. To examine the association between historical redlining and contemporary pedestrian fatalities across the United States. Methods. We analyzed 2010-2019 traffic fatality data, obtained from the Fatality Analysis Reporting System, for all US pedestrian fatalities linked by location of crash to 1930s Home Owners' Loan Corporation (HOLC) grades and current sociodemographic factors at the census tract level. We applied generalized estimating equation models to assess the relationship between the count of pedestrian fatalities and redlining. Results. In an adjusted multivariable analysis, tracts graded D ("Hazardous") had a 2.60 (95% confidence interval = 2.26, 2.99) incidence rate ratio (per residential population) of pedestrian fatalities compared with tracts graded A ("Best"). We found a significant dose‒response relationship: as grades worsened from A to D, rates of pedestrian fatalities increased. Conclusions. Historical redlining policy, initiated in the 1930s, has an impact on present-day transportation inequities in the United States. Public Health Implications. To reduce transportation inequities, understanding how structurally racist policies, past and present, have an impact on community-level investments in transportation and health is crucial. ( Am J Public Health . 2023;113(4):420-428. https://doi.org/10.2105/AJPH.2022.307192).

Adeno-associated viruses (AAVs) are being developed as gene therapy vectors due to their low pathogenicity and tissue tropism properties. However, the efficacy of these vectors is impeded by interactions with the host immune system. One potential immune barrier to vector transduction is innate immune host defense peptides, such as alpha-defensins, which are potent antiviral agents against other nonenveloped viruses. To investigate the interaction between AAVs and alpha-defensins, we utilized two closely related AAV serotypes, AAV1 and AAV6. Although their capsids differ by only six residues, these two serotypes exhibit markedly different tissue tropisms and transduction efficiencies. Using two abundant human alpha-defensins, enteric human defensin 5 (HD5) and myeloid human neutrophil peptide 1 (HNP1), we found both serotype-specific and defensin-specific effects on AAV infection. AAV6 infection was uniformly neutralized by both defensins at low micromolar concentrations; however, inhibition of AAV1 infection was profoundly influenced by the timing of defensin exposure to the virus relative to viral attachment to the cell. Remarkably, these differences in the defensin-dependent infection phenotype between the viruses are completely dictated by the identity of a single, surface-exposed amino acid (position 531) that varies between the two serotypes. These findings reveal a determinant for defensin activity against a virus with unprecedented precision. Furthermore, they provide a rationale for the investigation of other AAV serotypes not only to understand the mechanism of neutralization of defensins against AAVs but also to design more efficient vectors. IMPORTANCE The ability of adeno-associated viruses (AAVs) to infect and deliver genetic material to a range of cell types makes them favorable gene therapy vectors. However, AAV vectors encounter a wide variety of host immune factors throughout the body, which can impede efficient gene delivery. One such group of factors is the alpha-defensins, which are a key component of the innate immune system that can directly block viral infection. By studying the impact that alpha-defensins have on AAV infection, we found that two similar AAV serotypes (AAV1 and AAV6) have different sensitivities to inhibition. We also identified a single amino acid (position 531) that differs between the two AAV serotypes and is responsible for mediating their defensin sensitivity. By investigating the effects that host immune factors have on AAV infection, more efficient vectors may be developed to evade intervention by the immune system prior to gene delivery.

Recent research has demonstrated that consistent external attentional focus instructions produce more reliable jumping measurements compared to non-consistent focus of attention instructions. While previous research has examined the effects of different external attentional focus instructions, less is known about different external focus of attention instruction effects during a vertical jump. Given that previous work has demonstrated that consistent external focus of attention instructions produced reliable jumping estimations, we hypothesized that using multiple methods to direct attention externally would produce consistent vertical jump results. Using a within-participant design, college aged students ( n = 35) completed two vertical jumps on a Vertec TM within five conditions. Each condition was provided different external directing instructions conditions (control; external-lower near, -upper near, -upper far, -unreachable far). Data were analyzed using a repeated measures analysis of variance (ANOVA). Results showed that jump heights in the control and external focus of attention conditions were not significantly different from one another, p = .119. The findings of this study suggest there are numerous external focus of attention instructions that can be provided during a vertical jump producing consistent results.

Objective: To assess the governmental public health (GPH) workforce's awareness of and confidence to address health equity , social determinants of health ( SDoH ), and social determinants of equity ( SDoE ) in their work., Design, Setting, and Participants: A nationally representative population of US local and state GPH employees (n = 41 890) were surveyed through the 2021 Public Health Workforce Interests and Needs Survey (PH WINS 2021)., Main Outcome Measures: Self-reported awareness and confidence were explored by self-identified racial and ethnic group identity, public health degree attainment, and supervisory status., Results: GPH employees reported higher levels of awareness across concepts ( health equity -71%, 95% confidence interval [CI]: 70.5-71.6; SDoH -62%, 95% CI: 62.3-63.5; SDoE -48%, 95% CI: 47.2-48.4) than confidence ( health equity -48%, 95% CI: 47.8-49.0; SDoH -46%, 95% CI: 45.4-46.7; SDoE -34%, 95% CI: 33.4-34.6). Self-identified Black or African American employees reported higher confidence across all concepts ( health equity -56%, 95% CI: 54.3-57.6; SDoH -52%, 95% CI: 50.8-54.1; SDoE -43%, 95% CI: 41.3-44.6) compared to other self-identified racial groups. Employees with a PH degree reported higher confidence across all concepts ( health equity -65%, 95% CI: 63.8-68.8; SDoH -73%, 95% CI: 71.3-74.1; SDoE -39%, 95% CI: 36.9-40.1) compared with employees without a PH degree ( health equity -45%, 95% CI: 44.8-46.1; SDoH -41%, 95% CI: 40.6-41.9; SDoE -33%, 95% CI: 32.6-33.8). We found an inverse relationship between supervisory status and confidence to address SDoE : Nonsupervisors reported higher confidence (35%, 95% CI: 29.2-31.9) than supervisors (31%, 95% CI: 29.2-31.9), managers (31%, 95% CI: 28.8-32.6), and executives (32%, 95% CI: 27.5-34.4)., Conclusion: PH WINS 2021 reveals that GPH employees are aware of equity-related concepts but lack confidence to address them. Public health agencies should build employees' confidence by prioritizing and operationalizing equity internally and externally in collaboration with communities and partners., Competing Interests: The authors have indicated they have no potential conflicts of interests to disclose., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc.)

The aim of the study was to determine the impact of internal and external (proximal and distal) attentional focus on table tennis backhand stroke accuracy in low-skilled players. Fifty-one undergraduate physical education (PE) students were randomly assigned to 3 groups: Group G1 (IF) was instructed to focus on the hand holding the paddle, Group G2 (EFP) was instructed to focus on the ball, while Group G3 (EFD) was instructed to focus on targets marked on the tennis table. The experimental groups followed identical instructions except for the instruction about the focus of attention. Participants were asked to score as many points as possible by hitting the ball inside the three smallest targets marked on the tennis table. They were required to do so using a backhand stroke. The practice session consisted of 45 trials in three blocks of backhand (15 trials at each target). A special scoring system was used to determine the accuracy of the strokes. One of the most important findings from the current research was that groups with an external focus of attention revealed significant improvements in accuracy in the post-test, while the group with an internal focus of attention achieved low training effects. No significant difference was observed between G2 (EFP) and G3 (EFD) in the delayed retention test, which indicates that proximal and distal attentional focus had similar effects on table tennis backhand stroke accuracy in low-skilled players., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Niźnikowski et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The novice anesthesiology trainee is required to assimilate the technical and nontechnical skills required to safely perform a rapid sequence induction (RSI). Acquisition of this core competency is traditionally achieved using operating room-based experiential learning, which may be associated with significant gaps in early trainee preparation. We conducted a study to explore the role of a new, customized, high-fidelity simulation-based training program designed to address this gap in RSI training. We then assessed mean performance scores of participants in the simulator and 4 weeks later., Methods: This observational study assessed participants' performance in the simulator on the day of training and in the workplace 4 weeks later. There is no universally agreed checklist or cognitive aid incorporating nontechnical skills and planning for unanticipated difficult airway management in RSI, so we applied a new scoring checklist developed by 6 experts using the modified Delphi technique., Results: Our task scoring checklist included nontechnical skills and consisted of 37 weighted parameters with a maximum performance score of 171. On the day of training, mean performance score was 105 (SD of 16). At the workplace evaluation 4 weeks after simulation training, the mean performance score of participants had increased to 140 (SD of 14.5; P = .001). The 95% confidence intervals for the simulator and workplace participant scores were 92 to 118 and 128 to 152, respectively., Conclusions: The results suggest that this simulation-based training in RSI was associated with an improvement in RSI performance in novice trainees and may complement the current system of workplace-based training., Competing Interests: Conflicts of interest: None, (© 2022 Society for Education in Anesthesia.)

Objective: The aim of this study was to identify a mortality benefit with the use of whole blood (WB) as part of the resuscitation of bleeding trauma patients., Background: Blood component therapy (BCT) is the current standard for resuscitating trauma patients, with WB emerging as the blood product of choice. We hypothesized that the use of WB versus BCT alone would result in decreased mortality., Methods: We performed a 14-center, prospective observational study of trauma patients who received WB versus BCT during their resuscitation. We applied a generalized linear mixed-effects model with a random effect and controlled for age, sex, mechanism of injury (MOI), and injury severity score. All patients who received blood as part of their initial resuscitation were included. Primary outcome was mortality and secondary outcomes included acute kidney injury, deep vein thrombosis/pulmonary embolism, pulmonary complications, and bleeding complications., Results: A total of 1623 [WB: 1180 (74%), BCT: 443(27%)] patients who sustained penetrating (53%) or blunt (47%) injury were included. Patients who received WB had a higher shock index (0.98 vs 0.83), more comorbidities, and more blunt MOI (all P <0.05). After controlling for center, age, sex, MOI, and injury severity score, we found no differences in the rates of acute kidney injury, deep vein thrombosis/pulmonary embolism or pulmonary complications. WB patients were 9% less likely to experience bleeding complications and were 48% less likely to die than BCT patients ( P <0.0001)., Conclusions: Compared with BCT, the use of WB was associated with a 48% reduction in mortality in trauma patients. Our study supports the use of WB use in the resuscitation of trauma patients., Competing Interests: J.P.H.: Amsel Corporation: consultant; H.K.: UpToDate: consultant. The remaining authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)