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Objective To systematically investigate the prevalence of knee MRI findings among symptomatic pediatric soccer players with respect to skeletal maturity and to identify predictors of surgery. Methods This IRB-approved, HIPAA-compliant retrospective study included soccer players (< 18 years of age) who underwent MRI examinations in the past 5 years (2018–2023). Two radiologists retrospectively and independently reviewed all examinations to categorize skeletal maturity and to identify osseous and soft tissue findings. Findings were compared between maturation groups, and logistic regression models were used to identify predictors of surgery. Results Ninety-seven players (45 boys, 52 girls) included 39 skeletally immature, 21 maturing, and 37 mature knees. Kappa coefficient for interobserver reliability ranged between 0.65 and 1.00. Osgood-Schlatter disease (OSD) was more common among immature than maturing and mature knees (25% vs 14% and 5%, p = 0.04); anterior cruciate ligament (ACL) injury was more common among maturing and mature than immature knees (59% and 48%, vs 15%, p < 0.01); and meniscal tears were more common among mature than immature and maturing knees (medial, 41% vs 18% and 14%, p = 0.03; lateral, 43% vs 21% and 19%, p = 0.04). Players in the mature group were more likely to undergo surgery ( p = 0.01). The presence of an effusion (OR = 19.5, 95% CI 2.8–240.9, p = 0.01), ACL injury (OR = 170.0, 95% CI 1.3–6996.9, p < 0.01), and lateral meniscal tears (OR = 10.8, 95% CI 1.8–106.1, p = 0.02) were independent predictors of surgery. Conclusion Differential patterns of injury were found among symptomatic pediatric soccer players; the presence of an effusion, ACL injury, and lateral meniscal tears were independent predictors of surgery, likely contributing to the higher rates of surgery among skeletally mature players.

C₄ photosynthesis allows increased photosynthetic efficiency because carbon dioxide (CO₂) is concentrated around the key enzyme RuBisCO. Leaves of C₄ plants exhibit modified biochemistry, cell biology, and leaf development, but despite this complexity, C₄ photosynthesis has evolved independently in at least 45 lineages of plants. We found that two independent lineages of C₄ plant, whose last common ancestor predates the divergence of monocotyledons and dicotyledons about 180 million years ago, show conserved mechanisms controlling the expression of genes important for release of CO₂ around RuBisCO in bundle sheath (BS) cells. Orthologous genes from monocotyledonous and dicotyledonous C₃ species also contained conserved regulatory elements that conferred BS specificity when placed into C₄ species. We conclude that these conserved functional genetic elements likely facilitated the repeated evolution of C₄ photosynthesis.

Acute kidney injury (AKI) affects 10–15% of hospitalised patients and arises after severe infections, major surgeries, or exposure to nephrotoxic drugs. AKI diagnosis based on creatinine level changes lacks specificity and may be delayed. MicroRNAs are short non-coding RNA secreted by all cells. This review of studies measuring miRNAs in AKI aimed to verify miRNAs as diagnostic markers. The study included data from patients diagnosed with AKI due to sepsis, ischaemia, nephrotoxins, radiocontrast, shock, trauma, and cardiopulmonary bypass. Out of 71 studies, the majority focused on AKI in sepsis patients, followed by cardiac surgery patients, ICU patients, and individuals receiving nephrotoxic agents or experiencing ischaemia. Studies that used untargeted assays found 856 differentially regulated miRNAs, although none of these were confirmed by more than one study. Moreover, 68 studies measured miRNAs by qRT-PCR, and 2 studies reported downregulation of miR-495-3p and miR-370-3p in AKI patients with sepsis after the AKI diagnosis. In three studies, upregulation of miR-21 was reported at the time of the AKI diagnosis with a significant pooled effect of 0.56. MiR-21 was also measured 19–24 h after cardiac surgery in three studies. However, the pooled effect was not significant. Despite the considerable research into miRNA in AKI, there is a knowledge gap in their applicability as diagnostic markers of AKI in humans.

Background Polypharmacy in older adults can be associated with negative outcomes including falls, impaired cognition, reduced quality of life, and general and functional decline. It is not clear to what extent these are reversible if the number of medications is reduced. Primary care does not have a systematic approach for reducing inappropriate polypharmacy, and there are few, if any, approaches that account for the patient’s priorities and preferences. The primary objective of this study is to test the effect of TAPER (Team Approach to Polypharmacy Evaluation and Reduction), a structured operationalized clinical pathway focused on reducing inappropriate polypharmacy. TAPER integrates evidence tools for identifying potentially inappropriate medications, tapering, and monitoring guidance and explicit elicitation of patient priorities and preferences. We aim to determine the effect of TAPER on the number of medications (primary outcome) and health-related outcomes associated with polypharmacy in older adults. Methods We designed a multi-center randomized controlled trial, with the lead implementation site in Hamilton, Ontario. Older adults aged 70 years or older who are on five or more medications will be eligible to participate. A total of 360 participants will be recruited. Participants will be assigned to either the control or intervention arm. The intervention involves a comprehensive multidisciplinary medication review by pharmacists and physicians in partnership with patients. This review will be focused on reducing medication burden, with the assumption that this will reduce the risks and harms of polypharmacy. The control group is a wait list, and control patients will be given appointments for the TAPER intervention at a date after the final outcome assessment. All patients will be followed up and outcomes measured in both groups at baseline and 6 months. Discussion Our trial is unique in its design in that it aims to introduce an operationalized structured clinical pathway aimed to reduce polypharmacy in a primary care setting while at the same time recording patient’s goals and priorities for treatment. Trial registration Clinical Trials.gov NCT02942927. First registered on October 24, 2016.

Polypharmacy is associated with poorer health outcomes in older adults. It is challenging to minimize the harmful effects of medications while maximizing benefits of single-disease-focused recommendations. Integrating patient input can balance these factors. The objectives are to describe the goals, priorities, and preferences of participants asked about these in a structured process to polypharmacy, and to describe the extent that decision-making within the process mapped onto these, signaling a patient-centered approach. This is a single-group quasi-experimental study, nested within a feasibility randomized controlled trial. Patient goals and priorities were mapped to medication recommendations made during the intervention. Overall, there were 33 participants who reported 55 functional goals and 66 symptom priorities, and 16 participants reported unwanted medications. Overall, 154 recommendations for medication alterations occurred. Of those, 68 (44%) recommendations mapped to the individual's goals and priorities, whereas the rest were based on clinical judgment where no priorities were expressed. Our results signal this process supports a patient-centered approach: allowing conversations around goals and priorities in a structured process to polypharmacy should be integrated into subsequent medication decisions.

Teachers often address student wellness concerns such as health and mental health. Yet, this work goes largely unacknowledged and unsupported by professional preparation. COVID-19 intensified these concerns amid disrupted systems of student support and increased student distress. Our national survey (N = 1398) pursued the powerful opportunity present during the pandemic to understand the extent and distribution of demands on teachers to address student wellness and the support they receive for such work. We found that the demand for teachers’ wellness work was inequitably distributed across teachers, varying largely by their schools’ sociodemographic characteristics. Additionally, access to support for this work did not align with demand levels. We discuss these findings’ implications for teacher preparation, support, and workload equity.

Improper regulation of B cell responses leads to excessive production of antibodies and contributes to the development of autoimmune disease. T helper 17 (Th17) cells also drive the development of autoimmune disease, but the role of B cells in shaping Th17 cell-mediated immune responses, as well as the reciprocal regulation of B cell responses by IL-17 family cytokines, remains unclear. The aim of this study was to characterize the regulation of IL-17A and IL-17F in a model of T cell-dependent B cell activation. Stimulation of primary human B cell and peripheral blood mononuclear cell (BT) co-cultures with α-IgM and a non-mitogenic concentration of superantigens for three days promoted a Th17 cell response as evidenced by increased expression of Th17-related gene transcripts, including Il17f, Il21, Il22, and Il23r, in CD4 T cells, as well as the secretion of IL-17A and IL-17F protein. We tested the ability of 144 pharmacologic modulators representing 91 different targets or pathways to regulate IL-17A and IL-17F production in these stimulated BT co-cultures. IL-17A production was found to be preferentially sensitive to inhibition of the PI3K/mTOR pathway, while prostaglandin EP receptor agonists, including PGE2, increased IL-17A concentrations. In contrast, the production of IL-17F was inhibited by PGE2, but selectively increased by TLR2 and TLR5 agonists. These results indicate that IL-17A regulation is distinct from IL-17F in stimulated BT co-cultures and that this co-culture approach can be used to identify pathway mechanisms and novel agents that selectively inhibit production of IL-17A or IL-17F.

Background: Sport specialization is an important area of focus within pediatric sports medicine with studies relating specialization to the rising incidence of sport-related injuries. The relationship between sport specialization and concussion remains unexplored. Hypothesis/Purpose: The objective of this study was to assess the prevalence of sport specialization and its relationship to concussion in athletes seen in a tertiary concussion program. Methods: Athletes completed a sport specialization questionnaire as part of a comprehensive intake questionnaire and were classified into low, moderate, or high specialization groups using a previously published 3-point scale. Categories were derived from their responses to 3 binary questions: 1) Have you quit other sports to focus on 1 sport? 2) Do you train >8 months out of the year in 1 sport? 3) Do you consider your primary sport more important than other sports? Results: Of the 1,098 athletes, ages 8-19 years, who completed the questionnaire, 572 (52%) were female, 718 (65.5%) had a sports-related concussion (SRC) and 439 (40%) had a prior history of concussion. The cohort was categorized into low (n=568, 51.7%), moderate (n=339, 30.9%), or high (n=191, 17.4%) sport specialization groups. Athletes reported their primary sport was more important than other sports (702, 64%) and training >8 months out of the year in 1 sport (594, 54%) more commonly than quitting other sports to focus on 1 sport (270, 25%). Sport specialization differed by primary sport (Figure 1), but did not significantly differ when primary sport was grouped by level of contact (p=0.47). Sport specialization did not significantly differ by sex, race, or ethnicity, but significantly differed by insurance (p=0.014) and age (p=0.0001), with greater specialization among those with private insurance and adolescents, respectively. Moderately or highly specialized athletes were significantly more likely than less specialized athletes to present with a SRC compared to a non-SRC (p<0.0001) and to report prior history of concussion (p=0.005). After controlling for demographic and sport participation factors, only endorsement of training more than 8 months out of the year in one sport was significantly associated with SRC (p=0.001) and prior concussion (p=0.007). Conclusion: Sport specialization is prevalent among youth athletes with concussion. Training >8 months out of the year in a single sport is associated with SRC and prior history of concussion. Further research is warranted to evaluate how exposure among specialized athletes relates to concussion.

In leaves of most C₄ plants, the biochemistry of photosynthesis is partitioned between mesophyll and bundle sheath cells. In addition, their cell biology and development also differs from that in C₃ plants. We have a poor understanding of the mechanisms that generate the cell-specific accumulation of proteins used in the C₄ pathway, and there are few genes that have been shown to be important for the cell biology and development of C₄ leaves. To facilitate functional analysis of C₄ photosynthesis, and to enable knowledge from Arabidopsis thaliana to be translated to C₄ species, an Agrobacterium tumefaciens-mediated transformation protocol was developed for the C₄ species Cleome gynandra. A. tumefaciens, harbouring the binary vector SLJ1006, was used to transfer the uidA gene under the control of the CaMV 35S promoter into C. gynandra. Co-incubation of hypocotyls or cotyledons with SLJ1006 allowed efficient transfer of DNA into C. gynandra, and media that allowed callus production and then shoot regeneration were identified. Stable transformants of C. gynandra with detectable amounts of β-glucuronidase (GUS) were produced at an efficiency of 14%. When driven by the CaMV 35S promoter, GUS was visible in all leaf cells, whereas uidA translationally fused to a CgRbcS gene generated GUS accumulation specifically in bundle sheath cells. This transformation procedure is the first for an NAD-ME type C₄ plant and should significantly accelerate the analysis of mechanisms underlying C₄ photosynthesis.

Our most productive crops and native vegetation use a modified version of photosynthesis known as the C₄ pathway. Leaves of C₄ crops have increased nitrogen and water use efficiencies compared with C₃ species. Although the modifications to leaves of C₄ plants are complex, their faster growth led to the proposal that C₄ photosynthesis should be installed in C₃ crops in order to increase yield potential. Typically, a limited set of proteins become restricted to mesophyll or bundle sheath cells, and this allows CO₂ to be concentrated around the primary carboxylase RuBisCO. The role that these proteins play in C₃ species prior to their recruitment into the C₄ pathway is addressed here. Understanding the role of these proteins in C₃ plants is likely to be of use in predicting how the metabolism of a C₃ leaf will alter as components of the C₄ pathway are introduced as part of efforts to install characteristics of C₄ photosynthesis in leaves of C₃ crops.