Avulsion and Soft Tissue Injuries of the Ulnar Collateral Ligament in Children and Adolescents.

BACKGROUND: Although pediatric medial epicondylar fractures and apophysitis are well studied, patterns of subapophyseal avulsion and ligamentous injuries of the medial elbow in this population merit investigation to inform optimal treatment strategies. PURPOSE: To describe the occurrence and demographic correlates of ulnar collateral ligament (UCL) avulsion and soft tissue injuries of the pediatric and adolescent elbow. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: An institutional review board-approved review was conducted to identify consecutive patients with medial elbow injuries treated in a tertiary pediatric sports medicine practice between 2016 and 2021. Radiographs were obtained during injury evaluation, and patients with nondisplaced medial epicondylar apophysitis and complete epicondylar fracture were excluded, resulting in 150 patients with soft tissue injuries occurring distal to the medial epicondyle apophysis (subapophyseal) for study. Radiographs were evaluated for bony avulsion of the UCL from either the medial epicondyle proximally or the ulnar sublime tubercle distally. Injuries without radiographic evidence of bony avulsion, but with clinical examination findings consistent with ligamentous injury, were classified as radiographically negative UCL injuries, and magnetic resonance imaging (MRI) was performed to further evaluate these injuries if moderate to severe medial swelling of the elbow or significant concern for medial structural injury was present on examination. These MRI scans were evaluated to classify the UCL injury and assess for periosteal or cartilaginous avulsions. RESULTS: A total of 150 patients (mean age, 12.5 ± 3.4 years; 70 female), 55% (150/274) of the entire medial elbow injury population, had a subapophyseal injury. Of these patients, 62 had a bony avulsion detected on radiograph, and 88 had a radiographically negative injury. In addition to the 62 radiographic avulsions, the 61 MRI scans obtained on those radiographically negative injuries revealed 33 complete UCL disruptions, resulting in 63.3% (95/150) of patients sustaining a complete ligamentous disruption. With the MRI scans, 37 (61%) cases of cartilaginous or periosteal avulsion of the UCL were diagnosed. Overall, 66% of all 150 subapophyseal injuries had a bony, cartilaginous, or periosteal UCL avulsion. Patients with cartilaginous (mean age, 10.3 years) and bony (mean age, 10.6 years) avulsions were younger than those with central ligament injury (mean age, 14.2 years) or periosteal (mean age, 14.2 years) avulsions (P = .005). There was a significant association between the mechanism of injury and the location of UCL tear identified on MRI scans: traumatic falls were associated with distal tears, and throwing injuries were associated with proximal tears (P < .001). CONCLUSION: UCL central ligament and avulsion lesions may be frequently diagnosed after injury to the pediatric medial elbow, the majority of which are complete injuries, and may require MRI for diagnosis. The mechanism of injury may predict the location of ligamentous injury, and osteocartilaginous avulsions are more likely to present at younger ages than injuries to the soft tissue of the UCL or periosteum. The prevalence of these injuries merits further investigation into best protocols of nonoperative treatment or surgical repair techniques and outcomes.

A systematic review and meta-analysis of the relationship between youth drinking, self-posting of alcohol use and other social media engagement (2012-21).

BACKGROUND AND AIM: Social networking sites (SNS) are interactive internet-based social platforms that facilitate information sharing. A growing body of literature on exposure to, and self-posting of, alcohol-related content on SNS has examined the relationship between SNS use and alcohol consumption in young people. This study aims to synthesise the literature exploring the relationship between exposure (i.e. viewing or listening of alcohol-related media) and self-posting (i.e. uploading images or text of alcohol content) of alcohol-related media on SNS on alcohol consumption. METHODS: A pre-registered systematic review was conducted in June 2022 within PubMed, Scopus, PsycINFO and Web of Science. Original prospective and cross-sectional studies assessing youth and young adults (≤ 24 years of age) that measured exposure to alcohol-related media or posting of alcohol-related content on SNS and self-reported alcohol consumption outcomes were included. Meta-analyses were conducted on comparable methodologies. RESULTS: Thirty studies were included (n = 19,386). Meta-analyses of cross-sectional studies showed both greater exposure (five studies; pooled ß = 0.34, 95% confidence interval [CI] = 0.23, 0.44, i2 = 27.7%) and self-posting of alcohol-related content (six studies; pooled ß = 0.57, 95%CI = 0.25,0.88, i2 = 97.8%) was associated with greater alcohol consumption. Meta-analyses of three prospective studies also identified that greater exposure predicted greater future alcohol consumption (three studies; pooled ß = 0.13, 95%CI = 0.11,0.15, i2 = 0.0%). Narrative analyses of studies that could not be meta-analysed due to incompatible methodologies were also conducted. Most studies (all four prospective, one of two cross-sectional) identified positive associations between exposure to alcohol-related content and greater average consumption. Most studies (three of four prospective, four of six cross-sectional) reported a positive association between of alcohol-related self-posting and greater average alcohol consumption. CONCLUSIONS: Both exposure to, and self-posting of, alcohol-related content on social networking sites are positively associated with current average consumption, problem drinking, and drinking frequency.

Comparison of Gait and Functional Outcomes Between Open and Arthroscopic Treatment of Adolescent and Young Adult Femoroacetabular Impingement.

BACKGROUND: Management of femoroacetabular impingement (FAI) through an arthroscopic or surgical hip dislocation (SHD) approach has been shown to have similar clinical success and patient-reported outcomes. However, there are limited data comparing functional outcomes. The purpose of this study was to compare gait and functional outcomes of adolescent/young adult patients with FAI treated by either an arthroscopic or open SHD approach. METHODS: We identified prospectively enrolled adolescent/young adult patients (≤20 years old) who underwent surgical treatment for FAI through an SHD or arthroscopic approach. Participants were evaluated in a movement science lab preoperatively and postoperatively (minimum 8 months postoperatively) with barefoot walking and a 30-second single-limb balance trial on the affected side. Participants also completed the Harris Hip Score at the same timepoints. Differences from preoperative to postoperative were determined using a paired-samples t test for each surgical technique, and differences between the SHD and arthroscopic groups were determined using an independent samples t test (α=0.05). RESULTS: Fifty-five participants (42F, 16.2±1.4 y) were tested and grouped by surgical intervention. The SHD and arthroscopy groups consisted of 28 and 27 participants, respectively, with no significant difference between the SHD and arthroscopic cohorts in age (16.4±1.2 vs. 15.9±1.5 y, respectively, P =0.218) or sex distribution (78.6% vs. 74.1% females, respectively, P =0.75). Each group demonstrated significant postoperative improvement in Harris Hip Score (SHD: 64.8±16.4 to 81.8±17.8; arthroscopy: 57.0±16.7 to 84.7±19.7; preoperatively to postoperatively, respectively, both P <0.001). During gait, increased maximum hip flexion was observed following surgical intervention for the SHD group (32.3±5.7 vs. 36.1±5.2, P =0.003). No other clinically significant changes were detected in the SHD or arthroscopic groups preoperatively to postoperatively in trunk, pelvis, or hip kinematics in the coronal plane. During the balance task, neither cohort demonstrated markers of clinically significant abductor dysfunction. However, post operatively, the arthroscopy group was able to balance longer than the SHD group (18.8±7.8 vs. 14.2±2.7 s, respectively, P =0.008), although no differences were detected in trunk or pelvis position in the coronal plane during balance. CONCLUSIONS: Both open SHD and arthroscopic treatment of FAI resulted in improved clinical outcomes with no clinically significant abductor dysfunction 1 year post operatively. However, further study is needed to determine whether more dynamic tasks can potentially elicit subtle differences between the groups. LEVELS OF EVIDENCE: Level II-prospective study.

A complex of the lipid transport ER proteins TMEM24 and C2CD2 with band 4.1 at cell-cell contacts.

Junctions between the ER and the plasma membrane (ER/PM junctions) are implicated in calcium homeostasis, non-vesicular lipid transfer and other cellular functions. Two ER proteins that function both as membrane tethers to the PM via a polybasic motif in their C-terminus and as phospholipid transporters are brain-enriched TMEM24 (C2CD2L) and its paralog C2CD2. Based on an unbiased proximity ligation analysis, we found that both proteins can also form a complex with band 4.1 family members, which in turn can bind a variety of plasma membrane proteins including cell adhesion molecules such as SynCAM 1. This complex results in the enrichment of TMEM24 and C2CD2 containing ER/PM junctions at sites of cell contacts. Dynamic properties of TMEM24-dependent ER/PM contacts are impacted when in complex as TMEM24 present at cell adjacent junctions is not shed by calcium rise, unlike TMEM24 at non-cell adjacent junctions. These findings suggest that cell-contact interactions control ER/PM junctions via TMEM24 complexes involving band 4.1 proteins.

Anterior Displacement of Tibial Spine Fractures: Does Anatomic Reduction Matter?

Background: Operative treatment of displaced tibial spine fractures consists of fixation and reduction of the fragment in addition to restoring tension of the anterior cruciate ligament. Purpose: To determine whether residual displacement of the anterior portion of a tibial spine fragment affects the range of motion (ROM) or laxity in operatively and nonoperatively treated patients. Study Design: Cohort study; Level of evidence, 3. Methods: Data were gathered from 328 patients younger than 18 years who were treated for tibial spine fractures between 2000 and 2019 at 10 institutions. ROM and anterior lip displacement (ALD) measurements were summarized and compared from pretreatment to final follow-up. ALD measurements were categorized as excellent (0 to <1 mm), good (1 to <3 mm), fair (3 to 5 mm), or poor (>5 mm). Posttreatment residual laxity and arthrofibrosis were assessed. Results: Overall, 88% of patients (290/328) underwent operative treatment. The median follow-up was 8.1 months (range, 3-152 months) for the operative group and 6.7 months (range, 3-72 months) for the nonoperative group. The median ALD measurement of the cohort was 6 mm pretreatment, decreasing to 0 mm after treatment (P < .001). At final follow-up, 62% of all patients (203/328) had excellent ALD measurements, compared with 5% (12/264) before treatment. Subjective laxity was seen in 11% of the nonoperative group (4/37) and 5% of the operative group (15/285; P = .25). Across the cohort, there was no association between final knee ROM and final ALD category. While there were more patients with arthrofibrosis in the operative group (7%) compared with the nonoperative group (3%) (P = .49), this was not different across the ALD displacement categories. Conclusion: Residual ALD was not associated with posttreatment subjective residual laxity, extension loss, or flexion loss. The results suggest that anatomic reduction of a tibial spine fracture may not be mandatory if knee stability and functional ROM are achieved.

Longitudinal association between exposure to e-cigarette advertising and youth e-cigarette use in the United States.

BACKGROUND AND AIM: E-cigarette marketing strategies are targeting and appealing to youth, particularly through social media. This study examined the longitudinal relationship between recalled exposure to e-cigarette advertisements on social media and across five traditional advertising mediums, and e-cigarette use, a year later. DESIGN: Weighted regression analyses of waves 4 (W4; 2017), 4.5 (W4.5; 2018) and 5 (W5; 2019) from the Population Assessment of Tobacco and Health Study. SETTING: United States. PARTICIPANTS: Youth aged 12-17 years at W4 or W4.5 (N = 16,671). MEASUREMENTS: We examined the association between past 30-day recalled exposure to six different e-cigarette advertisement mediums (gas stations/convenience stores, social media/websites, newspaper/magazines, radio, billboard, TV) in W4.5 and past 30-day and past 12-month e-cigarette use in W5, while controlling for W4 e-cigarette use and covariates such as sociodemographic variables, academic performance, peer cigarette/e-cigarette use and other substance use. Associations between recalled exposure (W4.5) and lifetime use (W5) among e-cigarette naïve youth at W4.5 (N = 8,914) were also assessed. FINDINGS: Past 12-month and past 30-day e-cigarette use was significantly associated with recalled exposure to e-cigarette advertisement on social media/websites (aOR = 1.65 [99.17 %CI = 1.36,1.99; aOR = 1.49 [99.17 %CI = 1.13, 1.97]) and gas stations/convenience stores (aOR = 1.33; [99.17 %CI = 1.11,1.58]; aOR = 1.27 [99.17 %CI = 1.03,1.58]). Exposure to e-cigarette advertisement on social media/websites (aOR = 1.35 [99.17 %CI = 1.04,1.74]) and gas stations/convenience stores (aOR = 1.67 [99.17 %CI = 1.31,2.13]) was significantly associated with lifetime e-cigarette use among baseline youth who were e-cigarette naïve. CONCLUSIONS: Exposure to e-cigarette advertisement on social media/websites and gas stations/convenience stores was associated with youth e-cigarette use a year later. Stricter restrictions on marketing in these mediums is needed to limit youth exposure to e-cigarette marketing messages if we are to reduce e-cigarette use.

Experimental manifestation of redox-conductivity in metal-organic frameworks and its implication for semiconductor/insulator switching.

Electric conductivity in metal-organic frameworks (MOFs) follows either a band-like or a redox-hopping charge transport mechanism. While conductivity by the band-like mechanism is theoretically and experimentally well established, the field has struggled to experimentally demonstrate redox conductivity that is promoted by the electron hopping mechanism. Such redox conductivity is predicted to maximize at the mid-point potential of the redox-active units in the MOF, and decline rapidly when deviating from this situation. Herein, we present direct experimental evidence for redox conductivity in fluorine-doped tin oxide surface-grown thin films of Zn(pyrazol-NDI) (pyrazol-NDI = 1,4-bis[(3,5-dimethyl)-pyrazol-4-yl]naphthalenediimide). Following Nernstian behavior, the proportion of reduced and oxidized NDI linkers can be adjusted by the applied potential. Through a series of conductivity measurements, it is demonstrated that the MOF exhibits minimal electric resistance at the mid-point potentials of the NDI linker, and conductivity is enhanced by more than 10000-fold compared to that of either the neutral or completely reduced films. The generality of redox conductivity is demonstrated in MOFs with different linkers and secondary building units, and its implication for applications that require switching between insulating and semiconducting regimes is discussed.

Leptospermum extract (QV0) suppresses pleural mesothelioma tumor growth in vitro and in vivo by mitochondrial dysfunction associated apoptosis.

Pleural mesothelioma (PM) is a highly aggressive, fast-growing asbestos-induced cancer with limited effective treatments. There has been interest in using naturally occurring anticancer agents derived from plant materials for the treatment of PM. However, it is unclear if an aqueous extract from Leptospermum polygalifolium (QV0) has activity against PM. Here we investigated the anti-cancer properties of QV0 and Defender® (QV0 dietary formula) in vitro and in vivo, respectively. QV0 suppressed the growth of eight PM cell lines in a dose-dependent manner, effective at concentrations as low as 0.02% w/v (equivalent to 0.2 mg/ml). This response was found to be associated with inhibited cell migration, proliferation, and colony formation but without evident cell cycle alteration. We observed mitochondrial dysfunction post-QV0 treatment, as evidenced by significantly decreased basal and maximal oxygen consumption rates. Ten SCID mice were treated with 0.25 mg/g Defender® daily and exhibited reduced tumor size over 30 days, which was associated with an average extension of seven days of mouse life. There was no evidence of liver toxicity or increased blood glucose post-treatment in animals treated with Defender®. Significantly enhanced tumor apoptosis was observed in the Defender®-treated animals, correlating to mitochondrial dysfunction. Lastly, the high levels of polyphenols and antioxidant properties of QV0 and Defender® were detected in HPLC analysis. To the best of our knowledge, this study constitutes the first demonstration of an improved host survival (without adverse effects) response in a QV0-treated PM mouse model, associated with evident inhibition of PM cell growth and mitochondrial dysfunction-related enhancement of tumor apoptosis.

Molecular Catalysis of Energy Relevance in Metal-Organic Frameworks: From Higher Coordination Sphere to System Effects.

The modularity and synthetic flexibility of metal-organic frameworks (MOFs) have provoked analogies with enzymes, and even the term MOFzymes has been coined. In this review, we focus on molecular catalysis of energy relevance in MOFs, more specifically water oxidation, oxygen and carbon dioxide reduction, as well as hydrogen evolution in context of the MOF-enzyme analogy. Similar to enzymes, catalyst encapsulation in MOFs leads to structural stabilization under turnover conditions, while catalyst motifs that are synthetically out of reach in a homogeneous solution phase may be attainable as secondary building units in MOFs. Exploring the unique synthetic possibilities in MOFs, specific groups in the second and third coordination sphere around the catalytic active site have been incorporated to facilitate catalysis. A key difference between enzymes and MOFs is the fact that active site concentrations in the latter are often considerably higher, leading to charge and mass transport limitations in MOFs that are more severe than those in enzymes. High catalyst concentrations also put a limit on the distance between catalysts, and thus the available space for higher coordination sphere engineering. As transport is important for MOF-borne catalysis, a system perspective is chosen to highlight concepts that address the issue. A detailed section on transport and light-driven reactivity sets the stage for a concise review of the currently available literature on utilizing principles from Nature and system design for the preparation of catalytic MOF-based materials.

Epigenetic dosage identifies two major and functionally distinct ß cell subtypes.

The mechanisms that specify and stabilize cell subtypes remain poorly understood. Here, we identify two major subtypes of pancreatic ß cells based on histone mark heterogeneity (ßHI and ßLO). ßHI cells exhibit ∼4-fold higher levels of H3K27me3, distinct chromatin organization and compaction, and a specific transcriptional pattern. ßHI and ßLO cells also differ in size, morphology, cytosolic and nuclear ultrastructure, epigenomes, cell surface marker expression, and function, and can be FACS separated into CD24+ and CD24- fractions. Functionally, ßHI cells have increased mitochondrial mass, activity, and insulin secretion in vivo and ex vivo. Partial loss of function indicates that H3K27me3 dosage regulates ßHI/ßLO ratio in vivo, suggesting that control of ß cell subtype identity and ratio is at least partially uncoupled. Both subtypes are conserved in humans, with ßHI cells enriched in humans with type 2 diabetes. Thus, epigenetic dosage is a novel regulator of cell subtype specification and identifies two functionally distinct ß cell subtypes.

Alternating Metal-Ligand Coordination Improves Electrocatalytic CO2 Reduction by a Mononuclear Ru Catalyst.

Molecular electrocatalysts for CO2 -to-CO conversion often operate at large overpotentials, due to the large barrier for C-O bond cleavage. Illustrated with ruthenium polypyridyl catalysts, we herein propose a mechanistic route that involves one metal center that acts as both Lewis base and Lewis acid at different stages of the catalytic cycle, by density functional theory in corroboration with experimental FTIR. The nucleophilic character of the Ru center manifests itself in the initial attack on CO2 to form [Ru-CO2 ]0 , while its electrophilic character allows for the formation of a 5-membered metallacyclic intermediate, [Ru-CO2 CO2 ]0,c , by addition of a second CO2 molecule and intramolecular cyclization. The calculated activation barrier for C-O bond cleavage via the metallacycle is decreased by 34.9 kcal mol-1 as compared to the non-cyclic adduct in the two electron reduced state of complex 1. Such metallacyclic intermediates in electrocatalytic CO2 reduction offer a new design feature that can be implemented consciously in future catalyst designs.

Exploring MicroRNA and Exosome Involvement in Malignant Pleural Mesothelioma Drug Response.

Malignant pleural mesothelioma (MPM) is a deadly thoracic malignancy and existing treatment options are limited. Chemotherapy remains the most widely used first-line treatment regimen for patients with unresectable MPM, but is hampered by drug resistance issues. The current study demonstrated a modest enhancement of MPM cell sensitivity to chemotherapy drug treatment following microRNA (miRNA) transfection in MPM cell lines, albeit not for all tested miRNAs. This effect was more pronounced for FAK (PND-1186) small molecule inhibitor treatment; consistent with previously published data. We previously established that MPM response to survivin (YM155) small molecule inhibitor treatment is unrelated to basal survivin expression. Here, we showed that MPM response to YM155 treatment is enhanced following miRNA transfection of YM155-resistant MPM cells. We determined that YM155-resistant MPM cells secrete a higher level of exosomes in comparison to YM155-sensitive MPM cells. Despite this, an exosome inhibitor (GW4896) did not enhance MPM cell sensitivity to YM155. Additionally, our study showed no evidence of a correlation between the mRNA expression of inhibitor of apoptosis (IAP) gene family members and MPM cell sensitivity to YM155. However, two drug transporter genes, ABCA6 and ABCA10, were upregulated in the MPM cell lines and correlated with poor sensitivity to YM155.