Subchondral rafting wires reduce tibial plateau fracture subsidence.

PURPOSE: To determine if subchondral rafting wires retained as adjunctive tibial plateau fracture fixation affect postoperative articular subsidence. METHODS: A retrospective cohort study was conducted at one Level 1 trauma center and one academic university hospital. Consecutive adults with closed, displaced OTA/AO 41B/C tibial plateau fractures treated between 2018 and 2023 with open reduction internal fixation were included. Patients who were not ambulatory, with contralateral injuries limiting weight bearing, and without follow-up radiographs of the injured extremity were excluded. The intervention was retention of subchondral rafting wires as definitive fixation. The primary outcome was linear articular surface subsidence between postoperative and follow-up AP knee radiographs. Linear subsidence was compared between groups using Welch's two sample t test. Associations of linear subsidence with patient, injury, and treatment characteristics were assessed by multivariable linear regression. RESULTS: We identified 179 patients of a mean age of 44 ± 14 years, of whom 15 (8.4%) received subchondral rafting wires. Median follow-up was 121 days. No patients who received rafting wires as definitive implants experienced linear subsidence ≥ 2 mm, while 22 patients (13.4%) who did not receive rafting wires experienced linear subsidence ≥ 2 mm (p = 0.130). Subchondral rafting wires were associated with less linear subsidence (0.3 mm [95% confidence interval - 0.3-0.9 mm] vsersus 1.0 mm [- 0.9-2.9 mm], p < 0.001). The depth of linear subsidence was significantly associated on multivariable regression with male sex, depressed plateau area, active smoking, and retained rafting wires. CONCLUSION: Subchondral rafting wires were associated with a small reduction in articular subsidence after internal fixation of tibial plateau fractures. Routine rafting wires may be useful for patients and fractures at high risk of articular subsidence.

A Systematic Review of Characteristics Associated with COVID-19 in Children with Typical Presentation and with Multisystem Inflammatory Syndrome.

Setting off a global pandemic, coronavirus disease 2019 (COVID-19) has been marked by a heterogeneous clinical presentation that runs the gamut from asymptomatic to severe and fatal. Although less lethal in children than adults, COVID-19 has nonetheless afflicted the pediatric population. This systematic review used clinical information from published literature to assess the spectrum of COVID-19 presentation in children, with special emphasis on characteristics associated with multisystem inflammatory syndrome (MIS-C). An electronic literature search for English and Chinese language articles in COVIDSeer, MEDLINE, and PubMed from 1 January 2020 through 1 March 2021 returned 579 records, of which 54 were included for full evaluation. Out of the total 4811 patients, 543 (11.29%) exhibited MIS-C. The most common symptoms across all children were fever and sore throat. Children presenting with MIS-C were less likely to exhibit sore throat and respiratory symptoms (i.e., cough, shortness of breath) compared to children without MIS-C. Inflammatory (e.g., rash, fever, and weakness) and gastrointestinal (e.g., nausea/vomiting and diarrhea) symptoms were present to a greater extent in children with both COVID-19 and MIS-C, suggesting that children testing positive for COVID-19 and exhibiting such symptoms should be evaluated for MIS-C.

Quality of Life Changes during the COVID-19 Pandemic for Caregivers of Children with ADHD and/or ASD.

The COVID-19 pandemic has presented many challenges to caregivers of children. Families with children with attention-deficit/hyperactivity disorder (ADHD) and/or autism spectrum disorder (ASD) are an understudied but potentially vulnerable population to changes during the outbreak. As such, the aim of this study was to contrast quality of life for caregivers of children with ADHD and/or ASD, before and during the pandemic, compared to caregivers of neurotypical (NT) children. Total, Parent Health-Related Quality of Life, and Family Functioning Summary Scores from the Family Impact Module of the Pediatric Quality of Life InventoryTM were contrasted among caregivers of children with ADHD, ASD, comorbid ADHD and ASD, and NT development. For all scores, caregivers of ADHD and/or ASD children reported lower quality of life, both before and during the pandemic, in comparison to caregivers of NT children. For all diagnoses, quality of life decreased during the pandemic, but caregivers of children with ADHD and/or ASD reported a greater decrease in quality of life than caregivers for NT children. There are limitations to this study in terms of the composition of the sample and the survey methodology, but we are able to conclude that caregivers of children with ADHD and/or ASD have been disproportionately affected by the pandemic, and it is imperative that these families receive additional resources and support to improve their quality of life.

Subglottic Stenosis Position Affects Work of Breathing.

OBJECTIVES: Subglottic stenosis (SGS) is the most common type of laryngeal stenosis in neonates. SGS severity is currently graded based on percent area of obstruction (%AO) via the Myer-Cotton grading scale. However, patients with similar %AO can have widely different clinical courses. Computational fluid dynamics (CFD) based on patient-specific imaging can quantify the relationship between airway geometry and flow dynamics. We investigated the effect of %AO and axial position of SGS on work of breathing (WOB) in neonates using magnetic resonance imaging. METHODS: High-resolution ultrashort echo-time MRI of the chest and airway was obtained in three neonatal patients with no suspected airway abnormalities; images were segmented to construct three-dimensional (3D) models of the neonatal airways. These models were then modified with virtual SGSs of varying %AO and axial positioning. CFD simulations of peak inspiratory flow were used to calculate patient-specific WOB in nonstenotic and artificially stenosed airway models. RESULTS: CFD simulations demonstrated a relationship between stenosis geometry and WOB increase. WOB rapidly increased with %AO greater than about 70%. Changes in axial position could also increase WOB by approximately the same amount as a 10% increase in %AO. Increased WOB was particularly pronounced when the SGS lumen was misaligned with the glottic jet. CONCLUSION: The results indicate a strong, predictable relationship between WOB and axial position of the stenotic lumen relative to the glottis, which has not been previously reported. These findings may lead to precision diagnosis and treatment prediction tools in individual patients. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1220-E1226, 2021.

Evaluating BRCA mutation risk predictive models in a Chinese cohort in Taiwan.

Accurate estimation of carrier probabilities of cancer susceptibility gene mutations is an important part of pre-test genetic counselling. Many predictive models are available but their applicability in the Asian population is uncertain. We evaluated the performance of five BRCA mutation risk predictive models in a Chinese cohort of 647 women, who underwent germline DNA sequencing of a cancer susceptibility gene panel. Using areas under the curve (AUCs) on receiver operating characteristics (ROC) curves as performance measures, the models did comparably well as in western cohorts (BOADICEA 0.75, BRCAPRO 0.73, Penn II 0.69, Myriad 0.68). For unaffected women with family history of breast or ovarian cancer (n = 144), BOADICEA, BRCAPRO, and Tyrer-Cuzick models had excellent performance (AUC 0.93, 0.92, and 0.92, respectively). For women with both personal and family history of breast or ovarian cancer (n = 241), all models performed fairly well (BOADICEA 0.79, BRCAPRO 0.79, Penn II 0.75, Myriad 0.70). For women with personal history of breast or ovarian cancer but no family history (n = 262), most models did poorly. Between the two well-performed models, BOADICEA underestimated mutation risks while BRCAPRO overestimated mutation risks (expected/observed ratio 0.67 and 2.34, respectively). Among 424 women with personal history of breast cancer and available tumor ER/PR/HER2 data, the predictive models performed better for women with triple negative breast cancer (AUC 0.74 to 0.80) than for women with luminal or HER2 overexpressed breast cancer (AUC 0.63 to 0.69). However, incorporating ER/PR/HER2 status into the BOADICEA model calculation did not improve its predictive accuracy.

Adolescent Concussion and Mental Health Outcomes: A Population-based Study.

Objectives: Population-based research on the relationship between concussions and self-harm, depression, and suicidal behaviors among adolescents is limited. Methods: A statewide Youth Risk Behavior Surveillance Survey (YRBSS) was conducted among students from 98 high schools in Nevada in 2017. Students were asked if they had a concussion from playing a sport as well as their mental health outcomes 12 months before the survey. Weighted multiple logistic regression was used to assess the relationship between experiencing a concussion and adverse mental health outcomes. Results: Among 3427 students who were physically active at least 60 minutes per day on 5 or more days per week, or played on at least one sport team, 19.5% (95% CI: 17.31%-21.60%) reported they had a concussion during the past 12 months. After controlling for sex, age, race/ethnicity, and academic performance, students who had a concussion had higher odds of: self-harm [aOR = 1.59 (1.16-2.17), p = .003], depressive symptoms [aOR = 1.48 (1.12-1.94), p = .006], attempted suicide [aOR = 3.10 (2.12-4.53), p < .001] and injury from attempted suicide [aOR = 2.61 (1.31-5.20, p = .006]. Conclusions: Students who experience a concussion may be at increased risk for poor mental health outcomes, including suicide attempts. Psychological evaluation following a concussion should complement medical evaluation and treatment..

Full-length amyloid precursor protein regulates lipoprotein metabolism and amyloid-ß clearance in human astrocytes.

Mounting evidence suggests that alterations in cholesterol homeostasis are involved in Alzheimer's disease (AD) pathogenesis. Amyloid precursor protein (APP) or multiple fragments generated by proteolytic processing of APP have previously been implicated in the regulation of cholesterol metabolism. However, the physiological function of APP in regulating lipoprotein homeostasis in astrocytes, which are responsible for de novo cholesterol biosynthesis and regulation in the brain, remains unclear. To address this, here we used CRISPR/Cas9 genome editing to generate isogenic APP-knockout (KO) human induced pluripotent stem cells (hiPSCs) and differentiated them into human astrocytes. We found that APP-KO astrocytes have reduced cholesterol and elevated levels of sterol regulatory element-binding protein (SREBP) target gene transcripts and proteins, which were both downstream consequences of reduced lipoprotein endocytosis. To elucidate which APP fragments regulate cholesterol homeostasis and to examine whether familial AD mutations in APP affect lipoprotein metabolism, we analyzed an isogenic allelic series harboring the APP Swedish and APP V717F variants. Only astrocytes homozygous for the APP Swedish (APPSwe/Swe) mutation, which had reduced full-length APP (FL APP) due to increased ß-secretase cleavage, recapitulated the APP-KO phenotypes. Astrocytic internalization of ß-amyloid (Aß), another ligand for low-density lipoprotein (LDL) receptors, was also impaired in APP-KO and APPSwe/Swe astrocytes. Finally, impairing cleavage of FL APP through ß-secretase inhibition in APPSwe/Swe astrocytes reversed the LDL and Aß endocytosis defects. In conclusion, FL APP is involved in the endocytosis of LDL receptor ligands and is required for proper cholesterol homeostasis and Aß clearance in human astrocytes.

Structures of HIV-1 Env V1V2 with broadly neutralizing antibodies reveal commonalities that enable vaccine design.

Broadly neutralizing antibodies (bNAbs) against HIV-1 Env V1V2 arise in multiple donors. However, atomic-level interactions had previously been determined only with antibodies from a single donor, thus making commonalities in recognition uncertain. Here we report the cocrystal structure of V1V2 with antibody CH03 from a second donor and model Env interactions of antibody CAP256-VRC26 from a third donor. These V1V2-directed bNAbs used strand-strand interactions between a protruding antibody loop and a V1V2 strand but differed in their N-glycan recognition. Ontogeny analysis indicated that protruding loops develop early, and glycan interactions mature over time. Altogether, the multidonor information suggested that V1V2-directed bNAbs form an 'extended class', for which we engineered ontogeny-specific antigens: Env trimers with chimeric V1V2s that interacted with inferred ancestor and intermediate antibodies. The ontogeny-based design of vaccine antigens described here may provide a general means for eliciting antibodies of a desired class.

An on-demand four-way junction DNAzyme nanoswitch driven by inosine-based partial strand displacement.

A DNA four-way junction device capable of junction expansion and contraction cycles using an inosine-based partial strand displacement scheme is reported. These nanoscale positioning capabilities are used to provide on-demand activation and deactivation of a pair of split E6 DNAzymes on the device. The device also demonstrates a combined catalytic rate significantly higher than the original E6 DNAzyme under similar operational conditions. This approach can provide structural organization and spatially control other multicomponent molecular complexes.