Outcomes of Arthroscopy-assisted Closed Reduction and Percutaneous Pinning for a Displaced Pediatric Lateral Condylar Humeral Fracture.

BACKGROUND: Since 2015, we have performed arthroscopy-assisted closed reduction and percutaneous pinning (A/S-CRPP) for children with a displaced lateral condylar humeral fracture (LCF). The purpose of this study is to introduce our A/S-CRPP method and present its outcomes. METHODS: In total, 39 displaced (>2 mm) LCFs for which A/S-CRPP was initially attempted and with available follow-up data of >12 months were retrospectively reviewed. A/S-CRPP is performed in the following order: closed reduction, 1 provisional K-wire fixation, arthroscopic verification of the reduction status, rereduction if needed, and additional fixation. Our reduction technique using articulations of the ulnohumeral and radiohumeral joints and direct compression is introduced. For rereduction, modified reduction forces were applied based on the arthroscopic findings. To evaluate the learning curve effect, the initial 6 months after the first case of A/S-CRPP was regarded as the "initial period." There were 12 cases during this period. RESULTS: Among the 39 cases, surgical method was intraoperatively converted to open reduction and percutaneous pinning in 9 and A/S-CRPP was completed in 30. Among the 9 open reduction and percutaneous pinning conversion cases, 7 conversions occurred in the initial period. Among the 30 patients who underwent A/S-CRPP alone, 10 needed rereduction after an arthroscopic examination. No patients presented with >10-degree angular deformity or elbow motion limited >20 degrees, compared with the contralateral elbow. Postoperative radial nerve palsy occurred in 2 patients, all in the initial period. Both were resolved within 5 months, postoperatively. CONCLUSIONS: We suggested our A/S-CRPP surgical technique for displaced pediatric LCF. It may require a 6-month learning curve period. Although more studies are needed, it seems to be a safe and appropriate surgical technique for treatment. LEVEL OF EVIDENCE: Level IV-therapeutic study.

Dynamics of Mechanosensitive Neural Stem Cell Differentiation.

Stem cell differentiation can be highly sensitive to mechanical inputs from the extracellular matrix (ECM). Identifying temporal windows during which lineage commitment responds to ECM stiffness, and the signals that mediate these decisions, would advance both mechanistic insights and translational efforts. To address these questions, we investigate adult neural stem cell (NSC) fate commitment using an oligonucleotide-crosslinked ECM platform that for the first time offers dynamic and reversible control of stiffness. "Stiffness pulse" studies in which the ECM was transiently or permanently softened or stiffened at specified initiation times and durations pinpoint a 24-hour window in which ECM stiffness maximally impacts neurogenic commitment. Overexpression of the transcriptional coactivator Yes-associated protein (YAP) within this window suppressed neurogenesis, and silencing YAP enhanced it. Moreover, ablating YAP-ß-catenin interaction rescued neurogenesis. This work reveals that ECM stiffness dictates NSC lineage commitment by signaling via a YAP and ß-catenin interaction during a defined temporal window. Stem Cells 2017;35:497-506.

Does brace treatment following closed reduction of developmental dysplasia of the hip improve acetabular coverage?

Aims: Abduction bracing is commonly used to treat developmental dysplasia of the hip (DDH) following closed reduction and spica casting, with little evidence to support or refute this practice. The purpose of this study was to determine the efficacy of abduction bracing after closed reduction in improving acetabular index (AI) and reducing secondary surgery for residual hip dysplasia. Methods: We performed a retrospective review of patients treated with closed reduction for DDH at a single tertiary referral centre. Demographic data were obtained including severity of dislocation based on the International Hip Dysplasia Institute (IHDI) classification, age at reduction, and casting duration. Patients were prescribed no abduction bracing, part-time, or full-time wear post-reduction and casting. AI measurements were obtained immediately upon cast removal and from two- and four-year follow-up radiographs. Results: A total of 243 hips underwent closed reduction and 82% (199/243) were treated with abduction bracing. There was no difference between those treated with or without bracing with regard to sex, age at reduction, severity of dislocation, spica duration, or immediate post-casting AI (all p > 0.05). There was no difference in hips treated with or without abduction brace with regard to AI at two years post-reduction (32.4° (SD 5.3°) vs 30.9° (SD 4.6°), respectively; p = 0.099) or at four years post-reduction (26.4° (SD 5.2°) vs 25.4° (SD 5.1°), respectively; p = 0.231). Multivariate analysis revealed only IHDI grade predicted AI at two years post-reduction (p = 0.004). There was no difference in overall rate of secondary surgery for residual dysplasia between hips treated with or without bracing (32% vs 39%, respectively; p = 0.372). However, there was an increased risk of early secondary surgery (< two years post-reduction) in the non-braced group (11.4% vs 2.5%; p = 0.019). Conclusion: Abduction bracing following closed reduction for DDH treatment is not associated with decreased residual dysplasia at two or four years post-reduction but may reduce rates of early secondary surgery. A prospective study is indicated to provide more definitive recommendations.

Effect of thiol pendant conjugates on plasmid DNA binding, release, and stability of polymeric delivery vectors.

Polymers have attracted much attention as potential gene delivery vectors due to their chemical and structural versatility. However, several challenges associated with polymeric carriers, including low transfection efficiencies, insufficient cargo release, and high cytotoxicity levels have prevented clinical implementation. Strong electrostatic interactions between polymeric carriers and DNA cargo can prohibit complete cargo release within the cell. As a result, cargo DNA never reaches the cell's nucleus where gene expression takes place. In addition, highly charged cationic polymers have been correlated with high cytotoxicity levels, making them unsuitable carriers in vivo. Using poly(allylamine) (PAA) as a model, we investigated how pH-sensitive disulfide cross-linked polymer networks can improve the delivery potential of cationic polymer carriers. To accomplish this, we conjugated thiol-terminated pendant chains onto the primary amines of PAA using 2-iminothiolane, developing three new polymer vectors with 5, 13, or 20% thiol modification. Unmodified PAA and thiol-conjugated polymers were tested for their ability to bind and release plasmid DNA, their capacity to protect genetic cargo from enzymatic degradation, and their potential for endolysosomal escape. Our results demonstrate that polymer-plasmid complexes (polyplexes) formed by the 13% thiolated polymer demonstrate the greatest delivery potential. At high N/P ratios, all thiolated polymers (but not unmodified counterparts) were able to resist decomplexation in the presence of heparin, a negatively charged polysaccharide used to mimic in vivo polyplex-protein interactions. Further, all thiolated polymers exhibited higher buffering capacities than unmodified PAA and, therefore, have a greater potential for endolysosomal escape. However, 5 and 20% thiolated polymers exhibited poor DNA binding-release kinetics, making them unsuitable carriers for gene delivery. The 13% thiolated polymers, on the other hand, displayed high DNA binding efficiency and pH-sensitive release.

Normal cerebral ventricular volume growth in childhood.

OBJECTIVE: Normal percentile growth charts for head circumference, length, and weight are well-established tools for clinicians to detect abnormal growth patterns. Currently, no standard exists for evaluating normal size or growth of cerebral ventricular volume. The current standard practice relies on clinical experience for a subjective assessment of cerebral ventricular size to determine whether a patient is outside the normal volume range. An improved definition of normal ventricular volumes would facilitate a more data-driven diagnostic process. The authors sought to develop a growth curve of cerebral ventricular volumes using a large number of normal pediatric brain MR images. METHODS: The authors performed a retrospective analysis of patients aged 0 to 18 years, who were evaluated at their institution between 2009 and 2016 with brain MRI performed for headaches, convulsions, or head injury. Patients were excluded for diagnoses of hydrocephalus, congenital brain malformations, intracranial hemorrhage, meningitis, or intracranial mass lesions established at any time during a 3- to 10-year follow-up. The volume of the cerebral ventricles for each T2-weighted MRI sequence was calculated with a custom semiautomated segmentation program written in MATLAB. Normal percentile curves were calculated using the lambda-mu-sigma smoothing method. RESULTS: Ventricular volume was calculated for 687 normal brain MR images obtained in 617 different patients. A chart with standardized growth curves was developed from this set of normal ventricular volumes representing the 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles. The charted data were binned by age at scan date by 3-month intervals for ages 0-1 year, 6-month intervals for ages 1-3 years, and 12-month intervals for ages 3-18 years. Additional percentile values were calculated for boys only and girls only. CONCLUSIONS: The authors developed centile estimation growth charts of normal 3D ventricular volumes measured on brain MRI for pediatric patients. These charts may serve as a quantitative clinical reference to help discern normal variance from pathologic ventriculomegaly.

Actomyosin-Mediated Tension Orchestrates Uncoupled Respiration in Adipose Tissues.

The activation of brown/beige adipose tissue (BAT) metabolism and the induction of uncoupling protein 1 (UCP1) expression are essential for BAT-based strategies to improve metabolic homeostasis. Here, we demonstrate that BAT utilizes actomyosin machinery to generate tensional responses following adrenergic stimulation, similar to muscle tissues. The activation of actomyosin mechanics is critical for the acute induction of oxidative metabolism and uncoupled respiration in UCP1+ adipocytes. Moreover, we show that actomyosin-mediated elasticity regulates the thermogenic capacity of adipocytes via the mechanosensitive transcriptional co-activators YAP and TAZ, which are indispensable for normal BAT function. These biomechanical signaling mechanisms may inform future strategies to promote the expansion and activation of brown/beige adipocytes.

Microelastic mapping of the rat dentate gyrus.

The lineage commitment of many cultured stem cells, including adult neural stem cells (NSCs), is strongly sensitive to the stiffness of the underlying extracellular matrix. However, it remains unclear how well the stiffness ranges explored in culture align with the microscale stiffness values stem cells actually encounter within their endogenous tissue niches. To address this question in the context of hippocampal NSCs, we used atomic force microscopy to spatially map the microscale elastic modulus (E) of specific anatomical substructures within living slices of rat dentate gyrus in which NSCs reside during lineage commitment in vivo. We measured depth-dependent apparent E-values at locations across the hilus (H), subgranular zone (SGZ) and granule cell layer (GCL) and found a two- to threefold increase in stiffness at 500 nm indentation from the H (49 ± 7 Pa) and SGZ (58 ± 8 Pa) to the GCL (115 ± 18 Pa), a fold change in stiffness we have previously found functionally relevant in culture. Additionally, E exhibits nonlinearity with depth, increasing significantly for indentations larger than 1 µm and most pronounced in the GCL. The methodological advances implemented for these measurements allow the quantification of the elastic properties of hippocampal NSC niche at unprecedented spatial resolution.