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Glenohumeral instability is a challenging problem in children and adolescents. For patients with anterior glenoid bone loss, the Latarjet procedure is an effective treatment option. However, concerns about coracoid size and morphology may limit its utilization within this patient population. The purpose of this study was to establish normative data on coracoid and glenoid size and morphology among a large cohort of adolescent patients and describe the anatomic relationships with demographic factors.

Variable stiffness manipulators balance the trade-off between manipulation performance needing high stiffness and safe human-robot interaction desiring low stiffness. Variable stiffness links enable this flexible manipulation function during human-robot interaction. In this paper, we propose a novel variable stiffness link based on discrete variable stiffness units (DSUs). A DSU is a parallel guided beam that can adjust stiffness discretely by changing the cross-sectional area properties of the hollow beam segments. The variable stiffness link (Tri-DSU) consists of three tandem DSUs to achieve eight stiffness modes and the maximum stiffness change ratio of 31. To optimize the design, stiffness analysis of the DSU and Tri-DSU under various configurations and forces was performed by a derived linear analytical model which applies to small/intermediate deflections. The model is derived using the approach of serially connected beams and superposition combinations. 3-D printed prototypes were built to verify the feature and performance of the Tri-DSU in comparison with the FEA and analytical model results. It's demonstrated that our model can accurately predict the stiffnesses of the DSU and Tri-DSU within a certain range of parameters. Impact tests were also conducted to validate the performance of the Tri-DSU. The developed method and analytical model are extendable to multiple DSUs with parameter configurations to achieve modularization and customization, and also provide a tool for the design of reconfigurable cobot manipulators.

Hypoxia-inducible factors (HIFs) play pivotal roles in numerous diseases and high-altitude adaptation, and HIF stabilizers have emerged as valuable therapeutic tools. In our prior investigation, we identified a highland-adaptation 24-amino-acid insertion within the Epas1 protein. This insertion enhances the protein stability of Epas1, and mice engineered with this insertion display enhanced resilience to hypoxic conditions. In the current study, we delved into the biochemical mechanisms underlying the protein-stabilizing effects of this insertion. Our findings unveiled that the last 11 amino acids within this insertion adopt a helical conformation and interact with the α-domain of the von Hippel-Lindau tumor suppressor protein (pVHL), thereby disrupting the Eloc-pVHL interaction and impeding the ubiquitination of Epas1. Utilizing a synthesized peptide, E14–24, we demonstrated its favorable membrane permeability and ability to stabilize endogenous HIF-α proteins, inducing the expression of hypoxia-responsive element (HRE) genes. Furthermore, the administration of E14–24 to mice subjected to hypoxic conditions mitigated body weight loss, suggesting its potential to enhance hypoxia adaptation.

All chronic renal disorders eventually lead to renal interstitial fibrosis (RIF). Chronic inflammation and pro-fibrotic substances are familiar companions of the fibrotic process. The Sulforaphane (Sul) molecule is particularly useful in protecting the liver from oxidative damage. To investigate the Sul effects on fibrosis markers and inflammatory proteins in the kidney of NRK52E cell line and rats and clarify the mechanism of TGF-β/Smad signaling pathway in a rat model of RIF were developed in the present study. Sul (50, 100, and 200 ng/ml) remarkably reduced the gene expressions of tumor necrosis factor (TNF-α), interleukin-6 (IL-6), interleukin (IL)-1β, collagen 3 (COL3A1), collagen 1 (COL1A1), and α-smooth muscle actin (α-SMA) in fibrotic NRK52E cells compared with those in cells inspired by transforming growth factor-α (TGF-α). Histopathological investigations showed that Sul administration retained renal tissue structure and decreased kidney tissue fibrosis in rats subjected to unilateral ureteral blockage (UUO). The expression level of TNF-α, IL-6, IL-1β, COL3A1, COL1A1, and α-SMA in the rats’ kidneys exposed to UUO was also suppressed by the treatment of Sul. In the present study, western blot analysis showed that Sul upregulated the expressions of fibrotic NRK52E cells Smad7 and rat model UUO groups while simultaneously decreasing the stimulation of Smad2/3 and the expressions of cyclooxygenase-2, NF-κB, Smad4, activator protein-1, and high-mobility group protein B1. Ultimately, Sul’s ability to inhibit the TGF-β/Smad pathway and the development of inflammation factors may mitigate RIF.

Background: The management of displaced intraarticular calcaneus fractures (DIACFs) is a difficult problem with disappointing results from open reduction internal fixation (ORIF). Alternatively, ORIF with primary subtalar arthrodesis (PSTA) has gained increasing popularity. The purpose of this study is to review patient-centered and radiographic outcomes of ORIF plus PSTA using only screws through a sinus tarsi approach.Methods: A retrospective study of patients who underwent ORIF+PSTA for DIACFs was conducted. The same surgical technique was used in all cases consisting of only screws; no plates were used. Delayed surgeries past 8 weeks were excluded. Demographic and radiographic data were collected including worker’s compensation claims. Plain radiographs were used to characterize injuries and review outcomes.Results: Seventy-nine DIACFs underwent PSTA with a median follow-up of 200 days (n = 69 patients). Median time to weightbearing was 57.5 days postoperatively. Ten fractures were documented as Sanders II, 36 as Sanders III, and 32 as Sanders IV. Sixty-eight fractures (86.1%) achieved fusion on radiographs at a median of 126.5 (range, 54-518) days. Thirty-nine fractures (57.3%) demonstrated radiographic fusion in all 3 predefined locations. Nine of the 14 worker’s compensation patients returned to work within the period of observation. There were 8 complications: 3 requiring a secondary operation. Eleven of 79 fractures treated did not go on to achieve radiographic union.Conclusion: In this retrospective case series, we found that screws-only primary subtalar arthrodesis for the treatment of DIACFs through a sinus tarsi approach was associated with relatively high rates of return to work and radiographic fusion.Level of Evidence: Level IV, retrospective case series.

The Qinghai-Tibet Plateau (QTP) harbors hundreds of species well adapted to its extreme conditions, including its low-oxygen (hypoxic) atmosphere. Here, we show that the plateau pika—a keystone mammal of the QTP—lacks robust circadian rhythms. The major form of the plateau pika Epas1 protein includes a 24-residue insert caused by a point mutation at the 5′ juncture site of Intron14 and is more stable than other mammalian orthologs. Biochemical studies reveal that an Epas1-Bmal1 complex with lower trans-activation activity occupies the E1/E2 motifs at the promoter of the core-clock gene Per2, thus explaining how an Epas1mutation—selected in the hypoxic conditions of the QTP—disrupts the molecular clockwork. Importantly, experiments with hypoxic chambers show that mice expressing the plateau pika Epas1ortholog in their suprachiasmatic nucleus have dysregulated central clocks, and pika Epas1knockin mice reared in hypoxic conditions exhibit dramatically reduced heart damage compared with wild-type animals.