Activation and disruption of Wnt/β-catenin signaling both result in cartilage breakdown via unknown mechanisms. Here we show that both WNT-3A and the Wnt inhibitor DKK1 induced de-differentiation of ...human articular chondrocytes through simultaneous activation of β-catenin-dependent and independent responses. WNT-3A activates both the β-catenin-dependent canonical pathway and the Ca(2+)/CaMKII noncanonical pathways, with distinct transcriptional targets. WNT-3A promotes cell proliferation and loss of expression of the chondrocyte markers COL2A1, Aggrecan, and SOX9; however, proliferation and AXIN2 up-regulation are downstream of the canonical pathway and are rescued by DKK1, whereas the loss of differentiation markers is CaMKII dependent. Finally, we showed that in chondrocytes, the Ca(2+)/CaMKII-dependent and β-catenin-dependent pathways are reciprocally inhibitory, thereby explaining why DKK1 can induce loss of differentiation through de-repression of the CaMKII pathway. We propose a novel model in which a single WNT can simultaneously activate different pathways with distinct and independent outcomes and with reciprocal regulation. This offers an opportunity for selective pharmacological targeting.
Purpose:
Fractures of the femoral diaphysis are associated with a risk of morbidity in children. Various fixation methods have been developed, but with only limited evidence to support their use. ...This systematic review assesses the evidence regarding clinical outcomes of closed femoral diaphyseal fractures in children treated with plate fixation or flexible intramedullary nails.
Methods:
A PROSPERO-registered, PRISMA-compliant systematic review and meta-analysis were conducted. MEDLINE, Embase, and Web of Science (WoS) databases were searched from inception to February 2023. Inclusion criteria included clinical studies reporting adverse outcomes following surgical treatment of pediatric closed femoral diaphyseal fractures using plate fixation and flexible intramedullary nails. The ROBINS-I and RoB 2 tools evaluated the risk of bias.
Results:
Thirteen papers (2 prospective randomized controlled trials and 11 retrospective cohorts) reported 805 closed diaphyseal femoral fractures in 801 children (559 males, 242 females). There were 360 plate fixations and 445 flexible intramedullary nails. Two cases of osteomyelitis and one nonunion were reported. Meta-analysis showed that plate fixation had a lower risk of soft tissue infection (relative risk 0.26 (95% confidence interval 0.07–0.92)). There was no difference in the following outcomes: malunion (relative risk 0.68 (95% confidence interval 0.32–1.44)); unplanned reoperation (relative risk 0.59 (95% confidence interval 0.31–1.14)), and leg-length difference (relative risk 1.58 (95% confidence interval 0.66–3.77)). The risk of bias was high in all studies.
Conclusions:
An analysis of 805 fractures with minimal differences in meta-analyses is considered high quality even when the quality of the evidence is low. The findings are limited by important flaws in the methodology in the published literature. Well-designed multicentre prospective studies using standardized core outcomes are required to advise treatment recommendations.
Level of evidence:
III.
Pediatric meniscal injuries: Current concepts Asokan, Ajay; Ayub, Anouska; Ramachandran, Manoj
Journal of Children's Orthopaedics,
02/2023, Letnik:
17, Številka:
1
Book Review, Journal Article
Recenzirano
Odprti dostop
Meniscal pathology is widely prevalent in the adult population, secondary to acute trauma and chronic degeneration. It is less commonly seen in children, although its incidence is rising. The true ...prevalence in children remains unknown, as pathologies such as discoid menisci often go undiagnosed, or are found only incidentally. The rising incidence can be attributed to increased participation in sports at younger ages, both in intensity and frequency, with potentially year-round competition. Meniscal tears lead to pain and mechanical symptoms in the short to medium term, but more significantly, have been shown to lead to compartmental chondral degeneration and early arthritis in the long term. With advancing arthroscopic techniques, and children’s propensity for better healing, osteoarthritis secondary to meniscal pathology is a potentially preventable problem. This article discusses meniscal injuries in children and adolescents and their management.
Tin diselenide thin films were prepared by spray pyrolysis technique using SnCl2·H2O and 1,1-dimethyl-2-selenourea as precursor compounds with a Se:Sn atomic ratio of 1:1 in the starting solution. ...The deposition process was carried out in the substrate temperature range of 275°C to 400°C using two solution flow rates of 5ml/min and 8ml/min. The phases of SnSe2 were obtained when the deposition was carried ou at a flow rate of 5ml/min, while for the films deposited at 8ml/min mixed phases of SnSe2/SnSe were observed. Heat treatment of the deposited SnSe2/SnSe thin films in an atmosphere of 95% N2 and 5% H2 led to crystallization of the SnSe compound. The as deposited SnSe2 thin films have an optical band gap of 1.59eV with n-type electrical conductivity in the range of 10−1(Ωcm)−1 to 101(Ωcm)−1. The annealed thin films have an optical band gap of 0.81eV and show p-type electrical conductivity of 2×10−1(Ωcm)−1.
► SnSe and SnSe2 thin films were deposited by spray pyrolysis technique. ► Thin films of SnSe2 were deposited at a solution flow rate of 5ml/min. ► At a flow rate of 8ml/min, a mixture of SnSe2 and SnSe compounds was obtained. ► Films with good optoelectronic properties for photovoltaic applications were deposited.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a rapidly spreading disease causing increased morbidity and mortality across the globe. ...There is limited available knowledge regarding the natural history of the SARS-CoV-2 infection. Other factors that are also making this infection spread like a pandemic include global travelers, lack of proven treatment, asymptomatic carriers, potential reinfection, underprepared global health care systems, and lack of public awareness and efforts to prevent further spread. It is understood that certain preexisting medical conditions increase the risk of mortality with COVID-19; however, the outcome of this disease in traditionally vulnerable chronic illnesses such as end-stage renal disease is not well documented. We present a case of a 56-year-old African American lady with end-stage renal disease on the peritoneal dialysis who presented predominantly with nausea, vomiting, and subsequently found to have COVID-19. We use this case to illustrate an atypical presentation of the COVID-19 in a vulnerable patient and discuss the literature.
Developmental dysplasia of the hip (DDH) is the most common skeletal developmental disease. However, its genetic architecture is poorly understood. We conduct the largest DDH genome-wide association ...study to date and replicate our findings in independent cohorts. We find the heritable component of DDH attributable to common genetic variants to be 55% and distributed equally across the autosomal and X-chromosomes. We identify replicating evidence for association between
promoter variation and DDH (rs143384, effect allele A, odds ratio 1.44, 95% confidence interval 1.34-1.56,
= 3.55 × 10
). Gene-based analysis implicates
(
= 9.24 × 10
),
(
= 1.86 × 10
),
(
= 3.18 × 10
),
(
= 3.70 × 10
) and
(
= 1.06 × 10
) in DDH susceptibility. We find shared genetic architecture between DDH and hip osteoarthritis, but no predictive power of osteoarthritis polygenic risk score on DDH status, underscoring the complex nature of the two traits. We report a scalable, time-efficient recruitment strategy and establish for the first time to our knowledge a robust DDH genetic association locus at
.
Treatment of slipped capital femoral epiphysis remains a contentious and debated issue. The opinion for the correct method of treatment can differ not only between different continents and nations, ...but also between units and surgeons within individual units. We aim to review the European perspective on the treatment of slipped capital femoral epiphysis and consider the trends for treatment among the European orthopaedic surgical community.
Normal lower limb variants in children Yeo, Andrea; James, Kyle; Ramachandran, Manoj
BMJ (Online),
07/2015, Letnik:
351, Številka:
8016
Journal Article, Book Review
Recenzirano
Bow legs, knock knees, flat feet, intoeing, and out-toeing gaits in children are common but often cause undue parental anxiety, prompting frequent visits to general practice.1 2 3 4 5 A substantial ...proportion of referrals to paediatric orthopaedic clinics consist of normal physiological variants in growing children. Careful history, examination, and knowledge of the clinical course of rotational and angular deformities allow accurate assessment of children and provide reassurance to parents. Our review aims to assist general clinicians in recognising normal physiological variants in the lower limbs of children and to identify abnormal features that require specialist attention.
Highly conducting and transparent ZnO : Al thin films were grown by off-axis rf magnetron sputtering on amorphous silica substrates without any post-deposition annealing. The electrical and optical ...properties of the films deposited at various substrate temperatures and target to substrate distances were investigated in detail. Optimized ZnO : Al films have conductivity of 2200 S cm-1 and average transmission in the visible range is higher than 85%. The conductivity and mobility show very little temperature dependence.
PDF
