Pain among children and adults living with arthrogryposis multiplex congenita: A scoping review.

Clinical interventions and research have mostly focused on the orthopedic and genetic outcomes of individuals with arthrogryposis multiplex congenita (AMC), and although pain has gained recognition as an important issue experienced by individuals with AMC, it has received little attention within the AMC literature. The aims of this scoping review were to describe the pain experiences of children and adults with AMC, to identify pain assessment tools and management techniques, and document the impact of pain on participation in everyday activities among children and adults with AMC. A search of the literature was conducted in four search engines and identified a total of 89 articles.

Extracellular matrix composition of connective tissues: a systematic review and meta-analysis.

The function of connective tissues depends on the physical and biochemical properties of their extracellular matrix (ECM), which are in turn dictated by ECM protein composition. With the primary objective of obtaining quantitative estimates for absolute and relative amounts of ECM proteins, we performed a systematic review of papers reporting protein composition of human connective tissues. Articles were included in meta-analysis if they contained absolute or relative quantification of proteins found in the ECM of human bone, adipose tissue, tendon, ligament, cartilage and skeletal muscle.

International multidisciplinary collaboration toward an annotated definition of arthrogryposis multiplex congenita.

Arthrogryposis multiplex congenita (AMC) has been described and defined in thousands of articles, but the terminology used has been inconsistent in clinical and research communities. A definition of AMC was recently developed using a modified Delphi consensus method involving 25 experts in the field of AMC from 8 countries. Participants included health care professionals, researchers, and individuals with AMC.

A Multicenter Observational Cohort Study to Evaluate the Effects of Bisphosphonate Exposure on Bone Mineral Density and Other Health Outcomes in Osteogenesis Imperfecta.

Osteogenesis imperfecta (OI) is characterized by low bone mass and bone fragility. Using data from a large cohort of individuals with OI from the Osteogenesis Imperfecta Foundation's linked clinical research centers, we examined the association between exposure to bisphosphonate (BPN) treatment (past or present) and lumbar spine (LS) areal bone mineral density (aBMD), fractures, scoliosis, and mobility. From 466 individuals, we obtained 1394 participant-age LS aBMD data points.

Age-Related Changes in the Mechanical Regulation of Bone Healing Are Explained by Altered Cellular Mechanoresponse.

Increasing age is associated with a reduced bone regeneration potential and increased risk of morbidities and mortality. A reduced bone formation response to mechanical loading has been shown with aging, and it remains unknown if the interplay between aging and mechanical stimuli during regeneration is similar to adaptation. We used a combined in vivo/in silico approach to investigate age-related alterations in the mechanical regulation of bone healing and identified the relative impact of altered cellular function on tissue patterns during the regenerative cascade.

Burosumab versus conventional therapy in children with X-linked hypophosphataemia: a randomised, active-controlled, open-label, phase 3 trial.

Background: X-linked hypophosphataemia in children is characterised by elevated serum concentrations of fibroblast growth factor 23 (FGF23), hypophosphataemia, rickets, lower extremity bowing, and growth impairment. We compared the efficacy and safety of continuing conventional therapy, consisting of oral phosphate and active vitamin D, versus switching to burosumab, a fully human monoclonal antibody against FGF23, in paediatric X-linked hypophosphataemia.

Methods: In this randomised, active-controlled, open-label, phase 3 trial at 16 clinical sites, we enrolled children with X-linked hypophosphataemia aged 1-12 years.

Simultaneous Fluorescent Recordings of Extracellular ATP and IntracellularCalcium in Mammalian Cells.

Extracellular ATP is a potent signaling molecule that stimulates intracellular calcium responses through purinergic (P2) receptors in mammalian cells. While extracellular ATP and intracellular calcium can be measured separately, simultaneous monitoring can offer additional insights into P2 receptor physiology. This protocol takes advantage of the overlapping fluorescence spectra between the ATP-detection substrate luciferin and calcium indicator dye Fura2.

Transmission of Mechanical Information by Purinergic Signaling.

The skeleton constantly interacts and adapts to the physical world. We have previously reported that physiologically relevant mechanical forces lead to small repairable membrane injuries in bone-forming osteoblasts, resulting in release of ATP and stimulation of purinergic (P2) calcium responses in neighboring cells. The goal of this study was to develop a theoretical model describing injury-related ATP and ADP release, their extracellular diffusion and degradation, and purinergic responses in neighboring cells.

Meta-Analytic Methodology for Basic Research: A Practical Guide.

Basic life science literature is rich with information, however methodically quantitative attempts to organize this information are rare. Unlike clinical research, where consolidation efforts are facilitated by systematic review and meta-analysis, the basic sciences seldom use such rigorous quantitative methods. The goal of this study is to present a brief theoretical foundation, computational resources and workflow outline along with a working example for performing systematic or rapid reviews of basic research followed by meta-analysis.

NOTCH Signaling Is Activated through Mechanical Strain in Human Bone Marrow-Derived Mesenchymal Stromal Cells.

Skeletal development and remodeling of adult bone are critically controlled by activated NOTCH signaling in genetically modified mice. It is yet unclear whether NOTCH signaling is activated by mechanical strain sensed by bone cells. We found that expression of specific NOTCH target genes is induced after tibial mechanical loading in wild-type mice.

Hepatic posttranscriptional network comprised of CCR4-NOT deadenylase and FGF21 maintains systemic metabolic homeostasis.

Whole-body metabolic homeostasis is tightly controlled by hormone-like factors with systemic or paracrine effects that are derived from nonendocrine organs, including adipose tissue (adipokines) and liver (hepatokines). Fibroblast growth factor 21 (FGF21) is a hormone-like protein, which is emerging as a major regulator of whole-body metabolism and has therapeutic potential for treating metabolic syndrome. However, the mechanisms that control FGF21 levels are not fully understood.

Rehabilitation needs of youth with arthrogryposis multiplex congenita: Perspectives from key stakeholders.

Arthrogryposis multiplex congenita is a term used to describe congenital contractures in at least two body parts with an overall prevalence of 1 in 3000 live births. It is often caused by lack of fetal movement in utero and presents as contractures of varying severity, which may affect the upper and lower extremities, the spine and jaw. Currently, no practice recommendations exist to inform best clinical practice for arthrogryposis multiplex congenita.

Exosomal Release of L-Plastin by Breast Cancer Cells Facilitates Metastatic Bone Osteolysis.

Bone metastasis from breast and prostate carcinomas is facilitated by activation of bone-resorbing osteoclasts. Using proteomics approaches, we have identified peroxiredoxin-4 (PRDX4) as a cancer-secreted mediator of osteoclastogenesis. We now report characterization of L-plastin in the conditioned media (CM) of MDA-MB-231 human breast cancer cells using immunoblotting and mass spectrometry.

Mathematical modeling of calcium phosphate precipitation in biologically relevant systems: scoping review.

Biologically guided precipitation of calcium phosphates is important for the formation of calcified human tissues, such as bone and teeth, and is of practical significance in numerous industrial and agricultural processes, such as wastewater treatment and dairy ultrafiltration. Mineral precipitation is physicochemically complex and becomes even more complex in the presence of biological materials. The theoretical foundation of phase transition in general has been developed and is vital for many applications, such as metallurgy and weather prediction.

Effect of Anti-TGF-β Treatment in a Mouse Model of Severe Osteogenesis Imperfecta.

Osteogenesis imperfecta (OI) is a heritable bone fragility disorder that is usually caused by mutations affecting collagen type I encoding genes. Recent studies in mouse models of recessive OI, Crtap mice, and dominant OI, +/G610C mice, found that application of a transforming growth factor beta (TGF-β) neutralizing antibody 1D11 rescues the bone phenotype. In the present study, we investigated TGF-β signaling in a mouse model of severe dominant OI with a high incidence of spontaneous fractures, Col1a1 mice, and the effect of TGF-β neutralizing antibody 1D11 on bone phenotype in 8-week-old mice.

Evidence of impaired pain modulation in adolescents with idiopathic scoliosis and chronic back pain.

Background Context: Although 40% of adolescent idiopathic scoliosis (AIS) patients present with chronic back pain, the pathophysiology and underlying pain mechanisms remain poorly understood. We hypothesized that development of chronic pain syndrome in AIS is associated with alterations in pain modulatory mechanisms.

Purpose: To identify the presence of sensitization in nociceptive pathways and to assess the efficacy of the diffuse noxious inhibitory control in patients with AIS presenting with chronic back pain.

Mechanically stimulated ATP release from mammalian cells: systematic review and meta-analysis.

Body tissues are exposed to a complex mechanical environment, which is perceived by cells and converted to biochemical signals such as ATP release. We performed a meta-analysis of 278 systematically identified studies that investigated mechanically stimulated ATP release (MSAR) to quantify the amounts, kinetics and mechanisms of ATP release under normal and pathological conditions. Mechanically stimulated mammalian cells were shown to release 38.

Mechanically stimulated ATP release from murine bone cells is regulated by a balance of injury and repair.

Bone cells sense and actively adapt to physical perturbations to prevent critical damage. ATP release is among the earliest cellular responses to mechanical stimulation. Mechanical stimulation of a single murine osteoblast led to the release of 70 ± 24 amole ATP, which stimulated calcium responses in neighboring cells.

Collagen type I degradation fragments act through the collagen receptor LAIR-1 to provide a negative feedback for osteoclast formation.

The major organic component of bone is collagen type I. Osteoclasts are terminally differentiated multinucleated cells of hematopoietic origin that are essential for physiological development of bone and teeth. We examined if osteoclast differentiation from murine bone marrow precursors is affected by collagen type I, or by its degradation products produced by human recombinant cathepsin K.

Current Options for the Treatment of Pectus Carinatum: When to Brace and When to Operate?

Pectus carinatum has traditionally been described as a rare chest wall anomaly in comparison to pectus excavatum. However, recent data from chest wall anomaly clinics demonstrate that this deformity is probably much more frequent than once believed. In the past, invasive surgical correction by the Ravitch technique was essentially the only option for treatment of pectus carinatum.

deficiency leads to reduced mechanical strains at the tibia midshaft in strain-matched loading experiments in mice.

Sclerostin, a product of the gene, is a Wnt-inhibitor and thus negatively regulates bone accrual. Canonical Wnt/β-catenin signalling is also known to be activated in mechanotransduction. Sclerostin neutralizing antibodies are being tested in ongoing clinical trials to target osteoporosis and osteogenesis imperfecta but their interaction with mechanical stimuli on bone formation remains unclear.

Acute pain management in children: challenges and recent improvements.

Purpose Of Review: The evidence regarding the efficacy of analgesics available to guide postoperative pain treatment in pediatric patients is limited. Opioid medications are very often an important component of pediatric postoperative pain treatment but have been associated with perioperative complications. We will focus on initiatives aiming to provide effective treatment minimizing the use of opioids and preventing the long-term consequences of pain.

Establishing normative data for the Functional Dexterity Test in typically developing children aged 3-5 years.

Study Design: Cross-sectional.

Introduction: The Functional Dexterity Test (FDT) is a timed pegboard hand dexterity test. Normative data have been developed primarily in adults with some studies in the pediatric population.

Current methodological approaches in conditioned pain modulation assessment in pediatrics.

Conditioned pain modulation (CPM) paradigms have been used in various studies with healthy and non-healthy adult populations in an attempt to elucidate the mechanisms of pain processing. However, only a few studies so far have applied CPM in pediatric populations. Studies finding associations with chronic pain conditions suggest that deficiencies in underlying descending pain pathways may play an important role in the development and persistence of pain early in life.