Bone material properties and response to teriparatide in osteoporosis due to WNT1 and PLS3 mutations

Context: Patients with osteoporosis-associated WNT1 or PLS3 mutations have unique bone histomorphometric features and osteocyte-specific hormone expression patterns. Objective: To investigate the effects of WNT1 and PLS3 mutations on bone material properties. Design: Transiliac bone biopsies were evaluated by quantitative backscattered electron imaging, immunohistochemistry, and bone histomorphometry. Setting: Ambulatory patients. Patients: Three pediatric and eight adult patients with WNT1 or PLS3 mutations. Intervention: Bone mineralization density distribution and osteocyte protein expression was evaluated in 11 patients and repeated in six patients who underwent repeat biopsy after 24 months of teriparatide treatment. Main outcome measure: Bone mineralization density distribution and protein expression. Results: Children with WNT1 or PLS3 mutations had heterogeneous bone matrix mineralization, consistent with bone modeling during growth. Bone matrix mineralization was homogenous in adults and increased throughout the age spectrum. Teriparatide had very little effect on matrix mineralization or bone formation in patients with WNT1 or PLS3 mutations. However, teriparatide decreased trabecular osteocyte lacunae size and increased trabecular bone FGF23 expression. Conclusion: The contrast between preserved bone formation with heterogeneous mineralization in children and low bone turnover with homogenous bone mineral content in adults suggests that WNT1 and PLS3 have differential effects on bone modeling and remodeling. The lack of change in matrix mineralization in response to teriparatide, despite clear changes in osteocyte lacunae size and protein expression, suggests that altered WNT1 and PLS3 expression may interfere with coupling of osteocyte, osteoblast, and osteoclast function. Further studies are warranted to determine the mechanism of these changes.Peer reviewe

Investigating the effectiveness of oral ketamine on pain, mood and quality of life in treatment resistant chronic pain

IntroductionChronic pain is defined as pain lasting longer than 3 months. This often causes persistent emotional distress and functional disability that is refractory to conventional treatments. Emerging evidence suggests that oral Ketamine therapy may have a specific role in managing treatment-resistant chronic pain. This study aimed to assess the effectiveness of oral ketamine within a tertiary chronic pain management clinic.MethodsThis study was a clinic-based retrospective descriptive study of 79 patients with a broad range of chronic pain diagnoses and treated with oral ketamine over a period up to 12 years. Changes in pain, mood and quality of life (QoL) were assessed using a numerical pain severity score, the Brief Pain Inventory (BPI), the Public Health Questionnaire (PHQ-9) and American Chronic Pain Association Quality of Life (QoL) scale.Results73 patients were accessible for follow-up (mean daily dose and treatment duration were 193.84 mg and 22.6 months respectively). Pain scores decreased (p < 0.0001) on both numerical scores (41.6% decrease) and BPI scoring (mean decrease 2.61). Mood improved (p < 0.0001) across both PHQ-9 and BPI measurements. Patients also reported less difficulty with daily activities and improved QoL. The most common adverse reaction was drowsiness (21.9%), with 30.1% reporting no adverse reactions from Ketamine.DiscussionThis work adds to the growing body of evidence that under the supervision of a pain specialist, oral ketamine therapy may be a safe, tolerable and effective treatment for chronic pain conditions which have not responded to other management options. Further research is required to produce a more accurate understanding of its chronic use. Key messageThis real-world study shows that patients being treated with oral ketamine for chronic pain report decreased severity of pain, improved mood and increased quality of life across all conditions

Non fracture prediction of a C–Mn weld joint in brittle to ductile fracture transition temperature range. Part II: Determination of the stress-based criterion parameters and evaluation of its transferability

International audienceThis paper evaluates the brittle fracture risk for a C–Mn weld in the brittle-to-ductile transition: the criterion considered is based on a critical stress σth, with the failure probability related to the volume around the crack where the maximum principal stress exceeds σth. In Part II, the criterion is calibrated using more fracture tests at lower temperature. The capacity of the criterion to predict the probabilities of failure is validated. Finally, its transferability to another geometry is evaluated and appears to be possible

Simulation of communications using underwater acoustic signals impaired by wide band attenuation

We study simulation of underwater communications using acoustic signals impaired by attenuation and multipath propagation. Attenuation is sensitive to the source-receiver separation distance, sound speed profile and signal frequency. Multipath propagation is affected by reflection and refraction due to the environment boundaries, sea surface and seabed, and sound speed profile. Simulation of attenuation together with multipath propagation is approached by translating acoustic signals from the time domain to the frequency domain, applying attenuation on frequency components and translating attenuated frequency components back into the time domain. This algorithm is repeated for each copy of a signal created due to multipath propagation. Using this approach, we have developed a simulation of underwater acoustic data signals. The implementation has been done using the MATLAB and the BELLHOP software. Simulation results have been obtained and are compared with a universal model of signal quality