Bone growth and repair are under the control of biochemical and mechanical signals. Low-intensity pulsed ultrasound (LIPUS) stimulation at 30
mW/cm
2 is an established, widely used and FDA approved ...intervention for accelerating bone healing in fractures and non-unions. Although this LIPUS signal accelerates mineralization and bone regeneration, the actual intensity experienced by the cells at the target site might be lower, due to the possible attenuation caused by the overlying soft tissue. The aim of this study was to investigate whether LIPUS intensities below 30
mW/cm
2 are able to provoke phenotypic responses in bone cells. Rat bone marrow stromal cells were cultured under defined conditions and the effect of 2, 15, 30
mW/cm
2 and sham treatments were studied at early (cell activation), middle (differentiation into osteogenic cells) and late (biological mineralization) stages of osteogenic differentiation. We observed that not only 30
mW/cm
2 but also 2 and 15
mW/cm
2, modulated ERK1/2 and p38 intracellular signaling pathways as compared to the sham treatment. After 5
days with daily treatments of 2, 15 and 30
mW/cm
2, alkaline phosphatase activity, an early indicator of osteoblast differentiation, increased by 79%, 147% and 209%, respectively, compared to sham, indicating that various intensities of LIPUS were able to initiate osteogenic differentiation. While all LIPUS treatments showed higher mineralization, interestingly, the highest increase of 225% was observed in cells treated with 2
mW/cm
2. As the intensity increased to 15 and 30
mW/cm
2, the increase in the level of mineralization dropped to 120% and 82%. Our data show that LIPUS intensities lower than the current clinical standard have a positive effect on osteogenic differentiation of rat bone marrow stromal cells. Although Exogen™ at 30
mW/cm
2 continues to be effective and should be used as a clinical therapy for fracture healing, if confirmed
in vivo, the increased mineralization at lower intensities might be the first step towards redefining the most effective LIPUS intensity for clinical use.
Background
Over the last months, during the COVID‐19 pandemic, a growing number of chilblain‐like lesions were reported mainly in children and rarely in young adults. The relationship with SARS‐CoV‐2 ...infection was postulated, often without any laboratory, instrumental or clinical confirmation. The disclosure of information about chilblain‐like lesions as a COVID‐19 manifestation in social media has created concern in children’s families and paediatricians.
Objectives
To verify whether the chilblain‐like lesions were caused by SARS‐CoV‐2 infection.
Methods
Prospective study on a case series including children who presented with acral lesions at the Pediatric Dermatology Outpatient and Pediatric Emergency Unit of the University of Bologna, from 1 April to 30 April 2020. We reported demographical, laboratory and clinical features, history of close contact with COVID‐19 patients, presence of similar skin lesions in other family members, precipitating and risk factors for chilblain onset.
Results
We evaluated eight patients (five females, three males) aged between 11 and 15 years. We excluded acute or previous SARS‐CoV‐2 infection with RT‐PCR nasopharyngeal swab, serum antibody levels using chemiluminescent immunoassays. Other acute infections causing purpuric lesions at the extremities were negative in all patients. Skin lesion biopsy for histological and immunohistochemical evaluation was made in two cases and was consistent with chilblain. PCR assay on skin lesion biopsy for parvovirus B19, Mycoplasma pneumoniae and SARS‐CoV‐2 was performed in a patient and resulted negative. We identified common precipitating and risk factors: physical (cold and wet extremities, low BMI), cold and wet indoor and outdoor environment, behaviours, habits and lifestyle. We therefore reached a diagnosis of primary chilblains.
Conclusions
During the COVID‐19 pandemic, a ‘cluster’ of primary chilblains developed in predisposed subjects, mainly teenagers, due to cold exposure in the lockdown period. Laboratory findings support our hypothesis, although it is also possible that an unknown infectious trigger may have contributed to the pathogenesis.
The tongue is covered by fungiform, filiform and circumvallate papillae. Fungiform papillae may be mainly pigmented in dark‐skinned individuals. A single‐centre study aimed to examine the clinical ...and dermoscopic features of pigmented fungiform papulae of the tongue (PFPT) in children, and a concise review of the literature has been performed. The clinical and anamnestic data of eight children affected by PFPT visited at the Pediatric Dermatology Unit of Bologna between 2010 and 2017, and a systemic review of all studies of PFPT published on PubMed up to 31 August 2017 has been collected and analysed. The results of our data were consistent with the literature review: dark brown to black coloured pinhead papules or bumps were observed in all cases of PFPT, and three types of clinical patterns have been detected. Moreover, the dermoscopic examination showed a cobblestone‐like distribution and rose petal pattern. PFPT could be associated with hyperpigmentation of other sites such as the proximal nail folds and gums, and an intrafamiliar transmission is also possible. Clinical and dermoscopic features of PFPT may help clinicians to recognize this ethnic, acquired and benign condition.
Summary
Fixation of metallic implants to bone through osseointegration is important in orthopaedics and dentistry. Model systems for studying this phenomenon would benefit from a non‐destructive ...imaging modality so that mechanical and morphological endpoints can more readily be examined in the same specimens. The purpose of this study was to assess the utility of an automated microcomputed tomography (μCT) program for predicting bone–implant contact (BIC) and mechanical fixation strength in a rat model. Femurs in which 1.5‐mm‐diameter titanium implants had been in place for 4 weeks were either embedded in polymethylmethacrylate (PMMA) for preparation of 1‐mm‐thick cross‐sectional slabs (16 femurs: 32 slabs) or were used for mechanical implant pull‐out testing (n= 18 femurs). All samples were scanned by μCT at 70 kVp with 16 μm voxels and assessed by the manufacturer's software for assessing ‘osseointegration volume per total volume’ (OV/TV). OV/TV measures bone volume per total volume (BV/TV) in a 3‐voxel‐thick ring that by default excludes the 3 voxels immediately adjacent to the implant to avoid metal‐induced artefacts. The plastic‐embedded samples were also analysed by backscatter scanning electron microscopy (bSEM) to provide a direct comparison of OV/TV with a well‐accepted technique for BIC. In μCT images in which the implant was directly embedded within PMMA, there was a zone of elevated attenuation (>50% of the attenuation value used to segment bone from marrow) which extended 48 μm away from the implant surface. Comparison of the bSEM and μCT images showed high correlations for BV/TV measurements in areas not affected by metal‐induced artefacts. In addition for bSEM images, we found that there were high correlations between peri‐implant BV/TV within 12 μm of the implant surface and BIC (correlation coefficients ≥0.8, p < 0.05). OV/TV as measured on μCT images was not significantly correlated with BIC as measured on the corresponding bSEM images. However, OV/TV was significantly, but weakly, correlated with implant pull‐out strength (r= 0.401, p= 0.049) and energy to failure (r= 0.435, p= 0.035). Thus, the need for the 48‐μm‐thick exclusion zone in the OV/TV program to avoid metal‐induced artefacts with the scanner used in this study means that it is not possible to make bone measurements sufficiently close to the implant surface to obtain an accurate assessment of BIC. Current generation laboratory‐based μCT scanners typically have voxel sizes of 6–8 μm or larger which will still not overcome this limitation. Thus, peri‐implant bone measurements at these resolutions should only be used as a guide to predict implant fixation and should not be over‐interpreted as a measurement of BIC. Newer generation laboratory‐based μCT scanners have several improvements including better spatial resolution and X‐ray sources and appear to have less severe metal‐induced artefacts, but will need appropriate validation as they become available to researchers. Regardless of the μCT scanner being used, we recommend that detailed validation studies be performed for any study using metal implants because variation in the composition and geometry of the particular implants used may lead to different artefact patterns.