Imaging characteristics of infantile fibrosarcoma.

AIM: To highlight the imaging findings in a case series of histologically confirmed infantile fibrosarcoma (IF) and identify any features specific to this entity. MATERIALS AND METHODS: Retrospective identification was undertaken of patients with histologically confirmed IF from the electronic patient databases of two institutions between 1 January 2010 and 1 May 2021. Available pre-treatment imaging, histopathological reports, and clinical records were reviewed. RESULTS: Eighteen patients with IF met the inclusion criteria. There were 10 male and eight female patients with a mean age at presentation of 3 weeks. All patients had the t (12; 15) chromosomal translocation. Eleven (61%) tumours were located in the extremities, three were in the craniofacial region, two were intrathoracic, one abdominal and one paraspinal. A single patient had extensive metastases. The tumours were generally isointense to skeletal muscle on T1-weighted sequences and hyperintense on T2 with heterogeneous enhancement and high cellularity seen as diffusion restriction. Fifteen of the 18 lesions were evaluated on ultrasound and appeared as heterogeneous, hypervascular solid or mixed solid/cystic masses, mimicking benign vascular lesions in two cases. CONCLUSION: The present two-centre, retrospective study of the largest case series described thus far demonstrates that IF is always highly cellular on magnetic resonance imaging but has no other specific imaging features. It should be considered in the differential diagnosis of any enlarging soft-tissue, solid mass arising in the limbs or neck at birth or in infancy.

Comparison of the marine soundscape before and during the COVID-19 pandemic in dolphin habitat in Sarasota Bay, FL.

During the COVID-19 pandemic, changes in vessel activity and associated noise have been reported globally. Sarasota Bay is home to a large and increasing number of recreational vessels as well as a long-term resident community of bottlenose dolphins, Tursiops truncatus. Data were analyzed from two hydrophones to compare the soundscape during the COVID-19 pandemic to previous years (March-May 2020 and 2018/2019). Hourly metrics were calculated: vessel passes, 95th percentile sound levels [125 Hz and 16 kHz third octave bands (TOBs), and two broader bands: 88-1122 Hz and 1781-17 959 Hz], and dolphin whistle detection to understand changes in vessel activity and the effect on wildlife. Vessel activity increased during COVID-19 restrictions by almost 80% at one site and remained the same at the other site. Of the four sound level measures, only the 125 Hz TOB and 88-1122 Hz band increased with vessel activity at both sites, suggesting that these may be appropriate measures of noise from rapid pass-bys of small vessels in very shallow (<10 m) habitats. Dolphin whistle detection decreased during COVID-19 restrictions at one site but remained the same at the site that experienced increased vessel activity. The results suggest that pandemic effects on wildlife should not be viewed as homogeneous globally.

Radiation dose to the lens from CT of the head in young people.

AIM: To determine cumulative scan frequencies and estimate lens dose for paediatric computed tomography (CT) head examinations in the context of potential cataract risk. MATERIALS AND METHODS: The cumulative number of head-region CT examinations among a cohort of 410,997 children and young adults who underwent CT in the UK between 1985 and 2014 was calculated. Images from a sample of these head examinations (n=668) were reviewed to determine the level of eye inclusion. Lens dose per scan was estimated using the computer program, NCICT V1.0, for different levels of eye inclusion and exposure settings typical of past and present clinical practice. RESULTS: In total 284,878 patients underwent 448,108 head-region CT examinations. The majority of patients (72%) had a single recorded head-region examination. A small subset (∼1%, n=2,494) underwent ≥10 examinations, while 0.1% (n=387) underwent ≥20. The lens was included within the imaged region for 57% of reviewed routine head examinations. In many cases, this appeared to be intentional, i.e. protocol driven. In others, there appeared to have been an attempt to exclude the eyes through gantry angulation. Estimated lens doses were 20-75 mGy (mean: 47 mGy) where the eye was fully included within the examination range and 2-7 mGy (mean: 3.1 mGy) where the lens was fully excluded. Potential cumulative lens doses ranged from ∼3 mGy to ∼4,700 mGy, with 2,335 patients potentially receiving >500 mGy. CONCLUSION: The majority of young people will receive cumulative lens doses well below 500 mGy, meaning the risk of cataract induction is likely to be very small.

Shortage of paediatric radiologists acting as an expert witness: position statement from the British Society of Paediatric Radiology (BSPR) National Working Group on Imaging in Suspected Physical Abuse (SPA).

One of the most challenging areas of radiological imaging in children is the diagnosis of physical abuse. There is a dearth of paediatric radiologists willing to act as expert witnesses, particularly in the family courts. There are a number of reasons why radiologists may not be interested or willing to put themselves forward to work as expert witnesses in this field. A group of imaging experts recently formed the "British Society of Paediatric Radiology (BSPR) Working Group on Imaging in Suspected Physical Abuse (SPA)". The group comprises radiologists and neuroradiologists with current or previous experience of providing expert witness reports to the court in cases of SPA. The group met in January 2019 to explore pragmatic solutions to the chronic inefficiencies in both medical and legal practices and the challenges that arise from working in a legal arena with different structures, goals, and assessment criteria. Key issues concerned organisational inefficiencies, variable support from National Health Service Trusts and the Royal College of Radiologists to conduct this work, and the risk/benefit of involvement. This work is important for the patient, parents, and society in general, and highly rewarding for clinical practitioners who are involved, but there are several issues with current practices that discourage active participation. With several members of the group either retired or close to retirement, the shortage of experts is becoming a pressing issue within the UK, which requires an engaged multidisciplinary group to come up with creative solutions. Here, the group provide a consensus opinion highlighting the current barriers and potential facilitators to increasing the number of radiologists willing to provide opinions to the court.

Exosomes: novel regulators of bone remodelling and potential therapeutic agents for orthodontics.

Recent studies suggest that exosomes are involved in intercellular communication required for the maintenance of healthy bone. Exosomes are small (30-150 nm in diameter) extracellular vesicles that are formed in multivesicular bodies and are released from cells as the multivesicular bodies fuse with the plasma membrane. Regulatory exosomes have the capacity to exert profound control over target cells. They can stimulate plasma membrane receptors and are also internalized by the target cell delivering proteins, lipids, small molecules and functional RNAs from the cell of origin. We and others have recently reported on regulatory exosomes from osteoclasts and osteoblasts. Key candidate molecules identified in exosome-based regulation of bone remodelling include receptor activator of nuclear factor kappa B (RANK), RANK-ligand (RANKL), ephrinA2, semaphorin 4D, microRNA-146a and microRNA- 214-3p. Exosomes will likely prove to be crucial elements in the communication networks integrating bone cells (osteoclasts, osteoblasts, osteocytes) and linking bone to other tissue. Exosomes collected from bone cells grown in culture may prove useful to augment bone remodelling associated with orthodontic force application or required for the repair of craniofacial bone. Various technologies allow exosomes to be engineered to improve their targeting and efficacy for therapeutic purposes. In summary, exosomes have emerged as important elements of the machinery for intercellular communication between bone cells. They hold great promise as therapeutic targets, biomarkers and therapeutic agents for orthodontists.

The use of cell culture platforms to identify novel markers of bone and dentin resorption.

OBJECTIVES: 1) To test the hypothesis that there would be proteomic differences in the composition of exosomes isolated from osteoclasts and odontoclasts and 2) to determine the clinical usefulness of these in vitro biomarker candidates. MATERIALS AND METHODS: Mouse bone marrow-derived precursors were cultured on either dentin or bone slices and allowed to mature and begin resorption. Exosomes were isolated from cell culture media and characterized by mass spectrometry. The proteomic data obtained from this in vitro study were compared with the data obtained from human samples in our previous work. RESULTS: There was a difference in the proteomic composition of exosomes from osteoclasts and odontoclasts. A total of 40 exosomal proteins were only present in osteoclast media, whereas six unique exosomal proteins were identified in odontoclast supernatants. Approximately 50% of exosomal proteins released by clastic cells in vitro can be found in oral fluids. CONCLUSION: Our data suggest that the mineralized matrix type plays a role in the final phenotypic characteristics of mouse clastic cells. Many in vitro biomarker candidates of bone and dentin resorption can also be found in human oral fluids, thus indicating that this approach may be a viable alternative in biomarker discovery.

Looking Beyond Respiratory Cultures: Microbiome-Cytokine Signatures of Bacterial Pneumonia and Tracheobronchitis in Lung Transplant Recipients.

Bacterial pneumonia and tracheobronchitis are diagnosed frequently following lung transplantation. The diseases share clinical signs of inflammation and are often difficult to differentiate based on culture results. Microbiome and host immune-response signatures that distinguish between pneumonia and tracheobronchitis are undefined. Using a retrospective study design, we selected 49 bronchoalveolar lavage fluid samples from 16 lung transplant recipients associated with pneumonia (n = 8), tracheobronchitis (n = 12) or colonization without respiratory infection (n = 29). We ensured an even distribution of Pseudomonas aeruginosa or Staphylococcus aureus culture-positive samples across the groups. Bayesian regression analysis identified non-culture-based signatures comprising 16S ribosomal RNA microbiome profiles, cytokine levels and clinical variables that characterized the three diagnoses. Relative to samples associated with colonization, those from pneumonia had significantly lower microbial diversity, decreased levels of several bacterial genera and prominent multifunctional cytokine responses. In contrast, tracheobronchitis was characterized by high microbial diversity and multifunctional cytokine responses that differed from those of pneumonia-colonization comparisons. The dissimilar microbiomes and cytokine responses underlying bacterial pneumonia and tracheobronchitis following lung transplantation suggest that the diseases result from different pathogenic processes. Microbiomes and cytokine responses had complementary features, suggesting that they are closely interconnected in the pathogenesis of both diseases.

Reversible acute anuric kidney injury after surgical evacuation of perinephric hematomas as a complication of renal transplant biopsies.

Percutaneous renal transplant biopsy is the gold standard investigation to diagnose the cause of renal allograft dysfunction. There are inherent risks to this investigation, despite the procedure becoming safer due to the increased utilization of ultrasound-guided techniques. These biopsy risks can be increased when there is acute rejection present with a swollen transplanted kidney. Subcapsular hematomas are not uncommon after percutaneous renal transplant biopsies, but we describe two cases of post-biopsy subcapsular hematoma which were associated with acute renal allograft dysfunction in pediatric renal transplant recipients who did not have acute rejection.

Added value of abdominal cross-sectional imaging (CT or MRI) in staging of Wilms' tumours.

AIM: To assess the added information gained from computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen over abdominal ultrasound in children undergoing staging of Wilms' tumours. MATERIALS AND METHOD: Fifty-two consecutive patients with histologically proven Wilms' tumours were identified. Each had an initial staging abdominal ultrasound followed by either a CT or MRI examination of the abdomen. Details including tumour size, site, and characteristics, presence of lymph nodes, local invasion, evidence of nephroblastomatosis, and any other relevant finding were gathered from the report of each ultrasound and CT or MRI. Each CT/MRI was then re-reviewed by a consultant paediatric radiologist and a paediatric radiology fellow. The difference in findings between the ultrasound and cross-sectional imaging were noted. RESULTS: Twelve patients were excluded from the study because the CT/MRI was performed before the ultrasound, or imaging was incomplete. Twenty-six patients were female, 14 male. The ages ranged from 9 months to 10.8 years (mean 3.75 years). Twenty-one patients out of the remaining 40 had additional findings detected on the CT or MRI examination that had not been reported on the ultrasound. The most important additional findings included three patients with nephroblastomatosis and two with contralateral tumours. Other findings included two patients with tumour haemorrhage, four with abdominal lymph node enlargement, three with inferior vena cava (IVC)/renal vein thrombus, four with adjacent organ invasion, one patient where the origin of the abdominal tumour was confirmed as renal, and one patient where possible liver invasion was excluded. CONCLUSION: In over half the patients, CT or MRI added additional information in the local staging of Wilms' tumours. Sole reliance on ultrasound for Wilms' staging risks missing significant abnormalities.

Social support and religion: mental health service use and treatment of schizophrenia.

The perceptions and religious beliefs held by family members, mental health and health care professionals, and the community may affect the treatment of individuals with schizophrenia. To better identify and understand the influence of families, professionals and community members on individual's treatment for schizophrenia, this review paper examines: (1) the religious perceptions of families, professionals, and the public towards schizophrenia; (2) religious perceptions of the etiology of schizophrenia; (3) how others perceive religion as a coping mechanism; and (4) how religion influences treatment engagement and help-seeking behaviors. MEDLINE and PsycInfo databases were systematically searched from 1980 to 2010 using the terms schizophrenia, schizoaffective, schizophreniform, psychotic disorder not otherwise specified and religion, religiosity, spirituality, and faith. Forty-three (n = 43) original research studies met the inclusion criteria. This study found that religious beliefs influence the treatment of schizophrenia in the following ways: Religious themes were positively associated with coping, treatment engagement and help-seeking behavior. Evidence of religious underpinnings was found in perceptions of etiology. The findings also indicate that there is often both a preference among family members and caregivers to utilize religious-based professionals and caution toward mental health professionals. Researchers and professionals may find avenues for improving treatment through examining the interaction of religious and schizophrenia at the social support level.

Regulation of ITAM adaptor molecules and their receptors by inhibition of calcineurin-NFAT signalling during late stage osteoclast differentiation.

Osteoclasts are specialised bone resorptive cells responsible for both physiological and pathological bone loss. Osteoclast differentiation and activity is dependent upon receptor activator NF-kappa-B ligand (RANKL) interacting with its receptor RANK to induce the transcription factor, nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1). The immunoreceptor tyrosine-based activation motif (ITAM)-dependent pathway has been identified as a co-stimulatory pathway in osteoclasts. Osteoclast-associated receptor (OSCAR) and triggering receptor expressed in myeloid cells (TREM2) are essential receptors that pair with adaptor molecules Fc receptor common gamma chain (FcRγ) and DNAX-activating protein 12kDa (DAP12) respectively to induce calcium signalling. Treatment with calcineurin-NFAT inhibitors, Tacrolimus (FK506) and the 11R-VIVIT (VIVIT) peptide, reduces NFATc1 expression consistent with a reduction in osteoclast differentiation and activity. This study aimed to investigate the effects of inhibiting calcineurin-NFAT signalling on the expression of ITAM factors and late stage osteoclast genes including cathepsin K (CathK), Beta 3 integrin (ß3) and Annexin VIII (AnnVIII). Human peripheral blood mononuclear cells (PBMCs) were differentiated with RANKL and macrophage-colony stimulating factor (M-CSF) over 10days in the presence or absence of FK506 or VIVIT. Osteoclast formation (as assessed by tartrate resistant acid phosphatase (TRAP)) and activity (assessed by dentine pit resorption) were significantly reduced with treatment. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis demonstrated that FK506 treatment significantly (p<0.05) reduced the expression of NFATc1, CathK, OSCAR, FcRγ, TREM2 and DAP12 during the terminal stage of osteoclast formation. VIVIT treatment significantly (p<0.05) decreased CathK, OSCAR, FcRγ, and AnnVIII, gene expression. This data suggest FK506 and VIVIT act differently in targeting the calcineurin-NFAT signalling cascade to suppress key mediators of the ITAM pathway during late stage osteoclast differentiation and this is associated with a reduction in both osteoclast differentiation and activity.

Robotic-assisted transabdominal cerclage (RoboTAC) in the non-pregnant patient.

The use of cerclage, either through vaginal or abdominal routes, to assist in delaying pre-term delivery among select women with cervical insufficiency may be beneficial, but can also carry significant morbidity. Robotic-assisted transabdominal cervical cerclage (RoboTAC) in the non-pregnant patient has the ability to not only reduce associated morbidity, but also offer the same benefits as the more traditional laparotomy and laparoscopic approaches, while removing the risk to an in situ fetus. We report the use of robotic-assisted transabdominal cervical cerclage in 24 non-pregnant women. Feasibility of the procedure is discussed along with a description of the technical surgical details. In addition, limited pregnancy outcomes are presented. Our results suggest that RoboTAC is a safe alternative to the traditional laparotomy procedure with quicker recovery time.

The role of cell-substrate interaction in regulating osteoclast activation: potential implications in targeting bone loss in rheumatoid arthritis.

Analysis of tissues retrieved from the bone-pannus interface from patients with rheumatoid arthritis (RA) and studies in animal models of inflammatory arthritis provide strong evidence that osteoclasts, the cells that are essential for physiological bone resorption, are responsible for articular bone destruction in RA. However, current treatments that specifically target osteoclast-mediated bone resorption in RA have not been successful in preventing bone erosions, and new therapeutic strategies are needed. It has been noted that, although osteoclast precursors are present within the bone microenvironment at sites of pathological bone resorption, cells expressing the full morphological and functional properties of mature osteoclasts are restricted to the immediate bone surface and adjacent calcified cartilage. These findings provide evidence that, in addition to requirements for specific cytokines, interaction of osteoclast precursors with these mineralised matrices results in activation of specific signal pathways and the induction of unique gene products that are essential for terminal osteoclast differentiation and activation. These studies are designed to define the gene products and signalling pathways regulated by bone and calcified cartilage, to identify new molecular targets and novel therapeutic approaches for preventing osteoclast-mediated joint destruction in RA and related forms of pathological bone loss.

Ankylosing spondylitis monocytes show upregulation of proteins involved in inflammation and the ubiquitin proteasome pathway.

OBJECTIVES: To determine if peripheral blood monocytes from patients with ankylosing spondylitis (AS) differed in protein expression compared to rheumatoid arthritis (RA) and healthy controls (HC). METHODS: Monocyte protein expression was characterised by 2D gel electrophoresis and by label-free quantitative expression profiling, using nano-ultra performance liquid chromatography coupled to electrospray ionisation mass spectrometry (ESI-MS(E), where (E) refers to low/high collision energy switching). Data sets were analysed using the Waters expression profiling system and Ingenuity pathway analysis (IPA). RESULTS: Two-dimensional gel electrophoresis showed upregulation of proteasomal constituents in AS monocytes, including the beta subunit of proteasome activator (PA)28. Monocyte expression profiling and IPA showed that significant changes in protein expression within the ubiquitin proteasome pathway (UPP) were restricted to AS monocytes. Statistically significant differences in protein expression involving the leucocyte extravasation, vascular endothelial growth factor, integrin and Toll-like receptor signalling pathways were seen in AS and RA monocytes compared to healthy controls. No evidence of upregulation of proteins involved in the endoplasmic reticulum stress response pathway was found in either AS or RA monocytes. Finally, the PA28 complex was shown to increase the generation of human leucocyte antigen (HLA)-B27 antigenic epitopes by the proteasome in vitro. CONCLUSIONS: Our proteomic analyses support the hypothesis that monocytes play an important role in the pathogenesis of AS and RA, and further suggest a specific role in AS for the UPP. Quantitative proteomic expression profiling constitutes a powerful new tool for rheumatology research.

A role for the alphavbeta3 integrin in the transmigration of monocytes.

The beta2 integrins and intercellular adhesion molecule-1 (ICAM-1) are important for monocyte migration through inflammatory endothelium. Here we demonstrate that the integrin alphavbeta3 is also a key player in this process. In an in vitro transendothelial migration assay, monocytes lacking beta3 integrins revealed weak migratory ability, whereas monocytes expressing beta3 integrins engaged in stronger migration. This migration could be partially blocked by antibodies against the integrin chains alphaL, beta2, alphav, or IAP, a protein functionally associated with alphavbeta3 integrin. Transfection of beta3 integrin chain cDNA into monocytes lacking beta3 integrins resulted in expression of the alphavbeta3 integrin and conferred on these cells an enhanced ability to transmigrate through cell monolayers expressing ICAM-1. These monocytes also engaged in alphaLbeta2-dependent locomotion on recombinant ICAM-1 which was enhanced by alphavbeta3 integrin occupancy. Antibodies against IAP were able to revert this alphavbeta3 integrin-dependent cell locomotion to control levels. Finally, adhesion assays revealed that occupancy of alphavbeta3 integrin could decrease monocyte binding to ICAM-1. In conclusion, we show that alphavbeta3 integrin modulates alphaLbeta2 integrin-dependent monocyte adhesion to and migration on ICAM-1. This could represent a novel mechanism to promote monocyte motility on vascular ICAM-1 and initiate subsequent transendothelial migration.

Novel protective mechanism for interleukin-33 at the mucosal barrier during influenza-associated bacterial superinfection.

Influenza A is a highly contagious respiratory virus that causes seasonal epidemics and occasional worldwide pandemics. The primary cause of influenza-related mortality is bacterial superinfection. There are numerous mechanisms by which preceding influenza infection attenuates host defense, allowing for increased susceptibility to bacterial pneumonia. Herein, we demonstrate that influenza inhibits Staphylococcus aureus-induced production of interleukin-33 (IL-33). Restoration of IL-33 during influenza A and methicillin-resistant S. aureus superinfection enhanced bacterial clearance and improved mortality. Innate lymphoid Type 2 cells and alternatively activated macrophages are not required for IL-33-mediated protection during superinfection. We show that IL-33 treatment resulted in neutrophil recruitment to the lung, associated with improved bacterial clearance. These findings identify a novel role for IL-33 in antibacterial host defense at the mucosal barrier.

Field energetics and lung function in wild bottlenose dolphins, Tursiops truncatus, in Sarasota Bay Florida.

We measured respiratory flow rates, and expired O2 in 32 (2-34 years, body mass [Mb] range: 73-291 kg) common bottlenose dolphins (Tursiops truncatus) during voluntary breaths on land or in water (between 2014 and 2017). The data were used to measure the resting O2 consumption rate ([Formula: see text], range: 0.76-9.45 ml O2 min-1 kg-1) and tidal volume (VT, range: 2.2-10.4 l) during rest. For adult dolphins, the resting VT, but not [Formula: see text], correlated with body mass (Mb, range: 141-291 kg) with an allometric mass-exponent of 0.41. These data suggest that the mass-specific VT of larger dolphins decreases considerably more than that of terrestrial mammals (mass-exponent: 1.03). The average resting [Formula: see text] was similar to previously published metabolic measurements from the same species. Our data indicate that the resting metabolic rate for a 150 kg dolphin would be 3.9 ml O2 min-1 kg-1, and the metabolic rate for active animals, assuming a multiplier of 3-6, would range from 11.7 to 23.4 ml O2 min-1 kg-1.\absbreak Our measurements provide novel data for resting energy use and respiratory physiology in wild cetaceans, which may have significant value for conservation efforts and for understanding the bioenergetic requirements of this species.