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BACKGROUND: The pathophysiology of migraine remains poorly understood, yet a growing number of studies have shown structural connectivity disruptions across large-scale brain networks. Although both structural and functional changes have been found in the cerebellum of migraine patients, the cerebellum has barely been assessed in previous structural connectivity studies of migraine. Our objective is to investigate the structural connectivity of the entire brain, including the cerebellum, in individuals diagnosed with episodic migraine without aura during the interictal phase, compared with healthy controls. METHODS: To that end, 14 migraine patients and 15 healthy controls were recruited (all female), and diffusion-weighted and T1-weighted MRI data were acquired. The structural connectome was estimated for each participant based on two different whole-brain parcellations, including cortical and subcortical regions as well as the cerebellum. The structural connectivity patterns, as well as global and local graph theory metrics, were compared between patients and controls, for each of the two parcellations, using network-based statistics and a generalized linear model (GLM), respectively. We also compared the number of connectome streamlines within specific white matter tracts using a GLM. RESULTS: We found increased structural connectivity in migraine patients relative to healthy controls with a distinct involvement of cerebellar regions, using both parcellations. Specifically, the node degree of the posterior lobe of the cerebellum was greater in patients than in controls and patients presented a higher number of streamlines within the anterior limb of the internal capsule. Moreover, the connectomes of patients exhibited greater global efficiency and shorter characteristic path length, which correlated with the age onset of migraine. CONCLUSIONS: A distinctive pattern of heightened structural connectivity and enhanced global efficiency in migraine patients compared to controls was identified, which distinctively involves the cerebellum. These findings provide evidence for increased integration within structural brain networks in migraine and underscore the significance of the cerebellum in migraine pathophysiology.

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Isolated Tillaux fracture is a rare anterolateral distal tibia fracture frequently misdiagnosed in adults. It typically occurs in adolescents nearing skeletal maturity by avulsion of the anterior-inferior tibiofibular ligament. This case-based literature review study aims to elicit the existing information regarding this fracture in adults, and summarize its injury mechanism, diagnosis, and treatment procedures. According to the literature, this is only the eighth case described: a 46-year-old woman that suffered an isolated Tillaux fracture with 4 mm of displacement, and open reduction and fixation with double cannulated screws were performed. After proper rehabilitation, an excellent functional and radiological outcome was reached. It is important to recognize and appropriately treat these distinct injuries to prevent further instability, degenerative changes, and ankle joint function limitation. Early diagnosis and appropriate osteosynthesis play a significant role in a successful recovery prognosis.

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CASE: A 19-year-old man with Multiple Hereditary Exostoses presented with cervical pain without neurological symptoms and/or signs. Magnetic resonance revealed a large C2 osteochondroma, occupying a part of the medullary canal. He was submitted to an en bloc resection with hemilaminectomy without fusion. At the 1-year follow-up, he presented resolution of pain and no neurological symptoms or signs, without cervical instability or radiological signs of disease recurrence. CONCLUSION: Cervical osteochondroma is usually asymptomatic. Neurological compression and differentiation to chondrosarcoma are the main concerns. Surgical excision allows the local cure of the disease and is usually performed without fusion.

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BACKGROUND: The benefits of physical activity (PA) and adequate sleep are well documented, and their importance strengthens with the increasing prevalence of chronic diseases and multimorbidity (MM). Interventions to promote physical activity and sleep that use commercial activity trackers may be useful non-pharmacological approaches to managing individual health; however, limited evidence exists on their use to improve physical activity in older adult patients with MM. METHODS: This study aims to measure the effects of behavioral change techniques (BCTs) delivered by a wearable device on physical activity and quality of sleep (QS) in older adult patients with MM. We designed an open-label randomized controlled trial with participants recruited through primary care and a specialist outpatient clinic. Participants must be more than 65 years old, have MM, and have access to smartphones. All eligible participants will receive PA promotion content and will be randomly assigned to wear a smartwatch. The primary outcome will be the participants' PA measurement at baseline and at six months using the International Physical Activity Questionnaire - Short Form (IPAQ-SF). Secondary outcomes will include changes in the participants' frailty status, biometric measurements, quality of life, and biopsychosocial assessments. A sample size of 40 participants per arm was calculated to detect group differences, with 50 participants planned to recruit and randomize into each arm. DISCUSSION: This study aims to contribute to a better understanding of PA patterns and the impact of wearable-based PA interventions in patients with MM. In addition, we aim to contribute to more knowledge about the relationship between PA patterns, Patient Reported Outcomes Measures (PROMs), and healthcare resource utilization in patients with MM. To achieve this, the study will leverage a locally developed PROMs registry and assess data from participants' medical records, in order to understand the added impact of wearable data and medical information data on predicting PROMs and unplanned hospital admissions. TRIAL REGISTRATION: NCT05777291.

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OBJECTIVE: To investigate whether in radiographic axial spondyloarthritis (r-axSpA) inflammation is associated with lower trabecular bone density (TBD), and subsequently, if a lower TBD increases the likelihood of 2-year bone formation at the same vertebra. METHODS: Whole spine (C3-L5) data from patients included in the multicentre 2-year Sensitive Imaging in Ankylosing Spondylitis cohort was used. Two readers measured baseline TBD by Hounsfield units (HU) on low-dose CT (ldCT). Baseline MRI bone marrow oedema (BME) status scores and ldCT syndesmophyte formation and/or growth change-from-baseline scores were assessed by three and two readers, respectively. Average of readers' continuous measurements or readers' agreement in binary scores generated within the same vertebra (1-present in ≥1 quadrant/0-absent in all quadrants) were used. Multilevel generalised estimating equations models were used, the unit of analysis being the vertebra. RESULTS: In 50 patients with r-axSpA, TBD HU decreased from cranial to caudal vertebrae. Baseline MRI-BME was present in 300/985 (30%) and syndesmophytes in 588/910 (65%) vertebrae, both most prevalent at thoracolumbar region. Syndesmophyte formation or growth was observed in 18% of at-risk vertebrae (124/691). A significant confounder-adjusted association was found between inflammation and lower TBD (regression coefficient=-51; 95% CI-63 to -39). TBD was not associated with 2-year syndesmophyte formation or growth (adjusted OR 1.00; 95% CI 0.99 to 1.00). CONCLUSION: In r-axSpA, while vertebral inflammation was associated with lower vertebral TBD, lower vertebral TBD itself did not increase the risk for new bone formation at the same vertebra. In preventing syndesmophyte progression, targeting local inflammation seems more important than targeting vertebral trabecular bone loss.

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OBJECTIVES: To describe low dose Computed Tomography (ldCT) Hounsfield Units (HU) two-year change-from-baseline values (expressing trabecular bone density changes) and analyse their inter-reader reliability per vertebra in radiographic axial spondyloarthritis (r-axSpA). METHODS: We used 49 patients with r-axSpA from the multicentre two-year Sensitive Imaging in Ankylosing Spondylitis (SIAS) study. LdCT HU were independently measured by two trained readers at baseline and two years. Mean (standard deviation, SD) for the change-from-baseline HU values were provided per vertebra by reader. Intraclass correlation coefficients (ICC; absolute agreement, two-way random effect), Bland-Altman plots and smallest detectable change (SDC) were obtained. Percentages of vertebrae in which readers agreed on the direction of change and on change >|SDC| were computed. RESULTS: Overall, 1,053 (98% of all possible) vertebrae were assessed by each reader both at baseline and two years. Over two years, HU mean change values varied from -23 to 28 and 29 for reader 1 and 2, respectively. Inter-reader reliability of the two-year change-from-baseline values per vertebra was excellent: ICC:0.91-0.99; SDC:6-10; Bland-Altman plots were homoscedastic, with negligible systematic error between readers. Readers agreed on the direction of change in 88-96% and on change >|SDC| in 58-94% of vertebrae, per vertebral level, from C3 to L5. Overall, similar results were obtained across all vertebrae. CONCLUSION: LdCT measurement of HU is a reliable method to assess two-year changes in trabecular bone density at each vertebra from C3-L5. Being reliable across all vertebrae, this methodology can aid the study of trabecular bone density changes over time in r-axSpA, a disease affecting the whole spine.

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Advances in robotic construction are evident and increasing every year, bringing present and potential improvements. However, the economic and social impacts are hard to assess and quantify without physical in situ testing, which is expensive and time-consuming. This paper presents a methodology for the simulation of robotic construction technologies, namely drones, using a virtual reality environment. Our hypothesis is that a virtual reality simulation of a robotic construction (H1) has the potential of increasing the precision of predicting the construction duration and cost and (H2) allows for the detection of construction problems. The study begins with a review of the literature on drones, robotic arms, and hybrid automatic construction solutions, as well as virtual reality construction simulations, summarising the robotic technologies currently being used, mainly in academic research, to assemble construction elements. It then proposes a construction simulation methodology applied to three architectonic elements to analyse different approaches and different scenarios for robotic construction simulation methodology. A construction simulation is tested, and the data is analysed and compared with traditional construction methods, focussing on construction time and costs.

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Negative pressure pulmonary edema (NPPE) in the context of anesthesia is a rare condition, although pediatric patients are at higher risk. This case stands out for the severe respiratory clinic that quickly developed in a child with a cancer history whose radiological and clinical presentation suggested multiple differential diagnoses, including tumor recurrence with metastasis or pulmonary tuberculosis. NPPE is a well-described, but a probably underrecognized clinical syndrome, that occurs after intense inspiratory effort against an obstructed airway. In clinical practice, when unexplained pulmonary edema takes place, NPPE should be considered in the differential diagnosis. NPPE usually has a favorable prognosis but pediatricians, radiologists, and anesthesiologists should be aware of this complication.

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OBJECTIVE: Studying vertebral bone loss in radiographic axial spondyloarthritis (r-axSpA) has been challenging due to ectopic bone formation. We cross-sectionally analysed low-dose CT (ldCT) trabecular bone density Hounsfield units (HU) measurements and calculated inter-reader reliability at the vertebral level in patients with r-axSpA. METHODS: LdCT scans of 50 patients with r-axSpA from the sensitive imaging in ankylosing spondylitis study, a multicentre 2-year prospective cohort were included. Trabecular bone HU taken from a region of interest at the centre of each vertebra (C3-L5) were independently assessed by two trained readers. HU mean (SD), and range were provided at the vertebral level, for each reader and centre separately. Inter-reader reliability and agreement were assessed using intraclass correlation coefficients (ICC; single measurements, absolute agreement, two-way mixed effects models); smallest detectable difference and Bland-Altman plots. RESULTS: Overall, 1100 vertebrae were assessed by each reader. HU values decreased from cranial to caudal vertebrae. For readers 1 and 2 respectively, the highest mean (SD) HU value was obtained at C3 (354(106) and 355(108)), and the lowest at L3 (153(65) and 150 (65)). Inter-reader reliability was excellent (ICC(2,1):0.89 to 1.00). SDD varied from 4 to 8. For most vertebrae, reader 1 scored somewhat higher than reader 2 (mean difference of scores ranging from -0.6 to 2.9 HU). Bland-Altman plots showed homoscedasticity. CONCLUSION: LdCT measurement of HU is a feasible method to assess vertebral bone density in r-axSpA with excellent inter-reader reliability from C3 to L5. These results warrant further validation and longitudinal assessment of reliability.

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Perioperative management of patients with mediastinal masses still poses a challenge for the anesthesiologist, as the use of general anesthesia can be associated with acute perioperative cardiorespiratory impairment resulting from the mass collapsing on the airway or vascular structures. Dexmedetomidine can be used for procedural sedation due to its reversible sedative and anxiolytic properties with dose-dependent effects, while not interfering with ventilatory drive. These features are of particular interest for the perioperative management of patients with large anterior mediastinal masses. In this case, we report our anesthetic management of a 22-year-old male scheduled for anterior mediastinotomy, with a large anterior mediastinal mass, with 50% distal tracheal compression and marked collapse of the superior vena cava and brachiocephalic trunk. In the operation theatre, an infusion of dexmedetomidine was titrated to adequate anesthetic depth while keeping the patient under spontaneous ventilation with oxygen (O2) supplementation and local anesthetic infiltration of the surgical site. Mediastinotomy lasted for about 30 minutes, during which the patient maintained appropriate ventilation and hemodynamic stability. No adverse events occurred perioperatively. Diagnostic procedures such as mediastinotomy for tissue biopsy are necessary to achieve a histological diagnosis. High-risk patients may present with severe postural symptoms, stridor, cyanosis, and radiological evidence of more than 50% airway obstruction, tracheal compression with bronchial compression, pericardial effusion, or superior vena cava syndrome. Relaxation of bronchial smooth muscles under general anesthesia increases the risk of airway obstruction. In this case, with the use of dexmedetomidine combined with local anesthetic infiltration, spontaneous ventilation and muscle tone were preserved, decreasing the probability of intraoperative complications. It is our opinion that dexmedetomidine combined with local anesthetic infiltration can be a safe option for procedural sedation in patients presenting with high-risk anterior mediastinal masses for mediastinotomy.

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BACKGROUND: Fluorine-18 sodium fluoride (Na[18F]F) atherosclerotic plaque uptake in positron emission tomography with computed tomography (PET-CT) identifies active microcalcification. We aim to evaluate global cardiac microcalcification activity with Na[18F]F, as a measure of unstable microcalcification burden, in high cardiovascular (CV) risk patients. METHODS AND RESULTS: Thirty-four high CV risk individuals without previous CV events were scanned with Na[18F]F PET-CT. Cardiac Na[18F]F uptake was assessed through the global molecular calcium score (GMCS), which was calculated by summing the product of the mean standardized uptake value times the area of the cardiac regions of interest times the slice thickness for all cardiac transaxial slices, divided by the total number of slices. Mean age is 63.5 ± 7.8 years and 62% male. Median GMCS is 320.9 (240.8-402.8). Individuals with more than five CV risk factors (50%) have increased GMCS [356.7 (321.0-409.6) vs. 261.1 (225.6-342.1), P = 0.01], which is positively correlated with predicted fatal CV risk by SCORE (rs = 0.32, P = 0.04). There is a positive correlation between GMCS and weight (rs = 0.61), body mass index (rs = 0.66), abdominal perimeter (rs = 0.74), thoracic fat volume (rs = 0.47), and epicardial adipose tissue (rs = 0.41), all with P ≤ 0.01. There is no correlation between GMCS and coronary calcium score nor coronary artery wall Na[18F]F uptake. CONCLUSIONS: In a high CV risk group, the global cardiac microcalcification burden is related to CV risk factors, metabolic syndrome variables and cardiac fat. Cardiac GMCS is a promising risk stratification tool, combining a straightforward and objective methodology with a comprehensive analysis of both coronary and valvular microcalcification.

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Gene therapy and DNA vaccination are among the most expected biotechnological and medical advances for the coming years. However, the lack of cost-effective large-scale production and purification of pharmaceutical-grade plasmid DNA (pDNA) still hampers their wide application. Downstream processing, which is mainly chromatography-based, of pDNA remains the key manufacturing step. Despite its high resolution, the scaling-up of chromatography is usually difficult and presents low capacity, resulting in low yields. Alternative methods that are based on aqueous two-phase systems (ATPSs) have been studied. Although higher yields may be obtained, its selectivity is often low. In this work, modified polymers based on poly(ethylene glycol) (PEG) derivatisation with amino groups (PEG-amine) or conjugation with positively charged amino acids (PEG-lysine, PEG-arginine, and PEG-histidine) were studied to increase the selectivity of PEG-dextran systems towards the partition of a model plasmid. A two-step strategy was employed to obtain suitable pure formulations of pDNA. In the first step, a PEG-dextran system with the addition of the affinity ligand was used with the recovery of the pDNA in the PEG-rich phase. Then, the pDNA was re-extracted to an ammonium-sulphate-rich phase in the second step. After removing the salt, this method yielded a purified preparation of pDNA without RNA and protein contamination.

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The posterior cruciate ligament (PCL) avulsion fracture is a rare injury and occurs mainly in young patients. The development of arthroscopic techniques and fixation methods has improved the treatment of this entity. This report describes a modified arthroscopic suture fixation of a small tibial avulsion fracture of the PCL. A 17-year-old male, injured in a motorcycle crash, was admitted to the Emergency Department and diagnosed with left knee PCL tibial avulsion fracture, lateral collateral ligament (LCL) femoral avulsion fracture, and patella fracture. The PCL was fixed arthroscopically using a Knee Scorpion and two SutureTapes (Arthrex, Munich-Germany) through of an interlaced configuration at the base of the fragment using a transseptal approach and fixed distally over a cortical button on the anterior cortex. The LCL was repaired with two cannulated screws by a percutaneous approach. At 1 year of follow-up, the fragment was healed with tibiofemoral congruence, and the knee was stable with complete range of motion. The Tegner Lysholm Knee Scoring Scale (TLKSS) was 92.

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Advanced perfusion-weighted imaging (PWI) methods that combine gradient echo (GE) and spin echo (SE) data are important tools for the study of brain tumours. In PWI, single-shot, EPI-based methods have been widely used due to their relatively high imaging speed. However, when used with increasing spatial resolution, single-shot EPI methods often show limitations in whole-brain coverage for multi-contrast applications. To overcome this limitation, this work employs a new version of EPI with keyhole (EPIK) to provide five echoes: two with GEs, two with mixed GESE and one with SE; the sequence is termed "GESE-EPIK." The performance of GESE-EPIK is evaluated against its nearest relative, EPI, in terms of the temporal signal-to-noise ratio (tSNR). Here, data from brain tumour patients were acquired using a hybrid 3T MR-BrainPET scanner. GESE-EPIK resulted in reduced susceptibility artefacts, shorter TEs for the five echoes and increased brain coverage when compared to EPI. Moreover, compared to EPI, EPIK achieved a comparable tSNR for the first and second echoes and significantly higher tSNR for other echoes. A new method to obtain multi-echo GE and SE data with shorter TEs and increased brain coverage is demonstrated. As proposed here, the workflow can be shortened and the integration of multimodal clinical MR-PET studies can be facilitated.

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BACKGROUND: Three-dimensional (3D) models are increasingly used to help surgeons, guiding them through the complex hepatic vasculobiliary anatomy. The biliary tract is a relatively untapped territory with only a few case reports described in medical literature. Our aim is to present an innovative 3D reconstruction methodology for biliary imaging and surgical planning, applied to a case of iatrogenic biliary stricture, with fusion of segmented CT and MRI images. CASE PRESENTATION: A selected case of Bismuth type III iatrogenic biliary stenosis for 3D planning. CT and MR studies were acquired with dedicated protocols for segmentation. Two radiologists performed segmentation and 3D model post-processing, fusing both imaging techniques to faithfully render the anatomical structures. Measurements of anatomical landmarks were taken in both the CT/MRI and the 3D model to assure its accuracy and differences in measurement were calculated. The 3D model replicates anatomical structures and pathology with high accuracy, with only 2.2% variation between STL, CT and MRI measurements. The model was discussed with the surgical team and used in the surgical planning, improving confidence in this delicate procedure, due to the detailed prior knowledge of the patient's anatomy. CONCLUSION: Three-dimensional reconstructions are a rapidly growing area of research with a significant impact in the personalized and precision medicine. The construction of 3D models that combine vascular and biliary anatomy, using different imaging techniques, respectively CT and MRI, will predictably contribute to a more rigorous planning of complex liver surgeries.

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Analysis of the partition coefficients of small organic compounds and proteins in different aqueous two-phase systems under widely varied ionic compositions shows that logarithms of partition coefficients for any three compounds or proteins or two organic compounds and one protein are linearly interrelated, although for protein(s) there are ionic compositions when the linear fit does not hold. It is suggested that the established interrelationships are due to cooperativity of different types of solute-solvent interactions in aqueous media. This assumption is confirmed by analysis of distribution coefficients of various drugs in octanol-buffer systems with varied ionic compositions of the buffer. Analysis of the partition coefficients characterizing distribution of variety of drugs between blood and different tissues of rats in vivo reported in the literature showed that the above assumption is correct and enabled us to identify the tissues with the components of which the drug(s) may engage in presumably direct interactions. It shows that the suggested assumption is valid for even complex biological systems.

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BACKGROUND: In addition to the structural information afforded by 1H MRI, the use of X-nuclei, such as sodium-23 (23Na) or phosphorus-31 (31P), offers important complementary information concerning physiological and biochemical parameters. By then combining this technique with PET, which provides valuable insight into a wide range of metabolic and molecular processes by using of a variety of radioactive tracers, the scope of medical imaging and diagnostics can be significantly increased. While the use of multimodal imaging is undoubtedly advantageous, identifying the optimal combination of these parameters to diagnose a specific dysfunction is very important and is advanced by the use of sophisticated imaging techniques in specific animal models. METHODS: In this pilot study, rats with intracerebral 9L gliosarcomas were used to explore a combination of sequential multinuclear MRI using a sophisticated switchable coil set in a small animal 9.4 T MRI scanner and, subsequently, a small animal PET with the tumour tracer O-(2-[18F]-fluoroethyl)-L-tyrosine ([18F]FET). This made it possible for in vivo multinuclear MR-PET experiments to be conducted without compromising the performance of either multinuclear MR or PET. RESULTS: High-quality in vivo images and spectra including high-resolution 1H imaging, 23Na-weighted imaging, detection of 31P metabolites and [18F]FET uptake were obtained, allowing the characterisation of tumour tissues in comparison to a healthy brain. It has been reported in the literature that these parameters are useful in the identification of the genetic profile of gliomas, particularly concerning the mutation of the isocitrate hydrogenase gene, which is highly relevant for treatment strategy. CONCLUSIONS: The combination of multinuclear MR and PET in, for example, brain tumour models with specific genetic mutations will enable the physiological background of signal alterations to be explored and the identification of the optimal combination of imaging parameters for the non-invasive characterisation of the molecular profile of tumours.