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- Bonham, LW, et al.
(author)
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Genetic variation across RNA metabolism and cell death gene networks is implicated in the semantic variant of primary progressive aphasia
- 2019
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 10854-
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Journal article (peer-reviewed)abstract
- The semantic variant of primary progressive aphasia (svPPA) is a clinical syndrome characterized by neurodegeneration and progressive loss of semantic knowledge. Unlike many other forms of frontotemporal lobar degeneration (FTLD), svPPA has a highly consistent underlying pathology composed of TDP-43 (a regulator of RNA and DNA transcription metabolism). Previous genetic studies of svPPA are limited by small sample sizes and a paucity of common risk variants. Despite this, svPPA’s relatively homogenous clinicopathologic phenotype makes it an ideal investigative model to examine genetic processes that may drive neurodegenerative disease. In this study, we used GWAS metadata, tissue samples from pathologically confirmed frontotemporal lobar degeneration, and in silico techniques to identify and characterize protein interaction networks associated with svPPA risk. We identified 64 svPPA risk genes that interact at the protein level. The protein pathways represented in this svPPA gene network are critical regulators of RNA metabolism and cell death, such as SMAD proteins and NOTCH1. Many of the genes in this network are involved in TDP-43 metabolism. Contrary to the conventional notion that svPPA is a clinical syndrome with few genetic risk factors, our analyses show that svPPA risk is complex and polygenic in nature. Risk for svPPA is likely driven by multiple common variants in genes interacting with TDP-43, along with cell death,x` working in combination to promote neurodegeneration.
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- Castelnuovo, Gianluca, et al.
(author)
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What Is the Role of the Placebo Effect for Pain Relief in Neurorehabilitation? : Clinical Implications From the Italian Consensus Conference on Pain in Neurorehabilitation
- 2018
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In: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 9
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Research review (peer-reviewed)abstract
- Background: It is increasingly acknowledged that the outcomes of medical treatments are influenced by the context of the clinical encounter through the mechanisms of the placebo effect. The phenomenon of placebo analgesia might be exploited to maximize the efficacy of neurorehabilitation treatments. Since its intensity varies across neurological disorders, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCP) summarized the studies on this field to provide guidance on its use.Methods: A review of the existing reviews and meta-analyses was performed to assess the magnitude of the placebo effect in disorders that may undergo neurorehabilitation treatment. The search was performed on Pubmed using placebo, pain, and the names of neurological disorders as keywords. Methodological quality was assessed using a pre-existing checklist. Data about the magnitude of the placebo effect were extracted from the included reviews and were commented in a narrative form.Results: 11 articles were included in this review. Placebo treatments showed weak effects in central neuropathic pain (pain reduction from 0.44 to 0.66 on a 0-10 scale) and moderate effects in postherpetic neuralgia (1.16), in diabetic peripheral neuropathy (1.45), and in pain associated to HIV (1.82). Moderate effects were also found on pain due to fibromyalgia and migraine; only weak short-term effects were found in complex regional pain syndrome. Confounding variables might have influenced these results.Clinical implications: These estimates should be interpreted with caution, but underscore that the placebo effect can be exploited in neurorehabilitation programs. It is not necessary to conceal its use from the patient. Knowledge of placebo mechanisms can be used to shape the doctor-patient relationship, to reduce the use of analgesic drugs and to train the patient to become an active agent of the therapy.
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- Dewaraja, Yuni K., et al.
(author)
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Improved quantitative 90Y bremsstrahlung SPECT/CT reconstruction with Monte Carlo scatter modeling
- 2017
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In: Medical Physics. - : Wiley. - 0094-2405. ; 44:12, s. 6364-6376
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Journal article (peer-reviewed)abstract
- Purpose: In 90Y microsphere radioembolization (RE), accurate post-therapy imaging-based dosimetry is important for establishing absorbed dose versus outcome relationships for developing future treatment planning strategies. Additionally, accurately assessing microsphere distributions is important because of concerns for unexpected activity deposition outside the liver. Quantitative 90Y imaging by either SPECT or PET is challenging. In 90Y SPECT model based methods are necessary for scatter correction because energy window-based methods are not feasible with the continuous bremsstrahlung energy spectrum. The objective of this work was to implement and evaluate a scatter estimation method for accurate 90Y bremsstrahlung SPECT/CT imaging. Methods: Since a fully Monte Carlo (MC) approach to 90Y SPECT reconstruction is computationally very demanding, in the present study the scatter estimate generated by a MC simulator was combined with an analytical projector in the 3D OS-EM reconstruction model. A single window (105 to 195-keV) was used for both the acquisition and the projector modeling. A liver/lung torso phantom with intrahepatic lesions and low-uptake extrahepatic objects was imaged to evaluate SPECT/CT reconstruction without and with scatter correction. Clinical application was demonstrated by applying the reconstruction approach to five patients treated with RE to determine lesion and normal liver activity concentrations using a (liver) relative calibration. Results: There was convergence of the scatter estimate after just two updates, greatly reducing computational requirements. In the phantom study, compared with reconstruction without scatter correction, with MC scatter modeling there was substantial improvement in activity recovery in intrahepatic lesions (from > 55% to > 86%), normal liver (from 113% to 104%), and lungs (from 227% to 104%) with only a small degradation in noise (13% vs. 17%). Similarly, with scatter modeling contrast improved substantially both visually and in terms of a detectability index, which was especially relevant for the low uptake extrahepatic objects. The trends observed for the phantom were also seen in the patient studies where lesion activity concentrations and lesion-to-liver concentration ratios were lower for SPECT without scatter correction compared with reconstruction with just two MC scatter updates: in eleven lesions the mean uptake was 4.9 vs. 7.1 MBq/mL (P = 0.0547), the mean normal liver uptake was 1.6 vs. 1.5 MBq/mL (P = 0.056) and the mean lesion-to-liver uptake ratio was 2.7 vs. 4.3 (P = 0.0402) for reconstruction without and with scatter correction respectively. Conclusions: Quantitative accuracy of 90Y bremsstrahlung imaging can be substantially improved with MC scatter modeling without significant degradation in image noise or intensive computational requirements.
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- Girolami, Ilaria, et al.
(author)
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The Landscape of Digital Pathology in Transplantation : From the Beginning to the Virtual E-Slide
- 2019
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In: Journal of Pathology Informatics. - : Medknow Publications. - 2229-5089 .- 2153-3539. ; 10:21
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Journal article (peer-reviewed)abstract
- Digital pathology has progressed over the last two decades, with many clinical and nonclinical applications. Transplantation pathology is a highly specialized field in which the majority of practicing pathologists do not have sufficient expertise to handle critical needs. In this context, digital pathology has proven to be useful as it allows for timely access to expert second-opinion teleconsultation. The aim of this study was to review the experience of the application of digital pathology to the field of transplantation.
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- Johansson, Bengt, 1964, et al.
(author)
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EUROPEAN ELECTIONS MONITORING CENTER
- 2019
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In: 2019 European elections campaign. Images, topics, media in the 28 Member States (E. Novelli & B Johansson (eds.).. - Bryssel : Directorate-General for Communication (European Parliament) , University Roma Tre. - 9789284649853 ; , s. 13-32
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Book chapter (other academic/artistic)
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- Novelli, A., et al.
(author)
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Evaluation of OH and HO2 concentrations and their budgets during photooxidation of 2-methyl-3-butene-2-ol (MBO) in the atmospheric simulation chamber SAPHIR
- 2018
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In: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 18:15, s. 11409-11422
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Journal article (peer-reviewed)abstract
- Several previous field studies have reported unexpectedly large concentrations of hydroxyl and hydroperoxyl radicals (OH and HO2, respectively) in forested environments that could not be explained by the traditional oxidation mechanisms that largely underestimated the observations. These environments were characterized by large concentrations of biogenic volatile organic compounds (BVOC) and low nitrogen oxide concentration. In isoprene-dominated environments, models developed to simulate atmospheric photochemistry generally underestimated the observed OH radical concentrations. In contrast, HO2 radical concentration showed large discrepancies with model simulations mainly in non-isoprene-dominated forested environments. An abundant BVOC emitted by lodgepole and ponderosa pines is 2-methyl- 3-butene-2-ol (MBO), observed in large concentrations for studies where the HO2 concentration was poorly described by model simulations. In this work, the photooxidation of MBO by OH was investigated for NO concentrations lower than 200 pptv in the atmospheric simulation chamber SAPHIR at Forschungszentrum Julich. Measurements of OH and HO2 radicals, OH reactivity (kO(H)), MBO, OH precursors, and organic products (acetone and formaldehyde) were used to test our current understanding of the OH-oxidation mechanisms for MBO by comparing measurements with model calculations. All the measured trace gases agreed well with the model results (within 15 %) indicating a well understood mechanism for the MBO oxidation by OH. Therefore, the oxidation of MBO cannot contribute to reconciling the unexplained high OH and HO2 radical concentrations found in previous field studies.
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- Serino, Silvia, et al.
(author)
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A Novel Technique for Improving Bodily Experience in a Non-operable Super-Super Obesity Case
- 2016
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In: Frontiers in Psychology. - : Frontiers Media SA. - 1664-1078. ; 7
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Journal article (peer-reviewed)abstract
- Introduction: The available clinical guidelines for super-super obese patients (i.e., with body mass index (BMI) 60 kg/m(2)) that are not suitable for bariatric surgery mandate a palliative multidisciplinary treatment (i.e., production and maintenance of weight loss) provided in a center of excellence. However, the modality and the impact of this approach are still controversial. Moreover, it is not able to address the high level of body dissatisfaction and body distortions that are common among these patients. Clinical Presentation: We report the case of a non-operable super-super obesity - a 37 year old woman with a BMI of 62 kg/m(2) - receiving a specialized treatment for her obstructive sleep apnea. She entered a multidisciplinary program that promoted healthy behaviors, including physical activities and psychological intervention. To improve body dissatisfaction, which was linked to a significant multisensory impairment of body perception, she also entered a virtual reality (VR) body-swapping illusion protocol. At the end of the current investigation, the patient continued her multidisciplinary program, reporting an increase in the motivation for undertaking healthy behavior and a decrease in the anxiety feelings associated with her clinical condition. Conclusion: This case provides preliminary evidence that both body dissatisfaction and body-size distortions of non-operable super-super obesity patients could be addressed by a VR body-swapping protocol, which is important because the palliative multidisciplinary treatment recommended for these patients is not able to address them. Interestingly, the use of a VR body-swapping illusion protocol seems to be able to improve not only the experience of the body in these patients but their motivation for change, too.
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- Yamanaka, H., et al.
(author)
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Infection rates in patients from five rheumatoid arthritis (RA) registries: Contextualising an RA clinical trial programme
- 2017
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In: RMD Open. - : BMJ. - 2056-5933. ; 3:2
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Journal article (peer-reviewed)abstract
- Objective Patients with rheumatoid arthritis (RA) have an increased risk of serious infections. Comparing infection rates across RA populations is complicated by differences in background infection risk, population composition and study methodology. We measured infection rates from five RA registries globally, with the aim to contextualise infection rates from an RA clinical trials population. Methods We used data from Consortium of Rheumatology Research of North America (CORRONA) (USA), Swedish Rheumatology Quality of Care Register (Sweden), Norfolk Arthritis Register (UK), CORRONA International (multiple countries) and Institute of Rheumatology Rheumatoid Arthritis (Japan) and an RA clinical trial programme (fostamatinib). Within each registry, we analysed a main cohort of all patients with RA from January 2000 to last available data. Infection definitions were harmonised across registries. Sensitivity analyses to address potential confounding explored subcohorts defined by disease activity, treatment change and/or prior comorbidities and restriction by calendar time or follow-up. Rates of infections were estimated and standardised to the trial population for age/sex and, in one sensitivity analysis also, for Health Assessment Questionnaire (HAQ) score. Results Overall, age/sex-standardised rates of hospitalised infection were quite consistent across registries (range 1.14-1.62 per 100 patient-years). Higher and more consistent rates across registries and with the trial programme overall were seen when adding standardisation for HAQ score (registry range 1.86-2.18, trials rate 2.92) or restricting to a treatment initiation subcohort followed for 18 months (registry range 0.99-2.84, trials rate 2.74). Conclusion This prospective, coordinated analysis of RA registries provided incidence rate estimates for infection events to contextualise infection rates from an RA clinical trial programme and demonstrated relative comparability of hospitalised infection rates across registries. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved.
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