An Analysis From a Tertiary Pediatric Hospital: Does Physical Activity Play a Role in the Management of Children and Young Adults With Osteogenesis Imperfecta?

Introduction: Osteogenesis imperfecta (OI) is a hereditary connective tissue disorder characterized by reduced bone density and increased proneness to fractures. It manifests across a varied clinical spectrum of expressions in children and young adults. It is crucial for children with OI to have a multidisciplinary follow-up, including orthopedics, pediatrics, and physical medicine and rehabilitation. Although exercise may have no effect on the disease itself, it might improve the autonomy, self-esteem, and fitness of these children. Methods: Retrospective cohort analysis of children and young adults aged three or more years old followed-up in a Level III Pediatric Hospital between 1995 and 2020. Demographic and clinical data were obtained from the hospital records and from the caregivers via phone calls. To our knowledge, this is the first national case series published assessing exercise habits in children with this condition. Results: Among the 21 patients studied, the median age was 14 years, with no gender predominance. Eighteen (86%) practiced regular physical activity, while the remaining three (14%), all of whom were type III OI, were totally dependent. Of the aforementioned 18 children, 12 (67%) considered practicing the same level of physical activity compared to their healthy peers, although most of them needed adaptations. The most reported extracurricular activity was swimming, in 50% of the cases. About 39% engaged in physical activity two times or less per week, and 89% practiced for one hour or less per session. Discussion: Over the years, it has become clear that physical activity is an important part of OI management. While awareness of the importance of exercise already exists, proper planning, follow-up, and monitoring are essential.info:eu-repo/semantics/publishedVersio

Serum amyloid A proteins reduce bone mass during mycobacterial infections

IntroductionOsteopenia has been associated to several inflammatory conditions, including mycobacterial infections. How mycobacteria cause bone loss remains elusive, but direct bone infection may not be required. MethodsGenetically engineered mice and morphometric, transcriptomic, and functional analyses were used. Additionally, inflammatory mediators and bone turnover markers were measured in the serum of healthy controls, individuals with latent tuberculosis and patients with active tuberculosis. Results and discussionWe found that infection with Mycobacterium avium impacts bone turnover by decreasing bone formation and increasing bone resorption, in an IFN gamma- and TNF alpha-dependent manner. IFN gamma produced during infection enhanced macrophage TNF alpha secretion, which in turn increased the production of serum amyloid A (SAA) 3. Saa3 expression was upregulated in the bone of both M. avium- and M. tuberculosis-infected mice and SAA1 and 2 proteins (that share a high homology with murine SAA3 protein) were increased in the serum of patients with active tuberculosis. Furthermore, the increased SAA levels seen in active tuberculosis patients correlated with altered serum bone turnover markers. Additionally, human SAA proteins impaired bone matrix deposition and increased osteoclastogenesis in vitro. Overall, we report a novel crosstalk between the cytokine-SAA network operating in macrophages and bone homeostasis. These findings contribute to a better understanding of the mechanisms of bone loss during infection and open the way to pharmacological intervention. Additionally, our data and disclose SAA proteins as potential biomarkers of bone loss during infection by mycobacteria.This article is a result of the project HEALTH-UNORTE: Setting-up biobanks and regenerative medicine strategies to boost research in cardiovascular, musculoskeletal, neurological, oncological, immunological and infectious diseases (NORTE-01-0145-FEDER-000039), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This work was supported by KOG-202108-00929 from the European Haematology Society, awarded to AG. Work in the MS lab was financed by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundacao para a Ciencia e a Tecnologia/Ministerio da Ciencia, Tecnologia e Ensino Superior in the framework of the project POCI-01-0145-FEDER-028955 (PTDC/SAU-INF/28955/2017). AG and MS are supported by an Individual Scientific Employment contract (CEECIND/00048/2017; CEECIND/00241/2017 respectively). DS acknowledges the Portuguese Foundation for Science and Technology (FCT) for the Post-Doc fellowship (SFRH/BPD/115341/2016). RP, DS and AF have PhD grants (SFRH/BD/145217/2019; SFRH/BD/143536/2019; 2020.05949.BD, respectively) financed by FCT

Recommendations for the implementation of a national lung cancer screening program in Portugal—A consensus statement

Lung cancer (LC) is a leading cause of cancer-related mortality worldwide. Lung Cancer Screening (LCS) programs that use low-dose computed tomography (LDCT) have been shown to reduce LC mortality by up to 25 % and are considered cost-effective. The European Health Union has encouraged its Member States to explore the feasibility of LCS implementation in their respective countries. The task force conducted a comprehensive literature review and engaged in extensive discussions to provide recommendations. These recommendations encompass the essential components required to initiate pilot LCS programs following the guidelines established by the World Health Organization. They were tailored to align with the specific context of the Portuguese healthcare system. The document addresses critical aspects, including the eligible population, methods for issuing invitations, radiological prerequisites, procedures for reporting results, referral processes, diagnostic strategies, program implementation, and ongoing monitoring. Furthermore, the task force emphasized that pairing LCS with evidence-based smoking cessation should be the standard of care for a high-quality screening program. This document also identifies areas for further research. These recommendations aim to guarantee that the implementation of a Portuguese LCS program ensures high-quality standards, consistency, and uniformity across centres. © 2024 Sociedade Portuguesa de Pneumologi

Nutrient intakes related to osteoporotic fractures in men and women – The Brazilian Osteoporosis Study (BRAZOS)

<p>Abstract</p> <p>Background</p> <p>Adequate nutrition plays an important role in bone mass accrual and maintenance and has been demonstrated as a significant tool for the prevention of fractures in individuals with osteoporosis.</p> <p>Objective</p> <p>The aim of the present study was to evaluate bone health-related nutrients intake and its association with osteoporotic fractures in a representative sample of 2344 individuals aged 40 years or older in Brazil.</p> <p>Methods</p> <p>In a transversal population-based study, a total of 2420 individuals over 40 years old were evaluated from March to April 2006. Participants were men and women from all socio-economic classes and education levels living around the Brazilian territory Individuals responded a questionnaire including self reported fractures as well a 24-hour food recall. Nutrient intakes were evaluated by Nutrition Data System for Research software (NDSR, University of Minnesota, 2007). Low trauma fracture was defined as that resulting of a fall from standing height or less. Nutrient intakes adequacies were performed by using the DRI's proposed values. Statistical analysis comprises Oneway ANCOVA adjusted by age and use of nutritional supplements and multiple logistic regression. SAS software was used for statistical analysis.</p> <p>Results</p> <p>Fractures was reported by 13% of men and 15% of women. Women with fractures presented significantly higher calcium, phosphorus and magnesium intakes. However, in all regions and socio-economical levels mean intakes of bone related nutrients were below the recommended levels. It was demonstrated that for every 100 mg/phosphorus increase the risk of fractures by 9% (OR 1.09; IC95% 1.05–1.13, p < 0.001).</p> <p>Conclusion</p> <p>The results demonstrated inadequacies in bone related nutrients in our population as well that an increase in phosphorus intake is related to bone fractures.</p

Dynamics of Macrophage Trogocytosis of Rituximab-Coated B Cells

Macrophages can remove antigen from the surface of antibody-coated cells by a process termed trogocytosis. Using live cell microscopy and flow cytometry, we investigated the dynamics of trogocytosis by RAW264.7 macrophages of Ramos B cells opsonized with the anti-CD20 monoclonal antibody rituximab. Spontaneous and reversible formation of uropods was observed on Ramos cells, and these showed a strong enrichment in rituximab binding. RAW-Ramos conjugate interfaces were highly enriched in rituximab, and transfer of rituximab to the RAW cells in submicron-sized puncta occurred shortly after cell contact. Membrane from the target cells was concomitantly transferred along with rituximab to a variable extent. We established a flow cytometry-based approach to follow the kinetics of transfer and internalization of rituximab. Disruption of actin polymerization nearly eliminated transfer, while blocking phosphatidylinositol 3-kinase activity only resulted in a delay in its acquisition. Inhibition of Src family kinase activity both slowed acquisition and reduced the extent of trogocytosis. The effects of inhibiting these kinases are likely due to their role in efficient formation of cell-cell conjugates. Selective pre-treatment of Ramos cells with phenylarsine oxide blocked uropod formation, reduced enrichment of rituximab at cell-cell interfaces, and reduced the efficiency of trogocytic transfer of rituximab. Our findings highlight that dynamic changes in target cell shape and surface distribution of antigen may significantly influence the progression and extent of trogocytosis. Understanding the mechanistic determinants of macrophage trogocytosis will be important for optimal design of antibody therapies

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente