The crossroads between infection and bone loss

Bone homeostasis, based on a tight balance between bone formation and bone degradation, is affected by infection. On one hand, some invading pathogens are capable of directly colonizing the bone, leading to its destruction. On the other hand, immune mediators produced in response to infection may dysregulate the deposition of mineral matrix by osteoblasts and/or the resorption of bone by osteoclasts. Therefore, bone loss pathologies may develop in response to infection, and their detection and treatment are challenging. Possible biomarkers of impaired bone metabolism during chronic infection need to be identified to improve the diagnosis and management of infection-associated osteopenia. Further understanding of the impact of infections on bone metabolism is imperative for the early detection, prevention, and/or reversion of bone loss. Here, we review the mechanisms responsible for bone loss as a direct and/or indirect consequence of infection.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, immunologicalm, 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). A.C.G. is supported by a Junior Investigator Contract under the program CEEIND2017, from Fundação para a Ciência e Tecnologia (Portugal)

Food insecurity is associated with an unhealthy lifestyle score in middle- and older-aged adults: findings from the EPIPorto cohort

The association of food insecurity with the combined effect of lifestyles is still limited. This study evaluated the association between food insecurity and a lifestyle score in middle- and older-aged adults. A cross-sectional study (2013-2016) was performed among 595 individuals (>= 50 years) from the EPIPorto cohort (Porto, Portugal). Food security status was assessed using the US Household Food Security Survey Module: Six-Item Short Form. Information on fruit and vegetable consumption (F&V), physical activity (PA) practice, tobacco smoking, and alcohol consumption were included in a lifestyle score. Those with F&V one drink of alcoholic beverages in women, and > two in men were assigned with one point; all the others had nil points. The score could range from 0 to 4, and was further categorised into three categories. Food insecurity was positively associated with an unhealthy lifestyle profile (OR = 2.272; 95%CI:1.079-4.782), independently of the adjustment variables. Analysing each lifestyle component, food insecurity was associated with low PA practice (OR = 2.365; 95%CI:1.020-5.485). Individuals from food insecure households were more likely to have an unhealthy lifestyle profile. Public health strategies should be developed among food insecure individuals to promote healthy lifestyles

Determination of sulfur dioxide in wine using a quartz crystal microbalance

A new method for the analysis of both total and bound SO2 in wine is proposed, based on a quartz crystal microbalance (QCM), and it is compared with the widely used Ripper method. The proposed method is faster than the Ripper's, and the instrumentation is either homemade or widely available. When both methods are applied to the same sample, the results obtained using the QCM method are bracketed in an interval less than one-tenth the size of that obtained using the Ripper method. Although the SO2 concentrations found using the QCM method correlate well with the ones obtained with the Ripper method, the results are systematically higher, which can be explained as due to the absence of interferences known to affect the Ripper method

The association of problematic eating behaviours with food quality and body mass index at 7 years of age

Background/objectives: There is scarce evidence of how certain eating behaviours compromise the compliance with dietary guidelines and weight status in school-aged children. This study aims to evaluate the association of children’s problematic eating behaviours with food quality and body mass index at 7 years of age. Subjects/methods: Participants were children aged 7 years old from a population-based cohort study from Porto, Portugal-Generation XXI. Children’s quantity and speed of ingestion, food refusal at the table and food rewards requesting were evaluated by caregiver’s perception. Food consumption was evaluated by a food frequency questionnaire and compared with age-appropriate guidelines. Children’s weight status was assessed by objective measurements and parent’s perceptions. Associations were estimated by logistic regressions (odds ratio (OR), 95% confidence intervals (95% CI)) adjusted for maternal age, education, smoking during pregnancy, birth type, child’s sex, weight-for-gestational age and sports (n = 3801). Results: Children eating small amounts of food, refusing to eat at the table with the rest of the family during meals and asking for food rewards showed a higher consumption of energy-dense foods (OR = 1.51; 95% CI:1.23–1.86; OR = 1.58; 95% CI:1.16–2.16; OR = 1.56; 95% CI:1.14–2.12) and presented higher odds of consuming fruit and vegetables below recommendations (OR = 1.41; 95% CI:1.22–1.64; OR = 1.20; 95% CI:1.00–1.45; OR = 1.28; 95% CI:1.05–1.55). Children displaying these eating behaviours were less likely to be overweight/obese, hence their parents were less likely to show concern with their weight. Including food quality as covariate in the final models with obesity status did not change the associations. Conclusions: Problematic eating behaviours were associated with poorer food quality (more energy-dense foods and low fruit and vegetables), but food quality does not seem to explain the association with obesity status. Parents were less likely to be concerned about their child’s weight if the child ate slowly or poorly, and accordingly the odds of them being overweight or obese were lower.Generation XXI was funded by the Health Operational Programme—Saúde XXI, Community Support Framework III and the Regional Department of Ministry of Health. This study was supported through FEDER from the Operational Programme Factors of Competitiveness (COMPETE) and through national funding from the Foundation for Science and Technology (FCT; Portuguese Ministry of Education and Science) under the project PTDC/SAU-EPI/121532/2010 (FCOMP-01-0124-FEDER-021177) and through the Investigator Programme (IF/01350/2015–Andreia Oliveira and IF/01060/2015–Ana Cristina Santos). It also had support from the Calouste Gulbenkian Foundation

Personalized modeling for prediction with decision-path models

Deriving predictive models in medicine typically relies on a population approach where a single model is developed from a dataset of individuals. In this paper we describe and evaluate a personalized approach in which we construct a new type of decision tree model called decision-path model that takes advantage of the particular features of a given person of interest. We introduce three personalized methods that derive personalized decision-path models. We compared the performance of these methods to that of Classification And Regression Tree (CART) that is a population decision tree to predict seven different outcomes in five medical datasets. Two of the three personalized methods performed statistically significantly better on area under the ROC curve (AUC) and Brier skill score compared to CART. The personalized approach of learning decision path models is a new approach for predictive modeling that can perform better than a population approach

Bioenergetic dysfunction in Huntington's disease human cybrids

In this work we studied the mitochondrial-associated metabolic pathways in Huntington's disease (HD) versus control (CTR) cybrids, a cell model in which the contribution of mitochondrial defects from patients is isolated. HD cybrids exhibited an interesting increase in ATP levels, when compared to CTR cybrids. Concomitantly, we observed increased glycolytic rate in HD cybrids, as revealed by increased lactate/pyruvate ratio, which was reverted after inhibition of glycolysis. A decrease in glucose-6-phosphate dehydrogenase activity in HD cybrids further indicated decreased rate of the pentose-phosphate pathway. ATP levels of HD cybrids were significantly decreased under glycolysis inhibition, which was accompanied by a decrease in phosphocreatine. Nevertheless, pyruvate supplementation could not recover HD cybrids' ATP or phosphocreatine levels, suggesting a dysfunction in mitochondrial use of that substrate. Oligomycin also caused a decrease in ATP levels, suggesting a partial support of ATP generation by the mitochondria. Nevertheless, mitochondrial NADH/NAD(t) levels were decreased in HD cybrids, which was correlated with a decrease in pyruvate dehydrogenase activity and protein expression, suggesting decreased tricarboxylic acid cycle (TCA) input from glycolysis. Interestingly, the activity of alpha-ketoglutarate dehydrogenase, a critical enzyme complex that links the TCA to amino acid synthesis and degradation, was increased in HD cybrids. In accordance, mitochondrial levels of glutamate were increased and alanine was decreased, whereas aspartate and glutamine levels were unchanged in HD cybrids. Conversely, malate dehydrogenase activity from total cell extracts was unchanged in HD cybrids. Our results suggest that inherent dysfunction of mitochondria from HD patients affects cellular bioenergetics in an otherwise functional nuclear background

H-Ferritin Is Essential for Macrophages' Capacity to Store or Detoxify Exogenously Added Iron

Macrophages are central cells both in the immune response and in iron homeostasis. Iron is both essential and potentially toxic. Therefore, iron acquisition, transport, storage, and release are tightly regulated, by several important proteins. Cytosolic ferritin is an iron storage protein composed of 24 subunits of either the L- or the H-type chains. H-ferritin differs from L-ferritin in the capacity to oxidize Fe2+ to Fe3+. In this work, we investigated the role played by H-ferritin in the macrophages' ability to respond to immune stimuli and to deal with exogenously added iron. We used mice with a conditional deletion of the H-ferritin gene in the myeloid lineage to obtain bone marrow-derived macrophages. These macrophages had normal viability and gene expression under basal culture conditions. However, when treated with interferon-gamma and lipopolysaccharide they had a lower activation of Nitric Oxide Synthase 2. Furthermore, H-ferritin-deficient macrophages had a higher sensitivity to iron-induced toxicity. This sensitivity was associated with a lower intracellular iron accumulation but a higher production of reactive oxygen species. These data indicate that H-ferritin modulates macrophage response to immune stimuli and that it plays an essential role in protection against iron-induced oxidative stress and cell death.Tis work was fnanced by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE2020 - Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project PTDC/IMI-MIC/1683/2014 (POCI-01-0145-FEDER-016590). PFO and MGA acknowledge FCT for the Investigador FCT 2015. We thank the valuable collaboration of the following i3S Scientifc Platforms: Cell Culture and Genotyping Core Facility (CCGen), [Histology and Electron Microscopy Service (HEMS), and BioSciences Screening], member of the PPBI (PPBI-POCI-01-0145-FEDER-022122)], Animal Facility, and Flow Cytometry Unit (TraCy). We acknowledge Lukas Kuhn (Swiss Institute for Experimental Cancer Research, Lausanne, Switzerland) for kindly providing the frst breeding pairs of Fth1−/− mice. Te authors also acknowledge Marisa Castro, from Departamento de Biologia Molecular from ICBAS, Clara Bento, from i3S, and Edgar Pinto from LAQV – REQUIMTE for technical assistance at diferent stages of the project

Effects of therapeutic ultrasound on the mechanical properties of skeletal muscles after contusion

CONTEXTUALIZAÇÃO: O ultra-som terapêutico (UST) é um recurso comumente aplicado na aceleração do reparo tecidual de lesões musculares. A absorção das ondas ultra-sônicas é determinada pela freqüência e pela intensidade, sendo que, em uma mesma intensidade, a profundidade atingida por 1MHz é maior quando comparada a 3MHz. OBJETIVO: Analisar o comportamento das propriedades mecânicas de músculos submetidos à lesão aguda por impacto e tratados com UST, utilizando as freqüências de 1 e 3MHz. MATERIAIS E MÉTODOS: Foram utilizadas 40 ratas Wistar (200,1±17,8g), divididas em quatro grupos: (1) controle; (2) lesão muscular sem tratamento; (3) lesão muscular tratada com UST de freqüência 1MHz (0,5W/cm²) e (4) lesão muscular tratada com UST de freqüência 3MHz (0,5W/cm²). A lesão foi provocada no músculo gastrocnêmio por mecanismo de impacto. O tratamento foi de cinco minutos diários durante seis dias consecutivos. Os músculos foram submetidos a ensaios mecânicos de tração em uma máquina universal de ensaios. RESULTADOS: As médias e desvios-padrão das propriedades mecânicas dos grupos lesionados e tratados com UST foram significativamente maiores quando comparadas ao grupo lesionado sem tratamento (p<0,05). Em destaque, a propriedade de rigidez que, com a aplicação do UST, teve acréscimo de aproximadamente 38%. CONCLUSÕES: A intervenção, por meio do UST, promoveu aumento das propriedades mecânicas nos músculos lesionados aproximando-as do grupo controle. Entretanto, não foi observada diferença significativa entre as propriedades mecânicas dos grupos tratados com ultra-som de freqüências 1MHz e 3MHz.BACKGROUND: Therapeutic ultrasound is a resource commonly applied to speed up tissue repair in muscle injuries. The absorption of the ultrasound waves is determined by their frequency and intensity. For a given intensity, the depth reached by 1MHz is greater than the depth reached by 3MHz. OBJECTIVE: To analyze the mechanical properties of muscles subjected to acute impact injury treated with therapeutic ultrasound at the frequencies of 1 and 3MHz. METHODS: Forty female Wistar rats (200.1±17.8g) were used, divided into four groups: (1) control; (2) muscle injury without treatment; (3) muscle injury treated with therapeutic ultrasound at the frequency of 1MHz (0.5W/cm²); and (4) muscle injury treated with therapeutic ultrasound at the frequency of 3MHz (0.5W/cm²). The injury was produced in the gastrocnemius muscle by means of an impact mechanism. The treatment consisted of a single five-minute session per day, for six consecutive days. The muscles were subjected to mechanical traction tests in a universal test machine. RESULTS: Means and standard deviations for the mechanical properties of the injured groups that received therapeutic ultrasound were significantly greater than those of the injured group without treatment (p<0.05). The property of stiffness should be highlighted: the application of therapeutic ultrasound increased muscle stiffness by approximately 38%. CONCLUSIONS: Therapeutic ultrasound increased the mechanical properties of the injured muscles, and brought them to a level close to the control group. However, no significant difference in mechanical properties was observed between the groups treated with ultrasound at the frequencies of 1MHz and 3MHz

Five-year review of an international clinical research-training program

The exponential increase in clinical research has profoundly changed medical sciences. Evidence that has accumulated in the past three decades from clinical trials has led to the proposal that clinical care should not be based solely on clinical expertise and patient values, and should integrate robust data from systematic research. As a consequence, clinical research has become more complex and methods have become more rigorous, and evidence is usually not easily translated into clinical practice. Therefore, the instruction of clinical research methods for scientists and clinicians must adapt to this new reality. To address this challenge, a global distance-learning clinical research-training program was developed, based on collaborative learning, the pedagogical goal of which was to develop critical thinking skills in clinical research. We describe and analyze the challenges and possible solutions of this course after 5 years of experience (2008-2012) with this program. Through evaluation by students and faculty, we identified and reviewed the following challenges of our program: 1) student engagement and motivation, 2) impact of heterogeneous audience on learning, 3) learning in large groups, 4) enhancing group learning, 5) enhancing social presence, 6) dropouts, 7) quality control, and 8) course management. We discuss these issues and potential alternatives with regard to our research and background

Behind the Intents: An In-depth Empirical Study on Software Refactoring in Modern Code Review

Code refactorings are of pivotal importance in modern code review. Developers may preserve, revisit, add or undo refactorings through changes’ revisions. Their goal is to certify that the driving intent of a code change is properly achieved. Developers’ intents behind refactorings may vary from pure structural improvement to facilitating feature additions and bug fixes. However, there is little understanding of the refactoring practices performed by developers during the code review process. It is also unclear whether the developers’ intents influence the selection, composition, and evolution of refactorings during the review of a code change. Through mining 1,780 reviewed code changes from 6 systems pertaining to two large open-source communities, we report the first in-depth empirical study on software refactoring during code review. We inspected and classified the developers’ intents behind each code change into 7 distinct categories. By analyzing data generated during the complete reviewing process, we observe: (i) how refactorings are selected, composed and evolved throughout each code change, and (ii) how developers’ intents are related to these decisions. For instance, our analysis shows developers regularly apply non-trivial sequences of refactorings that crosscut multiple code elements (i.e., widely scattered in the program) to support a single feature addition. Moreover, we observed that new developers’ intents commonly emerge during the code review process, influencing how developers select and compose their refactorings to achieve the new and adapted goals. Finally, we provide an enriched dataset that allows researchers to investigate the context and motivations behind refactoring operations during the code review process