Pericarditis Due to Campylobacter Fetus Subsp. Fetus: a Case Report of an Uncommon Infection

Pericarditis is a common condition with numerous aetiologies. Bacteria other than the Mycobacterium tuberculosis complex are an exceptional cause. We present a case of subacute pericarditis highly probable due to Campylobacter fetus subsp. fetus in an immunosuppressed patient undergoing biologic therapy in relation to systemic lupus erythematosus (SLE). On admission, the patient presented with chest pain, dyspnea, and diaphoresis and has lately developed fever and a large pericardial effusion (PE) with a concomitant increase in the inflammatory parameters. The clinical presentation, along with the exclusion of a flare of the autoimmune disease and the isolation of Campylobacter fetus subsp. fetus on blood samples permitted the diagnosis. After therapy with antibiotics and colchicine, the patient showed full recovery.info:eu-repo/semantics/publishedVersio

Minimizing the Cost of Innovative Nuclear Technology Through Flexibility: The Case of a Demonstration Accelerator-Driven Subcritical Reactor Park

Presented is a methodology to analyze the expected Levelised Cost Of Electricity (LCOE) in the face of technology uncertainty for Accelerator-Driven Subcritical Reactors (ADSRs). It shows that flexibility in the design and deployment strategy of an ADSR park demonstrator significantly reduces its expected LCOE. The methodology recognizes in the conceptual design a range of possible technological outcomes for the ADSR accelerator system. It identifies flexibility “on” and “in” the design to modify the future development path in light of such uncertain scenarios. Uncertainty and flexibility are incorporated in the ADSR valuation. The resulting economic assessment is more realistic than typical discounted cash flow analysis that does not consider a range of development outcomes, or the flexibility to change development path

Prognosis following acute coronary syndromes according to prior coronary artery bypass grafting: Meta-analysis

PURPOSE: Conduct a meta-analysis to study the prognostic influence of a previous coronary artery bypass grafting (CABG) in patients admitted for an acute coronary syndrome (ACS). METHODS: A systematic review of the literature was performed using electronic reference databases through January 2013 (MEDLINE, Cochrane Library, Web of Knowledge, Google Scholar and references cited in other studies). Studies in which ACS outcomes with a previous history of CABG were compared with ACS outcomes with no history of previous CABG were considered for inclusion. The main endpoints of interest were mortality and non-fatal acute myocardial infarction. Data was aggregated at three follow-up times using random-effects meta-analysis models. RESULTS: Twenty-four studies were included which provided 387,181 patients for analysis. Previous CABG ACS patients were older, more diabetic and had a more frequent history of a previous myocardial infarction. Pooled in-hospital mortality was higher for the previous CABG ACS patients (OR 1.22 [1.04-1.44], p<0.01, I(2) 88%). The pooled adjusted OR showed no significant differences for the two groups (adjusted OR 1.13 [0.93-1.37], p=0.22, I(2) 92%). Previous CABG ACS patient had a higher pooled 30-day mortality (OR 1.28 [1.05-1.55], p=0.02, I(2) 74%); a higher non-adjusted (OR 1.61 [1.38-1.88], p<0.01, I(2) 70%) and adjusted (adjusted OR 1.37 [1.15-1.65], p<0.01, I(2) 0%) long-term mortality. Both the in-hospital and the long-term re-infarction rates were higher for the previous CABG ACS patients. CONCLUSIONS: According to our data, ACS patients with previous CABG history had a higher risk for short- and long-term adverse events

Macrophages down-regulate gene expression of intervertebral disc degenerative markers under a pro-inflammatory microenvironment

Low back pain is a highly prevalent clinical problem and intervertebral disc (IVD) degeneration is now accepted as the major pathophysiological mechanism responsible for this condition. Accumulating evidence suggests that inflammation plays a crucial role in the progression of human IVD degeneration, with macrophages being pointed as the key immune cell players in this process since their infiltration in degenerated IVD samples has been extensively demonstrated. Since they are highly plastic, macrophages can play different roles depending on the microenvironmental cues. The study of inflammation associated with IVD degeneration has been somehow neglected and one of the reasons is related with lack of adequate models. To overcome this, we established and characterized a new model of IVD organ culture under proinflammatory conditions to further dissect the role of macrophages in IVD associated immune response. For that, human monocyte-derived macrophages were co-cultured either with bovine caudal IVD punches in the presence of the pro-inflammatory cytokine IL-1ß, or IVD-conditioned medium (CM), to investigate how IVD-produced factors influence macrophage phenotype. After 72 h, metabolic activity, gene expression and cytokine profile of macrophages and IVD cells were measured. Our results show that macrophages and IVDs remain metabolically active in the presence of IL-1ß, significantly upregulate CCR7 gene expression and increase production of IL-6 on macrophages. When treating macrophages with IL-1ß-IVD-CM, CCR7 upregulation follows the same trend, while for IL-6 an opposite effect was observed. On the other hand, macrophages interfere with IVD ECM remodeling, decreasing MMP3 expression and downregulating aggrecan and collagen II gene expression in the presence of IL-1ß. Overall, the co-culture model established in this study can be considered a suitable approach to address the cellular and molecular pathways that regulate macrophage-IVD crosstalk, suggesting that degenerated IVD tissue tends to polarize human macrophages toward a more proinflammatory profile, which seems to aggravate IVD degeneration. This model could be used to improve the knowledge of the mechanisms that link IVD degeneration and the immune response.This work was financed by European Union funds through Bioengineered Therapies for infectious diseases and tissue regeneration (Norte-01-0145-FEDER-000012), Projetos Estruturados de I& D& I - Norte-01-0145-FEDER-000012, Portugal 2020 - FEDER, and through EUROSPINE TRF (2017_05) by the project Disc degeneration-, immune-, and neuro-modulation. The authors also acknowledge FCT – Fundação para a Ciência e a Tecnologia, in the framework of the FCT Investigator Grant of RMG (IF/00638/2014), CC Junior Research contract (DL 57/2016/CP1360/CT0004) and the Ph.D. grant of JF (PD/BI/128357/2017). The authors would like to thank Serviço de Imunohemoterapia of Centro Hospitalar Universitário de São João (CHUSJ), for kindly donating Buffy Coats

Transitory activation of AMPK at reperfusion protects the ischaemic-reperfused rat myocardium against infarction

PURPOSE: AMPK plays a crucial role in the regulation of the energy metabolism of the heart. During ischaemia, AMPK activation is a known adaptative prosurvival mechanism that helps to maintain the energy levels of the myocardium. However, it still remains unclear if activation of AMPK during reperfusion is beneficial for the heart. Two known AMPK activators (metformin and AICAR) were used to verify the hypothesis that a transitory activation of AMPK at reperfusion may exert cardioprotection, as reflected in a reduction in myocardial infarct size. METHODS: Perfused rat hearts were subjected to 35 min ischaemia and 120 min reperfusion. Metformin (50 microM) or AICAR (0.5 mM) were added for 15 min at the onset of reperfusion alone or with Compound C (CC, 10 microM), an AMPK inhibitor. Infarct size and alpha-AMPK phosphorylation were measured. RESULTS: Metformin significantly reduced infarct size from 47.8 +/- 1.7% in control to 31.4 +/- 2.9%, an effect abolished by CC when the drugs were given concomitantly. Similarly, AICAR also induced a significant reduction in infarct size to 32.3 +/- 4.8%, an effect also abrogated by CC. However, metformin's protection was not abolished if CC was administered later in reperfusion. In addition, alpha-AMPK phosphorylation was significantly increased in the metformin treated group during the initial 30 min of reperfusion. CONCLUSIONS: Our data demonstrated that, in our ex vivo model of myocardial ischaemia-reperfusion injury, AMPK activation in early reperfusion is associated with a reduction in infarct size

Effects of an aerobic physical training program on psychosocial characteristics, quality-of-life, symptoms and exhaled nitric oxide in individuals with moderate or severe persistent asthma

OBJETIVO: Avaliar o papel de um programa de condicionamento físico aeróbio nos aspectos psicossociais, qualidade de vida, sintomas e óxido nítrico exalado (NOe) de adultos com asma persistente moderada ou grave. MATERIAIS E MÉTODOS: Vinte pacientes foram divididos aleatoriamente em Grupo Controle (GC, n= 10; programa de educação e exercícios respiratórios) e Grupo Treinado (GT, n= 10; programa de educação e exercícios respiratórios mais condicionamento aeróbio, 70% potência máxima obtida). A intervenção aconteceu duas vezes por semana durante três meses. Antes e após, foram avaliados a capacidade aeróbia máxima, a função pulmonar, a dispnéia ao esforço, os níveis de ansiedade e depressão e a qualidade de vida. Mensalmente, eram avaliados o NOe em repouso e o número de dias livres de sintomas. RESULTADOS: Apenas o GT apresentou redução dos sintomas (GT 24,8 [IC95%= 23-27] versus GC 15,7 [IC95%= 9-21] dias livres de sintomas, p< 0,05), dos níveis de NOe (GT 25,8 [IC95%= 15,3-44] versus GC 44,3 [IC95%= 24-60] ppb, p< 0,05), da ansiedade (GT 39,3 [IC95%= 37-50] versus GC 40,9 [IC95%= 37-50] escore, p< 0,001) e da depressão (GT 6,6 [IC95%= 1-21] versus GC 9 [IC95%= 1-20] escore, p< 0,001), melhora da qualidade de vida (GT 42,8 [IC95%= 34,3-71,7] versus GC 69,7 [IC95%= 45,1-87,9] %, p< 0,001), e incremento da aptidão aeróbia (GT 25,7 [IC95%= 16,2-31,3] versus GC 20,5 [IC95%= 17,3-24,1] mL/kg/min, p< 0,001). CONCLUSÕES: Os resultados sugerem que o treinamento físico reduz o NOe, os sintomas e melhora a qualidade de vida e os aspectos psicossociais de adultos com asma persistente moderada ou grave.OBJECTIVE: To evaluate the role of an aerobic physical training program on psychosocial characteristics, quality of life, symptoms and exhaled nitric oxide of adults with moderate or severe persistent asthma. METHODS: Twenty patients were randomly assigned to a Control Group (CG, n= 10, education program and respiratory exercises) and a Trained Group (TG, n= 10, education program and respiratory exercises plus aerobic training at 70% of the maximum power obtained). The intervention took place twice a week for three months. Maximum aerobic capacity, pulmonary function, effort dyspnea, anxiety levels, depression levels and quality of life were assessed before and after the treatment. Exhaled nitric oxide at rest and the number of days without asthma symptoms were evaluated every month. RESULTS: The TG presented increased numbers of symptom-free days (TG 24.8 days [95%CI= 23-27] versus CG 15.7 days [95%CI= 9-21]; p< 0.05), decreased exhaled nitric oxide levels (TG 25.8 ppb [95%CI= 15.3-44.0] versus CG 44.3 ppb [95%CI= 24-60]; p< 0.05), decreased anxiety scores (TG 39.3 [95%CI= 37-50] versus CG 40.9 [95%CI= 37-50]; p< 0.001), decreased depression scores (TG 6.6 [95%CI= 1-21] versus CG 9 [95%CI= 1-20]; p< 0.001), improved quality of life (TG 42.8% [95%CI= 34.3-71.7] versus CG 69.6% [95%CI= 45.1-87.9]; p< 0.001) and improved aerobic aptitude (TG 25.7 mL/kg/min [95%CI= 6.2-31.3] versus CG 20.5 mL/kg/min [95%CI= 17.3-24.1]; p< 0.001). CONCLUSIONS: Our results suggest that physical training reduces exhaled nitric oxide and symptoms and improves the quality of life and psychosocial characteristics of adults with moderate or severe persistent asthma.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Pesquisa (CNPq

The inflammatory response in the regression of lumbar disc herniation

Lumbar disc herniation (LDH) is highly associated with inflammation in the context of low back pain. Currently, inflammation is associated with adverse symptoms related to the stimulation of nerve fibers that may lead to pain. However, inflammation has also been indicated as the main factor responsible for LDH regression. This apparent controversy places inflammation as a good prognostic indicator of spontaneous regression of LDH. This review addresses the molecular and cellular mechanisms involved in LDH regression, including matrix remodeling and neovascularization, in the scope of the clinical decision on conservative versus surgical intervention. Based on the evidence, a special focus on the inflammatory response in the LDH context is given, particularly in the monocyte/macrophage role. The phenomenon of spontaneous regression of LDH, extensively reported in the literature, is therefore analyzed here under the perspective of the modulatory role of inflammation.This work was financed by project “Bioengineered Therapies for infectious diseases and tissue regeneration” (NORTE-01-0145-FEDER-000012), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), by FEDER/COMPETE 2020 (POCI), Portugal 2020, and by Portuguese funds through FCT/MCTES in the framework of the project "Institute for Research and Innovation in Health Sciences" (POCI-01- 0145-FEDER-007274). Cunha C and Gonçalves RM acknowledge FCT by their postdoc fellowship (SFRH/BDP/87071/2012) and FCT Investigator Grant (IF/ 00638/2014), respectively. Silva AJ acknowledges her fellowship under the framework of the project Norte-01-0145-FEDER-000012

Genetically engineered-MSC therapies for non-unions, delayed unions and critical-size bone defects

The normal bone regeneration process is a complex and coordinated series of events involving different cell types and molecules. However, this process is impaired in critical-size/large bone defects, with non-unions or delayed unions remaining a major clinical problem. Novel strategies are needed to aid the current therapeutic approaches. Mesenchymal stem/stromal cells (MSCs) are able to promote bone regeneration. Their beneficial effects can be improved by modulating the expression levels of specific genes with the purpose of stimulating MSC proliferation, osteogenic differentiation or their immunomodulatory capacity. In this context, the genetic engineering of MSCs is expected to further enhance their pro-regenerative properties and accelerate bone healing. Herein, we review the most promising molecular candidates (protein-coding and non-coding transcripts) and discuss the different methodologies to engineer and deliver MSCs, mainly focusing on in vivo animal studies. Considering the potential of the MSC secretome for bone repair, this topic has also been addressed. Furthermore, the promising results of clinical studies using MSC for bone regeneration are discussed. Finally, we debate the advantages and limitations of using MSCs, or genetically-engineered MSCs, and their potential as promoters of bone fracture regeneration/repair.This project is supported by Fundação para a Ciência e a Tecnologia (FCT)—in the framework of the project POCI-01-0145-FEDER-031402-R2Bone, under the PORTUGAL 2020 Partnership Agreement, through ERDF, co-funded by FEDER/FNR, and national funding (through FCT – Fundação para a Ciência e a Tecnologia, I.P., provided by the contract-program and according to numbers 4, 5 and 6 of art. 23 of Law No. 57/2016 of 29 August 2016, as amended by Law No. 57/2017 of 19 July 2017). RG, JHT, and MIA are supported by FCT, through the FCT Investigator Program (IF/00638/2014), SFRH/BD/112832/2015, and DL 57/2016/CP1360/CT0008, respectively

Mesenchymal Stromal Cell Secretome: Influencing Therapeutic Potential by Cellular Pre-conditioning

Mesenchymal stromal cells (MSCs) are self-renewing, culture-expandable adult stem cells that have been isolated from a variety of tissues, and possess multipotent differentiation capacity, immunomodulatory properties, and are relatively non-immunogenic. Due to this unique set of characteristics, these cells have attracted great interest in the field of regenerative medicine and have been shown to possess pronounced therapeutic potential in many different pathologies. MSCs' mode of action involves a strong paracrine component resulting from the high levels of bioactive molecules they secrete in response to the local microenvironment. For this reason, MSCs' secretome is currently being explored in several clinical contexts, either using MSC-conditioned media (CM) or purified MSC-derived extracellular vesicles (EVs) to modulate tissue response to a wide array of injuries. Rather than being a constant mixture of molecular factors, MSCs' secretome is known to be dependent on the diverse stimuli present in the microenvironment that MSCs encounter. As such, the composition of the MSCs' secretome can be modulated by preconditioning the MSCs during in vitro culture. This manuscript reviews the existent literature on how preconditioning of MSCs affects the therapeutic potential of their secretome, focusing on MSCs' immunomodulatory and regenerative features, thereby providing new insights for the therapeutic use of MSCs' secretome.We would like to acknowledge Norte Portugal Regional Operational Programme (NORTE 2020) in the framework of the project “Bioengineered Therapies for Infectious Diseases and Tissue Regeneration” (NORTE-01-0145-FEDER-000012). We also acknowledge Fundação para a Ciência e a Tecnologia (FCT) and Fundo Europeu de Desenvolvimento Regional (FEDER) funds through the COMPETE 2020-Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020-in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274). We also acknowledge EUROSPINE TRF for the funded project “Disc Regeneration, Immuno, and Neuro Modulation” , ref. 2017_05 . In addition, JF and RG also acknowledge FCT for funding the BiotechHealth Ph.D. fellowship (PD/BD/135486/2018) and the FCT Investigator Grant (IF/00638/2014), respectively