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Total occlusion of the abdominal aorta is an uncommon but potentially devastating event. Clinical symptoms are usually sudden and may vary depending on the level of the aortic occlusion. Associated morbidity and mortality remain substantial with high rates of limb loss, acute renal failure, rhabdomyolysis, and death. We report a case of a bedridden 91-year-old woman with history of hypertension, hyperlipidemia, anemia and dementia, carried to the emergency department because of bilateral lower limb pallor. She had been at the same department the week before because of the same problems and high blood pressure (BP), but had been discharged after administration of hypotensive drugs and a short period of observation. No attention was paid to those perfusion alterations, or the global picture at all. The physical examination revealed cooling of the lower limbs and significant BP differential between upper and lower limbs (ankle-brachial index of 0.173), leading to the suspicion of bilateral acute limb ischemia. Abdominal, pelvic and lower limb CT was conducted, revealing calcification and important atheromatosis of the thoracic-abdominal aorta and a mural thrombus beginning above the origin of the celiac trunk, with complete occlusion below the origin of the renal arteries. After discussion with Vascular Surgery Department, given the advanced age, known co-morbidities and the timing of diagnosis, the patient was considered not eligible for revascularization surgery and comfort measures were honored. This case highlights the importance of stablishing a timely and correct diagnosis, even in the very elderly, emphasizing that they too benefit from secondary and tertiary prophylaxis, in order to prevent devastating outcomes as this.

Lately there has been a growing interest in the use of percutaneous surgery for the correction of hallux valgus (HV). The purpose of the present study was to systematically review the published data about this topic and establish the efficacy and safety, stressing the complication rates found on this percutaneous technique. A systematic review of the literature available in PubMed was performed. The radiological and clinical outcomes were evaluated as well as complication rates. A total of 16 studies were included and 1157 procedures reported for percutaneous HV on 1246 patients. The mean angle correction of HV deformity improved postoperatively. Reported complications vary among the studies. The highest complication rate was joint stiffness in 18.47% of cases, followed by HV recurrence and shortening of M1, both in 15.2%, material intolerance in 10.1%, osteoarthritic changes in 9.1%, infection in 7.6%, and transfer metatarsalgia in 5.4%. There is a lack of randomized control trials and insufficient comparative case control studies to assess whether one technique is more effective than another or if the percutaneous surgery is recommended rather than open surgery with respect to complications.

O ano de 2020 ficará marcado na memória mundial como o ano da pandemia de Covid-19. Embora a doença tenha eclodido na China no final de 2019, a sua propagação foi posterior e veio colocar em causa a sociedade globalizada, com efeitos sociais, políticos e económicos graves, mas ainda a serem determinados em toda a sua extensão. Na cobertura do surto o jornalismo, em crise há algu- mas décadas (Zelizer, 2004; 2009; 2015; 2017), reassumiu um papel central e ad- quiriu um novo vigor, viajando por múltiplos dispositivos e écrans (Deuze, 2019). Em Portugal, num cenário de isolamento, predominantemente familiar, a televisão emergiu como elo social (Wolton, 1994), confirmando que continua ser o médium dominante (ERC, 2016, 2019; OBERCOM, 2018; Statista, 2019). Neste contexto, a nossa homenagem a Nelson Traquina tem como objetivo apresentar, comen- tar e discutir a sua contribuição para o estudo do jornalismo em Portugal a partir da análise da cobertura jornalística televisiva da crise pandémica. Com este fim, recuperámos estudos teóricos sobre as Teorias da Notícia e os estudos empíri- cos sobre o HIV/SIDA realizados pelo autor (por exemplo, Traquina, 1993; 2002; 2004; 2010; Traquina e al., 2001). Elegemos um corpus de análise empírico, com- preendido por blocos de jornais televisivos dos canais generalistas RTP1, SIC e TVI. Utilizamos uma metodologia fundada na construção de uma base de dados em File Maker Pro inspirada nos trabalhos de Traquina sobre o HIV/SIDA. Os re- sultados obtidos, ainda que com caráter exploratório, permitem a discussão das teorias da notícia enquanto construção (Traquina, 1993) e o papel das rotinas na produção da informação televisiva.

Diabetic Retinopathy, the main cause of visual loss and blindness among working population, is a complication of Diabetes mellitus (DM), which has been described as a major public health challenge, so it is important to identify biomarkers to predict and to stratify patient´s possibility for developing DR. MicroRNAs (miRNAs) are small non-coding RNA molecules that have showed to be promising disease biomarkers and association of miRNAs with the possibility to develop DR has been reported. However, evaluating miRNA expression involves normalization of RT-qPCR data using internal reference genes that should be properly determined, considering their impact on expression levels calculation and, until date, there is no unanimity on reference miRNAs for the investigation of circulating miRNAs in DR. We aimed to estimate the appropriateness of a group of miRNAs as normalizers to identify which might be considered steady internal reference genes in expression studies on DR plasma samples. Expression levels of candidates were analyzed in 60 healthy controls, 48 DM without DR patients and 62 DR patients with two statistical tools: NormFinder and RefFinder. MiR-328-3p was the most stable gene and we also investigated the effect of gene normalization, demonstrating that different normalization strategies have important implications for accurate data interpretation.

Osteosarcoma (OS) is a fast-progressing bone tumor with high incidence in children and adolescents. The main diagnostic methods for OS are imaging exams and biopsies. In spite of the several resources available for detecting the disease, establishing an early diagnosis is still difficult, resulting in worse prognosis and lower survival rates for patients with OS. The identification of novel biomarkers would be helpful, and recently, circulating microRNAs (miRNAs) have been pointed to as possible non-invasive biomarkers. In order to assess the effectiveness of miRNA research, we performed a systematic review to assess the potential role of circulating miRNAs as biomarkers for OS diagnosis. We performed a search in various databases—PubMed, LILACS (Literatura Latino-americana e do Caribe em Ciências da Saúde), VHL (Virtual Health Library), Elsevier, Web of Science, Gale Academic One File—using the terms: “Circulating microRNAs” OR “plasma microRNAs” OR “serum microRNAs” OR “blood microRNAs” OR “cell-free microRNAs” OR “exosome microRNAs” OR “extracellular vesicles microRNAs” OR “liquid biopsy” AND “osteosarcoma” AND “diagnostic”. We found 35 eligible studies that were independently identified and had had their quality assessed according to Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) guidelines. Despite the useful number of publications on this subject and the fact that several microRNAs showed excellent diagnostic performance for OS, the lack of consistency in results suggests that additional prospective studies are needed to confirm the role of circulating miRNAs as non-invasive biomarkers in OS.

Since HIV was first identified, and in a relatively short period of time, AIDS has become one of the most devastating infectious diseases of the 21st century. Classical antiretroviral therapies were a major step forward in disease treatment options, significantly improving the survival rates of HIV-infected individuals. Even though these therapies have greatly improved HIV clinical outcomes, antiretrovirals (ARV) feature biopharmaceutic and pharmacokinetic problems such as poor aqueous solubility, short half-life, and poor penetration into HIV reservoir sites, which contribute to the suboptimal efficacy of these regimens. To overcome some of these issues, novel nanotechnology-based strategies for ARV delivery towards HIV viral reservoirs have been proposed. The current review is focused on the benefits of using lipid-based nanocarriers for tuning the physicochemical properties of ARV to overcome biological barriers upon administration. Furthermore, a correlation between these properties and the potential therapeutic outcomes has been established. Biotechnological advancements using lipid nanocarriers for RNA interference (RNAi) delivery for the treatment of HIV infections were also discussed., This research was funded by FCT/MCTES—Foundation for Science and Technology I.P. from the Minister of Science, Technology, and Higher Education (PIDDAC) and European Regional Development Fund (ERDF) by the COMPETE—Programa Operacional Factores de Competitividade (POFC) through the project CONCERT [POCI-01-0145-FEDER-032651 and PTDC/NANMAT/326512017] and the Strategic Funding UID/FIS/04650/2019 and “Contrato-Programa” UIDB/ 04469/2020 (CF-UM-UP and CBMA). Marlene Lúcio thanks FCT and ERDF for the doctoral position [CTTI-150/18-CF (1)] in the scope of the project CONCERT. Maria João Faria thanks FCT for PhD grant [2020.06561.BD].

Mucopolysaccharidosis type IIIC (MPSIIIC) is a severe, rare autosomal recessive disorder caused by variants in the heparan-α-glucosaminide N-acetyltransferase (HGSNAT) gene which result in lysosomal accumulation of heparan sulfate. We analyzed clinical presentation, molecular defects and their haplotype context in 78 (27 novel) MPSIIIC cases from 22 countries, the largest group studied so far. We describe for the first time disease-causing variants in the patients from Brazil, Algeria, Azerbaijan, and Iran, and extend their spectrum within Canada, Colombia, Turkey, and the USA. Six variants are novel: two missense, c.773A>T/p.N258I and c.1267G>T/p.G423W, a nonsense c.164T>A/p.L55*, a splice-site mutation c.494-1G>A/p.[P165_L187delinsQSCYVTQAGVRWHHLGSLQALPPGFTPFSYLSLLSSWNC,P165fs], a deletion c.1348delG/p.(D450fs) and an insertion c.1479dupA/p.(Leu494fs). The missense HGSNAT variants lacked lysosomal targeting, enzymatic activity, and likely the correct folding. The haplotype analysis identified founder mutations, p.N258I, c.525dupT, and p.L55* in the Brazilian state of Paraiba, c.493+1G>A in Eastern Canada/Quebec, p.A489E in the USA, p.R384* in Poland, p.R344C and p.S518F in the Netherlands and suggested that variants c.525dupT, c.372-2G>A, and c.234+1G>A present in cis with c.564-98T>C and c.710C>A rare single-nucleotide polymorphisms, have been introduced by Portuguese settlers in Brazil. Altogether, our results provide insights into the origin, migration roots and founder effects of HGSNAT disease-causing variants, and reveal the evolutionary history of MPSIIIC.

Introduction: A rare orphan disorder, Mucopolysaccharidosis III type C (MPS IIIC) is caused by mutations in the HGSNAT (heparan sulfate acetyl-CoA:α-glucosaminide N-acetyltransferase) gene resultin...

Spirometry and exhaled nitric oxide are two important complimentary tools to identify and assess asthma control in children. We aimed to determine the ability of a new suggested spirometry-adjusted fraction of exhaled nitric oxide (NO) index in doing that. A random sample of 1602 schoolchildren were screened by a health questionnaire, skin prick tests, spirometry with bronchodilation and exhaled NO. A total of 662 children were included with median (IQR) exhaled NO 11(14) ppb. Receiver operating characteristic (ROC) curves using exhaled NO equations from Malmberg, Kovesi and Buchvald, and spirometry-adjusted fraction of exhaled NO values were applied to identify asthmatic children and uncontrolled asthma. Receiver operating characteristic (ROC) curves failed to identify asthmatic children (all AUC < 0.700). Spirometry-adjusted fraction of exhaled NO/FEV1 (AUC = 0.712; P = .010) and NO/FEF25%-75% (AUC = 0.735 P = .004) had a fair and increased ability to identify uncontrolled disease compared with exhaled NO (AUC = 0.707; P = .011) or the Malmberg equation (AUC = 0.701; P = .014). Sensitivity and specificity identifying non-controlled asthma were 59% and 81%, respectively, for the cut-off value of 9.7 ppb/L for exhaled NO/FEV1 , and 40% and 100% for 15.7 ppb/L/s for exhaled NO/FEF25%-75% . Exhaled NO did not allow to identify childhood asthma. Spirometry-adjusted fraction of exhaled NO performed better-assessing asthma control in children. Thus, although more validation studies are needed, we suggest its use in epidemiological studies to assess asthma control. Health, Comfort and Energy in the Built Environment (HEBE), Grant/Award Number: NORTE-01-0145-FEDER-000010; Programa Operacional Regional do Norte, Grant/Award Number: NORTE2020; Fundo Europeu de Desenvolvimento Regional (FEDER); Foundation for Science and Technology schoolarships, Grant/Award Number: SFRH/BD/108605/2015 and SFRH/BD/112269/2015

INTRODUCTION: Asthma is one of the most prevalent chronic medical conditions to complicate pregnancy. Similarly, active management strategies that prioritise asthma control in this vulnerable population can have a far-reaching impact. AIM: To describe lung function parameters and results of the Control of Allergic Rhinitis and Asthma Test (CARAT) questionnaire in pregnant asthmatics and to analyse correlations between lung function tests and CARAT results. METHODS: All pregnant asthmatics who performed spirometry and CARAT between September 2014 and August 2015 were included. A medical records review was performed and data regarding demographics, sensitisation and medical prescriptions were recorded. Control of asthma and rhinitis was defined by CARAT total score (CARAT (T)) ≥ 24; upper airways (U) control if CARAT (U) > 8; lower airways (L) control if CARAT (L) > 15. RESULTS: Forty-two pregnant asthmatics were included, with a median age (interquartile range)of 32 (27-34) years; all had a previous medical diagnosis of asthma and rhinitis, 76% were atopic, 94% sensitised to dust mites and 43% were polissensitised. More than 80% presented poor control (CARAT (T) < 24) in the first assessment and 15% had a percentage forced expiratory volume in the first second < 80%. There were significant negative correlations between CARAT (L) and CARAT (T) scores and step-up of controller medication, (correlation coefficients = -0.453 and -0.392, respectively). CONCLUSION: The use of tools such as spirometry and validated questionnaires to objectively assess asthma control during pregnancy should be routinely applied to assist in the management of these patients. These data reinforce the importance of close monitoring of pregnant asthmatics to achieve and maintain better disease control. info:eu-repo/semantics/publishedVersion

Mesenchymal stem cells (MSCs) are precursors present in adult bone marrow that are able to differentiate into osteoblasts, adipocytes and chondroblasts that have gained great importance as a source for cell therapy. Recently, a number of studies involving the analysis of gene expression of undifferentiated MSCs and of MSCs in the differentiation into multiple lineage processes were observed but there is no information concerning the gene expression of MSCs from Osteogenesis Imperfecta (OI) patients. Osteogenesis Imperfecta is characterized as a genetic disorder in which a generalized osteopenia leads to excessive bone fragility and severe bone deformities. The aim of this study was to analyze gene expression profile during osteogenic differentiation from BMMSCs (Bone Marrow Mesenchymal Stem Cells) obtained from patients with Osteogenesis Imperfecta and from control subjects. Bone marrow samples were collected from three normal subjects and five patients with OI. Mononuclear cells were isolated for obtaining mesenchymal cells that had been expanded until osteogenic differentiation was induced. RNA was harvested at seven time points during the osteogenic differentiation period (D0, D+1, D+2, D+7, D+12, D+17 and D+21). Gene expression analysis was performed by the microarray technique and identified several differentially expressed genes. Some important genes for osteoblast differentiation had lower expression in OI patients, suggesting a smaller commitment of these patient's MSCs with the osteogenic lineage. Other genes also had their differential expression confirmed by RT-qPCR. An increase in the expression of genes related to adipocytes was observed, suggesting an increase of adipogenic differentiation at the expense osteogenic differentiation.

GM2-gangliosidosis, AB variant is an extremely rare autosomal recessive inherited disorder caused by mutations in the GM2A gene that encodes GM2 ganglioside activator protein (GM2AP). GM2AP is necessary for solubilisation of GM2 ganglioside in endolysosomes and its presentation to β-hexosaminidase A. Conversely GM2AP deficiency impairs lysosomal catabolism of GM2 ganglioside, leading to its storage in cells and tissues. We describe a 9-year-old child with an unusual juvenile clinical onset of GM2-gangliosidosis AB. At the age of 3 years he presented with global developmental delay, progressive epilepsy, intellectual disability, axial hypertonia, spasticity, seizures and ataxia, but without the macular cherry-red spots typical for GM2 gangliosidosis. Brain MRI detected a rapid onset of diffuse atrophy, whereas whole exome sequencing showed that the patient is a compound heterozygote for two mutations in GM2A: a novel nonsense mutation, c.259G > T (p.E87X) and a missense mutation c.164C > T (p.P55L) that was recently identified in homozygosity in patients of a Saudi family with a progressive chorea-dementia syndrome. Western blot analysis showed an absence of GM2AP in cultured fibroblasts from the patient, suggesting that both mutations interfere with the synthesis and/or folding of the protein. Finally, impaired catabolism of GM2 ganglioside in the patient's fibroblasts was demonstrated by metabolic labeling with fluorescently labeled GM1 ganglioside and by immunohistochemistry with anti-GM2 and anti-GM3 antibodies. Our observation expands the molecular and clinical spectrum of molecular defects linked to GM2-gangliosidosis and suggests novel diagnostic approach by whole exome sequencing and perhaps ganglioside analysis in cultured patient's cells.

POCI-01-0145-FEDER-007728 SFRH/BD/120030/2016 PD/BD/105734/2014 Pest-OE/UID/DTP/04138/2013 Resistance to chemotherapy is a major problem facing current cancer therapy, which is continuously aiming at the development of new compounds that are capable of tackling tumors that developed resistance toward common chemotherapeutic agents, such as doxorubicin (DOX). Alongside the development of new generations of compounds, nanotechnology-based delivery strategies can significantly improve the in vivo drug stability and target specificity for overcoming drug resistance. In this study, multifunctional gold nanoparticles (AuNP) have been used as a nanoplatform for the targeted delivery of an original anticancer agent, a Zn(II) coordination compound [Zn(DION)2]Cl2 (ZnD), toward better efficacy against DOX-resistant colorectal carcinoma cells (HCT116 DR). Selective delivery of the ZnD nanosystem to cancer cells was achieved by active targeting via cetuximab, NanoZnD, which significantly inhibited cell proliferation and triggered the death of resistant tumor cells, thus improving efficacy. In vivo studies in a colorectal DOX-resistant model corroborated the capability of NanoZnD for the selective targeting of cancer cells, leading to a reduction of tumor growth without systemic toxicity. This approach highlights the potential of gold nanoformulations for the targeting of drug-resistant cancer cells. publishersversion published

The anterolateral bowing of the tibia is closely associated with the development of its pseudarthrosis. Roughly, all deformities are unilateral so the shortening and angulation are easy to identify. We present a 6-year-old boy with an exuberant bilateral anterolateral bowing of tíbia. He has short stature, disturbed gait and callosity at the lateral border of the foot. Deformity was successfully treated by opening wedge tibia osteotomy and filled the remaining gap with structural fibular graft. It was fixed with two crossed K-wires and cast immobilization for 6 weeks. We decided to correct it before skeletal maturity due to the significant disturbance of the gait and esthetic impairment. It was obtained a satisfactory morphological and functional result with a simple and fast technique.

Objective To evaluate the expression of a set of miRNAs to identify differentially expressed miRNAs that might be considered reliable biomarkers on Diabetic Retinopathy (DR) blood samples. Results Expression levels of MiR-320a, MiR-342-3p, MiR-155, MiR-99a, MiR-29a and MiR-27b were analyzed in 60 healthy controls, 48 Diabetes Melitus (DM) without DR patients and 62 DR patients by qRT-PCR. MiR-320a was shown to be downregulated in the plasma of DR patients compared with DM patients without DR and healthy subjects. Target genes were predicted using miRWalk3.0, miR targeting data and target gene interaction data were imported to Cytoscape to visualize and merge networks and top ranked predicted genes were run through Ontology Genes to perform enrichment analysis on gene sets and classification system to identify biological processes and reactome pathways associated with DR. Highly scored target genes of miR-320a were categorized for various biological processes, including negative regulation of cell aging, negative regulation of cellular protein metabolic process and regulation of cellular response to stress that are critical to the development of DR. Our findings suggest that MiR-320a may have a role in the pathogenesis of DR and may represent novel biomarkers for this disease.

Metastatic colorectal cancer responds poorly to treatment and is a leading cause of cancer related deaths. Worldwide, chemotherapy of metastatic colorectal cancer remains plagued by poor efficacy, development of resistance and serious adverse effects. Copper-imidazo[1,2-a]pyridines were previously shown by our group to be selectively active against several cancer cell lines, with three complexes, JD46(27), JD47(29), and JD88(21), showing IC50 values between 0.8 and 1.8 μM against HT-29 cells. Here, we report that treatment with the copper complexes resulted in fragmented nuclei suggestive of apoptotic cell death, which was confirmed by increased annexin V binding and caspase-3/7 activity. The copper complexes caused a loss of mitochondrial membrane potential and increased caspase-9 activity. The absence of caspase-8 activity indicated activation of the intrinsic pathway. Proteomic analysis revealed that copper-imidazo[1,2-a]pyridines decreased the expression of phosphorylated forms of p53 [phospho-p53(S15), phospho-p53(S46) and phospho-p53(S392)]. The expression of inhibitor of apoptosis proteins, XIAP, cIAP1, livin, and the antiapoptotic proteins, Bcl-2 and Bcl-x, was decreased. HO/HMOX/HSP32, expression was notably increased, which suggested the accumulation of reactive oxygen species. Increased expression of TRAIL-R2/DR5 death receptor indicated the possible dual activation of both the extrinsic and intrinsic apoptotic pathways; however, caspase-8 activation could not be demonstrated. In conclusion, the copper-imidazo[1,2-a]pyridines were effective inducers of apoptotic cell death at low micromolar concentrations and changed the expression levels of proteins important for cell survival and cell death. These copper complexes may be useful tools to better understand the complexity of signalling networks in cancer cell death in response to cell stress.

Detection and quantification of microRNAs (miRNAs) in exhaled breath condensate (EBC) has been poorly explored. Therefore we aimed to assess miRNAs in EBC as potential biomarkers to diagnose and endotype asthma in school aged children. In a cross sectional, nested case control study, all the asthmatic children (n = 71) and a random sample of controls (n = 115), aged 7 to 12 years, attending 71 classrooms from 20 local schools were selected and arbitrarily allocated to the development or validation set. Participants underwent skin-prick testing, spirometry with bronchodilation, had exhaled level of nitric oxide determined and EBC collected. Based on previous studies eleven miRNAs were chosen and analyzed in EBC by reverse transcription-quantitative real-time PCR. Principal component analysis was applied to identify miRNAs profiles and associations were estimated using regression models. In the development set (n = 89) two clusters of miRNAs were identified. After adjustments, cluster 1 and three of its clustered miRNAs, miR-126-3p, miR-133a-3p and miR-145-5p were positively associated with asthma. Moreover miR-21-5p was negatively associated with symptomatic asthma and positively associated with positive bronchodilation without symptoms. An association was also found between miR-126-3p, cluster 2 and one of its clustered miRNA, miR-146-5p, with higher FEF25-75 reversibility. These findings were confirmed in the validation set (n = 97) where two identical clusters of miRNAs were identified. Additional significant associations were observed between miR-155-5p with symptomatic asthma, negative bronchodilation with symptoms and positive bronchodilation without symptoms. We showed that microRNAs can be measured in EBC of children and may be used as potential biomarkers of asthma, assisting asthma endotype establishment. Authors gratefully acknowledge the funding by Fundação para a Ciência e Tecnologia through the Project NORTE-01-0145-FEDER-000010 - Health, Comfort and Energy in the Built Environment (HEBE), cofinanced by Programa Operacional Regional do Norte (NORTE2020), through Fundo Europeu de Desenvolvimento Regional (FEDER) and EXALAR 21 project financed by FEDER/FNR and by Fundação para a Ciência e Tecnologia (EXALAR 21 02/SAICT/2017 - Project nº 30193). FCM kindly acknowledges the scholarship SFRH/BD/144563/2019 granted by Fundação para a Ciência e Tecnologia, as well as the Fulbright Research Grant 2019/2020 granted by Fulbright Portugal. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Background: The definitions of childhood asthma differ among epidemiological studies. We aimed to compare the diagnostic accuracy and agreement of previous asthma definitions and to evaluate questionnaire-driven asthma definition patterns. Methods: Data on 808 participants aged 7-12 years from 20 schools were analyzed. Asthma definitions based on symptoms assessed by questionnaire, parent-reported medical asthma diagnosis, current use of asthma medication, airway reversibility after bronchodilatation, and increased (35 ppb) levels of exhaled nitric oxide (eNO) were compared with a gold standard (medical diagnosis of asthma with asthma symptoms in the past 12 months and/or airway reversibility). Concordance was assessed by Cohen's kappa. Data-driven analysis was applied to the questionnaire, and six scores were determined asthma, rhinitis, cough, non-specific respiratory symptoms, treated asthma, and uncontrolled asthma. Tree decisions were built using these scores. Results: Definitions of asthma based on respiratory symptoms, airway reversibility, and parent-reported medical diagnosis had a low sensitivity but high specificity. Agreement between reported and objective measures was poor. Parent-reported medical asthma diagnosis, but not reversibility or eNO, was able to predict questionnaire-driven symptom patterns. Decision trees indicated that those with recent non-specific respiratory symptoms had a higher probability of positive bronchodilation. Conclusion: A standardized operational definition of asthma should include a composite score based on reported asthma medical diagnosis, symptoms, and lung function. (c) 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Background Indoor air contaminants may act as endocrine-disrupting chemicals (EDCs). However, to what extent these contaminants affect health is poorly known. We aimed to assess the association between EDCs exposure and asthma, respiratory symptoms and obesity in schoolchildren. Methods Data from a cross-sectional analysis of 815 participants from 20 schools in Porto, Portugal, were analysed. Symptoms were assessed, asthma was defined on lung function, and airway reversibility and body mass index (BMI) were calculated. The concentrations of 13 volatile organic compounds and 2 aldehydes identified as EDCs were measured in 71 classrooms throughout 1 week. Principal component analysis (PCA) was used to assess the effect of co-exposure. Associations were estimated by regression coefficients using linear and logistic regression models. Results Increased individual and combined EDCs levels were found in classrooms having more children with asthma and obesity. Higher levels of hexane, styrene, cyclohexanone, butylated hydroxytoluene and 2-butoxyethanol were associated with obesity, and higher levels of cyclohexanone were associated with increased child BMI. Toluene, o-xylene, m/p-xylene and ethylbenzene were significantly associated with nasal obstruction. A positive association was found between PC1 and the risk of obese asthma (OR = 1.43, 95% CI 1.01, 1.98) and between PC2 and overweight (OR = 1.51, 95% CI 1.28, 1.79). PC1 and PC2 were also associated with nasal obstruction, and PC2 was associated with breathing difficulties and lean body mass, although EDCs concentrations were low. Conclusions Our findings further support the role of EDCs in asthma and obesity development. Moreover, even low levels of indoor exposure may influence the risk of asthma, respiratory symptoms and obesity.

Introduction: The majority of compression fractures is stable and treated without major complications. One of the possible late consequences after trauma is the so called vertebral body avascular necrosis, also known as Kummel’s disease. This entity is clinically characterized by a progressively painful kyphosis within months after a minor trauma. The incidence of this finding is difficult to accurately precise because many designations have been used to describe it and it has been over diagnosed in many patients who don´t follow all the inclusion criteria. Clinical case: This paper presents the case of a 63-year-old female, with a background of Psoriatic Arthritis under biological treatment. She confirmed having a minor dorsolumbar trauma in the beginning of 2011, at the time without any complaints or new onset of pain. Five years after the trauma she came to the Emergency Room with back pain limiting her daily life. X-rays and a Computerized Tomography (CT) were taken and showed classical signs compatible with Kummel’s disease. It was suggested surgical treatment, accepted by the patient and in February 17th 2016 she was submitted to a percutaneous transpedicular fixation from D10 to L4, with cemented screws. She had a favorable outcome with clinical and radiological signs of bone consolidation Conclusion: Kummel’s disease is an exclusion diagnosis. There are clinical and imagiological criteria to help define this disease. Treatment consists of surgical fixation with anterior, posterior and both anterior/posterior approaches still being discussed on which of these gives the best results.

Leishmaniasis is a neglected disease caused by an intracellular protozoan parasite of the genus Leishmania. Infection starts when this protozoan replicates in a phagolysosomal compartment in macrophages, after evading host immune responses. The balance of Th1 and Th2 immune responses is crucial in leishmaniasis because it will determine whether the infection will be under control or if clinical complications will occur. The inflammasome, which is activated during Leishmania infection, involves the action of caspase-1 and release of the proinflammatory cytokines interleukin-1β and interleukin-18. Together, they contribute to the maintenance of an inflammatory response and pyroptosis. Here, we evaluated the serum levels of cytokines and the expression of circulating microRNAs related to inflammasome regulation in twenty-seven patients with cutaneous leishmaniasis in comparison to nine healthy individuals, in the context of the inflammasome activation. Evaluation of serum cytokines activation (IL-1β, IL-2, IL-4, IL-6, IL-10, and IL-17) was performed by flow cytometry using CBA kits (cytometric beads array) while the expression of circulating microRNAs (miR-7, miR-133a, miR-146b, miR-155, miR-223, miR-328, and miR-342) in plasma was measured by quantitative polymerase chain reaction. Our results showed an increase of the expression of miR-7-5p (p

This study is the result of two Portuguese case-control studies that examined the replication of retrospective correlates and preceding life events in anorexia nervosa (AN) and bulimia nervosa (BN) development. This study aims to identify retrospective correlates that distinguish AN and BNA case-control design was used to compare a group of women who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for AN (N = 98) and BN (N = 79) with healthy controls (N = 86) and with other psychiatric disorders (N = 68). Each control group was matched with AN patients regarding age and parental social categories. Risk factors were assessed by interviewing each person with the Oxford Risk Factor Interview.Compared to AN, women with BN reported significantly higher rates of paternal high expectations, excessive family importance placed on fitness/keeping in shape, and negative consequences due to adolescent overweight and adolescent objective overweight.Overweight during adolescence emerged as the most relevant retrospective correlate in the distinction between BN and AN participants. Family expectations and the importance placed on keeping in shape were also significant retrospective correlates in the BN group., This research was partially supported by a Portuguese Fundacao para a Ciencia e a Tecnologia/Foundation for Science and Technology research grant to the last author (PTDC/PSI-PCL/099981/2008) and a doctoral grant to the first author (FCT-SFRH/BD/22038/2005). The authors acknowledge Christopher G. Fairburn, MD, of the Department of Psychiatry at Oxford University (UK) for providing initial consultation and training and Helen A. Doll, PhD, for help with the initial data analysis., info:eu-repo/semantics/publishedVersion

Objective There have been few studies investigating the risk factors for bulimia nervosa (BN), and most have been in Anglo-Saxon countries. This study aimed to (i) replicate the uncontested retrospective correlates for BN and clarify the role of factors with inconsistent findings and (ii) evaluate the strength of these factors in a different culture. Method A case–control design was used to compare 60 women who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for BN to 60 healthy controls and 60 participants with other psychiatric disorders. Retrospective correlates were assessed by interviewing each person with the Oxford Risk Factor Interview. Results The primary retrospective correlates identified from the comparison of BN participants to healthy controls were general high maternal expectations, negative attitudes about parental weight and obesity in childhood and adolescence. Compared with participants with other psychiatric disorders, those with BN also reported higher rates of childhood obesity, deliberate self-harm, family conflicts, general high maternal expectations and feeling fat in childhood. Conclusions The common findings across cultures suggest that, at least, individuals subjectively experience a number of similar factors that increase risk for developing BN. In addition, the difference regarding self-harm is notable. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

Biomarker-driven research has been proposed as a successful method to assess the exposure of individuals to xenobiotics, including mycotoxins, through estimation of their metabolites in biological fluids. A methodology to determine patulin (PAT) and citrinin (CIT) in human urine and plasma using liquid chromatography coupled to tandem mass spectrometry was developed and validated in the present study. Selectivity/specificity, linearity, limit of detection and quantification, apparent recovery, intraday- and interday-precision and measurement uncertainty were investigated for validation purposes. Finally, the method was used to analyze human urine (n = 100) and plasma (n = 100) case-control samples, where 50 samples originated from colorectal cancer patients and 50 from age/sex-matched controls. This case-control study revealed that PAT was not detected in urine samples, however occurred in 25% of the analysed plasma samples with an average concentration of 11.62 ± 6.67 ng/mL in the positive samples. CIT was found in urine samples (74%) and plasma samples (36%) with average concentrations in the positive samples of 0.45 ± 0.24 ng/mL and 0.49 ± 0.2 ng/mL respectively. No statistically significant difference of PAT and CIT concentration among colorectal cancer and control patients (p > 0.05) was observed. Highlights: Development and validation of an LC-MS/MS method to determine patulin and citrinin in biological fluids; Patulin was detected in plasma (25%) for the first time; Citrinin was present in 74% of Tunisian urine samples; Citrinin was present in 36% of Tunisian plasma samples. The authors acknowledge the support of the Tunisian Ministry of Education and Scientific Research, the Toxicology and Environment Research Laboratory LR12SP07 (CAMUR, Tunis, Tunisia) and MYTOXSOUTH (https://mytoxsouth.org) (Ghent University and Global Minds International Thematic Network). Dr. Arnau Vidal expresses thanks to The Research Foundation Flanders(Wetenschappelijk Oderzoek- Vlaanderen, FWO) for the postdoctoral grant (12Y1719N). info:eu-repo/semantics/publishedVersion

Heart failure (HF) is a multifactorial chronic syndrome with progressive increasing incidence causing a huge financial burden worldwide.Remote monitoring should, in theory, improve HF management, but given increasing morbidity and mortality, a question remains: are we monitoring it properly?Device-based home monitoring enables objective and continuous measurement of vital variables and non-invasive devices should be first choice for elderly patients. There is no shortage of literature on the subject, however, most studies were designed to monitor a single variable or class of variables that were not properly assembled and, to the best of our knowledge, there are no large randomized studies about their impact on HF patient management. To overcome this problem, we carefully selected the most critical possible HF decompensating factors to design MONITORIA, a non-invasive device for comprehensive HF home monitoring.MONITORIA stands for MOnitoring Non-Invasively To Overcome mortality Rates of heart Insufficiency on Ambulatory, and in this paper, which is part I of a series of three articles, we discuss the theoretical basis for its design.MONITORIA and its inherent follow-up strategy will optimize HF patient care as it is a promising device, which will essentially adapt innovation not to the disease but rather to the patients. Resumo: A insuficiência cardíaca (IC) é uma síndrome crónica multifatorial com incidência progressivamente crescente e grande impacto financeiro a nível mundial.Teorizou-se que a telemonitorização contribuiria para uma melhor abordagem da IC. Contudo, face à crescente morbimortalidade desta síndrome, é pertinente colocar uma questão: será que estamos a monitorizar a IC adequadamente? A monitorização ambulatória, por meio de dispositivos, permite uma avaliação objetiva e contínua de diversos parâmetros vitais, sendo preferíveis os dispositivos não invasivos no caso dos pacientes idosos.Na literatura abundam artigos sobre estes dispositivos. Contudo, a maioria foi desenhada para monitorizar uma única variável ou uma classe de variáveis incorretamente reunidas. Além disso, até à data, não temos conhecimento de ensaios clínicos randomizados e controlados com intuito de avaliar o impacto destes dispositivos na abordagem da IC e seus outcomes. No sentido de tentar ultrapassar este problema, nós selecionamos cuidadosamente os fatores mais críticos nas exacerbações de IC, para desenhar o Monitoria, um dispositivo não invasivo para monitorização abrangente da IC em ambulatório.Monitoria significa MOnitoring Non-Invasively To Overcome mortality Rates of heart Insufficiency on Ambulatory e neste artigo, que é a parte I de uma série de três artigos, nós pretendemos discutir os fundamentos teóricos que estiveram na base do seu desenho.O Monitoria e a estratégia de follow-up que lhe é inerente aprimorará a abordagem do doente com IC, sendo um dispositivo promissor, essencialmente, por implicar um ajuste da inovação ao doente real, e não à sua doença ou a um conceito teórico de doente.

Recent studies have shown a high number of deaths from oral and oropharyngeal cancer worldwide, Brazil included. For this study, the deaths data (ICD-10, chapter II, categories C00 to C14) was obtained from Mortality Information System (SIM) and standardized by gender and population for each of the 554 Microregions of Brazil. The raw mortality rates were adopted as the standard and compared to the application of smoothing by the Bayesian model. In order to describe the geographical pattern of the occurrence of oral cancer, thematic maps were constructed, based on the distributions of mortality rates for Microregions and gender. Results: There were 7882 deaths registered due to oral and oropharyngeal cancer in Brazil, of which 6291 (79.81%) were male and 1591 (20.19%) female. The Empirical Bayesian Model presented greater scattering with mosaic appearance throughout the country, depicting high rates in Southeast and South regions interpolated with geographic voids of low rates in Midwest and North regions. For males, it was possible to identify expressive clusters in the Southeast and South regions. Conclusion: The Empirical Bayesian Model allowed an alternative interpretation of the oral and oropharynx cancer mortality mapping in Brazil.

Background Endurance swimming exercises coupled to disinfection by-products exposure has been associated with increased airways dysfunction and neurogenic inflammation in elite swimmers. However, the impact of swimming pool exposure at a recreational level on autonomic activity has never been explored. Therefore, this study aimed to investigate how swimming pool attendance is influencing lung and autonomic function in school-aged children. Methods A total of 858 children enrolled a cross sectional survey. Spirometry and airway reversibility to beta-2 agonist, skin-prick-tests and exhaled nitric oxide measurements were performed. Pupillometry was used to evaluate autonomic nervous function. Children were classified as current swimmers (CS), past swimmers (PS) and non-swimmers (NS), according to the amount of swimming practice. Results Current swimmers group had significantly lower maximum and average pupil constriction velocities when compared to both PS and NS groups (3.8 and 5.1 vs 3.9 and 5.3 vs 4.0 and 5.4 mm/s, p = 0.03 and p = 0.01, respectively). Moreover, affinity to the beta-2 agonist and levels of exhaled nitric oxide were significantly higher in CS when compared to NS (70 vs 60 mL and 12 vs 10 ppb, p

Tordo et al. present a novel AAV gene therapy vector, AAV-TT, which exceeds the current benchmark neurotropic serotypes AAV9 and AAVrh10 and enables unprecedented correction of a lysosomal transmembrane enzyme deficiency. AAV-TT based gene therapies may thus be suitable for the treatment of human neurological diseases characterised by global neuropathology., Recombinant adeno-associated viruses (AAVs) are popular in vivo gene transfer vehicles. However, vector doses needed to achieve therapeutic effect are high and some target tissues in the central nervous system remain difficult to transduce. Gene therapy trials using AAV for the treatment of neurological disorders have seldom led to demonstrated clinical efficacy. Important contributing factors are low transduction rates and inefficient distribution of the vector. To overcome these hurdles, a variety of capsid engineering methods have been utilized to generate capsids with improved transduction properties. Here we describe an alternative approach to capsid engineering, which draws on the natural evolution of the virus and aims to yield capsids that are better suited to infect human tissues. We generated an AAV capsid to include amino acids that are conserved among natural AAV2 isolates and tested its biodistribution properties in mice and rats. Intriguingly, this novel variant, AAV-TT, demonstrates strong neurotropism in rodents and displays significantly improved distribution throughout the central nervous system as compared to AAV2. Additionally, sub-retinal injections in mice revealed markedly enhanced transduction of photoreceptor cells when compared to AAV2. Importantly, AAV-TT exceeds the distribution abilities of benchmark neurotropic serotypes AAV9 and AAVrh10 in the central nervous system of mice, and is the only virus, when administered at low dose, that is able to correct the neurological phenotype in a mouse model of mucopolysaccharidosis IIIC, a transmembrane enzyme lysosomal storage disease, which requires delivery to every cell for biochemical correction. These data represent unprecedented correction of a lysosomal transmembrane enzyme deficiency in mice and suggest that AAV-TT-based gene therapies may be suitable for treatment of human neurological diseases such as mucopolysaccharidosis IIIC, which is characterized by global neuropathology.

Recent evidence suggests that cell-derived circulating miRNAs may serve as biomarkers of cardiovascular diseases. However, a few studies have investigated the potential of circulating miRNAs as biomarkers for left ventricular hypertrophy (LVH). In this study, we aimed to characterize the miRNA profiles that could distinguish hypertensive patients with LHV, hypertensive patients without LVH and control subjects, and identify potential miRNAs as biomarkers of LVH. LVH was defined by left ventricular mass indexed to body surface area >125 g/m2 in men and >110 g/m2 in women and patients were classified as hypertensive when presenting a systolic blood pressure of 140 mmHg or more, or a diastolic blood pressure of 90 mmHg or more. We employed miRNA PCR array to screen serum miRNAs profiles of patients with LVH, essential hypertension and healthy subjects. We identified 75 differentially expressed miRNAs, including 49 upregulated miRNAs and 26 downregulated miRNAs between LVH and control patients. We chose 2 miRNAs with significant differences for further testing in 59 patients. RT-PCR analysis of serum samples confirmed that miR-7-5p and miR-26b-5p were upregulated in the serum of LVH hypertensive patients compared with healthy subjects. Our findings suggest that these miRNAs may play a role in the pathogenesis of hypertensive LVH and may represent novel biomarkers for this disease.

Breast cancer is the most frequent type of nonskin malignancy among women worldwide. In general, conventional cancer treatment options (i.e., surgery, radiotherapy, chemotherapy, biological therapy, and hormone therapy) are not completely effective. Recurrence and other pathologic situations are still an issue in breast cancer patients due to side effects, toxicity of drugs in normal cells, and aggressive behaviour of the tumours. From this point of view, breast cancer therapy and adjuvant methods represent a promising and challenging field for researchers. In the last few years, the use of some types of complementary medicines by women with a history of breast cancer has significantly increased such as phytotherapeutic products and nutritional supplements. Despite this, the use of such approaches in oncologic processes may be problematic and patient’s health risks can arise such as interference with the efficacy of standard cancer treatment. The present review gives an overview of the most usual phytotherapeutic products and nutritional supplements with application in breast cancer patients as adjuvant approach. Regardless of the contradictory results of scientific evidence, we demonstrated the need to perform additional investigation, mainly well-designed clinical trials in order to establish correlations and allow for further validated outcomes concerning the efficacy, safety, and clinical evidence-based recommendation of these products.

Objective The first aim of the current study was to establish general population norms for the Portuguese version of the Eating Disorder Examination Questionnaire (EDE-Q) in a large community sample of female adolescents and young women, as well, for a diverse Eating Disorder (ED) clinical sample, and for women with obesity without an ED. A second aim of the study was to assess the discriminant validity of the EDE-Q and providing cut-off scores for the total scale and subscales. Method A sample of female adolescents and young women (N = 4091) from the general population, 416 women who met diagnostic criteria for an ED and 138 women seeking obesity treatment completed the EDE-Q. Results Norms for the EDE-Q global subscale were provided. Within the community sample, norms were provided for both high school and college samples. Receiver operating characteristic analysis showed that the EDE-Q total score accurately discriminate between participants with and without an ED. Current norm contributes to the clinical utility of the EDE-Q, providing both a cut-off score and reliable change index. Results showed that the EDE-Q is a reliable instrument, but the theorized four subscales structure was not supported by an explorative factor analysis. Conclusion Results will help both researchers and clinicians interpreting the EDE-Q scores and to establish comparison with data produced in different countries. Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association.

Background: Bulimia nervosa (BN) is often related to self-control difficulties and to dysregulated behaviours. This study aimed to evaluate the frequency of self-injurious behaviour, suicide attempts, and other dysregulated behaviours in BN, using two control groups (a healthy group and a general psychiatric group), and also to examine the association between these behaviours and alleged sexual abuse in BN.Method: Women (N = 233) aged between 13 and 38 years old were evaluated using a semi-structured interview.Results: Participants with BN reported more self-injurious behaviours, suicide attempts by drug intake, and poor control in smoking and illicit drugs use compared with participants in both control groups. Participants with BN also reported more spending behaviours when compared with the general psychiatric control group. The use of illegal drugs and medication was significantly related to alleged sexual abuse in BN participants.Conclusions: This study concluded that BN is often related to dysregulated behaviours, and clinicians must take into account the multi-impulsive spectrum behaviours of BN in their evaluation and treatment of BN., This study was supported by a grant from the Fundacaopara a Ciencia e a Tecnologia/Foundation for Science and Technology, Portugal (PTDC/PSI-PCL/099981/2008) to the last author., info:eu-repo/semantics/publishedVersion

Infection by Trypanosoma cruzi, the aetiological agent of Chagas disease, causes an intense inflammatory reaction in several tissues, including the myocardium. We have previously shown that transplantation of bone marrow cells (BMC) ameliorates the myocarditis in a mouse model of chronic Chagas disease. We investigated the participation of BMC in lesion repair in the heart and skeletal muscle, caused by T. cruzi infection in mice. Infection with a myotropic T. cruzi strain induced an increase in the percentage of stem cells and monocytes in the peripheral blood, as well as in gene expression of chemokines SDF-1, MCP1, 2, and 3 in the heart and skeletal muscle. To investigate the fate of BMC within the damaged tissue, chimeric mice were generated by syngeneic transplantation of green fluorescent protein (GFP+) BMC into lethally irradiated mice and infected with Trypanosoma cruzi. Migration of GFP+ BMC to the heart and skeletal muscle was observed during and after the acute phase of infection. GFP+ cardiomyocytes and endothelial cells were present in heart sections of chimeric chagasic mice. GFP+ myofibres were observed in the skeletal muscle of chimeric mice at different time points following infection. In conclusion, BMC migrate and contribute to the formation of new resident cells in the heart and skeletal muscle, which can be detected both during the acute and the chronic phase of infection. These findings reinforce the role of BMC in tissue regeneration

ObjectiveThe aetiology of anorexia nervosa (AN) is considered to be multifactorial. This study aims to identify potential risk factors for AN and whether these factors are specific to AN or precede the development of psychiatric disorders in general and to identify specific life events in the 12months immediately preceding the onset of eating disorder (ED) symptoms. MethodA case-control design was used to compare a group of women who meet Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for AN (N=86) with healthy controls (N=86) and with a group of controls with other psychiatric disorders (N=68), each group matched to the AN patients by age and parental socioeconomic status bands. Risk factors were assessed by interviewing each person with the Oxford Risk Factor Interview. ResultsWomen with AN reported significantly higher rates of perfectionism, negative attitudes toward parents' shape and weight, significant concern about feeling fat and a family history of AN or bulimia nervosa. Critical comments about weight, shape or eating was the most notable event in the year preceding AN onset. DiscussionPerfectionism and a family history of ED emerged as the most convergent findings in the development of AN, along with being critical toward parents' shape and weight, and feeling fat. Critical comments about appearance and eating seem to be an important precipitating factor in AN onset. Copyright (c) 2014 John Wiley & Sons, Ltd and Eating Disorders Association.

OBJECTIVE: Describing the demographic and epidemiological aspects of mortality from cancer of the penis.METHODS: A cross-sectional study consisting of 183 deaths registered in a public information system on mortality that had penile cancer as the primary cause of mortality. It was used descriptive statistics and the mortality rate was calculated.RESULTS: The mean coefficient of mortality was 0.45/100,000 that is an increase of 19.04%. The demographic data revealed a higher prevalence in men aged 60 years or older (50.8%), brown (54.1%), married (47.6%), retired (24%) and residents of the metropolitan region (44.8%).CONCLUSION: The demographic and epidemiological aspects revealed increase of mortality rates from cancer in the penis. OBJETIVO: Descrever os aspectos demográficos e epidemiológicos da mortalidade por câncer no pênis.MÉTODOS: Estudo transversal constituído por 183 óbitos registrados em um sistema público de informação sobre mortalidade que tiveram como causa básica de morte o câncer no pênis. Utilizou-se estatística descritiva e foi calculado o coeficiente de mortalidade.RESULTADOS: O coeficiente de mortalidade médio foi de 0,45/100 mil, com acréscimo de 19,04%. Os dados sociodemográficos revelaram um maior acometimento nos homens na faixa etária de 60 anos ou mais (50,8%), da cor parda (54,1%), casados (47,6%), aposentados (24%) e residentes em região metropolitana (44,8%).CONCLUSÃO: Os aspectos demográficos e epidemiológicos revelaram aumento no coeficiente de mortalidade por câncer no pênis.

Chagas disease, caused by Trypanosoma cruzi infection, is a leading cause of heart failure in Latin American countries. In a previous study, we showed beneficial effects of granulocyte colony-stimulating factor (G-CSF) administration in the heart function of mice with chronic T. cruzi infection. Presently, we investigated the mechanisms by which this cytokine exerts its beneficial effects. Mice chronically infected with T. cruzi were treated with human recombinant G-CSF (3 courses of 200 μg/kg/d for 5 d). Inflammation and fibrosis were reduced in the hearts of G-CSF-treated mice, compared with the hearts of vehicle-treated mice, which correlated with decreased syndecan-4, intercellular adhesion molecule-1, and galectin-3 expressions. Marked reductions in interferon-γ and tumor necrosis factor-α and increased interleukin-10 and transforming growth factor-β were found after G-CSF administration. Because the therapy did not induce a Th1 to Th2 immune response deviation, we investigated the role of regulatory T (Treg) cells. A significant increase in CD3(+)Foxp3(+) cells was observed in the hearts of G-CSF-treated mice. In addition, a reduction of parasitism was observed after G-CSF treatment. Our results indicate a role of Treg cells in the immunosuppression induced by G-CSF treatment and reinforces its potential therapeutic use for patients with Chagas disease.

Metabolomics is an important tool for the evaluation of the human condition, in both health or disease. This study analyzed the salivary components of type I diabetic children (DM1) under six years of age, to assess oral health related to diabetes control, as well as metabolite profiling using NMR. Partial least squared discriminant analysis (PLS-DA) was used to compare healthy (HG) and uncontrolled DM1 subjects that demonstrated a separation between the groups with classificatory performance of ACC = 0.80, R(2) = 0.92, Q(2) = 0.02 and for DM1 children with glycemia >200 mg/dL of ACC = 0.74, R(2) = 0.91, Q(2) = 0.06. The metabolites that mostly contributed to the distinction between the groups in the loading factor were acetate, n-acetyl-sugar, lactate, and sugar. The univariate analysis showed a decreased salivary concentration of succinic acid and increased levels of lactate, acetate, and sucrose in uncontrolled and DM1 children with glycemia >200 mg/dL. The present study demonstrates that the salivary profile of DM1 differs from that of HG children. It appears that diabetes status control has an important effect on the salivary composition.

Background Osteogenesis Imperfecta (OI) (OMIM %259450) is a heterogeneous group of inherited disorders characterized by increased bone fragility, with clinical severity ranging from mild to lethal. The majority of OI cases are caused by mutations in COL1A1 or COL1A2. Bruck Syndrome (BS) is a further recessively-inherited OI-like phenotype in which bone fragility is associated with the unusual finding of pterygia and contractures of the large joints. Notably, several studies have failed to show any abnormalities in the biosynthesis of collagen 1 in BS patientes. Evidence was obtained for a specific defect of the procollagen telopeptide lysine hydroxylation in BS, whereas mutations in the gene PLOD2 have been identified. Recently, several studies described FKBP10 mutations in OI-like and BS patients, suggesting that FKBP10 is a bonafide BS locus. Methods We analyzed the coding region and intron/exon boundaries of COL1A1, COL1A2, PLOD2 and FKBP10 genes by sequence analysis using an ABI PRISM 3130 automated sequencer and Big Dye Terminator Sequencing protocol. Mononuclear cells obtained from the bone marrow of BS, OI patients and healthy donors were cultured and osteogenic differentiation was induced. The gene expression of osteoblast specific markers were also evaluated during the osteoblastic differentiation of mesenchymal stem cell (MSC) by qRT-PCR using an ABI7500 Sequence Detection System. Results No mutations in COL1A1, COL1A2 or PLOD2 were found in BS patient. We found a homozygous 1-base-pair duplication (c.831dupC) that is predicted to produce a translational frameshift mutation and a premature protein truncation 17 aminoacids downstream (p.Gly278ArgfsX95). The gene expression of osteoblast specific markers BGLAP, COL1A1, MSX2, SPARC and VDR was evaluated by Real Time RT-PCR during differentiation into osteoblasts and results showed similar patterns of osteoblast markers expression in BS and healthy controls. On the other hand, when compared with OI patients, the expression pattern of these genes was found to be different. Conclusions Our work suggests that the gene expression profiles observed during mesenchymal stromal cell differentiation into osteoblast are distinct in BS patients as compared to OI patients. The present study shows for the first time that genes involved in osteogenesis are differentially expressed in BS and OI patients. Electronic supplementary material The online version of this article (doi:10.1186/s12881-016-0301-7) contains supplementary material, which is available to authorized users.

This study aimed to determine whether dental calculus formation is really higher among patients with chronic kidney disease undergoing hemodialysis than among controls. Furthermore, the study evaluated correlations between dental calculus formation and dental plaque, variables that are related to renal disease and/or saliva composition. The Renal Group was composed of 30 patients undergoing hemodialysis, whereas the Healthy Group had 30 clinically healthy patients. Stimulated whole saliva and parotid saliva were collected. Salivary flow rate and calcium and phosphate concentrations were determined. In the Renal Group the saliva collection was carried out before and after a hemodialysis session. Patients from both groups received intraoral exams, oral hygiene instructions, and dental scaling. Three months later, the dental calculus was measured by the Volpe–Manhold method to determine the rate of dental calculus formation. The Renal Group presented a higher rate of dental calculus formation (p

Approximately 30% of patients with mesial temporal lobe epilepsy do not respond to treatment with antiepileptic drugs. We have previously shown that transplantation of mononuclear bone marrow cells (BMC) has an anticonvulsant effect in acute epilepsy. Here, we used pilocarpine to induce epilepsy in rats and studied the effects of BMC injected intravenously either at the onset of seizures or after 10 months of recurrent seizures. BMC effectively decreased seizure frequency and duration. In addition, decreased levels of proinflammatory cytokines (TNF-α, IL-1β and IL-6) and increased levels of anti-inflammatory cytokine (IL-10) were observed in the brain and serum of BMC-treated rats. Transplants performed at seizure-onset protected against pilocarpine-induced neuronal loss and gliosis and stimulated the proliferation of new neurons in epileptic rats. Our data demonstrate that BMC transplantation has potent therapeutic effects and could be a potential therapy for clinically intractable epilepsies.

Background Elite swimmers are at increased risk of asthma, which has been related to chronic effects of pool chlorine environment. However acute effects of swimming on rhinitis remain unknown. Objective We aimed to assess the nasal response to exercise in competitive swimmers compared with competitive runners. Methods Measurements of nasal symptoms, peak nasal inspiratory flow, lung function, dyspnea, and of airway inflammation were obtained before and after a training session of 19 international-level swimmers and 13 professional runners. Exercise-induced rhinitis was defined as a fall in peak nasal inspiratory flow above 20% from baseline and atopy by positivity to skin-prick testing. Changes within groups were compared using paired t test and differences compared by analysis of covariance. Results Prevalence of exercise-induced rhinitis was similar between swimmers and runners, respectively 21% and 23%. Contrary to runners, swimmers experienced a decrease in nasal inspiratory flow levels and increase in sneezing, nasal congestion, itching, and postnasal drip after exercise. However, difference in changes was only significant for postnasal drip (p = 0.050). All subjects experiencing exercise-induced rhinitis were nonatopic. An overall improvement in nasal flows, sneezing, and itching after exercise was observed in atopic athletes, although no significant differences in changes compared with nonatopic athletes existed. Conclusion Swimmers, contrary to runners, experience a worsening of nasal function after training. Although these differences were only significant for postnasal drip, our results provide support to the existence of a “swimming-induced rhinitis” independent of the atopic status of the athlete.

We have described the oral status and salivary flow rate of 30 children and adolescents suffering from chronic renal failure (CRF) undergoing hemodialysis and compared the associated parameters with those of 30 clinically healthy subjects with no history of chronic disease. The subjects of the renal group (RG) and healthy group (HG) were paired by gender and age (7-19 years old). Anamneses and an interview consisting of questions on oral hygiene habits comprised the first step in the study, followed by whole and parotid saliva collection and intra-oral examination. No statistical significant difference was found between the RG and HG subjects in terms of the presence of gingival inflammation, dental history of caries, and enamel hypoplasia. However, statistical significant differences were found between the groups related to a sensation of dry mouth, salivary flow rate, delayed tooth eruption, dental staining by iron supplementation, presence of plaque, and dental calculus. Based on our results, we conclude that CRF children and adolescents undergoing hemodialysis present some oral manifestations related to their disease. These manifestations include a sensation of dry mouth, delayed tooth eruption, dental staining by iron supplementation, and dental calculus. A lower flow rate of whole and parotid saliva production just before hemodialysis was also observed.

Patients diagnosed with anorexia nervosa (n = 30) and bulimia nervosa (n = 27), their parents and therapists were recruited for this study aimed at examining differences between clinical groups and a control group (n = 35) in terms of attachment styles and perceptions of memories of parental rearing. Within the clinical groups, relations among these variables and therapeutic bond were explored. In addition, parents' and their daughters' attachment styles were compared. The results showed differences between clinical and control groups: the daughters in the control group reported lower levels of attachment anxiety compared to those of the clinical groups; their mothers exhibited higher security than mothers of anorectic patients and lower avoidance than mothers of bulimic patients. For the anorectic group, therapeutic bond was associated to higher father's emotional support and lower rejection; in the bulimic group, therapeutic bond was related to higher maternal emotional support and lower rejection as well as to lower paternal overprotection., info:eu-repo/semantics/publishedVersion

Background: Forced expiratory flows at lower lung volumes might be more adequate at detecting small airways involvement in early childhood asthma. Aims: To ascertain potential insights given by FEF 25–75% and FEF 75% measurements over FEV 1 and FEV 1 /FVC in young children functional assessment, as asthma predictors. Methods: Retrospective review of spirometry [with bronchodilation test after 400 µg salbutamol (BDT)], and clinical data of consecutive children aged 3-8 years old, evaluated between Jan/11 and Dec/14. Spirometries with restrictive pattern or not fulfilling set quality parameters were excluded. Results: Spirometry was performed in 377 children (59.4% male) – 256 (67.9%) with physician-diagnosed asthma. Based on reduced FEV 1 /FVC z-score ( 25–75% z-score 25-75% BDT (ΔFEF 25-75% ≥30.0%) was observed in 53 (20.4%) of the 260 patients with normal FEV 1 /FVC and negative FEV 1 BDT (ΔFEV 1 25-75% z-score. When asthma functional diagnosis criterion of a positive FEV 1 BDT (ΔFEV 1 ≥12.0%) was absent (n=281), ROC curves demonstrated that basal z-scores of FEF 25–75% or FEF 75% , or ΔFEF 25-75% , were unable to predict physician-diagnosed asthma (AUC: 0.60, 0.58 and 0.51, respectively). Conclusions: FEF 25-75% and FEF 75% z-scores, as well as ΔFEF 25-75% have limited usefulness as asthma predictors over established parameters, in the studied age group.

Introduction: Asthma is one of the most prevalent chronic medical conditions to complicate pregnancy. Active management strategies that prioritize control in this vulnerable population may have a far-reaching impact. Aim: To describe lung function parameters and results of CARAT® questionnaire in pregnant asthmatics. Methods: Retrospective study was carried out, including all pregnant asthmatics who performed spirometry and CARAT ® between September 2013 and February 2015 in our department. Medical records were reviewed and data regarding demographic characteristics, sensitization and medication were collected. Control of asthma and rhinitis was defined by CARAT total score (CARAT (T)) ≥24; upper airways (U) control if CARAT (U) ≥8; lower airways (L) control if CARAT (L)≥16. Those with only one measurement were excluded. Results: Twenty-six pregnant patients were included, with mean age (standard deviation) 31 (5.4) years; all had asthma and rhinitis, 73.1% were atopic, 69.2% sensitized to dust mites and 30.8% to grass pollens. Almost 70% presented poor control (CARAT (T)

International audience; Severe progressive neurological paediatric disease mucopolysaccharidosis III type C is caused by mutations in the HGSNAT gene leading to deficiency of acetyl-CoA: alpha-glucosaminide N-acetyltransferase involved in the lysosomal catabolism of heparan sulphate. To understand the pathophysiology of the disease we generated a mouse model of mucopolysaccharidosis III type C by germline inactivation of the Hgsnat gene. At 6-8 months mice showed hyperactivity, and reduced anxiety. Cognitive memory decline was detected at 10 months and at 12-13 months mice showed signs of unbalanced hesitant walk and urinary retention. Lysosomal accumulation of heparan sulphate was observed in hepatocytes, splenic sinus endothelium, cerebral microglia, liver Kupffer cells, fibroblasts and pericytes. Starting from 5 months, brain neurons showed enlarged, structurally abnormal mitochondria, impaired mitochondrial energy metabolism, and storage of densely packed autofluorescent material, gangliosides, lysozyme, phosphorylated tau, and amyloid-beta. Taken together, our data demonstrate for the first time that deficiency of acetyl-CoA: alpha-glucosaminide N-acetyltransferase causes lysosomal accumulation of heparan sulphate in microglial cells followed by their activation and cytokine release. They also show mitochondrial dysfunction in the neurons and neuronal loss explaining why mucopolysaccharidosis III type C manifests primarily as a neurodegenerative disease.

Introduction Short segment pedicle screw fixation is the most common treatment for thoracolumbar fractures. However, it may not be adequate to achieve and maintain reduction of the fracture and is associated with a high rate of failure. Additional procedures have been offered as alternative solutions to prevent this failure. Long segmental instrumentation or placements of screws at fracture site are some alternatives. Correction of sagittal deformity is important for the maintenance of fracture reduction and may have an effect on functional outcome. Intraoperative correction of sagittal deformity and fracture reduction can be managed easily through placement of screws at the fracture level. Objectives The purpose of this retrospective study was to evaluate the efficacy of screw placement at the fracture level in correction of deformity, maintenance of correction and preventing the failure of fixation in thoracolumbar fractures. Methods Retrospective study of patients with thoracolumbar fractures treated with 4 or 6-screw construct. Preoperative, postoperative and follow-up were evaluated. To evaluate the efficacy of fracture level screw fixation anterior vertebral height compression (%ABC), local kyphosis (KA) and load-sharing classification were compared. %ABC was calculated by using the formula adopted by Mumford et al. Local kyphosis was measured according to Cobb's method. Student t test was used for statistical analysis of variables. A p-value

The administration of stem cells holds promise as a potential therapy for spinal cord injury (SCI). Mesenchymal stem cells have advantages for clinical applications, since they can be easily obtained, are suitable for autologous transplantation and have been previously shown to induce regeneration of the spinal cord in experimental settings. Here we evaluated the feasibility, safety and potential efficacy of autologous transplantation of mesenchymal stem cells in subjects with chronic complete SCI. We conducted a phase I, non-controlled study in 14 subjects of both genders aging between 18 to 65 years, with chronic traumatic SCI (>6 months), at thoracic or lumbar levels, classified as American Spinal Injury Association (ASIA) A - complete injury. Baseline somatosensory evoked potentials (SSEP), spinal magnetic resonance imaging (MRI) and urodynamics were assessed before and after treatment. Pain rating was performed using the McGill Pain Questionnaire and a visual analogue score scale. Bone marrow-derived mesenchymal stem cells were cultured and characterized by flow cytometry, cell differentiation assays and G-band karyotyping. Mesenchymal stem cells were injected directly into the lesion following laminectomy and durotomy. Cell transplantation was an overall safe and well-tolerated procedure. All subjects displayed variable improvements in tactile sensitivity and eight subjects developed lower limbs motor functional gains, principally in the hip flexors. Seven subjects presented sacral sparing and improved American Spinal Injury Association impairment scale (AIS) grades to B or C – incomplete injury. Nine subjects had improvements in urologic function. One subject presented changes in SSEP 3 and 6 months after mesenchymal stem cells transplantation. Statistically significant correlations between the improvements in neurological function and both injury size and level were found. Intralesional transplantation of autologous mesenchymal stem cells in subjects with chronic, complete spinal cord injury is safe, feasible, and may promote neurological improvements. ClinicalTrials.gov NCT01325103 – Registered 28 March 2011

The present study aims to evaluate the occurrence of life events preceding the onset of eating problems in bulimia nervosa patients. A case-control design was used involving the comparison of 60 female subjects who meet DSM-IV criteria for bulimia nervosa with 60 healthy control subjects and 60 subjects with other psychiatric disorders. The RFI (Fairburn etal., 1998) subset of factors that represent exposure to life events in the 12 months immediately before the development of eating problems was used. Women with bulimia nervosa reported higher rates of major stress, criticism about eating, weight and shape and also a great number of antecedent life events during the year preceding the development of eating problems than the healthy control group. However, when compared with the general psychiatric control group only the exposure to critical comments about weight, shape, or eating emerged as a specific trigger for bulimia nervosa. Our findings support the fact that eating and shape/weight criticism in the year preceding the development of eating disturbance seems to be specifically related to bulimia nervosa., info:eu-repo/semantics/publishedVersion