An adolescent with sickle cell anaemia experiencing disease-related complications: priapism and leg ulcer--a management challenge.

Sickle-cell anaemia (SCA) is a multi-system disease, associated with episodes of acute illness and progressive organ damage. Disease severity shows substantial variation and it is often a burden for adolescents. Complications such as leg ulcer and priapism have a significant impact on quality of life. There are still no definitive treatment guidelines available. Considering the embarrassing nature of priapism and the dire consequences for erectile dysfunction, it is important to inform patients, parents and providers about the relationship of SCA to prolonged painful erections. This article will review the pathophysiology and treatment options of SCA focusing the complications of leg ulcers, priapism, cholelithiasis and retinopathy. The case study of a 14-year-old boy is used to present a management challenge of multiple SCA-related complications.info:eu-repo/semantics/publishedVersio

Fluorometric Liposome Screen for Inhibitors of a Physiologically Important Bacterial Ion Channel

The bacterial K+ homeostasis machinery is widely conserved across bacterial species, and different from that in animals. Dysfunction in components of the machinery has an impact on intracellular turgor, membrane potential, adaptation to changes in both extracellular pH and osmolarity, and in virulence. Using a fluorescence-based liposome flux assay, we have performed a high-throughput screen to identify novel inhibitors of the KtrAB ion channel complex from Bacillus subtilis, a component of the K+ homeostasis machinery that is also present in many bacterial pathogens. The screen identified 41 compounds that inhibited K+ flux and that clustered into eight chemical groups. Many of the identified inhibitors were found to target KtrAB with an in vitro potency in the low µM range. We investigated the mechanisms of inhibition and found that most molecules affected either the membrane component of the channel, KtrB alone or the full KtrAB complex without a preference for the functional conformation of the channel, thus broadening their inhibitory action. A urea derivative molecule that inhibited the membrane component of KtrAB affected cell viability in conditions in which KtrAB activity is essential. With this proof-of-concept study, we demonstrate that targeting components of the K+ homeostasis machinery has the potential as a new antibacterial strategy and that the fluorescence-based flux assay is a robust tool for screening chemical libraries.This work was supported by FEDER funds through COMPETE 2020-POCI, Portugal 2020, and FCT – Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior: POCI-01-0145-FEDER-029863 (PTDC/BIA-BQM/29863/2017), and by “Fundação Luso-Americana para o Desenvolvimento” FLAD Life Science 2020 awarded to JM-C. We acknowledge FCT fellowship SFRH/BPD/105672/2015 and contract DL 57/2016/CP1355/CT0026 awarded to AF, fellowship SFRH/BPD/107785/2015 to AP, and fellowship SFRH/BD/123761/2016 to CT-D

Regular physical activity-related awareness and knowledge in Portugal: results from a population-based survey

Background: Previous studies have shown that adequate physical activity (PA, defined as any bodily movement that requires energy expenditure) related awareness and knowledge is crucial to promote regular PA. Therefore, this study aims to characterize PA awareness and knowledge, and to quantify its association with sociodemographic characteristics, health literacy and frequency of exercise. Methods: In a cross-sectional study conducted in 2012, a total of 1624 Portuguese-speaking residents of mainland Portugal (16–79 years old) were assessed through face-to-face interviews using a structured questionnaire. Adjusted prevalence ratios, calculated using Poisson regression, were used to quantify associations with PA awareness and knowledge. Results: The most reported benefits of PA were “reduces abdominal fat accumulation” (95.8%), “reduces myocardial infarction risk” (92.9%) and “improves bone health” (90.7%), these were less referred by older participants, while more often identified by those who exercise daily. The most referred barrier for people to not practice PA regularly was “lack of time” (33.9%) with differences observed by sex, age, education, employment and health literacy. Over two-thirds of participants correctly identified at least 2 of 3 PAs (“running”, “soccer” and “tennis”) that require the most energy, particularly males, those with higher health literacy and who exercise twice or more times a week. Conclusions: An adequate PA-related awareness and knowledge was observed, and differences according to age, health literacy levels and frequency of exercise were found. As such, awareness-raising interventions to increase regular PA through improving physical literacy and motivation should focus on older adults, those with limited health literacy and who do not exercise.Financial support and sponsorship: This study was supported by FEDER funds through Operational Programme Competitiveness and Internationalization and by national funding from The Portuguese Foundation for Science and Technology – FCT (Portuguese Ministry of Education and Science) within the project (HMSPIISE/SAU-ICT/0004/2009) and the Epidemiology Research Unit – Institute of Public Health, University of Porto (EPIUnit; info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB/04750/2020/PT). SM was funded under the scope of the project "NEON-PC - Neuro-oncological complications of prostate cancer: longitudinal study of cognitive decline" (POCI-01-0145-FEDER-032358; Ref. PTDC/SAU-EPI/32358/2017). An individual grant attributed to ARC (SFRH/BD/102181/2014) was co-funded by FCT and the “Programa Operacional Capital Humano” (POCH/FSE). The funding sources had no role in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication

The occupational risk of Helicobacter pylori infection: a systematic review

The aim of this systematic review was to describe the prevalence of Helicobacter pylori infection in specific occupational groups and to compare them with the general population. We searched PubMedA (R) to identify original studies reporting the prevalence of H. pylori infection in occupational groups. The differences between occupational groups and the general population were analyzed taking into account the direction and statistical significance of the differences observed when comparing each occupational group with a reference group (either recruited in the same study or using an external comparator). A total of 98 studies addressing the prevalence of H. pylori infection in occupational groups were included in the systematic review. Overall, health professionals showed a significantly higher prevalence of H. pylori infection than the general population, especially among those working at gastrointestinal units. Similar results were found in subjects involved in agricultural, forestry and fishery, as well as in sewage workers, miners, and workers at institutions for the intellectually disabled, although differences were less pronounced. Our results show an occupational risk of H. pylori infection supporting the role of oral-oral, fecal-oral, and zoonotic transmission. Studies comparing specific occupational groups with adequate comparators may contribute to better identify groups at higher risk of infection. The recognition of this infection as an occupational disease would result in early detection and treatment, as well as prevention and control of its transmission in workplaces.This study was funded by FEDER through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology-FCT (Portuguese Ministry of Science, Technology and Higher Education), under the Unidade de Investigacao em Epidemiologia-Instituto de Saude Publica da Universidade do Porto (EPIUnit) (POCI-01-0145-FEDER-006862; Ref. UID/DTP/04750/2013). Individual PhD Grants attributed to AF (PD/BD/105823/2014), ARC (SFRH/BD/102181/2014) and SM (SFRH/BD/102585/2014), and a Post-Doc Grant attributed to BP (SFRH/BPD/108751/2015) were funded by FCT and the Programa Operacional Capital Humano (POCH/FSE)

Oxidized alginate hydrogels with the GHK peptide enhance cord blood mesenchymal stem cell osteogenesis: A paradigm for metabolomics-based evaluation of biomaterial design

Oxidized alginate hydrogels are appealing alternatives to natural alginate due to their favourable biodegradability profiles and capacity to self-crosslink with amine containing molecules facilitating functionalization with extracellular matrix cues, which enable modulation of stem cell fate, achieve highly viable 3-D cultures, and promote cell growth. Stem cell metabolism is at the core of cellular fate (proliferation, differentiation, death) and metabolomics provides global metabolic signatures representative of cellular status, being able to accurately identify the quality of stem cell differentiation. Herein, umbilical cord blood mesenchymal stem cells (UCB MSCs) were encapsulated in novel oxidized alginate hydrogels functionalized with the glycine-histidine-lysine (GHK) peptide and differentiated towards the osteoblastic lineage. The ADA-GHK hydrogels significantly improved osteogenic differentiation compared to gelatin-containing control hydrogels, as demonstrated by gene expression, alkaline phosphatase activity and bone extracellular matrix deposition. Metabolomics revealed the high degree of metabolic heterogeneity in the gelatin-containing control hydrogels, captured the enhanced osteogenic differentiation in the ADA-GHK hydrogels, confirmed the similar metabolism between differentiated cells and primary osteoblasts, and elucidated the metabolic mechanism responsible for the function of GHK. Our results suggest a novel paradigm for metabolomics-guided biomaterial design and robust stem cell bioprocessing. STATEMENT OF SIGNIFICANCE: Producing high quality engineered bone grafts is important for the treatment of critical sized bone defects. Robust and sensitive techniques are required for quality assessment of tissue-engineered constructs, which result to the selection of optimal biomaterials for bone graft development. Herein, we present a new use of metabolomics signatures in guiding the development of novel oxidised alginate-based hydrogels with umbilical cord blood mesenchymal stem cells and the glycine-histidine-lysine peptide, demonstrating that GHK induces stem cell osteogenic differentiation. Metabolomics signatures captured the enhanced osteogenesis in GHK hydrogels, confirmed the metabolic similarity between differentiated cells and primary osteoblasts, and elucidated the metabolic mechanism responsible for the function of GHK. In conclusion, our results suggest a new paradigm of metabolomics-driven design of biomaterials

Cognitive decline in patients with prostate cancer: study protocol of a prospective cohort, NEON-PC

Introduction: Prostate cancer is the most prevalent oncological disease among men in industrialised countries. Despite the high survival rates, treatments are often associated with adverse effects, including metabolic and cardiovascular complications, sexual dysfunction and, to a lesser extent, cognitive decline. This study was primarily designed to evaluate the trajectories of cognitive performance in patients with prostate cancer, and to quantify the impact of the disease and its treatments on the occurrence of cognitive decline. Methods: Participants will be recruited from two main hospitals providing care to approximately half of the patients with prostate cancer in Northern Portugal (Portuguese Institute of Oncology of Porto and São João Hospital Centre), and will comprise a cohort of recently diagnosed patients with prostate cancer proposed for different treatment plans, including: (1) radical prostatectomy; (2) brachytherapy and/or radiotherapy; (3) radiotherapy in combination with androgen deprivation therapy and (4) androgen deprivation therapy (with or without chemotherapy). Recruitment began in February 2018 and is expected to continue until the first semester of 2021. Follow-up evaluations will be conducted at 1, 3, 5, 7 and 10 years. Sociodemographic, behavioural and clinical characteristics, anxiety and depression, health literacy, health status, quality of life, and sleep quality will be assessed. Blood pressure and anthropometrics will be measured, and a fasting blood sample will be collected. Participants' cognitive performance will be evaluated before treatments and throughout follow-up (Montreal Cognitive Assessment and Cube Test as well as Brain on Track for remote monitoring). All participants suspected of cognitive impairment will undergo neuropsychological tests and clinical observation by a neurologist. Ethics and dissemination: The study was approved by the Ethics Committee of the hospitals involved. All participants will provide written informed consent, and study procedures will be developed to ensure data protection and confidentiality. Results will be disseminated through publication in peer-reviewed journals and presentation in scientific meetings.This study was funded by FEDER through the Operational Programme Competitiveness and Internationalisation and national funding from the Foundation for Science and Technology-FCT (Portuguese Ministry of Science, Technology and Higher Education) under the project ‘NEON-PC - Neuro-oncological complications of prostate cancer: longitudinal study of cognitive decline’ (POCI-01-0145-FEDER-032358; Ref. PTDC/SAU-EPI/32358/2017), and the Unidade de Investigação em Epidemiologia - Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB/04750/2020/PT) financed by national funds from FCT. SM was funded under the scope of the project ‘NEON-PC - Neuro-oncological complications of prostate cancer: longitudinal study of cognitive decline’ (POCI-01-0145-FEDER-032358; Ref. PTDC/SAU-EPI/32358/2017). Individual PhD grants attributed to ARC (SFRH/BD/102181/2014) and NA (SFRH/BD/119390/2016) were funded by FCT and the ‘Programa Operacional Capital Humano’ (POCH/FSE)

Effects of sea level rise on salinity and tidal flooding patterns in the Guadiana Estuary

Sea level rise is a worldwide concern as a high percentage of the population accommodates coastal areas. The focus of this study is the impact of sea level rise in the Guadiana Estuary, an estuary in the Iberian Peninsula formed at the interface of the Guadiana River and the Gulf of Cadiz. Estuaries will be impacted by sea level rise as these transitional environments host highly diverse and complex marine ecosystems. The major consequences of sea level rise are the intrusion of salt from the sea into fresh water and an increase in flooding area. As the physical, chemical, and biological components of estuaries are sensitive to changes in salinity, the purpose of this study is to further evaluate salt intrusion in the Guadiana Estuary caused by sea level rise. Hydrodynamics of the Guadiana Estuary were simulated in a two-dimensional numerical model with the MOHID water modeling system. A previously developed hydrodynamic model was implemented to further examine changes in salinity distribution in the estuary in response to sea level rise. Varying tidal amplitudes, freshwater discharge from the Guadiana River and bathymetries of the estuary were incorporated in the model to fully evaluate the impacts of sea level rise on salinity distribution and flooding areas of the estuary. Results show an overall increase in salinity and land inundation in the estuary in response to sea level rise.info:eu-repo/semantics/publishedVersio

The effects of chronic stress on hippocampal adult neurogenesis and dendritic plasticity are reversed by selective MAO-A inhibition.

Online first version - Oct 14, 2014There is accumulating evidence that adult neurogenesis and dendritic plasticity in the hippocampus are neuroplastic phenomena, highly sensitive to the effects of chronic stress and treatment with most classes of antidepressant drugs, being involved in the onset and recovery from depression. However, the effects of antidepressants that act through the selective inhibition of monoamine oxidase subtype A (MAO-A) in these phenomena are still largely unknown. In the present study, adult neurogenesis and neuronal morphology were examined in the hippocampus of rats exposed to chronic mild stress (CMS) and treated with the selective reversible MAO-A inhibitor (RIMA) drug, pirlindole and the selective serotonin reuptake inhibitor (SSRI), fluoxetine. The results provide the first demonstration that selective MAO-A inhibition with pirlindole is able to revert the behavioural effects of stress exposure while promoting hippocampal adult neurogenesis and rescuing the stress-induced dendritic atrophy of granule neurons.This research was funded by a collaborative research project established between ICVS and Grupo Tecnimede

Utility of Pacemaker With Sleep Apnea Monitor to Predict Left Ventricular Overload and Acute Decompensated Heart Failure

Pacemakers with sleep apnea monitor (SAM) provide an easy tool to assess obstructive sleep apnea over long periods of time. The link between respiratory disturbances at night and the incidence of acute decompensated heart failure (ADHF) is not well established. We aimed at (1) determining the ability of SAM pacemakers to evaluate the extent of left ventricular overload and (2) assess the impact of respiratory disturbances at night on the occurrence of ADHF over 1-year of follow-up. We conducted a single-center prospective study. Consecutive patients with SAM pacemakers were comprehensively assessed. SAM automatically computes a respiratory disturbance index (RDI, apneas/hypopneas per hour - AH/h) in the previous night and the percentage of nights with RDI >20 AH/h in the previous 6 months. Thirty-seven patients were included (79.3 ± 11.2 years, 46% males). A high RDI in the previous night and a higher %nights with increased RDI were associated with increased NT-proBNP values (p = 0.008 and p = 0.013, respectively) and were the sole predictors of increased noninvasive pulmonary capillary wedge pressures (PCWP) in the morning of assessment (p = 0.031 and p = 0.044, respectively). Receiver operating characteristic curve analysis revealed an area under the curve of 0.804 (95% confidence interval 0.656 to 0.953, p = 0.002) for %nights with RDI >20 AH/h in the prediction of high PCWP. Patients with >12.5% of nights with RDI >20AH/h tended to have more ADHF during follow-up (log-rank p = 0.067). In conclusion, a high burden of apneas/hypopneas at night is associated with elevated NT-proBNP and PCWP values and an increased risk of ADHF over 1 year. These patients might benefit from early tailored clinical management

Cis and Trans Effects of Human Genomic Variants on Gene Expression

This work was funded by the Louis-Jeantet Foundation (http://www.jeantet.ch/), the European Research Council (Grant ID: 260927 http://erc.europa.eu/), the Swiss National Foundation (Grant ID: 130342 http://www.snf.ch), NCCR Frontiers In Genetics (http://www.frontiers-in-genetics.org), the UK Medical Research Council (http://www.mrc.ac.uk) and the Wellcome Trust (Grant ID: 092731).