Metabolic miscommunication among organs: The missing links

Funding Information: The authors were funded by Fundação para a Ciência e Tecnologia (FCT), FEDER, Portugal2020, and co-financed by Lisboa2020 and Alentejo2020 (ALT20-03-0247-FEDER-113469 and LISBOA-01-0247-FEDER-113469), iNOVA4Health (UIDB/Multi/04462/2020), and by the Sociedade Portuguesa de Diabetologia, Acknowledgmentspublishersversionpublishe

Indoor tracking from multidimensional sensor data

Tracking the position of people or vehicles in large indoor settings with high accuracy is still a challenge despite the significant progress observed in indoor positioning technology in the last decade. To date, there is not a clearly dominant indoor positioning solution for general use, and challenges related to seamless indoor-outdoor positioning, reliable floor estimation and indoor maps are still needing more research. In this context, the IPIN 2016 conference is promoting a competition to evaluate a set of competing indoor positioning solutions in a realistic scenario. This paper describes the proposal of the UMINHO team and some of the obtained results.This work has been supported by COMPETE: POCI-01- 0145-FEDER-007043 and FCT – Fundação para a Ciência e Tecnologia within the Project Scope: UID/CEC/00319/2013

An integrated view

Funding Information: This work was supported by “Fundação para a Ciência e a Tecnologia”—FCT MJM (PD/BD/114256/2016), MPM (PTDC/BIM-MET/4265/2014 and PTDC/MEC-MET/29314/2017), MGA (PTDC/BIM-MET/4712/2014), iNOVA4Health (UIDB/Multi/04462/2020), by the European Commission Marie Skłodowska-Curie Action H2020 (mtFOIE GRAS, grant agreement n. 734719), by the Sociedade Portuguesa de Diabetologia, and by the research infrastructure CONGENTO, project LISBOA-01-0145-FEDER-022170, co-financed by Lisboa Regional Operational Programme (Lisboa2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund and by Fundação para a Ciência e Tecnologia (Portugal). NMR data were collected at the UC-NMR facility which is supported in part by FEDER – European Regional Development Fund through the COMPETE Programme (Operational Programme for Competitiveness) and by National Funds through FCT – Fundação para a Ciência e a Tecnologia (Portuguese Foundation for Science and Technology) through grants REEQ/481/QUI/2006, RECI/QEQ-QFI/0168/2012, CENTRO-07-CT62-FEDER-002012, and Rede Nacional de Ressonância Magnética Nuclear (RNRMN). Publisher Copyright: Copyright © 2022 Meneses, Sousa-Lima, Jarak, Raposo, Alves and Macedo.Objective: In the last years, changes in dietary habits have contributed to the increasing prevalence of metabolic disorders, such as non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). The differential burden of lipids and fructose on distinct organs needs to be unveiled. Herein, we hypothesized that high-fat and high-fructose diets differentially affect the metabolome of insulin-sensitive organs such as the liver, muscle, and different adipose tissue depots. Methods: We have studied the impact of 12 weeks of a control (11.50% calories from fat, 26.93% from protein, and 61.57% from carbohydrates), high-fat/sucrose (HFat), or high-fructose (HFruct) feeding on C57Bl/6J male mice. Besides glucose homeostasis, we analyzed the hepatic levels of glucose and lipid-metabolism-related genes and the metabolome of the liver, the muscle, and white (WAT) and brown adipose tissue (BAT) depots. Results: HFat diet led to a more profound impact on hepatic glucose and lipid metabolism than HFruct, with mice presenting glucose intolerance, increased saturated fatty acids, and no glycogen pool, yet both HFat and HFruct presented hepatic insulin resistance. HFat diet promoted a decrease in glucose and lactate pools in the muscle and an increase in glutamate levels. While HFat had alterations in BAT metabolites that indicate increased thermogenesis, HFruct led to an increase in betaine, a protective metabolite against fructose-induced inflammation. Conclusions: Our data illustrate that HFat and HFruct have a negative but distinct impact on the metabolome of the liver, muscle, WAT, and BAT.publishersversionpublishe

Encaminhamento com QoS para redes Ad Hoc com rotas estáveis

Devido às características próprias das redes móveis ad hoc (Mobile Ad hoc Network - MANET), dotar este tipo de redes de garantias de qualidade de serviço (QoS) no tráfego fim a fim torna-se um desafio. Este artigo apresenta um protocolo de encaminhamento com QoS para redes ad hoc, que se designa por Ad hoc QoS Multipath Routing with Route Stability (QMRS), que tem como objectivo suportar aplicações com requisitos de qualidade de serviço, nomeadamente requisitos no atraso fim a fim. Este protocolo tem a possibilidade de encontrar até três rotas de nós disjuntos que cumpram o requisito de QoS. Adicionalmente e com o objectivo de garantir a estabilidade do processo de encaminhamento, usa a potência de sinal das ligações entre nós vizinhos para eleger a rota mais estável, rota essa que passa a ser usada para o reenvio do tráfego. Quando se verifica a existência de rotas com uma estabilidade idêntica, dá-se preferência à rota com menor atraso fim a fim. O protocolo detém também um mecanismo de manutenção, recuperação e verificação de incumprimento do requisito de QoS nos caminhos encontrados. Os resultados obtidos na simulação realizada permitem verificar, que o protocolo QMRS implementado, reduz o atraso fim a fim e aumenta a taxa de entrega de pacotes no destino, comparativamente com protocolo Adhoc On-Demand Distance Vector (AODV).Fundação para a Ciência e a Tecnologia (FCT

From old indexes to new technologies

Funding Information: This work was supported by FEDER, Portugal2020, and co‐financed by Lisboa2020 and Alentejo2020 (ALT20‐03‐0247‐FEDER‐113469 and LISBOA‐01‐0247‐FEDER‐113469), ‘Fundação para a Ciência e a Tecnologia’—FCT iNOVA4Health (UIDB/Multi/04462/2020), European Commission Marie Skłodowska‐Curie Action H2020 (mtFOIE GRAS, grant agreement n. 734719) and the Sociedade Portuguesa de Diabetologia. Publisher Copyright: © 2022 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.Background: Diabetes is a heterogeneous and multifactorial disease. However, glycemia and glycated hemoglobin have been the focus of diabetes diagnosis and management for the last decades. As diabetes management goes far beyond glucose control, it has become clear that assessment of other biochemical parameters gives a much wider view of the metabolic state of each individual, enabling a precision medicine approach. Methods: In this review, we summarize and discuss indexes that have been used in epidemiological studies and in the clinical practice. Results: Indexes of insulin secretion, sensitivity/resistance and metabolism have been developed and validated over the years to account also with insulin, C-peptide, triglycerides or even anthropometric measures. Nevertheless, each one has their own objective and consequently, advantages and disadvantages for specific cases. Thus, we discuss how new technologies, namely new sensors but also new softwares/applications, can improve the diagnosis and management of diabetes, both for healthcare professionals but also for caretakers and, importantly, to promote the empowerment of people living with diabetes. Conclusions: In long-term, the solution for a better diabetes management would be a platform that allows to integrate all sorts of relevant information for the person with diabetes and for the healthcare practitioners, namely glucose, insulin and C-peptide or, in case of need, other parameters/indexes at home, sometimes more than once a day. This solution would allow a better and simpler disease management, more adequate therapeutics thereby improving patients' quality of life and reducing associated costs.publishersversionepub_ahead_of_prin

Trigger and Target of Renal Functions

This work was supported by “Fundação para a Ciência e a Tecnologia” – FCT to AP (PD/BD/136887/2018); MJM (PD/BD/114256/2016), MPM (PTDC/DTP-EPI/0207/2012), DOB e MPM (PTDC/BIM-MET/2115/2014); iNOVA4Health (UIDB/Multi/04462/2020), by the European Commission Marie Skłodowska -Curie Actions H2020 (grant agreements nos. 722619 and 734719), and by the Sociedade Portuguesa de Diabetologia.Kidney function in metabolism is often underestimated. Although the word “clearance” is associated to “degradation”, at nephron level, proper balance between what is truly degraded and what is redirected to de novo utilization is crucial for the maintenance of electrolytic and acid–basic balance and energy conservation. Insulin is probably one of the best examples of how diverse and heterogeneous kidney response can be. Kidney has a primary role in the degradation of insulin released in the bloodstream, but it is also incredibly susceptible to insulin action throughout the nephron. Fluctuations in insulin levels during fast and fed state add another layer of complexity in the understanding of kidney fine-tuning. This review aims at revisiting renal insulin actions and clearance and to address the association of kidney dysmetabolism with hyperinsulinemia and insulin resistance, both highly prevalent phenomena in modern society.publishersversionpublishe

Multiple simultaneous Wi-Fi measurements in fingerprinting indoor positioning

The accuracy of fingerprinting-based positioning methods accuracy is limited by the fluctuations in the radio signal intensity mainly due to reflections, refractions, and multipath interference, among other factors. We consider that the fluctuations (often modelled as a Gaussian process for simplification purposes) can be minimized by exploiting the richness of multiple signals collected simultaneously through independent network interfaces. This paper introduces an analysis of Wi-Fi signals' statistics using simultaneous measurements which shows that RSSI values obtained from independent devices are not highly correlated. The low correlation between Wi-Fi interfaces might be exploited to improve the positioning accuracy. The validation of the proposed fingerprinting approach in a real scenario shows that the mean and maximum error in positioning can be reduced by more than 40% when five Wi-Fi interfaces are simultaneously used for fingerprinting.This work has been supported by COMPETE: POCI-01- 0145-FEDER-007043 and FCT—Fundação para a Ciência e Tecnologia within the scope of project UID/CEC/00319/2013, by the Portugal Incentive System for Research and Technological Development in the scope of the projects in co- promotion no 002814/2015 (iFACTORY 2015-2018), and by the José Castillejo mobility grant (CAS16/00072).info:eu-repo/semantics/publishedVersio

Phage engineering for the detection of Pseudomonas aeruginosa

Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium. Due to its high antibiotic resistance and capacity to adapt and survive in hostile conditions, P. aeruginosa is responsible for a wide range of human infections, such as surgical site infections, bacteremia, urinary tract infections, and mostly, pneumonia. In COVID-19 patients, P. aeruginosa is a common co-infecting pathogen, associated with increased disease severity and worse clinical outcomes. Considering the slow turnover of conventional diagnostic methods and the problems associated with the molecular and immunogenic methods, this study aimed at assembling a bioluminescence-based reporter phage for the fast and sensitive detection of P. aeruginosa in clinical care. Phage vB_PaeP_PE3 was genetically engineered using the yeast-based phage engineering platform. The genome of this phage was previously reduced by deleting genes with unknown function, and here, this phage genome was used as a scaffold for the insertion of the NanoLuc® luciferase. The gene encoding NanoLuc was swapped with gene gp55, encoding a hypothetical protein with unknown function. The sensitivity of this phage-based detection system was evaluated through the infection of serial dilutions of P. aeruginosa suspensions with the synthetic phage, and subsequent quantification of luminescence (in relative light units, RLU). Our data showed that the reporter phage was able to reliably detect 10^2 CFU in 1 mL of contaminated sample in less than 8 h. Overall, the NanoLuc-based reporter phage allows for the rapid and sensitive detection and differentiation of viable P. aeruginosa cells using a simple protocol, 45 h faster than culture-dependent approaches. Therefore, this phage-based detection system is a promising alternative to the common methods for the accurate detection of P. aeruginosa in clinical settings.info:eu-repo/semantics/publishedVersio

Fast and sensitive detection of pseudomonas aeruginosa in clinical settings using engineered reporter phages

P. aeruginosa is a bacterial pathogen responsible for a wide range of infections. As a result, the World Health Organization identified it as one of the top priority pathogens that urgently calls for the development of novel treatments. Bacteriophages have emerged as a promising therapeutic approach and their properties can be enhanced by phage-engineering. This opens an extensive variety of possibilities, allowing to assemble chimeric phages with new functions. Considering the slow turnover of conventional diagnostic methods and the problems associated with the molecular and immunogenic methods, this study aimed at assembling a bioluminescence-based reporter phage for the fast and sensitive detection of P. aeruginosa in clinical care. Using the yeast-based phage engineering platform, the phage vB_PaeP_PE3 was genetically modified by removing genes with unknown function (g1-g12) and then used as a scaffold for the insertion of the NanoLuc® luciferase gene that was swapped with gene g53. The assembled reporter phage (vB_PaeP_PE3gp1-gp12,gp53:NLuc) was then used for sensitivity and specificity assays. The detection limit was evaluated through the infection of serial dilutions of P. aeruginosa suspensions with the reporter phage, and subsequent quantification of luminescence. Our data showed that the assembled reporter phage was capable of reliably detect 500 CFU/mL within 7h or an average 1 CFU/mL after 24h, and no false positives were observed. Similar results were also obtained when the reporter phage was tested in blood, being capable of detecting an average of 8 CFU/mL within 24 hours. Overall, compared to culture-dependent methods, the NanoLuc-based reporter phage allows a fast and sensitive detection of P. aeruginosa cells using a simple protocol. Therefore, this phage-based detection system is a promising alternative to the common methods for the accurate detection of P. aeruginosa in clinical settings.info:eu-repo/semantics/publishedVersio