Estimating the Underwater Diffuse Attenuation Coefficient with a Low-Cost Instrument: The KdUINO DIY Buoy

A critical parameter to assess the environmental status of water bodies is the transparency of the water, as it is strongly affected by different water quality related components (such as the presence of phytoplankton, organic matter and sediment concentrations). One parameter to assess the water transparency is the diffuse attenuation coefficient. However, the number of subsurface irradiance measurements obtained with conventional instrumentation is relatively low, due to instrument costs and the logistic requirements to provide regular and autonomous observations. In recent years, the citizen science concept has increased the number of environmental observations, both in time and space. The recent technological advances in embedded systems and sensors also enable volunteers (citizens) to create their own devices (known as Do-It-Yourself or DIY technologies). In this paper, a DIY instrument to measure irradiance at different depths and automatically calculate the diffuse attenuation Kd coefficient is presented. The instrument, named KdUINO, is based on an encapsulated low-cost photonic sensor and Arduino (an open-hardware platform for the data acquisition). The whole instrument has been successfully operated and the data validated comparing the KdUINO measurements with the commercial instruments. Workshops have been organized with high school students to validate its feasibility

An analytical solver for the multi-group two-dimensional neutron-diffusion equation by integral transform techniques

In this work, we present an analytical solver for neutron diffusion in a rectangular two-dimensional geometry by a two-step integral transform procedure. To this end, we consider a regionwise homogeneous problem for two energy groups, i.e. fast and thermal neutrons, respectively. Each region has its specific physical properties, specified by cross-sections and diffusion constants. The problem is set up by two coupled bi-dimensional diffusion equations in agreement with general perturbation theory. These are solved by integral transforms Laplace transform and generalized integral transform technique yielding analytical expressions for the scalar neutron fluxes. The solutions for neutron fluxes are presented for fast and thermal neutrons in the four regions

Ripretinib in gastrointestinal stromal tumor: the long-awaited step forward

Ripretinib; Sarcoma; Inhibidor de la tirosina cinasaRipretinib; Sarcoma; Inhibidor de la tirosina quinasaRipretinib; Sarcoma; Tyrosine kinase inhibitorGastrointestinal stromal tumor (GIST) represents a paradigm for clinically effective targeted inhibition of oncogenic driver mutations in cancer. Five drugs are currently positioned as the standard of care for the treatment of advanced or metastatic GIST patients. This is the result of continuous, deep understanding of KIT and PDGFRA GIST oncogenic drivers as well as the resistance mechanisms associated to tumor progression. However, the complexity of GIST molecular heterogeneity is an evolving field, and critical questions remain open. Specifically, the clinical benefit of approved and/or investigated targeted agents is strikingly modest at advanced stages of the disease when compared with the activity of first-line imatinib. Ripretinib is a novel switch-pocket inhibitor with broad activity against KIT and PDGFRA oncoproteins and has recently demonstrated antitumoral activity across phase I to phase III clinical trials. Therefore, ripretinib has emerged as a new standard of care for advanced, multi-resistant GIST patients. Based on this data, the Food and Drug Administration has granted in 2020 the approval of ripretinib for GIST patients after progression to imatinib, sunitinib and regorafenib. This, in turn, constitutes a major breakthrough in sarcoma drug development, as there have not been new treatment approvals in GIST for nearly a decade. Herein, we provide a critical review on the preclinical and clinical development of ripretinib in GIST. Furthermore, we seek to assess the biological and clinical impact of this new standard of care on the course of the disease, aiming to provide an insight on future treatments strategies for the next coming years.The authors received no financial support for the research, authorship, and/or publication of this article

Bluetooth Mesh Analysis, Issues, and Challenges

BLE is a widely used short-range technology which has gained a relevant position inside the Internet-of-Things (IoT) paradigm development thanks to its simplicity, low-power consumption, low-cost and robustness. New enhancements over BLE have focused on supporting mesh network topology. Compared to other mesh networks, BLE mesh has only considered a managed flooding protocol in its first version. Managed flooding may generally seem inefficient in many contexts, but it is a high desirable option when data transmission is urgent, the network is small or its configuration changes in a very dynamic way. Knowing the interest to many application contexts, this paper analyses the impact of tweaking several features over the reliability and efficiency of the mesh network. These features are configured and controlled in different layers: message repetition schemes, the transmission randomization, the election of a scheme based on an acknowledged or unacknowledged transmission, etc. In order to estimate the real performance of a mesh network deployment, this paper evaluates the effects of the interaction of the chosen parameters, their appropriate adjustment in relation with the characteristics of real implementations and the true overhead related to the whole protocol stack. The paper identifies configuration challenges, proposes network tuning criteria and outlines possible standard improvements. For this purpose, a detailed assessment on the implementation and execution of real devices has been performed with their chipset limitations

Amidated and ibuprofen-conjugated kyotorphins promote neuronal rescue and memory recovery in cerebral hypoperfusion dementia model

Copyright © 2016 Sá Santos, Santos, Pinto, Ramu, Heras, Bardaji, Tavares and Castanho. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Chronic brain ischemia is a prominent risk factor for neurological dysfunction and progression for dementias, including Alzheimer's disease (AD). In rats, permanent bilateral common carotid artery occlusion (2VO) causes a progressive neurodegeneration in the hippocampus, learning deficits and memory loss as it occurs in AD. Kyotorphin (KTP) is an endogenous antinociceptive dipeptide whose role as neuromodulator/neuroprotector has been suggested. Recently, we designed two analgesic KTP-derivatives, KTP-amide (KTP-NH2) and KTP-NH2 linked to ibuprofen (IbKTP-NH2) to improve KTP brain targeting. This study investigated the effects of KTP-derivatives on cognitive/behavioral functions (motor/spatial memory/nociception) and hippocampal pathology of female rats in chronic cerebral hypoperfusion (2VO-rat model). 2VO-animals were treated with KTP-NH2 or IbKTP-NH2 for 7 days at weeks 2 and 5 post-surgery. After behavioral testing (week 6), coronal sections of hippocampus were H&E-stained or immunolabeled for the cellular markers GFAP (astrocytes) and NFL (neurons). Our findings show that KTP-derivatives, mainly IbKTP-NH2, enhanced cognitive impairment of 2VO-animals and prevented neuronal damage in hippocampal CA1 subfield, suggesting their potential usefulness for the treatment of dementia.Funding was provided by the Portuguese Agency Fundação para a Ciência e a Tecnologia SFRH/BPD/79542/2011 fellowship)info:eu-repo/semantics/publishedVersio

TCA cycle metabolites associated with adverse outcomes after acute coronary syndrome: mediating effect of renal function

AimsTo examine relationships of tricarboxylic acid (TCA) cycle metabolites with risk of cardiovascular events and mortality after acute coronary syndrome (ACS), and evaluate the mediating role of renal function in these associations.MethodsThis is a prospective study performed among 309 ACS patients who were followed for a mean of 6.7 years. During this period 131 patients developed major adverse cardiovascular events (MACE), defined as the composite of myocardial infarction, hospitalization for heart failure, and all-cause mortality, and 90 deaths were recorded. Plasma concentrations of citrate, aconitate, isocitrate, succinate, malate, fumarate, α-ketoglutarate and d/l-2-hydroxyglutarate were quantified using LC-tandem MS. Multivariable Cox regression models were used to estimate hazard ratios, and a counterfactual-based mediation analysis was performed to test the mediating role of estimated glomerular filtration rate (eGFR).ResultsAfter adjustment for traditional cardiovascular risk factors and medications, positive associations were found between isocitrate and MACE (HR per 1 SD, 1.25; 95% CI: 1.03, 1.50), and between aconitate, isocitrate, d/l-2-hydroxyglutarate and all-cause mortality (HR per 1 SD, 1.41; 95% CI: 1.07, 1.84; 1.58; 95% CI: 1.23, 2.02; 1.38; 95% CI: 1.14, 1.68). However, these associations were no longer significant after additional adjustment for eGFR. Mediation analyses demonstrated that eGFR is a strong mediator of these associations.ConclusionThese findings underscore the importance of TCA metabolites and renal function as conjunctive targets in the prevention of ACS complications

Corrigendum: Chronic Exposure to Malaria Is Associated with Inhibitory and Activation Markers on Atypical Memory B Cells and Marginal Zone-Like B Cells

[This corrects the article DOI: 10.3389/fimmu.2017.00966.]

The Neuroprotective Action of Amidated-Kyotorphin on Amyloid β Peptide-Induced Alzheimer’s Disease Pathophysiology

Kyotorphin (KTP, l-tyrosyl-l-arginine) is an endogenous dipeptide initially described to have analgesic properties. Recently, KTP was suggested to be an endogenous neuroprotective agent, namely for Alzheimer’s disease (AD). In fact, KTP levels were shown to be decreased in the cerebrospinal fluid of patients with AD, and recent data showed that intracerebroventricular (i.c.v.) injection of KTP ameliorates memory impairments in a sporadic rat model of AD. However, this administration route is far from being a suitable therapeutic strategy. Here, we evaluated if the blood-brain permeant KTP-derivative, KTP-NH2, when systemically administered, would be effective in preventing memory deficits in a sporadic AD animal model and if so, which would be the synaptic correlates of that action. The sporadic AD model was induced in male Wistar rats through i.c.v. injection of amyloid β peptide (Aβ). Animals were treated for 20 days with KTP-NH2 (32.3 mg/kg, intraperitoneally (i.p.), starting at day 3 after Aβ administration) before memory testing (Novel object recognition (NOR) and Y-maze (YM) tests). Animals were then sacrificed, and markers for gliosis were assessed by immunohistochemistry and Western blot analysis. Synaptic correlates were assessed by evaluating theta-burst induced long term potentiation (LTP) of field excitatory synaptic potentials (fEPSPs) recorded from hippocampal slices and cortical spine density analysis. In the absence of KTP-NH2 treatment, Aβ-injected rats had clear memory deficits, as assessed through NOR or YM tests. Importantly, these memory deficits were absent in Aβ-injected rats that had been treated with KTP-NH2, which scored in memory tests as control (sham i.c.v. injected) rats. No signs of gliosis could be detected at the end of the treatment in any group of animals. LTP magnitude was significantly impaired in hippocampal slices that had been incubated with Aβ oligomers (200 nM) in the absence of KTP-NH2. Co-incubation with KTP-NH2 (50 nM) rescued LTP toward control values. Similarly, Aβ caused a significant decrease in spine density in cortical neuronal cultures, and this was prevented by co-incubation with KTP-NH2 (50 nM). In conclusion, the present data demonstrate that i.p. KTP-NH2 treatment counteracts Aβ-induced memory impairments in an AD sporadic model, possibly through the rescuing of synaptic plasticity mechanisms.publishersversionpublishe

Prevalence and prognostic implications of myocardial injury across different waves of COVID-19

IntroductionThe prognostic ability of myocardial injury across different waves of the COVID-19 pandemic is not well established. The purpose of this study was to evaluate the prevalence and prognostic implications of myocardial injury in the first and sixth wave of COVID-19.MethodsWe conducted a retrospective observational study that included patients admitted to the emergency department with COVID-19 with data on concentrations of cardiac troponin during the first and sixth wave. We compared the prevalence of myocardial injury and its predictive capacity for 30-day all-cause death in both waves.Results and discussionA total of 346 patients were included (1st wave 199 and 6th wave 147 patients). The prevalence of myocardial injury was 21% with non-significant differences between waves. Myocardial injury was associated, in both waves, with a higher prevalence of comorbidities and with an increased risk of 30-day all-cause death [1st wave HR: 3.73 (1.84–7.55); p < 0.001 and 6th wave HR: 3.13 (1.23–7.92); p = 0.016], with non-significant differences in predictive capacity between groups after ROC curve analysis [AUC: 1st wave 0.829 (95% CI: 0.764–0.895) and 6th wave 0.794 (95% CI: 0.711–0.876)]. As limitations, this is a retrospective study with a relatively small simple size and troponin assay was performed at the discretion of the emergency physician so selection bias could be present. In conclusion, the prevalence of myocardial injury and its prognostic capacity was similar in both waves despite vaccination programs. Myocardial injury predicts short-term mortality in all COVID-19 patients, so they should be treated intensively