Effects of ultraviolet radiation to Solea senegalensis during early development

Ultraviolet radiation (UVR) reaching the Earth surface is increasing and scarce information is available regarding effects of this stressor to early life stages of marine vertebrates. Therefore, this work aims to study the effects of UVR exposure during early development stages of the flatfish Solea senegalensis. Firstly, fish were exposed to UVR (six daily doses between 3.4 ± 0.08 and 8.6 ± 0.14 kJ m-2) at the following moments: gastrula stage (24 h post fertilization, hpf), 1 and 2 days after hatching (dah, 48 and 72 hpf, respectively). In a second bioassay, fish at the beginning of metamorphosis were exposed to UVR (one or two daily doses of 7.2 ± 0.39 or 11.1 ± 0.49 kJ m-2) and then maintained until the end of metamorphosis. Mortality and effects on development, growth and behaviour were evaluated at the end of both bioassays (3 dah and 18 dah, respectively). Biomarkers of neurotransmission (acetylcholinesterase, AChE), oxidative stress (catalase, CAT) and biotransformation (glutathione S-transferase, GST) were also determined at the end of the early larvae bioassay, and metamorphosis progression was evaluated during the second bioassay. UVR exposure caused distinct effects depending on life stage. Altered pigmentation, decreased growth, impaired fish behaviour and AChE and GST inhibition were observed at the earlier larval phase. Whereas, decrease in growth was the main effect observed at the metamorphosis stage. In summary, the exposure of S. senegalensis early stages to environmentally relevant UVR doses led to adverse responses at different levels of biological organization, which might lead to implications in later life stages.publishe

Fiber Fabry-Perot interferometer for curvature sensing

A curvature sensor based on an Fabry-Perot (FP) interferometer was proposed. A capillary silica tube was fusion spliced between two single mode fibers, producing an FP cavity. Two FP sensors with different cavity lengths were developed and subjected to curvature and temperature. The FP sensor with longer cavity showed three distinct operating regions for the curvature measurement. Namely, a linear response was shown for an intermediate curvature radius range, presenting a maximum sensitivity of 68.52 pm/m-1. When subjected to temperature, the sensing head produced a similar response for different curvature radii, with a sensitivity varying from 0.84 pm/°C to 0.89 pm/°C, which resulted in a small cross-sensitivity to temperature when the FP sensor was subjected to curvature. The FP cavity with shorter length presented low sensitivity to curvature

Diabetic and Elder Patients Experience Superior Cardiovascular Benefits After Gastric Bypass Induced Weight Loss

Background/Objetives: Obesity and obesity related co-morbidities are well-recognized risks for cardiovascular (CV) disease and mortality. Weight loss improves CV risk factors and the efficacy of bariatric surgery in decreasing CV mortality is now well-established. Our aim was to assess CV risk progression and occurrence of CV events in a cohort of patients that underwent Roux-en-Y gastric bypass (RYGB) for obesity treatment in a single academic public center.Subjects and Methods: Ten year CV risk was estimated using the Framingham Equation at baseline and 2 years after RYGB surgery in our patients cohort (n = 260). In the subgroup with a follow-up time longer than 4 years after surgery (n = 185; mean 5.4 ± 0.1 years), CV risk adjusted for the time length after RYGB was similarly estimated and the occurrence of CV events for outcome adjudication was monitored during the same time period by reviewing the hospital patients' record, the electronic national health system patient register and our center outpatient clinic records.Results: Ten year CV risk was significantly reduced 2 years after surgery when compared to baseline, with reductions of 1.65 ± 0.25% in the risk of CV disease. Patients with prior type 2 diabetes and aged 50 years or older experienced a significantly superior CV risk reduction, with diabetic patients experiencing a reduction of their 10–year CV disease risk of 3.58 ± 1.11% vs. a reduction of 1.31 ± 0.20% in non-diabetic patients and with the 10–year risk of CV disease dropping 3.41 ± 0.75% in patients older than 50 vs. a reduction of 0.99 ± 0.18 in patients up to 50 years. For the subgroup of patients with a longer follow-up time, baseline CV risk estimation predicted the occurrence of 6.08 ± 0.56 cardiovascular disease (CVD) events, 3.87 ± 0.39 coronary heart disease (CHD) events, 1.49 ± 0.22 myocardial infarctions (MI), 0.71 ± 0.09 strokes, 0. 28 ± 0.05 deaths from CHD and 0.35 ± 0.05 deaths from CVD. No CV events were adjudicated in this subgroup during follow-up.Conclusions: RYGB significantly improves CV risk and prevents the occurrence of CV events. For similar weight loss, diabetic and elder patients experience a superior CV risk improvement and may have additional CV benefits after bariatric surgery

Assay optimisation and age-related baseline variation in biochemical markers in lesser black-backed gulls

Free-ranging animals are often used as bioindicators of both short- and long-term changes in ecosystem health, mainly to detect the presence and effects of contaminants. Birds, and gulls in particular, have been used as bioindicators over a broad range of marine and terrestrial ecosystems. In this study, we standardise the conditions for the use of a suite of biochemical markers in non-destructive matrices of Lesser Black-backed Gull (Larus fuscus) to facilitate future biomonitoring of marine and terrestrial contaminants. We characterized cholinesterase (ChE) in plasma and optimized assay conditions for ChE activity as a marker of neurotoxic damage. Moreover, we quantified variation in activity of ChE, lactate dehydrogenase (LDH), glutathione-S-transferase (GST) and catalase (CAT) as well as variation ranges of lipid peroxidation (LPO), in free-ranging adults and captive chicks. The main ChE form present in plasma of both adults and chicks was butyrylcholinesterase (BChE) followed by acetylcholinesterase (AChE), whose relative proportion in plasma tended to decrease with increased chick age. LPO levels and GST activity in blood cells (BCs) decreased significantly with increasing chick age, while BChE and LDH activity in plasma were not age-dependent. CAT in BCs tended to decline non-significantly in older chicks. Results of this study underscore the importance of standardising assay conditions and assessing intrinsic baseline variation in biochemical markers, before biochemical quantification. Data presented here provide a foundation for future use of BChE and LDH activity in plasma, as well as oxidative stress markers (LPO, CAT and GST) in BCs, to monitor environmental stress effects in Lesser Black-backed gulls

Tlx3 exerts direct control in specifying excitatory over inhibitory neurons in the dorsal spinal cord

© 2021 Monteiro, Miranda, Samina, Dias, Raposo, Oliveira, Reguenga, Castro and Lima. 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) and the copyright owner(s) 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.The spinal cord dorsal horn is a major station for integration and relay of somatosensory information and comprises both excitatory and inhibitory neuronal populations. The homeobox gene Tlx3 acts as a selector gene to control the development of late-born excitatory (dILB) neurons by specifying glutamatergic transmitter fate in dorsal spinal cord. However, since Tlx3 direct transcriptional targets remain largely unknown, it remains to be uncovered how Tlx3 functions to promote excitatory cell fate. Here we combined a genomics approach based on chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq) and expression profiling, with validation experiments in Tlx3 null embryos, to characterize the transcriptional program of Tlx3 in mouse embryonic dorsal spinal cord. We found most dILB neuron specific genes previously identified to be directly activated by Tlx3. Surprisingly, we found Tlx3 also directly represses many genes associated with the alternative inhibitory dILA neuronal fate. In both cases, direct targets include transcription factors and terminal differentiation genes, showing that Tlx3 directly controls cell identity at distinct levels. Our findings provide a molecular frame for the master regulatory role of Tlx3 in developing glutamatergic dILB neurons. In addition, they suggest a novel function for Tlx3 as direct repressor of GABAergic dILA identity, pointing to how generation of the two alternative cell fates being tightly coupled.This work is a result of the project Norte-01-0145-FEDER-000008 – Porto Neurosciences and Neurologic Disease Research Initiative at I3S, supported by Norte Portugal Regional Operational Program (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). This work was also supported by FCT – Fundação para a Ciência e Tecnologia (Grants PTDC/SAU-OBD/099886/2008 to DL and PTDC/NEU-NMC/0315/2012 to DC) and Universidade do Porto/Banco Santander Totta (Projetos Pluridisciplinares to FM). We acknowledge the support of POCI-01-0145-FEDER-022122, granted to i3S Scientific Platform Advanced Light Microscopy, member of the national infrastructure PPBI-Portuguese Platform of BioImaging.info:eu-repo/semantics/publishedVersio

In vitro protective effect and antioxidant mechanism of Resveratrol induced by Dapsone Hydroxylamine in human cells

Dapsone (DDS) hydroxylamine metabolites cause oxidative stress- linked adverse effects in patients, such as methemoglobin formation and DNA damage. This study evaluated the ameliorating effect of the antioxidant resveratrol (RSV) on DDS hydroxylamine (DDSNHOH) mediated toxicity in vitro using human erythrocytes and lymphocytes. The antioxidant mechanism was also studied using in-silico methods. In addition, RSV provided intracellular protection by inhibiting DNA damage in human lymphocytes induced by DDS-NHOH. However, whilst pretreatment with RSV (10-1000 μM significantly attenuated DDS-NHOH-induced methemoglobinemia, but it was not only significantly less effective than methylene blue (MET), but also post-treatment with RSV did not reverse methemoglobin formation, contrarily to that observed with MET. DDS-NHOH inhibited catalase (CAT) activity and reactive oxygen species (ROS) generation, but did not alter superoxide dismutase (SOD) activity in erythrocytes. Pretreatment with RSV did not alter these antioxidant enzymes activities in erythrocytes treated with DDS-NHOH. Theoretical calculations using density functional theory methods showed that DDS-NHOH has a pro-oxidant effect, whereas RSV and MET have antioxidant effect on ROS. The effect on methemoglobinemia reversion for MET was significantly higher than that of RSV. These data suggest that the pretreatment with resveratrol may decrease heme-iron oxidation and DNA damage through reduction of ROS generated in cells during DDS therapy

Beyond restrictive: Sleeve Gastrectomy to Single Anastomosis Duodenoileal Bypass with Sleeve Gastrectomy as a spectrum of one single procedure

Introduction: Single Anastomosis Duodenal-Ileal Bypass with Sleeve Gastrectomy (SADI-S) is a restrictive/hypoabsorptive procedure recommended for patients with obesity class 3. For safety reasons, SADI-S can be splited into a two-step procedure by performing a sleeve gastrectomy (SG) first. This stepwise approach also provides an unprecedented opportunity to disentangle the weight loss mechanisms triggered by each component. The objective was to compare weight trajectories and postprandial endocrine and metabolic responses of patients with obesity class 3 submitted to SADI-S or sleeve gastrectomy (SG) as the first step of SADI-S. Methods: Subjects submitted to SADI-S (n=7) or SG (n=7) at a tertiary referral public academic hospital, underwent anthropometric evaluation and a liquid mixed meal tolerance test (MMTT) pre-operatively and at 3, 6, and 12 months post-operatively. Results: Anthropometric parameters, as well as metabolic and micronutrient profiles, were not significantly different between groups, neither before nor after surgery. There were no significant differences in fasting or post-prandial glucose, insulin, C-peptide, ghrelin, insulin secretion rate (ISR) and insulin clearance during the MMTT between subjects submitted to SADI-S and SG. There was no lost to follow-up. Conclusions: The restrictive component seems to be the main driver for weight loss and metabolic adaptations observed during the first 12 months after SADI-S, given that the weight trajectories and metabolic profiles do not differ from SG. This data provides support for a surgeons’ choice of a two-step SADI-S without jeopardizing the weight loss outcomes

The use of comet assay to assess global DNA methylation in human biomonitoring studies

The Comet assay is a valuable tool for the detection of DNA damage in genotoxicity and human biomonitoring studies. Throughout the years, this biomarker has undergone several adaptations in their protocol in order to increase its sensitivity and the possible outcomes. By including an additional step of DNA digestion with lesion-specific endonucleases, the comet assay can provide information regarding the type of DNA damage detected in cells. The use of these enzymes has also allowed the development of a methylation-sensitive modified version of the comet assay. This version enables the routine measurement of global methylation, as well as CpG island DNA methylation in a variety of cells while simultaneously determining the genetic integrity of examined cells (Wentzel, 2012). Briefly, it makes use of isochizomeric restriction enzymes HpaII and MspI (that display differential sensitivity to DNA methylation) to characterize methylation outside CpG islands and restriction enzyme NotI to determine DNA methylation in CpG islands. The technique has been recently adapted to a medium-throughput version (Lewies, 2014) that allows the simultaneous analysis of a larger number of samples and overcomes some technical problems. Nevertheless, this technique has not yet been carried out in human biomonitoring studies. In this context, the aim of this work was to make use of this version of the comet assay to characterize global DNA methylation in approximately 50 human samples. Samples were analysed by the methylation-sensitive modified version of the comet assay (medium-throughput) and by ELISA based assay. Data obtained with both methods were compared and reproducibility of the methylation-sensitive modified version of the comet assay determined. Results obtained contribute to knowledge on the feasibility of this version of the comet assay and its possible usage in human biomonitoring studies as an epigenetic biomarker.This work was supported by The Portuguese Science Foundation (FCT) through CESAM (UID/AMB/50017/2013) and CNRS/INEE - National Center for Scientific Research/Institute of Ecology and Environment, via OHMI – International Observatory Hommes-Millieux. Carla Costa and Marta S. Monteiro are supported by the grants SFRH/BPD/96196/2013 and SFRH/BPD/45911/2008, respectively, funded by FCT (QREN – POPH – Type 4.1 – Advanced training, subsidized by the European Social Fund and national funds of MEC)

Effects of Fluoride on Submandibular Glands of Mice: Changes in Oxidative Biochemistry, Proteomic Profile, and Genotoxicity

Although fluoride (F) is well-known to prevent dental caries, changes in cell processes in different tissues have been associated with its excessive exposure. Thus, this study aimed to evaluate the effects of F exposure on biochemical, proteomic, and genotoxic parameters of submandibular glands. Twenty one old rats (n = 30) were allocated into three groups: 60 days administration of drinking water containing 10 mgF/L, 50 mgF/L, or only deionized water (control). The submandibular glands were collected for oxidative biochemistry, protein expression profile, and genotoxic potential analyses. The results showed that both F concentrations increased the levels of thiobarbituric acid–reactive substances (TBARS) and reduced glutathione (GSH) and changed the proteomic profile, mainly regarding the cytoskeleton and cellular activity. Only the exposure to 50 mgF/L induced significant changes in DNA integrity. These findings reinforce the importance of continuous monitoring of F concentration in drinking water and the need for strategies to minimize F intake from other sources to obtain maximum preventive/therapeutic effects and avoid potential adverse effects

Quality of life in caregivers of patients with multiple myeloma

Objectives: This study aimed to assess the relationship between sociodemographic, clinical, and psychological variables with quality of life (QoL) and the moderating role of caregivers' age and caregiving duration in caregivers of patients with Multiple Myeloma.Method: The sample included 118 caregivers who completed questionnaires that assessed psychological morbidity, satisfaction with social support, coping, burden, unmet needs, and QoL.Results: High psychological morbidity, burden and information, financial and emotional unmet needs were associated with lower QoL, while higher satisfaction with social support and more effective use of coping strategies were associated with better QoL. Women caregivers reported more satisfaction with social support and those who did not choose to care reported greater financial unmet needs and more use of coping strategies. The relationship between caregivers' psychological morbidity/social support and QoL was mediated by emotional needs and double mediated by coping and burden. The caregivers' age moderated the relationship between psychological morbidity/social support and emotional needs.Conclusion: Interventions to support the caregiver's emotional needs to promote their QoL are needed. These should be particularly tailored for older caregivers reporting greater psychological morbidity and younger caregivers less satisfied with their social support, as they have a negative indirect impact on their QoL.Portuguese Associations of Portuguese Association against Leukemia and the PortugueseAssociation of Leukemias and Lymphoma