The consumption of antidepressants, such as fluoxetine, has increased over the years and, as a result, they are increasingly found in aquatic systems. Given the increasing use of zebrafish as an animal model in toxicological studies, this work proposed to evaluate the effects of chronic exposure, for 21 days, to fluoxetine at environmentally relevant concentrations (1, 10, 100, and 1000 ng/L). The behavioral tests performed did not reveal significant effects of fluoxetine. However, oxidative stress and changes in energy metabolism were detected after exposure to the highest concentrations of fluoxetine tested, namely a decrease in glutathione S-transferase (GST) activity (decrease of ca. 31%), increase in catalase (CAT) activity (increase of ca. 71%), and decrease in lactate dehydrogenase (LDH) activity (decrease of ca. 53%). Analysis of the fatty acid profile (FA) revealed a decrease in the omega-3 FA, docosahexaenoic acid (DHA), C22:6 (decrease in relative abundance between 6% and 8% for both the head and body), an increase in omega-6 FA, linoleic acid (LA), C18:2, (increased relative abundance between 8% and 11% in the head and between 5% and 9% in the body), which may suggest changes in the inflammatory state of these organisms. The integrated analysis adopted proved to be useful in detecting subindividual effects of fluoxetine and modes of action in fish.
Behavior, Animal , Fatty Acids , Fluoxetine , Oxidative Stress , Water Pollutants, Chemical , Zebrafish , Fluoxetine/toxicity , Animals , Water Pollutants, Chemical/toxicity , Behavior, Animal/drug effects , Oxidative Stress/drug effects , Fatty Acids/metabolism , Glutathione Transferase/metabolism , Catalase/metabolism
Atomic force microscopy (AFM) is a scanning probe microscopy technique which has a physical principle, the measurement of interatomic forces between a very thin tip and the surface of a sample, allowing the obtaining of quantitative data at the nanoscale, contributing to the surface study and mechanical characterization. Due to its great versatility, AFM has been used to investigate the structural and nanomechanical properties of several inorganic and biological materials, including neurons affected by tauopathies. Tauopathies are neurodegenerative diseases featured by aggregation of phosphorylated tau protein inside neurons, leading to functional loss and progressive neurotoxicity. In the broad universe of neurodegenerative diseases, tauopathies comprise the most prevalent, with Alzheimer's disease as its main representative. This review highlights the use of AFM as a suitable research technique for the study of cellular damages in tauopathies, even in early stages, allowing elucidation of pathogenic mechanisms of these diseases.
Alzheimer Disease , Neurodegenerative Diseases , Tauopathies , Humans , Microscopy, Atomic Force/methods , Tauopathies/metabolism , tau Proteins/metabolism , Alzheimer Disease/metabolism , Neurodegenerative Diseases/metabolism , Neurons/metabolism
Chronic non-communicable diseases are growing global health problems. The objective of this study was to promote pharmaceutical care for a patient with multimorbidities in order to improve its quality of life. A pharmacotherapeutic follow-up was performed using the SOAP method, registered in the form of clinical evolution, along with laboratory tests, anthropometric measurements and application of validated instruments to assess pharmacological adherence, mental health and quality of life. The report deals with a female patient, 55 years old, obese and dyslipidemic, sedentary, hypertensive, diabetic and on the control phase of breast cancer. Self-medication with antibiotics and a proton pump inhibitor was identified. Despite the good pharmacological adherence, the patient had decompensated diabetes, accompanied by dyslipidemia without treatment and interruption of supplements. After pharmacological and non- pharmacological interventions, the patient showed a significant improvement in the reduction of anthropometric measurements and in biochemical parameters. At the end of the follow-up, pharmaceutical care proved to be fundamental in identifying the patient's health problems, contributing to obtain a more rational pharmacotherapy.
As doenças crônicas não transmissíveis são problemas de saúde globais crescentes. O objetivo deste estudo foi promover a assistência farmacêutica a um paciente com multimorbidades, a fim de melhorar sua qualidade de vida. Foi realizado acompanhamento farmacoterapêutico pelo método SOAP e aplicação de instrumentos validados para avaliar adesão farmacológica, saúde mental e qualidade de vida. O relato trata de uma paciente do sexo feminino, 55 anos, obesa e dislipidêmica, sedentária, hipertensa, diabética e em fase de controle do câncer de mama. Foi identificada automedicação com antibióticos e inibidor de bomba de prótons. Apesar da boa adesão farmacológica, a paciente apresentava diabetes descompensado, acompanhada de dislipidemia sem tratamento e interrupção das suplementações. Após intervenções farmacológicas e não farmacológicas, a paciente apresentou melhora significativa na redução das medidas antropométricas e nos parâmetros bioquímicos. Ao final do acompanhamento, a assistência farmacêutica mostrou-se fundamental na identificação dos problemas de saúde do paciente.
Las enfermedades crónicas no transmisibles constituyen un creciente problema de salud mundial. El objetivo de este estudio fue promover la asistencia farmacéutica a un paciente con multimorbilidades para mejorar su calidad de vida. Se realizó seguimiento farmacoterapéutico por el método SOAP y aplicación de instrumentos validados para evaluar adherencia farmacológica, salud mental y calidad de vida. O relato trata de uma paciente do sexo feminino, 55 anos, obesa e dislipidêmica, sedentária, hipertensa, diabética e em fase de controle do câncer de mama. Se identificó automedicación con antibióticos e inhibidor de la bomba de protones. A pesar del buen cumplimiento farmacológico, la paciente presentó diabetes descompensada, acompañada de dislipidemia no tratada e interrupción de la suplementación. Tras intervenciones farmacológicas y no farmacológicas, la paciente mostró una mejoría significativa en la reducción de las medidas antropométricas y los parámetros bioquímicos. Al final del seguimiento, la asistencia farmacéutica demostró ser fundamental en la identificación de los problemas de salud del paciente.
Humans , Female , Middle Aged , Patients , Quality of Life , Women , Case Reports as Topic , Hypertension
There are several overlapping clinical practice guidelines in acute pancreatitis (AP), however, none of them contains suggestions on patient discharge. The Hungarian Pancreatic Study Group (HPSG) has recently developed a laboratory data and symptom-based discharge protocol which needs to be validated. (1) A survey was conducted involving all members of the International Association of Pancreatology (IAP) to understand the characteristics of international discharge protocols. (2) We investigated the safety and effectiveness of the HPSG-discharge protocol. According to our international survey, 87.5% (49/56) of the centres had no discharge protocol. Patients discharged based on protocols have a significantly shorter median length of hospitalization (LOH) (7 (5;10) days vs. 8 (5;12) days) p < 0.001), and a lower rate of readmission due to recurrent AP episodes (p = 0.005). There was no difference in median discharge CRP level among the international cohorts (p = 0.586). HPSG-protocol resulted in the shortest LOH (6 (5;9) days) and highest median CRP (35.40 (13.78; 68.40) mg/l). Safety was confirmed by the low rate of readmittance (n = 35; 5%). Discharge protocol is necessary in AP. The discharge protocol used in this study is the first clinically proven protocol. Developing and testifying further protocols are needed to better standardize patients' care.
Pancreatitis , Patient Discharge , Humans , Pancreatitis/therapy , Acute Disease , Hospitalization , Cohort Studies
Sugar-induced metabolic imbalances are a major health problem since an excessive consumption of saccharides has been linked to greater obesity rates at a global level. Sucrose, a disaccharide composed of 50% glucose and 50% fructose, is commonly used in the food industry and found in a range of fast, restaurant, and processed foods. Herein, we investigated the effects of a TRPC4/TRPC5 blocker, ML204, in the metabolic imbalances triggered by early exposure to sucrose-enriched diet in mice. TRPC4 and TRPC5 belong to the family of non-selective Ca+2 channels known as transient receptor potential channels. High-sucrose (HS)-fed animals with hyperglycaemia and dyslipidaemia, were accompanied by increased body mass index. mesenteric adipose tissue accumulation with larger diameter cells and hepatic steatosis in comparison to those fed normal diet. HS mice also exhibited enhanced adipose, liver, and pancreas TNFα and VEGF levels. ML204 exacerbated hyperglycaemia, dyslipidaemia, fat tissue deposition, hepatic steatosis, and adipose tissue and liver TNFα in HS-fed mice. Normal mice treated with the blocker had greater hepatic steatosis and adipose tissue cell numbers/diameter than those receiving vehicle, but showed no significant changes in tissue inflammation, glucose, and lipid levels. The results indicate that TRPC4/TRPC5 protect against the metabolic imbalances caused by HS ingestion.
A considerable amount of coastal contamination is caused by wastes deriving from household and the degradation and the metabolism of plants and animals, even if our attention is commonly focused on industrial pollutants and contaminants. Waste pollutants are mainly represented by highly diluted soluble compounds and particles deriving from dead organisms. This complex combination, consisting of suspended particles and dissolved nutrients, has a significant impact on coastal planktonic and benthic organisms, also playing an active role in the global cycles of carbon. In addition, production practices are nowadays shifting towards recirculated aquaculture systems (RAS) and the genic responses of target organisms to the pollution deriving from animal metabolism are still scarcely addressed by scientific investigations. The reservoir of organic matter dissolved in the seawater is by far the least understood if compared to that on land, cause only a few compounds have been identified and their impacts on animals and plants are poorly understood. The tendency of these compounds to concentrate at interfaces facilitates the absorption of dissolved organic compound (DOC) onto suspended particles. Some DOC components are chemically combined with dissolved metals and form complexes, affecting the chemical properties of the seawater and the life of the coastal biota. In this research, we compared the reproductive performances of the common sea urchin Paracentrotus lividus cultured in open-cycle tanks to those cultured in a recirculating aquaculture system (RAS), where pollution progressively increased during the experiment due to animal escretions. Sea urchins were cultured for 7 months under these two conditions and their gametes were collected. Embryos resulting by in vitro fertilization were analyzed by Real Time qPCR to identify possible effects of pollution-induced stress. The fertility of sea urchins was evaluated, as well as the gonadosomatic indices and the histological features of gonads. Our results indicate that pollution due to excess of nutrients, event at sub-lethal concentrations, may hardly impact the reproductive potential of this key species and that chronic effects of stress are revealed by the analyses of survival rates and gene expression.
The way the media portrays aquaculture-related events can influence how this industry is perceived by the public and affect its success. Since media are an important source of public information, media content analysis has been carried out in several regions of the world. This study aimed to determine which aspects of aquaculture were more exposed and how they were discussed by regional media in the Madeira archipelago, an oceanic group of Portuguese islands. Analysis of aquaculture's media coverage in the two most-read regional newspapers of Madeira was carried out over a 5-year period (2017 to 2021). For each news article, the assessment focused on the geographic scope, the main topics covered, the stakeholders with access to the debate, and the general tone of the article (risk/benefit framework). A total of 297 articles were analyzed. Results indicate the occurrence of trigger events that contributed to a shift in the amount of news published and in the way media framed aquaculture. In general, political and economic issues dominated the coverage, whereas social, environmental, scientific, and landscape matters received less media attention. The voice of the government was predominant throughout the 5 years in analysis and aquaculture was generally framed with a balanced tone, slightly more negative. Open and transparent communication between the stakeholders and the media is fundamental for the sustainable development of the aquaculture industry.
A síndrome hemofagocítica é determinada por desregulação do sistema imunológico, caracterizada por ativação excessiva de macrófagos, resultando em fagocitose de células sanguíneas normais no fígado, baço e medula óssea. Pode ser primária (genética) ou secundária (adquirida). Em adultos quase sempre é secundária, tendo infecções, neoplasias e doenças autoimunes como frequentes desencadeadores. Entre as principais manifestações da síndrome estão febre prolongada e hepatoesplenomegalia. O diagnóstico até o momento é confirmado pelo achado de hemofagocitose em biópsia de medula óssea. Entretanto, é descrito que a biópsia de medula óssea é normal nos primeiros dias de manifestações da síndrome. O presente relato tem como objetivo mostrar a observação de hemofagocitose em cultura de células de sangue periférico de paciente de 29 anos precedendo a hemofagocitose em biópsia de medula óssea. A paciente apresentava diferentes infecções, com grave comprometimento do estado geral e sem melhora com o tratamento das infecções. O achado laboratorial permitiu o tratamento precoce da síndrome hemofagocítica e a melhora da paciente. No presente relato a técnica utilizada está descrita detalhadamente para que possa ser reproduzida, além de ser apresentada uma revisão não sistemática da literatura sobre a síndrome.
Hemophagocytic syndrome, which is caused by dysregulation of the immune system, is characterized by excessive macrophage activation, resulting in phagocytosis of normal blood cells in the liver, spleen, and bone marrow. It can be primary (genetic) or secondary (acquired). In adults, it is almost always secondary, with infections, neoplasms, and autoimmune diseases as frequent triggers. The main manifestations of this syndrome are prolonged fever and hepatosplenomegaly. Currently, diagnosis is confirmed through finding hemophagocytosis in a bone marrow biopsy. However, it has been reported that bone marrow biopsy results are still normal on the first day the syndrome manifests. Here we report observing hemophagocytosis in cultured peripheral blood cells from a 29-year-old patient prior to finding hemophagocytosis in bone marrow biopsy. The patient had various infections and a poor general condition, which did not improve after treating the infections. The laboratory findings allowed early treatment of hemophagocytic syndrome and the patient improved. We describe our technique in detail so it can be reproduced, and we provide a non-systematic review of the literature on the syndrome.
Humans , Female , Adult , HIV
The assembly of biopolymers into a hydrated elastic network often goes along with syneresis, a spontaneous process during which the hydrogel slowly shrinks and releases solvent. The tendency to syneresis of calcium-alginate hydrogels, widely used biocompatible materials, is a hindrance to applications for which dimensional integrity is crucial. Although calcium-induced aggregation of specific block-sequences has been long known as the microscopic process at work in both primary cross-linking and syneresis, the nature of the coupling between these structural events and the global deswelling flow has remained so far elusive. We have tackled this issue within the regime of entangled pregels that yield highly cross-linked, self-crowded hydrogels with stiff networks. Using an original, stopped-flow extrusion experiment, we have unveiled a robust, stretched-exponential kinetics of shrinking, spanning more than six decades of time and quasi-independent of the alginate concentration. A careful analysis of the puzzling dynamical features of syneresis in these gels has led us to propose that due to the network rigidity, the calcium-fueled, random collapse events that drive solvent locally, are not thermally activated but rather controlled by the average poroelastic flow itself, according to a self-sustained mechanism described here for the first time.
Peripheral arterial disease (PAD) causes blockage of the arteries, altering the blood flow to the lower limbs. This blockage can cause the individual with PAD to feel severe pain in the lower limbs. The main contribution of this research is the discovery of a solution that allows the automatic detection of the onset of claudication based on data analysis from patients' smartphones. For the data-collection procedure, 40 patients were asked to walk with a smartphone on a thirty-meter path, back and forth, for six minutes. Each patient conducted the test twice on two different days. Several machine learning models were compared to detect the onset of claudication on two different datasets. The results suggest that we can identify the onset of claudication using inertial sensors with a best case accuracy of 92.25% for the Extreme Gradient Boosting model.
Intermittent Claudication , Peripheral Arterial Disease , Humans , Intermittent Claudication/diagnosis , Intermittent Claudication/etiology , Smartphone , Peripheral Arterial Disease/diagnosis , Peripheral Arterial Disease/complications , Walking/physiology , Machine Learning
The media play an important role in informing us about new developments in our understanding of the sea and raising awareness about its sustainability. However, press coverage of marine issues seems to be modest, compared with the importance oceans have in our lives. In this study, we examine science journalists' working contexts, motivations, and difficulties in writing about the sea in Europe. We conducted semi-structured interviews with 26 journalists who write for quality newspapers from 13 European countries. We found that the recent production of press news on marine issues is mainly conditioned by working contexts in newspapers, the personal and professional interests of journalists, and the available resources to write news. More studies are needed to compare our findings, including with other regions outside Europe.
Mass Media , Motivation , Europe , Writing
Blight is a concept not commonly discussed. However, blight is a problem that exists in the lives of many people, especially if they reside in urban areas. Blight originates whenever properties are neglected, contributing to both a functional and social depreciation process and ultimately leading to uninhabitable dwellings. Despite being blighted, these properties and surrounding neighborhoods often are occupied by families who fail to have sufficient income to afford residences that meet minimum standards or to live in neighborhoods free from drug trafficking and prostitution or other forms of crime. Blight may spread rapidly, thus, experts must, in a timely manner, analyze its causes, which are essential to preventing and mitigating blight problems. The purpose of this study is to seek an understanding of blight and identify its causal factors. The generic methods commonly applied in previous blight research present limitations that this study aims to overcome by using cognitive mapping and the decision making trial and evaluation laboratory (DEMATEL) technique. This dual methodology provides a more transparent and less restrictive approach for analyzing and complying with the dynamics of cause-and-effect relationships among variables. Group debate involving a panel of specialists in this field identified six causation clusters based on the experts' experience and knowledge. The resulting framework and its application were validated both by these specialists and the head of the Territorial and Environmental Assessment and Monitoring Division of Cascais City Council Strategic Planning Department, Portugal.
As doenças crônicas não transmissíveis (DCNT's) são responsáveis por cerca de 74% da mortalidade global. Nesse contexto, o acompanhamento farmacoterapêutico surge como uma importante ferramenta para garantir uma farmacoterapia racional em prol da melhoria da qualidade de vida do paciente. Levando isso em consideração, este estudo tem como objetivo avaliar o impacto do acompanhamento farmacêutico na qualidade de vida de um paciente idoso com tratamento irracional da hipertensão arterial sistêmica (HAS), diabetes mellitus e outros sintomas da síndrome metabólica. Paciente M.M.D., masculino, 67 anos, hiperglicêmico, dislipidêmico e que se automedicava para hipertensão sem diagnóstico médico com uma série de medicamentos potencialmente inapropriados (PIM's). Após as intervenções farmacêuticas apresentou melhora nos quadros e maior adesão à terapia medicamentosa atrelada a melhores hábitos de vida. Dessa forma, o impacto positivo das intervenções durante o acompanhamento farmacêutico reforça a importância do profissional na atenção básica e na promoção da saúde.
Chronic non-communicable diseases (NCDs) account for about 74% of global mortality. In this context, pharmacotherapeutic follow-up appears to be an important tool for ensuring rational pharmacotherapy in favor of improving the patient's quality of life. Taking this into consideration, this study aims to evaluate the impact of pharmaceutical follow-up on the quality of life of an elderly patient with irrational treatment of systemic arterial hypertension (SAH), diabetes mellitus and other symptoms of metabolic syndrome. M.M.D. patient, male, 67 years old, hyperglycemic, dyslipidemic and self-medicating for hypertension without medical diagnosis with a series of potentially inappropriate medications (PIM's). After the pharmaceutical interventions showed an improvement in the conditions and greater adherence to drug therapy coupled to better habits of life. Thus, the positive impact of interventions during pharmaceutical follow-up reinforces the importance of the professional in basic care and health promotion.
Las enfermedades no transmisibles crónicas representan aproximadamente el 74% de la mortalidad mundial. En este contexto, el seguimiento farmacoterapéutico es una herramienta importante para garantizar una farmacoterapia racional para mejorar la calidad de vida del paciente. Teniendo esto en cuenta, este estudio tiene por objeto evaluar el impacto del seguimiento farmacéutico en la calidad de vida de un paciente de edad avanzada con el tratamiento irracional de la hipertensión arterial sistémica (HAS), la diabetes mellitus y otros síntomas del síndrome metabólico. Paciente con M.M.D. masculino de 67 años de edad, hiperglucemia, dislipidemia y automedicación para la hipertensión sin diagnóstico médico con una serie de medicamentos potencialmente inapropiados (PIMs). Después de las intervenciones farmacéuticas, mostró una mejoría en las tablas y una mayor adherencia a la terapia con medicamentos, junto con mejores hábitos de vida. De esta manera, el impacto positivo de las intervenciones durante el seguimiento farmacéutico refuerza la importancia del profesional en la atención básica y la promoción de la salud.
The increase in the demand for Paracentrotus lividus roe, a food delicacy, causes increased pressure on its wild stocks. In this scenario, aquaculture facilities will mitigate the effects of anthropogenic pressures on the wild stocks of P. lividus. Consequently, experimental studies should be conducted to enhance techniques to improve efficient aquaculture practices for these animals. Here, we for the first time performed molecular investigations on cultured sea urchins. We aimed at understanding if maternal influences may significantly impact the life of future offspring, and how the culture conditions may impact the development and growth of cultured specimens. Our findings demonstrate that the outcomes of in vitro fertilization of P. lividus are influenced by maternal influences, but these effects are largely determined by culture conditions. In fact, twenty-three genes involved in the response to stress and skeletogenesis, whose expressions were measured by Real Time qPCR, were differently expressed in sea urchins cultured in two experimental conditions, and the results were largely modified in offspring deriving from two groups of females. The findings herein reported will be critical to develop protocols for the larval culture of the most common sea urchin, both for research and industrial production purposes for mass production.
Paracentrotus , Animals , Female , Paracentrotus/genetics , Survival Rate , Reproduction/genetics , Larva , Gene Expression
Patients with chronic kidney disease (CKD-5D) in dialysis have been associated with higher rates of SARS-CoV-2 infection. Objective: To identify the CKD-5D patients' immune system behavior regarding the Pfizer-BioNTech (BNT162b2 mRNA) vaccine (Comirnaty©). This was a multicenter study carried out in 38 dialysis units in NephroCare Portugal. Eligible patients from two cohortsone composed of completely vaccinated patients with Comirnaty© (vaccinated group) against a second cohort of patients who recovered from SARS-CoV-2 infection (control group)were selected through representative sampling for each cohort. Humoral response was assessed at 3 (t0) and 6 months (t1) after complete vaccination and, in the control group, 6 months after COVID-19 recovery. In the vaccinated group, at t0, the median anti-Spike IgG level was 1120 AU/mL and, at t1, all participants' antibody level decreased to a median of 455 AU/mL. In the control group, the median serum SARS-CoV-2 antibodies level was 1836 AU/mL. In the vaccinated group, at t0, patients < 70 years presented a significantly (p = 0.002) higher level of anti-Spike IgG titres. In contrast, older patients from the control group presented a significantly (p = 0.038) higher IgG. No correlation was found between age and anti-Spike IgG antibodies level in any of the studied groups. Patients with a higher body mass index showed a greater immune response in both the vaccinated and control group, although without significance. We concluded that, in the vaccinated group, elderly patients developed a lower immune response than younger patients and the levels of anti-Spike IgG antibodies declined faster between t0 and t1, while in the control group, the oldest and overweight patients developed the best humoral response.
COVID-19 , Renal Insufficiency, Chronic , Aged , Antibodies, Viral , BNT162 Vaccine , Body Mass Index , COVID-19/prevention & control , Humans , Immunoglobulin G , Renal Dialysis , SARS-CoV-2 , Vaccination
Metabolic dysfunctions, such as hyperglycemia and insulin resistance, have been associated to cognitive impairment and dementia regardless of advanced age, although the underlying mechanisms are still elusive. Thus, this study investigates the deleterious effects of metabolic syndrome (MetS) induced by long-term exposure to a high-sucrose diet on motor and cognitive functions of male adult rats and its relationship with hippocampal endoplasmic reticulum (ER) stress. Weaned Wistar male rats were fed a high-sucrose diet until adulthood (HSD; 6 months old) and compared to both age-matched (CTR; 6 months old) and middle-aged chow-fed rats (OLD; 20 months old). MetS development, serum redox profile, behavioral, motor, and cognitive functions, and hippocampal gene/protein expressions for ER stress pro-adaptive and pro-apoptotic pathways, as well as senescence markers were assessed. Prolonged exposure to HSD induced MetS hallmarked by body weight gain associated to central obesity, hypertriglyceridemia, insulin resistance, and oxidative stress. Furthermore, HSD rats showed motor and cognitive decline similar to that in OLD animals. Noteworthy, HSD rats presented marked hippocampal ER stress characterized by failure of pro-adaptive signaling and increased expression of Chop, p21, and Parp-1 cleavage, markers of cell death and aging. This panorama resembles that found in OLD rats. In toto, our data showed that early and sustained exposure to a high-sucrose diet induced MetS, which subsequently led to hippocampus homeostasis disruption and premature impairment of motor and cognitive functions in adult rats.
Protocadherin 19 gene-related epilepsy or protocadherin 19 clustering epilepsy is an infantile-onset epilepsy syndrome characterized by psychiatric (including autism-related), sensory, and cognitive impairment of varying degrees. Protocadherin 19 clustering epilepsy is caused by X-linked protocadherin 19 protein loss of function. Due to random X-chromosome inactivation, protocadherin 19 clustering epilepsy-affected females present a mosaic population of healthy and protocadherin 19-mutant cells. Unfortunately, to date, no current mouse model can fully recapitulate both the brain histological and behavioural deficits present in people with protocadherin 19 clustering epilepsy. Thus, the search for a proper understanding of the disease and possible future treatment is hampered. By inducing a focal mosaicism of protocadherin 19 expression using in utero electroporation in rats, we found here that protocadherin 19 signalling in specific brain areas is implicated in neuronal migration, heat-induced epileptic seizures, core/comorbid behaviours related to autism and cognitive function.
The prevalence of inflammatory skin diseases continues to increase with a high incidence in children and adults. These diseases are triggered by environmental factors, such as UV radiation, certain chemical compounds, infectious agents, and in some cases, people with a genetic predisposition. The pathophysiology of inflammatory skin diseases such as psoriasis or atopic dermatitis, but also of skin cancers, is the result of the activation of inflammation-related metabolic pathways and the overproduction of pro-inflammatory cytokines observed in in vitro and in vivo studies. Inflammatory skin diseases are also associated with oxidative stress, overproduction of ROS, and impaired antioxidant defense, which affects the metabolism of immune cells and skin cells (keratinocytes and fibroblasts) in systemic and skin disorders. Lipids from algae have been scarcely applied to modulate skin diseases, but they are well known antioxidant and anti-inflammatory agents. They have shown scavenging activities and can modulate redox homeostasis enzymes. They can also downmodulate key inflammatory signaling pathways and transcription factors such as NF-κB, decreasing the expression of pro-inflammatory mediators. Thus, the exploitation of algae lipids as therapeutical agents for the treatment of inflammatory skin diseases is highly attractive, being critically reviewed in the present work.
Major depressive disorder (MDD), also called depression, is a serious disease that impairs the quality of life of patients and has a high incidence, affecting approximately 3.8% of the world population. Its diagnosis is very subjective and is not supported by measurable biomarkers mainly due to the lack of biochemical markers. Recently, disturbance of lipid profiling has been recognized in MDD, in animal models of MDD or in depressed patients, which may contribute to unravel the etiology of the disease and find putative new biomarkers, for a diagnosis or for monitoring the disease and therapeutics outcomes. In this review, we provide an overview of current knowledge of lipidomics analysis, both in animal models of MDD (at the brain and plasma level) and in humans (in plasma and serum). Furthermore, studies of lipidomics analyses after antidepressant treatment in rodents (in brain, plasma, and serum), in primates (in the brain) and in humans (in plasma) were reviewed and give evidence that antidepressants seem to counteract the modification seen in lipids in MDD, giving some evidence that certain altered lipid profiles could be useful MDD biomarkers for future precision medicine.
Depression/metabolism , Lipid Metabolism , Animals , Biomarkers/metabolism , Depression/diagnosis , Depression/drug therapy , Humans , Oxidative Stress
INTRODUCTION: Despite the impact needling has had on vascular access survival and patient outcome, there is no universal or standardized method proposed for proper cannulation. Rigorous studies are needed, examining cannulation practices, and challenges to achieving complication-free cannulation. METHODS: This randomized, open-label trial was conducted at 18 dialysis units owned by a large private dialysis provider operating in Portugal. Eligible patients were adults on chronic hemodialysis, with a new arteriovenous fistula (AVF); cannulated for at least 4 weeks complication-free. Patients were randomly assigned in a 1:1 ratio to one of three cannulation techniques (CT): Multiple Single cannulation Technique (MuST), rope-ladder (RLC), and buttonhole (BHC). The primary endpoint was AVF primary patency at 1 year. FINDINGS: One hundred seventy-two patients were enrolled between March 2014 and March 2017. Fifty-nine patients were allocated to MuST, 56 to RLC, and 57 to BHC. MuST and RLC were associated with a better AVF primary patency than BHC. Primary patency at 12 months was 76.3% in MuST, 59.6% in BHC, and 76.8% in RLC group. Mean AVF survival times were 10.5 months (95% CI = 9.6, 11.3) in the MuST group, 10.4 months (95% CI = 9.5, 11.2) in RLC, and 9.5 months (95% CI = 8.6, 10.4) in BHC. BHC was a significant risk predictor for AVF survival with 2.13 times more events than the other two CT (HR 2.13; 95% CI = 1.07, 4.21; p = 0.03). DISCUSSION: MuST was easy to implement without a diagram and there is no need to use blunt needles. This study showed MuST was efficacious and safe in maintaining the longevity of AVF in dialysis patients.
Arteriovenous Fistula , Arteriovenous Shunt, Surgical , Adult , Arteriovenous Shunt, Surgical/methods , Catheterization/methods , Humans , Renal Dialysis/methods
