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In Canada, recreational use of cannabis was legalized in October 2018. This policy change along with recent publications evaluating the efficacy of cannabis for the medical treatment of epilepsy and media awareness about its use have increased the public interest about this agent. The Canadian League Against Epilepsy Medical Therapeutics Committee, along with a multidisciplinary group of experts and Canadian Epilepsy Alliance representatives, has developed a position statement about the use of medical cannabis for epilepsy. This article addresses the current Canadian legal framework, recent publications about its efficacy and safety profile, and our understanding of the clinical issues that should be considered when contemplating cannabis use for medical purposes.
The University of São Paulo Twin Panel (Painel USP de Gêmeos), based at the Institute of Psychology of the University of São Paulo, started formally in 2017. Our registry is new, but in only two years of formal existence, it comprises a volunteer sample of 4826 registered individuals (98% twins and 2% higher-order multiples), recruited at the University of São Paulo and by social media campaigns. Our main aim is to conduct and promote research with twins on psychological processes and behavior. The University of São Paulo is the largest higher education and research institution in South America, and the Painel USP de Gêmeos has great potential for fostering research on twin-related issues from a psychological perspective in Brazil and South America.
Studies have shown that daily exposure to different products, whether chemical or natural, can cause irreversible damage to women’s reproductive health. Therefore it is necessary to use tests that evaluate the safety and efficacy of these products. Most reproductive toxicology tests are performed in vivo. However, in recent years, various cell culture methods, including embryonic stem cells and tissues have been developed with the aim of reducing the use of animals in toxicological tests. This is a major advance in the area of toxicology, as these systems have the potential to become a widely used tool compared with in vivo tests routinely used in reproductive biology and toxicology. The present review describes and highlights data on in vitro culture processes used to evaluate reproductive toxicity as an alternative to traditional methods using in vivo tests.
Long-acting injectable antipsychotic therapies may offer benefits over oral antipsychotics in patients with schizophrenia. However, there is still a lack of real-world studies assessing the effectiveness of these therapies.
This study aimed to explore the safety, tolerability, and treatment response of aripiprazole monohydrate (AOM) once monthly in non-acute but symptomatic adult patients switched from previous therapy with frequently used oral or injectable atypical antipsychotics.
This was a post hoc analysis of a prospective, interventional, single-arm, open-label, 6-month study.
The patients (N=54) were switched to aripiprazole monohydrate once-monthly (AOM) from daily oral treatment or monthly injectable treatment with either aripiprazole (n=25), olanzapine (n=7), paliperidone extended-release (PP1M) (n=10), quetiapine (n=4), or risperidone (n=8). In all groups, mean Positive and Negative Syndrome Scale total (p=0.0001) and Clinical Global Impression-Severity scores improved significantly (p=0.0001). A reduction of ≥50% reduction of BPRS total-score and a CGI severity-score ≤4 in the Positive and Negative Syndrome Scale total score were observed in 16.7% (aripiprazole), 21.2% (olanzapine), 35.1% (PP1M), 27.3% (quetiapine), and 37.2% (risperidone) of patients. The patients showed significant improvements involving safety features as they experienced significant overall weight loss (p=0.0001) and prolactine decrease (risperidone p=0.0001, paliperidone extended-release p=0.0001). AOM once-monthly was well tolerated, presenting no new safety signals. Patient also reported an overall significant improvement on their quality of life measured with the Quality of Life Rating Scale (QLS) (p=0.0004) as well as in sexual functioning PRSexDQ-SALSEX (p=0.0001). In addition, the all cause treatment discontinuation rate after6-month follow-up was small (n=3; 5,55%)
These data illustrate that stable, non-acute but symptomatic patients either on oral antipsychotic therapy or under monthly antipsychotic treatment may show clinically meaningful improvement of psychotic symptoms, tolerability involving relevant side effects and quality of life perception. The findings are limited by the naturalistic study design; thus, further studies are required to confirm the current findings.
Decision making regarding national population-based prenatal and newborn screening policies is recognized to be highly challenging. This paper aims to describe the formalized collaboration that has been established between the Spanish National Public Health Screening Advisory Committee (PHSAC) and the Spanish Network of Health Technology Assessment (HTA) agencies to support the development of evidence- and consensus-based recommendations to support this process.
In-depth description and analysis of the strategic and methodological processes that have been implemented within the Spanish National Health System prenatal and newborn screening frameworks, with special emphasis on the role, actions, and responsibilities of HTA agencies.
The role of HTA agencies is threefold: (i) support the PHSAC by providing evidence on safety, effectiveness and cost/effectiveness of the screening tests/strategies, as well as contextualized information regarding costs, organizational, social, legal and ethical issues; (ii) collaborate with the PHSAC in the development of formal evidence- and consensus-based recommendations for defining population screening programs, when required; (iii) analyze real-world data that is generated by piloted programs. This paper will provide real-life examples of how these processes were implemented in practice, with a special focus on the development of the non-invasive prenatal testing (NIPT) policy. Recommendations for NIPT were developed by a multidisciplinary group based on the European network for Health Technology Assessment (EUnetHTA) rapid assessment report and the predictive models that were built using national statistics and other contextualized data.
The current work represents an innovative approach for prenatal and newborn screening policymaking, which are commonly difficult to evaluate due to the low quality of evidence and the confounding public health issues. The paper raises awareness regarding the importance of joint collaborations in areas where evidence is commonly insufficient for decision making.
In December 2017, a patient involvement (PI) Interest Group was created in the Spanish Network of Agencies for Assessing National Health System Technologies and Performance (RedETS) Annual conference. It started as a voluntary group of health technology assessment (HTA) methodologists interested in PI. The objective of the Group is to promote and facilitate PI in HTA. With the support of the Spanish Ministry of Health and the RedETS Council the Interest Group grew to at least one member for each of the eight RedETS regional agencies and units. It currently has 22 members. The PI Interest Group works in periodic online meetings and an annual offline meeting to establish a space for experiences exchange and reach consensus on main issues regarding PI.
RedETS published a strategy to facilitate effective and efficient PI in HTA processes in 2017. The long-term objective is to mainstream PI in all RedETS products. This strategy was built on a literature review and a qualitative study with semi-structured interviews. The interviews detected capacity building needs for technicians and methodologist in the network to be able to actively engage patients in HTA reports.
Since the kick-off meeting the PI Interest Group has worked in a number of activities. The main lines of action since its creation were: (i) evaluation of PI process in RedETS HTA reports in 2017 and in current reports, (ii) discussion on main methodological and procedural aspects, and feasibility of different patient participation approaches, (iii) development of technical protocols and templates to facilitate PI, (iv) the creation/adaptation of educational materials for patients and (v) translation of the HTAi Glossary for patients to Spanish.
Peer-to-peer learning processes can foster technical capacity of HTA methodologist in the Spanish HTA Network and may favor the implementation of the PI strategy.
Healthcare organizations have invested efforts on hospital-based health technology assessment (HB-HTA) and enterprise risk management (ERM) processes for novel systems to obtain more accurate data on which to base strategic decisions. This study proposes to analyze how HB-HTA and ERM processes can share personal resources and skills to achieve principles with value-oriented results.
Literature on ERM and HB-HTA and data from interviews with healthcare managers compose the research data sources, which were submitted to a qualitative data analysis. It was oriented to identify the association between ERM and HB-HTA application in hospitals and the common principles between both processes, in addition to proposing the capability to share personal resources between both teams in a matrix.
The common principles and personal background suggested for HB-HTA and ERM teams allowed the build of a matrix identifying how both teams can work in an integrated manner being more effective and value-oriented. The shared resource matrix reports how each professional (with a specific background) may interact with each activity associated to HB-HTA or ERM implementation guidelines.
The identification of common principles and capabilities between ERM and HB-HTA suggested advances with the literature from both research areas. The opportunity to share personal resources also contributes to the implementation of those processes in hospitals with less financial resources, approaching its own management to be more efficient with the care chain.
The present work expands the existing knowledge on M. mola ecology by assessing, for the first time, its abundance (and body size distribution) in the southern waters of Portugal and relating the associated temporal variations with environmental variables. There were significant seasonal differences in abundance, with peaks in spring and autumn and lower values throughout the summer. Ocean sunfish abundance was positively correlated with sea surface temperature and chlorophyll a, indicating that a combination of both temperature and productivity dictates spatial use. Complementarily, the absence of a relationship between abundance and water transparency may reveal a strategy in spatial use favouring a medium-term steady food supply over short-term improved feeding opportunities. Specimens ranged between 31.8 and 230.0 cm (total length), with 98% of all individuals measuring between 31.8 and 59.9 cm. As the vast majority of specimens analysed were immature, seasonal differences in abundance should not be related to spawning.
EPA (20 : 5n-3) and DHA (22 : 6n-3) fatty acids have weight-reducing properties with physiological activity depending on their molecular structure – that is, as TAG or ethyl esters (EE). Aquaporins (AQP) are membrane protein channels recognised as important players in fat metabolism, but their differential expression in white adipose tissue (WAT) and brown adipose tissue (BAT), as well as their modulation by dietary n-3 long-chain PUFA (LCPUFA) such as EPA and DHA, has never been investigated. In this study, the transcriptional profiles of AQP3, AQP5, AQP7 and selected lipid markers of WAT (subcutaneous and visceral) and BAT (interscapular) from hamsters fed diets containing n-3 LCPUFA in different lipid structures such as fish oil (FO, rich in EPA and DHA in the TAG form) and FO-EE (rich in EPA and DHA in the EE form) were used and compared with linseed oil (LSO) as the reference group. A clear effect of fat depot was observed for AQP3 and leptin (LEP), with the lowest values of mRNA found in BAT relative to WAT. The opposite occurred for PPARα. AQP7 was affected by diet, with FO-fed hamsters having higher mRNA levels compared with LSO-fed hamsters. The relative gene expression of AQP5, adiponectin (ADIPO), GLUT4 and PPARγ was influenced by both fat tissue and diet. Taken together, our results revealed a differential expression profile of AQP and some markers of lipid metabolism in both WAT and BAT in response to feeding n-3 LCPUFA in two different structural formats: TAG v. EE.
To examine timing of eating across ten European countries.
Cross-sectional analysis of the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study using standardized 24 h diet recalls collected during 1995–2000. Eleven predefined food consumption occasions were assessed during the recall interview. We present time of consumption of meals and snacks as well as the later:earlier energy intake ratio, with earlier and later intakes defined as 06.00–14.00 and 15.00–24.00 hours, respectively. Type III tests were used to examine associations of sociodemographic, lifestyle and health variables with timing of energy intake.
Ten Western European countries.
In total, 22 985 women and 13 035 men aged 35–74 years (n 36 020).
A south–north gradient was observed for timing of eating, with later consumption of meals and snacks in Mediterranean countries compared with Central and Northern European countries. However, the energy load was reversed, with the later:earlier energy intake ratio ranging from 0·68 (France) to 1·39 (Norway) among women, and from 0·71 (Greece) to 1·35 (the Netherlands) among men. Among women, country, age, education, marital status, smoking, day of recall and season were all independently associated with timing of energy intake (all P<0·05). Among men, the corresponding variables were country, age, education, smoking, physical activity, BMI and day of recall (all P<0·05).
We found pronounced differences in timing of eating across Europe, with later meal timetables but greater energy load earlier during the day in Mediterranean countries compared with Central and Northern European countries.
The objectives were to develop an effective protocol for transfection of ovine secondary follicles and to assess the effect of attenuating aquaporin 3 (AQP3) using a small interfering RNA (siRNA-AQP3) on antrum formation and follicular growth in vitro. Various combinations of Lipofectamine® volumes (0.5, 0.75 or 1.0 µl), fluorescent oligonucleotide (BLOCK-iT ™) concentrations (3.18, 27.12 or 36.16 nM) and exposure times (12, 14, 16, 18 or 20 h) were tested. The BLOCK-iT™ was replaced by siRNA-AQP3 in the transfection complex. Ovine secondary follicles were isolated and cultured in vitro for 6 days using standard protocols. Follicles were transfected on day 0 or 3 or on both days (0 and 3) and then cultured for an additional 3 or 6 days. As revealed by the fluorescence signal, the Lipofectamine®/BLOCK-iT™ complex (0.75 µl + 27.12 nM by 12 h of incubation) crossed the basement membrane and granulosa cell and reached the oocytes. In general, the rate of intact follicles was higher and the rate of antrum formation was lower in transfected follicles compared with control follicles. In conclusion, ovine secondary follicles can be successfully transfected during in vitro culture, and siRNA-mediated attenuation of AQP3 gene reduced antrum formation of secondary follicles.
Plant–animal mutualistic interactions through ecological network systems and the environmental conditions in which they occur, allow us to understand patterns of species composition and the structure and dynamics of communities. We evaluated whether flower morphologies with different pollination syndromes (ornithophilous and non-ornithophilous) are used by hummingbirds and whether these characteristics affect the structure (core-peripheral species) of hummingbird networks. Observations were made in flowering patches, where plant–hummingbird interactions were recorded at three altitudes (300–2500 m) during three seasons (dry, rainy and post-rainy) from 2015 to 2016 at El Triunfo Biosphere Reserve, Chiapas, Mexico. We recorded 15 hummingbird species interacting with 58 plant species, and the greatest number of interacting hummingbird species (11; 14) and plant species (28; 40) were found at middle altitudes and during the dry season, respectively. In all study sites, most of the plant species visited by hummingbirds had an ornithophilous syndrome (67%) at high altitudes (22 plant species) and during the dry season (26 plant species), but more individual hummingbirds visited non-ornithophilous plant species. The hummingbird species at high altitudes exhibited the greatest level of specialization towards plants (H2′ = 0.74), but the networks of plant-hummingbird interactions were generalist (H2′ = 0.25); i.e. visiting plants with both syndromes, at low altitudes. The core generalist hummingbird species remained constant with altitude and season, but the core generalist plant species varied between different altitudes and seasons according to the phenology of the species.
Selenium (Se) is an essential micronutrient for humans, yet its dietary intake is low, mostly due to the low bioavailability in soils and therefore in edible plant tissues. To overcome Se deficiency, the breeding approach (i.e., genetic biofortification), namely in rice, is largely dependent on available Se pools. To ensure the success of genetic biofortification with Se, agronomic biofortification can be accomplished through foliar Se application. Considering this background, the main hypothesis of this work was centered in the foliar application of Se to attain agronomic biofortification of rice crops. This study also aimed to assess the full potential for increasing grain Se concentrations during rice filling, as well as the types of nutrients deposition. An experimental design applying two foliar fertilizers (sodium selenite and sodium selenate) was developed. As test systems, four rice genotypes (Ariete, Albatros, OP1105 and OP1109) were used and the kinetics of micro- and macro-nutrients accumulation and deposition were assessed. Biofortification was performed in field trials for two years with foliar fertilization ranging between 0 and 300 g Se ha−1. At the end of the plant cycle, selenite applications triggered 427- to 884-fold increases in grain Se concentrations among rice genotypes (Albatros > OP1105 > OP1109 > Ariete). The application of selenate also prompted 128- to 347-fold increases in grain Se concentrations in rice crops (Albatros > OP1105 > Ariete > OP1109). Regardless of the foliar fertilizer applied, Se deposition among genotypes occurred throughout the grain without relevant inhibitory effects on yields. In each genotype, micro and macronutrients varied among crop tissues.
Here we evaluated the effect of fermented milk supplemented with whey protein (approximately 80 % protein), probiotic (Bifidobacterium animalis subsp. lactis BB12) and pomegranate juice (Punica granatum L.) on the physical performance, intestinal motility and villi structure, inflammatory markers and intestinal microbiota of rats under high-intensity acute exercise. In all, twenty-four Wistar rats were separated into groups: control (Ctrl), supplemented (Supp), exercised (Exe) and exercised and supplemented (Exe+Supp). Rats in the Supp groups received fermented milk during 6 weeks by oral administration. At the end of the supplementation period, the Exe groups were submitted to high-intensity acute exercise on a treadmill. We found that intense acute exercise caused changes in the intestinal villi interspace, changes in the proportion of Lactobacillus species and an increase in Clostridium species, as well as a decrease in intestinal motility. Supplementation increased intestinal motility, and maintained the intestinal villi interspace and the natural microbiota proportions of the exercised rats. Physical performance was not improved by fermented milk supplementation. We conclude that the fermented milk containing whey protein, B. animalis (BB12) and pomegranate juice can re-establish intestinal microbiota and protect the animals from the undesirable effects of intense acute exercise.
Isotopic composition of leaf carbon (δ13C) and nitrogen (δ15N) is determined by biotic and abiotic factors. In order to determine the influence of leaf habit and site on leaf δ13C and δ15N in the understorey of two Atlantic forests in Brazil that differ in annual precipitation (1200 and 1900 mm), we measured these isotopes in the shaded understorey of 38 tropical tree species (20 in the 1200-mm site and 18 in the 1900-mm site). Mean site values for δ15N were significantly lower at the 1200-mm site (−1.4‰) compared with the 1900-mm site (+3.0‰), and δ13C was significantly greater in the 1200-mm site (−30.4‰) than in the 1900-mm site (−31.6‰). Leaf C concentration was greater and leaf N concentration was lower at 1200-mm than at 1900-mm. Leaf δ15N was negatively correlated with δ13C across the two sites. Leaf δ13C and δ15N of evergreen and deciduous species were not significantly different within a site. No significant phylogenetic signal for any traits among the study species was found. Overall, site differences were the main factor distinguishing traits among species, suggesting strong functional convergence to local climate and soils within each site for individuals in the shaded understorey.
Surface electroencephalogram (EEG) recording remains the gold standard for noninvasive assessment of electrical brain activity. It is the most efficient way to diagnose and classify epilepsy syndromes as well as define the localization of the epileptogenic zone. The EEG is useful for management decisions and for establishing prognosis in some types of epilepsy. Electroencephalography is an evolving field in which new methods are being introduced. The Canadian Society of Clinical Neurophysiologists convened an expert panel to develop new national minimal guidelines. A comprehensive evidence review was conducted. This document is organized into 10 sections, including indications, recommendations for trained personnel, EEG yield, paediatric and neonatal EEGs, laboratory minimal standards, requisitions, reports, storage, safety measures, and quality assurance.
The present study aimed to describe the reproductive cycle and estimate the size at sexual maturity of the Manila clam (Ruditapes philippinarum) in the Tagus Estuary (Portugal). Specimens were collected monthly from September 2013 to December 2015 during fishing surveys using bivalve dredges. The gametogenic cycle was described in detail using gonad histology and monitored throughout the study period by the monthly variation in the frequency of gonad maturation stages, mean gonadal index and mean oocyte diameter. This invasive population of R. philippinarum displayed synchronous gonadal development between sexes, with ripening occurring mainly in April and May followed by an extensive spawning period until November–December. Individuals reached the size at first sexual maturity at 29.4 mm in shell length (i.e. before 1 year old). Furthermore, the reproductive strategy, dynamics and potential were compared between the invasive R. philippinarum and the native congeneric carpet shell clam (Ruditapes decussatus). Overall, the data gathered in this study constitutes valuable baseline information to propose conservation strategies and implement management measures to minimize the harmful impacts caused by this invasive species on local ecosystems and native biodiversity, particularly over populations of autochthonous bivalves.
Scuticociliatosis is a severe disease in farmed flatfish. However, the causative agent is not always accurately identified. In this study, we identified two isolates of scuticociliates from an outbreak in cultured fine flounder Paralichthys adspersus. Scuticociliate identification was based on morphological data, examination of life stages and the use of molecular approaches. The isolates were compared with a strain of Philasterides dicentrachi from turbot Scophthalmus maximus and with a strain deposited in the American Type Culture Collection as Miamiensis avidus ATCC® 50180™. The use of morphological, biological and molecular methods enabled us to identify the isolates from the fine flouder as P. dicentrarchi. Comparison of P. dicentrachi isolates and M. avidus revealed some differences in the buccal apparatus. Unlike P. dicentrarchi, M. avidus has a life cycle with three forms: macrostomes (capable of feeding on P. dicentrarchi), microstomes and tomites. Additionally, we found differences in the 18S rRNA and α- and β-tubulin gene sequences, indicating that P. dicentrarchi and M. avidus are different species. We therefore reject the synonymy/conspecificity of the two taxa previously suggested. Finally, we suggest that a combination of morphological, biological, molecular (by multigene analysis) and serological techniques could improve the identification of scuticociliates parasites in fish.
The aim of this study was to report the frequency of autoimmune disorders and autoantibodies in 22 patients with neuromyelitis optica (NMO), as well as whether the seropositivity for autoantibodies differs between anti-aquaporin 4 (AQP4) positive and AQP4 negative NMO patients.
Demographic, medical records, and a profile of autoantibodies were evaluated in 22 NMO patients, including AQP4, anti-thyroid-stimulating hormone receptor, antinuclear antibodies (ANA), anti-thyroperoxidase (anti-TPO), anti-thyroglobulin (anti-Tg), anti-double-stranded DNA, anti-neutrophil cytoplasmic, anti-cyclic citrullinate peptide, rheumatoid factor, anti-SSA/Ro, anti-SSB/La, anti-Smith antibodies (anti-Sm), anti-ribonucleoprotein, anti-nucleosome, and anti-Scl70. Thyroid-stimulating hormone and free thyroxin were measured.
The frequency of women was higher than men (95.5% vs. 4.5%) and 68.2% were Afro-Brazilians. Six (27.3%) patients presented other autoimmune disorders, such as Hashimoto thyroiditis (n=2), Graves’ disease (n=1), juvenile idiopathic arthritis (n=1), systemic lupus erythematosus and systemic sclerosis (n=1), and Raynaud’s phenomenon (n=1). The most frequent autoantibodies were anti-AQP4 (54.5%), anti-nucleosome (31.8%), ANA (27.3%), anti-TPO (22.7%), and anti-Tg (22.7%). Difference was not observed in the frequency of autoimmune disorders when the patients were compared according to their anti-AQP4 status.
The results of the present study underscored that the NMO patients present high frequency of autoantibodies against cellular antigens and the presence of autoimmune disorders. Further studies with large number of NMO patients may contribute to advances in the understanding of NMO disease mechanisms.
Improvements in colorectal cancer (CRC) detection and treatment have led to greater numbers of CRC survivors, for whom there is limited evidence on which to provide dietary guidelines to improve survival outcomes. Higher intake of red and processed meat and lower intake of fibre are associated with greater risk of developing CRC, but there is limited evidence regarding associations with survival after CRC diagnosis. Among 3789 CRC cases in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, pre-diagnostic consumption of red meat, processed meat, poultry and dietary fibre was examined in relation to CRC-specific mortality (n 1008) and all-cause mortality (n 1262) using multivariable Cox regression models, adjusted for CRC risk factors. Pre-diagnostic red meat, processed meat or fibre intakes (defined as quartiles and continuous grams per day) were not associated with CRC-specific or all-cause mortality among CRC survivors; however, a marginal trend across quartiles of processed meat in relation to CRC mortality was detected (P 0·053). Pre-diagnostic poultry intake was inversely associated with all-cause mortality among women (hazard ratio (HR)/20 g/d 0·92; 95 % CI 0·84, 1·00), but not among men (HR 1·00; 95 % CI 0·91, 1·09) (Pfor heterogeneity=0·10). Pre-diagnostic intake of red meat or fibre is not associated with CRC survival in the EPIC cohort. There is suggestive evidence of an association between poultry intake and all-cause mortality among female CRC survivors and between processed meat intake and CRC-specific mortality; however, further research using post-diagnostic dietary data is required to confirm this relationship.