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First-degree relatives of patients with psychotic disorder have higher levels of polygenic risk (PRS) for schizophrenia and higher levels of intermediate phenotypes.
We conducted, using two different samples for discovery (n = 336 controls and 649 siblings of patients with psychotic disorder) and replication (n = 1208 controls and 1106 siblings), an analysis of association between PRS on the one hand and psychopathological and cognitive intermediate phenotypes of schizophrenia on the other in a sample at average genetic risk (healthy controls) and a sample at higher than average risk (healthy siblings of patients). Two subthreshold psychosis phenotypes, as well as a standardised measure of cognitive ability, based on a short version of the WAIS-III short form, were used. In addition, a measure of jumping to conclusion bias (replication sample only) was tested for association with PRS.
In both discovery and replication sample, evidence for an association between PRS and subthreshold psychosis phenotypes was observed in the relatives of patients, whereas in the controls no association was observed. Jumping to conclusion bias was similarly only associated with PRS in the sibling group. Cognitive ability was weakly negatively and non-significantly associated with PRS in both the sibling and the control group.
The degree of endophenotypic expression of schizophrenia polygenic risk depends on having a sibling with psychotic disorder, suggestive of underlying gene–environment interaction. Cognitive biases may better index genetic risk of disorder than traditional measures of neurocognition, which instead may reflect the population distribution of cognitive ability impacting the prognosis of psychotic disorder.
It is crucial to identify people at risk for type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM) to implement preventive interventions in order to address these pandemics. A simple score exclusively based on dietary components, the Dietary-Based Diabetes-Risk Score (DDS) showed a strong inverse association with incident T2DM. The objective was to assess the association between DDS and the risk of GDM in a cohort of Spanish university graduates. The ‘Seguimiento Universidad de Navarra’ project is a prospective and dynamic cohort which included data of 3455 women who notified pregnancies between 1999 and 2012. The diagnosis of GDM is self-reported and further confirmed by physicians. A validated 136-item semi-quantitative FFQ was used to assess pre-gestational dietary habits. The development of the DDS was aimed to quantify the association between the adherence to this a priori dietary score and T2DM incidence. The score exclusively included dietary components (nine food groups with reported inverse associations with T2DM incidence and three food groups which reported direct associations with T2DM). Three categories of adherence to the DDS were assessed: low (11–24), intermediate (25–39) and high (40–60). The upper category showed an independent inverse association with the risk of incident GDM compared with the lowest category (multivariate-adjusted OR 0·48; 95 % CI 0·24, 0·99; P for linear trend: 0·01). Several sensitivity analyses supported the robustness of these results. These results reinforce the importance of pre-gestational dietary habits for reducing GDM and provide a brief tool to practically assess the relevant dietary habits in clinical practice.
This study examined (1) the association of dietary energy density from solid (EDS) and solid plus liquids (EDSL) with adiposity and cardiometabolic risk factors (CRF) in children with overweight and obesity, (2) the effect of under-reporting on the mentioned associations and (3) whether the association between ED and body composition and CRF is influenced by levels of physical activity. In a cross-sectional design, 208 overweight and obese children (8–12-year-old; 111 boys) completed two non-consecutive 24 h recalls. ED was calculated using two different approaches: EDS and EDSL. Under-reporters were determined with the Goldberg method. Body composition, anthropometry and fasting blood sample measurements were performed. Moderate to vigorous physical activity (MVPA) was registered with accelerometers (7-d-register). Linear regressions were performed to evaluate the association of ED with the previously mentioned variables. Neither EDS nor EDSL were associated with body composition or CRF. However, when under-reporters were excluded, EDS was positively associated with BMI (P=0·019), body fat percentage (P=0·005), abdominal fat (P=0·008) and fat mass index (P=0·018), while EDSL was positively associated with body fat percentage (P=0·008) and fat mass index (P=0·026). When stratifying the group according to physical activity recommendations, the aforementioned associations were only maintained for non-compliers. Cluster analysis showed that the low-ED and high-MVPA group presented the healthiest profile for all adiposity and CRF. These findings could partly explain inconsistencies in literature, as we found that different ED calculations entail distinct results. Physical activity levels and excluding under-reporters greatly influence the associations between ED and adiposity in children with overweight and obesity.
Polyphenols are a wide family of phytochemicals present in diverse foods. They might play a role in cancer development and progression. In vivo and in vitro studies have suggested beneficial properties and potential mechanisms. We aimed to evaluate the association between total and main classes of polyphenol intake and breast cancer (BC) risk in the Seguimiento Universidad de Navarra project – a prospective Mediterranean cohort study. We included 10 713 middle-aged, Spanish female university graduates. Polyphenol intake was derived from a semi-quantitative FFQ and matching food consumption data from the Phenol-Explorer database. Women with self-reported BC were asked to return a copy of their medical report for confirmation purposes; death certificates were used for fatal cases. Cox models were fitted to estimate multivariable-adjusted hazard ratios (HR) and 95 % CI for the association between tertiles (T) of polyphenol intake and BC. After 10·3 years of median follow-up, 168 probable incident BC cases were identified, out of which 100 were confirmed. We found no association between polyphenol intake and the overall BC risk. Nevertheless, we observed a significant inverse association between total polyphenol intake and BC risk for postmenopausal women, either for probable or only for confirmed cases (HRT3 v. T1 0·31 (95 % CI 0·13, 0·77; Ptrend=0·010)). Also, phenolic acid intake was inversely associated with postmenopausal BC. In summary, we observed no significant association between total polyphenol intake and BC risk. Despite a low number of incident BC cases in our cohort, higher total polyphenol intake was associated with a lower risk of postmenopausal BC.
The aim of this study was to develop and to assess a specific Multi-Criteria Decision Analysis (MCDA) framework to evaluate new drugs in an hospital pharmacy and therapeutics committee (P&TC) setting.
A pilot criteria framework was developed based on the EVIDEM (Evidence and Value: Impact on DEcisionMaking) framework, together with other relevant criteria, and assessed by a group of P&TC's members. The weighting of included criteria was done using a 5-point weighting technique. Two drugs were chosen by evaluation: an orphan-drug for Gaucher disease, and a nonorphan drug for the treatment of inflammatory bowel disease. Evidence matrices were developed, and value contribution of each drug was evaluated by P&TC's members. An agreed final framework was obtained through a discussion between the P&TC's members.
After criteria assessment, the pilot framework included eight quantitative criteria: “disease severity,” “unmet needs,” “comparative efficacy/effectiveness,” “comparative safety/tolerability,” “comparative patient-reported outcomes,” “comparative cost consequences-cost of treatment,” “comparative cost consequences-other medical costs,” and “quality of evidence”; and one contextual criterion: “opportunity costs and affordability.” The most valued criteria were: “comparative safety/tolerability,” “disease severity,” and “comparative efficacy/effectiveness.” When assessing the drugs most valued characteristics of the MCDA were the possibility that all team may contribute to drug assessment by means of scoring the matrices and the discussion to reach a consensus in drug positioning and value decision making.
The reflective MCDA would integrate quantitative and qualitative criteria relevant for a P&TC setting, allowing reflective discussions based on the criteria weighting score.
Human fascioliasis is a worldwide, pathogenic food-borne trematodiasis. Impressive clinical pictures comprising puzzling polymorphisms, manifestation multifocality, disease evolution changes, sequelae and mortality, have been reported in patients presenting with neurological, meningeal, neuropsychic and ocular disorders caused at distance by flukes infecting the liver. Proteomic and mass spectrometry analyses of the Fasciola hepatica excretome/secretome identified numerous, several new, plasminogen-binding proteins enhancing plasmin generation. This may underlie blood-brain barrier leakage whether by many simultaneously migrating, small-sized juvenile flukes in the acute phase, or by breakage of encapsulating formations triggered by single worm tracks in the chronic phase. Blood-brain barrier leakages may subsequently occur due to a fibrinolytic system-dependent mechanism involving plasmin-dependent generation of the proinflammatory peptide bradykinin and activation of bradykinin B2 receptors, after different plasminogen-binding protein agglomeration waves. Interactions between diverse parasitic situations and non-imbalancing fibrinolysis system alterations are for the first time proposed that explain the complexity, heterogeneity and timely variations of neurological disorders. Additionally, inflammation and dilation of blood vessels may be due to contact system–dependent generation bradykinin. This baseline allows for search of indicators to detect neurological risk in fascioliasis patients and experimental work on antifibrinolytic treatments or B2 receptor antagonists for preventing blood-brain barrier leakage.
In this work, the stopping power of a partially ionized helium plasma due to its free and bound electrons is analyzed for an electron temperature and density in which local thermal equilibrium (LTE) or non-local thermal equilibrium (NLTE) regimes can be possible. In particular by means of collisional-radiative models, the average ionization of the plasma as well as the abundances of different helium species (HeI, HeII, and HeIII) are analyzed in both LTE and NLTE thermodynamic states. The influence of this ionization and of the different ion abundances on the stopping power of the helium plasma is shown to be quite significant. Finally, our theoretical model is compared with experimental results on slowing down of swift argon ions in helium plasma.
This work characterizes Late Cretaceous calc-alkaline volcanic rocks in Gastre, Northern Patagonia, Argentina. These newly found porphyritic rocks bear an 40Ar–39Ar amphibole age of ~ 74–76 Ma, a subduction-type geochemical signature and a deep, garnet-bearing source. Extruded in a stage of low magmatic activity in the Northern Patagonian Andes (~ 41–44° S), they could represent an eastward migration of the Late Cretaceous magmatic arc that was associated with a regional compressive deformational stage in the South American margin.
Magnesium (Mg2+) has received considerable attention with regards to its potential role in the pathophysiology of the mood disorders, but the available evidence seems inconclusive.
To review and quantitatively summarise the human literature on Mg2+ intake and Mg2+ blood levels in the mood disorders and the effects of Mg2+ supplements on mood.
Systematic review and meta-analyses.
Adherence to a Mg2+-rich diet was negatively associated with depression in cross-sectional (odds ratio = 0.66) but not in prospective studies. Mg2+ levels in bodily fluids were on average higher in patients with a mood disorder (Hedge's g = 0.19), but only in patients treated with antidepressants and/or mood stabilisers. There was no evident association between Mg2+ levels and symptom severity. Mg2+ supplementation was associated with a decline in depressive symptoms in uncontrolled (g = −1.60) but not in placebo-controlled trials (g = −0.21).
Our results provide little evidence for the involvement of Mg2+ in the mood disorders.
The aim of this study is to provide an overview of the development of premature children, including attachment, child psychological adjustment and parental variables. 130 children < 1,500 g or < 32 weeks at birth from two public hospitals, assessed at two years corrected age, together with their parents. Parental socio-demographic data was collected. Infant development, attachment and child psychological adjustment were evaluated, as was parental stress. The percentage of preterm children with developmental delays ranged from 5% to 21%. Girls tend to show higher levels of development than boys with effect sizes ranging from small, η2p = .02, to medium, η2p = .07. Secure attachment was the most frequent pattern in the sample. No significant differences, p < .05, between preterm children and the normative population were found on children´s behavioral problems and maternal stress levels. Despite the fact prematurity is considered to be a risk factor for a child´s development, a significant proportion of these children do not show problems in terms of developmental levels, attachment pattern and maternal stress. However, socio-emotional and affective domains, as well as psychological support programs for parenthood, should be followed up from a multidisciplinary perspective.
During the INDEMARES/CHICA 0610, 0211 and 0412 expeditions, carried out in the northern Spanish sector of the Gulf of Cádiz (Spain), samples were collected with a box-corer in 11 mud volcanoes and their adjacent bottoms. Chemoautotrophic communities were found in nine mud volcanoes. Among Decapoda, a rare eucalliacid, belonging to the genus Calliax and related to the Mediterranean infralittoral species C. lobata (de Gaillande and Lagardère 1966), was present in three of them. Data on its morphology, biogeographic distribution, vertical distribution within the burrows, sediment composition, pH and redox potential values (each in 5 cm intervals) are given; information on the chemoautotrophic communities associated with this species are also provided.
A large collection of maize macro-specimens has been gathered from archaeological sites across the American continent, but only a few have been directly dated by accelerator mass spectrometry (AMS). We recently conducted two new excavations in several rock shelters of Tehuacán valley (San Marcos, Coxcatlán, and Purrón) and uncovered 132 non-manipulated macro-specimens of maize suitable for morphological and paleogenomic analysis, including many complete cobs, stalks, internodes, and leaves. Direct AMS dates for 43 samples found in San Marcos or Coxcatlán confirm the previously reported chronologies for these sites. By contrast, a cob found in Purrón was dated to 3060±30 before present (3360–3180 cal BP) (2σ), demonstrating that maize was present at that site at least 1500 calendar years earlier than previously expected, and suggesting that other specimens of similar age are still likely to be found in the southeastern region of the Tehuacán valley. A global comparison of macro-specimen chronology across the continent shows that the current archaebotanical record does not yet reflect the chronology of dispersal from central Mexico to northern or southern regions, opening the possibility for finding the missing links in subsequent expeditions within Mexico and Central America.
The use of chimeric molecules fusing several antigenic determinants is a promising strategy for the development of low-cost, standardized and reliable kits to determine specific antibodies. In this study, we designed and assessed a novel recombinant chimera that complements the performance of our previously developed chimera, CP1 [FRA and SAPA antigens (Ags)], to diagnose chronic Chagas disease. The new chimeric protein, named CP3, is composed of MAP, TcD and TSSAII/V/VI antigenic determinants. We compared the performance of both chimeric Ags using a panel of 67 Trypanosoma cruzi-reactive sera and 67 non-reactive ones. The sensitivity of CP3 vs CP1 was 100 and 90.2%, and specificity was 92.5 and 100%, respectively. The mixture of CP1 + CP3 achieved 100% of sensitivity and specificity. More importantly, an additional subset of 17 sera from patients with discordant results of conventional serological methods was analysed; the CP1 + CP3 mixture allowed us to accurately classify 14 of them with respect to IIF, the usual technique used in most of the reference centres. These results show an improved performance of the CP1 + CP3 mixture in comparison with enzyme-linked immunosorbent assay and indirect haemagglutination commercial assays.
This article summarises the current position of evidence-based psychodynamic psychotherapies aimed at the treatment of borderline personality disorder – mentalisation-based treatment and transference-focused psychotherapy – noting the main challenges they face, especially in the area of dissemination.
How food is produced and consumed has consequences for ecosystems, such as resource use and greenhouse gas (GHG) emission among others. The Mediterranean diet (MedDiet) was proposed as a sustainable dietary model, due to its nutritional, environmental, economic and sociocultural dimensions. However, further evidence is needed. Thus, our objective was to evaluate the impact on resource (land, water and energy) use and GHG emission of better adherence to the MedDiet in a Mediterranean Spanish cohort.
We analysed the dietary pattern of participants through a validated FFQ. The outcomes were land use, water and energy consumption and GHG emission according to MedDiet adherence. The specific environmental footprints of food item production and processing were obtained from different available life-cycle assessments.
Spanish university graduates.
Participants (n 20 363) in the Seguimiento Universidad de Navarra (SUN) cohort.
Better adherence to the MedDiet was associated with lower land use (−0·71 (95 % CI −0·76, −0·66) m2/d), water consumption (−58·88 (95 % CI −90·12, −27·64) litres/d), energy consumption (−0·86 (95 % CI −1·01, −0·70) MJ/d) and GHG emission (−0·73 (95 % CI −0·78, −0·69) kg CO2e/d). A statistically significant linear trend (P<0·05) was observed in all these analyses.
In this Mediterranean cohort, better adherence to the MedDiet was an eco-friendly option according to resource consumption and GHG emission.
Cognitive deficits are a core feature of early stages in schizophrenia. However, the extent to which antipsychotic (AP) have a deleterious effect on cognitive performance remains under debate. We aim to investigate whether anticholinergic loadings and dose of AP drugs in first episode of psychosis (FEP) in advanced phase of remission are associated with cognitive impairment and the differences between premorbid intellectual quotient (IQ) subgroups.
Two hundred and sixty-six patients participated. The primary outcomes were cognitive dimensions, dopaminergic/anticholinergic load of AP [in chlorpromazine equivalents (Eq-CPZ) and the Anticholinergic Risk Scale (ARS), respectively].
Impairments in processing speed, verbal memory and global cognition were significantly associated with high Eq-CPZ and verbal impairment with high ARS score. Moreover, this effect was higher in the low IQ subgroup.
Clinicians should be aware of the potential cognitive impairment associated with AP in advanced remission FEP, particularly in lower premorbid IQ patients.
The association between added sugars or sugar-sweetened beverage consumption and the risk of depression, as well as the role of carbohydrate quality in depression risk, remains unclear. Among 15 546 Spanish university graduates from the Seguimiento Universidad de Navarra (SUN) prospective cohort study, diet was assessed with a validated 136-item semi-quantitative FFQ at baseline and at 10-year follow-up. Cumulative average consumption of added sugars, sweetened drinks and an overall carbohydrate quality index (CQI) were calculated. A better CQI was associated with higher whole-grain consumption and fibre intake and lower glycaemic index and consumption of solid (instead of liquid) carbohydrates. Clinical diagnoses of depression during follow-up were classified as incident cases. Multivariable time-dependent Cox regression models were used to estimate hazard ratios (HR) of depression according to consumption of added sugars, sweetened drinks and CQI. We observed 769 incident cases of depression. Participants in the highest quartile of added sugars consumption showed a significant increment in the risk of depression (HR=1·35; 95 % CI 1·09, 1·67, P=0·034), whereas those in the highest quartile of CQI (upper quartile of the CQI) showed a relative risk reduction of 30 % compared with those in the lowest quartile of the CQI (HR=0·70; 95 % CI 0·56, 0·88). No significant association between sugar-sweetened beverage consumption and depression risk was found. Higher added sugars and lower quality of carbohydrate consumption were associated with depression risk in the SUN Cohort. Further studies are necessary to confirm the reported results.
The aim of this study was to investigate the association between the adherence to empirically derived dietary patterns and gestational diabetes mellitus (GDM) risk and of healthy lifestyles with the prevention of GDM defining an overall healthy score. The Seguimiento Universidad de Navarra project is a Mediterranean cohort of university graduates started in 1999. We included 3455 pregnant women. During a mean follow-up of 10·3 (sd 3·3) years, we identified 173 incident GDM cases. Two major dietary patterns were identified using principal component analysis: the Western dietary pattern (WDP) (characterised by a high consumption of meat-based products and processed foods) and the Mediterranean dietary pattern (MDP) (characterised by a high consumption of vegetables, fruits, fish and non-processed foods). A low-risk score for GDM was defined taking into account important risk factors (age, BMI and unhealthy dietary pattern) for GDM. Positive association was found in the multivariable model between the highest quartile of adherence to WDP and GDM incidence compared with the lowest quartile (OR 1·56; 95 % CI 1·00, 2·43). No association was found between adherence to the MDP and GDM incidence (OR 1·08; 95 % CI 0·68, 1·70 for the highest quartile compared with the lowest). Women who adhered to all three low-risk factors had a 76 % lower risk of GDM (OR 0·24; 95 % CI 0·10, 0·55) compared with women who did not adhere to any factor before pregnancy. In conclusion, our results reinforce the importance of dietary recommendations and other two factors (low BMI and young age at pregnancy) in pre-gravid women.
Since dirofilariosis caused by Dirofilaria immitis is a vector-borne disease, its distribution depends on environmental conditions as well as demographic factors and the management of pets by humans. In the province of Salamanca (west-central Spain) the disease has been known for many years, appearing in an area with extensive irrigated crops along the Tormes river. Because recent demographic changes have occurred in this area, the present study has been carried out with the aim of monitoring the distribution and prevalence of the disease in the canine population of this area. For that purpose, 191 dogs were analysed through antigen and microfilaria tests and geo-referenced in a map. The overall prevalence was 5.8%, although the disease was only present in dogs from municipalities with irrigated crops in which the prevalence was 16.7%. These results indicate that D. immitis continues to be present in the province of Salamanca, and that it is associated with the presence of irrigation, but with a clear decrease in the prevalence. Causes of the decrease in prevalence, as well as the potential zoonotic risk, are discussed.