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Schizophrenia (SZ) is a severe mental health condition involving gene-environment interactions, with obstetric complications (OCs) conferring an elevated risk for the disease. Current research suggests that OCs may exacerbate SZ symptoms. This study conducted a systematic review and meta-analysis to comprehensively evaluate differences in psychopathology between individuals with and without exposure to OCs in relation to SZ and related disorders. We systematically searched PubMed, PsycINFO, and SCOPUS to identify eligible studies. A total of 4091 records were retrieved through systematic and citation searches. 14 studies were included in the review, and 12 met the criteria for meta-analysis, involving 2992 patients. The analysis revealed that SZ patients who had been exposed to OCs exhibited significantly higher levels of positive symptoms (SMD=0.10, 95 %CI=0.01,0.20; p=0.03), general psychopathology (SMD=0.37, 95 %CI=0.22,0.52; p<0.001), total clinical symptomatology (SMD=0.44, 95 %CI=0.24,0.64; p<0.001) and depressive symptoms (SMD=0.47, 95 %CI=0.09,0.84; p=0.01). No significant differences were found in negative symptomatology and functioning. Our results suggest that OCs are not only associated with an increased risk of developing psychosis but with more severe symptomatology., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Given the shared ectodermal origin and integrated development of the face and the brain, facial biomarkers emerge as potential candidates to assess vulnerability for disorders in which neurodevelopment is compromised, such as schizophrenia (SZ) and bipolar disorder (BD). The sample comprised 188 individuals (67 SZ patients, 46 BD patients and 75 healthy controls (HC)). Using a landmark-based approach on 3D facial reconstructions, we quantified global and local facial shape differences between SZ/BD patients and HC using geometric morphometrics. We also assessed correlations between facial and brain cortical measures. All analyses were performed separately by sex. Diagnosis explained 4.1 % - 5.9 % of global facial shape variance in males and females with SZ, and 4.5 % - 4.1 % in BD. Regarding local facial shape, we detected 43.2 % of significantly different distances in males and 47.4 % in females with SZ as compared to HC, whereas in BD the percentages decreased to 35.8 % and 26.8 %, respectively. We detected that brain area and volume significantly explained 2.2 % and 2 % of facial shape variance in the male SZ - HC sample. Our results support facial shape as a neurodevelopmental marker for SZ and BD and reveal sex-specific pathophysiological mechanisms modulating the interplay between the brain and the face., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The International Rare Diseases Research Consortium (IRDiRC) Diagnostic Scientific Committee (DSC) is charged with discussion and contribution to progress on diagnostic aspects of the IRDiRC core mission. Specifically, IRDiRC goals include timely diagnosis, use of globally coordinated diagnostic pipelines, and assessing the impact of rare diseases on affected individuals. As part of this mission, the DSC endeavored to create a list of research priorities to achieve these goals. We present a discussion of those priorities along with aspects of current, global rare disease needs and opportunities that support our prioritization. In support of this discussion, we also provide clinical vignettes illustrating real-world examples of diagnostic challenges., (Copyright © 2024. Published by Elsevier Masson SAS.)

River widening, defined as a lateral expansion of the channel, is a critical process that maintains fluvial ecosystems and is part of the regular functioning of rivers. However, in areas with high population density, channel widening can cause damage during floods. Therefore, for effective flood risk management it is essential to identify river reaches where abrupt channel widening may occur. Despite numerous efforts to predict channel widening, most studies have been limited to single rivers and single flood events, which may not be representative of other conditions. Moreover, a multi-catchment scale approach that covers various settings and flood magnitudes has been lacking. In this study, we fill this gap by compiling a large database comprising 1564 river reaches in several mountain regions in Europe affected by floods of varying magnitudes in the last six decades. By applying a meta-analysis, we aimed to identify the types of floods responsible for more extensive widening, the river reach types where intense widening is more likely to occur, and the hydraulic and morphological variables that explain widening and can aid in predicting widening. Our analysis revealed seven groups of reaches with significantly different responses to floods regarding width ratios (i.e., the ratio between channel width after and before a flood). Among these groups, the river reaches located in the Mediterranean region and affected by extreme floods triggered by short and intense precipitation events showed significantly larger widening than other river reaches in other regions. Additionally, the meta-analysis confirmed valley confinement as a critical morphological variable that controls channel widening but showed that it is not the only controlling factor. We proposed new statistical models to identify river reaches prone to widening, estimate potential channel width after a flood, and compute upper bound width ratios. These findings can inform flood hazard evaluations and the design of mitigation measures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

This paper studies spill-over effects of parental labour market shocks at two time points in the Covid-19 crisis: right after its onset in April 2020, and in January 2021. We use rich data from the UK to look at the consequences of immediate and persistent shocks that hit parents' economic livelihoods. These negative labour market shocks have substantially larger impacts when suffered by fathers than by mothers. Children of fathers that suffered the most severe shocks - earnings dropping to zero - are the ones that are consistently impacted. In April 2020, they were 10 percentage points less likely to have received additional paid learning resources, but their fathers were spending about 30 more minutes per day helping them with school work. However, by January 2021, this latter association switches sign, as the negative spill-over onto children's education occurred for those fathers facing more persistent, negative labour market shocks as the crisis progressed. The paper discusses potential mechanisms driving these results, finding a sustained deterioration of household finances and a worsening of father's mental health to be factors at play., (© 2023 The Authors. Published by Elsevier B.V.)

Background: Although there is scientific evidence of the presence of immunometabolic alterations in major depression, not all patients present them. Recent studies point to the association between an inflammatory phenotype and certain clinical symptoms in patients with depression. The objective of our study was to classify major depression disorder patients using supervised learning algorithms or machine learning, based on immunometabolic and oxidative stress biomarkers and lifestyle habits., Methods: Taking into account a series of inflammatory and oxidative stress biomarkers (C-reactive protein (CRP), tumor necrosis factor (TNF), 4-hydroxynonenal (HNE) and glutathione), metabolic risk markers (blood pressure, waist circumference and glucose, triglyceride and cholesterol levels) and lifestyle habits of the participants (physical activity, smoking and alcohol consumption), a study was carried out using machine learning in a sample of 171 participants, 91 patients with depression (71.42% women, mean age = 50.64) and 80 healthy subjects (67.50% women, mean age = 49.12). The algorithm used was the support vector machine, performing cross validation, by which the subdivision of the sample in training (70%) and test (30%) was carried out in order to estimate the precision of the model. The prediction of belonging to the patient group (MDD patients versus control subjects), melancholic type (melancholic versus non-melancholic patients) or resistant depression group (treatment-resistant versus non-treatment-resistant) was based on the importance of each of the immunometabolic and lifestyle variables., Results: With the application of the algorithm, controls versus patients, such as patients with melancholic symptoms versus non-melancholic symptoms, and resistant versus non-resistant symptoms in the test phase were optimally classified. The variables that showed greater importance, according to the results of the area under the ROC curve, for the discrimination between healthy subjects and patients with depression were current alcohol consumption (AUC = 0.62), TNF-α levels (AUC = 0.61), glutathione redox status (AUC = 0.60) and the performance of both moderate (AUC = 0.59) and vigorous physical exercise (AUC = 0.58). On the other hand, the most important variables for classifying melancholic patients in relation to lifestyle habits were past (AUC = 0.65) and current (AUC = 0.60) tobacco habit, as well as walking routinely (AUC = 0.59) and in relation to immunometabolic markers were the levels of CRP (AUC = 0.62) and glucose (AUC = 0.58). In the analysis of the importance of the variables for the classification of treatment-resistant patients versus non-resistant patients, the systolic blood pressure (SBP) variable was shown to be the most relevant (AUC = 0.67). Other immunometabolic variables were also among the most important such as TNF-α (AUC = 0.65) and waist circumference (AUC = 0.64). In this case, sex (AUC = 0.59) was also relevant along with alcohol (AUC = 0.58) and tobacco (AUC = 0.56) consumption., Conclusions: The results obtained in our study show that it is possible to predict the diagnosis of depression and its clinical typology from immunometabolic markers and lifestyle habits, using machine learning techniques. The use of this type of methodology could facilitate the identification of patients at risk of presenting depression and could be very useful for managing clinical heterogeneity., Competing Interests: Declaration of Competing Interest The authors report no biomedical financial interests or potential conflicts of interest regarding this work., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Alterations in cognitive performance have been described in patients with major depressive disorder (MDD). However, the specific risk factors of these changes are not yet known. This study aimed to explore whether inmunometabolic parameters are related to cognitive performance in MDD in comparison to healthy controls (HC) METHODS: Sample consisted of 84 MDD patients and 78 HC. Both groups were compared on the results of cognitive performance measured with the Cambridge Neuropsychological Test Automated Battery (CANTAB), the presence of metabolic syndrome (MetS) and an inflammatory/oxidative index calculated by a principal component analysis of peripheral biomarkers (tumor necrosis factor, C-reactive protein and 4-hydroxynonenal). A multiple linear regression was carried out, to study the relationship between inmunometabolic variables and the global cognitive performance, being the latter the dependent variable., Results: Significant differences were obtained in the inflammatory/oxidative index between both groups (F (1157) = 12.93; p < .001), also in cognitive performance (F (1157) = 56.75; p < .001). The inmunometabolic covariate regression model (i.e., condition (HC/MDD), sex, age and medication loading, MetS, inflammatory/oxidative index and the interaction between MetS and inflammatory/oxidative index) was statistically significant (F (7157) = 11.24; p < .01) and explained 31% of variance. The condition, being either MDD or HD, (B=-0.97; p < .001), age (B=-0.28; p < .001) and the interaction between inflammatory/oxidative index and MetS (B=-0.38; p = .02) were factors associated to cognitive performance., Limitations: Sample size was relatively small. The cross-sectional design of the study limits the possibilities of analysis., Conclusions: Our results provide evidence on the conjoint influence of metabolic and inflammatory dysregulation on cognitive dysfunction in MDD patients. In this way, our study opens a line of research in immunometabolic agents to deal with cognitive decline associated with MDD., (Copyright © 2021. Published by Elsevier Ltd.)

Soil-applied biochar has been reported to possess the potential to mitigate nitrate leaching and thus, exert beneficial effects beyond carbon sequestration. The main objective of the present study is to confirm if a pine gasification biochar that has proven able to decrease soil-soluble nitrate in previous research can indeed exert such an effect and to determine by which mechanism. For this purpose, lysimeters containing soil-biochar mixtures at 0, 12 and 50 t biochar ha -1 were investigated in two different scenarios: a fresh biochar scenario consisting of fresh biochar and a fallow-managed soil, and an aged biochar scenario with a 6-yr naturally aged biochar in a crop-managed soil. Soil columns were assessed under a mimicked Mediterranean ambient within a greenhouse setting during an 8-mo period which included a barley crop cycle. A set of parameters related to nitrogen cycling, and particularly to mechanisms that could directly or indirectly explain nitrate content reduction (i.e., sorption, leaching, microbially-mediated processes, volatilisation, plant uptake, and ecotoxicological effects), were assessed. Specific measurements included soil solution and leachate ionic composition, microbial biomass and activity, greenhouse gas (GHG) emissions, N and O isotopic composition of nitrate, crop yield and quality, and ecotoxicological endpoints, among others. Nitrate content reduction in soil solution was verified for the fresh biochar scenario in both 12 and 50 t ha -1 treatments and was coupled to a significant reduction of chloride, sodium, calcium and magnesium. This effect was noticed only after eight months of biochar application thus suggesting a time-dependent process. All other mechanisms tested being discarded, the formation of an organo-mineral coating emerges as a plausible explanation for the ionic content decrease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Mitochondrial cholesterol accumulation is a hallmark of alcoholic and non-alcoholic fatty liver diseases and impairs the function of specific solute carriers through changes in membrane physical properties. However, its impact on mitochondrial respiration and organization of respiratory supercomplexes has not been determined so far. Here we fed mice a cholesterol-enriched diet (HC) supplemented with sodium cholate to examine the effect of cholesterol in mitochondrial function. HC feeding increased liver cholesterol content, which downregulated Srebp2 and Hmgcr expression, while sodium cholate administration decreased Cyp7a1 and Cyp8b1 mRNA levels, suggesting the downregulation of bile acid synthesis through the classical pathway. HC-fed mice exhibited increased expression of Stard1 and Mln64 and enhanced mitochondrial free cholesterol levels (2-3 fold), leading to decreased membrane fluidity. Mitochondria from HC-fed mice displayed increased cholesterol loading in both outer and inner mitochondrial membranes. Cholesterol loading decreased complex I and complex II-driven state 3 respiration and mitochondrial membrane potential. Decreased respiratory and uncoupling control ratio from complex I was also observed after in situ enrichment of mouse liver mitochondria with cholesterol or enantiomer cholesterol, the mirror image of natural cholesterol. Moreover, in vivo cholesterol loading decreased the level of complex III 2 and the assembly of respiratory supercomplexes I 1 +III 2 +IV and I 1 +III 2 . Moreover, HC feeding caused oxidative stress and mitochondrial GSH (mGSH) depletion, which translated in hepatic steatosis and liver injury, effects that were rescued by replenishing mGSH with GSH ethyl ester. Overall, mitochondrial cholesterol accumulation disrupts mitochondrial functional performance and the organization of respiratory supercomplexes assembly, which can contribute to oxidative stress and liver injury., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

The use of low-cost inorganic sorbents as a new sustainable strategy to enhance the valorization of nutrients (N-P-K), from the urban water cycle (e.g., side streams from sewage sludge anaerobic digestion), in agriculture applications is presented. The simultaneous recovery and stabilization of ammonium and phosphate by using a mixture of two reactive sorbents (Na and K zeolites and magnesium oxide) was evaluated. The nutrients stabilization process, favoured at alkaline pH values, is carried out by a) the precipitation of phosphate ions with magnesium and/or ammonium ions and b) the sorption of ammonium by Na- and K-zeolites. MgO(s) promoted the stabilization of phosphate as bobierrite (Mg 3 (PO 4 ) 2 (s)) or struvite (MgNH 4 PO 4 (s)) depending on the applied dose. Doses with the stoichiometric molar ratio of Mg/P promote the formation of bobierrite, while molar ratios higher than 3 favour the formation of struvite. Na zeolites (NaP1-NA, NaP1-IQE) demonstrated efficiency on ammonium stabilization between 60±2 (for 15gZ/L) to 90±3% (for 50gZ/L). The ammonium recovery efficiency is limited by the zeolite sorption capacity. If the target of the fertilizing criteria should include K, then the use of a K-zeolite (e.g., 5AH-IQE) provides a good solution. The optimum pH for the precipitation of struvite and bobierrite is 9.5 and the optimum pH for ammonium removal is between 4 and 8.5. N is present in higher concentrations (up 0.7-1gNH 4 + /L) when pH is ranged between 8.2 and 8.6. The ammonium recovery ratios were better than those previously reported using only magnesium oxide or even a more expensive reagent as newberrite (MgHPO 4 (s)). The recovery mechanisms described generate low-solubility stabilized nutrients forms that potentially can be applied as slow-release fertilizers in agriculture. Thus, the use in agriculture of blends of digested sludge with low-solubility stabilized nutrients forms will improve soils quality properties in terms of organic matter and nutrients availability., (Copyright © 2018. Published by Elsevier B.V.)

In recent years, intriguing hints for the violation of lepton flavor universality (LFU) have been accumulated in semileptonic B decays, both in the charged-current transitions b→cℓ^{-}ν[over ¯]&#95;{ℓ} (i.e., R&#95;{D}, R&#95;{D^{*}}, and R&#95;{J/ψ}) and the neutral-current transitions b→sℓ^{+}ℓ^{-} (i.e., R&#95;{K} and R&#95;{K^{*}}). Hints for LFU violation in R&#95;{D^{(*)}} and R&#95;{J/ψ} point at large deviations from the standard model (SM) in processes involving tau leptons. Moreover, LHCb has reported deviations from the SM expectations in b→sμ^{+}μ^{-} processes as well as in the ratios R&#95;{K} and R&#95;{K^{*}}, which together point at new physics (NP) affecting muons with a high significance. These hints for NP suggest the possibility of huge LFU-violating effects in b→sτ^{+}τ^{-} transitions. In this Letter, we predict the branching ratios of B→Kτ^{+}τ^{-}, B→K^{*}τ^{+}τ^{-}, and B&#95;{s}→ϕτ^{+}τ^{-}, taking into account NP effects in the Wilson coefficients C&#95;{9(^{'})}^{ττ} and C&#95;{10(^{'})}^{ττ}. Assuming a common NP explanation of R&#95;{D}, R&#95;{D^{(*)}}, and R&#95;{J/ψ}, we show that a very large enhancement of b→sτ^{+}τ^{-} processes, of around 3 orders of magnitude compared to the SM, can be expected under fairly general assumptions. We find that the branching ratios of B&#95;{s}→τ^{+}τ^{-}, B&#95;{s}→ϕτ^{+}τ^{-}, and B→K^{(*)}τ^{+}τ^{-} under these assumptions are in the observable range for LHCb and Belle II.

The aim of this prospective study was to expand previously reported evidence on the 10-year clinical and functional course of borderline personality disorder (BPD) in a Spanish sample. Participants diagnosed with BPD were assessed at baseline and at 10-year follow-up to evaluate BPD symptomatology and other relevant clinical measures, suicidal behavior, dimensional personality traits, Axis I and II comorbidity, use of mental health resources, and psychosocial functioning. At the 10-year follow up, significant improvements were observed on BPD domains, suicidal behavior, and other clinical measures. Neuroticism, impulsiveness, and aggression-hostility features trended toward normalization, whereas activity and sociability were impaired over time. Comorbidity with Axis I and personality disorders remained high. Social functioning and occupational functioning were largely unchanged. These findings confirm the tendency toward a symptomatic remission of BPD over the long term with regard to symptom criteria and characteristic dimensional traits. However, psychosocial functioning remains impaired.

Leishmaniasis is a vector-borne disease transmitted by phlebotomine sand flies. Information about blood meal preferences in sand flies is essential to understand the epidemiology of the disease to adopt control measures. In previous studies, a polymerase chain reaction (PCR) of 359bp fragment of the conserved gene cytochrome b (cyt b) and further sequencing were applied in the study of blood meal sources in sand flies collected in the area of a leishmaniasis outbreak in southwest Madrid, Spain, providing significant information about blood meal preferences in the focus. In this work, a PCR-restriction fragment length polymorphism (RFLP) targeting a fragment of 359bp of vertebrate cyt b gene was developed. Restriction endonucleases HaeIII and HinfI generated specific patterns consistent with the blood meal sources found in sand flies. The protocol has been validated with twenty six engorged females collected in the field with CDC traps. Blood meals from nine vertebrates were identified based on PCR-cyt b and sequencing-human, dog, cat, horse, hare, rabbit, sheep, goat and chicken - and mixed blood meals (sheep/human; sheep/goat) - and successfully distinguished by PCR-RFLP. Therefore, this approach is an efficient and reliable alternative method to be applied in entomological surveys., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The Ordesa and Monte Perdido National Park, located in the Southern Pyrenees, constitutes the highest karst system in Western Europe. No previous studies regarding its geochemical and isotopic groundwater characterization are available in this area. This work presents the results of field and sampling campaigns carried out between July 2007 and September 2013. The groundwater presents high calcium bicarbonate contents due to the occurrence of upper Cretaceous and lower Paleocene-Eocene carbonate materials in the studied area. Other relevant processes include dissolution of anhydrite and/or gypsum and incongruent dissolution of Mg-limestone and dolomite. The water stable isotopes (δ(18)O, δ(2)H) show that the oceanic fronts from the Atlantic Ocean are responsible for the high levels of precipitation. In autumn, winter, and spring, a deuterium excess is found in the recharge water, which could be related to local atmospheric transport of low-altitude snow sublimation vapour and its later condensation on the snow surface at higher altitude, where recharge is mostly produced. The recharge zones are mainly between 2500m and 3200ma.s.l. The tritium content of the water suggests short groundwater transit times. The isotopic composition of dissolved sulphate points to the existence of regional fluxes mixed with local discharge in some of the springs. This work highlights the major role played by the altitude difference between the recharge and discharge zones in controlling the chemistry and the vertical variability of the isotopic composition in high-altitude karst aquifers., (Copyright © 2014 Elsevier B.V. All rights reserved.)

We report the insertion of a transmembrane protein, lactose permease (LacY) from Escherichia coli (E. coli), in supported lipid bilayers (SLBs) of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG), in biomimetic molar proportions. We provide evidence of the preferential insertion of LacY in the fluid domains. Analysis of the self-assembled protein arrangements showed that LacY: (i) is inserted as a monomer within fluid domains of SLBs of POPE:POPG (3:1, mol/mol), (ii) has a diameter of approx. 7.8nm; and (iii) keeps an area of phospholipids surrounding the protein that is compatible with shells of phospholipids., (2009 Elsevier B.V. All rights reserved.)

One of the hallmarks of Alzheimer's disease is the self-aggregation of the amyloid beta peptide (Abeta) in extracellular amyloid fibrils. Among the different forms of Abeta, the 42-residue fragment (Abeta1-42) readily self-associates and forms nucleation centers from where fibrils can quickly grow. The strong tendency of Abeta1-42 to aggregate is one of the reasons for the scarcity of data on its fibril formation process. We have used atomic force microscopy (AFM) to visualize in liquid environment the fibrillogenesis of synthetic Abeta1-42 on hydrophilic and hydrophobic surfaces. The results presented provide nanometric resolution of the main structures characteristic of the several steps from monomeric Abeta1-42 to mature fibrils in vitro. Oligomeric globular aggregates of Abeta1-42 precede the appearance of protofibrils, the first fibrillar species, although we have not obtained direct evidence of oligomer-protofibril interconversion. The protofibril dimensions deduced from our AFM images are consistent with a model that postulates the stacking of the peptide in a hairpin conformation perpendicular to the long axis of the protofibril, forming single beta-sheets ribbon-shaped. The most abundant form of Abeta1-42 fibril exhibits a nodular structure with a ~100-nm periodicity. This length is very similar 1) to the length of protofibril bundles that are the dominant feature at earlier stages in the aggregation process, 2) to the period of helical structures that have been observed in the core of fibrils, and 3) to the distance between regularly spaced, structurally weak fibril points. Taken together, these data are consistent with the existence of a ~100-nm long basic protofibril unit that is a key fibril building block.