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Emerging evidence suggests brain white matter alterations in adolescents with early-onset psychosis (EOP; age of onset d = 0.37), posterior corona radiata (d = 0.32), and superior fronto‐occipital fasciculus (d = 0.31). We also found widespread higher RD and more localized higher MD and AD. We detected significant effects of diagnostic subgroup, sex, and duration of illness, but not medication status. Using the largest EOP DTI sample to date, our findings suggest a profile of widespread white matter microstructure alterations in adolescents with EOP, most prominently in male individuals with early-onset schizophrenia and individuals with a shorter duration of illness.

Although parasitism is one of the most common species interactions in nature, the role of parasites in their hosts' thermal tolerance is often neglected. This study examined the ability of the trematode Podocotyle atomon to modulate the feeding and stress response of Gammarus locusta towards temperature. To accomplish this, infected and uninfected females and males of Gammarus locusta were exposed to temperatures (2, 6, 10, 14, 18, 22, 26, 30 °C) for six days. Shredding (change in food biomass) and defecation rates (as complementary measure to shredding rate) were measured as proxies for feeding activity. Lipid and glycogen concentrations (energy reserves), catalase (oxidative stress indicator), and phenoloxidase (an immunological response in invertebrates) were additionally measured. Gammarid survival was optimal at 10 °C as estimated by the linear model and was unaffected by trematode infection. Both temperature and sex influenced the direction of infection effect on phenoloxidase. Infected females presented lower phenoloxidase activity than uninfected females at 14 and 18 °C, while males remained unaffected by infection. Catalase activity increased at warmer temperatures for infected males and uninfected females. Higher activity of this enzyme at colder temperatures occurred only for infected females. Infection decreased lipid content in gammarids by 14 %. Infected males had significantly less glycogen than uninfected, while infected females showed the opposite trend. The largest infection effects were observed for catalase and phenoloxidase activity. An exacerbation of catalase activity in infected males at warmer temperatures might indicate (in the long-term) unsustainable, overwhelming, and perhaps lethal conditions in a warming sea. A decrease in phenoloxidase activity in infected females at warmer temperatures might indicate a reduction in the potential for fighting opportunistic infections. Results highlight the relevance of parasites and host sex in organismal homeostasis and provide useful insights into the organismal stability of a widespread amphipod in a warming sea.

Lesbian, gay and bisexual (LGB) people have more risk of suffering from violence and situations of discrimination than heterosexual people. The current study compares LGB people with heterosexual people in protective factors, violence, health and well-being factors. The sample comprises 609 Spanish people between 14 and 25 years old. We established a cross-sectional design. A survey including questions about sociodemographic information and protective, violence and health and well-being factors was designed ad hoc for this study. The results show that the LGB group (n = 342) is more at risk of verbal and physical violence and feels more isolated than the heterosexual participants (n = 267). In contrast, heterosexual participants report having more employment discrimination. No significant differences were found in social support or psychological health. These results are important to understand the state of social normalization and non-discrimination for LGB people in certain contexts in Spain, and its impact on psychological health.

[Background]: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life., [Methods]: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed., [Results]: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth., [Conclusions]: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy., This work was supported by the German Research Foundation (DFG Grant Nos. HA7070/2-2, HA7070/3, HA7070/4 [to TH]) and IZKF of the medical faculty of Münster (Grants No. Dan3/012/17 [to UD] and MzH 3/020/20 [to TH]), and NHMRC projects (Grant No. 1064643 [to BJH] and 1024570 [to CGD]). The CIAM study was supported by the University of Cape Town Research Committee, South African National Research Foundation, and the South African Medical Research Council (principal investigator [PI], Fleur M. Howells) and Grant No. R01MH117601 (to NJ). This work was funded by the German Research Foundation (Grant Nos. FOR2107 JA 1890/7-1 and FOR2107 JA 1890/7-2 [to AJ]) and Swinburne University scholarship/Australian Postgraduate Award (to JK). Collection of the COGSBD cohort was funded by the Jack Brockhoff Foundation, University of Melbourne, Barbara Dicker Brain Sciences Foundation, Rebecca L Cooper Foundation, and the Society of Mental Health Research (to JK). This work was funded by the German Research Foundation (Grant Nos. FOR2107 KI588/14-1 and FOR2107 KI588/14-2 [to TK]). The St. Göran study was supported by grants from the Swedish Research Council (Grant No. 2018-02653 [to ML]), the Swedish foundation for Strategic Research (Grant No. KF10-0039 [to ML]), the Swedish Brain foundation (Grant No. FO2020-0261 [to ML]), and the Swedish Government under the LUA/ALF agreement (Grant Nos. ALF 20170019 and ALFGBG-716801 [to ML]). This work was supported by RFBR (Grant No. 20-013-00748 [to IL, AST]) and funded by the Health Research Board (Grant No. HRA_POR/2011/100 [to CM]). The Australian Schizophrenia Research Bank (ASRB) was supported by the NHMRC (Enabling Grant No. 386500), the Pratt Foundation, Ramsay Health Care, the Viertel Charitable Foundation, and the Schizophrenia Research Institute. Chief investigators for ASRB were VC, US, RSc, AJ, BM, PTM, SVC, FH, and CPa. This work was supported by Deutsche Forschungsgemeinschaft (Grant Nos. DFG NE 2254/2-1, NE 2254/3-1, NE2254/4-1 [to IN]), the University Research Priority Program “Integrative Human Physiology” at the University of Zurich (to ROT), an NHMRC Senior Principal Research Fellowship (Grant No. 1105825 [to CPa]), an NHMRC L3 Investigator Grant (Grant No. 1196508 [to CPa]), and NHMRC Program Grant (Grant No. 1150083 [to CPa]). ASRB was supported by the NHMRC (Enabling Grant No. 386500), the Pratt Foundation, Ramsay Health Care, the Viertel Charitable Foundation and the Schizophrenia Research Institute. Chief investigators for ASRB were VC, US, RSc, AJ, BM, PTM, SVC, FH, and CPa. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant (Agreement No. 798181 [to GP]). ASRB was supported by the NHMRC (Enabling Grant, ID 386500), the Pratt Foundation, Ramsay Health Care, the Viertel Charitable Foundation and the Schizophrenia Research Institute. Chief investigators for ASRB were VC, US, RSc, AJ, BM, PTM, SVC, FH, and CPa. The Imaging Genetics in Psychosis study was funded by Project Grants from the NHMRC (Grant Nos. APP630471 and APP1081603 [to YQ]) and the Macquarie University’s Australian Research Council (ARC) Centre of Excellence in Cognition and its Disorders (Grant No. CE110001021 [to YQ]). This work was supported by the Spanish Ministry of Science, Innovation and Universities/Economy and Competitiveness/Instituto de Salud Carlos III (Grant Nos. PI11/01766 and CPII19/00009 [to JR]), co-financed by European Regional Development Fund funds from the European Commission (“A Way of Making Europe”). ASRB was supported by the NHMRC (Enabling Grant No. 386500), the Pratt Foundation, Ramsay Health Care, the Viertel Charitable Foundation, and the Schizophrenia Research Institute. Chief investigators for ASRB were VC, US, RSc, AJ, BM, PTM, SVC, FH, and CPa. SR was supported by an NHMRC Senior Fellowship (Grant No. GNT1154651). Collection of the COGSBD cohort was funded by the Jack Brockhoff Foundation, University of Melbourne, Barbara Dicker Brain Sciences Foundation, Rebecca L Cooper Foundation, and the Society of Mental Health Research (to SR). This work was supported by NIHR; MRC (to KR), NIH (Grant Nos. MH-094268, MH-105660, and MH-107730 [to ASS]). The Neuroimaging of the Children's Attention Project cohort was funded by NHMRC, Australia (Grant No. 1065895). Earlier funding for the cohort as also provided by NHMRC (Grant No. 1008522) and a grant from the Collier Foundation. The ACPU cohort was funded by NHMRC, Australia (Project Grant Nos. 384419 and 569533 [to TS]). This work was supported by research grants from the National Healthcare Group, Singapore (Grant Nos. SIG/05004, SIG/05028, and SIG /1103), and the Singapore Bioimaging Consortium (RP C009/2006 [to KS]), and the Ministry of Health, Czech Republic - conceptual development of research organization (“Institute for Clinical and Experimental Medicine - IKEM, IN 00023001” [to ASk]). This study was supported by the Italian Ministry of Health (Grant No. RC/17-18-19-20-21/A [to GS]) and Ministry of Health of the Czech Republic (Grant No. NU20-04-00393 [to FS]). The Drakenstein Child Health Study (DCHS) cohort is funded by the Bill and Melinda Gates Foundation (Grant No. OPP 1017641) and the South African Medical Research Council. This DCHS contribution was made possible in part by a grant from Carnegie Corporation of New York. The statements made and views expressed are solely the responsibility of the author (DJS). STRADL study was supported and funded by the Wellcome Trust Strategic Award “Stratifying Resilience and Depression Longitudinally” (Grant No. 104036/Z/14/Z), and the Medical Research Council Mental Health Pathfinder Award “Leveraging routinely collected and linked research data to study the causes and consequences of common mental disorders” (MRC, Grant No. MC_PC_17209). Scottish Bipolar Family Study (SBFS) was supported by National Health Service Research Scotland, through the Scottish Mental Health Research Network (www.smhrn.org.uk), who provided assistance with subject recruitment and assessments. SBFS was conducted at the Brain Research Imaging Centre (http://www.bric.ed.ac.uk), which is supported by SINAPSE (Scottish Imaging Network, a Platform for Scientific Excellence, http://www.sinapse.ac.uk). Processing of the datasets used the resources provided by the Edinburgh Compute and Data Facility (http://www.ecdf.ed.ac.uk/) (ASt). TVR was supported by an NHMRC Early Career Fellowship (Grant No. GNT1088785). Collection of the COGSBD cohort was funded by the Jack Brockhoff Foundation, University of Melbourne, Barbara Dicker Brain Sciences Foundation, Rebecca L Cooper Foundation, and the Society of Mental Health Research (to TVR). EV was supported by the Spanish Ministry of Science and Innovation (PI18/00805) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII-Subdirección General de Evaluación and the FEDER; the Instituto de Salud Carlos III; the CIBERSAM (Centro de Investigación Biomédica en Red de Salud Mental); by the CERCA Programme/Generalitat de Catalunya and the Secretaria d’Universitats i Recerca del Departament d’Economia I Coneixement (Grant No. 2017SGR1355). This study was also supported by the Departament de Salut de la Generalitat de Catalunya, Pla Estratègic de Recerca i Innovació en Salut (PERIS) 2016-2020 (Grant No. SLT006/17/00345) and the European Union Horizon 2020 research and innovation program (EU.3.1.1. Understanding health, wellbeing and disease: Grant Nos. 754907 and EU.3.1.3 [to EB]; Treating and managing disease: Grant No. 945151 [to EV]). This study was supported by the National Center for Complementary and Integrative Health (Grant Nos. R21AT009173 and R61AT009864 [to TTY]); by the National Center for Advancing Translational Sciences (CTSI), National Institutes of Health, through UCSF-CTSI (Grant No. UL1TR001872 [to TTY]); by the American Foundation for Suicide Prevention (Grant No. SRG-1-141-18 [to TTY]); by UCSF Research Evaluation and Allocation Committee (REAC) and J. Jacobson Fund (to TTY); by the NIMH (Grant No. R01MH085734 [to TTY]); and by the Brain and Behavior Research Foundation (formerly NARSAD) (to TTY). This work was supported by a personal Veni grant to MH from the Netherlands Organization for Scientific Research (NWO, Grant No. 91619115 [to MH]) and European Community’s Horizon 2020 Programme (H2020/2014 – 2020) (Grant Agreements Nos. 667302 [CoCA], 728018 [Eat2beNICE], and 847879 [PRIME] [to BF]). JBu has been supported by the EU-AIMS (European Autism Interventions) and AIMS-2-TRIALS programmes, which receive support from Innovative Medicines Initiative Joint Undertaking Grant Nos. 115300 and 777394, the resources of which are composed of financial contributions from the European Union’s FP7 and Horizon 2020 Programmes, and from the European Federation of Pharmaceutical Industries and Associations companies’ in-kind contributions, and AUTISM SPEAKS, Autistica and SFARI; and by the Horizon 2020–supported programme CANDY (Grant No. 847818 [to JBu]). This work is supported by Grant No. NIA T32AG058507 and NIH Grant No. U54EB020403 from the Big Data to Knowledge (BD2K) Program (to CRKC). ENIGMA MDD work is supported by NIH (Grant Nos. U54 EB020403 [to PT], R01 MH116147 [to PT], and R01 MH117601 [to NJ and LS]). LS was supported by an NHMRC Career Development Fellowship (Grant No. 1140764). This work was supported by the National Center for Research Resources at the NIH (Grant Nos. NIH 1 U24 RR021992 [Function Biomedical Informatics Research Network], NIH 1 U24 RR025736-01 [Biomedical Informatics Research Network Coordinating Center; http://www.birncommunity.org]). TGMvE is supported by ENIGMA’s NIH BD2K initiative (Grant No. U54 EB020403), ENIGMA Sex Differences (Grant No. R01MH116147), and ENIGMA-COINSTAC: Advanced Worldwide Transdiagnostic Analysis of Valence System Brain Circuits (Grant No. R01MH121246). This work was supported by the NIH (Grant No. R01MH121246 [to JT, Calhoun, and TGMvE]). This work was supported in part by NIH (Grant No. U54 EB020403 [to PT]).

Background Secondary hyperparathyroidism (SHPT) is a complication of chronic kidney disease (CKD) and is associated with changes in calcium and phosphate. These related changes have been associated with increased cardiovascular mortality and CKD progression. It is not clear whether negative outcomes linked to SHPT are confounded by such factors. The present study was designed to assess the possible independent effects of SHPT [defined as patients with excessive parathyroid hormone (PTH) levels or on treatment with PTH-reducing agents] on the risk of CKD progression and cardiovascular event (CVE) incidence in CKD patients, as well as whether hypercalcaemia and/or hyperphosphataemia act as effect modifiers. Methods The study enrolled 2445 CKD patients without previous CVE from the National Observatory of Atherosclerosis in Nephrology (NEFRONA) cohort (Stage 3, 950; Stage 4, 612; Stage 5, 195; on dialysis, 688). Multivariate logistic and Fine and Gray regression analysis were used to determine the risk of patients suffering CKD progression or a CVE. Results The prevalence of SHPT in the cohort was 65.6% (CKD Stage 3, 54.7%; CKD Stage 4, 74.7%; CKD Stage 5, 71.4%; on dialysis, 68.6%). After 2 years, 301 patients presented CKD progression. During 4 years of follow-up, 203 CVEs were registered. Patients with SHPT showed a higher adjusted risk for CKD progression and CVE. Furthermore, hyperphosphataemia was shown to be an independent risk factor in both outcomes and did not modify SHPT effect. No significant interactions were detected between the presence of SHPT and hypercalcaemia or hyperphosphataemia. Conclusions We conclude that SHPT and hyperphosphataemia are independently associated with CKD progression and the incidence of CVE in CKD patients.

The relationship between psychotic symptoms and global measures of functioning has been widely studied. No previous study has assessed so far the interplay between specific clinical symptoms and particular areas of functioning in first-episode psychosis (FEP) using network analysis methods. A total of 191 patients with FEP (age 24.45 ± 6.28 years, 64.9% male) participating in an observational and longitudinal study (AGES-CM) comprised the study sample. Functioning problems were assessed with the WHO Disability Assessment Schedule (WHODAS), whereas the Positive and Negative Syndrome Scale (PANSS) was used to assess symptom severity. Network analysis were conducted with the aim of analysing the patterns of relationships between the different dimensions of functioning and PANSS symptoms and factors at baseline. According to our results, the most important nodes were “conceptual disorganization”, “emotional withdrawal”, “lack of spontaneity and flow of conversation”, “delusions”, “unusual thought content”, “dealing with strangers” and “poor rapport”. Our findings suggest that these symptoms and functioning dimensions should be prioritized in the clinical assessment and management of patients with FEP. These areas may also become targets of future early intervention strategies, so as to improve quality of life in this population, This work was supported by the Madrid Regional Government (R&D activities in Biomedicine (grant number S2017/BMD-3740 - AGES-CM 2-CM)) and Structural Funds of the European Union. Ana Izquierdo’s work is supported by the PFIS predoctoral program (FI17/00138) from the Instituto de Salud Carlos III (Spain) and co-funded by the European Union (ERDF/ESF, "A way to make Europe”/ “Investing in your future”) and The Biomedical Research Foundation of La Princesa University Hospital. Angela Ib´a˜nez thanks the support of CIBERSAM and of the Spanish Ministry of Science, Innovation and Universities. Instituto de Salud Carlos III (PI16/00834 and PI19/01295) co-financed by ERDF Funds from the European Commission. Covadonga M. Díaz-Caneja holds a Juan Rod´es Grant from Instituto de Salud Carlos III (JR19/00024). Celso Arango was supported by the Spanish Ministry of Science and Innovation. Instituto de Salud Carlos III (SAM16PE07CP1, PI16/02012, PI19/ 024), co-financed by ERDF Funds from the European Commission, “A way of making Europe”, CIBERSAM. Madrid Regional Government (B2017/BMD-3740 AGES-CM-2), European Union Structural Funds. European Union Seventh Framework Program under grant agreements FP7-4-HEALTH-2009-2.2.1-2-241909 (Project EU-GEI), FP7- HEALTH- 2013-2.2.1-2-603196 (Project PSYSCAN) and FP7- HEALTH-2013- 2.2.1-2-602478 (Project METSY); and European Union H2020 Program under the Innovative Medicines Initiative 2 Joint Undertaking (grant agreement No 115916, Project PRISM, and grant agreement No 777394, Project AIMS-2-TRIALS), Fundaci´on Familia Alonso, Fundaci´on Alicia Koplowitz and Fundaci´on Mutua Madrile˜na

Individuals with psychoses have brain alterations, particularly in frontal and temporal cortices, that may be particularly prominent, already at illness onset, in those more likely to have poorer symptom remission following treatment with the first antipsychotic. The identification of strong neuroanatomical markers of symptom remission could thus facilitate stratification and individualized treatment of patients with schizophrenia. We used magnetic resonance imaging at baseline to examine brain regional and network correlates of subsequent symptomatic remission in 167 medication-naïve or minimally treated patients with first-episode schizophrenia, schizophreniform disorder, or schizoaffective disorder entering a three-phase trial, at seven sites. Patients in remission at the end of each phase were randomized to treatment as usual, with or without an adjunctive psycho-social intervention for medication adherence. The final follow-up visit was at 74 weeks. A total of 108 patients (70%) were in remission at Week 4, 85 (55%) at Week 22, and 97 (63%) at Week 74. We found no baseline regional differences in volumes, cortical thickness, surface area, or local gyrification between patients who did or did not achieved remission at any time point. However, patients not in remission at Week 74, at baseline showed reduced structural connectivity across frontal, anterior cingulate, and insular cortices. A similar pattern was evident in patients not in remission at Week 4 and Week 22, although not significantly. Lack of symptom remission in first-episode psychosis is not associated with regional brain alterations at illness onset. Instead, when the illness becomes a stable entity, its association with the altered organization of cortical gyrification becomes more defined.

Schizophrenia is a biologically complex disorder with multiple regional deficits in cortical brain morphology. In addition, interindividual heterogeneity of cortical morphological metrics is larger in patients with schizophrenia when compared to healthy controls. Exploiting interindividual differences in the severity of cortical morphological deficits in patients instead of focusing on group averages may aid in detecting biologically informed homogeneous subgroups. The person-based similarity index (PBSI) of brain morphology indexes an individual’s morphometric similarity across numerous cortical regions amongst a sample of healthy subjects. We extended the PBSI such that it indexes the morphometric similarity of an independent individual (eg, a patient) with respect to healthy control subjects. By employing a normative modeling approach on longitudinal data, we determined an individual’s degree of morphometric dissimilarity to the norm. We calculated the PBSI for sulcal width (PBSI-SW) in patients with schizophrenia and healthy control subjects (164 patients and 164 healthy controls; 656 magnetic resonance imaging scans) and associated it with cognitive performance and cortical sulcation index. A subgroup of patients with markedly deviant PBSI-SW showed extreme deficits in cognitive performance and cortical sulcation. Progressive reduction of PBSI-SW in the schizophrenia group relative to healthy controls was driven by these deviating individuals. By explicitly leveraging interindividual differences in the severity of PBSI-SW deficits, neuroimaging-driven subgrouping of patients is feasible. As such, our results pave the way for future applications of morphometric similarity indices for subtyping of clinical populations.

Scaling between subcomponents of folding and total brain volume (TBV) in healthy individuals (HIs) is allometric. It is unclear whether this is true in schizophrenia (SZ) or first-episode psychosis (FEP). This study confirmed normative allometric scaling norms in HIs using discovery and replication samples. Cross-sectional and longitudinal diagnostic differences in folding subcomponents were then assessed using an allometric framework. Structural imaging from a longitudinal (Sample 1: HI and SZ, nHI Baseline= 298, nSZ Baseline= 169, nHI Follow-up= 293, nSZ Follow-up= 168, totaling 1087 images, all individuals ≥ 2 images, age 16-69 years) and a cross-sectional sample (Sample 2: nHI= 61 and nFEP= 89, age 10-30 years), all human males and females, is leveraged to calculate global folding and its nested subcomponents: sulcation index (SI, total sulcal/cortical hull area) and determinants of sulcal area: sulcal length and sulcal depth. Scaling of SI, sulcal area, and sulcal length with TBV in SZ and FEP was allometric and did not differ from HIs. Longitudinal age trajectories demonstrated steeper loss of SI and sulcal area through adulthood in SZ. Longitudinal allometric analysis revealed that both annual change in SI and sulcal area was significantly stronger related to change in TBV in SZ compared with HIs. Our results detail the first evidence of the disproportionate contribution of changes in SI and sulcal area to TBV changes in SZ. Longitudinal allometric analysis of sulcal morphology provides deeper insight into lifespan trajectories of cortical folding in SZ.SIGNIFICANCE STATEMENTPsychotic disorders are associated with deficits in cortical folding and brain size, but we lack knowledge of how these two morphometric features are related. We leverage cross-sectional and longitudinal samples in which we decompose folding into a set of nested subcomponents: sulcal and hull area, and sulcal depth and length. We reveal that, in both schizophrenia and first-episode psychosis, (1) scaling of subcomponents with brain size is different from expected scaling laws and (2) caution is warranted when interpreting results from traditional methods for brain size correction. Longitudinal allometric scaling points to loss of sulcal area as a principal contributor to loss of brain size in schizophrenia. These findings advance the understanding of cortical folding atypicalities in psychotic disorders.

Introduction: Attitudes toward risky driving behaviors are commonly evaluated through direct self-report measures. Nevertheless, these instruments have limitations, such as socially-desirable responding. This study examines the validity of the Implicit Association Test (IAT) as an indirect measure of attitudes towards risky driving. An IAT with “risky” vs. “safe” driving behaviors categories was evaluated. Method: A sample of 100 participants (ranging from 18 to 70 years of age) completed the IAT and measures of attitudes, driving styles, personality traits, risk-taking (IOWA Gambling Task), and social desirability (Driver Social Desirability Scale). Results: A high level of internal consistency was found for IAT scores. The IAT was correlated with driving styles (risky, dissociative, and careful dimensions), risk-related personality traits (impulsive/sensation seeking and aggression/hostility) and risk-taking measures. IAT scores were also associated with self-reported risky driving behaviors (r = 0.33). As expected, a higher level of negative implicit attitudes was found among young drivers. The driver social desirability scale was correlated with most self-report measures, but not with the IAT. Conclusion: The present study provides reliability and validity evidence for the IAT as an indirect measure of attitudes towards risky driving. The IAT can serve as an important complement to conventional self-report measures of driving attitudes. Practical Applications: Potential use of global measure of implicit attitudes toward risky driving behaviors in the evaluation, education, and training of drivers are discussed.

Social cognition impairment is a core shared phenotype in both schizophrenia spectrum disorders (SSD) and autism spectrum disorders (ASD). This study compares social cognition performance through four different instruments in a sample of 147 individuals with ASD or SSD and in healthy controls. We found that both clinical groups perform similarly to each other and worse than healthy controls in all social cognition tasks. Only performance on the Movie for the Assessment of Social Cognition (MASC) test was independent of age and intelligence. Proportionately, individuals in the control group made significantly more overmentalization errors than both patients group did and made fewer undermentalization errors than patients with SSD did. AUC analyses showed that the MASC was the instrument that best discriminated between the clinical and control groups. Multivariate analysis showed negative symptom severity as a potential mediator of the association between social cognition deficit and poor global functioning.

Negative symptoms are associated with poor clinical and psychosocial outcome in schizophrenia. Their prevalence and identification in first-episode patients remains controversial. In a large cohort of patients in the early stage of schizophrenia, schizophreniform or schizoaffective disorder, we investigated, over the different phases of the OPTiMiSE trial (baseline, 4, 10 and 22 weeks of treatment), the prevalence of negative symptoms of moderate severity, unconfounded by depression and extrapyramidal symptoms at baseline. Moreover, we assessed symptomatic remission, attrition rate and psychosocial functioning in subjects with short-term (4 weeks) persistent unconfounded negative symptoms (PNS) and in those with negative symptoms that did not persist at follow-up and/or were confounded at baseline (N-PNS). Negative symptoms of moderate severity were observed in 59% of subjects at baseline. They were associated with worse psychosocial functioning and longer duration of psychosis at intake in the study. Eleven percent of subjects had PNS unconfounded at baseline and 7.9% had PNS unconfounded at both baseline and end of 4-week treatment. Psychosocial functioning was comparable in PNS and N-PNS subjects at baseline but it was significantly worse in the former group after 4-weeks. PNS subjects showed lower remission and higher attrition rates at the end of all treatment phases. Fifty-six percent of subjects completing phase 3 (clozapine treatment) had PNS, and 60% of them were non-remitters at the end of this phase. The presence of short-term PNS during the first phases of psychosis was associated with poor clinical outcome and resistance to antipsychotic treatment, including clozapine.

Aims: Patients with a first episode of psychosis (FEP) often display different metabolic disturbances even independently of drug therapy. However, antipsychotic (AP) treatment, especially with second-generation APs, is strongly linked to weight gain, which increases patients’ risk of developing obesity and other metabolic diseases. There is an important genetic risk component that can contribute to the appearance of these disturbances. The aim of the present study was to evaluate the effect of polymorphisms in selected candidate genes on obesity and other anthropometric and metabolic traits in 320 AP-treated FEP patients over the course of a 2-year follow-up. Methods: These patients were recruited in the multicentre PEPs study (Phenotype−genotype and environmental interaction; Application of a predictive model in first psychotic episodes). A total of 127 validated single nucleotide polymorphisms (SNPs) in 18 candidate genes were included in the genetic analysis. Results: After Bonferroni correction, SNPs in ADRA2A, FTO, CNR1, DRD2, DRD3, LEPR and BDNF were associated with obesity, abdominal circumference, triglycerides, HDL cholesterol, and/or percentage of glycated haemoglobin. Conclusions: Although our results should be interpreted as exploratory, they support previous evidence of the impact of these candidate genes on obesity and metabolic status. Further research is required to gain a better knowledge of the genetic variants that can be considered relevant metabolic risk factors. The ability to identify FEP patients at higher risk for these metabolic disturbances would enable clinicians to better select and control their AP treatment.

BACKGROUND: Emotion recognition constitutes a pivotal process of social cognition. It involves decoding social cues (e.g., facial expressions) to maximise social adjustment. Current theoretical models posit the relationship between social withdrawal factors (social disengagement, lack of social interactions and loneliness) and emotion decoding.OBJECTIVE: To investigate the role of social withdrawal in patients with schizophrenia (SZ) or probable Alzheimer's disease (AD), neuropsychiatric conditions associated with social dysfunction.METHODS: A sample of 156 participants was recruited: schizophrenia patients (SZ; n = 53), Alzheimer's disease patients (AD; n = 46), and two age-matched control groups (SZc, n = 29; ADc, n = 28). All participants provided self-report measures of loneliness and social functioning, and completed a facial emotion detection task.RESULTS: Neuropsychiatric patients (both groups) showed poorer performance in detecting both positive and negative emotions compared with their healthy counterparts (p CONCLUSIONS: Our findings help to detail the similarities and differences in social function and facial emotion recognition in two disorders rarely studied in parallel, AD and SZ. Transdiagnostic patterns in these results suggest that social withdrawal is associated with heightened sensitivity to negative emotion expressions, potentially reflecting hypervigilance to social threat. Across the neuropsychiatric groups specifically, this hypervigilance associated with social withdrawal extended to positive emotion expressions, an emotional-cognitive bias that may impact social functioning in people with severe mental illness.

Oviparous elasmobranch embryos (Chondrichthyes) have been the focus of several embryological studies; they are useful models for studying early ontogeny in vertebrates, as can help explore the existence of common developmental patterns among species. Skates (Rajiformes) are the most speciose order of oviparous elasmobranchs, however, few studies are focused on embryo development and only based on one skate family: Rajidae. Here, we extended the study of embryo development to other skate family, Arhynchobatidae, which represent about 1/3 of all skate species. Three adult female bignose fanskates (Sympterygia acuta) were held in captivity in order to provide the first complete embryonic development timeline for any species within the Arhynchobatidae family. Our results allowed further comparisons at the embryonic scale of different oviparous elasmobranch families, providing an updated cross-species overview of the early ontogeny. Incubation in S. acuta lasted 97 ± 1.4 days at 11-21.7 °C, and hatching size was 93.2 ± 0.2 mm in total length and 49.2 ± 0.3 mm in disc width. Early embryos of S. acuta were anatomically similar to other oviparous elasmobranch embryos, with several structures appearing at the same time, but late embryonic development was comparatively delayed. The late resorption of both the external yolk sac and the external gill filaments, and also the delay in the slit opening could indicate a low metabolic demand in S. acuta, which would probably be coupled with its seasonal reproductive cycle. Some structures such as external gill filaments and claspers appeared at a similar time in some species of Rajidae and also in Arhynchobatidae, but at different times in species of the same family, showing an inconsistency also found within shark families. Although the sequential scheme remained relatively constant, small heterochronies would be present within skates, within sharks, and also between skates and sharks.

Overweight and obesity have become a world-health public problem, mainly for developing countries. Both health conditions have a higher prevalence among women of childbearing age. Physiopathology, overweight and obesity are characterized by a chronic oxidative stress status, which has deleterious effects on mothers and children. Hence, we determine whether the qualities of diet during pregnancy and maternal pregestational body mass index (BMI) are associated with increased oxidative stress markers in mothers and newborns. Two hundred forty-two (242) mother-newborn pairs were classified according to their pregestational BMI. Information on food intake was collected using a food frequency questionnaire in the third trimester of pregnancy. Levels of Malondialdehyde (MDA) and Nitric Oxide (NO) were measured in plasma from mothers at the end of the third trimester of pregnancy and from cord blood at birth. MDA and NO levels in mother–newborn pairs with maternal pregestational overweight or obesity were higher than in mother–newborn pairs with pregestational normal weight. For women (and newborns) who had a higher intake of fruit and vegetables, the levels of NO and MDA were lower. Lastly, women with pregestational obesity had lower fruit and vegetable intake during pregnancy and higher levels of oxidative stress and in their newborns.

This work was supported by the Spanish Ministry of Science and Innovation. Instituto de Salud Carlos III (SAM16PE07CP1, PI16/02012, PI17/00997, PI19/01024, PI20/00721), co-financed by ERDF Funds from the European Commission, “A way of making Europe”, CIBERSAM. Madrid Regional Government (B2017/BMD-3740 AGES-CM-2), European Union Structural Funds. European Union Seventh Framework Program under grant agreements FP7-4-HEALTH-2009-2.2.1-2-241909 (Project EU-GEI), FP7- HEALTH-2013-2.2.1-2-603196 (Project PSYSCAN), and FP7- HEALTH-2013-2.2.1-2- 602478 (Project METSY); and European Union H2020 Program under the Innovative Medicines Initiative 2 Joint Undertaking (grant agreement No 115916, Project PRISM, and grant agreement No 777394, Project AIMS-2-TRIALS), Fundación Familia Alonso, Fundación Alicia Koplowitz, and Fundación Mutua Madrileña. We are grateful to Paloma Pantoja for her assistance in the design of the figures. A.A.-B. holds a Rio Hortega Grant from Instituto de Salud Carlos III (CM20/00114). C.M.D.-C. holds a Juan Rodés Grant from Instituto de Salud Carlos III (JR19/00024)., Andreu-Bernabeu, Á., Díaz-Caneja, C.M., Costas, J., De Hoyos, L., Stella, C., Gurriarán, X., Alloza, C., Fañanás, L., Bobes, J., González-Pinto, A., Crespo-Facorro, B., Martorell, L., Vilella, E., Muntané, G., Nacher, J., Molto, M.D., Aguilar, E.J., Parellada, M., Arango, C., González-Peñas, J.

Boerhaave syndrome consists of a spontaneous perforation of the esophagus, with high mortality.To describe a case with Boerhaave syndrome with double esophageal perforation.33-year-old female who came to the hospital for emetic symptoms, followed by retrosternal chest pain; chest drainage is performed. Esophageal perforation was diagnosed late and he was transferred to a tertiary level institution. Successive treatments were performed: videothoracoscopy and pleural decortication; alimentary jejunostomy; esophageal stent placement, diagnosis of new perforation, pyloric exclusion, new stent placement, and esophageal exclusion.The delay in diagnosis contributed to the fatal outcome of the patient.El síndrome de Boerhaave consiste en una perforación espontánea del esófago, con alta mortalidad.Describir un caso de síndrome de Boerhaave con doble perforación esofágica.Mujer de 33 años que acude al hospital por un cuadro emético, seguido de dolor torácico retroesternal; se realiza drenaje torácico. Se diagnostica tardíamente perforación esofágica y se traslada a una institución de nivel terciario. Se realizaron sucesivos tratamientos: videotoracoscopia y decorticación pleural, yeyunostomía alimentaria, colocación de endoprótesis esofágica, diagnóstico de nueva perforación, exclusión pilórica, colocación de nueva endoprótesis y exclusión esofágica.El retardo en el diagnóstico contribuyó al desenlace fatal de la paciente.

Sex differences in development and aging of human sulcal morphology have been understudied. We charted sex differences in trajectories and inter-individual variability of global sulcal depth, width, and length, pial surface area, exposed (hull) gyral surface area, unexposed sulcal surface area, cortical thickness, and cortex volume across the lifespan in a longitudinal sample (700 scans, 194 participants two scans, 104 three scans, age range: 16-70 years) of neurotypical males and females. After adjusting for brain volume, females had thicker cortex and steeper thickness decline until age 40 years; trajectories converged thereafter. Across sexes, sulcal shortening was faster before age 40, while sulcal shallowing and widening were faster thereafter. While hull area remained stable, sulcal surface area declined and was more strongly associated with sulcal shortening than with sulcal shallowing and widening. Males showed greater variability for cortex volume and thickness and lower variability for sulcal width. Across sexes, variability decreased with age for all measures except for cortical volume and thickness. Our findings highlight the association between loss of sulcal area, notably through sulcal shortening, with cortex volume loss. Studying sex differences in lifespan trajectories may improve knowledge of individual differences in brain development and the pathophysiology of neuropsychiatric conditions.

Altres ajuts: SRB: The Australian Schizophrenia Research Bank (ASRB) was supported by the National Health and Medical Research Council of Australia (NHMRC) (Enabling Grant, ID 386500), the Pratt Foundation, Ramsay Health Care, the Viertel Charitable Foundation and the Schizophrenia Research Institute. Chief Investigators for ASRB were Carr, V., Schall, U., Scott, R., Jablensky, A., Mowry, B., Michie, P., Catts, S., Henskens, F., Pantelis, C. We thank Loughland, C., the ASRB Manager, and acknowledge the help of Jason Bridge for ASRB database queries. CP was supported by NHMRC Senior Principal Research Fellowships (IDs: 628386 & 1105825); GC was supported by the Schizophrenia Research Institute utilizing infrastructure funding from the New South Wales Ministry of Health and New South Wales Ministry of Trade and Investment (Australia); JMF was supported by NHMRC project grant (1063960) and the Janette Mary O'Neil Research Fellowship; MJG was supported by NHMRC as an R.D. Wright Biomedical Career Development Fellow (1061875). MJC was supported by NHMRC Senior Research Fellowship (1121474). CASSI: CSW is funded by the NSW Ministry of Health, Office of Health and Medical Research. CSW is a recipient of a National Health and Medical Research Council (Australia) Principal Research Fellowship (PRF) (#1117079). CIAM: The CIAM study (FMH - PI) was supported by the University Research Committee, University of Cape Town and South African funding bodies National Research Foundation and Medical Research Council. COBRE: The COBRE dataset and investigators were supported by NIH grants R01EB006841 & P20GM103472, as well as NSF grant 1539067. JT (senior author) and VDC are supported by 5R01MH094524. JMS is supported by R01 AA021771 and P50 AA022534. EONCKS: This work was supported by a New Partnership for Africa's Development (NEPAD) grant through the Department of Science and Technology of South Africa, the Medical Research Council of South Africa (grant number 65174). ESO: The ESO study was funded by NPU I - LO1611 and Ministry of Health, Czech Republic - Conceptual Development of Research Organization 00023001 (IKEM). FIDMAG/Project: This work was supported by the Catalan Government and several grants from the Instituto de Salud Carlos III and co-funded by European Union (ERDF/ESF, 'Investing in your future'): Miguel Servet Research Contracts and Research Project Grants. FOR2107 Marburg: The FOR2107 Marburg study was funded by the German Research Foundation (DFG), Tilo Kircher (speaker FOR2107; DFG grant numbers KI588/14-1, KI588/14-2), Axel Krug (KR 3822/5-1, KR 3822/7-2), Igor Nenadic (NE 2254/1-2), Carsten Konrad (KO 4291/3-1). FOR2107 Muenster: The FOR2107 Muenster study was funded by the German Research Foundation (DFG, grant FOR2107 DA1151/5-1 and DA1151/5-2 to UD) and the Interdisciplinary Center for Clinical Research (IZKF) of the medical faculty of Münster (grant Dan3/012/17 to UD). TH was supported by grants from the German Research Foundation (DFG grants HA7070/2-2, HA7070/3, HA7070/4). Frankfurt: MRI was performed at the Frankfurt Brain Imaging Center, supported by the German Research Council (DFG) and the German Ministry for Education and Research (BMBF; Brain Imaging Center Frankfurt/Main, DLR 01GO0203). GIPSI: This study was supported by Colciencias PRISMA-U.T. Huilong1 & Huilong2: This study was funded by the National Natural Science Foundation of China (81761128021; 31671145; 81401115; 81401133), Beijing Municipal Science and Technology Commission grant (Z141107002514016) and Beijing Natural Science Foundation(7162087, Beijing Municipal Administration of Hospitals Clinical medicine Development of special funding (XMLX201609; zylx201409). IGP: This study was funded by Project Grants from the Australian National Health and Medical Research Council of Australia (NHMRC; APP630471 and APP1081603), the Macquarie University's Australian Research Council Centre of Excellence in Cognition and its Disorders (CE110001021). Johns Hopkins: Supported by National Institutes of Health Grant Nos. MH-092443, MH-094268 (Silvio O. Conte Center), MH-105660, and MH-107730; foundation grants from Stanley, RUSK/S-R, and NARSAD/Brain and Behavior Research Foundation. Madrid: Supported by the Spanish Ministry of Science, Innovation and Universities, Instituto de Salud Carlos III, co-financed by ERDF Funds from the European Commission, "A way of making Europe", CIBERSAM. Madrid Regional Government (B2017/BMD-3740 AGES-CM-2), European Union Structural Funds and European Union Seventh Framework Program and H2020 Program; Fundación Familia Alonso, Fundación Alicia Koplowitz and Fundación Mutua Madrileña. MPRC1 & MPRC2: Support was received from NIH grants U01MH108148, 2R01EB015611, R01MH112180, R01DA027680, R01MH085646, P50MH103222 and T32MH067533, a State of Maryland contract (M00B6400091) and NSF grant (1620457). OLIN: The Olin study was supported by NIH grants R37MH43375 and R01MH074797. Oxford: The Oxford study MRC G0500092. SLF Rome: Support from the Italian Ministry of Health grants RC-12-13-14-15-16-17-18-19/A. RSCZ: RSCZ data collection was supported by RFBR 15-06-05758 grant. SCORE: This study was supported in part by grant 3232BO_119382 from the Swiss National Science Foundation. We thank the FePsy (Frueherkennung von Psychosen; early detection of psychosis) Study Group from the University of Basel, Department of Psychiatry, Switzerland, for the recruitment of the study participants. The FePsy Study was supported in part by grant No. SNF 3200-057216/1, ext./2, ext./3. Singapore: This study was supported by research grants from the National Healthcare Group, Singapore (SIG/05004; SIG/11003), and the Singapore Bioimaging Consortium (RP C-009/2006) research grants awarded to KS. SNUH: This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (Grant no. 2013R1A2A1A03071089 and 2017M3C7A1029610). UCISZ: The UCISZ study was supported by the National Institutes of Mental Health grant number R21MH097196 to TGMvE. UCISZ data were processed by the UCI High Performance Computing cluster supported by Joseph Farran, Harry Mangalam, and Adam Brenner and the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant UL1 TR000153. UNIBA: The UNIBA study was supported by grant funding from the Italian Ministry of Health (PE-2011-02347951). UNIMAAS: The study was supported by Dutch Organization for Health Research and Development (ZonMw 91112002) and a personal grant to Thérèse van Amelsvoort (ZonMw-VIDI: 91712394). The data was collected in a clinical trial registered in the Dutch clinical trial registry under ID: NTR5094 (http://www.trialregister.nl). UPenn: This study was supported by the National Institute of Mental Health grants MH064045, MH 60722, MH019112, MH085096 (DHW), and R01MH112847 (RTS and TDS). Zurich: This study was supported by the Swiss National Science Foundation (105314_140351 to S.K.). Matthias Kirschner acknowledges support from the National Bank Fellowship (McGill University) and the Swiss National Foundation (P2SKP3_178175). Research reported in this publication was also supported by the following National Institutes of Health grants: U54 EB020403 to PMT, R01 MH116147, U24 RR21992, R21MH097196, and TR000153 to TGMvE, S10 OD023696 and R01EB015611 to PK, T32 AG058507and 5T32 MH073526 to CRKC, R01 MH117601 to NJ, ENIGMA's NIH Big Data to Knowledge (BD2K) initiative U54 EB020403, ENIGMA Sex Differences R01MH116147, and ENIGMA-COINSTAC: Advanced World-wide Transdiagnostic Analysis of Valence System Brain Circuits R01MH121246. A common limitation of neuroimaging studies is their small sample sizes. To overcome this hurdle, the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium combines neuroimaging data from many institutions worldwide. However, this introduces heterogeneity due to different scanning devices and sequences. ENIGMA projects commonly address this heterogeneity with random-effects meta-analysis or mixed-effects mega-analysis. Here we tested whether the batch adjustment method, ComBat, can further reduce site-related heterogeneity and thus increase statistical power. We conducted random-effects meta-analyses, mixed-effects mega-analyses and ComBat mega-analyses to compare cortical thickness, surface area and subcortical volumes between 2897 individuals with a diagnosis of schizophrenia and 3141 healthy controls from 33 sites. Specifically, we compared the imaging data between individuals with schizophrenia and healthy controls, covarying for age and sex. The use of ComBat substantially increased the statistical significance of the findings as compared to random-effects meta-analyses. The findings were more similar when comparing ComBat with mixed-effects mega-analysis, although ComBat still slightly increased the statistical significance. ComBat also showed increased statistical power when we repeated the analyses with fewer sites. Results were nearly identical when we applied the ComBat harmonization separately for cortical thickness, cortical surface area and subcortical volumes. Therefore, we recommend applying the ComBat function to attenuate potential effects of site in ENIGMA projects and other multi-site structural imaging work. We provide easy-to-use functions in R that work even if imaging data are partially missing in some brain regions, and they can be trained with one data set and then applied to another (a requirement for some analyses such as machine learning).

We described clinical characteristics and outcome of 160 patients over 65 years (01 September to 31 August 2021) who had a first positive SARS-CoV-2 PCR- test more than 14 days after full vaccination and were hospitalized with COVID-19. Median age of included patients was 84 years, 61.2% were over 80 years; 50.6% were male and most (82.5%) has at least one comorbidity. Up to 84% received specific treatment against COVID-19, including 76.9% low-flow oxygen therapy. We found that overall mortality was 25.6% and 30.6% in those older than 80 years. A higher mortality was significantly associated with older age and treatment with tocilizumab. Our data showed that although COVID-19 vaccines continue protecting elderly patients against hospitalization and death and might improve the prognosis after hospitalization in patients with breakthrough infections, mortality in this population -especially in those older than 80 years- remains very high.

Objective: To study the differences in early-life characteristics between patients with an early onset of psychotic disorders (EOP, aged < 18 years) versus adult onset of psychotic disorders (AOP, aged >= 18 years) and to identify predictors of earlier onset. Methods: 278 patients with a first episode of psychosis between the ages of 7 and 35 years were recruited as part of a multicenter prospective longitudinal study conducted in Spain between January 1, 2009, and December 31, 2011, with diagnoses made for AOP using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) and for EOP using the Schedule for Affective Disorders and Schizophrenia for School-Aged Children (K-SADS). Early-stage factors such as prenatal, perinatal, and other premorbid factors were registered and compared between EOP and AOP patients. To analyze the association between baseline variables and outcome, univariate and multivariate logistic regression models were used, and the association or odds ratios (ORs) for significant risk factors were calculated. Results: 224 patients with AOP (mean +/- SD age = 25.6 +/- 5.0 years; 65.6% male) and 54 patients with EOP (16.1 +/- 1.7 years; 68.5% male) were included. Univariate analysis revealed significant differences between the groups. Specifically, compared to AOP subjects, EOP patients had more frequent obstetric complications (OCs) (P

This study is part of a coordinated-multicentre Project, funded by the Ministerio deEconomia y Competitividad (PI08/0208; PI11/00325; PI14/00612), Instituto de Salud Car-los III–Fondo Europeo de Desarrollo Regional, Union Europea, Una manera de hacer Eu-ropa, Centro de Investigacion Biomedica en Red de salud Mental, CIBERSAM, by theCERCA Programme/Generalitat de Catalunya and Secretaria d’Universitats i Recerca delDepartament d’Economia I Coneixement (2017SGR1355), Departament de Salut de laGeneralitat de Catalunya, en la convocatoria corresponent a l’any 2017 de concessio desubvencions del Pla Estrategic de Recerca i Innovacio en Salut (PERIS) 2016-2020,modalitat Projectes de recerca orientats a l’atencio primaria, amb el codi d’expedientSLT006/17/00345

BackgroundPositive symptoms are a useful predictor of aggression in schizophrenia. Although a similar pattern of abnormal brain structures related to both positive symptoms and aggression has been reported, this observation has not yet been confirmed in a single sample.MethodTo study the association between positive symptoms and aggression in schizophrenia on a neurobiological level, a prospective meta-analytic approach was employed to analyze harmonized structural neuroimaging data from 10 research centers worldwide. We analyzed brain MRI scans from 902 individuals with a primary diagnosis of schizophrenia and 952 healthy controls.ResultsThe result identified a widespread cortical thickness reduction in schizophrenia compared to their controls. Two separate meta-regression analyses revealed that a common pattern of reduced cortical gray matter thickness within the left lateral temporal lobe and right midcingulate cortex was significantly associated with both positive symptoms and aggression.ConclusionThese findings suggested that positive symptoms such as formal thought disorder and auditory misperception, combined with cognitive impairments reflecting difficulties in deploying an adaptive control toward perceived threats, could escalate the likelihood of aggression in schizophrenia.

This study explored the potential association between chronic exposure to pesticide mixtures including paraquat and respiratory outcomes among Colombian farmers. Sociodemographic and occupational data, respiratory symptoms and spirometric data were collected. Paraquat in spot urine samples were quantified with solid-phase extraction high-performance liquid chromatography. Multiple Poisson regressions with robust variance were used to determine factors associated with respiratory outcomes. Profiles of pesticide mixtures used were identified among 217 farmwork-ers, but profenofos and methamidophos-based mixtures were more frequent. Chronic paraquat exposure was slightly associated with self-reported asthma (PR: 1.06; 95% CI 1.00 to 1.13). Different pesticide mixtures were associated with flu, thoracic pain, allergic rhinitis, and obstructive pattern in spirometry. Although acute exposure to paraquat is low among Colombian farmers participating in the study, associations between respiratory outcomes and chronic pesticide mixtures exposure including profenofos, methamidophos or glyphosate require further specific studies. © 2020 National Institute of Occupational Safety and Health.

Objective: The identification of predictors of psychosis remission could guide early clinical decision-making for treatment of first-episode schizophrenia (FES).Methods: We analyzed two non-independent subsamples of patients with FES ages 18-40 years from the OPTiMiSE study dataset to investigate the demographic and clinical factors that might help to differentiate "late" re-mitters (i.e., not in remission at week 2 or 4, but achieving remission within a 10-week follow-up period) from non-remitters within the same period.Results: Subsample 1 included 216 individuals (55 females, mean age 25.9 years) treated with amisulpride in an open-label design who were not in remission at week 2. Early symptomatic response between baseline and week 2 (odds ratio (OR)- 4.186, 95% confidence interval (CI)- 2.082-8.416, p < 0.001) and older age (OR- 1.081, 95% = CI 1.026-1.138, p- 0.003) were the only variables significantly associated with a higher probability of psychosis remission at week 4. Subsample 2 was composed of the 72 participants (19 females, mean age 25.1 years) who were not in remission at week 4 and completed a 6-week double-blind randomized trial comparing continuation of amisulpride with switch to olanzapine. Depression at baseline (as measured with the Calgary Depression Scale for Schizophrenia) was significantly associated with a nearly 3-fold lower likelihood of psychosis remission during the 10-week follow-up (hazard ratio = 2.865, 95% CI = 1.187-6.916, p = 0.019).Conclusion: Our results reinforce the importance of assessing depressive symptoms in people with FES and support the relevance of an early response (as early as 2 weeks) as a predictor of clinical outcome in this population. (C) 2021 Elsevier B.V. All rights reserved.

Buschke-Fischer-Brauer (BFB) disease is a rare keratoderma characterized by multiple hyperkeratotic lesions on the palms and soles, with an autosomal dominant pattern. In several countries, some genetic alterations have been associated with this clinical entity. A 68-year-old Peruvian woman presenting with hyperkeratotic lesions on both her palms and soles was diagnosed with BFB keratoderma. After sequencing of the genes that had previously been related to this disease, a mutation (c.249CG) that was predicted to generate a termination codon (Tyr83*) was found in the alpha and gamma adaptin binding protein P34 gene (AAGAB). After treatment with 30% urea plus 10% salicylic acid, the patient experienced an improvement in her condition. Here we report a novel mutation in the AAGAB gene of a patient diagnosed with BFB keratoderma and a treatment that improved her symptoms.

In an attempt to evaluate the susceptibility of the mosquito Culex quinquefasciatus to bacterial agents, a population naturally infected with a Wolbachia pipientis wPipSJ native strain was tested against the action of three bacterial mosquitocides, Bacillus thuringiensis subsp. israelensis, Bacillus wiedmannii biovar thuringiensis and Lysinibacillus sphaericus. Tests were carried out on mosquito larvae with and without Wolbachia (controls). Cx. quinquefasciatus naturally infected with the native wPipSJ strain proved to be more resistant to the pathogenic action of the three mosquitocidal bacterial strains. Additionally, wPipSJ was fully characterised using metagenome-assembled genomics, PCR–RFLP (PCR-Restriction Fragment Length Polymorphism) and MLST (MultiLocus Sequence Typing) analyses. This Wolbachia strain wPipSJ belongs to haplotype I, group wPip-III and supergroup B, clustering with other mosquito wPip strains, such as wPip PEL, wPip JHB, wPip Mol, and wAlbB; showing the southernmost distribution in America. The cytoplasmic incompatibility phenotype of this strain was revealed via crosses between wildtype (Wolbachia+ ) and antibiotic treated mosquito populations. The results of the tests with the bacterial agents suggest that Cx. quinquefasciatus naturally infected with wPipSJ is less susceptible to the pathogenic action of mosquitocidal bacterial strains when compared with the antibiotic-treated mosquito isoline, and is more susceptible to B. thuringiensis subsp. israelensis than to the other two mosquitocidal agents. Fil: Díaz Nieto, Leonardo Martín. Fundación para Investigaciones Biológicas Aplicadas; Argentina. Universidad Nacional de San Juan; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Biodiversidad y Biotecnología; Argentina Fil: Gil, María Florencia. Fundación para Investigaciones Biológicas Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones En Biodiversidad y Biotecnología. Grupo de Investigación en Química Analítica y Modelado Molecular; Argentina Fil: Lazarte, Jorge Nicolás. Fundación para Investigaciones Biológicas Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones En Biodiversidad y Biotecnología. Grupo de Investigación en Química Analítica y Modelado Molecular; Argentina Fil: Perotti, Maria Alejandra. University of Reading; Reino Unido Fil: Berón, Corina Marta. Fundación para Investigaciones Biológicas Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones En Biodiversidad y Biotecnología. Grupo de Investigación en Química Analítica y Modelado Molecular; Argentina

The COVID-19 pandemic has compelled university students to adapt to remote learning modalities resulting in increased of anxiety symptoms. This study explores levels of anxiety, and risk and protection factors among Social Work students at two universities in southern Spain. Thirty four percent were experiencing severe anxiety, and 28.5% mild to moderate, revealing that anxiety levels had increased significantly. Greater concern about academic situation and future economic scenario, living in an urban area and leave the habitual residence increased anxiety symptoms. By contrast, family income stability and higher social support from relatives reduced anxiety symptoms. These results support the planning of emotional support services for college students, as well as the incorporation in the study plans the acquisition of skills to live better in these conditions.

To analyze work, demographic, and social parameters in order to learn about the working status of pediatric surgeons in Spain.A survey inspired in job satisfaction models and designed by the authors was performed. It was an observational, descriptive, cross-border online survey intended for pediatric surgeons from the Spanish Society of Pediatric Surgery (SECIPE).Of the 290 SECIPE pediatric surgeons, 133 responded to the survey (45.8% response rate), of whom 49.6% were 30-39 years old. The number of male and female respondents was virtually the same. 69% of respondents devoted 75-100% of their working hours to healthcare, 89.4% devoted 0-25% to research, and 80% devoted 0-25% to teaching. The survey demonstrated job satisfaction in terms of colleagues, healthcare role, professional development expectations, and social consideration. However, respondents showed disconformity with their pay, the time devoted to research and teaching, and their relationship with the executive board.This study sheds light on the Spanish professionals' working status, which can help identify measures for improvement. The survey shows widespread disconformity with the short time devoted to research, and little satisfaction with teaching. Most of the working hours are devoted to clinical practice, with poor pay satisfaction, which can contribute to dissatisfaction in the development of healthcare activity.Analizar parámetros sociolaborales y sociodemográficos para conocer la situación de los cirujanos pediátricos en España.Se realizó una encuesta de elaboración propia inspirada en modelos de satisfacción laboral. Es un estudio observacional, descriptivo y transversal, realizado online a los cirujanos pediátricos pertenecientes a la Sociedad Española de Cirugía Pediátrica (SECIPE).De los 290 cirujanos pediátricos de la SECIPE, 133 contestaron a la encuesta (tasa de respuesta de 45,8%). De estos, el 49,6% tienen entre 30-39 años, habiendo casi igualdad entre hombres y mujeres. El 69% de los encuestados dedican entre el 75 y el 100% de su tiempo de trabajo a la asistencia, el 89,4% dedica entre 0-25% a la investigación y el 80% entre 0 y 25 % a la docencia. Los resultados mostraron satisfacción laboral tanto en relación con el equipo de trabajo como con la calidad asistencial, las posibilidades de desarrollo profesional o la consideración social. Sin embargo los encuestados mostraron su disconformidad con respecto al sueldo, al tiempo dedicado a la investigación y a la docencia, y a la relación con la dirección.Este estudio permite conocer la situación laboral de los profesionales en España, lo que puede ayudar a identificar medidas de mejora. La encuesta señala un descontento generalizado con el escaso tiempo dedicado a la investigación y poca satisfacción en el trabajo docente. La mayor parte del tiempo se dedica a la práctica clínica, existiendo baja satisfacción salarial, circunstancias que pueden contribuir a la insatisfacción en el desarrollo de la actividad asistencial.

Background Palbociclib and ribociclib are novel oral agents in hormone receptor-positive metastatic breast cancer. Neutropenia is a common adverse event associated with these treatments and its clinical management often requires regimen changes, such as cycle delays and dose adjustments. Objective To provide a real-world experience of the effectiveness and toxicities associated with these drugs and to evaluate the impact of regimen changes in disease progression. Setting This study was performed at Hospital Universitario La Paz, in Spain. Methods Observational, retrospective study which included hormone receptor-positive metastatic breast cancer patients who initiated treatment with palbociclib or ribociclib between March 1st, 2018 and March 1st, 2019. Main outcome measure The primary effectiveness variable was progression-free survival. Safety evaluation was performed to determine neutropenia-incidence and severity, as well as its clinical management, including dose adjustments and treatment interruptions. Correlations between these regimen changes and effectiveness were also evaluated. Results Sixty-one patients were included, 33 treated with palbociclib and 28 with ribociclib. Palbociclib was mainly used as second line of treatment in the metastatic setting (81.8%) and ribociclib as first line (67.9%). The median progression-free survival was 12.76 months (95% CI 7.5 to not estimable) in palbociclib and not reached in ribociclib. After 12 months, the progression-free survival rate was 51.5% (95% CI 34-69) in palbociclib and 78.6% (95% CI 63-94.1) in ribociclib. Neutropenia was the most common adverse event with an incidence rate of 87.9% in palbociclib and 82.1% in ribociclib. Cycle delays were needed in more than half of the patients treated with palbociclib and ribociclib (63.6% and 64.3%). Dose adjustments were seen in 42.4% and 53.6% of the patients receiving palbociclib and ribociclib, respectively. Regimen changes did not involve statistically significant differences in 12-month PFS rates in the cohort investigated. Conclusion Palbociclib and ribociclib outcomes are comparable to those reached in the phase III trials, PALOMA-3 and MONALEESA-2, respectively, and cannot be compared as they were used in different treatment settings. The toxicity profile is favourable, being neutropenia the most common adverse event, easily managed with regimen changes. Further studies are needed to confirm the observed tendency of no detrimental impact on effectiveness of these regimen changes.

In cancer cells, epithelial-to-mesenchymal transition (EMT) is controlled by Snail1, a transcriptional factor also required for the activation of cancer-associated fibroblasts (CAF). Snail1 is short-lived in normal epithelial cells as a consequence of its coordinated and continuous ubiquitination by several F-box-specific E3 ligases, but its degradation is prevented in cancer cells and in activated fibroblasts. Here, we performed an siRNA screen and identified USP27X as a deubiquitinase that increases Snail1 stability. Expression of USP27X in breast and pancreatic cancer cell lines and tumors positively correlated with Snail1 expression levels. Accordingly, downregulation of USP27X decreased Snail1 protein in several tumor cell lines. USP27X depletion impaired Snail1-dependent cell migration and invasion and metastasis formation and increased cellular sensitivity to cisplatin. USP27X was upregulated by TGFβ during EMT and was required for TGFβ-induced expression of Snail1 and other mesenchymal markers in epithelial cells and CAF. In agreement with this, depletion of USP27X prevented TGFβ-induced EMT and fibroblast activation. Collectively, these results indicate that USP27X is an essential protein controlling Snail1 expression and function and may serve as a target for inhibition of Snail1-dependent tumoral invasion and chemoresistance. SIGNIFICANCE: These findings show that inhibition of USP27X destabilizes Snail1 to impair EMT and renders tumor cells sensitive to chemotherapy, thus opening new strategies for the inhibition of Snail1 expression and its protumoral actions.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/1/33/F1.large.jpg. This study was funded by grants awarded by Ministerio de Economía y Competitividad (MINECO) and Fondo Europeo de Desarrollo Regional-FEDER to A. García de Herreros (SAF2013-48849-C2-1-R and SAF2016-76461-R) and to V.M. Díaz (SAF2013-48849-C2-2-R). Research at the A. García de Herreros lab is supported by funds from the Fundación Científica de la Asociación Española contra el Cáncer and from the Instituto de Salud Carlos III (PIE15/00008). Research at the B.S. Atanassov lab is supported by the Rosswell Park Cancer Institute and NCI grant P30CA016056. Research at the J. Arribas lab is supported by funds from the Breast Cancer Research Foundation (BCRF-17-008) and Instituto de Salud Carlos III (PI16/00253).

International audience; Suicidality in the child and adolescent population is a major public health concern. There is, however, a lack of developmentally sensitive valid and reliable instruments that can capture data on risk, and clinical and psychosocial mediators of suicidality in young people. In this study, we aimed to develop and assess the validity of instruments evaluating the psychosocial risk and protective factors for suicidal behaviours in the adolescent population. In Phase 1, based on a systematic literature review of suicidality, focus groups, and expert panel advice, the risk factors and protective factors (resilience factors) were identified and the adolescent, parent, and clinician versions of the STOP-Suicidality Risk Factors Scale (STOP-SRiFS) and the Resilience Factors Scale (STOP-SReFS) were developed. Phase 2 involved instrument validation and comprised of two samples (Sample 1 and 2). Sample 1 consisted of 87 adolescents, their parents/carers, and clinicians from the various participating centres, and Sample 2 consisted of three sub-samples: adolescents (n = 259) who completed STOP-SRiFS and/or the STOP-SReFS scales, parents (n = 213) who completed one or both of the scales, and the clinicians who completed the scales (n = 254). The STOP-SRiFS demonstrated a good construct validity-the Cronbach Alpha for the adolescent (α = 0.864), parent (α = 0.842), and clinician (α = 0.722) versions of the scale. Test-retest reliability, inter-rater reliability, and content validity were good for all three versions of the STOP-SRiFS. The sub-scales generated using Exploratory Factor Analysis (EFA) were the (1) anxiety and depression risk, (2) substance misuse risk, (3) interpersonal risk, (4) chronic risk, and (5) risk due to life events. For the STOP-SRiFS, statistically significant correlations were found between the Columbia-Suicide Severity Rating Scale (C-SSRS) total score and the adolescent, parent, and clinical versions of the STOP-SRiFS sub-scale scores. The STOP-SRiFS showed good psychometric properties. This study demonstrated a good construct validity for the STOP-SReFS-the Cronbach Alpha for the three versions were good (adolescent: α = 0.775; parent: α = 0.808; α = clinician: 0.808). EFA for the adolescent version of the STOP-SReFS, which consists of 9 resilience factors domains, generated two factors (1) interpersonal resilience and (2) cognitive resilience. The STOP-SReFS Cognitive Resilience sub-scale for the adolescent was negatively correlated (r = - 0.275) with the C-SSRS total score, showing that there was lower suicidality in those with greater Cognitive Resilience. The STOP-SReFS Interpersonal resilience sub-scale correlations were all negative, but none of them were significantly different to the C-SSRS total scores for either the adolescent, parent, or clinician versions of the scales. This is not surprising, because the items in this sub-scale capture a much larger time-scale, compared to the C-SSRS rating period. The STOP-SReFS showed good psychometric properties. The STOP-SRiFS and STOP-SReFS are instruments that can be used in future studies about suicidality in children and adolescents.

Autism spectrum disorders (ASD) and early‐onset psychosis (EOP) are neurodevelopmental disorders that share genetic, clinical and cognitive facets; it is unclear if these disorders also share spatially overlapping cortical thickness (CT) and surface area (SA) abnormalities. MRI scans of 30 ASD, 29 patients with early‐onset first‐episode psychosis (EO‐FEP) and 26 typically developing controls (TD) (age range 10–18 years) were analyzed by the FreeSurfer suite to calculate vertex‐wise estimates of CT, SA, and cortical volume. Two publicly available datasets of ASD and EOP (age range 7–18 years and 5–17 years, respectively) were used for replication analysis. ASD and EO‐FEP had spatially overlapping areas of cortical thinning and reduced SA in the bilateral insula (all p’s

Insight has long been linked to both prognosis and functioning in patients with schizophrenia; likewise, it is key to treatment adherence. This study seeks to assess the association between insight, adherence to pharmacological treatment, and disability in schizophrenia, and to study the potential mediating role of adherence between insight and disability. Insight (SUMD), adherence (CRS), and disability (WHO-DAS) were measured in 80 clinically stable patients with DSM-IV TR paranoid schizophrenia. Psychopathology was assessed with the Positive and Negative Syndrome Scale (PANSS). In a first step, predictors of disability were identified using linear regression to identify variables related to disability and further a mediation analysis was carried out. Negative symptoms, insight, and adherence account for 54.2% of the variance in disability. Negative symptoms act directly on disability, while the effect of insight on disability is partially mediated by adherence. Insight is key in disability in schizophrenia and should be leveraged in treatment programs.

Background It has been documented that anxiety and depression are prevalent in patients with asthma and are associated with greater frequency of exacerbations, increased use of health care resources, and poor asthma control. Objective To examine the association of asthma diagnosis with symptoms of depression/anxiety and asthma control not only at baseline but also over a 6-month period of specialist supervision. Methods We enrolled 3182 patients with moderate to severe asthma. All were evaluated with spirometry, the Asthma Control Test, and the Hospital Anxiety and Depression Scale at baseline and at 6 months. Treatments were decided by specialists according to published guidelines. Results At baseline, 24.2% and 12% of the patients were diagnosed with anxiety and depression, respectively, according to the Hospital Anxiety and Depression Scale. After 6 months, anxiety and depression improved, affecting 15.3% and 8.1% of patients, respectively (P Conclusion Under standardized asthma care and after a specific visit with the specialist, patients present significant improvement in these psychological disorders and exhibit better asthma control and functional parameters.

In chronic kidney disease (CKD), high serum phosphate concentration is associated with cardiovascular disease and deterioration in renal function. In early CKD, the serum phosphate concentration is normal due to increased fractional excretion of phosphate. Our premise was that high phosphate intake even in patients with early CKD would result in an excessive load of phosphate causing tubular injury and accelerating renal function deterioration. In CKD 2–3 patients, we evaluated whether increased phosphaturia accelerates CKD progression. To have a uniform group of patients with early CKD, 95 patients with metabolic syndrome without overt proteinuria were followed for 2.7 ± 1.6 years. The median decline in eGFR was 0.50 ml/min/1.73 m2/year. Patients with a more rapid decrease in eGFR had greater phosphaturia. Moreover, the rate of decrease in eGFR inversely correlated with the degree of phosphaturia. Additionally, phosphaturia independently predicted renal function deterioration. In heminephrectomized rats, a high phosphate diet increased phosphaturia resulting in renal tubular damage associated with inflammation, oxidative stress and low klotho expression. Moreover, in rats with hyperphosphatemia and metabolic syndrome antioxidant treatment resulted in attenuation of renal lesions. In HEK-293 cells, high phosphate promoted oxidative stress while melatonin administration reduced ROS generation. Our findings suggest that phosphate loading in early CKD, results in renal damage and a more rapid decrease in renal function due to renal tubular injury.

Shared vulnerability in offspring of individuals with schizophrenia (SzO) and bipolar disorder (BpO) might manifest early during development through common temperament traits. Temperament dimensions in child and adolescent BpO (N = 80), SzO (N = 34) and the offspring of community controls (CcO) (N = 101) were assessed using the Revised Dimensions of Temperament Survey. The association between temperament dimensions and lifetime psychopathology (including threshold and subthreshold DSM-IV-TR diagnoses) and current socio-academic adjustment was assessed using logistic regression. Fully adjusted models showed that both BpO and SzO scored significantly lower in the positive mood dimension and in the adaptability factor than CcO, with small-medium effect sizes (Cohen's d ~ 0.3-0.5). BpO also scored lower in the activity factor and the activity dimensions than CcO (Cohen's d ~ 0.3). Lower scores in the positive mood dimension were associated with increased risk of impaired adjustment both in BpO [OR 2.30, 95% CI (1.18-4.46)] and in SzO [OR 2.87, 95% CI (1.07-7.66)]. In BpO, lower scores in positive mood were also associated with increased likelihood of internalizing [OR 1.84, 95% CI (1.28-2.64)] and externalizing disorders [OR 1.48, 95% CI (1.01-2.18)]; in SzO, higher scores in activity and flexibility were associated with increased likelihood of internalizing [OR 2.31, 95% CI (1.22-4.38)] and externalizing disorders [OR 3.28, 95% CI (1.2-9)], respectively. Early difficulties in emotion regulation might represent a shared vulnerability phenotype in BpO and SzO. The identification of extreme temperament traits could help to characterize subgroups at greater risk of psychopathology and impaired adjustment, in which targeted interventions are warranted.

Objective To compare the offspring of patients with SZ (SZoff) with those of a community control group (CC-off) to determine the variables associated with attenuated psychotic symptoms (APS), general symptomatology and functioning that may help to differentiate those at genetic risk for SZ. Methods 41 SZ-off and 107 CC-off aged 6–17 years were included. The Structured Interview for Prodromal Symptoms (SIPS), scored on the Scale of Prodromal Symptoms (SOPS), was administered by a child psychiatrist blinded to parental diagnoses, together with other clinical and functional scales. Results The SZ-off group presented higher scores in positive (p = 0.000), negative (p = 0.012), and disorganized (p = 0.009) subscale scores, as well as in the total score (p = 0.001) on the SOPS when compared with the CC-off group. Other scales indicated significant emotional (p = 0.028), behavioral (p = 0.000) and peer-related problems (p = 0.025), lower performance at school (p = 0.025) and increased dysfunction score (p = 0.005) in the SZ-off group. Logistic regression analysis revealed lower socioeconomic statuses (OR: 0.92, 95%CI: 0.87–0.97) and higher SOPS positive subscale scores (OR: 2.41, 95%CI: 1.31–4.42) in the SZ-off group. Conclusions SZ-off presented significantly more APS and higher mean scores in psychopathological scales than CC-off, together with increased dysfunction scores. These early warning signs and follow-up for those at genetic high risk for schizophrenia will provide useful information about symptom progression, facilitating early intervention to improve short and long-term outcomes in youths with a positive family history.

Introduction Recent prospective studies support the feasibility of performing sentinel lymph node biopsy following neoadjuvant chemotherapy in initially fine-needle aspiration cytology or ultrasound-guided biopsy-proven node-positive breast cancer. The main aid is to identify preoperative features that help us predict a complete axillary response to neoadjuvant chemotherapy in these patients and thus select the candidates for sentinel lymph node biopsy post-neoadjuvant chemotherapy to avoid unnecessary axillary lymphadenectomy. Materials and methods A retrospective observational study with a total of 150 patients, biopsy-proven node-positive breast cancer who underwent neoadjuvant chemotherapy followed by breast surgery and axillary lymphadenectomy were included and retrospectively analysed. A predictive model was generated by a multivariate logistic regression analysis for pathological complete response-dependent variable. Results The response of the primary lesion to neoadjuvant chemotherapy according to post-treatment magnetic resonance imaging, Her2/neu overexpression and a low estrogen receptor expression are associated with a higher rate of nodal pathologically complete response. The multivariant model generated a receiver operating characteristic curve with an area under the curve of 0.79 and a confidence interval of 0.72–0.87 at a 95% level of significance. Conclusions This model could be a helpful tool for the surgeon to help in predicting which cases have a higher likelihood of achieving a pathologically complete response and therefore selecting those who may benefit from a post-neoadjuvant chemotherapy sentinel lymph node biopsy and avoid unnecessary axillary lymphadenectomy.

Objective Magnetic resonance imaging (MRI) studies in bipolar I disorder (BD-I) suggest that lithium is associated with increased volumes of cortico-limbic structures. However, more rigorous control of confounding factors is needed to obtain further support for this hypothesis. The aim of the present study was to assess differences in brain volumes among long-term lithium-treated BD-I patients, unmedicated BD-I patients, and healthy controls. Methods This was a cross-sectional study with 32 euthymic BD-I patients (16 on lithium monotherapy for a mean of 180 months, and 16 receiving no medication for at least the 2 months prior to the study) and 20 healthy controls. Patients were euthymic (Hamilton Depression Rating Scale [HDRS]

There has been growing scientific evidence in recent years that schizophrenia and bipolar disorder share clinical, cognitive, neuroimaging and genetic characteristics. This overlap might also be present in their offspring, who have an increased risk of developing both disorders. Comparing the characteristics of these samples may have important implications for understanding etiological processes. This study aimed to assess the development of cognitive functions over two years in a sample of child and adolescent offspring of patients diagnosed with schizophrenia (SZoff) or bipolar disorder (BDoff), comparing them with a community control group (CCoff). Methods 90 BDoff, 41 SZoff and 107 CCoff aged between 6 and 17 years were included at baseline. At the two-year follow-up, 84.9% of the sample was re-assessed (78 BDoff, 32 SZoff and 92 CCoff). All subjects were assessed with a comprehensive neuropsychological test battery at baseline and at the two-year follow-up to evaluate: intelligence quotient, working memory, processing speed, verbal memory and learning, visual memory, executive functions and sustained attention. Results Processing speed, verbal memory and executive functions showed different developmental patterns among the SZoff, BDoff and CCoff groups. The SZoff group maintained baseline performances in the three variables over time, while the BDoff group presented improved processing speed and executive functioning and the CCoff group showed improvements in verbal memory and executive functions at follow-up. Conclusions These findings suggest that the development of some cognitive functions might differ between child and adolescent SZoff and BDoff, indicating different trajectories during neurodevelopment.

Introduction: Preoperative treatment and adequate surgery increase local control in rectal cancer. However, modalities and indications for neoadjuvant treatment may be controversial. Aim of this study was to assess the trends of preoperative treatment and outcomes in patients with rectal cancer included in the Rectal Cancer Registry of the Spanish Associations of Surgeons. Method: This is a STROBE-compliant retrospective analysis of a prospective database. All patients operated on with curative intention included in the Rectal Cancer Registry were included. Analyses were performed to compare the use of neoadjuvant/adjuvant treatment in three timeframes: I)2006–2009; II)2010–2013; III)2014–2017. Survival analyses were run for 3-year survival in timeframes I-II. Results: Out of 14, 391 patients, 8871 (61.6%) received neoadjuvant treatment. Long-course chemo/radiotherapy was the most used approach (79.9%), followed by short-course radiotherapy ± chemotherapy (7.6%). The use of neoadjuvant treatment for cancer of the upper third (15-11 cm) increased over time (31.5%vs 34.5%vs 38.6%, p = 0.0018). The complete regression rate slightly increased over time (15.6% vs 16% vs 18.5%; p = 0.0093); the proportion of patients with involved circumferential resection margins (CRM) went down from 8.2% to 7.3%and 5.5% (p = 0.0004). Neoadjuvant treatment significantly decreased positive CRM in lower third tumors (OR 0.71, 0.59–0.87, Cochrane-Mantel-Haenszel P = 0.0008). Most ypN0 patients also received adjuvant therapy. In MR-defined stage III patients, preoperative treatment was associated with significantly longer local-recurrence-free survival (p < 0.0001), and cancer-specific survival (p < 0.0001). The survival benefit was smaller in upper third cancers. Conclusion: There was an increasing trend and a potential overuse of neoadjuvant treatment in cancer of the upper rectum. Most ypN0 patients received postoperative treatment. Involvement of CRM in lower third tumors was reduced after neoadjuvant treatment. Stage III and MRcN + benefited the most.

The observed heterogeneity in negative symptom treatment response may be partly attributable to inadequate measurement tools or limitations in methods of analysis. Previous Item Response Theory models of the Positive and Negative Syndrome Scale (PANSS) have only examined samples of chronic patients and with mixed results. We examined the scalability of the negative subscale embedded in the PANSS and subsequently explored negative symptom trajectories across four weeks of amisulpride treatment. Data were derived from the OPTiMiSE trial comprising 446 patients with first-episode schizophrenia or schizophreniform disorder. Using the Rasch Model to examine psychometric properties of the PANSS negative subscale, we found that the composite score across items was not an adequate measure of negative symptom severity. Consequently, we chose an exploratory statistical approach involving Principal Component Analysis which yielded one significant component clustering into two significant symptom trajectories: 1) Subtle but constant decrease in negative symptom severity (N = 323; 72%), and 2) symptom instability across visits (N = 19; 4%). Explorative analytic methods as presented here may pave the way for more efficient and sensitive methods of analyzing negative symptom response in research and in clinical practice.

Methanol poisoning is often described in the literature, but not transdermal or inhalational poisoning. It usually involves variable multi-organ damage, among which visual, neurological, and gastrointestinal involvement, as well as the metabolic and electrolyte changes that can lead to death. Contact with toluene by occupational or intentional inhalation may also cause neurological abnormalities. This article describes the case of a female patient who was seen in the Emergency Department due to bilateral visual loss secondary to accidental poisoning (inhalation-transdermal) with a solvent containing methanol and toluene. She had a favourable outcome during admission after treatment with ethanol in perfusion and corticosteroids.

The successful performance of ostomies for the treatment of different diseases has been described since 1706. We report herein the first case of successful ostomy utilizing a synthetic stoma created in a patient with peritoneal carcinomatosis.A 40-year-old woman presented with abdominal carcinomatosis due to psammomatous papillotubular adenocarcinoma consistent with primary ovarian carcinoma. The patient had negative estrogen and progesterone receptors and Ki-67 proliferative activity was 83%. She was initially treated with cytoreduction therapy, chemotherapy, and hyperthermic intraperitoneal chemotherapy. Because the patient presented with enteric perforations and the extensive tumor invasion and adhesions in all the intestinal segments made it impossible to create autologous decompression stomas, a synthetic stoma was constructed.Synthetic stomas can be a good treatment option when autologous stomas can not be created.Desde el año 1706 se han descrito ostomías realizadas con éxito para el tratamiento de diferentes enfermedades; los autores describen el primer caso de éxito en una ostomía sintética en la carcinomatosis peritoneal.Mujer de 40 años de edad con carcinomatosis abdominal por adenocarcinoma papilar tubulopapilar psamomatoso más consistente con cáncer primario de ovario, negativo a receptores de estrógenos y progesterona, con marcador Ki-67 al 83% de actividad. De modo inicial se trató con cirugía de citorreducción, quimioterapia, quimioterapia intraperitoneal hipertérmica y por último realización de estomas sintéticos debido a perforaciones entéricas e imposibilidad de realizar estomas descompresivos autólogos por la invasión tumoral extensa y adherencias de todas las asas intestinales.Los estomas sintéticos pueden ser una buena opción terapéutica cuando es imposible realizar estomas autólogos.

Primary hyperhidrosis is a benign disease that consists in the excessive production of sweat, mainly in the hands, axillas and feet. It may to interfere with the social and work life of the sufferer. It affects up to 3% of the population. In Cuba there are no epidemiological studies on its prevalence. One of the treatment modalities is videothoracoscopic sympathicotomy.To describe the results of the videothoracoscopic sympathicotomy technique for two ports using apneic oxygenation to achieve lung collapse.Descriptive, retrospective study of 27 cases operated by primary hyperhidrosis in the period from May 2015 to June 2018. Demographic and clinical characteristics of operated patients, results of the endoscopic surgical technique, postoperative complications and satisfaction were described.The 27 patients were adolescents with ages ranging from 11 to 19 years old, it was more frequent in the female sex. All patients had total solution of the symptoms in the intraoperative period, demonstrated by the cessation of sweat in the palms or axillas and by the verification of the increase of the palmar temperature in the monitor. No patient had intraoperative complications. Compensatory sweating occurred in four patients and one had intercostal neuritis. 100% of the patients were satisfied with the result at 30 days of treatment.It is a safe technique, with few complications, high satisfaction with the results and feasible to perform in pediatric hospitals with basic resources of minimal access surgery.La hiperhidrosis primaria es una enfermedad benigna que consiste en la excesiva producción de sudor, principalmente en manos, axilas y pies, y por ello puede llegar a condicionar la vida social y laboral de quien la padece. Afecta hasta el 3% de la población. En Cuba no hay estudios epidemiológicos sobre su prevalencia. Una de las modalidades de tratamiento es la simpaticotomía videotoracoscópica.Describir los resultados de la técnica de simpaticotomía videotoracoscópica por dos puertos usando oxigenación apneica para lograr el colapso pulmonar.Estudio descriptivo, retrospectivo, de una serie de 27 casos operados por hiperhidrosis primaria en el periodo de mayo de 2015 a junio de 2018. Se describen características demográficas y clínicas de pacientes operados, resultados de la técnica quirúrgica endoscópica, complicaciones postoperatorias y satisfacción.Los 27 pacientes eran adolescentes con edades comprendidas entre 11 y 19 años, siendo más frecuente en el sexo femenino. Todos los pacientes tuvieron solución total de los síntomas en el periodo intraoperatorio, demostrados por el cese del sudor en palmas o axilas y por la comprobación del aumento de la temperatura palmar en el monitor. Ningún paciente tuvo complicaciones intraoperatorias. El sudor compensatorio se presentó en cuatro pacientes y un paciente tuvo neuritis intercostal. El 100% de los pacientes estuvieron satisfechos con el resultado a los 30 días del tratamiento.Es una técnica segura, con pocas complicaciones, elevada satisfacción con los resultados y factible de realizar en hospitales pediátricos con recursos básicos de cirugía de mínimo acceso.

CONTEXT: Dietary interventions such as restrictive diets or supplements are common treatments for young people with autism spectrum disorder (ASD). Evidence for the efficacy of these interventions is still controversial. OBJECTIVE: To assess the efficacy of specific dietary interventions on symptoms, functions, and clinical domains in subjects with ASD by using a meta-analytic approach. DATA SOURCES: Ovid Medline, PsycINFO, Embase databases. STUDY SELECTION: We selected placebo-controlled, double-blind, randomized clinical trials assessing the efficacy of dietary interventions in ASD published from database inception through September 2017. DATA EXTRACTION: Outcome variables were subsumed under 4 clinical domains and 17 symptoms and/or functions groups. Hedges’ adjusted g values were used as estimates of the effect size of each dietary intervention relative to placebo. RESULTS: In this meta-analysis, we examined 27 double-blind, randomized clinical trials, including 1028 patients with ASD: 542 in the intervention arms and 486 in the placebo arms. Participant-weighted average age was 7.1 years. Participant-weighted average intervention duration was 10.6 weeks. Dietary supplementation (including omega-3, vitamin supplementation, and/or other supplementation), omega-3 supplementation, and vitamin supplementation were more efficacious than the placebo at improving several symptoms, functions, and clinical domains. Effect sizes were small (mean Hedges’ g for significant analyses was 0.31), with low statistical heterogeneity and low risk of publication bias. LIMITATIONS: Methodologic heterogeneity among the studies in terms of the intervention, clinical measures and outcomes, and sample characteristics. CONCLUSIONS: This meta-analysis does not support nonspecific dietary interventions as treatment of ASD but suggests a potential role for some specific dietary interventions in the management of some symptoms, functions, and clinical domains in patients with ASD.

Linguistic negation acts by inhibiting the representation of information under its scope, often leading to the representation of positive alternative states of affairs. Motivational direction refers to approach/avoidance intentionality in our interactions with environmental stimuli expressed by means of verbs (e.g., "accept" vs "reject"). We consider it plausible that negation interacts with direction to represent the true motivation of the protagonist in sentence understanding (e.g., if an approach action is negated it is represented as avoidance). In the first study, we examine this interaction offline by asking participants to judge approach or avoidance meaning of affirmative (e.g., "he/she included/excluded meat") and negative sentences ("he/she did not include/exclude meat"). Results support that negation reversed participants' interpretation of sentence motivational direction. In a further study, we carried out two probe recognition experiments to examine the interaction during sentence comprehension; in both, the critical probe was the word referring to the target of the action (e.g., "meat"). In the first experiment, participants had to recognize the probe word presented 1500 milliseconds after sentence offset, while for the second one, the delay was 500 milliseconds. Results showed that at 1500 ms, target recognition took significantly more time for negated avoidance sentences than for the other conditions. Therefore, representing negated avoidance sentences seems to imply more complex processing, as avoidance verbs would be implicitly negative. By contrast, at the 500 ms delay, negation impaired target recognition for both approach and avoidance sentences, suggesting an unspecific inhibitory effect of negation at that sentence processing stage. Implication of these results for both research on negation and in action understanding are discussed.

Frontal fibrosing alopecia is an increasingly common form of scarring alopecia. The aim of this study was to describe the demographic and clinical characteristics of patients with FFA seen at the trichology unit of a medium-sized regional hospital and to report on treatments used.We reviewed the medical records of all patients with FFA seen at the trichology unit of Hospital Universitario Infanta Sofía in Madrid, Spain between May 2016 and May 2018. We analyzed associations between disease severity, clinical patterns, need for oral medications, and other characteristics.Seventy-five patients (73 women and 2 men) were studied. Diagnosis was clinical in most cases and 13 cases (17.3%) were confirmed histologically. Median (interquartile range) age at reported onset of symptoms was 61 (12) years. Involvement of the eyebrows was recorded in 70 patients (93.3%) and signs of oral and genital lichen planus in 7 (9.6%). Eleven patients (14.7%) had hypothyroidism and 15 (20.0%) had signs of rosacea. Only 5 of the patients who presented a linear pattern (21.7%) had severe hairline recession. Patients with unstable and/or symptomatic disease (n=24) were treated with oral medications (5-alpha reductase inhibitors, hydroxychloroquine, corticosteroids, and isotretinoin) or intralesional corticosteroids. Eighteen patients (75.0%) achieved disease stability. Ten of the 15 patients with signs of rosacea and 10 of those with facial papules required systemic treatment.Most of the patients in this series of FFA were postmenopausal women. The prevalence of oral and genital lichen planus was higher than that observed in the general population. Patients with a linear pattern had less severe disease. Facial papules were more common in younger patients and both facial papules and rosacea were associated with a greater need for oral treatment.