Molecular and thermodynamic properties of zwitterions versus ionic liquids: A comprehensive computational analysis to develop advanced separation processes

WILEY: "This is the peer reviewed version of the following article: ChemPhysChem 19.7 (2018): 801-815, which has been published in final form at http://doi.org/10.1002/cphc.201701093. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions." Este artículo apareció anteriormente con el siguiente título "Exploring molecular and thermodynamic properties of zwitterions vs ionic liquids: A comprehensive computational analysis to develop advanced separation processes"Zwitterion ionic liquids (ZIs) are compounds in which both counterions are covalently tethered, conferring them with unique characteristics; however, most of their properties are still unknown, representing a bottleneck to exploit their practical applications. Herein, the molecular and fluid properties of ZIs and their mixtures were explored by means of quantum chemical analysis based on the density functional theory (DFT) and COSMO-RS method, and compared against homologous ionic liquids (ILs) to provide a comprehensive overview of the effect of the distinct structures on their physicochemical and thermodynamic behavior. Overall, ZIs were revealed as compounds with higher polarity and stronger hydrogen-bonding capacity, implying higher density, viscosity, melting point, and even lower volatility than structurally similar ILs. The phase equilibrium of binary and ternary systems supports stronger attractive interactions between ZIs and polar compounds, whereas higher liquid–liquid immiscibility with nonpolar compounds may be expected. Ultimately, the performance of ZIs in the wider context of separation processes is illustrated, while providing molecular insights to allow their selection and design for relevant applicationsThe authors would like to acknowledge to Comunidad Autónoma de Madrid for the Project S2013/MAE-2800 and to Ministerio de Economía y Competitividad (MINECO) of Spain for financial support of Projects CTQ2014-52288-R. We are very grateful to Centro de Computación Científica de la Universidad Autónoma de Madrid for computational facilities. We all would like to acknowledge kind support in the framework of the COST Action EXIL-Exchange on Ionic Liquids (CM1206)

Alkaloids as alternative probes to characterize the relative hydrophobicity of aqueous biphasic systems

In order to overcome the lack of characterization on the relative hydrophobicity of aqueous biphasic systems (ABS), the partition of three alkaloids as alternative probes, was evaluated in a series of biocompatible ABS composed of cholinium-based salts or ionic liquids (ILs) and polyethylene glycol (PEG). The caffeine partitioning in ABS was firstly addressed to infer on the effect of the phase-forming components composition. In all systems, caffeine preferentially concentrates in the lower water content PEG-rich phase. Additionally, a linear dependence between the logarithmic function of the partition coefficients and the water content ratio was found. To confirm this linear dependency, the partition coefficients of caffeine, theobromine and theophylline were determined in other ABS formed by different cholinium-based salts/ILs. In most systems, it is shown that all alkaloids partition to the most hydrophobic phase. To support the experimental results, COSMO-RS (Conductor-like Screening Model for Real Solvents) was used to compute the screening charge distributions of both phaseforming components of ABS and alkaloids, the excess enthalpy of mixing and the activity coefficients at infinite dilution. It is here demonstrated that the partition trend of alkaloids can be used to address the relative hydrophobicity of the coexisting phases in polymer-salt/-IL ABS

Label-Free Plasmonic Biosensor for Rapid, Quantitative, and Highly Sensitive COVID-19 Serology: Implementation and Clinical Validation

COVID-19; Biosensor plasmónico; SerologíaCOVID-19; Biosensor plasmònic; SerologiaCOVID-19; Plasmonic biosensor; SerologySerological tests are essential for the control and management of COVID-19 pandemic (diagnostics and surveillance, and epidemiological and immunity studies). We introduce a direct serological biosensor assay employing proprietary technology based on plasmonics, which offers rapid (<15 min) identification and quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in clinical samples, without signal amplification. The portable plasmonic device employs a custom-designed multiantigen (RBD peptide and N protein) sensor biochip and reaches detection limits in the low ng mL–1 range employing polyclonal antibodies. It has also been implemented employing the WHO-approved anti-SARS-CoV-2 immunoglobulin standard. A clinical validation with COVID-19 positive and negative samples (n = 120) demonstrates its excellent diagnostic sensitivity (99%) and specificity (100%). This positions our biosensor as an accurate and easy-to-use diagnostics tool for rapid and reliable COVID-19 serology to be employed both at laboratory and decentralized settings for the disease management and for the evaluation of immunological status during vaccination or treatment.ICN2 and UVE acknowledge financial support from H2020 Research and Innovation Programme of the European Commission (H202-SC1-PHE-Coronavirus-2020, CONVAT Project, No. 101003544). The ICN2 is funded by the CERCA program/Generalitat de Catalunya and supported by the Severo Ochoa Centres of Excellence program funded by the Spanish Research Agency (AEI, grant no. SEV-2017-0706). ICN2 group is very grateful to EPI Industries (Barcelona, Spain) for its kind donation supporting our research in COVID-19. O.C.-L. acknowledges the economic support from the Spanish Ministry of Science and Innovation and the Spanish Research Agency and the European Social Fund (ESF) (ref. BES-2017-080527) linked to the TEC 2016-78515-R project Predict. A part of the work was supported by the European Virus Archive GLOBAL (EVA-GLOBAL) project that has received funding from the EU Horizon 2020 (grant agreement No. 871029). A.T. and L.F.-B. acknowledge financial support from GENCAT-DGRIS COVID. We are indebted to all the patients who accepted to participate contributing to science advancement. We are indebted to the HCB-IDIBAPS Biobank for the human samples and data procurement and to the Fundació Glòria Soler for its support to the COVIDBANK collection. We thank the IDIBAPS Biobank for its valuable contribution to sample processing and storage. The authors acknowledge the EU Horizon 2020 Program under grant agreement no. 644956 (RAIS project) for funding the Hospital Vall d’Hebron Biobank. The VHIR-HUVH is supported by Plan Nacional de I + D + i 2013-2016 and ISCIII-Ministerio de Ciencia e Innovación, and Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0003)─cofinanced by European Development Regional Fund “A way to achieve Europe,” Operative program Intelligent Growth 2014. Part of the samples and data from patients included in this study were provided by the Vall d’Hebron University Hospital Biobank (PT17/0015/0047), integrated in the Spanish National Biobanks Network, and they were processed following standard operating procedures with the appropriate approval of the Ethical and Scientific Committee. The authors kindly appreciate the generous donation of samples and clinical data of the donors of the Sepsis Bank of HUVH Biobank and COVID-19 patients attended at HUVH

Gene co-expression architecture in peripheral blood in a cohort of remitted first-episode schizophrenia patients

A better understanding of schizophrenia subtypes is necessary to stratify the patients according to clinical attributes. To explore the genomic architecture of schizophrenia symptomatology, we analyzed blood co-expression modules and their association with clinical data from patients in remission after a first episode of schizophrenia. In total, 91 participants of the 2EPS project were included. Gene expression was assessed using the Clariom S Human Array. Weighted-gene co-expression network analysis (WGCNA) was applied to identify modules of co-expressed genes and to test its correlation with global functioning, clinical symptomatology, and premorbid adjustment. Among the 25 modules identified, six modules were significantly correlated with clinical data. These modules could be clustered in two groups according to their correlation with clinical data. Hub genes in each group showing overlap with risk genes for schizophrenia were enriched in biological processes related to metabolic processes, regulation of gene expression, cellular localization and protein transport, immune processes, and neurotrophin pathways. Our results indicate that modules with significant associations with clinical data showed overlap with gene sets previously identified in differential gene-expression analysis in brain, indicating that peripheral tissues could reveal pathogenic mechanisms. Hub genes involved in these modules revealed multiple signaling pathways previously related to schizophrenia, which may represent the complex interplay in the pathological mechanisms behind the disease. These genes could represent potential targets for the development of peripheral biomarkers underlying illness traits in clinical remission stages after a first episode of schizophrenia

Predictors of adherence to a Mediterranean-type diet in the PREDIMED trial.

BACKGROUND: Determinants of dietary changes obtained with a nutritional intervention promoting the Mediterranean diet have been rarely evaluated. AIM: To identify predictors of higher success of an intervention aimed to increase adherence to a Mediterranean diet (MeDiet) in individuals at high cardiovascular risk participating in a trial for primary prevention of cardiovascular disease: the PREDIMED (PREvención con DIeta MEDiterránea) trial. Candidate predictors included demographic and socioeconomic characteristics, cardiovascular risk factors, and baseline dietary habits. METHODS: A total of 1,048 asymptomatic subjects aged 55-80 years allocated to the active intervention groups (subjects in the control group were excluded). Participants' characteristics were assessed at baseline among subjects. Dietary changes were evaluated after 12 months. Main outcome measures were: attained changes in five dietary goals: increases in (1) fruit consumption, (2) vegetable consumption, (3) monounsaturated fatty acid (MUFA)/saturated fatty acid (SFA) ratio, and decreases in (4) sweets and pastries consumption, (5) and meat consumption. Univariate and multivariate logistic regression analyses were used to examine associations between the candidate predictors and likelihood of attaining optimum dietary change (improved adherence to a MeDiet). RESULTS: Among men, positive changes toward better compliance with the MeDiet were more frequent among non-diabetics, and among those with worse dietary habits at baseline (higher consumption of meat, higher SFA intake, lower consumption of fruit and vegetables). Among women, marital status (married) and worse baseline dietary habits (high in meats, low in fruits and vegetables) were the strongest predictors of success in improving adherence to the MeDiet. CONCLUSIONS: Some participant characteristics (marital status and baseline dietary habits) could contribute to predicting the likelihood of achieving dietary goals in interventions aimed to improve adherence to a MeDiet, and may be useful for promoting individualized long-term dietary changes and improving the effectiveness of dietary counseling

Primary prevention of cardiovascular disease with a Mediterranean diet

BACKGROUND: Observational cohort studies and a secondary prevention trial have shown an inverse association between adherence to the Mediterranean diet and cardiovascular risk. We conducted a randomized trial of this diet pattern for the primary prevention of cardiovascular events. METHODS: In a multicenter trial in Spain, we randomly assigned participants who were at high cardiovascular risk, but with no cardiovascular disease at enrollment, to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). Participants received quarterly individual and group educational sessions and, depending on group assignment, free provision of extra-virgin olive oil, mixed nuts, or small nonfood gifts. The primary end point was the rate of major cardiovascular events (myocardial infarction, stroke, or death from cardiovascular causes). On the basis of the results of an interim analysis, the trial was stopped after a median follow-up of 4.8 years. RESULTS: A total of 7447 persons were enrolled (age range, 55 to 80 years); 57% were women. The two Mediterranean-diet groups had good adherence to the intervention, according to self-reported intake and biomarker analyses. A primary end-point event occurred in 288 participants. The multivariable-adjusted hazard ratios were 0.70 (95% confidence interval [CI], 0.54 to 0.92) and 0.72 (95% CI, 0.54 to 0.96) for the group assigned to a Mediterranean diet with extra-virgin olive oil (96 events) and the group assigned to a Mediterranean diet with nuts (83 events), respectively, versus the control group (109 events). No diet-related adverse effects were reported. CONCLUSIONS: Among persons at high cardiovascular risk, a Mediterranean diet supplemented with extra-virgin olive oil or nuts reduced the incidence of major cardiovascular events

The effect of early life events on glucose levels in first-episode psychosis

First episode of psychosis (FEP) patients display a wide variety of metabolic disturbances at onset, which might underlie these patients’ increased morbidity and early mortality. Glycemic abnormalities have been previously related to pharmacological agents; however, recent research highlights the impact of early life events. Birth weight (BW), an indirect marker of the fetal environment, has been related to glucose abnormalities in the general population over time. We aim to evaluate if BW correlates with glucose values in a sample of FEP patients treated with different antipsychotics. Two hundred and thirty-six patients were included and evaluated for clinical and metabolic variables at baseline and at 2, 6, 12, and 24 months of follow-up. Pearson correlations and linear mixed model analysis were conducted to analyze the data. Antipsychotic treatment was grouped due to its metabolic risk profile. In our sample of FEP patients, BW was negatively correlated with glucose values at 24 months of follow-up [r=-0.167, p=0.037]. BW showed a trend towards significance in the association with glucose values over the 24-month period (F=3.22; p=0.073) despite other confounders such as age, time, sex, body mass index, antipsychotic type, and chlorpromazine dosage. This finding suggests that BW is involved in the evolution of glucose values over time in a cohort of patients with an FEP, independently of the type of pharmacological agent used in treatment. Our results highlight the importance of early life events in the later metabolic outcome of patients

Early-Stage Breast Cancer Detection in Breast Milk

Breast cancer; Breast milkCáncer de mama; Leche maternaCàncer de mama; Llet maternaBreast cancer occurring during pregnancy (PrBC) and postpartum (PPBC) is usually diagnosed at more advanced stages compared with other breast cancer, worsening its prognosis. PPBC is particularly aggressive, with increased metastatic risk and mortality. Thus, effective screening methods to detect early PrBC and PPBC are needed. We report for the first time that cell-free tumor DNA (ctDNA) is present in breast milk (BM) collected from patients with breast cancer. Analysis of ctDNA from BM detects tumor variants in 87% of the cases by droplet digital PCR, while variants remain undetected in 92% of matched plasma samples. Retrospective next-generation sequencing analysis in BM ctDNA recapitulates tumor variants, with an overall clinical sensitivity of 71.4% and specificity of 100%. In two cases, ctDNA was detectable in BM collected 18 and 6 months prior to standard diagnosis. Our results open up the potential use of BM as a new source for liquid biopsy for PPBC detection. Significance: For the first time, we show that BM obtained from patients with breast cancer carries ctDNA, surpassing plasma-based liquid biopsy for detection and molecular profiling of early-stage breast cancer, even prior to diagnosis by image.We thank the patients who participated in the study and donated samples for analysis for their generous contribution, with particular thanks to the first patient, Maite, and her daughter Àneu, who inspired us to initiate this study (oral consent to name the patient and her daughter was provided by the patient, and her legal partner provided written consent after patient's exitus). We are grateful to Javier Carmona for his valuable contributions and support in the manuscript's conceptualization, preparation, and revision. VHIO would like to acknowledge the Cellex Foundation for providing research facilities and equipment and the CERCA Programme from the Generalitat de Catalunya for their support of this research. The authors from VHIO acknowledge the State Agency for Research (Agencia Estatal de Investigación) for the financial support as a Center of Excellence Severo Ochoa (CEX2020-001024-S/AEI/10.13039/501100011033). This research is financially supported by the “El paseíco de la mama” Foundation. C. Saura was the recipient of a II FERO-GHD grant from the FERO Foundation (FERO/5086), a Junior Clinical award from the Spanish Association Against Cancer Foundation (FAECC; CLJUN212026ORTI), and a SEOM-Daiichi Sankyo grant for its support on the Breast Cancer Research Projects 2021 (SEOM/FECMA2022) and received funding from the Department of Health (Generalitat de Catalunya SLT008/18/00198) and from the Instituto de Salud Carlos III (ISCIII) and Fondo Europeo de Desarrollo Regional (FEDER), cofunded by the European Union (PI21/01020). C. Ortiz was the recipient of a Junior Clinician award from the FAECC (CLJUN212026ORTI) and a SEOM-Daiichi Sankyo grant for its support on the Breast Cancer Research Projects 2021 (SEOM/FECMA2022), and received funding from the Department of Health (Generalitat de Catalunya SLT008/18/00198). N. Bayó-Puxan received funding from the Department of Health (Generalitat de Catalunya SLT008/18/00205), MCIN/AEI/10.13039/501100011033 (GPE2022-001029) and MCIN/AEI/10.130.39/501100011033, and the European Union “Next GenerationEU/PRTR” (ECT2020-000827). J.M. Miquel received funding from the Department of Health (Generalitat de Catalunya SLT008/18/00205), MCIN/AEI/10.130.39/501100011033, and the European Union “Next GenerationEU/PRTR” (ECT2020-000827). J. Arribas is funded by the Breast Cancer Research Foundation (BCRF-23-008), Instituto de Salud Carlos III (project reference numbers AC15/00062, CB16/12/00449, and PI22/00001), and the European Commission under the framework of the ERA-NET TRANSCAN-2 initiative cofinanced by FEDER and Asociación Española Contra el Cáncer. A. Vivancos was the recipient of a project award from the FAECC (AVP/18/AECC/3219) and received funding from the Advanced Molecular Diagnostic (DIAMAV) program from the FERO Foundation (8361) and from ISDIN for supporting the development of liquid biopsy applications at the Cancer Genomics Lab (1848). M. Sansó was the recipient of a II FERO-GHD grant from the FERO Foundation (FERO/5086) and an investigator award from the FAECC (INVES19056SANS), and received funding from the Health Research Institute of the Balearic Islands (IdISBa), the RADIX-Janssen program (RADIX/JANSSEN21/01), and the Miguel Servet Program funded by the ISCIII (CP22/00131)

Barriers of mental health treatment utilization among first-year college students: First cross-national results from the WHO World Mental Health International College Student Initiative.

BACKGROUND: Although mental disorders and suicidal thoughts-behaviors (suicidal thoughts and behaviors) are common among university students, the majority of students with these problems remain untreated. It is unclear what the barriers are to these students seeking treatment. AIMS: The aim of this study is to examine the barriers to future help-seeking and the associations of clinical characteristics with these barriers in a cross-national sample of first-year college students. METHOD: As part of the World Mental Health International College Student (WMH-ICS) initiative, web-based self-report surveys were obtained from 13,984 first-year students in eight countries across the world. Clinical characteristics examined included screens for common mental disorders and reports about suicidal thoughts and behaviors. Multivariate regression models adjusted for socio-demographic, college-, and treatment-related variables were used to examine correlates of help-seeking intention and barriers to seeking treatment. RESULTS: Only 24.6% of students reported that they would definitely seek treatment if they had a future emotional problem. The most commonly reported reasons not to seek treatment among students who failed to report that they would definitely seek help were the preference to handle the problem alone (56.4%) and wanting to talk with friends or relatives instead (48.0%). Preference to handle the problem alone and feeling too embarrassed were also associated with significantly reduced odds of having at least some intention to seek help among students who failed to report that they would definitely seek help. Having 12-month major depression, alcohol use disorder, and suicidal thoughts and behaviors were also associated with significantly reduced reported odds of the latter outcome. CONCLUSIONS: The majority of first-year college students in the WMH-ICS surveys report that they would be hesitant to seek help in case of future emotional problems. Attitudinal barriers and not structural barriers were found to be the most important reported reasons for this hesitation. Experimental research is needed to determine whether intention to seek help and, more importantly, actual help-seeking behavior could be increased with the extent to which intervention strategies need to be tailored to particular student characteristics. Given that the preference to handle problems alone and stigma and appear to be critical, there could be value in determining if internet-based psychological treatments, which can be accessed privately and are often build as self-help approaches, would be more acceptable than other types of treatments to student who report hesitation about seeking treatment.status: publishe

Limitations in predicting PAM50 intrinsic subtype and risk of relapse score with Ki67 in estrogen receptor-positive HER2-negative breast cancer

PAM50/Prosigna gene expression-based assay identifies three categorical risk of relapse groups (ROR-low, ROR-intermediate and ROR-high) in post-menopausal patients with estrogen receptor estrogen receptor-positive (ER+)/ HER2-negative (HER2-) early breast cancer. Low risk patients might not need adjuvant chemotherapy since their risk of distant relapse at 10-years is below 10% with endocrine therapy only. In this study, 517 consecutive patients with ER+/HER2- and node-negative disease were evaluated for Ki67 and Prosigna. Most of Luminal A tumors (65.6%) and ROR-low tumors (70.9%) had low Ki67 values (0-10%); however, the percentage of patients with ROR-medium or ROR-high disease within the Ki67 0-10% group was 42.7% (with tumor sizes ≤2 cm) and 33.9% (with tumor sizes > 2 cm). Finally, we found that the optimal Ki67 cutoff for identifying Luminal A or ROR-low tumors was 14%. Ki67 as a surrogate biomarker in identifying Prosigna low-risk outcome patients or Luminal A disease in the clinical setting is unreliable. In the absence of a well-validated prognostic gene expression-based assay, the optimal Ki67 cutoff for identifying low-risk outcome patients or Luminal A disease remains at 14%