Health service and psychotropic medication use for mental health conditions among healthcare workers active during the Spain Covid-19 Pandemic - A prospective cohort study using web-based surveys.

Little is known about healthcare workers' (HCW) use of healthcare services for mental disorders. This study presents data from a 16-month prospective cohort study of Spanish HCW (n = 4,809), recruited shortly after the COVID-19 pandemic onset, and assessed at four timepoints using web-based surveys. Use of health services among HCW with mental health conditions (i.e., those having a positive screen for mental disorders and/or suicidal thoughts and behaviours [STB]) was initially low (i.e., 18.2 %) but increased to 29.6 % at 16-month follow-up. Service use was positively associated with pre-pandemic mental health treatment (OR=1.99), a positive screen for major depressive disorder (OR=1.50), panic attacks (OR=1.74), suicidal thoughts and behaviours (OR=1.22), and experiencing severe role impairment (OR=1.33), and negatively associated with being female (OR = 0.69) and a higher daily number of work hours (OR=0.95). Around 30 % of HCW with mental health conditions used anxiolytics (benzodiazepines), especially medical doctors. Four out of ten HCW (39.0 %) with mental health conditions indicated a need for (additional) help, with most important barriers for service use being too ashamed, long waiting lists, and professional treatment not being available. Our findings delineate a clear mental health treatment gap among Spanish HCW.

Traumatic stress symptoms among Spanish healthcare workers during the COVID-19 pandemic: a prospective study.

AIM: To investigate the occurrence of traumatic stress symptoms (TSS) among healthcare workers active during the COVID-19 pandemic and to obtain insight as to which pandemic-related stressful experiences are associated with onset and persistence of traumatic stress. METHODS: This is a multicenter prospective cohort study. Spanish healthcare workers (N = 4,809) participated at an initial assessment (i.e., just after the first wave of the Spain COVID-19 pandemic) and at a 4-month follow-up assessment using web-based surveys. Logistic regression investigated associations of 19 pandemic-related stressful experiences across four domains (infection-related, work-related, health-related and financial) with TSS prevalence, incidence and persistence, including simulations of population attributable risk proportions (PARP). RESULTS: Thirty-day TSS prevalence at T1 was 22.1%. Four-month incidence and persistence were 11.6% and 54.2%, respectively. Auxiliary nurses had highest rates of TSS prevalence (35.1%) and incidence (16.1%). All 19 pandemic-related stressful experiences under study were associated with TSS prevalence or incidence, especially experiences from the domains of health-related (PARP range 88.4-95.6%) and work-related stressful experiences (PARP range 76.8-86.5%). Nine stressful experiences were also associated with TSS persistence, of which having patient(s) in care who died from COVID-19 had the strongest association. This association remained significant after adjusting for co-occurring depression and anxiety. CONCLUSIONS: TSSs among Spanish healthcare workers active during the COVID-19 pandemic are common and associated with various pandemic-related stressful experiences. Future research should investigate if these stressful experiences represent truly traumatic experiences and carry risk for the development of post-traumatic stress disorder.

AZ12756122, a novel fatty acid synthase inhibitor, decreases resistance features in EGFR-TKI resistant EGFR-mutated NSCLC cell models.

Different EGFR tyrosine kinase inhibitors (TKIs) have been developed for the treatment of non-small cell lung cancer (NSCLC) patients harboring sensitizing mutations in the EGFR gene. Apart from acquired secondary mutations, multiple resistance mechanisms have been reported, such as the overexpression of fatty acid synthase (FASN), a multi-functional enzyme essential for the de novo lipogenesis, or the increase of cancer stem cells, a small subpopulation within the tumor responsible for relapse, metastasis, and resistance to therapies. Hence, the purpose of this work is to evaluate the novel FASN inhibitor AZ12756122, both alone and in combination with gefitinib and osimertinib, in EGFR-mutated (EGFRm) lung adenocarcinoma cell models sensitive and resistant to EGFR-TKIs. The molecular effect of AZ12756122 (alone and in combination with EGFR-TKI) on FASN, EGFR/STAT3, Akt/mTOR, and MAPK signaling pathways was analyzed using RT-qPCR and Western blot. FASN expression was also evaluated in samples from patients with EGFRm NSCLC through immunohistochemistry. Our findings revealed that AZ12756122 caused cytotoxic effects inducing apoptosis, downregulated FASN expression and activity, decreased the activation of EGFR and Akt/mTOR pathway, and reduced cancer stem-like cells. Furthermore, the combination of AZ12756122 and osimertinib sensitized cells to EGFR-TKI, showing a synergistic effect that resulted in a reduction in the activation of EGFR, Akt/mTOR, and MAPK signaling pathways. Our study also showed that FASN+ EGFRm NSCLC patients exhibited a longer mPFS in patients who responded to EGFR-TKI treatment. In conclusion, FASN inhibition should be further studied for the treatment, alone or in combination with EGFR-TKIs, for EGFRm NSCLC patients.

The solvent chosen for the manufacturing of electrospun polycaprolactone scaffolds influences cell behavior of lung cancer cells.

The development of a trustworthy in vitro lung cancer model is essential to better understand the illness, find novel biomarkers, and establish new treatments. Polycaprolactone (PCL) electrospun nanofibers are a cost-effective and ECM-like approach for 3D cell culture. However, the solvent used to prepare the polymer solution has a significant impact on the fiber morphology and, consequently, on the cell behavior. Hence, the present study evaluated the effect of the solvent employed in the manufacturing on the physical properties of 15%-PCL electrospun scaffolds and consequently, on cell behavior of NCI-H1975 lung adenocarcinoma cells. Five solvents mixtures (acetic acid, acetic acid-formic acid (3:1, v/v), acetone, chloroform-ethanol (7:3, v/v), and chloroform-dichloromethane (7:3, v/v)) were tested. The highest cell viability ([Formula: see text] = 33.4%) was found for cells cultured on chloroform-ethanol (7:3) PCL scaffolds. Chloroform-dichloromethane (7:3) PCL scaffolds exhibited a roughness that enhanced the quality of electrospun filament, in terms of cell viability. Our findings highlighted the influence of the solvent on fiber morphology and protein adsorption capacity of nanofilaments. Consequently, these features directly affected cell attachment, morphology, and viability.

Application of the adverse outcome pathway to identify molecular changes in prenatal brain programming induced by IUGR: Discoveries after EGCG exposure.

Following a multi-disciplinary approach integrating information from several experimental models we have collected new evidence supporting, expanding and redesigning the AOP "Disrupted laminin/int-ß1 interaction leading to decreased cognitive function". Investigations in vitro in rabbit and rat neurospheres and in vivo in mice exposed to EGCG (epigallocatechin-gallate) during neurodevelopment are combined with in vitro evaluations in neural progenitor cells overexpressing int-ß1 and literature information from int-ß1 deficiency models. We have discovered for the first time that neural progenitor cells from intrauterine growth restricted (IUGR) animals overexpress int-ß1 at gene and protein level and due to this change in prenatal brain programming they respond differently than control neurospheres to the exposure of EGCG, a compound triggering neural progenitor cell migration alterations. We have also identified that EGCG developmental exposure has deleterious effects on neuronal branching and arborization in vitro and in vivo. Our results warn that a thorough developmental neurotoxicity characterization of this and other catechin-based food supplements is needed before recommending their consumption during pregnancy.

Chemical and Microstructural Nanoscale Homogeneity in Superconducting YBa2Cu3O7-x Films Derived from Metal-Propionate Fluorine-free Solutions.

Research involved in developing alternative energy sources has become a necessity to face global warming. In this context, superconductivity is an appealing solution to enhance clean electrical energy provided that lower production costs can be attained. By implementation of chemical solution deposition techniques and high-throughput growth methods, low-cost nanostructured epitaxial cuprate superconductors are timely candidates. Here, we present a versatile and tunable solution method suitable for the preparation of high-performance epitaxial cuprate superconducting films. Disregarding the renowned trifluoroacetate route, we center our focus on the transient liquid-assisted growth (TLAG) that meets the requirement of being a greener chemical process together with ultrafast growth rates beyond 100 nm/s. We developed a facile, fast, and cost-effective method, starting from the synthesis of metal-propionate powders of Y, Ba, and Cu of high purity and high yields, being the precursors of the fluorine-free solutions, which enable the chemical and microstructural nanoscale homogeneity of YBa2Cu3O7-x (YBCO) precursor films. These solutions present endured stability and enable precise tunability of the composition, concentration, porosity, and film thickness. Homogeneous precursor films up to thicknesses of 2.7 µm through eight layer multidepositions are demonstrated, thus establishing the correct basis for epitaxial growth using the fast kinetics of the TLAG process. YBCO films of 500 nm thickness with a critical current density of 2.6 MA/cm2 at 77 K were obtained, showing the correlation of precursor film homogeneity to the final YBCO physical properties.

Kinetic Control of Ultrafast Transient Liquid Assisted Growth of Solution-Derived YBa2 Cu3 O7 -x Superconducting Films.

Transient liquid assisted growth (TLAG) is an ultrafast non-equilibrium growth process mainly governed by kinetic parameters, which are only accessible through fast in situ characterizations. In situ synchrotron X-ray diffraction (XRD) analysis and in situ electrical resistivity measurements are used to derive kinetic diagrams of YBa2 Cu3 O7- x (YBCO) superconducting films prepared via TLAG and to reveal the unique peculiarities of the process. In particular, diagrams for the phase evolution and the YBCO growth rates have been built for the two TLAG routes. It is shown that TLAG transient liquids can be obtained upon the melting of two barium cuprate phases (and not just one), differentiated by their copper oxidation state. This knowledge serves as a guide to determine the processing conditions to reach high performance films at high growth rates. With proper control of these kinetic parameters, films with critical current densities of 2-2.6 MA cm-2 at 77 K and growth rates between 100-2000 nm s-1 are reached. These growth rates are 1.5-3 orders of magnitude higher than those of conventional methods.

Efficacy of SARS-CoV-2 vaccination in patients with monoclonal gammopathies: A cross sectional study.

SARS-CoV-2 vaccination is the most effective strategy to protect individuals with haematologic malignancies against severe COVID-19, while eliciting limited vaccine responses. We characterized the humoral responses following 3 mo after mRNA-based vaccines in individuals at different plasma-cell disease stages: monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), and multiple myeloma on first-line therapy (MM), compared with a healthy population. Plasma samples from uninfected MM patients showed lower SARS-CoV-2-specific antibody levels and neutralization capacity compared with MGUS, SMM, and healthy individuals. Importantly, COVID-19 recovered MM individuals presented significantly higher plasma neutralization capacity compared with their uninfected counterparts, highlighting that hybrid immunity elicit stronger immunity even in this immunocompromised population. No differences in the vaccine-induced humoral responses were observed between uninfected MGUS, SMM and healthy individuals. In conclusion, MGUS and SMM patients could be SARS-CoV-2 vaccinated following the vaccine recommendations for the general population, whereas a tailored monitoring of the vaccine-induced immune responses should be considered in uninfected MM patients.

Defining inkjet printing conditions of superconducting cuprate films through machine learning.

The design and optimization of new processing approaches for the development of rare earth cuprate (REBCO) high temperature superconductors is required to increase their cost-effective fabrication and promote market implementation. The exploration of a broad range of parameters enabled by these methods is the ideal scenario for a new set of high-throughput experimentation (HTE) and data-driven tools based on machine learning (ML) algorithms that are envisaged to speed up this optimization in a low-cost and efficient manner compatible with industrialization. In this work, we developed a data-driven methodology that allows us to analyze and optimize the inkjet printing (IJP) deposition process of REBCO precursor solutions. A dataset containing 231 samples was used to build ML models. Linear and tree-based (Random Forest, AdaBoost and Gradient Boosting) regression algorithms were compared, reaching performances above 87%. Model interpretation using Shapley Additive Explanations (SHAP) revealed the most important variables for each study. We could determine that to ensure homogeneous CSD films of 1 micron thickness without cracks after the pyrolysis, we need average drop volumes of 190-210 pl, and no. of drops between 5000 and 6000, delivering a total volume deposited close to 1 µl.

Chemical Solution Deposition of Insulating Yttria Nanolayers as Current Flow Diverter in Superconducting GdBa2Cu3O7-δ Coated Conductors.

The primary benefit of a metallic stabilization/shunt in high temperature superconductor (HTS) coated conductors (CCs) is to prevent joule heating damage by providing an alternative path for the current flow during the HTS normal state transition (i.e., quench). However, the shunt presence in combination with unavoidable fluctuations in the critical current (I c) of the HTS film can develop a localized quench along the CC's length if the operational current is kept close to I c. This scenario, also known as the hot-spot regime, can lead to the rupture of the CC if the local quench does not propagate fast enough. The current flow diverter (CFD) is the CC architecture concept that has proven to increase the conductor's robustness against a hot-spot regime by simply boosting the quench velocity in the CC, which avoids the shunt compromise in some applications. This work investigates a practical manufacturing route for incorporating the CFD architecture in a reel-to-reel system via the preparation of yttrium oxide (Y2O3) as an insulating thin nanolayer (∼100 nm) on top of a GdBa2Cu3O7 (GdBCO) superconductor. Chemical solution deposition (CSD) using ink jet printing (IJP) is shown to be a suitable manufacturing approach. Two sequences of the experimental steps have been investigated, where oxygenation of the GdBCO layer is performed after or before the solution deposition and the Y2O3 nanolayer thermal treatment formation step. A correlated analysis of the microstructure, in situ oxygenation kinetics, and superconducting properties of the Ag/Y2O3/GdBCO trilayer processed under different conditions shows that a new customized functional CC can be prepared. The successful achievement of the CFD effect in the case of the preoxygenated customized CC was confirmed by measuring the current transfer length, thus demonstrating the effectiveness of the CSD-IJP as a processing method.

Patient experience, satisfaction and shared decision-making in colorectal cancer screening: protocol of the mixed-methods study CyDESA.

INTRODUCTION: Colorectal cancer (CRC) screening programmes can reduce incidence and mortality from this condition if adherence to them is high. As patient experience and satisfaction are key factors in determining adherence to screening programmes, they need to be measured. Furthermore, to promote highly patient-centred healthcare, the perception of patients regarding shared decision-making during CRC screening needs to be known. This study aims to assess the experience, satisfaction and participation in decision-making of participants in a CRC screening programme and of patients diagnosed with CRC through this programme in relation to the diagnostic and therapeutic processes of cancer. METHODS AND ANALYSIS: The CyDESA study is a mixed-methods study with a four phase sequential design. In phase 1, we will conduct a systematic review of patient-reported experience measures (PREMs) for patient experience or satisfaction with CRC screening. In case no located PREM can be applied, in phase 2, we will develop a new PREM. We will use the Delphi methodology to reach consensus among experts and patients and will conduct a pilot test of the developed PREM. Phase 3 is a multicentric cross-sectional study based on self-reported questionnaires that will be conducted at three Spanish hospitals (n=843). The objective is to find out about the experience, satisfaction and participation in decision-making of participants in the CRC screening programme who have had a positive screening test result according to their final screening diagnosis: false positives, colorectal polyps or CRC. Phase 4 is a qualitative phenomenological study based on individual interviews. It will explore the experiences of participants in the CRC screening programme and of those diagnosed with CRC. ETHICS AND DISSEMINATION: Ethics approval by the Ethics Committees of Corporació Sanitària Parc Taulí, Hospital de Sant Pau and Parc de Salut Mar. Findings will be published in peer-reviewed journals and presented at conferences. TRIAL REGISTRATION NUMBER: NCT04610086.

Reduced humoral response 3 months following BNT162b2 vaccination in SARS-CoV-2 uninfected residents of long-term care facilities.

BACKGROUND: SARS-CoV-2 vaccination is the most effective strategy to protect older residents of long-term care facilities (LTCF) against severe COVID-19, but primary vaccine responses are less effective in older adults. Here, we characterised the humoral responses of institutionalised seniors 3 months after they had received the mRNA/BNT162b2 vaccine. METHODS: plasma levels of SARS-CoV-2-specific total IgG, IgM and IgA antibodies were measured before and 3 months after vaccination in older residents of LTCF. Neutralisation capacity was assessed in a pseudovirus neutralisation assay against the original WH1 and later B.1.617.2/Delta variants. A group of younger adults was used as a reference group. RESULTS: three months after vaccination, uninfected older adults presented reduced SARS-CoV-2-specific IgG levels and a significantly lower neutralisation capacity against the WH1 and Delta variants compared with vaccinated uninfected younger individuals. In contrast, COVID-19-recovered older adults showed significantly higher SARS-CoV-2-specific IgG levels after vaccination than their younger counterparts, whereas showing similar neutralisation activity against the WH1 virus and an increased neutralisation capacity against the Delta variant. Although, similarly to younger individuals, previously infected older adults elicit potent cross-reactive immune responses, higher quantities of SARS-CoV-2-specific IgG antibodies are required to reach the same neutralisation levels. CONCLUSIONS: although hybrid immunity seems to be active in previously infected older adults 3 months after mRNA/BNT162b2 vaccination, humoral immune responses are diminished in COVID-19 uninfected but vaccinated older residents of LTCF. These results suggest that a vaccine booster dose should be prioritised for this particularly vulnerable population.

Interim opioid agonist treatment for opioid addiction: a systematic review.

BACKGROUND: Opioid use disorder is a public health problem and treatment variability, coverage and accessibility poses some challenges. The study's objective is to review the impact of interim opioid agonist treatment (OAT), a short-term approach for patients awaiting standard OAT, in terms of treatment retention, access to standard OAT, quality of life and satisfaction with treatment. METHOD: We conducted a systematic review searching MEDLINE, EMBASE, PsycINFO, and CENTRAL up to May 2020. Due to variability between studies and outcome measurements, we did not pool effect estimates and reported a narrative synthesis of findings rating their certainty according to GRADE. RESULTS: We identified 266 unique records and included five randomized trials with some limitations in risk of bias and one observational study limited by selection bias. The studies assessed similar approaches to interim OAT but were compared to three different control conditions. Four studies reported on treatment retention at 4 months or less with no significant differences between interim OAT and waiting list or standard OAT. Two studies reported treatment retention at 12 months with no differences between interim OAT and standard OAT. Two trials assessed access to standard OAT and showed significant differences between interim OAT and waiting list for standard OAT. We rated the quality of evidence for these outcomes as moderate due to the impact of risk of bias. Data on quality of life or satisfaction with treatment was suboptimal. CONCLUSIONS: Interim OAT is likely more effective than a waiting list for standard OAT in access to treatment, and it is probably as effective as standard OAT regarding treatment retention. PROSPERO registration CRD42018116269.

Fatty acid synthase as a feasible biomarker for triple negative breast cancer stem cell subpopulation cultured on electrospun scaffolds.

There is no targeted therapy for triple negative breast cancer (TNBC), which presents an aggressive profile and poor prognosis. Recent studies noticed the feasibility of breast cancer stem cells (BCSCs), a small population responsible for tumor initiation and relapse, to become a novel target for TNBC treatments. However, new cell culture supports need to be standardized since traditional two-dimensional (2D) surfaces do not maintain the stemness state of cells. Hence, three-dimensional (3D) scaffolds represent an alternative to study in vitro cell behavior without inducing cell differentiation. In this work, electrospun polycaprolactone scaffolds were used to enrich BCSC subpopulation of MDA-MB-231 and MDA-MB-468 TNBC cells, confirmed by the upregulation of several stemness markers and the existence of an epithelial-to-mesenchymal transition within 3D culture. Moreover, 3D-cultured cells displayed a shift from MAPK to PI3K/AKT/mTOR signaling pathways, accompanied by an enhanced EGFR and HER2 activation, especially at early cell culture times. Lastly, the fatty acid synthase (FASN), a lipogenic enzyme overexpressed in several carcinomas, was found to be hyperactivated in stemness-enriched samples. Its pharmacological inhibition led to stemness diminishment, overcoming the BCSC expansion achieved in 3D culture. Therefore, FASN may represent a novel target for BCSC niche in TNBC samples.

Polycaprolactone Electrospun Scaffolds Produce an Enrichment of Lung Cancer Stem Cells in Sensitive and Resistant EGFRm Lung Adenocarcinoma.

The establishment of a three-dimensional (3D) cell culture model for lung cancer stem cells (LCSCs) is needed because the study of these stem cells is unable to be done using flat surfaces. The study of LCSCs is fundamental due to their key role in drug resistance, tumor recurrence, and metastasis. Hence, the purpose of this work is the evaluation of polycaprolactone electrospun (PCL-ES) scaffolds for culturing LCSCs in sensitive and resistant EGFR-mutated (EGFRm) lung adenocarcinoma cell models. We performed a thermal, physical, and biological characterization of 10% and 15%-PCL-ES structures. Several genes and proteins associated with LCSC features were analyzed by RT-qPCR and Western blot. Vimentin and CD133 tumor expression were evaluated in samples from 36 patients with EGFRm non-small cell lung cancer through immunohistochemistry. Our findings revealed that PC9 and PC9-GR3 models cultured on PCL-ES scaffolds showed higher resistance to osimertinib, upregulation of ABCB1, Vimentin, Snail, Twist, Sox2, Oct-4, and CD166, downregulation of E-cadherin and CD133, and the activation of Hedgehog pathway. Additionally, we determined that the non-expression of CD133 was significantly associated with a low degree of histological differentiation, disease progression, and distant metastasis. To sum up, we confirmed PCL-ES scaffolds as a suitable 3D cell culture model for the study of the LCSC niche.

Prevalence of Peripheral Arterial Disease and Associated Vascular Risk Factors in 65-Years-Old People of Northern Barcelona.

OBJECTIVE: To determine the prevalence and risk factors associated with peripheral arterial disease (PAD) in Northern Barcelona at 65 years of age. METHODS: A single-center, cross-sectional study, including males and females 65 years of age, health care cardholders of Barcelona Nord. PAD was defined as an ankle-brachial index (ABI) < 0.9. Attending subjects were evaluated for a history of common cardiovascular risk factors. A REGICOR score was obtained, as well as a physical examination and anthropometric measurements. RESULTS: From November 2017 to December 2018, 1174 subjects were included: 479 (40.8%) female and 695 (59.2%) male. Overall prevalence of PAD was 6.2% (95% CI: 4.8-7.6%), being 7.9% (95% CI: 5.9-9.9%) in males and 3.8% (95% CI: 2.1-5.5%) in females. An independent strong association was seen in male smokers and diabetes, with ORs pf 7.2 (95% CI: 2.8-18.6) and 1.8 (95% CI: 1.0-3.3), respectively, and in female smokers and hypertension, with ORs of 5.2 (95% CI: 1.6-17.3) and 3.3 (95% CI: 1.2-9.0). Male subjects presented with higher REGICOR scores (p < 0.001). CONCLUSION: Higher-risk groups are seen in male subjects with a history of smoking and diabetes and female smokers and arterial hypertension, becoming important subgroups for our primary healthcare centers and should be considered for ABI screening programs.

HIV/HBV coinfection: temporal trends and patient characteristics, Spain, 2002 to 2018.

BackgroundRecent and reliable estimates on the prevalence of coinfection with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) in Europe are lacking.AimLeveraged on a study designed to assess HIV/HCV coinfection prevalence, we assessed the prevalence of HIV/HBV coinfection in Spain in 2018 and compared the results with five similar studies performed since 2002.MethodsThis cross-sectional prevalence study was carried out in 43 centres, and patients were selected using simple random sampling. The reference population comprised 40,322 patients and the sample size were 1,690 patients.ResultsThe prevalence of HIV/HBV coinfection in Spain at the end of 2018 was 3.2%. The prevalence in 2002, 2009, 2015, 2016 and 2017 was 4.9%, 3.4%, 3%, 3.9% and 3%, respectively. Among the HIV/HBV-coinfected patients identified in 2018, 16.7% had cirrhosis according to transient elastography and 26.3% tested positive for antibodies against hepatitis D virus. All HIV/HBV-coinfected patients were receiving drugs with activity against HBV, and 97% of those tested for HBV DNA had an HBV DNA load < 80 IU/mL.ConclusionsThe prevalence of HIV/HBV coinfection in Spain remained stable at around 3% for a decade. Our data could facilitate the design of national programmes to control HBV infection and help identify areas of patient management that need improvement.