Effectiveness of early and intensive intervention on suicide prevention: CARS programme.

The aim of this study was to evaluate the outcomes of the Programme for Management of Suicidal Behaviour and Suicide Prevention (CARS). Individuals treated in the emergency department of University Hospital Marqués de Valdecilla for suicidal thoughts or attempts (N = 401) between 1-March-2016 and 31-December-2018 were considered. No randomization by patients or groups was performed. Student's t-test, chi-square and repeated measure analysis of variance were used. Kaplan-Meier survival function and Cox proportional hazard regression models were employed to estimate the risks of relapse. Outcome of those who voluntary enrol CARS were compared with treatment as usual (TAU) at 6- and 12-months follow-up. The results indicate a significant reduction and delayed occurrence of suicidal behaviour over a 12-month follow-up period with the CARS programme compared to TAU, along with a decreased frequency of hospital admissions. CARS programme demonstrates a substantial impact, significantly reducing the risk of recurrent suicidal behaviour by 35.5 % and the risk of repeated suicidal attempts by 47.2 % at the 12-month follow-up. The programme exhibits a dual protective effect, diminishing suicidal behaviour and fostering improved long-term outcomes. In conclusion, CARS effectively reduced suicidal behaviour recurrence, achieving significant decreases in suicidal thoughts, plans and attempts.

Exosomes isolated from IMMUNEPOTENT CRP, a hemoderivative, to accelerate diabetic wound healing.

The increasing risk of amputation due to diabetic foot ulcer calls for new therapeutic options; for that, we determined the role of IMMUNEPOTENT CRP (ICRP) and its parts in the wound healing process of superficial wounds in diabetic BALB/c mice. A potency test was performed to confirm the batch of ICRP, and then its parts were separated into pellets, supernatants, and exosomes, and another group of exosomes loaded with insulin was added. Viability and scratch healing were assessed in NIH-3T3, HUVEC, and HACAT cell lines. Diabetes was induced with streptozotocin, and wounds were made by dissecting the back skin. Treatments were topically applied, and closure was monitored; inflammatory cytokines in sera were also evaluated by flow cytometry, and histological analysis was performed by Masson's staining and immunohistochemistry for p-AKT, p-FOXO, p-P21, and p-TSC2. ICRP pellets and exosomes increased cellular viability, and exosomes and exosome-insulin accelerated scratch healing in vitro. Exosome-insulin releases insulin constantly over time in vitro. In vivo, treatments accelerated wound closure, and better performance was observed in pellet, exosome, and exosome-insulin treatments. Best collagen expression was induced by ICRP. P-AKT and p-FOXO were overexpressed in healing tissues. Inflammatory cytokines were downregulated by all treatments. In conclusion, IMMUNEPOTENT CRP components, especially exosomes, and the process of encapsulation of exosome-insulin accelerate diabetic wound healing and enhance cellular proliferation, collagen production, and inflammation modulation through the phosphorylation of components of the AKT pathway.

Osteopontin as a Biomarker in Interstitial Lung Diseases.

Osteopontin (OPN) is a glycoprotein involved in Th1 and Th17 differentiation, and inflammation and tissue remodeling. OPN is a biomarker of disease activity in patients with autoimmune inflammatory conditions. This study aimed to assess the diagnostic and prognostic value of OPN in interstitial lung diseases (ILDs). Between May 2016 and October 2019, 344 patients with ILD were recruited at the Hospital Universitario Marqués de Valdecilla (Spain) and were prospectively followed-up. This study involved the determination of OPN serum levels by ELISA and OPN RNA expression quantified using qPCR. Six genetic polymorphisms in OPN (rs28357094, rs2853749, rs2853750, rs11728697, rs7695531, and rs1126616) were genotyped using TaqMan assays. OPN serum levels were also assessed in 140 healthy controls. OPN serum levels (median [interquartile range]) were significantly higher in ILD patients than in controls (1.05 [0.75-1.51] ng/mL versus 0.81 [0.65-0.98] ng/mL in healthy controls; p < 0.01). OPN serum levels were inversely correlated with the forced vital capacity. OPN serum levels were also higher in ILD patients who died or underwent lung transplantation when compared with the remaining ILD patients (1.15 [0.80-1.72] ng/mL versus 0.99 [0.66-1.32] ng/mL; p = 0.05). Survival worsened in ILD patients with OPN > 1.03 ng/mL at 1, 3, and 5 years. No statistically significant differences in the genetic frequencies of OPN polymorphisms or the RNA expression were found among the different ILD groups. Elevated levels of OPN in the serum may be a useful indicator in identifying patients with ILD who are more likely to experience poor outcomes.

Patterns of cognitive-emotional change after cognitive-behavioural treatment in emotional disorders: A 12-month longitudinal cluster analysis.

INTRODUCTION: The aim of this study was to use cluster analysis based on the trajectory of five cognitive-emotional processes (worry, rumination, metacognition, cognitive reappraisal and expressive suppression) over time to explore differences in clinical and performance variables in primary care patients with emotional symptoms. METHODS: We compared the effect of adding transdiagnostic cognitive-behavioural therapy (TD-CBT) to treatment as usual (TAU) according to cluster membership and sought to determine the variables that predicted cluster membership. 732 participants completed scales about cognitive-emotional processes, anxiety and depressive symptoms, functioning, and quality of life (QoL) at baseline, posttreatment, and at 12 months. Longitudinal cluster analysis and logistic regression analyses were carried out. RESULTS: A two-cluster solution was chosen as the best fit, named as "less" or "more" improvement in cognitive-emotional processes. Individuals who achieved more improvement in cognitive-emotional processes showed lower emotional symptoms and better QoL and functioning at all three time points. TAU+TD-CBT, income level, QoL and anxiety symptoms were significant predictors of cluster membership. CONCLUSIONS: These results underscore the value of adding TD-CBT to reduce maladaptive cognitive-emotional regulation strategies. These findings highlight the importance of the processes of change in therapy and demonstrate the relevance of the patient's cognitive-emotional profile in improving treatment outcomes.

Reinforcing the Evidence of Mitochondrial Dysfunction in Long COVID Patients Using a Multiplatform Mass Spectrometry-Based Metabolomics Approach.

Despite the recent and increasing knowledge surrounding COVID-19 infection, the underlying mechanisms of the persistence of symptoms for a long time after the acute infection are still not completely understood. Here, a multiplatform mass spectrometry-based approach was used for metabolomic and lipidomic profiling of human plasma samples from Long COVID patients (n = 40) to reveal mitochondrial dysfunction when compared with individuals fully recovered from acute mild COVID-19 (n = 40). Untargeted metabolomic analysis using CE-ESI(+/-)-TOF-MS and GC-Q-MS was performed. Additionally, a lipidomic analysis using LC-ESI(+/-)-QTOF-MS based on an in-house library revealed 447 lipid species identified with a high confidence annotation level. The integration of complementary analytical platforms has allowed a comprehensive metabolic and lipidomic characterization of plasma alterations in Long COVID disease that found 46 relevant metabolites which allowed to discriminate between Long COVID and fully recovered patients. We report specific metabolites altered in Long COVID, mainly related to a decrease in the amino acid metabolism and ceramide plasma levels and an increase in the tricarboxylic acid (TCA) cycle, reinforcing the evidence of an impaired mitochondrial function. The most relevant alterations shown in this study will help to better understand the insights of Long COVID syndrome by providing a deeper knowledge of the metabolomic basis of the pathology.

Effect of Operational Variables on Supercritical Foaming of Caffeic Acid-Loaded Poly(lactic acid)/Poly(butylene adipate-co-terephthalate) Blends for the Development of Sustainable Materials.

Expanded polystyrene will account for 5.3% of total global plastic production in 2021 and is widely used for food packaging due to its excellent moisture resistance and thermal insulation. However, some of these packages are often used only once before being discarded, generating large amounts of environmentally harmful plastic waste. A very attractive alternative to the conventional methods used for polymer processing is the use of supercritical carbon dioxide (scCO2) since it has mass-transfer properties adapted to the foam morphology, generating different path lengths for the diffusion of active compounds within its structure and can dissolve a wide range of organic molecules under supercritical conditions. The objective of this research was to evaluate the effect of operational variables on the process of caffeic acid (CA) impregnation and subsequent foaming of polylactic acid (PLA) as well as two PLA/poly(butylene-co-terephthalate-adipate) (PBAT) blends using scCO2. The results showed an increase in the degree of crystallinity of the CA-impregnated samples due to the nucleation effect of the active compound. On the other hand, SEM micrographs of both films and foams showed significant differences due to the presence of PBAT and its low miscibility with PLA. Finally, the results obtained in this work contribute to the knowledge of the important parameters to consider for the implementation of the impregnation and foaming process of PLA and PLA/PBAT blends with potential use in food packaging.

Inflammasome-Related Genetic Polymorphisms as Severity Biomarkers of COVID-19.

The most critical forms of coronavirus disease 2019 (COVID-19) are associated with excessive activation of the inflammasome. Despite the COVID-19 impact on public health, we still do not fully understand the mechanisms by which the inflammatory response influences disease prognosis. Accordingly, we aimed to elucidate the role of polymorphisms in the key genes of the formation and signaling of the inflammasome as biomarkers of COVID-19 severity. For this purpose, a large and well-defined cohort of 377 COVID-19 patients with mild (n = 72), moderate (n = 84), severe (n = 100), and critical (n = 121) infections were included. A total of 24 polymorphisms located in inflammasome-related genes (NLRP3, NLRC4, NLRP1, CARD8, CASP1, IL1B, IL18, NFKB1, ATG16L1, and MIF) were genotyped in all of the patients and in the 192 healthy controls (HCs) (who were without COVID-19 at the time of and before the study) by RT-qPCR. Our results showed that patients with mild, moderate, severe, and critical COVID-19 presented similar allelic and genotypic distribution in all the variants studied. No statistically significant differences in the haplotypic distribution of NLRP3, NLRC4, NLRP1, CARD8, CASP1, IL1B, and ATG16L1 were observed between COVID-19 patients, who were stratified by disease severity. Each stratified group of patients presented a similar genetic distribution to the HCs. In conclusion, our results suggest that the inflammasome polymorphisms studied are not associated with the worsening of COVID-19.

Effect of Reliable Recovery on Health Care Costs and Productivity Losses in Emotional Disorders.

Despite the high economic costs associated with emotional disorders, relatively few studies have examined the variation in costs according to whether the patient has achieved a reliable recovery. The aim of this study was to explore differences in health care costs and productivity losses between primary care patients from a previous randomized controlled trial (RCT)-PsicAP-with emotional symptoms who achieved a reliable recovery and those who did not after transdiagnostic cognitive-behavioral therapy (TD-CBT) plus treatment as usual (TAU) or TAU alone. Sociodemographic and cost data were obtained for 134 participants treated at five primary care centers in Madrid for the 12-month posttreatment period. Reliable recovery rates were higher in the patients who received TD-CBT + TAU versus TAU alone (66% vs. 34%, respectively; chi-square = 13.78, df = 1, p < .001). Patients who did not achieve reliable recovery incurred more costs, especially associated with general practitioner consultations (t = 3.01, df = 132, p = .003), use of emergency departments (t = 2.20, df = 132, p = .030), total health care costs (t = 2.01, df = 132, p = .040), and sick leaves (t = 1.97, df = 132, p = .048). These findings underscore the societal importance of achieving a reliable recovery in patients with emotional disorders, and further support the value of adding TD-CBT to TAU in the primary care setting.

Pharmacokinetics and Safety of Lurbinectedin Administrated with Itraconazole in Cancer Patients: A Drug-Drug Interaction Study.

This open-label, two-part, phase Ib drug-drug interaction study investigated whether the pharmacokinetic (PK) and safety profiles of lurbinectedin (LRB), a marine-derived drug, are affected by co-administration of itraconazole (ITZ), a strong CYP3A4 inhibitor, in adult patients with advanced solid tumors. In Part A, three patients were sequentially assigned to Sequence 1 (LRB 0.8 mg/m2, 1-h intravenous [IV] + ITZ 200 mg/day oral in Cycle 1 [C1] and LRB alone 3.2 mg/m2, 1 h, IV in Cycle 2 [C2]). In Part B, 11 patients were randomized (1:1) to receive either Sequence 1 (LRB at 0.9 mg/m2 + ITZ in C1 and LRB alone in C2) or Sequence 2 (LRB alone in C1 and LRB + ITZ in C2). Eleven patients were evaluable for PK analysis: three in Part A and eight in Part B (four per sequence). The systemic total exposure of LRB increased with ITZ co-administration: 15% for Cmax, area under the curve (AUC) 2.4-fold for AUC0-t and 2.7-fold for AUC0-∞. Co-administration with ITZ produced statistically significant modifications in the unbound plasma LRB PK parameters. The LRB safety profile was consistent with the toxicities described in previous studies. Co-administration with multiple doses of ITZ significantly altered LRB systemic exposure. Hence, to avoid LRB overexposure when co-administered with strong CYP3A4 inhibitors, an LRB dose reduction proportional to CL reduction should be applied.

Long-term depressive symptom trajectories and related baseline characteristics in primary care patients: Analysis of the PsicAP clinical trial.

BACKGROUND: There is heterogeneity in the long-term trajectories of depressive symptoms among patients. To date, there has been little effort to inform the long-term trajectory of symptom change and the factors associated with different trajectories. Such knowledge is key to treatment decision-making in primary care, where depression is a common reason for consultation. We aimed to identify distinct long-term trajectories of depressive symptoms and explore pre-treatment characteristics associated with them. METHODS: A total of 483 patients from the PsicAP clinical trial were included. Growth mixture modeling was used to identify long-term distinct trajectories of depressive symptoms, and multinomial logistic regression models to explore associations between pre-treatment characteristics and trajectories. RESULTS: Four trajectories were identified that best explained the observed response patterns: "recovery" (64.18%), "late recovery" (10.15%), "relapse" (13.67%), and "chronicity" (12%). There was a higher likelihood of following the recovery trajectory for patients who had received psychological treatment in addition to the treatment as usual. Chronicity was associated with higher depressive severity, comorbidity (generalized anxiety, panic, and somatic symptoms), taking antidepressants, higher emotional suppression, lower levels on life quality, and being older. Relapse was associated with higher depressive severity, somatic symptoms, and having basic education, and late recovery was associated with higher depressive severity, generalized anxiety symptoms, greater disability, and rumination. CONCLUSIONS: There were different trajectories of depressive course and related prognostic factors among the patients. However, further research is needed before these findings can significantly influence care decisions.

Foaming of 3D-Printed PLA/CaCO3 Composites by Supercritical CO2 Process for Sustainable Food Contact Materials.

In the last decade, among the emerging technologies in the area of bioplastics, additive manufacturing (AM), commonly referred to as 3D printing, stands out. This technology has gained great interest in the development of new products, mainly due to its capability to easily produce customized and low-cost plastic products. This work aims to evaluate the effect of supercritical foaming of 3D-printed parts based on a commercial PLA matrix loaded with calcium carbonate, for single-use sustainable food contact materials. 3D-printed PLA/CaCO3 parts were obtained by 3D printing with a 20% and 80% infill, and two infill patterns, rectilinear and triangular, were set for each of the infill percentages selected. Supercritical fluid foaming of PLA/CaCO3 composite printed parts was performed using a pressure of 25 MPa, a temperature of 130 °C for 23 min, with a fast depressurization rate (1 s). Closed-cell foams were achieved and the presence of CaCO3 did not influence the surface of the foams or the cell walls, and no agglomerations were observed. Foam samples with 80% infill showed subtle temperature fluctuations, and thermogravimetric analysis showed that samples were thermally stable up to ~300 °C, while the maximum degradation temperature was around 365 °C. Finally, tensile test analysis showed that for lower infill contents, the foams showed lower mechanical performance, while the 80% infill and triangular pattern produced foams with good mechanical performance. These results emphasize the interest in using the supercritical CO2 process to easily produce foams from 3D-printed parts. These materials represent a sustainable alternative for replacing non-biodegradable materials such as Expanded Polystyrene, and they are a promising option for use in many industrial applications, such as contact materials.

rhIL-7-hyFc and hIL-2/TCB2c combination promotes an immune-stimulatory tumor microenvironment that improves antitumor efficacy of checkpoint inhibitors.

BACKGROUND: Recombinant human interleukin (rhIL)-7-hyFc (efineptakin alfa; NT-I7) is a potent T-cell amplifier, with two IL-7 molecules fused to IgD/IgG4 elements. rhIL-7-hyFc promotes extensive infiltration of CD8+ T cells into the tumor, concurrently increasing the numbers of intratumoral PD-1+CD8+ T cells. The hIL-2/TCB2 complex (SLC-3010) inhibits tumor growth by preferential activation of CD122 (IL-2Rß)high CD8+ T cells and natural killer cells, over regulatory T cells (Tregs). We investigated the underlying mechanisms of rhIL-7-hyFc and hIL-2/TCB2c antitumor activity and the potential synergistic efficacy, specifically focusing on tumor-specific CD8+ cells within the tumor and the tumor-draining lymph nodes (tdLN). METHODS: MC38 and CT26 tumor-bearing mice were administered with 10 mg/kg rhIL-7-hyFc intramuscularly and 0.9 mg/kg hIL-2/TCB2c intravenously. Anti-PD-1 monoclonal antibody was administered intraperitoneally three times at 3-day intervals at a dose of 5 mg/kg. Tumor volume was measured to assess efficacy. To compare the composition of immune cells between each monotherapy and the combination therapy, we analyzed tumors and tdLNs by flow cytometry. RESULTS: Our data demonstrate that the combination of rhIL-7-hyFc and hIL-2/TCB2c increases efficacy and generates an immune-stimulatory tumor microenvironment (TME). The TME is characterized by an increased infiltration of tumor-specific CD8+ T cells, and a decreased frequency of CD39highTIM-3+ Treg cells. Most importantly, rhIL-7-hyFc increases infiltration of a CD62L+Ly108+ early progenitor population of exhausted CD8+ T cells (TPEX), which may retain long-term proliferation capacity and replenish functional effector CD8+ T cells. hIL-2/TCB2c induces differentiation of CD62L+Ly108+ TPEX rapidly into CD101+ terminally differentiated subsets (terminally exhausted T cell (TEX term)). Our study also demonstrates that rhIL-7-hyFc significantly enhances the proliferation rate of TPEX in the tdLNs, positively correlating with their abundance within the tumor. Moreover, rhIL-7-hyFc and hIL-2/TCB2c can overcome the limited therapeutic effectiveness of PD-1 blockade, culminating in the complete regression of tumors. CONCLUSIONS: rhIL-7-hyFc can expand and maintain the progenitor pool of exhausted CD8+ T cells, whereas hIL-2/TCB2c promotes their differentiation into TEX term. Together, this induces an immune-stimulatory TME that improves the efficacy of checkpoint blockade.

Retinal vessel volume reference database derived from volume-rendered optical coherence tomography angiography.

Optical coherence tomography angiography (OCTA) enables three-dimensional reconstruction of the functional blood vessels in the retina. Therefore, it enables the quantification of 3D retinal vessel parameters such as surface area and vessel volume. In spite of the widespread use of OCTA, no representative volume-rendered vessel volume (VV) data are published to date. In this study, OCTA 3 × 3 mm macular cubes were processed with volume-rendering techniques to measure VV in 203 eyes from 107 healthy volunteers. Generalized linear models (GLM) were constructed to assess the impact of age, gender, visual acuity (VA), spherical equivalent (SE), and axial length (AL) on VV. Overall mean VV was 0.23 ± 0.05mm3. Age and axial length showed a negative correlation with VV. However, GLM model analysis found that AL exerted the most pronounced influence on VV. No statistically significant associations were identified between gender or between left and right eyes. This is the first study to assess 3D OCTA VV and its naturally occurring variations in a large series of healthy subjects. It offers novel insights into the characterization of normal retinal vascular anatomy in healthy individuals, contributing to a valuable reference for future research in this field.

An IROA Workflow for correction and normalization of ion suppression in mass spectrometry-based metabolomic profiling data.

Ion suppression is a major problem in mass spectrometry (MS)-based metabolomics; it can dramatically decrease measurement accuracy, precision, and signal-to-noise sensitivity. Here we report a new method, the IROA TruQuant Workflow, that uses a stable isotope-labeled internal standard (IROA-IS) plus novel companion algorithms to 1) measure and correct for ion suppression, and 2) perform Dual MSTUS normalization of MS metabolomic data. We have evaluated the method across ion chromatography (IC), hydrophilic interaction liquid chromatography (HILIC), and reverse phase liquid chromatography (RPLC)-MS systems in both positive and negative ionization modes, with clean and unclean ion sources, and across different biological matrices. Across the broad range of conditions tested, all detected metabolites exhibited ion suppression ranging from 1% to 90+% and coefficient of variations ranging from 1% to 20%, but the Workflow and companion algorithms were highly effective at nulling out that suppression and error. Overall, the Workflow corrects ion suppression across diverse analytical conditions and produces robust normalization of non-targeted metabolomic data.

Short physical performance battery is not associated with falls and injurious falls in older persons: longitudinal data of the SCOPE project.

INTRODUCTION: Falls and fall-related injuries in older persons are a major public health problem. Our objective was to study the predictive value of the Short Physical Performance Battery (SPPB) in the cohort of the SCOPE project on falls, injurious falls, and possible difference of prediction between indoors and outdoors falls. METHODS: For this sub-study of the SCOPE project participants reporting no falls at baseline, and survey data on falls at the 12-month and 24-month follow-up were included. Participant´s characteristics were assessed during the baseline interview and medical examinations. Falls as well as injurious falls and fall circumstances were obtained self-reported. SPPB and its association with fallers vs. no fallers at 12 and at 24 months were studied with logistic regression models. RESULTS: The 1198 participants had a median age of 79 years (77-82), and a median SPPB of 10 (8-11), with a 52.5% of female. A total of 227 and 277 falls (12- and 24- month visits, respectively) were reported. In the crude model, the SPPB sum scores (p < 0.001) as well as most single item scores were significant different between fallers and non-fallers over time. However, the association was attenuated in models adjusted for age, sex, marital status, number of medications, quality of life, handgrip strength, and muscle mass [e.g., 12 months; OR 0.94 (0.87-1.02)]. While SPPB fails to differentiate between injurious and non-injurious falls (p = 0.48), a lower SPPB score was associated with falls at home (p < 0.01) after 24 months. CONCLUSION: SBPP was not able to significantly predict the risk of falling as well as experiencing an injurious fall. TRIAL REGISTRATION: This study was registered prospectively on 25th February 2016 at clinicaltrials.gov (NCT02691546).

Versican accumulation drives Nos2 induction and aortic disease in Marfan syndrome via Akt activation.

Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening condition associated with Marfan syndrome (MFS), a disease caused by fibrillin-1 gene mutations. While various conditions causing TAAD exhibit aortic accumulation of the proteoglycans versican (Vcan) and aggrecan (Acan), it is unclear whether these ECM proteins are involved in aortic disease. Here, we find that Vcan, but not Acan, accumulated in Fbn1C1041G/+ aortas, a mouse model of MFS. Vcan haploinsufficiency protected MFS mice against aortic dilation, and its silencing reverted aortic disease by reducing Nos2 protein expression. Our results suggest that Acan is not an essential contributor to MFS aortopathy. We further demonstrate that Vcan triggers Akt activation and that pharmacological Akt pathway inhibition rapidly regresses aortic dilation and Nos2 expression in MFS mice. Analysis of aortic tissue from MFS human patients revealed accumulation of VCAN and elevated pAKT-S473 staining. Together, these findings reveal that Vcan plays a causative role in MFS aortic disease in vivo by inducing Nos2 via Akt activation and identify Akt signaling pathway components as candidate therapeutic targets.

Familiality of the Intelligence Quotient in First Episode Psychosis: Is the Degree of Family Resemblance Associated With Different Profiles?

BACKGROUND AND HYPOTHESIS: There is uncertainty about the relationship between the family intelligence quotient (IQ) deviation and the risk for schizophrenia spectrum disorders (SSD). This study tested the hypothesis that IQ is familial in first episode psychosis (FEP) patients and that their degree of familial resemblance is associated with different profiles. STUDY DESIGN: The participants of the PAFIP-FAMILIAS project (129 FEP patients, 143 parents, and 97 siblings) completed the same neuropsychological battery. IQ-familiality was estimated through the Intraclass Correlation Coefficient (ICC). For each family, the intra-family resemblance score (IRS) was calculated as an index of familial similarity. The FEP patients were subgrouped and compared according to their IRS and IQ. STUDY RESULTS: IQ-familiality was low-moderate (ICC = 0.259). A total of 44.9% of the FEP patients had a low IRS, indicating discordancy with their family-IQ. Of these patients, those with low IQ had more schizophrenia diagnosis and a trend towards poorer premorbid adjustment in childhood and early adolescence. Whereas FEP patients with low IQ closely resembling their family-IQ were characterized by having the lowest performance in executive functions. CONCLUSIONS: The deviation from the familial cognitive performance may be related to a particular pathological process in SSD. Individuals with low IQ who do not reach their cognitive familial potential show difficulties in adjustment since childhood, probably influenced by environmental factors. Instead, FEP patients with high phenotypic family resemblance might have a more significant genetic burden for the disorder.

Normothermic Machine Perfusion Systems: Where Do We Go From Here?

Normothermic machine perfusion (NMP) aims to preserve organs ex vivo by simulating physiological conditions such as body temperature. Recent advancements in NMP system design have prompted the development of clinically effective devices for liver, heart, lung, and kidney transplantation that preserve organs for several hours/up to 1 d. In preclinical studies, adjustments to circuit structure, perfusate composition, and automatic supervision have extended perfusion times up to 1 wk of preservation. Emerging NMP platforms for ex vivo preservation of the pancreas, intestine, uterus, ovary, and vascularized composite allografts represent exciting prospects. Thus, NMP may become a valuable tool in transplantation and provide significant advantages to biomedical research. This review recaps recent NMP research, including discussions of devices in clinical trials, innovative preclinical systems for extended preservation, and platforms developed for other organs. We will also discuss NMP strategies using a global approach while focusing on technical specifications and preservation times.

Biodegradable nanocomposite poly(lactic acid) foams containing carvacrol-based cocrystal prepared by supercritical CO2 processing for controlled release in active food packaging.

Compounds derived from essential oils have been used in active packaging, but their volatility and degradability negatively affect stability and leads to high release rates. The present study aimed to develop PLA bionanocomposite foams loaded with carvacrol cocrystal by supercritical CO2 and its release into a food simulant for control release in food packaging. For this purpose, 4,4'-bipyridine was used as coformer and carvacrol as active agent. Cocrystallized closed cell foams were obtained using supercritical CO2 and were characterized in terms of their physicochemical and mechanical properties, and release kinetics to a D1 simulant were evaluated as well as the antioxidant ability. A better overall mechanical behavior due to the nanoclay promoting a higher interfacial adhesion with the polymeric matrix was revealed. A higher incorporation of carvacrol was observed in samples with higher C30B content. The incorporated cocrystals showed a decrease of one order of magnitude in the estimated effective diffusion coefficient of carvacrol and showed antioxidant activity. These results suggest that the nanocomposite foam containing carvacrol-based cocrystals could be used in active packaging systems with controlled release characteristics, especially with highly volatile compounds, and can be proposed for other fields such as biomedical applications.

Deep Learning-Based Predictive Model for Revascularization of Chronic Total Occlusions on Angiographic Imaging.

Revascularization of chronic total occlusions (CTO) is currently one of the most complex procedures in percutaneous coronary intervention (PCI), requiring the use of specific devices and a high level of experience to obtain good results. Once the clinical indication for extensive ischemia or angina uncontrolled with medical treatment has been established, the decision to perform coronary intervention is not simple, since this procedure has a higher rate of complications than non-PCI percutaneous intervention, higher ionizing radiation doses and a lower success rate. However, CTO revascularization has been shown to be helpful in symptomatic improvement of angina, reduction of ischemic burden, or improvement of ejection fraction. The aim of this work is to determine whether a model developed using deep learning techniques, and trained with angiography images, can better predict the likelihood of a successful revascularization procedure for a patient with a chronic total occlusion (CTO) lesion in their coronary artery (measured as procedure success and the duration of time during which X-ray imaging technology is used to perform a medical procedure) than the scales traditionally used. As a preliminary approach, patients with right coronary artery CTO will be included since they present standard angiographic projections that are performed in all patients and present less technical variability (duration, projection angle, image similarity) among them.The ultimate objective is to develop a predictive model to help the clinician in the decision to intervene and to analyze the performance in terms of predicting the success of the technique for the revascularization of chronic occlusions.Clinical Relevance- The development of a deep learning model based on the angiography images could potentially overcome the gold standard and help interventional cardiologists in the treatment decision for percutaneous coronary intervention, maximizing the success rate of coronary intervention.