[Effects of the COVID-19 pandemic on the mental health of patients with pre-existing psychopathology]. / Efectos de la pandemia de la COVID-19 en la salud mental de pacientes con psicopatología previa.

OBJECTIVE: Several studies stated greater impact on mental health among psychiatric population during the first wave of the COVID-19 pandemic. The aim of this paper was to study the pandemic effects more than a year after its outbreak on the mental state of adult patients with pre-existing psychopathology attending a Mental Health Center in Madrid (Spain). METHODS: A cross-sectional observational study was carried out with a sample of fifty-eight patients using a questionnaire that collected different descriptive variables. Results of the PHQ-9 Depression Scale, the GAD-7 Anxiety Scale, the IES-R Impact of Event Scale-Revised, the Clinical Global Impression scale CGI-GI, and the assessment of the professionals responsible for the patients about their clinical state were also collected. A descriptive analysis and binary logistic regression models were performed. RESULTS: There was a prevalence of 70% anxiety, 76% depression and 57% stress due to a stressful event more than one year after the start of the pandemic. Likewise, associations were found between the symptoms and certain clinical, mediating variables and gender. CONCLUSIONS: The psychological state of patients with pre-existing psychopathology attended at the Mental Health Center is negatively affected by the COVID-19 pandemic up to a year and a half after its onset.

OBJETIVO: Numerosos estudios han confirmado que las personas con un diagnóstico psiquiátrico se vieron más afectadas en su salud mental que la población general en una primera fase de la pandemia de la COVID-19. El objetivo de este trabajo fue estudiar los efectos de la pandemia, más de un año después de su inicio, en el estado psíquico de pacientes adultos con psicopatología previa de un Centro de Salud Mental (CSM) en Madrid. METODOS: Se realizó un estudio observacional transversal en una muestra de cincuenta y ocho pacientes mediante un cuestionario que recogía diferentes variables descriptivas. Se administraron la Escala de Depresión PHQ-9, la Escala de Ansiedad GAD-7, la Escala Revisada de Impacto del Estresor EIE-R, la Escala de Impresión Clínica Global CGI-GI y la valoración de los facultativos responsables de los pacientes sobre su estado clínico. Se realizó un análisis descriptivo y se aplicaron modelos de regresión logística binaria. RESULTADOS: Hubo una prevalencia de 70% de ansiedad, 76% de depresión y 57% de estrés por evento estresante más de un año después de iniciarse la pandemia. Asimismo, se encontró asociación de los síntomas clínicos con determinadas variables clínicas, con variables mediadoras y con el género. CONCLUSIONES: El estado psíquico de los pacientes con psicopatología previa atendidos en el CSM se ve negativamente afectado por la pandemia de la COVID-19 hasta año y medio después de su inicio.

COVID-19 Outcomes in Patients with Hematologic Malignancies in the Era of COVID-19 Vaccination and the Omicron Variant.

A greater understanding of clinical trends in COVID-19 outcomes among patients with hematologic malignancies (HM) over the course of the pandemic, particularly the Omicron era, is needed. This ongoing, observational, and registry-based study with prospective data collection evaluated COVID-19 clinical severity and mortality in 1818 adult HM patients diagnosed with COVID-19 between 27 February 2020 and 1 October 2022, at 31 centers in the Madrid region of Spain. Of these, 1281 (70.5%) and 537 (29.5%) were reported in the pre-Omicron and Omicron periods, respectively. Overall, patients aged ≥70 years (odds ratio 2.16, 95% CI 1.64-2.87), with >1 comorbidity (2.44, 1.85-3.21), or with an underlying HM of chronic lymphocytic leukemia (1.64, 1.19-2.27), had greater odds of severe/critical COVID-19; odds were lower during the Omicron BA.1/BA.2 (0.28, 0.2-0.37) or BA.4/BA.5 (0.13, 0.08-0.19) periods and among patients vaccinated with one or two (0.51, 0.34-0.75) or three or four (0.22, 0.16-0.29) doses. The hospitalization rate (75.3% [963/1279], 35.7% [191/535]), rate of intensive care admission (30.0% [289/963], 14.7% [28/191]), and mortality rate overall (31.9% [409/1281], 9.9% [53/536]) and in hospitalized patients (41.3% [398/963], 22.0% [42/191]) decreased from the pre-Omicron to Omicron period. Age ≥70 years was the only factor associated with higher mortality risk in both the pre-Omicron (hazard ratio 2.57, 95% CI 2.03-3.25) and Omicron (3.19, 95% CI 1.59-6.42) periods. Receipt of prior stem cell transplantation, COVID-19 vaccination(s), and treatment with nirmatrelvir/ritonavir or remdesivir were associated with greater survival rates. In conclusion, COVID-19 mortality in HM patients has decreased considerably in the Omicron period; however, mortality in hospitalized HM patients remains high. Specific studies should be undertaken to test new treatments and preventive interventions in HM patients.

A perspective on the role of physiological stresses in cancer, diabetes and cognitive disease as environmental diseases.

With rapid industrialization, urbanization, and climate change, the impact of environmental factors on human health is becoming increasingly evident and understanding the complex mechanisms involved is vital from a healthcare perspective. Nevertheless, the relationship between physiological stress resulting from environmental stressors and environmental disease is complex and not well understood. Chronic exposure to environmental stressors, such as air and water contaminants, pesticides, and toxic metals, has been recognized as a potent elicitor of physiological responses ranging from systemic inflammation to immune system dysregulation causing or progressing environmental diseases. Conversely, physiological stress can exacerbate susceptibility to environmental diseases. Stress-induced alterations in immune function and hormonal balance may impair the ability to detoxify harmful substances and combat pathogens. Additionally, prolonged stress can impact lifestyle choices, leading to harmful behaviors. Understanding the link between physiological stress and environmental disease requires a systematic, multidisciplinary approach. Addressing this complex relationship necessitates the establishment of a global research network. This perspective discusses the intricate interplay between physiological stress and environmental disease, focusing on common environmental diseases, cancer, diabetes, and cognitive degeneration. Furthermore, we highlight the intricate and reciprocal nature of the connection between physiological stress and these environmental diseases giving a perspective on the current state of knowledge as well as identifying where further information is necessary. Recognizing the role of physiological stress in environmental health outcomes will aid in the development of comprehensive strategies to safeguard public health and promote ecological balance.

Novel Biorefinery Approach for Phycocyanin Extraction and Purification and Biocrude Production from Arthrospira platensis.

A new biorefinery from Arthrospira platensis was proposed to obtain phycocyanin (PC) and a biocrude by hydrothermal liquefaction (HTL). PC is a high-added-value phycobiliprotein widely used as a food colorant and in the nutraceutical and pharmaceutical industries. However, the use of conventional solvents in the extraction process and the purity grade of the extract are shortcomings in bioproduct production. PC was extracted using a reusable ionic liquid [EMIM][EtSO4], achieving a PC purity of the lowest commercial grade. Therefore, two downstream processes were applied: (1) dialysis + precipitation and (2) aqueous two-phase system (ATPS) + dialysis + precipitation. After the second purification process, the PC purity increased remarkably to reach the analytical grade for pharmaceutical and nutraceutical applications. The waste biomass (WB) obtained in the PC extraction was valorized by hydrothermal liquefaction (HTL) to produce a biocrude. The biocrude yield and composition remarkably enhanced using isopropanol at 350 °C as a cosolvent.

COVID-19 Severity and Survival over Time in Patients with Hematologic Malignancies: A Population-Based Registry Study.

Mortality rates for COVID-19 have declined over time in the general population, but data in patients with hematologic malignancies are contradictory. We identified independent prognostic factors for COVID-19 severity and survival in unvaccinated patients with hematologic malignancies, compared mortality rates over time and versus non-cancer inpatients, and investigated post COVID-19 condition. Data were analyzed from 1166 consecutive, eligible patients with hematologic malignancies from the population-based HEMATO-MADRID registry, Spain, with COVID-19 prior to vaccination roll-out, stratified into early (February-June 2020; n = 769 (66%)) and later (July 2020-February 2021; n = 397 (34%)) cohorts. Propensity-score matched non-cancer patients were identified from the SEMI-COVID registry. A lower proportion of patients were hospitalized in the later waves (54.2%) compared to the earlier (88.6%), OR 0.15, 95%CI 0.11-0.20. The proportion of hospitalized patients admitted to the ICU was higher in the later cohort (103/215, 47.9%) compared with the early cohort (170/681, 25.0%, 2.77; 2.01-3.82). The reduced 30-day mortality between early and later cohorts of non-cancer inpatients (29.6% vs. 12.6%, OR 0.34; 0.22-0.53) was not paralleled in inpatients with hematologic malignancies (32.3% vs. 34.8%, OR 1.12; 0.81-1.5). Among evaluable patients, 27.3% had post COVID-19 condition. These findings will help inform evidence-based preventive and therapeutic strategies for patients with hematologic malignancies and COVID-19 diagnosis.

Targeting carnitine palmitoyltransferase 1 isoforms in the hypothalamus: A promising strategy to regulate energy balance.

Tackling the growing incidence and prevalence of obesity urgently requires uncovering new molecular pathways with therapeutic potential. The brain, and in particular the hypothalamus, is a major integrator of metabolic signals from peripheral tissues that regulate functions such as feeding behavior and energy expenditure. In obesity, hypothalamic capacity to sense nutritional status and regulate these functions is altered. An emerging line of research is that hypothalamic lipid metabolism plays a critical role in regulating energy balance. Here, we focus on the carnitine palmitoyltransferase 1 (CPT1) enzyme family responsible for long-chain fatty acid metabolism. The evidence suggests that two of its isoforms expressed in the brain, CPT1A and CPT1C, play a crucial role in hypothalamic lipid metabolism, and their promise as targets in food intake and bodyweight management is currently being intensively investigated. In this review we describe and discuss the metabolic actions and potential up- and downstream effectors of hypothalamic CPT1 isoforms, and posit the need to develop innovative nanomedicine platforms for selective targeting of CPT1 and related nutrient sensors in specific brain areas as potential next-generation therapy to treat obesity.

Nanomedicine targeting brain lipid metabolism as a feasible approach for controlling the energy balance.

Targeting brain lipid metabolism is a promising strategy to regulate the energy balance and fight metabolic diseases such as obesity. The development of stable platforms for selective delivery of drugs, particularly to the hypothalamus, is a challenge but a possible solution for these metabolic diseases. Attenuating fatty acid oxidation in the hypothalamus via CPT1A inhibition leads to satiety, but this target is difficult to reach in vivo with the current drugs. We propose using an advanced crosslinked polymeric micelle-type nanomedicine that can stably load the CPT1A inhibitor C75-CoA for in vivo control of the energy balance. Central administration of the nanomedicine induced a rapid attenuation of food intake and body weight in mice via regulation of appetite-related neuropeptides and neuronal activation of specific hypothalamic regions driving changes in the liver and adipose tissue. This nanomedicine targeting brain lipid metabolism was successful in the modulation of food intake and peripheral metabolism in mice.

Central Regulation of Brown Fat Thermogenesis in Response to Saturated or Unsaturated Long-Chain Fatty Acids.

Sensing of long-chain fatty acids (LCFA) in the hypothalamus modulates energy balance, and its disruption leads to obesity. To date, the effects of saturated or unsaturated LCFA on hypothalamic-brown adipose tissue (BAT) axis and the underlying mechanisms have remained largely unclear. Our aim was to characterize the main molecular pathways involved in the hypothalamic regulation of BAT thermogenesis in response to LCFA with different lengths and degrees of saturation. One-week administration of high-fat diet enriched in monounsaturated FA led to higher BAT thermogenesis compared to a saturated FA-enriched diet. Intracerebroventricular infusion of oleic and linoleic acids upregulated thermogenesis markers and temperature in brown fat of mice, and triggered neuronal activation of paraventricular (PaV), ventromedial (VMH) and arcuate (ARC) hypothalamic nuclei, which was not found with saturated FAs. The neuron-specific protein carnitine palmitoyltransferase 1-C (CPT1C) was a crucial effector of oleic acid since the FA action was blunted in CPT1C-KO mice. Moreover, changes in the AMPK/ACC/malonyl-CoA pathway and fatty acid synthase expression were evoked by oleic acid. Altogether, central infusion of unsaturated but not saturated LCFA increases BAT thermogenesis through CPT1C-mediated sensing of FA metabolism shift, which in turn drive melanocortin system activation. These findings add new insight into neuronal circuitries activated by LCFA to drive thermogenesis.

To be or not to be a fat burner, that is the question for cpt1c in cancer cells.

There is an urgent need to identify reliable genetic biomarkers for accurate diagnosis, prognosis, and treatment of different tumor types. Described as a prognostic marker for many tumors is the neuronal protein carnitine palmitoyltransferase 1 C (CPT1C). Several studies report that CPT1C is involved in cancer cell adaptation to nutrient depletion and hypoxia. However, the molecular role played by CPT1C in cancer cells is controversial. Most published studies assume that, like canonical CPT1 isoforms, CPT1C is a mediator of fatty acid transport to mitochondria for beta-oxidation, despite the fact that CPT1C has inefficient catalytic activity and is located in the endoplasmic reticulum. In this review, we collate existing evidence on CPT1C in neurons, showing that CPT1C is a sensor of nutrients that interacts with and regulates other proteins involved in lipid metabolism and transport, lysosome motility, and the secretory pathway. We argue, therefore, that CPT1C expression in cancer cells is not a direct regulator of fat burn, but rather is a regulator of lipid metabolic reprograming and cell adaptation to environmental stressors. We also review the clinical relevance of CPT1C as a prognostic indicator and its contribution to tumor growth, cancer invasiveness, and cell senescence. This new and integrated vision of CPT1C function can help better understand the metabolic plasticity of cancer cells and improve the design of therapeutic strategies.

Integrated Metabolomics, Lipidomics, and Genomics Reveal the Presence of a New Biomarker, Butanediol Glucuronide, Associated with the Activation of Liver Ketogenesis and Lipid Oxidation by Tomato-Based Sofrito in Obese Rats.

The increasing prevalence of obesity worldwide has promoted research on human metabolism and foods such as sofrito, a tomato and olive oil-based sauce from the Mediterranean diet, has shown beneficial effects on obesity and related complications. Sofrito has been associated with better cardiovascular health, metabolic syndrome, and anti-inflammatory effects. The aim of this study was to understand how sofrito intake could contribute to the control of energy metabolism in obese rats. For this purpose, integrative untargeted lipidomics, metabolomics, and targeted gene expression approaches were used in the liver and adipose tissue to identify metabolic changes and the mechanism of action promoted by sofrito intake. A new biomarker was identified in the liver, butanediol glucuronide, an indicator of ketogenic activation and lipid oxidation after the sofrito intervention. Gene expression analysis revealed an increase in the uptake and liver oxidation of lipids for energy production and ketogenesis activation as fuel for other tissues in sofrito-fed animals. Sofrito altered the lipidomic profile in the fat depots of obese rats. This multiomics study identifies a new biomarker linked to the beneficial actions of sofrito against obesity and provides further insight into the beneficial effect of the Mediterranean diet components.

Coupling phytoremediation of Pb-contaminated soil and biomass energy production: A comparative Life Cycle Assessment.

Phytoremediation is an in-situ remediation technology based on the ability of plants to fix pollutants from the soil. In this sense, plants such as Festuca arundinacea are a promising for heavy metal removal in contaminated soils. The present work studies phytoremediation for Pb removal from a contaminated soil located in Spain using F. arundinacea by applying the Life Cycle Assessment (LCA) approach. Two different options for biomass management were assessed: direct disposal in a security landfill (case 1A) and energy recovery (case 1B). For the latter option, cogeneration was simulated using SuperPro Designer 9.5. In addition, traditional treatments such as soil washing (case 2) and excavation + landfill (case 3) were evaluated in terms of environmental impacts by LCA. The former was simulated using SuperPro Designer 9.5, whereas data from literature were used for the latter to perform the LCA. Results showed that biomass disposal in a landfill was the most important contributor to the overall impact in case 1A. In contrast, biomass conditioning and cogeneration were the main steps responsible for environmental impacts in case 1B. Comparing cases 1A and 1B, the energy recovery from biomass was superior to direct landfill disposal, reducing the environmental impacts in most of the studied categories. Regarding the rest of the treatments, chemical production and soil disposal presented the most critical environmental burdens in cases 2 and 3, respectively. Finally, the comparison between the studied cases revealed that phytoextraction + energy recovery was the most environmentally friendly option for the studied conditions, reducing impacts by 30-100%.

Experiencias sobre la implementación del Expediente Clínico Electrónico / Experiences on the implementation of the Electronic Medical Record

Resumen Introducción. Un elemento de la e-salud que ha cobrado gran relevancia es el Expediente Clínico Electrónico (ECE) ya que es un medio para lograr mejores resultados en la práctica médica. Al momento, han sido pocas las investigaciones que se han centrado en analizar e identificar la situación de esta estrategia en el mundo. Por ello, el objetivo de esta investigación es analizar el panorama actual del ECE en diversos países considerando las ventajas, desventajas, desafíos y factores de éxito en su implementación. Metodología: Se realizó una revisión de la literatura existente sobre el ECE en base de datos especializadas. Para obtener estos estudios se utilizó la base de datos de scopus y sciencedirect , utilizando palabras de búsqueda como como registro electrónico de salud, registro médico electrónico o expediente clínico electrónico; se seleccionaron solamente aquellos estudios con un alto factor de impacto, mismo que se refiere al número de veces que se hayan citado los artículos consultados. Se seleccionaron y analizaron 64 estudios académicos. Resultados. Se encontró que aún existen importantes desafíos y desventajas en la implementación del ECE como la interoperabilidad semántica y el estrés laboral que genera en los usuarios este sistema. Conclusiones. Existen cuestiones importantes que aún quedan por resolver para una implementación eficaz del ECE. Es necesario integrar a todos los involucrados en el proceso de cambio, así como establecer las medidas de seguridad necesarias para garantizar la privacidad de la información.

Abstract Introduction. An element of e-health that has gained great relevance is the Electronic Medical Record (ECE) since it is a means to achieve better results in medical practice. At the moment, few investigations have focused on analyzing and identifying the situation of this strategy in the world. Therefore, the objective of this research is to analyze the current panorama of ECE in various countries considering the advantages, disadvantages, challenges and success factors in its implementation. Methodology. A review of the existing literature on ECE was carried out in specialized databases. To obtain these studies, the scopus and sciencedirect databases were used, using search words such as "electronic health record", "electronic medical record" or "electronic medical record"; Only those studies with a high impact factor were selected, which refers to the number of times the articles consulted have been cited. 64 academic studies were selected and analyzed. Results. It was found that there are still important challenges and disadvantages in the implementation of ECE such as semantic interoperability and the work stress that this system generates in users. Conclusions. There are important issues that remain to be resolved in the effective implementation of the ECE. It is necessary to integrate all those involved in the change process as well as to establish the necessary security measures to guarantee the privacy of the information.

Molecular Mechanisms Underlying the Effects of Olive Oil Triterpenic Acids in Obesity and Related Diseases.

Dietary components exert protective effects against obesity and related metabolic and cardiovascular disturbances by interfering with the molecular pathways leading to these pathologies. Dietary biomolecules are currently promising strategies to help in the management of obesity and metabolic syndrome, which are still unmet medical issues. Olive oil, a key component of the Mediterranean diet, provides an exceptional lipid matrix highly rich in bioactive molecules. Among them, the pentacyclic triterpenic acids (i.e., oleanolic acid) have gained clinical relevance in the last decade due to their wide range of biological actions, particularly in terms of vascular function, obesity and insulin resistance. Considering the promising effects of these triterpenic compounds as nutraceuticals and components of functional foods against obesity and associated complications, the aim of our review is to decipher and discuss the main molecular mechanisms underlying these effects driven by olive oil triterpenes, in particular by oleanolic acid. Special attention is paid to their signaling and targets related to glucose and insulin homeostasis, lipid metabolism, adiposity and cardiovascular dysfunction in obesity. Our study is aimed at providing a better understanding of the impact of dietary components of olive oil in the long-term management of obesity and metabolic syndrome in humans.

Comparison of antibody response to SARS-CoV-2 after two doses of inactivated virus and BNT162b2 mRNA vaccines in kidney transplant.

BACKGROUND: Antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after mRNA or adenoviral vector-based vaccines is weak in kidney transplant (KT) patients. However, few studies have focused on humoral response after inactivated virus-based vaccines in KT. Here, we compare antibody response following vaccination with inactivated virus (CoronaVac®) and BNT162b2 mRNA. METHODS: A national multicentre cross-sectional study was conducted. The study group was composed of patients from all KT centres in Uruguay, vaccinated between 1 and 31 May 2021 (CoronaVac®, n = 245 and BNT162b2, n = 39). The control group was constituted of 82 healthy individuals. Participants had no prior confirmed coronavirus disease 2019 (COVID-19) test. Blood samples were collected between 30 and 40 days after the second dose. Serum-specific immunoglobulin G (IgG) antibodies against the receptor-binding domain (RBD) of SARS-CoV-2 Spike protein were determined using the COVID-19 IgG QUANT ELISA Kit. RESULTS: Only 29% of KT recipients showed seroconversion (36.5% BNT162b2, 27.8% inactivated virus, P = 0.248) in comparison with 100% in healthy control with either vaccine. Antibody levels against RBD were higher with BNT162b mRNA than with inactivated virus [median (interquartile range) 173 (73-554) and 29 (11-70) binding antibody units (BAU)/mL, P < 0.034] in KT and 10 times lower than healthy control [inactivated virus: 308 (209-335) and BNT162b2: 2638 (2608-3808) BAU/mL, P < 0.034]. In multivariate analysis, variables associated with negative humoral response were age, triple immunosuppression, estimated glomerular filtration rate and time post-KT. CONCLUSION: Seroconversion was low in KT patients after vaccination with both platforms. Antibody levels against SARS-CoV-2 were lower with inactivated virus than BNT162b mRNA. These findings support the need for strategies to improve immunogenicity in KT recipients after two doses of either vaccine.

Hypothalamic Regulation of Obesity.

Obesity has now reached pandemic proportions and represents a major socioeconomic and health problem in our societies [...].

Polyphosphate degradation by Nudt3-Zn2+ mediates oxidative stress response.

Polyphosphate (polyP) is a polymer of hundreds of phosphate residues present in all organisms. In mammals, polyP is involved in crucial physiological processes, including coagulation, inflammation, and stress response. However, after decades of research, the metabolic enzymes are still unknown. Here, we purify and identify Nudt3, a NUDIX family member, as the enzyme responsible for polyP phosphatase activity in mammalian cells. We show that Nudt3 shifts its substrate specificity depending on the cation; specifically, Nudt3 is active on polyP when Zn2+ is present. Nudt3 has in vivo polyP phosphatase activity in human cells, and importantly, we show that cells with altered polyP levels by modifying Nudt3 protein amount present reduced viability upon oxidative stress and increased DNA damage, suggesting that polyP and Nudt3 play a role in oxidative stress protection. Finally, we show that Nudt3 is involved in the early stages of embryo development in zebrafish.