Metabolic and mitochondria alterations induced by SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10.

Antiviral signaling, immune response and cell metabolism are dysregulated by SARS-CoV-2, the causative agent of COVID-19. Here, we show that SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10 induce a significant mitochondrial and metabolic reprogramming in A549 lung epithelial cells. While ORF9b, ORF9c and ORF10 induced largely overlapping transcriptomes, ORF3a induced a distinct transcriptome, including the downregulation of numerous genes with critical roles in mitochondrial function and morphology. On the other hand, all four ORFs altered mitochondrial dynamics and function, but only ORF3a and ORF9c induced a marked alteration in mitochondrial cristae structure. Genome-Scale Metabolic Models identified both metabolic flux reprogramming features both shared across all accessory proteins and specific for each accessory protein. Notably, a downregulated amino acid metabolism was observed in ORF9b, ORF9c and ORF10, while an upregulated lipid metabolism was distinctly induced by ORF3a. These findings reveal metabolic dependencies and vulnerabilities prompted by SARS-CoV-2 accessory proteins that may be exploited to identify new targets for intervention.

Nanogel-Mediated antigen delivery: Biocompatibility, immunogenicity, and potential for tailored vaccine design across species.

Nanotechnology has emerged as a promising avenue for enhancing the efficacy of vaccine delivery systems. This study investigates the utilization of nanogels as carriers for the model antigen ovalbumin, with a focus on in vivo assessments in equine and murine models. Nanogels, owing to their biocompatibility and tunable physicochemical properties, offer a versatile platform for efficient antigen encapsulation and controlled release. The encapsulation efficiency and physicochemical characteristics of ovalbumin-loaded nanogels were comprehensively characterized. In vitro biocompatibility was evaluated, finding excellent properties of these nanogels. In vivo evaluations were conducted on both equine and murine subjects, assessing immunogenicity through antibody and splenic cell response. Furthermore, the study propose the potential use of nanogels in tailoring immune responses through the modulation of antigen release kinetics. The results obtained in the in vitro assays showed an increase in the uptake of nanogels by APCs compared to free antigen (OVA). In mice, an absence of inflammatory response in the inoculation site was observed, without systemic damage in the evaluated organs. In addition, non-significant humoral response was found nor cellular proliferation and proinflammatory cytokine production, compared with a traditional adjuvant as aluminum hydroxide, in both animal models. These findings allow further insights into nanogel-based delivery systems and offer valuable insights into their application in various animal models. In conclusion, this research establishes the utility of nanogels as effective carriers for antigens-based vaccines, with interesting biocompatibility properties and highly taken affinity by antigen-presenting cells, without inducing inflammation at the injection site. The study underscores the potential of nanogel technology in revolutionizing vaccine design and highlights the importance of tailored approaches for diverse target species.

Effects of removing in-feed antibiotics and zinc oxide on the taxonomy and functionality of the microbiota in post weaning pigs.

BACKGROUND: Post weaning diarrhoea (PWD) causes piglet morbidity and mortality at weaning and is a major driver for antimicrobial use worldwide. New regulations in the EU limit the use of in-feed antibiotics (Ab) and therapeutic zinc oxide (ZnO) to prevent PWD. New approaches to control PWD are needed, and understanding the role of the microbiota in this context is key. In this study, shotgun metagenome sequencing was used to describe the taxonomic and functional evolution of the faecal microbiota of the piglet during the first two weeks post weaning within three experimental groups, Ab, ZnO and no medication, on commercial farms using antimicrobials regularly in the post weaning period. RESULTS: Diversity was affected by day post weaning (dpw), treatment used and diarrhoea but not by the farm. Microbiota composition evolved towards the dominance of groups of species such as Prevotella spp. at day 14dpw. ZnO inhibited E. coli overgrowth, promoted higher abundance of the family Bacteroidaceae and decreased Megasphaera spp. Animals treated with Ab exhibited inconsistent taxonomic changes across time points, with an overall increase of Limosilactobacillus reuteri and Megasphaera elsdenii. Samples from non-medicated pigs showed virulence-related functions at 7dpw, and specific ETEC-related virulence factors were detected in all samples presenting diarrhoea. Differential microbiota functions of pigs treated with ZnO were related to sulphur and DNA metabolism, as well as mechanisms of antimicrobial and heavy metal resistance, whereas Ab treated animals exhibited functions related to antimicrobial resistance and virulence. CONCLUSION: Ab and particularly ZnO maintained a stable microbiota composition and functionality during the two weeks post weaning, by limiting E. coli overgrowth, and ultimately preventing microbiota dysbiosis. Future approaches to support piglet health should be able to reproduce this stable gut microbiota transition during the post weaning period, in order to maintain optimal gut physiological and productive conditions.

Síntomas depresivos en una muestra de mujeres con hipotiroidismo subclínico y su relación con los cloratos del agua del grifo / Depressive symptoms in a sample of women with subclinical hypothyroidism and their relationship to chlorates in tap water

Introducción: en el hipotiroidismo subclínico pueden aparecer síntomas depresivos y su presencia suele facilitar la instauración de un tratamiento de reemplazo; sin embargo, estudios recientes no han encontrado una asociación entre ambos. Por otra parte, la función tiroidea puede verse afectada por disruptores endocrinos y, algunos de ellos, como los cloratos, pueden encontrarse en el agua que bebemos. Objetivos: conocer si el tipo de consumo de agua puede influir en la aparición de síntomas depresivos en pacientes con hipotiroidismo subclínico. Métodos: participaron 96 mujeres con hipotiroidismo subclínico, sin tratamiento tiroideo, de un área de salud de España. Estudiamos, entre otras variables, la presencia de síntomas depresivos, el tipo de consumo de agua (grifo/embotellada o manantial) y el nivel de cloratos en el agua del grifo. Resultados: el 41,7 % (40) de las mujeres presentaban síntomas depresivos y estos se relacionaban con el consumo de agua del grifo (p = 0,001), resultando este un predictor confiable (OR: 27,79; p = 0,007). El nivel de cloratos en el agua del grifo era de 250 µg/L, valor situado en el límite máximo permitido por la ley. Conclusiones: en mujeres con hipotiroidismo subclínico, la exposición crónica a cloratos en el agua, en niveles autorizados por la ley, podría favorecer la inhibición del transporte de yodo y la aparición de síntomas depresivos. Sería interesante comprobar esta hipótesis, así como su posible efecto sobre otros perfiles poblacionales.(AU)

Introduction: depressive symptoms may develop in subclinical hypothyroidism and their presence usually facilitates recognition and the establishment of replacement treatment; however, recent studies have found no association between the two. Besides, thyroid function can be affected by endocrine disruptors and some of them, such as chlorates, can be found in the water we drink. Objectives: to know if the type of water consumed may influence the development of depressive symptoms in patients with subclinical hypothyroidism. Methods: 96 women with subclinical hypothyroidism, without thyroid treatment, were enrolled. We studied, among other variables, the presence of depressive symptoms, type of water consumption (tap, bottled or spring) and the level of chlorates in the tap water. Results: 41.7 % (40) of women presented depressive symptoms and these were related to the consumption of tap water (p = 0.001), resulting in a reliable predictor (OR, 27.79; p = 0.007). Chlorate level in the tap water was 250 μg/L, a value within the maximum limit allowed by law. Conclusions: chronic exposure to chlorates in water, in women with subclinical hypo-thyroidism, at levels authorized by law, could favor the inhibition of iodine transport and the appearance of depressive symptoms. It would be interesting to test this hypothesis as well as its possible effect on other population profiles.(AU)

Nuevas Adaptaciones Para la Aplicación del Mindfulness a la Psicosis / New Adaptations in the Application of Mindfulness to Psychosis Spectrum Disorders

El uso clínico del mindfulness adaptado a la psicosis ha sido rechazado por algunos profesionales de la Salud Mental debido a prejuicios y falta de información. Sin embargo, la evidencia actual ha demostrado que las Intervenciones Basadas en Mindfulness (MBI) son seguras y tienen numerosos beneficios en los trastornos del espectro psicótico. Las MBI son adaptables a diferentes contextos y situaciones clínicas, incluido el deterioro cognitivo, y aunque no constituye su objetivo principal, pueden facilitar la reducción de la sintomatología negativa en la psicosis. Las MBI permiten a las personas con psicosis enfrentar las experiencias alucinatorias desde una perspectiva diferente, fomentando la flexibilidad, la regulación emocional y la aceptación. Es importante adaptar las intervenciones a las características de la psicosis, así como distinguir entre los diferentes tipos de prácticas, para aplicarlas de manera diferencial según la sintomatología específica y las características de la persona.(AU)

The clinical use of psychosis-adapted mindfulness has been rejected by some mental health professionals due to biases and lack of information. However, current evidence has demonstrated the safety and numerous benefits of mindfulness-based interventions (MBIs) in psychotic spectrum disorders. MBIs are adaptable to diverse clinical contexts and situations, including cognitive impairment, and although it is not their primary objective, they can facilitate the reduction of negative symptomatology in psychosis. MBIs enable individuals with psychosis toapproach hallucinatory experiences from an alternative perspective, fostering flexibility, emotional regulation, and acceptance. It is crucial to tailor interventions to the characteristics of the psychosis, as well as to differentiate between the various types of practices, in order to apply them differentially depending on the specific symptoms and characteristics of the individual.(AU)

[Depressive symptoms in a sample of women with subclinical hypothyroidism and their relationship to chlorates in tap water]. / Síntomas depresivos en una muestra de mujeres con hipotiroidismo subclínico y su relación con los cloratos del agua del grifo.

Introduction: Introduction: depressive symptoms may develop in subclinical hypothyroidism and their presence usually facilitates recognition and the establishment of replacement treatment; however, recent studies have found no association between the two. Besides, thyroid function can be affected by endocrine disruptors and some of them, such as chlorates, can be found in the water we drink. Objectives: to know if the type of water consumed may influence the development of depressive symptoms in patients with subclinical hypothyroidism. Methods: 96 women with subclinical hypothyroidism, without thyroid treatment, were enrolled. We studied, among other variables, the presence of depressive symptoms, type of water consumption (tap, bottled or spring) and the level of chlorates in the tap water. Results: 41.7 % (40) of women presented depressive symptoms and these were related to the consumption of tap water (p = 0.001), resulting in a reliable predictor (OR, 27.79; p = 0.007). Chlorate level in the tap water was 250 µg/L, a value within the maximum limit allowed by law. Conclusions: chronic exposure to chlorates in water, in women with subclinical hypothyroidism, at levels authorized by law, could favor the inhibition of iodine transport and the appearance of depressive symptoms. It would be interesting to test this hypothesis as well as its possible effect on other population profiles.

Introducción: Introducción: en el hipotiroidismo subclínico pueden aparecer síntomas depresivos y su presencia suele facilitar la instauración de un tratamiento de reemplazo; sin embargo, estudios recientes no han encontrado una asociación entre ambos. Por otra parte, la función tiroidea puede verse afectada por disruptores endocrinos y, algunos de ellos, como los cloratos, pueden encontrarse en el agua que bebemos. Objetivos: conocer si el tipo de consumo de agua puede influir en la aparición de síntomas depresivos en pacientes con hipotiroidismo subclínico. Métodos: participaron 96 mujeres con hipotiroidismo subclínico, sin tratamiento tiroideo, de un área de salud de España. Estudiamos, entre otras variables, la presencia de síntomas depresivos, el tipo de consumo de agua (grifo/embotellada o manantial) y el nivel de cloratos en el agua del grifo. Resultados: el 41,7 % (40) de las mujeres presentaban síntomas depresivos y estos se relacionaban con el consumo de agua del grifo (p = 0,001), resultando este un predictor confiable (OR: 27,79; p = 0,007). El nivel de cloratos en el agua del grifo era de 250 µg/L, valor situado en el límite máximo permitido por la ley. Conclusiones: en mujeres con hipotiroidismo subclínico, la exposición crónica a cloratos en el agua, en niveles autorizados por la ley, podría favorecer la inhibición del transporte de yodo y la aparición de síntomas depresivos. Sería interesante comprobar esta hipótesis, así como su posible efecto sobre otros perfiles poblacionales.

Fine-tuning of post-weaning pig microbiome structure and functionality by in-feed zinc oxide and antibiotics use.

Introduction: Post-weaning diarrhoea (PWD) is a multifactorial disease that affects piglets after weaning, contributing to productive and economic losses. Its control includes the use of in-feed prophylactic antibiotics and therapeutic zinc oxide (ZnO), treatments that, since 2022, are no longer permitted in the European Union due to spread of antimicrobial resistance genes and pollution of soil with heavy metals. A dysbiosis in the microbiota has been suggested as a potential risk factor of PWD onset. Understanding pig's microbiota development around weaning and its changes in response to ZnO and antibiotics is crucial to develop feasible alternatives to prophylactic and metaphylactic antimicrobial use. Methods: This study used shotgun metagenomic sequencing to investigate the environmental and faecal microbiota on 10 farms using (Treated) or not using (ZnO-free) in-feed antibiotics and ZnO during the first 14 days post-weaning (dpw). Environmental samples from clean pens were collected at weaning day (0dpw), and faecal samples at 0, 7 and 14dpw. Diarrhoeic faecal samples were collected at 7dpw when available. Results: The analysis of data revealed that the faecal microbiota composition and its functionality was impacted by the sampling time point (microbiota maturation after weaning) but not by the farm environment. Treatment with antibiotics and ZnO showed no effects on diversity indices while the analyses of microbiota taxonomic and functional profiles revealed increased abundance of taxa and metabolic functions associated with Phascolarctobacterium succinatutens or different species of Prevotella spp. on the Treated farms, and with Megasphaera elsdenii and Escherichia coli on the ZnO-free farms. The analysis of diarrhoea samples revealed that the treatment favoured the microbiota transition or maturation from 0dpw to 14dpw in Treated farms, resembling the composition of healthy animals, when compared to diarrhoea from ZnO-free farms, which were linked in composition to 0dpw samples. Discussion: The results provide a comprehensive overview of the beneficial effects of ZnO and antibiotics in PWD in the microbiota transition after weaning, preventing the overgrowth of pathogens such as pathogenic E. coli and revealing the key aspects in microbiota maturation that antibiotics or ZnO alternatives should fulfil.

Association between exposure to air pollution and blood lipids in the general population of Spain.

BACKGROUND AND AIMS: We aimed to assess the associations of exposure to air pollutants and standard and advanced lipoprotein measures, in a nationwide sample representative of the adult population of Spain. METHODS: We included 4647 adults (>18 years), participants in the national, cross-sectional, population-based di@bet.es study, conducted in 2008-2010. Standard lipid measurements were analysed on an Architect C8000 Analyzer (Abbott Laboratories SA). Lipoprotein analysis was made by an advanced 1 H-NMR lipoprotein test (Liposcale®). Participants were assigned air pollution concentrations for particulate matter <10 µm (PM10 ), <2.5 µm (PM2.5 ) and nitrogen dioxide (NO2 ), corresponding to the health examination year, obtained by modelling combined with measurements taken at air quality stations (CHIMERE chemistry-transport model). RESULTS: In multivariate linear regression models, each IQR increase in PM10 , PM2.5 and NO2 was associated with 3.3%, 3.3% and 3% lower levels of HDL-c and 1.3%, 1.4% and 1.1% lower HDL particle (HDL-p) concentrations (p < .001 for all associations). In multivariate logistic regression, there was a significant association between PM10 , PM2.5 and NO2 concentrations and the odds of presenting low HDL-c (<40 mg/dL), low HDL-p (

Principal Component Analysis Applied to Digital Pulse Shape Analysis for Isotope Discrimination.

Digital pulse shape analysis (DPSA) techniques are becoming increasingly important for the study of nuclear reactions since the development of fast digitizers. These techniques allow us to obtain the (A, Z) values of the reaction products impinging on the new generation solid-state detectors. In this paper, we present a computationally efficient method to discriminate isotopes with similar energy levels, with the aim of enabling the edge-computing paradigm in future field-programmable gate-array-based acquisition systems. The discrimination of isotope pairs with analogous energy levels has been a topic of interest in the literature, leading to various solutions based on statistical features or convolutional neural networks. Leveraging a valuable dataset obtained from experiments conducted by researchers in the FAZIA Collaboration at the CIME cyclotron in GANIL laboratories, we aim to establish a comparative analysis regarding selectivity and computational efficiency, as this dataset has been employed in several prior publications. Specifically, this work presents an approach to discriminate between pairs of isotopes with similar energies, namely, 12,13C, 36,40Ar, and 80,84Kr, using principal component analysis (PCA) for data preprocessing. Consequently, a linear and cubic machine learning (ML) support vector machine (SVM) classification model was trained and tested, achieving a high identification capability, especially in the cubic one. These results offer improved computational efficiency compared to the previously reported methodologies.

Estimación del envejecimiento en población laboral y relación con salud psicofísica y condiciones de trabajo / Estimation of aging in the working population and relationship with psychophysical health and working conditions

Introducción:El envejecimiento de la población conlleva una mayor prevalencia de trabajadores con patología psicofísica y cognitiva con riesgo de fragilidad.Objetivo:Estimar la relación entre envejecimiento asociado a la edad en hombres y mujeres, y la salud psicofísica, emocional y deterioro cognitivo en población laboral y su repercusión según tipo de trabajo y turnicidad.Material y Método:Estudio transversal en 389 trabajadores. Se valora <50 y ≥50 años con prensión manual, circunferencia del gemelo, Fragilidad-Frail, depresión-Beck, Ansiedad-Estado-Rasgo y deterioro cognitivo-Pfeiffer y la influencia del tipo de trabajo y turnicidad.Resultados:Existe mayor fragilidad-Frail en hombres ≥ 50 años (p<0,05). El resto de variables relacionadas con estado físico, emocional y cognitivo no muestra diferencias por edad, ni con el tipo de trabajo y turnicidad (p>0,05).Conclusiones:La fragilidad estimada con el cuestionario de Frail muestra los resultados más precoces de fragilidad en hombres ≥ 50 años. (AU)

Introduction:The aging of the population leads to a higher prevalence of workers with psychophysical and cognitive pathologies at risk of frailty.Objective:To estimate the relationship between age-associated aging in men and women and psychophysical, emotional health, and cognitive impairment in the working population and its impact according to the type of work and shift work.Material and Method:Cross-sectional study with 389 workers. We assessed individuals aged <50 and ≥50 years using handgrip strength, calf circumference, Frailty-Frail assessment, Beck Depression Inventory for depression, State-Trait Anxiety Inventory for anxiety, and Pfeiffer test for cognitive impairment, while also considering the influence of the type of work and shift work.Results:There is a higher prevalence of frailty in men aged ≥50 years (p<0.05). The rest of the variables related to physical, emotional, and cognitive status do not show significant differences based on age, type of work, or shift work (p>0.05).Conclusions:Frailty, as assessed by the Frail questionnaire, reveals the earliest signs of frailty in men aged ≥50 years. (AU)

Silver-Exchanged Zeolite Y Catalyzes a Selective Insertion of Carbenes into C-H and O-H Bonds.

Commercially available zeolite Y modulates the catalytic activity and selectivity of ultrasmall silver species during the Buchner reaction and the carbene addition to methylene and hydroxyl bonds, by simply exchanging the counter cations of the zeolite framework. The zeolite acts as a macroligand to tune the silver catalytic site, enabling the use of this cheap and recyclable solid catalyst for the in situ formation of carbenes from diazoacetate and selective insertion in different C-H (i.e., cyclohexane) and C-O (i.e., water) bonds. The amount of catalyst in the reaction can be as low as ≤0.1 mol % silver. Besides, this reactivity allows deeply drying the HY zeolite framework by making the strongly adsorbed water molecules react with the in situ formed carbenes.

Predictors of mortality in patients with COVID-19 by flow cytometry.

Despite the great impact of severe acute respiratory syndrome caused by coronavirus 2 (SARS-CoV-2), we still lack techniques that allow us to anticipate the natural history of the disease in order to avoid or shorten the clinical period of the disease. The values of nine cytokines were measured in COVID-19+ patients admitted to the Hospital Universitario Reina Sofía (HURS) using flow cytometry. The cytokines measured are IL-1ß, IL-6, MCP-1, IP-10, IL-10, IL-8, IL-12, IFN-γ and TNF-α. Given the absence of previous studies on cytokine values in healthy patients using the flow cytometry technique, and the low availability of resources in the first waves of COVID-19, a control group was lacking, all resources were employed for monitoring sick patients. However, this study has revealed a greater increase in two specific cytokines, which are also found to be higher than the rest in healthy patients: MCP-1 and IP-10, which are mainly responsible for cytokine storm and post-disease thrombosis.

Rescue of Normal Excitability in LGI1-Deficient Epileptic Neurons.

Leucine-rich glioma inactivated 1 (LGI1) is a glycoprotein secreted by neurons, the deletion of which leads to autosomal dominant lateral temporal lobe epilepsy. We previously showed that LGI1 deficiency in a mouse model (i.e., knock-out for LGI1 or KO-Lgi1) decreased Kv1.1 channel density at the axon initial segment (AIS) and at presynaptic terminals, thus enhancing both intrinsic excitability and glutamate release. However, it is not known whether normal excitability can be restored in epileptic neurons. Here, we show that the selective expression of LGI1 in KO-Lgi1 neurons from mice of both sexes, using single-cell electroporation, reduces intrinsic excitability and restores both the Kv1.1-mediated D-type current and Kv1.1 channels at the AIS. In addition, we show that the homeostatic-like shortening of the AIS length observed in KO-Lgi1 neurons is prevented in neurons electroporated with the Lgi1 gene. Furthermore, we reveal a spatial gradient of intrinsic excitability that is centered on the electroporated neuron. We conclude that expression of LGI1 restores normal excitability through functional Kv1 channels at the AIS.SIGNIFICANCE STATEMENT The lack of leucine-rich glioma inactivated 1 (LGI1) protein induces severe epileptic seizures that leads to death. Enhanced intrinsic and synaptic excitation in KO-Lgi1 mice is because of the decrease in Kv1.1 channels in CA3 neurons. However, the conditions to restore normal excitability profile in epileptic neurons remain to be defined. We show here that the expression of LGI1 in KO-Lgi1 neurons in single neurons reduces intrinsic excitability, and restores both the Kv1.1-mediated D-type current and Kv1.1 channels at the axon initial segment (AIS). Furthermore, the homeostatic shortening of the AIS length observed in KO-Lgi1 neurons is prevented in neurons in which the Lgi1 gene has been rescued. We conclude that LGI1 constitutes a critical factor to restore normal excitability in epileptic neurons.

SARS-CoV-2 accessory proteins involvement in inflammatory and profibrotic processes through IL11 signaling.

SARS-CoV-2, the cause of the COVID-19 pandemic, possesses eleven accessory proteins encoded in its genome. Their roles during infection are still not completely understood. In this study, transcriptomics analysis revealed that both WNT5A and IL11 were significantly up-regulated in A549 cells expressing individual accessory proteins ORF6, ORF8, ORF9b or ORF9c from SARS-CoV-2 (Wuhan-Hu-1 isolate). IL11 is a member of the IL6 family of cytokines. IL11 signaling-related genes were also differentially expressed. Bioinformatics analysis disclosed that both WNT5A and IL11 were involved in pulmonary fibrosis idiopathic disease and functional assays confirmed their association with profibrotic cell responses. Subsequently, data comparison with lung cell lines infected with SARS-CoV-2 or lung biopsies from patients with COVID-19, evidenced altered profibrotic gene expression that matched those obtained in this study. Our results show ORF6, ORF8, ORF9b and ORF9c involvement in inflammatory and profibrotic responses. Thus, these accessory proteins could be targeted by new therapies against COVID-19 disease.

Effects of ozone therapy on anxiety and depression in patients with refractory symptoms of severe diseases: a pilot study.

Background: Patients with refractory symptoms of severe diseases frequently experience anxiety, depression, and an altered health-related quality of life (HRQOL). Some publications have described the beneficial effect of ozone therapy on several symptoms of this kind of patient. The aim of this study was to preliminarily evaluate, in patients treated because of refractory symptoms of cancer treatment and advanced nononcologic diseases, if ozone therapy has an additional impact on self-reported anxiety and depression. Methods: Before and after ozone treatment, we assessed (i) anxiety and depression according to the Hospital Anxiety and Depression Scale (HADS); (ii) the HRQOL (according to the EQ-5D-5L questionnaire), which includes a dimension on anxiety and depression and a visual analog scale (VAS) measuring self-perceived general health. Results: Before ozone therapy, 56% of patients were on anxiolytic and/or antidepressant treatment. Before and after ozone therapy, the anxiety and depression HADS subscales (i) significantly correlated with the anxiety/depression dimension of the EQ-5D-5L questionnaire and (ii) inversely correlated with the health status as measured by the VAS. After ozone therapy, we found a significant improvement in anxiety and depression measured by both the (i) HADS subscales and (ii) EQ-5D-5L questionnaire. Conclusion: The addition of ozone therapy for patients with refractory symptoms of cancer treatment and advanced chronic nononcologic diseases can decrease anxiety and depression severity levels. Additional, more focused studies are ongoing to provide the needed explanatory information for this finding.

Metalloenzymes play major roles to achieve high-rate nitrogen removal in N-damo communities: Lessons from metaproteomics.

Nitrite-driven anaerobic methane oxidation (N-damo) is a promising biological process to achieve carbon-neutral wastewater treatment solutions, aligned with the sustainable development goals. Here, the enzymatic activities in a membrane bioreactor highly enriched in N-damo bacteria operated at high nitrogen removal rates were investigated. Metaproteomic analyses, with a special focus on metalloenzymes, revealed the complete enzymatic route of N-damo including their unique nitric oxide dismutases. The relative protein abundance evidenced that "Ca. Methylomirabilis lanthanidiphila" was the predominant N-damo species, attributed to the induction of its lanthanide-binding methanol dehydrogenase in the presence of cerium. Metaproteomics also disclosed the activity of the accompanying taxa in denitrification, methylotrophy and methanotrophy. The most abundant functional metalloenzymes from this community require copper, iron, and cerium as cofactors which was correlated with the metal consumptions in the bioreactor. This study highlights the usefulness of metaproteomics for evaluating the enzymatic activities in engineering systems to optimize microbial management.

Artificial intelligence for detection of ventricular oversensing: Machine learning approaches for noise detection within nonsustained ventricular tachycardia episodes remotely transmitted by pacemakers and implantable cardioverter-defibrillators.

BACKGROUND: Pacemakers (PMs) and implantable cardioverter-defibrillators (ICDs) increasingly automatically record and remotely transmit nonsustained ventricular tachycardia (NSVT) episodes, which may reveal ventricular oversensing. OBJECTIVES: We aimed to develop and validate a machine learning algorithm that accurately classifies NSVT episodes transmitted by PMs and ICDs in order to lighten health care workload burden and improve patient safety. METHODS: PMs or ICDs (Boston Scientific, St Paul, MN) from 4 French hospitals with ≥1 transmitted NSVT episode were split into 3 subgroups: training set, validation set, and test set. Each NSVT episode was labeled as either physiological or nonphysiological. Four machine learning algorithms-2DTF-CNN, 2D-DenseNet, 2DTF-VGG, and 1D-AgResNet-were developed using training and validation data sets. Accuracies of the classifiers were compared with an analysis of the remote monitoring team of the Bordeaux University Hospital using F2 scores (favoring sensitivity over predictive positive value) using an independent test set. RESULTS: A total of 807 devices transmitted 10,471 NSVT recordings (82% ICD; 18% PM), of which 87 devices (10.8%) transmitted 544 NSVT recordings with nonphysiological signals. The classification by the remote monitoring team resulted in an F2 score of 0.932 (sensitivity 95%; specificity 99%) The 4 machine learning algorithms showed high and comparable F2 scores (2DTF-CNN: 0.914; 2D-DenseNet: 0.906; 2DTF-VGG: 0.863; 1D-AgResNet: 0.791), and only 1D-AgResNet had significantly different labeling from that of the remote monitoring team. CONCLUSION: Machine learning algorithms were accurate in detecting nonphysiological signals within electrograms transmitted by PMs and ICDs. An artificial intelligence approach may render remote monitoring less resourceful and improve patient safety.

Evidence for Ruthenium(II) Peralkene Complexes as Catalytic Species during the Isomerization of Terminal Alkenes in Solution.

The isomerization (chain-walking) reaction of terminal to internal alkenes is catalyzed by part-per-million amounts of practically any Ru source when the reaction is carried out with a neat terminal alkene. Here, we provide evidence that the soluble starting Ru sources evolve to catalytically active peralkene Ru(II) species under reaction conditions. These species may also explain the isomerization products found during other Ru-catalyzed alkene processes, i.e., alkene metathesis reactions. A Finke-Watzky mechanism for catalyst formation is consistent with the evidence obtained.

How efficiently does a metabolically enhanced system with denitrifying anaerobic methane oxidizing microorganisms remove antibiotics?

In this work, the novel N-damo (Nitrite dependent anaerobic methane oxidation) process was investigated at high biomass activities for its potential to remove simultaneously nitrite and methane, as well as selected antibiotics commonly found in sewage in trace amounts. For this purpose, two MBRs were operated at three high nitrite loading rates (NLRs), namely 76 ± 9.9, 161.5 ± 11.4 and 215.2 ± 24.2 mg N-NO⁻2 L-1 d-1, at long-term operation. The MBRs performance achieved a significantly high nitrite removal activity for an N-damo process (specific denitrifying activity of up to 540 mg N-NO⁻2 g-1 VSS d-1), even comparable to heterotrophic denitrification values. In this study, we have implemented a novel operational strategy that sets our work apart from previous studies with similar bioreactors. Specifically, we have introduced Cerium as a trace element in the feeding medium, which serves as a key differentiating factor. It allowed maintaining a stable reactor operation at high NLRs. Microbial community composition evidenced that both MBRs were dominated with N-damo bacteria (67-87% relative abundance in period III and I, respectively). However, a decrease in functional N-damo bacteria (Candidatus Methylomirabilis) abundance was observed during the increase in biomass activity and concentration, concomitantly with an increase of the other minor families (Hypomicrobiaceae and Xanthobacteraceae). Most of the selected antibiotics showed high biotransformation such as sulfamethoxazole, trimethoprim, cefalexin and azithromycin, whereas others such as roxithromycin and clarithromycin were only partially degraded (20-35%). On the contrary, ciprofloxacin showed almost no removal. Despite the metabolic enhancement, no apparent increase on the antibiotic removal was observed throughout the operation, suggesting that microbiological composition was of greater influence than its primary metabolic activity on the removal of antibiotics.