Entangled microwaves as a resource for entangling spatially separate solid-state qubits: Superconducting qubits, nitrogen-vacancy centers, and magnetic molecules

13 págs.; 10 figs.; 2 apps.Quantum correlations present in a broadband two-line squeezed microwave state can induce entanglement in a spatially separated bipartite system consisting of either two single qubits or two-qubit ensembles. By using an appropriate master equation for a bipartite quantum system in contact with two separate but entangled baths, the generating entanglement process in spatially separated quantum systems is thoroughly characterized. Decoherence thermal effects on the entanglement transfer are also discussed. Our results provide evidence that this entanglement transfer by dissipation is feasible, yielding to a steady-state amount of entanglement in the bipartite quantum system which can be optimized for a wide range of realistic physical systems that include state-of-the-art experiments with nitrogen-vacancy centers in diamond, superconducting qubits, or even magnetic molecules embedded in a crystalline matrix. ©2016 American Physical SocietyA.V.G., F.J.R., and L.Q. acknowledge financial support from Facultad de Ciencias at UniAndes-2015 Project “Transfer of Correlations from Non-classically Correlated Reservoirs to Solid State Systems” and Project “Quantum Control of Non-equilibrium Hybrid Systems-Part II,” UniAndes-2015. J.J.G.R. acknowledges support from Spanish Mineco Project No. FIS2012-33022, from EU FP7 Project PROMISCE, from CAM Research Network QUITEMAD+.Peer Reviewe

New microRNA biomarkers for drug-induced steatosis and their potential to predict the contribution of drugs to non-alcoholic fatty liver disease

Background and Aims: Drug-induced steatosis is a major reason for drug failure in clinical trials and post-marketing withdrawal; and therefore, predictive biomarkers are essential. These could be particularly relevant in non-alcoholic fatty liver disease (NAFLD), where most patients show features of the metabolic syndrome and are prescribed with combined chronic therapies, which can contribute to fatty liver. However, specific biomarkers to assess the contribution of drugs to NAFLD are lacking. We aimed to find microRNAs (miRNAs) responsive to steatotic drugs and to investigate if they could become circulating biomarkers for drug-induced steatosis. Methods: Human HepG2 cells were treated with drugs and changes in miRNA levels were measured by microarray and qRT-PCR. Drug-induced fat accumulation in HepG2 was analyzed by high-content screening and enzymatic methods. miRNA biomarkers were also analyzed in the sera of 44 biopsy-proven NAFLD patients and in 10 controls. Results: We found a set of 10 miRNAs [miR-22-5p, -3929, -24-2-5p, -663a, -29a-3p, -21 (5p and 3p), -27a-5p, -1260 and -202-3p] that were induced in human HepG2 cells and secreted to the culture medium upon incubation with model steatotic drugs (valproate, doxycycline, cyclosporin A and tamoxifen). Moreover, cell exposure to 17 common drugs for NAFLD patients showed that some of them (e.g., irbesartan, fenofibrate, and omeprazole) also induced these miRNAs and increased intracellular triglycerides, particularly in combinations. Finally, we found that most of these miRNAs (60%) were detected in human serum, and that NAFLD patients under fibrates showed both induction of these miRNAs and a more severe steatosis grade. Conclusion: Steatotic drugs induce a common set of hepatic miRNAs that could be used in drug screening during preclinical development. Moreover, most of these miRNAs are serum circulating biomarkers that could become useful in the diagnosis of iatrogenic steatosis

Utility of PHQ-2, PHQ-8 and PHQ-9 for detecting major depression in primary health care: a validation study in Spain

Background: Primary health care (PHC) professionals may play a crucial role in improving early diagnosis of depressive disorders. However, only 50% of cases are detected in PHC. The most widely used screening instrument for major depression is the Patient Health Questionnaire (PHQ), including the two-, eight- and nine-item versions. Surprisingly, there is neither enough evidence about the validity of PHQ in PHC patients in Spain nor indications about how to interpret the total scores. This study aimed to gather validity evidence to support the use of the three PHQ versions to screen for major depression in PHC in Spain. Additionally, the present study provided information for helping professionals to choose the best PHQ version according to the context. Methods: The sample was composed of 2579 participants from 22 Spanish PHC centers participating in the EIRA-3 study. The reliability and validity of the three PHQ versions for Spanish PHC patients were assessed based on responses to the questionnaire. Results: The PHQ-8 and PHQ-9 showed high internal consistency. The results obtained confirm the theoretically expected relationship between PHQ results and anxiety, social support and health-related QoL. A single-factor solution was confirmed. Regarding to the level of agreement with the CIDI interview (used as the criterion), our results indicate that the PHQ has a good discrimination power. The optimal cut-off values were: ⩾2 for PHQ-2, ⩾7 for PHQ-8 and ⩾8 for PHQ-9. Conclusions: PHQ is a good and valuable tool for detecting major depression in PHC patients in Spain

Utility of PHQ-2, PHQ-8 and PHQ-9 for detecting major depression in primary health care: a validation study in Spain

Primary health care (PHC) professionals may play a crucial role in improving early diagnosis of depressive disorders. However, only 50% of cases are detected in PHC. The most widely used screening instrument for major depression is the Patient Health Questionnaire (PHQ), including the two-, eight- and nine-item versions. Surprisingly, there is neither enough evidence about the validity of PHQ in PHC patients in Spain nor indications about how to interpret the total scores. This study aimed to gather validity evidence to support the use of the three PHQ versions to screen for major depression in PHC in Spain. Additionally, the present study provided information for helping professionals to choose the best PHQ version according to the context

SARS-CoV-2 ORF8 accessory protein is a virulence factor

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encodes six accessory proteins (3a, 6, 7a, 7b, 8, and 9b) for which limited information is available on their role in pathogenesis. We showed that the deletion of open reading frames (ORFs) 6, 7a, or 7b individually did not significantly impact viral pathogenicity in humanized K18-hACE2 transgenic mice. In contrast, the deletion of ORF8 partially attenuated SARS-CoV-2, resulting in reduced lung pathology and 40% less mortality, indicating that ORF8 is a critical determinant of SARS-CoV-2 pathogenesis. Attenuation of SARS-CoV-2-∆8 was not associated with a significant decrease in replication either in the lungs of mice or in organoid-derived human airway cells. An increase in the interferon signaling at early times post-infection (1 dpi) in the lungs of mice and a decrease in the pro-inflammatory and interferon response at late times post-infection, both in the lungs of mice (6 dpi) and in organoid-derived human airway cells [72 hours post-infection (hpi)], were observed. The early, but not prolonged, interferon response along with the lower inflammatory response could explain the partial attenuation of SARS-CoV-∆8. The presence of ORF8 in SARS-CoV-2 was associated with an increase in the number of macrophages in the lungs of mice. In addition, the supernatant of SARS-CoV-2-WT (wild-type)-infected organoid-derived cells enhanced the activation of macrophages as compared to SARS-CoV-2-∆8-infected cells. These results show that ORF8 is a virulence factor involved in inflammation that could be targeted in COVID-19 therapies. IMPORTANCE The relevance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ORF8 in the pathogenesis of COVID-19 is unclear. Virus natural isolates with deletions in ORF8 were associated with wild milder disease, suggesting that ORF8 might contribute to SARS-CoV-2 virulence. This manuscript shows that ORF8 is involved in inflammation and in the activation of macrophages in two experimental systems: humanized K18-hACE2 transgenic mice and organoid-derived human airway cells. These results identify ORF8 protein as a potential target for COVID-19 therapies.</p

SARS-CoV-2 ORF8 accessory protein is a virulence factor

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encodes six accessory proteins (3a, 6, 7a, 7b, 8, and 9b) for which limited information is available on their role in pathogenesis. We showed that the deletion of open reading frames (ORFs) 6, 7a, or 7b individually did not significantly impact viral pathogenicity in humanized K18-hACE2 transgenic mice. In contrast, the deletion of ORF8 partially attenuated SARS-CoV-2, resulting in reduced lung pathology and 40% less mortality, indicating that ORF8 is a critical determinant of SARS-CoV-2 pathogenesis. Attenuation of SARS-CoV-2-∆8 was not associated with a significant decrease in replication either in the lungs of mice or in organoid-derived human airway cells. An increase in the interferon signaling at early times post-infection (1 dpi) in the lungs of mice and a decrease in the pro-inflammatory and interferon response at late times post-infection, both in the lungs of mice (6 dpi) and in organoid-derived human airway cells [72 hours post-infection (hpi)], were observed. The early, but not prolonged, interferon response along with the lower inflammatory response could explain the partial attenuation of SARS-CoV-∆8. The presence of ORF8 in SARS-CoV-2 was associated with an increase in the number of macrophages in the lungs of mice. In addition, the supernatant of SARS-CoV-2-WT (wild-type)-infected organoid-derived cells enhanced the activation of macrophages as compared to SARS-CoV-2-∆8-infected cells. These results show that ORF8 is a virulence factor involved in inflammation that could be targeted in COVID-19 therapies. IMPORTANCE The relevance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ORF8 in the pathogenesis of COVID-19 is unclear. Virus natural isolates with deletions in ORF8 were associated with wild milder disease, suggesting that ORF8 might contribute to SARS-CoV-2 virulence. This manuscript shows that ORF8 is involved in inflammation and in the activation of macrophages in two experimental systems: humanized K18-hACE2 transgenic mice and organoid-derived human airway cells. These results identify ORF8 protein as a potential target for COVID-19 therapies.</p

Augmentation of EMDR with multifocal transcranial current stimulation (MtCS) in the treatment of fibromyalgia : study protocol of a double-blind randomized controlled exploratory and pragmatic trial

Fibromyalgia (FM) is a generalized, widespread chronic pain disorder affecting 2.7% of the general population. In recent years, different studies have observed a strong association between FM and psychological trauma. Therefore, a trauma-focused psychotherapy, such as eye movement desensitization and reprocessing (EMDR), combined with a non-invasive brain stimulation technique, such as multifocal transcranial current stimulation (MtCS), could be an innovative adjunctive treatment option. This double-blind randomized controlled trial (RCT) analyzes if EMDR therapy is effective in the reduction of pain symptoms in FM patients and if its potential is boosted with the addition of MtCS. Forty-five patients with FM and a history of traumatic events will be randomly allocated to Waiting List, EMDR + active-MtCS, or EMDR + sham-MtCS. Therapists and patients will be kept blind to MtCS conditions, and raters will be kept blind to both EMDR and MtCS. All patients will be evaluated at baseline, post-treatment, and follow-up at 6 months after post-treatment. Evaluations will assess the following variables: sociodemographic data, pain, psychological trauma, sleep disturbance, anxiety and affective symptoms, and wellbeing. This study will provide evidence of whether EMDR therapy is effective in reducing pain symptoms in FM patients, and whether the effect of EMDR can be enhanced by MtCS. ClinicalTrials.gov . Registered on 2 August 2019. The online version contains supplementary material available at 10.1186/s13063-021-05042-w

La obesidad es una enfermedad crónica. Posicionamiento del grupo de trabajo de Diabetes, Obesidad y Nutrición de la Sociedad Española de Medicina Interna (SEMI) por un abordaje centrado en la persona con obesidad

Introducción: La obesidad es una enfermedad metabólica crónica, compleja y multifactorial, implicada en el desarrollo de enfermedades crónicas no transmisibles como la diabetes mellitus tipo 2, las enfermedades cardiovasculares y el cáncer. Es necesario que la atención a las personas con obesidad sea una parte esencial de la visión integral que la medicina interna aporta a la persona enferma. Material y métodos: Entre septiembre de 2019 y enero de 2020 se difundió una encuesta en línea a los socios de la Sociedad Espanola ˜ de Medicina Interna; se elaboró un análisis DAFO con las respuestas y, mediante la técnica de Grupo Nominal, se elaboraron las recomendaciones. Resultados: Obtuvimos 599 respuestas. Edad media 44,4 ± 11 anos; ˜ 52,1% mujeres. El 91,8% de los internistas evalúa a los pacientes para descartar las comorbilidades asociadas a la obesidad, principalmente la diabetes mellitus tipo 2 (96,2%), la enfermedad cardiovascular (88,9%) o el síndrome de hipoventilación asociada a obesidad (73%), entre otros. El 79,9% proporciona indicaciones sobre modificación del estilo de vida. El 64,1% y el 74,9% conocen las indicaciones de los fármacos y de la cirugía bariátrica, respectivamente. El 93,8% y el 83% consideran la obesidad y el sobrepeso una enfermedad crónica y el 88,7% una patología propia del internista, debiendo tener un papel activo y protagonista en su tratamiento (85,3%). Conclusiones: El objetivo del presente documento es dar a conocer el grado de conocimiento y de sensibilidad de los internistas frente al manejo de la obesidad y elaborar un consenso de recomendaciones de la Sociedad Espanola ˜ de Medicina Interna basadas en la evidencia científica y en la opinión de sus miembros