Multimodal decoding of human liver regeneration.

The liver has a unique ability to regenerate1,2; however, in the setting of acute liver failure (ALF), this regenerative capacity is often overwhelmed, leaving emergency liver transplantation as the only curative option3-5. Here, to advance understanding of human liver regeneration, we use paired single-nucleus RNA sequencing combined with spatial profiling of healthy and ALF explant human livers to generate a single-cell, pan-lineage atlas of human liver regeneration. We uncover a novel ANXA2+ migratory hepatocyte subpopulation, which emerges during human liver regeneration, and a corollary subpopulation in a mouse model of acetaminophen (APAP)-induced liver regeneration. Interrogation of necrotic wound closure and hepatocyte proliferation across multiple timepoints following APAP-induced liver injury in mice demonstrates that wound closure precedes hepatocyte proliferation. Four-dimensional intravital imaging of APAP-induced mouse liver injury identifies motile hepatocytes at the edge of the necrotic area, enabling collective migration of the hepatocyte sheet to effect wound closure. Depletion of hepatocyte ANXA2 reduces hepatocyte growth factor-induced human and mouse hepatocyte migration in vitro, and abrogates necrotic wound closure following APAP-induced mouse liver injury. Together, our work dissects unanticipated aspects of liver regeneration, demonstrating an uncoupling of wound closure and hepatocyte proliferation and uncovering a novel migratory hepatocyte subpopulation that mediates wound closure following liver injury. Therapies designed to promote rapid reconstitution of normal hepatic microarchitecture and reparation of the gut-liver barrier may advance new areas of therapeutic discovery in regenerative medicine.

Executive summary of the 2023 update on the consensus regarding basic conduct during hospital admission for patients with acute heart failure.

Acute heart failure (AHF) is associated with significant morbidity and mortality and it stands as the primary cause of hospitalization for individuals over the age of 65 in Spain. This document outlines the main recommendations as follows: (1) Upon admission, it is crucial to conduct a comprehensive assessment, taking into account the patient's standard treatment and comorbidities, as these factors determine the prognosis of the disease. (2) During the initial hours of hospital care, prioritizing decongestive treatment is essential. It is recommended to adopt an early staged diuretic therapeutic approach based on the patient's response. (3) In order to manage patients in the stable phase, it is advisable to consider initiating and/or adjusting evidence-based drug treatments such as sacubitril/valsartan or angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, beta blockers, aldosterone antagonists, and SGLT2 inhibitors. (4) Upon hospital discharge, utilizing a checklist is recommended to optimize the patient's management and identify the most efficient options for ensuring continuity of care post-discharge.

Norovirus infection as a model of chronic or recurrent infection in common variable immunodeficiency.

Common variable immunodeficiency (CVID) is the most frequent symptomatic primary immunodeficiency (PID) in general population. PID are genetic diseases that share a dysfunction in the immune system entailing a greater risk of both chronic and recurrent infections. These patients can also develop chronic gastrointestinal infections caused by norovirus with persistent viral dissemination, which can be detected months after primoinfection. Additionally, a proportion of CVID patients show a typical severe enteropathy presenting with recurrent diarrhoea, intestinal malabsorption, inflammatory lesions, and villous atrophy. Some studies have related this enteropathy with chronic intestinal infection caused by norovirus.

Draft Genome Sequence of Pseudomonas sp. Strain RGM 3321, a Phyllosphere Endophyte from Fragaria chiloensis subsp. chiloensis f. patagonica.

Pseudomonas sp. strain RGM 3321 is a phyllosphere endophyte from Fragaria chiloensis subsp. chiloensis f. patagonica that harbors genes associated with plant growth promotion pathways, as well as genes typically found in plant pathogens.

Efecto perjudicial de la pandemia por SARS-CoV-2 en la sintomatología digestiva en pacientes con síndrome de intestino irritable / Detrimental impact of SARS-CoV-2 pandemic in the symptomatology of patients with irritable bowel syndrome

Irritable Bowel Syndrome (IBS) is a more frequent disorder in the brain-gut axis interaction in the world. COVID-19 has affected the population's mental health, and its impact on clinical severity in patients with IBS is unknown. Objective: To evaluate the effect of psychosocial stress produced by the pandemic on the severity of gastrointestinal symptoms. Methodology: 54 women and three men with IBS were interviewed by telephone. Factors associated with quality of life, comorbidities, IBS subtype, and COVID-19 diagnosis were asked. Calls were developed between June 2020 to January 2021. Results: 75% had Diarrheal IBS (IBS-D), 67% had comorbidities, 47% with busy work, and 70% in person, five patients (9%) were diagnosed with COVID-19. Of the total, 88% referred to change in gastrointestinal symptoms, 56% increased abdominal pain, and 95% bloating. Abdominal pain was negatively associated with quality of life (p < 0.036), and the incomplete evacuation's sensation positively with difficulty sleeping (p < 0.034). Conclusion: In this study, IBS patients interviewed by telephone reported higher abdominal pain and subjective bloating associated with the pandemic by SARS-CoV-2. Keywords: Irritable

El Síndrome de Intestino Irritable (SII) es uno de los trastornos en la interacción cerebrointestino más frecuentes en el mundo. La pandemia COVID-19 ha afectado la salud mental de la población, siendo desconocido su impacto en la severidad clínica en pacientes con SII. Objetivo: Evaluar el efecto del estrés psicosocial producido por la pandemia en la severidad de síntomas gastrointestinales de pacientes con SII. Metodología: 54 mujeres y 3 hombres con SII fueron entrevistados vía telefónica. Se preguntó por factores asociados a calidad de vida, comorbilidades, subtipo de SII y diagnóstico de COVID-19. Las llamadas se realizaron entre junio de 2020 hasta enero de 2021. Resultados: Un 75% presentó SII Diarreico (SII-D), el 67% comorbilidades, el 47% con trabajo activo y 70% presencial, 5 pacientes (9%) diagnosticados COVID-19. Del total, 88% refirió cambio en síntomas gastrointestinales, 56% aumentó el dolor abdominal y 95% la distensión abdominal. El dolor abdominal se asoció negativamente con la calidad de vida (p < 0,036), y la sensación de evacuación incompleta positivamente con la dificultad para dormir (p < 0,034). Conclusión: En este estudio, los pacientes con SII entrevistados vía telefónica reportaron mayor dolor y distensión abdominal subjetiva asociado a la pandemia por SARS-CoV-2.

Pointing Out Some Issues Regarding Reproduction Management in Murciano-Granadina Goats.

Two of the most important problems in high-yielding dairy goat farms are early and accurate pregnancy diagnosis and the appropriate dry off of lactating does before the next kidding. The hypothesis posits that it could be possible to identify pregnant does through maximum progesterone milk levels at any time during the pregnancy, and that there is an optimal time to apply a lactation inhibitor to help dry off lactating does. Therefore, 114 Murciano-Granadina breed goats were used, from which 74 goats were inseminated at week 20 of lactation and samples of milk from pregnant and non-pregnant goats were taken at two-week intervals. The average maximum progesterone milk levels were higher outside the natural breeding season (40° latitude) than in the breeding season (11.6 ± 1.13 vs. 8.6 ± 1.02 ng/mL), although the levels from pregnant and non-pregnant goats were similar (10.85 ± 1.3 vs. 9.74 ± 1.6 ng/mL), except in the case of pregnancy with four foetuses (12.5 ± 1.3 ng/mL). Milk yield at mating does not affect fertility until a value of at least 3250 mL/day. Pregnancy started to affect milk yield up to the +7th week and was 59.9% lower in the +10th week after mating, so the use of lactation inhibitors could be more effective from this latter week. In conclusion, the results show that it is not possible to detect gestation in goats reliably through the maximum concentration of progesterone in milk at any time during lactation, except in the case of goats gestating four foetuses, that the milk yield of goats at mating does not affect fertility until a value of at least 3250 mL/day, and that from the 10th week post-mating, the application of lactation inhibitors would be optimal.

Consensus on basic conduct during the hospital admission of patients with acute heart failure.

Acute heart failure (AHF) is a highly prevalent clinical entity in individuals older than 45 years in Spain. AHF is associated with significant morbidity and mortality and is the leading cause of hospitalisation for individuals older than 65 years in Spain, a quarter of whom die within 1 year of the hospitalisation. In recent years, there has been an upwards trend in hospitalisations for AHF, which increased 76.7% from 2003 to 2013. Readmissions at 30 days for AHF have also increased (from 17.6% to 22.1%), at a relative mean rate of 1.36% per year, with the consequent increase in the use of resources and the economic burden for the healthcare system. The aim of this document (developed by the Heart Failure and Atrial Fibrillation Group of the Spanish Society of Internal Medicine) is to guide specialists on the most important aspects of treatment and follow-up for patients with AHF during hospitalisation and the subsequent follow-up. The main recommendations listed in this document are as follows: 1) At admission, perform a comprehensive assessment, considering the patient's standard treatment and comorbidities, given that these determine the disease prognosis to a considerable measure. 2) During the first few hours of hospital care, decongestive treatment is a priority, and a staged diuretic therapeutic approach based on the patient's response is recommended. 3) To manage patients in the stable phase, consider starting and/or adjusting evidence-based drug treatment (e.g., sacubitril/valsartan or angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, beta blockers and aldosterone antagonists). 4) At hospital discharge, use a checklist to optimise the patient's management and identify the most efficient options for maintaining continuity of care after discharge.

Enhancing the Capacity of Local Health Departments to Address Birth Equity: The Institute for Equity in Birth Outcomes.

INTRODUCTION: Significant and persistent racial and ethnic disparities exist related to infant mortality and other birth outcomes. Few models exist that aim to prepare organizations to implement essential features, such as community engagement or intervening on social determinants of health. METHODS: Between 2013 and 2015, teams from seven local health departments participated in the Institute for Equity in Birth Outcomes (EI) with the goals of building capacity and implementing changes to address equity in birth outcomes. Four of the teams enrolled in the first cohort (2013-2015), and three enrolled in cohort two (2014-2015). To examine the EI effort and its impact on capacity and implementation of changes, two types of assessments were completed. Capacities of the teams in specific key areas were assessed using "Best Change Process" instruments at the completion of participation in the EI. Teams also documented on an ongoing basis implementation of interventions. The data were analyzed using descriptive statistics and Pearson Correlation tests. RESULTS: Best Change Process capacity scores were higher in the first cohort than in the second and were highly correlated with implementation of changes (Pearson's Correlation = 0.838, p = 0.037). Collectively, the teams implemented about 32 new programs, policies, practices, and systems changes aimed at addressing equity in birth outcomes. Most interventions were based on scientific recommendations and local epidemiologic data. DISCUSSION: The results of the study suggest the EI is a promising approach that may result in strong capacity and ability to implement interventions aimed at addressing equity in birth outcomes.

Influence functions for a hysteretic deformable mirror with a high-density 2D array of actuators.

We present modeling and analysis of a hysteretic deformable mirror where the facesheet interacts with a continuous layer of piezoelectric material that can be actuated distributively by a matrix of electrodes through multiplexing. Moreover, a method to calculate the actuator influence functions is described considering the particular arrangement of electrodes. The results are presented in a semi-analytical model to describe the facesheet's deformation caused by a high-density array of actuators, and validated in a simulation. The proposed modeling of an interconnection layout of electrodes is used to determine the optimal pressures the actuators must exert to achieve a desired surface deformation.

Ethanolic extract of Artemisia campestris subsp. glutinosa (Besser) Batt. inhibits HIV-1 replication in vitro through the activity of terpenes and flavonoids on viral entry and NF-κB pathway.

ETHNO-PHARMACOLOGICAL RELEVANCE: The genus Artemisia spp. is well known for its anti-infectious properties and its high content in anti-infectious compounds, like the well-known sweet wormwood (Artemisia annua L.). Another Artemisia species, Artemisia campestris subsp. glutinosa (Besser) Batt., field wormwood, has been traditionally used as medicinal plant in the Mediterranean region. AIM OF THE STUDY: The aim of this study is to investigate the anti-HIV activity of field wormwood, to identify the compounds responsible for this activity and their structure and mechanism of action. MATERIALS AND METHODS: Antiviral activity of isolated compounds and extracts was evaluated in HIV-1 infections of lymphoblastoid cells. We also evaluated the mechanism of action of isolated compounds. Viral entry was studied comparing the inhibitory effect of isolated compounds on wild type HIV-1 and VSV pseudotyped HIV-1. To assess the viral transcriptional effect, plasmids encoding luciferase reporter genes under the control of the whole genome of HIV-1 or NF-κB or Sp1 transcription factors were transfected in the presence of the compounds under evaluation. Finally, antioxidant activity was assessed by quantitation of reduced and total glutathione in treated cell cultures. RESULTS: Ethanolic and aqueous extracts of Artemisia campestris subsp. glutinosa (Besser) Batt. subsp. glutinosa displayed anti-HIV activity in vitro, although ethanolic extract was more powerful (IC50 14.62 µg/mL). Bio-guided ethanolic extract fractionation leads to the isolation and characterization of two terpenes, damsin and canrenone, and four flavonoids, 6, 2', 4'-trimethoxyflavone, acerosin, cardamonin and xanthomicrol. All the isolated compounds inhibited HIV-1 replication in vitro with IC50 values between the middle nanomolar and the low micromolar range. Their anti-HIV mechanism of action is due to the bloking of viral entry and/or transcription inhibition, without correlation with the antioxidant activity, through interference with the cellular transcription factors NF-κB and Sp1, which are targets that are not currently reached by antiretroviral therapy. CONCLUSION: We describe here the anti-HIV activity of field wormwood, Artemisia campestris subsp. glutinosa (Besser) Batt., and the isolation and study of the mechanism of action of two terpenes and four flavonoids, responsible, at least in part, for its activity, through the inhibition of two different cellular targets affecting the HIV replication cycle. The activity of these compounds in cellular targets could explain why plant extracts can be used in the treatment of different diseases. Besides, the presence of several compounds with dual and different mechanisms of action could prove useful in the treatment of HIV-1 infection, since it could aid to overcome drug resistances and simplify drug therapy. This work is a further step in understanding the anti-infectious activity of wormwood species and their use in treating infectious diseases.

Neoadjuvant chemotherapy in locally advanced colon cancer: a systematic review.

BACKGROUND: Preoperative or neoadjuvant chemotherapy (NAC) has emerged as a novel alternative to treat locally advanced colon cancer (LACC), as in other gastrointestinal malignancies. However, evidence of its efficacy and safety has not yet been gathered in the literature. The aim of the present study was to perform an extensive review of the scientific evidence for NAC in patients with LACC. METHODS: PubMed, EMBASE, MEDLINE and Cochrane Library were searched for a systematic review of the literature from 2010 to 2019. Six eligible studies were included, with a total of 27,937 patients, 1232 of them (4.4%) treated with NAC. There were only one randomized controlled trial, three phase II non-randomized single arm studies and two retrospective studies. RESULTS: The baseline computed tomography scan showed that most of patients had a T3 tumor. The completion rate of the planned neoadjuvant treatment ranged from 52.5 to 93.8%. Between 97.2 and 100% of patients had the scheduled surgery. The median tumor volume reduction after NAC ranged from 62.5 to 63.7%. The anastomotic leak rate in the NAC group ranged from 0 to 7%, with no cases of postoperative mortality. There was major pathological tumor regression in 4-34.7% of cases. Between 84 and 100% of NAC patients had R0-surgery. Survival after NAC seems to be encouraging although significant improvement has only been proven in T4b tumours. CONCLUSIONS: According to our systematic review, the NAC may be a safe and effective emerging therapeutic alternative for treating LACC. This approach, which is still being tested, increases the reliance on accurate radiological staging.

Prevalence of hypertriglyceridemia in adults and related cardiometabolic factors. SIMETAP-HTG study. / Prevalencia de hipertrigliceridemia en adultos y factores cardiometabólicos asociados. Estudio SIMETAP-HTG.

AIM: To determine in the adult population the crude and the sex- and age-adjusted prevalence rates of hypertriglyceridaemia (HTG) and to assess its association with cardiovascular risk factors, chronic kidney disease, cardiovascular and cardiometabolic diseases. METHODS: Cross-sectional observational study conducted in Primary Care, with 6,588 adult study subjects, randomly selected on base-population. Patients had HTG if the triglyceride level was≥150mg/dL (≥1.7mmol/L), or were on lipid-lowering therapy to lower triglyceride. Associations were assessed by univariate and multivariate analysis, and crude and sex- and age-adjusted prevalence rates were determined. RESULTS: The arithmetic and geometric means of triglyceride levels were respectively 120.5 and 104.2mg/dL in global population, 135.7 and 116.0mg/dL in men, and 108.6 and 95.7mg/dL in women. The crude HTG prevalence rates were 29.6% in global population, 36.9% in men and 23.8% in women. The sex- and age-adjusted HTG prevalence rates were 27.0% in global population, 34.6% in men and 21.4% in women. The independent variables that were most associated with HTG were hypercholesterolemia (OR: 4.6), low HDL-C (OR: 4.1), hepatic steatosis (OR: 2.8), diabetes (OR: 2.0), and obesity (OR: 1.9). CONCLUSIONS: The means of triglyceride levels and HTG prevalence rates are intermediate between those of other national and international studies. A fifth of the female adult population and more than a third of the male population had HTG. The independent factors associated with HTG were hypercholesterolemia and low HDL-C, and the cardiometabolic variables diabetes, hepatic steatosis and obesity.

Análisis de la distribución del tiempo en materia de cuidado crítico por profesionales de enfermería mediante TISS-28 / Analysis of the distribution of time in critical care by nursing professionals using TISS-28 / Análise da distribuição do tempo em cuidados intensivos por profissionais de enfermagem usando o TISS-28

RESUMEN Introducción: Hoy en día, las intervenciones terapéuticas son más especializadas y complejas. Se ha identificado que el Therapeutic Intervention Scoring System-28 (TISS-28) es un instrumento adecuado para planear las actividades de enfermería. Objetivo: Determinar mediante la aplicación del instrumento TISS-28 el grado de complejidad de las intervenciones realizadas al brindar cuidados de enfermería a pacientes en estado crítico. Métodos: Estudio descriptivo, 270 pacientes (adultos, pediátricos y neonatales) en estado crítico; se recabó información sociodemográfica tanto del personal de enfermería como de los pacientes a través de un instrumento, se aplicó el TISS-28 para identificar el grado de complejidad de las intervenciones que se le brindaron al paciente. El análisis estadístico fue descriptivo para variables sociodemográficas y laborales, para las acciones realizadas por enfermería mediante niveles de grados de complejidad se hizo uso del análisis bivariado y la regresión logística. Resultados: Las intervenciones brindadas por el personal de enfermería en el servicio de medicina interna en el Grado II es de 9.8 veces más que en el resto de los pacientes, grado III aumenta 68 veces cuando el paciente tiene una sobre estancia hospitalaria. Discusión: Los pacientes que se encuentran en los servicios de cuidados intensivos o quirúrgicos requieren mayores cuidados. Conclusión: El TISS-28 permite predecir el estado del paciente crítico y su evolución. Determina el tiempo de atención requerido según la gravedad de este, además facilita la asignación idónea de enfermera-paciente.

ABSTRACT Introduction: Currently, therapeutic interventions have become more complex and specialized, but the Therapeutic Intervention Scoring System-28 (TISS-28) has been identified as an adequate tool in the planning of the corresponding nursing activities. Objective: To estimate through the Therapeutic Intervention Scoring System-28 (TISS-28) the degree of complexity of the necessary nursing interventions to provide care to patients in critical status. Methods: This is a descriptive study on 270 adult, pediatric, and neonatal patients in critical status. The TISS-28, and nursing and patient sociodemographic instruments were used. A descriptive statistical analysis using the sociodemographic and work-related variables was carried out. Bi-variate analysis and logistic regression were calculated in order to analyze the nursing performance by levels of complexity. Results: The interventions provided by the nursing staff in the internal medicine service in Grade II is 9.8 times more than in the rest of the patients, grade III increases by 68 times when the patient has an excess hospital stay. Discussion: Patients in the intensive care or surgical services require more care. Conclusion: The TISS-28 offers an estimate on the evolution and attention time required by patients in critical status as well as the corresponding ideal nurse-patient ratios.

RESUMO Introdução: Atualmente as intervenções terapêuticas são mais especializadas e complexas, identificou-se que o Therapeutic Intervention Scoring System-28 (TISS-28) é um instrumento adequado para planejar as atividades de enfermagem. Objetivo: Determinar mediante a aplicação do instrumento TISS-28, o grau de complexidade das intervenções realizadas na assistência de cuidados de enfermagem a pacientes em estado crítico. Métodos: Estudo descritivo, 270 pacientes (adultos, pediátricos e neonatais) em estado crítico; foi coletada informação sociodemográfica tanto do pessoal de enfermagem quanto dos pacientes através de um instrumento, aplicou-se o TISS-28 para identificar o grau de complexidade das intervenções que foram prestadas ao paciente. A análise estatística foi descritiva para variáveis sociodemográficas e laborais; a análise bivariada e a regressão logística foi utilizada para as ações realizadas por enfermagem mediante níveis de graus de complexidade. Resultados: As intervenções realizadas pela equipe de enfermagem no serviço de clínica médica do Grau II são 9,8 vezes mais do que no restante dos pacientes, o grau III aumenta em 68 vezes quando o paciente tem um tempo de internação excessivo. Discussão: Os pacientes que se encontram nos serviços de cuidados intensivos ou cirúrgicos requerem maiores cuidados. Conclusão: O TISS-28 permite prever do estado do paciente crítico e sua evolução. Determina o tempo de atenção requerido conforme a gravidade deste, aliás facilita a atribuição idónea de enfermeira-paciente.

Short communication: Volatile profile of matured Tronchón cheese affected by oxytetracycline in raw goat milk.

The presence of antibiotics in milk destined for cheese production may affect the biological processes responsible for the formation of volatile compounds, leading to alterations in the characteristic cheese flavor expected by consumers. The aim of this study was to evaluate the effect of the presence of oxytetracycline in goat milk on the volatile profile of ripened cheeses. Traditional mature Tronchón cheeses were manufactured from raw goat milk spiked with different concentrations of oxytetracycline (50, 100, and 200 µg/kg). Cheese made from antibiotic-free goat milk was used as control. We analyzed the residual amounts of the antibiotic and the volatile profile of the experimental cheeses on a fortnightly basis during maturation using liquid chromatography tandem mass spectrometry and then solid-phase microextraction followed by gas chromatography-mass spectrometry. Our results suggested that oxytetracycline was widely transferred from milk to cheese: drug concentrations in the cheeses were 3.5 to 4.3 times higher than those in raw milk. Although the residual amounts of oxytetracycline significantly decreased during maturation (88.8 to 96.5%), variable amounts of residues remained in cheese matured for 60 d (<10 to 79 µg/kg). In general, the presence of oxytetracycline in goat milk did not affect the volatile profile of Tronchón cheeses; volatile profile was significantly modified by ripening time. Still, the presence of oxytetracycline residues in cheeses ripened for 60 d could be of great concern for public health.

4-Deoxyphorbol inhibits HIV-1 infection in synergism with antiretroviral drugs and reactivates viral reservoirs through PKC/MEK activation synergizing with vorinostat.

Latent HIV reservoirs are the main obstacle to eradicate HIV infection. One strategy proposes to eliminate these viral reservoirs by pharmacologically reactivating the latently infected T cells. We show here that a 4-deoxyphorbol ester derivative isolated from Euphorbia amygdaloides ssp. semiperfoliata, 4ß-dPE A, reactivates HIV-1 from latency and could potentially contribute to decrease the viral reservoir. 4ß-dPE A shows two effects in the HIV replication cycle, infection inhibition and HIV transactivation, similarly to other phorboids PKC agonists such PMA and prostratin and to other diterpene esters such SJ23B. Our data suggest 4ß-dPE A is non-tumorigenic, unlike the related compound PMA. As the compounds are highly similar, the lack of tumorigenicity by 4ß-dPE A could be due to the lack of a long side lipophilic chain that is present in PMA. 4ß-dPE activates HIV transcription at nanomolar concentrations, lower than the concentration needed by other latency reversing agents (LRAs) such as prostratin and similar to bryostatin. PKCθ/MEK activation is required for the transcriptional activity, and thus, anti-latency activity of 4ß-dPE A. However, CD4, CXCR4 and CCR5 receptors down-regulation effect seems to be independent of PCK/MEK, suggesting the existence of at least two different targets for 4ß-dPE A. Furthermore, NF-κb transcription factor is involved in 4ß-dPE HIV reactivation, as previously shown for other PKCs agonists. We also studied the effects of 4ß-dPE A in combination with other LRAs. When 4ß-dPE A was combined with another PKC agonists such as prostratin an antagonic effect was achieved, while, when combined with an HDAC inhibitor such as vorinostat, a strong synergistic effect was obtained. Interestingly, the latency reversing effect of the combination was synergistically diminishing the EC50 value but also increasing the efficacy showed by the drugs alone. In addition, combinations of 4ß-dPE A with antiretroviral drugs as CCR5 antagonist, NRTIs, NNRTIs and PIs, showed a consistent synergistic effect, suggesting that the combination would not interefer with antiretroviral therapy (ART). Finally, 4ß-dPE A induced latent HIV reactivation in CD4 + T cells of infected patients under ART at similar levels than the tumorigenic phorbol derivative PMA, showing a clear reactivation effect. In summary, we describe here the mechanism of action of a new potent deoxyphorbol derivative as a latency reversing agent candidate to decrease the size of HIV reservoirs.

Consensus on basic conduct during the hospital admission of patients with acute heart failure. / Consenso de actuación básica durante el ingreso hospitalario por insuficiencia cardiaca aguda.

Acute heart failure (AHF) is a highly prevalent clinical entity in individuals older than 45years in Spain. AHF is associated with significant morbidity and mortality and is the leading cause of hospitalisation for individuals older than 65years in Spain, a quarter of whom die within 1year of the hospitalisation. In recent years, there has been an upwards trend in hospitalisations for AHF, which increased 76.7% from 2003 to 2013. Readmissions at 30days for AHF have also increased (from 17.6% to 22.1%), at a relative mean rate of 1.36% per year, with the consequent increase in the use of resources and the economic burden for the healthcare system. The aim of this document (developed by the Heart Failure and Atrial Fibrillation Group of the Spanish Society of Internal Medicine) is to guide specialists on the most important aspects of treatment and follow-up for patients with AHF during hospitalisation and the subsequent follow-up. The main recommendations listed in this document are as follows: (1)At admission, perform a comprehensive assessment, considering the patient's standard treatment and comorbidities, given that these determine the disease prognosis to a considerable measure. (2)During the first few hours of hospital care, decongestive treatment is a priority, and a staged diuretic therapeutic approach based on the patient's response is recommended. (3)To manage patients in the stable phase, consider starting and/or adjusting evidence-based drug treatment (e.g., sacubitril/valsartan or angiotensin-converting enzyme inhibitors/angiotensinII receptor blockers, beta blockers and aldosterone antagonists). (4)At hospital discharge, use a checklist to optimise the patient's management and identify the most efficient options for maintaining continuity of care after discharge.

Synaptic weighting in single flux quantum neuromorphic computing.

Josephson junctions act as a natural spiking neuron-like device for neuromorphic computing. By leveraging the advances recently demonstrated in digital single flux quantum (SFQ) circuits and using recently demonstrated magnetic Josephson junction (MJJ) synaptic circuits, there is potential to make rapid progress in SFQ-based neuromorphic computing. Here we demonstrate the basic functionality of a synaptic circuit design that takes advantage of the adjustable critical current demonstrated in MJJs and implement a synaptic weighting element. The devices were fabricated with a restively shunted Nb/AlOx-Al/Nb process that did not include MJJs. Instead, the MJJ functionality was tested by making multiple circuits and varying the critical current, but not the external shunt resistance, of the oxide Josephson junction that represents the MJJ. Experimental measurements and simulations of the fabricated circuits are in good agreement.