Metabolic pathways for biosynthesis and degradation of starch in Tetraselmis chui during nitrogen deprivation and recovery.

Tetraselmis chui is known to accumulate starch when subjected to stress. This phenomenon is widely studied for the purpose of industrial production and process development. Yet, knowledge about the metabolic pathways involved is still immature. Hence, in this study, transcription of 27 starch-related genes was monitored under nitrogen deprivation and resupply in 25 L tubular photobioreactors. T. chui proved to be an efficient starch producer under nitrogen deprivation, accumulating starch up to 56% of relative biomass content. The prolonged absence of nitrogen led to an overall down-regulation of the tested genes, in most instances maintained even after nitrogen replenishment when starch was actively degraded. These gene expression patterns suggest post-transcriptional regulatory mechanisms play a key role in T. chui under nutrient stress. Finally, the high productivity combined with an efficient recovery after nitrogen restitution makes this species a suitable candidate for industrial production of high-starch biomass.

TetraSOD®, a Unique Marine Microalgae Ingredient, Promotes an Antioxidant and Anti-Inflammatory Status in a Metabolic Syndrome-Induced Model in Rats.

Increased oxidative stress has been linked to the pathogenic process of obesity and can trigger inflammation, which is often linked with the risk factors that make up metabolic syndrome (MetS), including obesity, insulin resistance, dyslipidaemia and hypertension. TetraSOD®, a natural marine vegan ingredient derived from the microalgae Tetraselmis chuii that is high in the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) has recently demonstrated in vitro increased activity of these key antioxidant enzymes. In the present study, the potential bioactive effects of three dietary dosages of TetraSOD® in enhancing antioxidant and anti-inflammatory mechanisms to combat the metabolic disturbances that compose MetS were assessed in rats given a cafeteria (CAF) diet. Chronic supplementation with 0.17, 1.7, and 17 mg kg-1 day-1 of TetraSOD® for 8 weeks ameliorated the abnormalities associated with MetS, including oxidative stress and inflammation, promoting endogenous antioxidant defence mechanisms in the liver (GPx and GSH), modulating oxidative stress and inflammatory markers in plasma (NOx, oxLDL and IL-10), and regulating genes involved in antioxidant, anti-inflammatory and immunomodulatory pathways in the liver, mesenteric white adipose tissue (MWAT), thymus, and spleen. Overall, TetraSOD® appears to be a potential therapeutic option for the management of MetS.

Selection and validation of reference genes for quantitative real-time PCR in the green microalgae Tetraselmis chui.

Quantitative real-time reverse transcription PCR (RT-qPCR) is a highly sensitive technique that can be applied to analyze how genes are modulated by culture conditions, but identification of appropriate reference genes for normalization is a critical factor to be considered. For this reason, the expression stability of 18 candidate reference genes was evaluated for the green microalgae Tetraselmis chui using the widely employed algorithms geNorm, NormFinder, BestKeeper, the comparative ΔCT method, and RefFinder. Microalgae samples were collected from large scale outdoor photobioreactors during the growing phase (OUT_GP), and during the semi-continuous phase at different times of the day (OUT_DC). Samples from standard indoor cultures under highly controlled conditions (IND) were also collected to complement the other data. Different rankings for the candidate reference genes were obtained depending on the culture conditions and the algorithm employed. After comparison of the achieved ranks with the different methods, the references genes selected for samples from specific culture conditions were ALD and EFL in OUT_GP, RPL32 and UBCE in OUT_DC, and cdkA and UBCE in IND. Moreover, the genes EFL and cdkA or EFL and UBCE appeared as appropriate combinations for pools generated from all samples (ALL). Examination in the OUT_DC cultures of genes encoding the large and small subunits of ADP-glucose pyrophosphorylase (AGPL and AGPS, respectively) confirmed the reliability of the identified reference genes, RPL32 and UBCE. The present study represents a useful contribution for studies of gene expression in T. chui, and also represents the first step to set-up an RT-qPCR platform for quality control of T. chui biomass production in industrial facilities.

Andalusian program for early detection of diabetic retinopathy: implementation and 15-year follow-up of a population-based screening program in Andalusia, Southern Spain.

INTRODUCTION: Diabetic retinopathy (DR) is a preventable cause of vision loss and blindness worldwide. We aim at analyzing the impact of a population-based screening program of DR using retinal photography with remote reading in terms of population coverage, diagnosis of asymptomatic DR and impact on visual disability, in the region of Andalusia, Spain, in the period 2005-2019. RESEARCH DESIGN AND METHODS: Descriptive study. Sociodemographic and clinical features included in the Andalusian program for early detection of diabetic retinopathy (APDR) were analyzed. Population coverage, annual incidence of DR, and DR severity gradation were analyzed. Estimated data on prevalence and incidence of legal blindness due to DR were included. RESULTS: 407 762 patients with at least one successful DR examination during the study period were included. Most of the performed retinographies (784 584, 84.3%) were 'non-pathological.' Asymptomatic DR was detected in 52 748 (5.9%) retinographies, most of them (94.2%) being classified as 'mild to moderate non-proliferative DR.' DR was detected in 44 815 patients, while sight-threatening DR (STDR) in 6256 patients; cumulative incidence of DR was 11.0% and STDR was 1.5%, as DR and STDR was detected in 44 815 and 6256 patients, respectively. Annual incidence risk per patient recruitment year progressively decreased from 22.0% by January 2005 to 3.2% by June 2019. CONCLUSIONS: Implementation of a long-term population-based screening program for early detection of DR is technically feasible and clinically viable. Thus, after 15 years of existence, the program has enabled the screening of the vast majority of the target population allowing the optimization of healthcare resources and the identification of asymptomatic DR.

Can Integrated Care Help in Meeting the Challenges Posed on Our Health Care Systems by COVID-19? Some Preliminary Lessons Learned from the European VIGOUR Project.

The COVID-19 pandemic puts health and care systems under pressure globally. This current paper highlights challenges arising in the care for older and vulnerable populations in this context and reflects upon possible perspectives for different systems making use of nested integrated care approaches adapted during the work of the EU-funded project VIGOUR ("Evidence based Guidance to Scale-up Integrated Care in Europe", funded by the European Union's Health Programme 2014-2020 under Grant Agreement Number 826640).

Assessing the Pilot Implementation of the Integrated Multimorbidity Care Model in Five European Settings: Results from the Joint Action CHRODIS-PLUS.

Multimorbidity, the coexistence of several chronic conditions in a patient, represents a great challenge for healthcare systems and society. The Integrated Multimorbidity Care Model (IMCM) was recently designed within the Joint Action on chronic diseases and promoting healthy ageing across the life cycle (CHRODIS) to ensure the continuity of care for patients with multimorbidity. The IMCM was implemented in five European pilot sites in Spain, Italy, and Lithuania, within the Joint Action CHRODIS-PLUS. The effect of these pilot interventions was assessed pre- and post-implementation by 17 healthcare managers, using the Assessment of Chronic Illness Care (ACIC) measure, and by 226 patients with the Patient Assessment of Care for Chronic Conditions (PACIC+) survey. The ACIC total score significantly increased (5.23 to 6.71, p = 0.022) after the intervention, with differences across sites. A significant increase in the PACIC+ summary score was found ranging from 3.25 at baseline to 4.03 after the intervention (p < 0.001), and 58% of the sample perceived an improvement in care. Higher PACIC+ scores after the intervention were associated to lower baseline values in the respective PACIC+ dimension and to greater changes in ACIC Part 1 (delivery system organization). The IMCM implementation can help improve the quality of care for patients with multimorbidity.

A Methodological Approach for Implementing an Integrated Multimorbidity Care Model: Results from the Pre-Implementation Stage of Joint Action CHRODIS-PLUS.

Patients with multimorbidity (defined as the co-occurrence of multiple chronic diseases) frequently experience fragmented care, which increases the risk of negative outcomes. A recently proposed Integrated Multimorbidity Care Model aims to overcome many issues related to fragmented care. In the context of Joint Action CHRODIS-PLUS, an implementation methodology was developed for the care model, which is being piloted in five sites. We aim to (1) explain the methodology used to implement the care model and (2) describe how the pilot sites have adapted and applied the proposed methodology. The model is being implemented in Spain (Andalusia and Aragon), Lithuania (Vilnius and Kaunas), and Italy (Rome). Local implementation working groups at each site adapted the model to local needs, goals, and resources using the same methodological steps: (1) Scope analysis; (2) situation analysis-"strengths, weaknesses, opportunities, threats" (SWOT) analysis; (3) development and improvement of implementation methodology; and (4) final development of an action plan. This common implementation strategy shows how care models can be adapted according to local and regional specificities. Analysis of the common key outcome indicators at the post-implementation phase will help to demonstrate the clinical effectiveness, as well as highlight any difficulties in adapting a common Integrated Multimorbidity Care Model in different countries and clinical settings.

Supercritical CO2 extraction of beta-carotene from a marine strain of the cyanobacterium Synechococcus species.

Dynamic extraction of carotenoids from a marine strain of Synechococcus sp. (Cyanophyceae) with supercritical CO2 (SC-CO2) was investigated with regard to operation pressure and temperature effects on extraction efficiency. Extraction yield (milligrams of pigment per gram of dry weight) for SC-CO2) was compared with the extraction yield for dimethylformamide (DMF). Carotenoids extracted with SC-CO2 were beta-carotene (Ct), zeaxanthin (Z), beta-cryptoxanthin (Cr), and equinenone; chlorophyll a was poorly extracted, whereas myxoxanthophyll, another major carotenoid, was not extracted under any experimental condition. The highest relative yield, which is defined here as y(r) = [(mg of pigment(SC-CO2)/mg of pigment(DMF))] x 100, was 76.1 +/- 8.6% for Ct, but it rose to 87.0 +/- 3.4% when 15% ethanol was used as cosolvent. The pressure effect on y(r) was found to be significant (p < 0.05) for both Cr and Z, along with total carotenoids, whereas the effect of square T (TT) was significant for only Ct. From empirical correlations, pairwise pressure (bar) and temperature (degrees C), respectively, for optimal extraction were determined to be (358, 50) for Ct, (454, 59) for Cr, and (500, 60) for Z. Cell disruption by sonication or detergent treatment of the biomass did not improve the extraction efficiency. Matrix structure together with material state could explain the low carotenoid extraction yield obtained with SC-CO2 as compared to DMF in Synechococcus sp. However, the process can be applied to selective extraction of different carotenoids.

Metabolic syndrome in Spain: prevalence and coronary risk associated with harmonized definition and WHO proposal. DARIOS study.

INTRODUCTION AND OBJECTIVES: To update the prevalence of metabolic syndrome and associated coronary risk in Spain, using the harmonized definition and the new World Health Organization proposal (metabolic premorbid syndrome), which excludes diabetes mellitus and cardiovascular disease. METHODS: Individual data pooled analysis study of 24,670 individuals from 10 autonomous communities aged 35 to 74 years. Coronary risk was estimated using the REGICOR function. RESULTS: Prevalence of metabolic syndrome was 31% (women 29% [95% confidence interval, 25%-33%], men 32% [95% confidence interval, 29%-35%]). High blood glucose (P=.019) and triglycerides (P<.001) were more frequent in men with metabolic syndrome, but abdominal obesity (P<.001) and low high-density lipoprotein cholesterol (P=.001) predominated in women. Individuals with metabolic syndrome showed moderate coronary risk (8% men, 5% women), although values were higher (P<.001) than in the population without the syndrome (4% men, 2% women). Women and men with metabolic syndrome had 2.5 and 2 times higher levels of coronary risk, respectively (P<.001). Prevalence of metabolic premorbid syndrome was 24% and the increase in coronary risk was also proportionately larger in women than in men (2 vs 1.5, respectively; P<.001). CONCLUSIONS: Prevalence of metabolic syndrome is 31%; metabolic premorbid syndrome lowers this prevalence to 24% and delimits the population for primary prevention. The increase in coronary risk is proportionally larger in women, in both metabolic syndrome and metabolic premorbid syndrome.

Hepatolitiasis: Estudio de 10 casos / Hepatolithiasis: Study of 10 cases

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Liver transplantation in patients with hepatic hydrothorax.

Hepatic hydrothorax is a uncommon complication of cirrhotic patients and the results of liver transplantation (OLT) in patients with this complication are not well defined. We studied postoperative complications and survival of 28 patients with hepatic hydrothorax transplanted at our center during a period of 12 years, comparing them with a control group of 56 patients transplanted immediately before and after each case. There were no differences between hydrothorax group and control group in days of mechanical ventilation after surgery, transfusion requirements, postoperative mortality and long-term survival (70% vs. 55% at 8 years, P = 0.11). Long-term evolution was similar between patients with refractory hepatic hydrothorax or spontaneous bacterial empyema and those with noncomplicated hepatic hydrothorax. Hepatic transplantation is an excellent therapeutic option for patients with hepatic hydrothorax. Presence of hepatic hydrothorax does not imply more postoperative complications, and long-term survival is similar to other indications of hepatic cirrhosis.

Intraoperative red blood cell transfusion in liver transplantation: influence on patient outcome, prediction of requirements, and measures to reduce them.

Objectives of this study are to quantify the need for blood transfusion during liver transplantation (LT) and confirm the importance of intraoperative blood transfusion as an independent prognostic factor for postoperative outcome. Furthermore, we try to detect useful variables for the preoperative identification of patients likely to require transfusion of packed red blood cell units (PRCUs) and identify measures to reduce transfusion needs. Data were collected prospectively between September 1998 and November 2000. One hundred twenty-two LTs were included in the study. Forty-two patients (34%) did not require transfusion of PRCUs. In multivariate analysis, transfusion of more than three PRCUs was found to be the only significant variable associated with prolonged hospital stay. In addition, excluding perioperative deaths, PRCU transfusion, using a cutoff value of six units, was the only variable to reach statistical significance (P =.008; risk ratio, 4.93; 95% confidence interval, 15 to 15.9) to predict survival in a multivariate analysis that also included Child's class and United Network for Organ Sharing (UNOS) classification. Moreover, only preoperative hemoglobin (Hb) level was found to significantly predict the need for transfusion of one or more PCRUs. Finally, only UNOS classification and placement of an intraoperative portacaval shunt were found to be statistically significant to predict the need to transfuse more than six PRCUs. We found the requirement of even a moderate number of blood transfusions is associated with longer hospital stay, and transfusion of more than six PRCUs is associated with diminished survival. Preoperative normalization of Hb levels and placement of an intraoperative portacaval shunt can diminish the number of blood transfusions during LT.

Is MELD really the definitive score for liver allocation?

The best system for organ allocation is still a controversial issue. The aim of this study was to study the accuracy of four different scores to predict mortality on the waiting list and, thus, their usefulness to determine organ allocation. We retrospectively compared two groups of patients, those who died on waiting list (group D) and those who successfully underwent transplantation (group T) during the same time period. Four scores, at the time of entering the waiting list and just before liver transplantation or death, were evaluated. The evaluated scores were as follows: (1) the Child-Pugh classification; (2) the Model for End-Stage Liver Disease (MELD) score; (3) the Freeman scale; and (4) the Guardiola et al index. The mortality rate on waiting list was 15.9%. All studied scores, except Freeman scale, were higher in group D at the time of entrance on waiting list (MELD, 17.4 +/- 8 v 12.3 +/- 6, P = .02; Child, 9.9 +/- 2 v 7.7 +/- 2, P = .002; Freeman, 9.7 +/- 4 v 7.3 +/- 3.9, P = .09; Guardiola, 2.6 +/- 0.9 v 1.7 +/- 0.7, P = .001). C-statistics of all scores were similar and in all cases lower than 0.8 (MELD, 0.75; Child, 0.78; Freeman, 0.65; Guardiola, 0.79). None of the studied scores have an excellent accuracy to predict prognosis of patients on waiting list, mainly in case of populations with high proportion of hepatocellular carcinoma. Although the MELD score is rapidly available, standardized, and objective, it does not reflect the severity of patients with cancer or metabolic disorders.

Influence of endothelin-1 on hemodynamics during liver transplantation with and without temporary portocaval shunt: results of a clinical randomized study.

Aims of this study are to analyze the influence of endothelin-1 (ET-1) on hemodynamic evolution during liver transplantation (LT) and study the role of a temporary portacaval shunt in ET-1 synthesis. Forty LTs in patients with cirrhosis were studied. Two groups were analyzed: the first group had a temporary portacaval shunt during the anhepatic phase, and the second group did not. Portal and systemic ET-1 levels were measured at several times. At the end of the anhepatic phase, systemic (16.1 +/- 6.5 pg/mL) and portal (19.2 +/- 7 pg/mL) ET-1 levels increased, whereas they decreased after reperfusion (systemic, 11.8 +/- 7.1 pg/mL; portal, 13.2 +/- 6.8 pg/mL). Portal flow at the beginning of LT correlated with systemic ET-1 levels (R2 = 0.3; P =.004). A temporary portacaval shunt reduced portal pressure during the anhepatic phase, but did not modify ET-1 levels. Patients with reperfusion syndrome had greater systemic ET-1 levels in the anhepatic phase (19.1 +/- 6.9 v 15.1 +/- 6.1 pg/mL; P =.07). Although there is a relationship between ET-1 levels and portal flow and reperfusion syndrome, no clear clinical effect on hemodynamics could be shown. Creation of a portacaval shunt made no change in ET-1 levels.

Расширение ответных мер первичной медико-санитарной помощи для решения проблемы сахарного диабета: комплексная программа раннего выявления нарушений зрения у больных диабетом в Андалузии: информационный обзор по передовому опыту

В 2004 году в рамках комплексного плана лечения диабета в Андалузии была разработана программа раннего выявления диабетической ретинопатии. В регионе проживает 8,4 млн. человек; по оценкам, уровень заболеваемости сахарным диабетом составляет около 12%. В настоящее время в рамках программы было обследовано 424 648 пациентов, выполнено 753 523 ретинографий, и охват целевого населения достиг 95%. Программа способствует более широкому вовлечению специалистов первичной медико-санитарной помощи и использованию цифровых решений.

Strengthening the primary care response to diabetes: a comprehensive early detection programme of vision impairment among people with diabetes in Andalusia, Spain: good practice brief

In 2004, a programme for early detection of diabetic retinopathy was introduced within the comprehensive plan for diabetes in Andalusia. The region has 8.4 million inhabitants and an estimated rate of diabetes mellitus of about 12%. Currently, 424 648 patients have participated in the programme, with 753 523 retinographies performed, reaching 95% of the target population. The programme enhances the participation of primary health care professionals and the use of digital solutions.