Bispecific immune cell engager enhances the anticancer activity of CD16+ NK cells and macrophages in vitro, and eliminates cancer metastasis in NK humanized NOG mice.

BACKGROUND: In a prior report, we detailed the isolation and engineering of a bispecific killer cell engager, referred to as BiKE:E5C1. The BiKE:E5C1 exhibits high affinity/specificity for the CD16a activating receptor on natural killer (NK) cells and human epidermal growth factor receptor 2 (HER2) on cancer cells. In vitro studies have demonstrated that BiKE:E5C1 can activate the NK cells and induce the killing of HER2+ ovarian and breast cancer cells, surpassing the performance of the best-in-class monoclonal antibody, Trazimera (trastuzumab). To advance this BiKE technology toward clinical application, the objective of this research was to demonstrate the ability of BiKE:E5C1 to activate CD16+ immune cells such as NK cells and macrophages to kill cancer cells, and eradicate metastatic HER2+ tumors in NK humanized NOG mice. METHODS: We assessed BiKE:E5C1's potential to activate CD16-expressing peripheral blood (PB)-NK cells, laNK92 cells, and THP-1-CD16A monocyte-macrophages through flowcytometry and antibody-dependent cell-mediated cytotoxicity/phagocytosis (ADCC) assays. Subsequently, laNK92 cells were selected as effector cells and genetically modified to express the nanoluciferase gene, enabling the monitoring of their viability in NK humanized NOG mice using quantitative bioluminescent imaging (qBLI). To evaluate the functionality of BiKE:E5C1 in vivo, we introduced firefly luciferase-expressing ovarian cancer cells via intraperitoneal injection into hIL-15 and hIL-2 NOG mice, creating a model of ovarian cancer metastasis. Once tumor establishment was confirmed, we treated the mice with laNK92 cells plus BiKE:E5C1 and the response to therapy was assessed using qBLI. RESULTS: Our data demonstrate that BiKE:E5C1 activates not only laNK92 cells but also PB-NK cells and macrophages, significantly enhancing their anticancer activities. ADCC assay demonstrated that IgG1 Fc region had no impact on BiKE:E5C1's anticancer activity. In vivo results reveal that both hIL-15 and hIL-2 NOG mouse models support the viability and proliferation of laNK92 cells. Furthermore, it was observed that BiKE:E5C1 activates laNK92 cells in mice, leading to eradication of cancer metastasis in both NK humanized hIL-15 and hIL-2 NOG mouse models. CONCLUSIONS: Collectively, our in vivo findings underscore BiKE:E5C1's potential as an immune cell engager capable of activating immune cells for cancer cell elimination, thereby expanding the arsenal of available BiKEs for cancer immunotherapy.

Antagonism of the Platelet-Activating Factor Pathway Mitigates Inflammatory Adverse Events Driven by Anti-erythrocyte Antibody Therapy in Mice.

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by low platelet counts primarily due to antiplatelet autoantibodies. Anti-D is a donor-derived polyclonal Ab against the rhesus D Ag on erythrocytes used to treat ITP. Unfortunately, adverse inflammatory/hypersensitivity reactions and a Food and Drug Administration-issued black box warning have limited its clinical use. This underscores the imperative to understand the inflammatory pathway associated with anti-erythrocyte Ab-based therapies. TER119 is an erythrocyte-specific Ab with anti-D-like therapeutic activity in murine ITP, while also exhibiting a distinct inflammatory signature involving production of CCL2, CCL5, and CXCL9 but not IFN-γ. Therefore, TER119 has been used to elucidate the potential mechanism underlying the adverse inflammatory activity associated with anti-erythrocyte Ab therapy in murine ITP. Prior work has demonstrated that TER119 administration is associated with a dramatic decrease in body temperature and inflammatory cytokine/chemokine production. The work presented in the current study demonstrates that inhibiting the highly inflammatory platelet-activating factor (PAF) pathway with PAF receptor antagonists prevents TER119-driven changes in body temperature and inhibits the production of the CCL2, CCL5, and CXCL9 inflammatory cytokines in CD-1 mice. Phagocytic cells and a functional TER119 Fc region were found to be necessary for TER119-induced body temperature changes and increases in CXCL9 and CCL2. Taken together, this work reveals the novel requirement of the PAF pathway in causing adverse inflammatory activity associated with anti-erythrocyte Ab therapy in a murine model and provides a strategy of mitigating these potential reactions without altering therapeutic activity.

Human Fc gamma receptor IIIA blockade inhibits platelet destruction in a humanized murine model of ITP.

ABSTRACT: Fc gamma receptor (FcγR) IIIA is an important receptor for immunoglobulin G (IgG) and is involved in immune defense mechanisms as well as tissue destruction in some autoimmune diseases including immune thrombocytopenia (ITP). FcγRIIIA on macrophages can trigger phagocytosis of IgG-sensitized platelets, and prior pilot studies observed blockade of FcγRIIIA increased platelet counts in patients with ITP. Unfortunately, although blockade of FcγRIIIA in patients with ITP increased platelet counts, its engagement by the blocking antibody drove serious adverse inflammatory reactions. These adverse events were postulated to originate from the antibody's Fc and/or bivalent nature. The blockade of human FcγRIIIA in vivo with a monovalent construct lacking an active Fc region has not yet been achieved. To effectively block FcγRIIIA in vivo, we developed a high affinity monovalent single-chain variable fragment (scFv) that can bind and block human FcγRIIIA. This scFv (17C02) was expressed in 3 formats: a monovalent fusion protein with albumin, a 1-armed human IgG1 antibody, and a standard bivalent mouse (IgG2a) antibody. Both monovalent formats were effective in preventing phagocytosis of ITP serum-sensitized human platelets. In vivo studies using FcγR-humanized mice demonstrated that both monovalent therapeutics were also able to increase platelet counts. The monovalent albumin fusion protein did not have adverse event activity as assessed by changes in body temperature, whereas the 1-armed antibody induced some changes in body temperature even though the Fc region function was impaired by the Leu234Ala and Leu235Ala mutations. These data demonstrate that monovalent blockade of human FcγRIIIA in vivo can potentially be a therapeutic strategy for patients with ITP.

Trogocytosis drives red blood cell antigen loss in association with antibody-mediated immune suppression.

ABSTRACT: Red blood cell (RBC) alloimmunization to paternal antigens during pregnancy can cause hemolytic disease of the fetus and newborn (HDFN). This severe and potentially fatal neonatal disorder can be prevented by the administration of polyclonal anti-D through a mechanism referred to as antibody-mediated immune suppression (AMIS). Although anti-D prophylaxis effectively prevents HDFN, a lack of mechanistic clarity has hampered its replacement with recombinant agents. The major theories behind AMIS induction in the hematologic literature have classically centered around RBC clearance; however, antigen modulation/loss has recently been proposed as a potential mechanism of AMIS. To explore the primary mechanisms of AMIS, we studied the ability of 11 different antibodies to induce AMIS, RBC clearance, antigen loss, and RBC membrane loss in the HOD (hen egg lysozyme-ovalbumin-human Duffy) murine model. Antibodies targeting different portions of the HOD molecule could induce AMIS independent of their ability to clear RBCs; however, all antibodies capable of inducing a strong AMIS effect also caused significant in vivo loss of the HOD antigen in conjunction with RBC membrane loss. In vitro studies of AMIS-inducing antibodies demonstrated simultaneous RBC antigen and membrane loss, which was mediated by macrophages. Confocal live-cell microscopy revealed that AMIS-inducing antibodies triggered RBC membrane transfer to macrophages, consistent with trogocytosis. Furthermore, anti-D itself can induce trogocytosis even at low concentrations, when phagocytosis is minimal or absent. In view of these findings, we propose trogocytosis as a mechanism of AMIS induction.

Serum from half of patients with immune thrombocytopenia trigger macrophage phagocytosis of platelets.

Humoral antiplatelet factors, such as autoantibodies, are thought to primarily clear platelets by triggering macrophage phagocytosis in immune thrombocytopenia (ITP). However, there are few studies characterizing the capacity and mechanisms of humoral factor-triggered macrophage phagocytosis of platelets using specimens from patients with ITP. Here, we assessed sera from a cohort of 24 patients with ITP for the capacity to trigger macrophage phagocytosis of normal donor platelets and characterized the contribution of humoral factors to phagocytosis. Sera that produced a phagocytosis magnitude greater than a normal human serum mean + 2 standard deviations were considered phagocytosis-positive. Overall, 42% (8/19) of MHC I alloantibody-negative ITP sera were phagocytosis-positive. The indirect monoclonal antibody immobilization of platelet antigens assay was used to detect immunoglobulin G (IgG) autoantibodies to glycoproteins (GP)IIb/IIIa, GPIb/IX, and GPIa/IIa. Autoantibody-positive sera triggered a higher mean magnitude of phagocytosis than autoantibody-negative sera. Phagocytosis correlated inversely with platelet counts among autoantibody-positive patients but not among autoantibody-negative patients. Select phagocytosis-positive sera were separated into IgG-purified and -depleted fractions via protein G and reassessed for phagocytosis. Phagocytosis was largely retained in the purified IgG fractions. In addition, we assessed serum concentrations of C-reactive protein, serum amyloid P, and pentraxin 3 as potential phagocytosis modulators. Pentraxin 3 concentrations correlated inversely with platelet counts among patients positive for autoantibodies. Taken together, sera from approximately half of the patients with ITP studied triggered macrophage phagocytosis of platelets beyond a normal level. An important role for antiplatelet autoantibodies in phagocytosis is supported; a role for pentraxins such as pentraxin 3 may be suggested.

Could foliar applications of methyl jasmonate and methyl jasmonate + urea improve must grape aroma composition?

BACKGROUND: Grape aromas are formed by a great number of volatile compounds. Methyl jasmonate (MeJ) and urea (Ur) foliar applications have been studied to improve grape quality, but their combined application has never been studied. RESULTS: In both seasons, MeJ application enhanced terpenoids and C6 compounds synthesis, though decreased alcohols content. Moreover, MeJ + Ur treatment reduced benzenoids and alcohols and did not affect C13 -norisoprenoids content. However, there was no clear effect of these treatments on the rest of the volatile compounds. Multifactorial analysis showed a season effect on all volatile compounds, except terpenoids. Discriminant analysis showed a good separation among samples under treatment criterion. The great effect of MeJ treatment on terpenoids was probably due to this elicitor influencing their biosynthesis. CONCLUSION: Season has a strong influence on grapes aromatic composition since it affects all volatile compound families except terpenoids. MeJ foliar application enhanced terpenoids, C13 -norisoprenoids and C6 compounds synthesis, whereas decreased alcohols content; however, MeJ + Ur foliar treatment did not affect C13 -norisoprenoids and C6 compounds, and decreased benzenoids and alcohols grape compounds. Therefore, no synergistic effect was observed between Ur and MeJ on grape volatile compounds biosynthesis. Foliar application of MeJ seems to be sufficient to improve the aromatic quality of grapes. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Postcardiac Surgery Euglycemic Diabetic Ketoacidosis in Patients on Sodium-Glucose Cotransporter 2 Inhibitors.

OBJECTIVES: To evaluate sodium-glucose cotransporter 2 inhibitors (SGLT2i) use and complications (euglycemic diabetic ketoacidosis [eDKA] rate, mortality, infection, hospital, and cardiovascular intensive care unit [CVICU] length of stay [LOS]) in patients undergoing cardiac surgery. DESIGN: A retrospective study. SETTING: At an academic university hospital. PARTICIPANTS: Adult patients undergoing cardiac surgery. INTERVENTIONS: SGLT2i use versus no SGLT2i use. MEASUREMENTS AND MAIN RESULTS: The authors evaluated patients undergoing cardiac surgery within 24 hours of hospital admission (between February 2, 2019 to May 26, 2022) for SGLT2i prevalence and eDKA frequency. The outcomes were compared using Wilcoxon rank sum and chi-square testing as appropriate. The cohort included 1,654 patients undergoing cardiac surgery, of whom 53 (3.2%) were prescribed an SGLT2i before surgery; 8 (15.1%) of 53 had eDKA. The authors found no differences between patients with and without SGLT2i use in hospital LOS (median [IQR]: 4.5 [3.5-6.3] v 4.4 [3.4-5.6] days, p = 0.46) or CVICU LOS (median [IQR]: 1.2 [1.0-2.2] v 1.1 [1.0-1.9] days, p = 0.22), 30-day mortality (1.9% v 0.7%, p = 0.31), or sternal infections (0.0% v 0.3%, p = 0.69). Among patients prescribed an SGLT2i, those with and without eDKA had similar hospital LOS (5.1 [4.0-5.8] v 4.4 [3.4-6.3], p = 0.76); however, CVICU LOS was longer in patients with eDKA (2.2 [1.5-2.9] v 1.2 [0.9-2.0], p = 0.042). Mortality (0.0% v 2.2%, p = 0.67) and wound infections (0.0% v 0.0%, p > 0.99) were similarly rare. CONCLUSIONS: Postoperative eDKA occurred in 15% of patients on an SGLT2i prior to cardiac surgery, and was associated with longer CVICU LOS. Future studies into SGLT2i management perioperatively are important.

Vine Foliar Treatments at Veraison and Post-Veraison with Methyl Jasmonate Enhanced Aromatic, Phenolic and Nitrogen Composition of Tempranillo Blanco Grapes.

Methyl jasmonate (MeJ) is an elicitor that, when applied in the vineyard, can improve grape quality. There are several studies about the MeJ influence on red grape varieties; however, to our knowledge, there is little information about white grape varieties, specifically Tempranillo Blanco. Therefore, the aim of this work is to evaluate the effect of MeJ foliar treatments, carried out at veraison and post-veraison, on the aromatic, phenolic and nitrogen composition of Tempranillo Blanco grapes. The results showed that grape volatile compounds content increased after MeJ application, especially terpenoids, C13 norisoprenoids, benzenoids and alcohols, and, in general, mainly at post-veraison. Regarding phenolic and nitrogen compounds, their concentrations were enhanced after MeJ treatments, regardless of application time. Consequently, MeJ treatment improved grape volatile, phenolic and nitrogen composition, particularly when this elicitor was applied post-veraison. Therefore, this is a good and easy tool to modulate white grape quality.

Hepatopathy of Mauriac syndrome. The importance of therapeutic adherence.

The Pierre Mauriac syndrome described in the year 1930, is characterized by growth failure, cushingoid appearance, hepatomegaly and hypertransaminasemia, in a patient with chronic uncontrolled DM1. The most common age of presentation is usually in adolescence, although cases have been described in both children and adults. The hallmark of this syndrome is extreme liver enlargement from massive acucumulation of glycogen. The diagnosis of hepatopathy requires high clinical suspicion and the presence of glycogen accumulation must be corroborated with a liver biopsy. The accumulation of glycogen in hepatocytes is partly caused by long periods of hyperglycemia, in which glucose enters the hepatocyte independently of insulin and is converted to glycogen. Mauriac syndrome is currently a rare cause of liver disease, due to improvements in control and treatment of patients with DM1. However, some cases are described in people with complicated social situations or without therapeutic compliance. This is a reversible condition after improvement in glycemic control with adequate insulinization. For this reason, we believe it convenient to suspect this clinical picture in patients with poor glycemic control and symptoms of pain and abdominal distension.

THP-1 cells transduced with CD16A utilize Fcγ receptor I and III in the phagocytosis of IgG-sensitized human erythrocytes and platelets.

Fc gamma receptors (FcγRs) are critical effector receptors for immunoglobulin G (IgG) antibodies. On macrophages, FcγRs mediate multiple effector functions, including phagocytosis, but the individual contribution of specific FcγRs to phagocytosis has not been fully characterized. Primary human macrophage populations, such as splenic macrophages, can express FcγRI, FcγRIIA, and FcγRIIIA. However, there is currently no widely available monocyte or macrophage cell line expressing all these receptors. Common sources of monocytes for differentiation into macrophages, such as human peripheral blood monocytes and the monocytic leukemia cell line THP-1, generally lack the expression of FcγRIIIA (CD16A). Here, we utilized a lentiviral system to generate THP-1 cells stably expressing human FcγRIIIA (CD16F158). THP-1-CD16A cells treated with phorbol 12-myristate 13-acetate for 24 hours phagocytosed anti-D-opsonized human red blood cells primarily utilizing FcγRI with a lesser but significant contribution of IIIA while phagocytosis of antibody-opsonized human platelets equally utilized FcγRI and Fcγ IIIA. Despite the well-known ability of FcγRIIA to bind IgG in cell free systems, this receptor did not appear to be involved in either RBC or platelet phagocytosis. These transgenic cells may constitute a valuable tool for studying macrophage FcγR utilization and function.

Muskuloskeletal injuries in mountain running races: A 5 seasons study.

INTRODUCTION: Mountain running races have grown in popularity in the recent years. Nonetheless, there are few studies on injuries and injury rates. Moreover, these studies have focused on long-distance events such as ultramarathons (>42 km). Therefore, the aim of the present study was to examine the severity, type, and body location of musculoskeletal injuries during 20-42 km mountain running races. In addition, the injury rates in this type of races were examined. METHODS: Data on injuries were collected during 36 mountain running races over 5 consecutive seasons from 2015 to 2019. The participants reported all musculoskeletal injuries on a standardized injury report form. The results were presented as the number of injuries per 1000 h exposure and per 1000 participants. RESULTS: Twenty eight injuries were reported. Most injuries occurred in the ankle (32%) followed by the knee (14%) and foot/toe (11%). The number of injuries represented an overall injury rate of 1.6 injuries per 1000 h running and 5.9 injuries per 1000 runners. The case fatality rate was 0. CONCLUSIONS: The incidence of musculoskeletal injuries during 20-42 km mountain running races is low. In addition, the majority of injuries experienced by runners are minor in nature and located in lower extremities, mainly the ankles.

Influence of seaweed foliar application to Tempranillo grapevines on grape and wine phenolic compounds over two vintages.

The study of seaweeds is increasing in viticulture due to their implications on plant protection and grape quality. This trial aimed to study the effects of foliar applications of an Ascophyllum nodosum extract at low (0.25%, v v-1) and high (0.50%, v v-1) dosages on grape and wine phenolic compounds in 2017 and 2018. In grapes, seaweed biostimulation increased the content of malvidin-3-glc, myricetin-3-glc and myricetin-3-gal in 2017 season. Moreover, both treatments improved the synthesis of trans-piceid and total stilbenes in both seasons. Sensory analysis revealed that 2017 wines had more color than the 2018 wines, which coincided with color intensity parameters. Therefore, seaweed applications to grapevines improved stilbenes content in grapes independently of the season and its effects on the rest of phenolic compounds in grapes and wines depended strongly of season factor.

Ischemic colitis and short bowel disease due to choronavirus disease 2019 (COVID 19).

COVID-19 has spread worldwide, with more than 2.5 million cases and over 80,000 deaths reported by the end of April 2020. In addition to pulmonary symptoms, gastrointestinal symptoms have been increasingly recognized as part of the disease spectrum. COVID-19-associated coagulopathy has recently emerged as a major component of the disease, leading to high morbidity and mortality. Ischemic colitis has been reported to be associated with a hypercoagulable state, However few cases have been reported of COVID-19 associated with ischemic colitis. We would like to report a case of a 53 year old man with medical history of type 2 diabetes, and hypercholesterolemia, with ishchemic colitis as first manifestation of infection of COVID 19.

Mesa 1: Diabetes mellitus tipo 1 y enfermedad cardiovascular / Table 1: type 1 diabetess mellitus and cardiovascular disease

La principal causa de muerte en personas con diabetes mellitus tipo 1 (DM1) es de origen cardiovascular (CV). La duración de la DM1 es uno de los predictores más importantes para infarto agudo de miocardio (IAM), junto con el colesterol de lipoproteínas de baja densidad (cLDL) y HbA1c. El desarrollo de DM1 antes de los 10 años de edad se asocia con un riesgo 90 veces mayor de IAM en mujeres. En la DM1 habría una mayor contribución de un estado de inflamación sistémica de bajo de grado. La combinación de electrocardiograma de ejercicio y una técnica de imagen proporciona valor diagnóstico para la detección de isquemia miocárdica y pronóstico. La evaluación del riesgo CV en el adulto mayor debe ser individualizado y categorizarlo según funcionalidad y comorbilidades a fin de fijar objetivos de control de factores glucémicos y no glucémicos personalizados. Las personas con enfermedad cardíaca conocida o múltiples factores de riesgo cardiovascular (FRCV) deben tener recomendaciones de ejercicio personalizadas; se recomienda el tratamiento intensificado de la glucemia y de los FRCV asociados. En la población pediátrica y adolescentes con DM1 es esencial la detección y tratamiento precoz de los FRCV a fin de prevenir o retrasar el inicio y progresión de eventos CV

The leading cause of death in type 1 diabetes mellitus (T1DM) is cardiovascular. The duration of diabetes is one of the most important predictors for acute myocardial infarction (AMI), along with low-density lipoprotein cholesterol (cLDL) and HbA1c. Being diagnosed of T1DM before age 10 is been associated with a 90 times higher risk of AMI in women. It has been proposed, that a low-grade systemic inflammation state to be great prompt contributor. The combination of exercise electrocardiogram and an imaging technique provides diagnostic value for myocardial ischemia detection and future prognosis. Cardiovascular risk assessment in the older adult should be individualized by categorizing it, according to functionality and patient's co morbidity and customized glycaemic and non-glycaemic targets. People with known heart disease or multiple cardiovascular risk factors should have personalized exercise recommendations, blood glucose intensified treatment and associated risk factors. In paediatric and adolescent population with T1DM, cardiovascular risk factors early screening, recognition and treatment has become essential to prevent or delay the onset and progression of cardiovascular events.

Ultrastructural, Cytochemical, and Comparative Genomic Evidence of Peroxisomes in Three Genera of Pathogenic Free-Living Amoebae, Including the First Morphological Data for the Presence of This Organelle in Heteroloboseans.

Peroxisomes perform various metabolic processes that are primarily related to the elimination of reactive oxygen species and oxidative lipid metabolism. These organelles are present in all major eukaryotic lineages, nevertheless, information regarding the presence of peroxisomes in opportunistic parasitic protozoa is scarce and in many cases it is still unknown whether these organisms have peroxisomes at all. Here, we performed ultrastructural, cytochemical, and bioinformatic studies to investigate the presence of peroxisomes in three genera of free-living amoebae from two different taxonomic groups that are known to cause fatal infections in humans. By transmission electron microscopy, round structures with a granular content limited by a single membrane were observed in Acanthamoeba castellanii, Acanthamoeba griffini, Acanthamoeba polyphaga, Acanthamoeba royreba, Balamuthia mandrillaris (Amoebozoa), and Naegleria fowleri (Heterolobosea). Further confirmation for the presence of peroxisomes was obtained by treating trophozoites in situ with diaminobenzidine and hydrogen peroxide, which showed positive reaction products for the presence of catalase. We then performed comparative genomic analyses to identify predicted peroxin homologues in these organisms. Our results demonstrate that a complete set of peroxins-which are essential for peroxisome biogenesis, proliferation, and protein import-are present in all of these amoebae. Likewise, our in silico analyses allowed us to identify a complete set of peroxins in Naegleria lovaniensis and three novel peroxin homologues in Naegleria gruberi. Thus, our results indicate that peroxisomes are present in these three genera of free-living amoebae and that they have a similar peroxin complement despite belonging to different evolutionary lineages.

Evaluation of grape ripeness, carbonic maceration and pectolytic enzymes to improve the chemical and sensory quality of red sparkling wines.

BACKGROUND: Red sparkling wines are and innovative product for the oenology market, and oenologists are looking for technologies to improve their winemaking. The present study aimed to use both carbonic maceration and pectolytic enzymes applied to premature grapes during the winemaking of red sparkling wines. Both could modify the release of polyphenols, as well as improve the foaming, aroma and sensory properties of the wines. RESULTS: Red sparkling wines made with mature grapes showed the highest content of polyphenols, ethyl esters, alcohol acetates, total volatile acids and foam stability time. They were characterised by a high foam collar and foam area, full-body, astringency, persistence, and olfactory intensity, and were the best evaluated with respect to global perception in the sensory analysis. Treatment with pectolytic enzymes was not effective with unripe grapes. These wines showed a high content of total ethyl esters and the highest content of lactones, producing wines with high olfactory intensity and fruity aromas. Red sparkling wines made by carbonic maceration showed the lowest content of total polyphenols, anthocyanins and proanthocyanidins, as well as high contents of C6 alcohols and total ethyl esters, and were characterised by vegetal aroma notes. Both treatments produced red sparkling wines with good foam characteristics. CONCLUSION: Winemaking of red sparkling wines with premature grapes and pectinolytic enzymes or carbonic maceration did not achieve an improvement with respect to their chemical and sensory qualities. The use of mature grapes and traditional winemaking is the best option for elaborating red quality sparkling wines. © 2020 Society of Chemical Industry.

Effects of different oenological techniques on the elaboration of adequate base wines for red sparkling wine production: phenolic composition, sensory properties and foam parameters.

BACKGROUND: In red sparkling winemaking it is essential to obtain base wines with moderate alcohol content, adequate mouthfeel and color intensity. The aim of this work was to study oenological techniques to obtain adequate base wines for production of red sparkling wine by traditional methods: pre-fermentative cold maceration with dry ice and délestage with premature grapes; and sugar reduction in must and partial dealcoholisation of wine with mature grapes. The effect on oenological parameters, e.g. phenolic content, foam and sensory characteristics, was studied in sparkling wines aged on the lees in bottles for 9 months followed by aging for12 months in bottles after disgorging. RESULTS: Pre-fermentative cold maceration was the only treatment that increased the content of anthocyanins in sparkling wines at both stages of aging. Sparkling wines elaborated using délestage showed the highest mean values of the degree of polymerization of proanthocyanidins. Sparkling wines from mature grapes were given higher valuation in the gustatory phase. Sparkling wines elaborated using pre-fermentative cold maceration were given the highest valuation for foam quality. CONCLUSIONS: Pre-fermentative cold maceration is a viable alternative to common techniques for increasing the anthocyanin content in wines from premature grapes. It would therefore be a good option to obtain adequate base wines. © 2019 Society of Chemical Industry.

Mesa 3: Diabetes Mellitus Tipo 2 y actividad física / Table 3: Type 2 diabetes and physical activity

La prevalencia de diabetes mellitus (DM) actividad física es cada vez mayor asociada a bajos niveles de actividad física (AF) y aumento de sobrepeso-obesidad. Los beneficios de la AF incluyen la prevención de la DM, reducción de hemoglobina glicosilada y glucemia postprandial, mejoría del perfil cardiovascular (descenso Presión arterial y triglicéridos, aumento de colesterol HDL), descenso significativo de biomarcadores proinflamatorios. Además, la AF mejora la disfunción sexual, la función endotelial, el óxido nítrico biodisponible y la insulinosensibilad, incrementa la testosterona, mejora el humor y la autoestima, la ansiedad y la depresión. El ejercicio incrementa la producción de glucosa, la secreción de insulina compensatoria está alterada y se exacerba por una mayor secreción de catecolaminas. Las personas con insulinopenia marcada tienen riesgo de cetosis. El aumento de hipoglucemias está dado por una mayor captación de glucosa. La AF mejora la polineuropatía y la neuropatía autonómica cardíaca, previene la enfermad renal crónica y se asocia a menores niveles de retinopatía diabética. En pacientes con retinopatía preproliferativa y proliferativa o degradación macular, se desaconsejan las actividades que aumentan considerablemente la presión intraocular. Está contraindicado el ejercicio en caso de hemorragia vítrea. El requerimiento energético depende del tipo, intensidad y duración del ejercicio. Se debe considerar el cuidado del pie. Las recomendaciones son disminuir el tiempo sedentario, ejercicio aeróbico al menos 150 min/semana y ejercicio de resistencia. Al aumentar la intensidad o ante riesgo elevado se debe realizar chequeo que incluya electrocardiograma y test de esfuerzo. Considerar ecocardiograma bidimensional y doppler