The Potential of Using Cochayuyo (Durvillaea incurvata) Extract Obtained by Ultrasound-Assisted Extraction to Fight against Aging-Related Diseases.

The world's population is in a demographical transition, with an increase in the number of older adults and prevalence of diseases related to aging. This study evaluated in vitro the potential of using Durvillaea incurvata extract (extracted using ultrasound-assisted extraction) to inhibit key enzymes associated with the development of age-related diseases. Our results show that an extract extracted via ultrasound-assisted extracted, as well as an extract conventional extracted from Durvillaea incurvata, presented antidiabetes potential by exhibiting inhibitory activity against α-glucosidase (91.8 ± 1.0% and 93.8 ± 0.3%, respectively, at 500 µg/mL) and α-amylase (42.2 ± 1.4% and 61.9 ± 0.9%, respectively, at 1500 µg/mL) enzymes related to starch digestion and postprandial glycemic response. Also, the extracts showed inhibitory activity against the enzymes acetylcholinesterase (51.5% and 50.8%, respectively, at 500 µg/mL) and butyrylcholinesterase (32.8% and 34.4%, respectively, at 0.5 mg/mL), the biomarkers associated with Alzheimer's disease, and angiotensin-converting enzyme (98.7 ± 7.4% and 93.0 ± 3.4%, respectively, at 2.0 mg/mL), which is key in the regulation of vascular tone and blood pressure and helps to prevent the development of hypertension. In conclusion, the extract of Durvillaea incurvata obtained from ultrasound-assisted extraction has the potential to prevent the development of age-related pathologies such as diabetes, Alzheimer's disease, and hypertension.

Results of phase 2 randomized multi-center study to evaluate the safety and efficacy of infusion of memory T cells as adoptive therapy in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia and/or lymphopenia (RELEASE NCT04578210).

BACKGROUND AIMS: There are currently no effective anti-viral treatments for coronavirus disease 2019 (COVID-19)-hospitalized patients with hypoxemia. Lymphopenia is a biomarker of disease severity usually present in patients who are hospitalized. Approaches to increasing lymphocytes exerting an anti-viral effect must be considered to treat these patients. Following our phase 1 study, we performed a phase 2 randomized multicenter clinical trial in which we evaluated the efficacy of the infusion of allogeneic off-the-shelf CD45RA- memory T cells containing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells from convalescent donors plus the standard of care (SoC) versus just the SoC treatment. METHODS: Eighty-four patients were enrolled in three Spanish centers. The patients were randomized into the infusion of 1 × 106/kg CD45RA- memory T cells or the SoC. We selected four unvaccinated donors based on the expression of interferon gamma SARS-CoV-2-specific response within the CD45RA- memory T cells and the most frequent human leukocyte antigen typing in the Spanish population. RESULTS: We analyzed data from 81 patients. The primary outcome for recovery, defined as the proportion of participants in each group with normalization of fever, oxygen saturation sustained for at least 24 hours and lymphopenia recovery through day 14 or at discharge, was met for the experimental arm. We also observed faster lymphocyte recovery in the experimental group. We did not observe any treatment-related adverse events. CONCLUSIONS: Adoptive cell therapy with off-the-shelf CD45RA- memory T cells containing SAR-CoV-2-specific T cells is safe, effective and accelerates lymphocyte recovery of patients with COVID-19 pneumonia and/or lymphopenia. TRIAL REGISTRATION: NCT04578210.

Cochayuyo (Durvillaea incurvata) Extracts: Their Impact on Starch Breakdown and Antioxidant Activity in Pasta during In Vitro Digestion.

Seaweeds, notably cochayuyo (Durvillaea incurvata), are recognized for their rich macro- and micronutrient content, along with their inhibitory effects on the α-glucosidase enzyme. The present study aims to evaluate the effectiveness of this inhibition in actual starchy food products under in vitro gastrointestinal conditions. This study utilized freeze-dried cochayuyo, extracted using hot pressurized liquid extraction with 50% ethanol at 120 °C and 1500 psi. The inhibition mechanism of α-glucosidase was determined, and the polyphenol composition of the extract was analyzed using Ultra-High-Performance Liquid Chromatography. This study further evaluated the extract's impact on starch digestibility, total phenolic content, and antioxidant capacity in pasta (noodles) as representative starchy food under gastrointestinal conditions. The results indicate that the α-glucosidase inhibition mechanism is of mixed type. Phenolic compounds, primarily tetraphloroethol, could contribute to this anti-enzymatic activity. The extract was observed to decrease starch digestibility, indicated by a lower rate constant (0.0158 vs. 0.0261 min-1) and digested starch at an infinite time (77.4 vs. 80.5 g/100 g). A significant increase (~1200 vs. ~390 µmol TROLOX/100 g) in antioxidant activity was also noted during digestion when the extract was used. Thus, this study suggests that the cochayuyo extract can reduce starch digestion and enhance antioxidant capacity under gastrointestinal conditions.

Safety and immunogenicity of the protein-based PHH-1V compared to BNT162b2 as a heterologous SARS-CoV-2 booster vaccine in adults vaccinated against COVID-19: a multicentre, randomised, double-blind, non-inferiority phase IIb trial.

Background: A SARS-CoV-2 protein-based heterodimer vaccine, PHH-1V, has been shown to be safe and well-tolerated in healthy young adults in a first-in-human, Phase I/IIa study dose-escalation trial. Here, we report the interim results of the Phase IIb HH-2, where the immunogenicity and safety of a heterologous booster with PHH-1V is assessed versus a homologous booster with BNT162b2 at 14, 28 and 98 days after vaccine administration. Methods: The HH-2 study is an ongoing multicentre, randomised, active-controlled, double-blind, non-inferiority Phase IIb trial, where participants 18 years or older who had received two doses of BNT162b2 were randomly assigned in a 2:1 ratio to receive a booster dose of vaccine-either heterologous (PHH-1V group) or homologous (BNT162b2 group)-in 10 centres in Spain. Eligible subjects were allocated to treatment stratified by age group (18-64 versus ≥65 years) with approximately 10% of the sample enrolled in the older age group. The primary endpoints were humoral immunogenicity measured by changes in levels of neutralizing antibodies (PBNA) against the ancestral Wuhan-Hu-1 strain after the PHH-1V or the BNT162b2 boost, and the safety and tolerability of PHH-1V as a boost. The secondary endpoints were to compare changes in levels of neutralizing antibodies against different variants of SARS-CoV-2 and the T-cell responses towards the SARS-CoV-2 spike glycoprotein peptides. The exploratory endpoint was to assess the number of subjects with SARS-CoV-2 infections ≥14 days after PHH-1V booster. This study is ongoing and is registered with ClinicalTrials.gov, NCT05142553. Findings: From 15 November 2021, 782 adults were randomly assigned to PHH-1V (n = 522) or BNT162b2 (n = 260) boost vaccine groups. The geometric mean titre (GMT) ratio of neutralizing antibodies on days 14, 28 and 98, shown as BNT162b2 active control versus PHH-1V, was, respectively, 1.68 (p < 0.0001), 1.31 (p = 0.0007) and 0.86 (p = 0.40) for the ancestral Wuhan-Hu-1 strain; 0.62 (p < 0.0001), 0.65 (p < 0.0001) and 0.56 (p = 0.003) for the Beta variant; 1.01 (p = 0.92), 0.88 (p = 0.11) and 0.52 (p = 0.0003) for the Delta variant; and 0.59 (p ≤ 0.0001), 0.66 (p < 0.0001) and 0.57 (p = 0.0028) for the Omicron BA.1 variant. Additionally, PHH-1V as a booster dose induced a significant increase of CD4+ and CD8+ T-cells expressing IFN-γ on day 14. There were 458 participants who experienced at least one adverse event (89.3%) in the PHH-1V and 238 (94.4%) in the BNT162b2 group. The most frequent adverse events were injection site pain (79.7% and 89.3%), fatigue (27.5% and 42.1%) and headache (31.2 and 40.1%) for the PHH-1V and the BNT162b2 groups, respectively. A total of 52 COVID-19 cases occurred from day 14 post-vaccination (10.14%) for the PHH-1V group and 30 (11.90%) for the BNT162b2 group (p = 0.45), and none of the subjects developed severe COVID-19. Interpretation: Our interim results from the Phase IIb HH-2 trial show that PHH-1V as a heterologous booster vaccine, when compared to BNT162b2, although it does not reach a non-inferior neutralizing antibody response against the Wuhan-Hu-1 strain at days 14 and 28 after vaccination, it does so at day 98. PHH-1V as a heterologous booster elicits a superior neutralizing antibody response against the previous circulating Beta and the currently circulating Omicron BA.1 SARS-CoV-2 variants in all time points assessed, and for the Delta variant on day 98 as well. Moreover, the PHH-1V boost also induces a strong and balanced T-cell response. Concerning the safety profile, subjects in the PHH-1V group report significantly fewer adverse events than those in the BNT162b2 group, most of mild intensity, and both vaccine groups present comparable COVID-19 breakthrough cases, none of them severe. Funding: HIPRA SCIENTIFIC, S.L.U.

Tenofovir Disoproxil Fumarate/Emtricitabine and Baricitinib for Patients at High Risk of Severe Coronavirus Disease 2019: The PANCOVID Randomized Clinical Trial.

BACKGROUND: This study was designed to evaluate if patients with high risk for severe coronavirus disease 2019 (COVID-19) would benefit from treatment with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) followed by baricitinib in case of hypoxemia and systemic inflammation. METHODS: PANCOVID is an open-label, double-randomized, phase 3 pragmatic clinical trial including adults with symptomatic COVID-19 with ≥2 comorbidities or aged ≥60 years and was conducted between 10 October 2020 and 23 September 2021. In the first randomization, patients received TDF/FTC or no TDF/FTC. In the second randomization, patients with room air oxygen saturation <95% and at least 1 increased inflammatory biomarker received baricitinib plus dexamethasone or dexamethasone alone. The primary endpoint was 28-day mortality. Main secondary endpoint was 28-day disease progression or critical care unit admission or mortality. The trial was stopped before reaching planned sample size due to the decrease in the number of cases and a mortality rate substantially lower than expected. RESULTS: Of the 355 included participants, 97% were hospitalized at baseline. Overall, 28-day mortality was 3.1%. The 28-day mortality relative risk (RR) for participants treated with TDF/FTC was 1.76 (95% confidence interval [CI], .52-5.91; P = .379); it was 0.42 (95% CI, .11-1.59; P = .201) for those treated with baricitinib. The 28-day RR for the main secondary combined endpoint for participants treated with TDF/FTC was 0.95 (95% CI, .66-1.40; P = .774); it was 0.90 (95% CI, .61-1.33; P = .687) for those treated with baricitinib. CONCLUSIONS: Our results do not suggest a beneficial effect of TDF/FTC; nevertheless, they are compatible with the beneficial effect of baricitinib already established by other clinical trials. CLINICAL TRIALS REGISTRATION: EudraCT: 2020-001156-18.

Melatonin in the Prophylaxis of SARS-CoV-2 Infection in Healthcare Workers (MeCOVID): A Randomised Clinical Trial.

We evaluated in this randomised, double-blind clinical trial the efficacy of melatonin as a prophylactic treatment for prevention of SARS-CoV-2 infection among healthcare workers at high risk of SARS-CoV-2 exposure. Healthcare workers fulfilling inclusion criteria were recruited in five hospitals in Spain and were randomised 1:1 to receive melatonin 2 mg administered orally for 12 weeks or placebo. The main outcome was the number of SARS-CoV-2 infections. A total of 344 volunteers were screened, and 314 were randomised: 151 to placebo and 163 to melatonin; 308 received the study treatment (148 placebo; 160 melatonin). We detected 13 SARS-CoV-2 infections, 2.6% in the placebo arm and 5.5% in the melatonin arm (p = 0.200). A total of 294 adverse events were detected in 127 participants (139 in placebo; 155 in melatonin). We found a statistically significant difference in the incidence of adverse events related to treatment: 43 in the placebo arm and 67 in the melatonin arm (p = 0.040), and in the number of participants suffering from somnolence related to treatment: 8.8% (n = 14) in the melatonin versus 1.4% (n = 2) in the placebo arm (p = 0.008). No severe adverse events related to treatment were reported. We cannot confirm our hypothesis that administration of melatonin prevents the development of SARS-CoV-2 infection in healthcare workers.

Pressurized Hot Liquid Extraction with 15% v/v Glycerol-Water as An Effective Environment-Friendly Process to Obtain Durvillaea incurvata and Lessonia spicata Phlorotannin Extracts with Antioxidant and Antihyperglycemic Potential.

Brown seaweed phlorotannins have shown the potential to promote several health benefits. Durvillaea incurvata and Lessonia spicata-species that are widely distributed in central and southern Chile-were investigated to obtain phlorotannin extracts with antioxidant and antihyperglycemic potential. The use of an environmentally friendly and food-grade glycerol-based pressurized hot liquid extraction (PHLE) process (15% v/v glycerol water) was assessed for the first time to obtain phlorotannins. Multiple effects were analyzed, including the effect of the species, harvesting area (Las Cruces and Niebla), and anatomical part (holdfast, stipe, and frond) on the extracts' polyphenol content (TPC), antioxidant capacity (AC), and carbohydrate-hydrolyzing enzyme-α-glucosidase and α-amylase-inhibitory activity. Contaminants, such as mannitol, heavy metals (As, Cd, Pb, Hg, and Sn), and 5-hydroxymethylfurfural (HMF), were also determined. The anatomical part used demonstrated a significant impact on the extracts' TPC and AC, with holdfasts showing the highest values (TPC: 95 ± 24 mg phloroglucinol equivalents/g dry extract; DPPH: 400 ± 140 µmol Trolox equivalents/g dry extract; ORAC: 560 ± 130 µmol TE/g dry extract). Accordingly, holdfast extracts presented the most potent α-glucosidase inhibition, with D. incurvata from Niebla showing an activity equivalent to fifteen times that of acarbose. Only one frond and stipe extract showed significant α-glucosidase inhibitory capacity. No α-amylase inhibition was found in any extract. Although no HMF was detected, potentially hazardous cadmium levels (over the French limit) and substantial mannitol concentrations-reaching up to 50% of the extract dry weight-were found in most seaweed samples and extracts. Therefore, further purification steps are suggested if food or pharmaceutical applications are intended for the seaweed PHLE extracts obtained in this study.

Chemical Properties of Vitis Vinifera Carménère Pomace Extracts Obtained by Hot Pressurized Liquid Extraction, and Their Inhibitory Effect on Type 2 Diabetes Mellitus Related Enzymes.

Grape pomace polyphenols inhibit Type 2 Diabetes Mellitus (T2DM)-related enzymes, reinforcing their sustainable recovery to be used as an alternative to the synthetic drug acarbose. Protic co-solvents (ethanol 15% and glycerol 15%) were evaluated in the hot pressurized liquid extraction (HPLE) of Carménère pomace at 90, 120, and 150 °C in order to obtain extracts rich in monomers and oligomers of procyanidins with high antioxidant capacities and inhibitory effects on α-amylase and α-glucosidase. The higher the HPLE temperature (from 90 °C to 150 °C) the higher the total polyphenol content (~79%, ~83%, and ~143% for water-ethanol, water-glycerol and pure water, respectively) and antioxidant capacity of the extracts (Oxygen Radical Absorbance Capacity, ORAC), increased by ~26%, 27% and 13%, while the half maximal inhibitory concentration (IC50) decreased by ~65%, 67%, and 59% for water-ethanol, water-glycerol, and pure water extracts, respectively). Water-glycerol HPLE at 150 and 120 °C recovered the highest amounts of monomers (99, 421, and 112 µg/g dw of phenolic acids, flavanols, and flavonols, respectively) and dimers of procyanidins (65 and 87 µg/g dw of B1 and B2, respectively). At 90 °C, the water-ethanol mixture extracted the highest amounts of procyanidin trimers (13 and 49 µg/g dw of C1 and B2, respectively) and procyanidin tetramers of B2 di-O-gallate (13 µg/g dw). Among the Carménère pomace extracts analyzed in this study, 1000 µg/mL of the water-ethanol extract obtained, at 90 °C, reduced differentially the α-amylase (56%) and α-glucosidase (98%) activities. At the same concentration, acarbose inhibited 56% of α-amylase and 73% of α-glucosidase activities; thus, our grape HPLE extracts can be considered a good inhibitor compared to the synthetic drug.

Thyme essential oil loaded microspheres for fish fungal infection: microstructure, in vitro dynamic release and antifungal activity.

AIMS: Evaluate the effect of varying the droplet size of microspheres charged with thyme essential oil (TEO-MS) on their swelling (Sw), release rate (%RR) and in vitro antifungal activity against Saprolegnia sp. METHODS: TEO-MS obtained by ionic gelation were characterised through SEM microscopy and X-ray microtomography. Their Sw and RR% were evaluated at simulated fish-gastrointestinal conditions using gravimetric and spectrophotometric techniques. RESULTS: For all evaluated droplet sizes (p ≥ 0.05), TEO was heterogeneously distributed inside of the MS and TEO-MS experimented agglomeration and sphericity loss after the drying process. Under gastric conditions, the acid pH (2.9) limited the Sw (50-100%) of TEO-MS, generating a low RR% (14-18%). Contrary, the slightly alkaline intestinal pH (8.1) favoured the Sw (∼3.2 to 3.8 times) and therefore the RR% (42-63%). CONCLUSIONS: TEO-MS (5-100 mg/mL) presented antifungal capacity onto Saprolegnia sp. after the simulated fish digestion, being the small droplet size once the most effective.

Bioactive Polyphenols from Southern Chile Seaweed as Inhibitors of Enzymes for Starch Digestion.

The increment of non-communicable chronic diseases is a constant concern worldwide, with type-2 diabetes mellitus being one of the most common illnesses. A mechanism to avoid diabetes-related hyperglycemia is to reduce food digestion/absorption by using anti-enzymatic (functional) ingredients. This research explored the potential of six common Chilean seaweeds to obtain anti-hyperglycemic polyphenol extracts, based on their capacity to inhibit key enzymes related with starch digestion. Ethanol/water hot pressurized liquid extraction (HPLE), which is an environmentally friendly method, was studied and compared to conventional extraction with acetone. Total polyphenols (TP), antioxidant activity, cytotoxicity and inhibition capacity on α-glucosidase and α-amylase were analyzed. Results showed that the Durvillaea antarctica (cochayuyo) acetone extract had the highest TP content (6.7 ± 0.7 mg gallic acid equivalents (GAE)/g dry seaweed), while its HPLE ethanol/water extract showed the highest antioxidant activity (680.1 ± 11.6 µmol E Trolox/g dry seaweed). No extract affected cell viability significantly. Only cochayuyo produced extracts having relevant anti-enzymatic capacity on both studied enzymes, showing a much stronger inhibition to α-glucosidase (even almost 100% at 1000 µg/mL) than to α-amylase. In conclusion, from the Chilean seaweeds considered in this study, cochayuyo is the most suitable for developing functional ingredients to moderate postprandial glycemic response (starchy foods), since it showed a clear enzymatic inhibition capacity and selectivity.

A randomized multicenter clinical trial to evaluate the efficacy of melatonin in the prophylaxis of SARS-CoV-2 infection in high-risk contacts (MeCOVID Trial): A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: Primary objective: to evaluate the efficacy of melatonin as a prophylactic treatment on prevention of symptomatic SARS-CoV-2 infection among healthcare workers at high risk of SARS-CoV-2 exposure. Secondary objectives: To evaluate the efficacy of melatonin as a prophylactic treatment on prevention of asymptomatic SARS-CoV-2 infection.To evaluate the efficacy of melatonin to prevent the development of severe COVID-19 in the participants enrolled in this study who develop SARS-CoV-2 infection along the trial.To evaluate the duration of COVID-19 symptoms in participants receiving melatonin before the infection.To evaluate seroconversion timing post-symptom onset. Exploratory objectives:To compare severity of COVID-19 between men and women.To evaluate the influence of sleep and diet on prevention from SARS-CoV-2 infection.To evaluate the effect of melatonin on the incidence and characteristics of lymphopenia and increase of inflammatory cytokines related to COVID-19. TRIAL DESIGN: This is a two-arm parallel randomised double-blind controlled trial to evaluate the efficacy of melatonin versus placebo in the prophylaxis of coronavirus disease 2019 among healthcare workers. PARTICIPANTS: Inclusion Criteria: Male or female participants ≥ 18 and ≤ 80 years of age.Healthcare workers from the public and private Spanish hospital network at risk of SARS-CoV 2 infection.Not having a previous COVID19 diagnosis.Understanding the purpose of the trial and not having taken any pre-exposure prophylaxis (PrEP) including HIV PrEP from March 1st 2020 until study enrolment.Having a negative SARS-CoV 2 reverse-transcription PCR (RT-PCR) result or a negative serologic rapid test (IgM/IgG) result before randomization.Premenopausal women must have a negative urinary pregnancy test in the 7 days before starting the trial treatment.Premenopausal women and males with premenopausal couples must commit to using a high efficiency anticonceptive method. EXCLUSION CRITERIA: HIV infection.Active hepatitis B infection.Renal failure (CrCl < 60 mL/min/1.73 m2) or need for hemodialysis.Osteoporosis.Myasthenia gravis.Pre-existent maculopathy.Retinitis pigmentosa.Bradycardia (less than 50 bpm).Weight less than 40 Kg.Participant with any immunosuppressive condition or hematological disease.Treatment with drugs that may prolong QT in the last month before randomization for more than 7 days including: azithromycin, chlorpromazine, cisapride, clarithromycin, domperidone, droperidol, erythromycin, halofantrine, haloperidol, lumefantrine, mefloquine, methadone, pentamidine, procainamide, quinidine, quinine, sotalol, sparfloxacin, thioridazine, amiodarone.Hereditary intolerance to galactose, Lapp lactase deficiency or glucose or galactose malabsorption.Treatment with fluvoxamine.Treatment with benzodiazepines or benzodiazepine analogues such as zolpidem, zopiclone or zaleplon.Pregnancy.Breastfeeding.History of potentially immune derived diseases such as: lupus, Crohn's disease, ulcerative colitis, vasculitis or rheumatoid arthritis.Insulin-dependent diabetes mellitus.Known history of hypersensitivity to the study drug or any of its components.Patients that should not be included in the study at the judgment of the research team. Participants will be recruited from the following eight hospitals in Madrid, Spain: Hospital Universitario La Paz, Hospital Ramón y Cajal, Hospital Infanta Sofía, Hospital 12 de Octubre, Hospital Clínico San Carlos, Hospital Central de la defensa Gómez Ulla,Hospital de La Princesa and Hospital Infanta Leonor. INTERVENTION AND COMPARATOR: Experimental: Melatonin (Circadin®, Exeltis Healthcare, Spain): 2 mg of melatonin orally before bedtime for 12 weeks. Comparator: Identical looking placebo (Laboratorios Liconsa, Spain) orally before bedtime for 12 weeks. MAIN OUTCOMES: Number of SARS-CoV-2 (COVID-19) symptomatic infections confirmed by polymerase chain reaction (PCR) test or serologic test or according to each centre diagnosis protocol. Primary outcome will be measured until the end of treatment for each participant (until the date of the last dose taken by each patient). RANDOMISATION: Patients who meet all inclusion and no exclusion criteria will be randomised, stratified by centres, sex and age (<50 and ≥ 50 years old). The randomisation sequence was created using SAS version 9.4 statistical software (procedure 'PROC PLAN') with a 1:1 allocation. No randomisation seed was specified. The randomisation seed was generated taking the hour of the computer where the program was executed. Randomization will be done centrally through the electronic system RedCAP® in order to conceal the sequence until interventions are assigned BLINDING (MASKING): Participants, caregivers, and those assessing the outcomes are blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 450 participants are planned to be enrolled in this clinical trial, 225 in the experimental arm and 225 in the placebo arm. TRIAL STATUS: Protocol version 3.0, 17th of April 2020. Recruitment ongoing. First participant was recruited on the 21st of April 2020. The final participant is anticipated to be recruited on the 31st of May 2020. As of May 18th, 2020, a total of 312 participants have been enrolled (154 at Hospital La Paz, 85 at Hospital Infanta Sofía and 73 at Hospital 12 de Octubre). TRIAL REGISTRATION: EU Clinical Trials Register: 2020-001530-35; Date of trial registration: 13th of April 2020; https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001530-35/ES FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Microencapsulation of Anthocyanin Extracted from Purple Flesh Cultivated Potatoes by Spray Drying and Its Effects on In Vitro Gastrointestinal Digestion.

Purple flesh cultivated potato (PP) is a foodstuff scarcely cultivated in the world but with high potential because of its anthocyanin content. Moreover, it has been little explored as a source of anthocyanins (AT) for further applications in formulated food products. The main goal of this research was to study the effect of maltodextrin (MD) and spray drying conditions on the encapsulation efficiency (EE) and bioaccesibility of AT from purple flesh cultivated potato extract (PPE). The anthocyanin-rich extract was obtained from PP and microencapsulated by spray-drying, using MD as the encapsulating agent. A statistical optimization approach was used to obtain optimal microencapsulation conditions. The PPE microparticles obtained under optimal conditions showed 86% of EE. The protector effect of microencapsulation on AT was observed to be stable during storage and in vitro digestion. The AT degradation rate constant was significantly lower for the PPE-MD than for the PPE. The assessed bioaccesibility of AT from the PPE-MD was 20% higher than that of the PPE, which could be explained by the protective effect of encapsulation against environmental conditions. In conclusion, microencapsulation is an effective strategy to protect AT from PP, suggesting that AT may be an alternative as a stable colorant for use in the food industry.

Role of maltodextrin and inulin as encapsulating agents on the protection of oleuropein during in vitro gastrointestinal digestion.

Olive leaves extract (OLE) was spray-dried with maltodextrin (MD) or inulin (IN) to study the evolution of oleuropein (OE) during in vitro gastrointestinal digestion, its bioaccessibility and potential bioavailability. In the case of OLE-MD, OE was partially degraded in gastric and intestinal conditions; whereas in OLE-IN, OE was released under gastric conditions and partially degraded under intestinal conditions. In both cases, the encapsulation of OLE led to higher OE contents at the end of digestion, compared with non-encapsulated OLE, suggesting a protective role of the polysaccharides by the formation of non-covalent polysaccharides-OE complexes. OE bioaccessibility was ten times higher (p ≤ 0.05) in OLE-MD and OLE-IN than in non-encapsulated OLE. However, OE potential bioavailability, evaluated by tangential filtration, was not detected. Encapsulation technology and the encapsulant agent used may determine the release of the encapsulated compounds at a specific-site and their effect on health.

Microstructure of starch-based meals with either palm or soybean oils alter in vitro starch digestibility with no major effects on glycaemic responses.

Glycaemic response (GR) to starch-based meals depends on their food composition and microstructure. We studied the effect of palm and soybean oils on the microstructure of a solid starch-oil-gluten matrix, on the starch gelatinisation and in vitro digestibility. Additionally, a pilot cross-over study was carried out to assess GR after eating gelatinised starch/gluten-based foods with the addition of either palm or soybean oil in 8 young non-diabetic female volunteers (ISRCTN39636850). Both types of foods generated similar starch gelatinisation temperature. Starch/gluten-based food with soybean oil had rougher microstructure compared to food with palm oil, showing a higher initial and lower final in vitro digestion. Administration of starch/gluten-based meals with either palm or soybean oils to volunteers show very similar postprandial glucose or insulin responses. In conclusion, differences in fatty acid composition changes food microstructure and in vitro starch digestibility, with no major effects on glycaemic responses in female volunteers.

Fractura expuesta de pierna con defecto óseo segmentario: reconstrucción con técnica de inducción de membrana tipo masquelet. A propósito de un caso / Exposed fracture of leg with a segmentary bone defect: reconstruction with masquelet or induced membrane technique. A clinical case

Las fracturas expuestas de tibia por alta energía se asocian a conminución, pérdida de stock óseo y daño de partes blandas. El manejo inicial debe incluir el aseo quirúrgico con desbridamiento adecuado. La evidencia actual sugiere realizar un manejo por etapas, conforme el estado de cobertura de partes blandas permita realizar la reconstrucción ósea definitiva. Los defectos óseos segmentarios críticos agregan el problema de requerir de una técnica de reconstrucción ósea para disminuir riesgo de infección, retardo en la consolidación y no unión. Se presenta un caso clínico con defecto óseo crítico de tibia con falta de cobertura de partes blandas, tratado con colgajo de sural anterógrado y técnica de inducción de membrana tipo Masquelet.

High energy, exposed fractures of the tibia are associated with comminution, bone loss, and soft tissue damage. It should be managed initially with surgical cleaning and debridement. If the soft tissue envelope permits definitive osseus reconstruction, the evidence at present suggests managing it in stages. Critical segmentary bone defects require osseous reconstruction for reduction of infection risk, consolidation delay and nonunion. We present a clinical case with a critical bone defect and significant soft tissue loss treated with an anterograde sural flap and induced membrane or Masquelet technique.

The Microencapsulation of Maqui (Aristotelia chilensis (Mol.) Stuntz) Juice by Spray-Drying and Freeze-Drying Produces Powders with Similar Anthocyanin Stability and Bioaccessibility.

The microencapsulation of maqui juice by spray-drying and freeze-drying was studied as a strategy to protect anthocyanins in new food formulations in order to improve the anthocyanin retention before consumption and the bioaccessibility. It is well known that the encapsulation method affects both the shape and size of powders, being assumed that undefined forms of freeze-drying powders might affect their stability due to the high permeability to oxygen. The objective of this study was to compare the microencapsulation of maqui juice by spray-drying and freeze-drying, evaluating the stability of specific anthocyanins in yogurt and after in vitro digestion. Results indicated that most relevant differences between spray-drying and freeze-drying powders were the morphology and particle size that affect their solubility (70.4⁻59.5%) when they were reconstituted in water. Nevertheless these differences did not affect the stability of anthocyanins as other research have proposed. Both encapsulation methods generated powders with a high stability of 3-O-monoglycosylated anthocyanins in yogurt (half-life values of 75⁻69 days for delphinidin-3-sambubioside). Furthermore, no significant differences in the bioaccessibility of anthocyanins between maqui juice powders (44.1⁻43.8%) were found. In conclusion, the microencapsulation of maqui juice by freeze-drying is as effective as spray-drying to produce new value-added food formulations with stable anthocyanins.

Leptin/Adiponectin Ratios Using Either Total Or High-Molecular-Weight Adiponectin as Biomarkers of Systemic Insulin Sensitivity in Normoglycemic Women.

Plasma leptin/adiponectin ratio (LAR) is negatively associated with insulin sensitivity indexes. High-molecular-weight adiponectin (HMWA) was proposed as the most biologically active form of this insulin-sensitizing adipokine. There are no studies assessing the relative merits of leptin/HMWA ratio over LAR as a biomarker of systemic insulin sensitivity. A standard 2-hour oral glucose tolerance test (OGTT; 75 g of glucose) and a short minimal-model intravenous glucose tolerance test (IVGTT; 0.3 g/kg body weight) were performed in 58 Chilean normoglycemic women (age: 27 ± 6.3 years, BMI 23.6 ± 3.2 kg/m2). LAR was negatively associated with HOMA-S (r = -0.49; p < 0.0001), Matsuda-ISICOMP (r = -0.54; p < 0.0001), and the calculated sensitivity index (CSi) derived from IVGTT (r = -0.38; p = 0.007). In comparison to LAR, leptin/HMWA ratio did not increase neither the linear fit (r2) nor the magnitude of association with insulin sensitivity indexes (slope of multiple linear regression). The discriminatory capacity of both ratios to classify insulin-resistant versus insulin-sensitive subjects was similar for HOMA-S (p = 0.84), Matsuda-ISICOMP (p = 0.43), or CSi (p = 0.50). In conclusion, LAR showed consistent negative associations with different systemic insulin sensitivity indexes. The use of HMWA to generate leptin/HMWA ratio did not show any advantage over LAR as a biomarker of systemic insulin sensitivity in normoglycemic women.

Development of alginate microspheres containing thyme essential oil using ionic gelation.

Essential oils are a good antimicrobial and antioxidant agent alternative in human or animal feed. However, their direct use has several disadvantages such as volatilization or oxidation. The development of essential oil microspheres may help to avoid these problems. The objective of the present research was to microencapsulate thyme essential oil by generating emulsions with different dispersion degrees. The emulsions were encapsulated in calcium-alginate microspheres by ionic gelation. The microspheres were evaluated regarding size, shape, encapsulation efficiency, loading capacity and antimicrobial properties. The results indicate that encapsulation efficiency and loading capacity are dependent on concentration and degree of dispersion. The best encapsulation conditions were obtained at 2% v/v of thyme essential oil with a high dispersion degree (18,000rpm/5min), which was achieved with an efficiency of 85%. Finally, the microspheres obtained showed significant antimicrobial effect, especially in gram-positive bacteria.

The effect of vacuum frying on starch gelatinization and its in vitro digestibility in starch-gluten matrices.

Starch digestibility in a food matrix depends on processing conditions that may affect its physical state and microstructure. Starch gelatinization is one critical change that takes place during frying which could be affected during low-pressure processing. This study assessed the effect of vacuum frying on starch gelatinization and its in vitro digestibility. Laminated dough was made of a reconstituted blend of wheat starch (88% d.b.) and gluten (12% d.b.). Samples were fried under vacuum (6.5 kPa, Twater-boiling-point=38°C) or atmospheric conditions up to bubble-end point, maintaining a thermal driving force of 70°C (Toil-Twater-boiling-point=70°C). Vacuum fried samples showed less starch gelatinization (28%), less rapidly available glucose (27%), and more unavailable glucose (70%) than their atmospheric counterparts (which presented 99% starch gelatinization, 40% rapidly available glucose, and 46% unavailable glucose), and the values were close to those of raw dough. These results show how vacuum processing may be used to control the degree of starch gelatinization and related digestibility.

Interactions between Starch, Lipids, and Proteins in Foods: Microstructure Control for Glycemic Response Modulation.

In real food, starch is usually forming part of a matrix with lipids and proteins. However, research on this ternary system and interactions between such food components has been scarce so far. The control of food microstructure is crucial to determine the product properties, including sensorial and nutritionals ones. This paper reviews the microstructural principles of interactions between starch, lipids, and proteins in foods as well as their effect on postprandial glycemic response, considering human intrinsic differences on postprandial glycemic responses. Several lines of research support the hypothesis that foods without rapidly digestible starch will not mandatorily generate the lowest postprandial glycemic response, highlighting that the full understanding of food microstructure, which modulates starch digestion, plays a key role on food design from a nutritional viewpoint.