Consequences of the Covid-19 pandemic on complex multimorbid elderly: Follow-up of a community-based cohort. SAMAC3 Study.

BACKGROUND: The restrictions imposed during the management of the pandemic led to lack of care of other health problems. PURPOSE: To assess changes in the health status of complex multimorbidity elderly, functional and cognitive capacities, perception of the social surroundings, care provided by the nurses, including nursing diagnosis and interventions, use of health services, adverse events, and use of devices and technical help during the first 6 months of the Covid-19 pandemic. DESIGN: A 1-year longitudinal cohort study was conducted. METHODS: Ninety-seven complex multimorbid elderly attended in primary care were evaluated every 3 months in a health area of the Spanish National Health System (SNHS). The research was called "SAMAC3 study". RESULTS: Significant negative changes were observed in the functional and cognitive capacity of the elderly, and in several nursing diagnoses. A decrease was observed in the frequency of visit to the nurses, hospital admittance, length of hospital stays, and falls. CONCLUSIONS: The functional and cognitive capacities of the cohort became worse. However, a significant decrease in the frequency of use of health services was observed. The nurses detected significant changes in activity-exercise, cognitive-perception, and roles-relationships, but their interventions were mostly centered on resolving clinical matters that required immediate attention. CLINICAL RELEVANCE: The present study allowed us to observe that a situation of social and health stress has worsened the health indicators of multimorbid elderly, and the clinical care of community nurses was insufficient to providing care for the deterioration of the physical and cognitive domains.

A reduced 1D stochastic model of bleb-driven cell migration.

Blebs are pressure-driven protrusions that have been observed in cells undergoing apoptosis, cytokinesis, or migration, including tumor cells that use blebs to escape their organs of origin. Here, we present a minimal 1D model of bleb-driven cell motion that combines a simple mechanical model with turnover kinetics of the actin cortex and adhesions between the membrane and the cortex. The deterministic version of this model is used to study the properties of individual blebbing events. We further introduce stochastic turnover of the adhesions, which allows for spontaneous initiation of repeated blebbing events, thus leading to sustained cell travel. We explore how the main parameters of the system control the properties of the blebbing events and the speed of cell travel. Finally, we derive a further simplification by deriving a Langevin approximation to this stochastic model.

Improving type 2 diabetes mellitus glycaemic control through lifestyle modification implementing diet intervention: a systematic review and meta-analysis.

PURPOSE: Type 2 diabetes mellitus represents a significant health problem. Many studies have reported that intensive nutritional intervention by itself or in addition to medications is the best method to improve glycaemic control in type 2 diabetes mellitus. However, in clinical practice, dietary education is not implemented as an integral part in the management of type 2 diabetes mellitus. The purpose of this systematic review and meta-analysis is to analyse the scientific evidence concerning the role of nutritional intervention in the glycaemic control of type 2 diabetes mellitus. METHODS: We searched Pubmed, Scopus, Cochrane Library and Web of Science databases from inception till May 2019 for randomised controlled trials (RCTs) that include dietary interventions in the management of patients with type 2 diabetes mellitus. RESULTS: A total of 28 studies were included. Our results demonstrated that lifestyle interventions significantly lowered glycosylated haemoglobin (HbA1c) levels compared to the usual care for patients with type 2 diabetes mellitus, overall weighted mean difference, WMD = - 0.51 (- 0.67, - 0.35). Strategies combining individualized and group-based activities were the most effective, WMD = - 0.95 (- 1.24, - 0.66). Most of stratified analyses did not totally resolve heterogeneity, but improvement in HbA1c levels has been consistently observed. CONCLUSIONS: The available evidence from RCTs shows that lifestyle intervention is more effective than the standard care regarding the glycaemic control of type 2 diabetic patients, particularly when there is a weight loss. It is time to translate this evidence to the primary health care practice. The protocol of the present systematic review was registered in PROSPERO, registration number CRD42018090469.

Insight meditation and telomere biology: The effects of intensive retreat and the moderating role of personality.

A growing body of evidence suggests that meditation training may have a range of salubrious effects, including improved telomere regulation. Telomeres and the enzyme telomerase interact with a variety of molecular components to regulate cell-cycle signaling cascades, and are implicated in pathways linking psychological stress to disease. We investigated the effects of intensive meditation practice on these biomarkers by measuring changes in telomere length (TL), telomerase activity (TA), and telomere-related gene (TRG) expression during a 1-month residential Insight meditation retreat. Multilevel analyses revealed an apparent TL increase in the retreat group, compared to a group of experienced meditators, similarly comprised in age and gender, who were not on retreat. Moreover, personality traits predicted changes in TL, such that retreat participants highest in neuroticism and lowest in agreeableness demonstrated the greatest increases in TL. Changes observed in TRGs further suggest retreat-related improvements in telomere maintenance, including increases in Gar1 and HnRNPA1, which encode proteins that bind telomerase RNA and telomeric DNA. Although no group-level changes were observed in TA, retreat participants' TA levels at post-assessment were inversely related to several indices of retreat engagement and prior meditation experience. Neuroticism also predicted variation in TA across retreat. These findings suggest that meditation training in a retreat setting may have positive effects on telomere regulation, which are moderated by individual differences in personality and meditation experience. (ClinicalTrials.gov #NCT03056105).

Individualized embryo transfer training: timing and performance.

STUDY QUESTION: How long is the individualized training and the stability of competence for the embryo transfer (ET) technique? SUMMARY ANSWER: The embryo transfer technique is easy-to-learn, hardly unlearned, and training should be individualized by monitoring with learning curve-cumulative summation (LC-CUSUM) curves. WHAT IS KNOWN ALREADY: Like many medical procedures, embryo transfer is an operator-dependent technique. Individualized or standardized training of these medical procedures should be monitored to determine when competence is acquired. STUDY DESIGN, SIZE, DURATION: This prospective, monocentric study involving five embryo transfer trainees was carried out between August 2011 and November 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was carried out in a large private clinic. Five gynaecologist trainees during their first year of assisted reproduction subspecialty performed embryo transfer for patients undergoing either fresh IVF, oocyte donor IVF, or frozen embryo transfer. There were 586 embryo transfers performed in 96 sessions of 3-10 embryo transfers each. An embryo transfer was considered successful if it gave rise to a positive pregnancy test 14 days later. LC-CUSUM and cumulative summation (CUSUM) curves were used to determine when competence was acquired and whether it was maintained over time, respectively. The length of time between two consecutive sessions was assessed for an effect on consolidation of the acquired competence. MAIN RESULTS AND THE ROLE OF CHANCE: We observed that all five trainees became proficient in embryo transfer by procedure 15 (after procedure 15, 9, 7, 13 and 9, respectively). Once competence was achieved, one of the five trainees showed a loss of proficiency. After having acquired competence, the median pregnancy rate per embryo transfer session was significantly lower when the interval between consecutive embryo transfer sessions was ≥10 days compared with <10 days (20.0 versus 46.7%; P = 0.006). LIMITATIONS, REASONS FOR CAUTION: The patient groups included in the study were heterogeneous (IVF, oocyte donor IVF and frozen embryo transfer) and their outcomes are very variable; thus the distribution and proportion of these groups can determine the timing of competence acquisition. Our data show that low numbers of embryo transfer are needed to acquire competence, but since a relative high percentage of embryo transfers in our practice are from oocyte donor IVF, extrapolation of the findings to other clinical context should be done with caution. WIDER IMPLICATIONS OF THE FINDINGS: Personalized embryo transfer training is feasible and useful, allowing clinics, on one hand, to offer a maximum chances of pregnancy with fully trained personnel, and the other hand, to avoid the superfluous and costly overtraining of already proficient trainees. Furthermore, it is advisable to maintain a short interval of time between consecutive embryo transfer sessions after a trainee has acquired competence, to avoid a significant drop in the resulting pregnancy rate. STUDY FUNDING/COMPETING INTEREST(S): This work was supported in part by funding from Fundació Privada EUGIN. There are no conflicts of interest to declare.

Learning curves in 3-dimensional sonographic follicle monitoring during controlled ovarian stimulation.

OBJECTIVES: Three-dimensional (3D) sonographically based automated volume calculation (SonoAVC; GE Healthcare, Zipf, Austria) is being introduced in folliculometry during ovarian stimulation; however, clear training assessments in this technique are lacking. The learning curve-cumulative summation (LC-CUSUM) test provides a quantitative tool to determine when a trainee has learned a procedure. The aim of this prospective study was to assess 3D SonoAVC LC-CUSUM curves in folliculometry. METHODS: Analyses were performed on 98 oocyte donors by capturing the ovarian image in 3D and applying the 3D SonoAVC software during ovarian stimulation cycles. Each patient was scanned by an expert operator and by a trainee. Independent LC-CUSUM tests for 4 follicular diameters tracked the competency of 3 trainees in 3D SonoAVC. RESULTS: We found that the numbers of sonographic examinations required by the 3 trainees to identify the correct number of follicles of 10 mm or larger were 38, 32, and 28, respectively; for follicles of 14 mm or larger, they were 29, 28, and 28; for follicles of 18 mm or larger, they were 24, 19, and 27; and for follicles of 21 mm or larger, they were 29, 19, and 24. CONCLUSIONS: A variable number of procedures are needed to reach proficiency in 3D SonoAVC, even for trained 2-dimensional sonographers. Assessment of learning curves should be implemented when incorporating 3D SonoAVC in reproduction units.

Experiences and perceptions of people with celiac disease, food allergies and food intolerance when dining out.

Introduction: Eating out is a common practice in modern society. Celiac disease (CeD) and food allergy (FA) are among the most common conditions responsible for adverse reactions to food. Despite their different origins, both require treatment with restrictive diets (avoidance of gluten and/or specific allergens) and this results posing similar challenges when eating out. Our objective was to learn about the experiences/perceptions of consumers with CeD and FA when dining out, as well as the challenges they face in food service environments. Methods: An ad hoc questionnaire was used to record consumer perceptions, food service characteristics and resulting adverse reactions. Results: 377 individuals living in Santiago, Chile, provided complete information and were analyzed (160 CeD, 105 FA). 301 participants (79.8%) declared eating out, 33.6% reported experiencing an adverse reaction at least once while eating out. 94.4% of the 377 participants believed that the serving staff had little or no knowledge about his/her condition. Consumers reporting symptoms as severe adverse reactions were more common among celiac than allergic patients (p < 0.001). Discussion: The study showed no significant differences based on consumer-related characteristics (p:NS). The consequences of eating out did not vary based on individual's data, including diagnosis, age, frequency of eating out, adverse reactions experienced, or intensity. These findings suggest that the most important determinants of risk associated with eating out are characteristics of the food service, like availability of information, staff training, and establishment's facilities like equipment available, exclusive utensils for customers with special dietary needs and kitchen and bathrooms organization.

Results of a 7-week school-based physical activity and nutrition pilot program on health-related parameters in primary school children in southern Spain.

The goal of this study was to determine the effect of nutrition education combined with sessions of vigorous extracurricular physical activity (VEPA) on the improvement of health related parameters in children in primary education. The sample group consisted of 54 children in the fifth year of primary education divided into two groups: an intervention group (IG) of 25 students and a control group (CG) of 29 students. The intervention lasted 7 weeks and consisted of 13 sessions of VEPA combined with sessions of nutritional education that were attended by the students in the IG as well as their parents. During the intervention the IG showed a decrease in the body fat percentage, total cholesterol, cholesterol linked to low- density lipoproteins and blood pressure, together with an increase in cholesterol linked to high-density lipoproteins, and an improvement in the maximum oxygen uptake and dietary intake profile compared with the CG, which showed an increase in the percentage of fats and no significant changes (p < .05) in other parameters. The results of this study provide evidence that a 7-week program of nutritional education and vigorous short-duration physical activity can improve health related parameters in children.

Validation of the Spanish electronic version of the BREAST-Q questionnaire.

BACKGROUND: Patient-reported outcome measures (PROMs) have gained considerable interest in health care moving beyond traditional outcome measures of morbidity and mortality. In breast cancer surgery, women's' perceptions of appearance, function and quality of life have become increasingly important. The BREAST-Q questionnaire is a validated PROM for use in cosmetic and reconstructive breast surgery in clinical practice. The objective of this study was to validate the Spanish electronic version of the BREAST-Q questionnaire, to verify the measurement equivalence of digital and paper versions and to identify the possible disadvantages and advantages of implementing this new tool. METHODS: The study population included 113 patients undergoing breast cancer survey at a single hospital in Barcelona (Spain) who were able to complete both the electronic and paper versions of the preoperative module of the BREAST-Q questionnaire. RESULTS: The intraclass correlation coefficient (ICC) in the four domains of the questionnaire between the two versions of the questionnaire was >0.9, with a weighted kappa of >0.74 at item level. The reliability of the internal consistency was also excellent, with Cronbach's alpha coefficient of >0.70 in all domains. Age was a limiting factor for the delivery of the electronic version of BREAST-Q, with 69 years of age as the cut-off point to obtain reliable results. CONCLUSIONS: The interchangeability of the electronic and paper versions of the BREAST-Q questionnaire facilitates implementation of this instrument in routine surgical oncological practice.

Impact of COVID-19 Restrictions in Childbirth and Puerperium: A Cross-Sectional Study.

Introduction (1): The COVID-19 pandemic led to changes in healthcare during pregnancy, childbirth and puerperium. The objective of this study was to know the impact of visit restrictions, PCR performance and use of masks on delivery and puerperium care. Methods (2): A descriptive cross-sectional study was carried out. A survey was used to assess the impact of COVID-19-related measures on women who had given birth in hospitals in the Region of Murcia, Spain, between March 2020 and February 2022. Results (3): The final sample size was 434 women. The average scores were 4.27 for dimension 1 (Visit restrictions), 4.15 for dimension 2 (PCR testing) and 3.98 for dimension 3 (Mask use). More specifically, we found that the restriction of visits was considered a positive measure for the establishment of the mother-newborn bond (mean score 4.37) and that the use of masks at the time of delivery should have been made more flexible (mean score 4.7). Conclusions (4): The policy of restricting hospital visits during the pandemic caused by COVID-19 has been considered beneficial by mothers, who expressed that they did not feel lonely during their hospital stay.

Effects of a Clinical Simulation-Based Training Program for Nursing Students to Address Social Isolation and Loneliness in the Elderly: A Quasi-Experimental Study.

INTRODUCTION: The population of older adults is rapidly increasing worldwide, presenting both prospects and complexities for society and healthcare professionals to maximize the functional capacity of this age group. Social isolation and loneliness significantly affect this population. The objective was to determine the effectiveness, satisfaction, and perceptions of the simulation-based education practices of a training program for nursing students, which was created to palliate the social isolation and loneliness of older adults. METHOD: A quasi-experimental study was conducted with nursing students who participated in an online training program using teleservice based on high-fidelity clinical simulation. The program included asynchronous theoretical training and synchronous practical training using an online platform. Five scenarios were designed using simulated phone calls to address the social isolation and loneliness of older adults. RESULTS: Twenty-five nursing students participated in the program, and they had a mean age of 27.44, with 76% of them being women. After the training program, the participants showed statistically significant improvements (p < 0.05) with respect to their knowledge and attitudes towards older adults, and the program was adapted to the best educational practices in simulations. CONCLUSIONS: Simulation-based online training efficiently improved the knowledge and attitudes of nursing students towards older adults, improving their ability to address social isolation and loneliness. The high satisfaction and adhesion to the best educational practices underline the usefulness of high-fidelity online simulations, especially in situations in which face-to-face training is not feasible, and accessibility and equilibrium could be guaranteed between work and personal life.

Altered ß-adrenergic response in mice lacking myotonic dystrophy protein kinase.

The protein kinase product of the gene mutated in myotonic dystrophy 1 (DMPK) is reported to play a role in cardiac pathophysiology. To gain insight into the molecular mechanisms modulated by DMPK, we characterize the impact of DMPK ablation in the context of cardiac ß-adrenergic function. Our data demonstrate that DMPK knockout mice present altered ß-agonist-induced responses and suggest that this is due, at least in part, to a reduced density of ß(1)-adrenergic receptors in cardiac plasma membranes.

Melatonin induces fat browning by transdifferentiation of white adipocytes and de novo differentiation of mesenchymal stem cells.

The role of melatonin in obesity control is extensively accepted, but its mechanism of action is still unclear. Previously we demonstrated that chronic oral melatonin acts as a brown-fat inducer, driving subcutaneous white adipose tissue (sWAT) into a brown-fat-like function (beige) in obese diabetic rats. However, immunofluorescence characterization of beige depots in sWAT and whether melatonin is a beige-fat inducer by de novo differentiation and/or transdifferentiation of white adipocytes are still undefined. Lean (ZL) and diabetic fatty (ZDF) Zücker rats were subdivided into two groups, control (C) and oral melatonin-supplemented (M, 10 mg kg-1 day-1) for 6 weeks. Mesenchymal stem cells (MSCs) were isolated from both rat inguinal fat and human lipoaspirates followed by adipogenesis assays with or without melatonin (50 nM for 12 h in a 24 h period, 12 h+/12 h-) mimicking the light/dark cycle. Immunofluorescence and western-blot assays showed the partial transdifferentiation of white adipocytes in both ZL and ZDF rats, with increasing thermogenic and beige markers, UCP1 and CITED1 and decreasing white adipocyte marker ASC-1 expression. In addition, melatonin increased UCP1, CITED1, and PGC1-α expression in differentiated adipocytes in both rats and humans. These results demonstrate that melatonin increases brown fat in obese diabetic rats by both adipocyte transdifferentiation and de novo differentiation. Furthermore, it promotes beige MSC adipogenesis in humans. This may contribute to the control of body weight attributed to melatonin and its metabolic benefits in human diabesity.

Changes in the expression of inflammatory and epigenetic-modulatory genes after an intensive meditation retreat.

Background: Meditation retreats are characterized by intensive or concentrated periods of meditation practice, commonly undertaken in a residential setting. Although research indicates that meditation training can positively influence physical and mental health outcomes, the biological consequences of meditation retreat interventions are relatively understudied. In this study, we examined the influence of a month-long, silent meditation retreat on the expression of genes involved in epigenetic modulation and immune processes. Method: We assessed gene expression changes in experienced meditators attending a month-long Insight meditation retreat (n = 28), as compared to a community control group (n = 34) of experienced practitioners living their everyday lives. Blood samples were collected on day two of the retreat (Time 1) and again 3 weeks later (Time 2). Control participants were also assessed across a 3-week interval, during which they maintained their regular daily routines. Results: As compared to controls, retreat participants showed differential changes in the expression of several genes involved in chromatin modulation and inflammation. The most substantive finding was downregulation of the TNF pathway in retreat participants, which was not observed in controls. Conclusions: These findings indicate that meditation retreat participation may influence some of the inflammatory mechanisms involved in the development of chronic diseases, and that this style of psychosocial intervention may have therapeutic potential, particularly in experienced practitioners.

Mental health benefits of a 1-week intensive multimodal group program for adolescents with multiple adverse childhood experiences.

BACKGROUND: Adverse childhood experiences (ACEs) are associated with a wide range of diseases, unsafe behavior and shorter life expectancy. However, there is scarce evidence on effective interventions for children or adolescents who report multiple ACEs, including abuse, neglect and household dysfunction. OBJECTIVE: The aim of this study was to evaluate the mental health outcomes of a multimodal program designed for adolescents with multiple ACEs. PARTICIPANTS: Forty-four girls (aged 13-16 years, mean ACE score > 5) were randomized to an intervention group or a care-as-usual control group. METHODS: The intervention included mindfulness-based practices, expressive arts and EMDR (Eye Movement Desensitization and Reprocessing Integrative) group treatment. We used questionnaires for adolescents to assess trauma (SPRINT, CPSS) and attention/awareness-related outcomes (MAAS-A) at baseline (T1), post-intervention (T2) and two-months post-discharge (T3). RESULTS: Linear mixed effects model analyses showed significant Group by Time interactions on all the scales (F = 11.0, p = 0.015; F = 12.5 p < 0.001; and F = 6.4, p = 0.001, for SPRINT, CPSS and MAAS-A, respectively). After completing the program, the intervention group showed significant reduction in trauma-related outcomes (SPRINT, Δ%(T2-T1) = -73%, p < 0.001; CPSS, Δ%(T2-T1) = -26%, p < 0.001) while attention/awareness-related outcomes were improved by 57% (p < 0.001). These changes remained stable two months after discharge. SPRINT and CPSS scales were highly correlated (r = 0.833, p < 0.001) and outcomes from both trauma-related scales negatively correlated with mindfulness scores (MAAS-A/SPRINT, r = -0.515, p = 0.007; MAAS-A/CPSS, r = -0.553, p < 0.001). CONCLUSIONS: Results presented here support this multimodal group intervention as a feasible and promising program for reducing the psychological burden in adolescents with a history of multiple ACEs.

Palliative sedation and mortality in emergency departments: descriptive study of cases in the MORCAT registry. / Registro MORCAT: descripción de la sedación paliativa y la mortalidad en los servicios de urgencias.

OBJECTIVES: To describe the clinical management of palliative sedation and the characteristics of sedated patients in 11 Catalan hospital emergency departments. MATERIAL AND METHODS: Prospective descriptive study of a cohort of patients given palliative sedation between April and July 2018. We registered patient demographic and disease data, the Charlson comorbidity index (CCI), patient's point of origin before emergency department arrival, times related to emergency care, and medications used. RESULTS: We included 323 patients (48.9% men) with a mean (SD) age of 84 (12) years. The CCIs were significantly higher in patients attended in level-I hospitals. Palliative sedation was the first option in 27% and was initiated within 18 (28) hours of arrival on average, an interval that was significantly shorter in level-II hospitals. Most patients (74.2%) died in the emergency department. CONCLUSION: Patients treated with palliative sedation in hospital emergency departments are older and have serious concomitant conditions. Most patients are first treated with intention to cure. Time until the start of palliative sedation differs significantly according to hospital level.

OBJETIVO: Describir las características y manejo de los pacientes con sedación paliativa (SP) en 11 servicios de urgencias hospitalarios (SUH) catalanes. METODO: Estudio prospectivo descriptivo de pacientes que recibieron SP entre abril y julio de 2018. Se recogieron variables demográficas, enfermedades del paciente, índice de Charlson (IC), procedencia, tiempos en urgencias y fármacos utilizados. RESULTADOS: Se incluyeron 323 pacientes (48,9% varones) con una edad media de 84 (DE 12) años. El IC fue significativamente mayor en hospitales de primer nivel. La SP se consideró primera opción de tratamiento en el 27% y se inició en una media de 18 (DE 28) horas tras su llegada, significativamente diferente en hospitales de segundo nivel. Fallecieron mayoritariamente en el SUH (74,2%). CONCLUSIONES: Los pacientes que reciben SP en los SUH son ancianos con comorbilidad grave, y en su mayoría reciben tratamiento con intención curativa como primera opción terapéutica. Existen diferencias significativas del tiempo transcurrido hasta el inicio de la SP según la complejidad del centro.

Risk of Cancer in Family Members of Patients with Lynch-Like Syndrome.

Lynch syndrome (LS) is a common cause of hereditary colorectal cancer (CRC). Some CRC patients develop mismatch repair deficiency without germline pathogenic mutation, known as Lynch-like syndrome (LLS). We compared the risk of CRC in first-degree relatives (FDRs) in LLS and LS patients. LLS was diagnosed when tumors showed immunohistochemical loss of MSH2, MSH6, and PMS2; or loss of MLH1 with BRAF wild type; and/or no MLH1 methylation and absence of pathogenic mutation in these genes. CRC and other LS-related neoplasms were followed in patients diagnosed with LS and LLS and among their FDRs. Standardized incidence ratios (SIRs) were calculated for CRC and other neoplasms associated with LS among FDRs of LS and LLS patients. In total, 205 LS (1205 FDRs) and 131 LLS families (698 FDRs) had complete pedigrees. FDRs of patients with LLS had a high incidence of CRC (SIR, 2.08; 95% confidence interval (CI), 1.56-2.71), which was significantly lower than that in FDRs of patients with LS (SIR, 4.25; 95% CI, 3.67-4.90; p < 0.001). The risk of developing other neoplasms associated with LS also increased among FDR of LLS patients (SIR, 2.04; 95% CI, 1.44-2.80) but was lower than that among FDR of patients with LS (SIR, 5.01, 95% CI, 4.26-5.84; p < 0.001). FDRs with LLS have an increased risk of developing CRC as well as LS-related neoplasms, although this risk is lower than that of families with LS. Thus, their management should take into account this increased risk.

An extra-virgin olive oil rich in polyphenolic compounds has antioxidant effects in OF1 mice.

Extra-virgin olive oil (OO) is becoming more important in daily diets due to its beneficial effects on health, most of which are because of its antioxidant content. We studied the antioxidant activity and mechanisms of an extra-virgin OO that is rich in phenolics on pancreatic islets and liver in control mice (CTL) fed a nonpurified diet and in mice supplemented with 50 microL/d sunflower oil (SO) or 50 microL/d extra-virgin OO for 4 d. Plasma hydroxytyrosol concentration was determined by HPLC-diode array detector. Plasma antioxidant capacity, enzymatic activities, and lipid peroxidation were measured by spectrophotometry. Islet function was studied by measuring insulin release. Islet cell gene expression was examined using quantitative RT-PCR. The plasma hydroxytyrosol concentration was greater in OO mice than in CTL or SO mice (P < 0.05) and was greater in SO mice than in CTL mice. The ratio of reduced:oxidized glutathione and the antioxidant capacity in plasma was greater in OO mice than in CTL or SO mice (P < 0.05) and higher in SO mice than in CTL mice. Glucose-stimulated insulin secretion was greater in OO mice than in CTL or SO mice (P < 0.05) and was also higher in SO mice than in CTL mice. Protection against liver cell and beta cell membrane lipid peroxidation was greater in OO mice than in CTL or SO mice (P < 0.05) and was greater in SO mice than in CTL mice. Catalase (CAT) expression in the islet of Langerhans was higher in OO mice than in CTL mice and SO mice (P < 0.05). The CAT and glutathione peroxidase 1 activities in the islet of Langerhans were 25% greater in OO mice than in CTL mice and higher than in SO mice (P < 0.05) and they were greater in SO mice than in CTL mice. These results indicate that, in metabolic tissues, protection by extra-virgin OO against oxidative stress occurs primarily through a direct antioxidant effect as well as through an indirect mechanism that involves greater expression and activity of certain enzymes with antioxidant activities.

Prone positioning in acute respiratory distress syndrome: a multicenter randomized clinical trial.

OBJECTIVE: We examined the effect on survival of prone positioning as an early and continuous treatment in ARDS patients already treated with protective ventilation. DESIGN AND SETTING: Open randomized controlled trial in 17 medical-surgical ICUs. PATIENTS: Forty mechanically ventilated patients with early and refractory ARDS despite protective ventilation in the supine position. INTERVENTIONS: Patients were randomized to remain supine or be moved to early (within 48[Symbol: see text]h) and continuous (> or = 20 h/day) prone position until recovery or death. The trial was prematurely stopped due to a low patient recruitment rate. MEASUREMENTS AND RESULTS: Clinical characteristics, oxygenation, lung pressures, and hemodynamics were monitored. Need for sedation, complications, length of MV, ICU, and hospital stays, and outcome were recorded. PaO(2)/FIO(2) tended to be higher in prone than in supine patients after 6[Symbol: see text]h (202 +/-78 vs. 165+/-70 mmHg); this difference reached statistical significance on day 3 (234+/-85 vs. 159+/-78). Prone-related side effects were minimal and reversible. Sixty-day survival reached the targeted 15% absolute increase in prone patients (62% vs. 47%) but failed to reach significance due to the small sample. CONCLUSIONS: Our study adds data that reinforce the suggestion of a beneficial effect of early continuous prone positioning on survival in ARDS patients.

Chronic ethanol intake modifies pyrrolidon carboxypeptidase activity in mouse frontal cortex synaptosomes under resting and K+ -stimulated conditions: role of calcium.

Pyrrolidon carboxypeptidase (Pcp) is an omega peptidase that removes pyroglutamyl N-terminal residues of peptides such as thyrotrophin-releasing hormone (TRH), which is one of the neuropeptides that has been localized into many areas of the brain and acts as an endogenous neuromodulator of several parameters related to ethanol (EtOH) consumption. In this study, we analysed the effects of chronic EtOH intake on Pcp activity on mouse frontal cortex synaptosomes and their corresponding supernatant under basal and K+ -stimulated conditions, in presence and absence of calcium (Ca2+) to know the regulation of Pcp on TRH. In basal conditions, chronic EtOH intake significantly decreased synaptosomes Pcp activity but only in absence of Ca2+. However, supernatant Pcp activity is also decreased in presence and absence of calcium. Under K+-stimulated conditions, chronic EtOH intake decreased synaptosomes Pcp activity but only in absence of Ca2+, whereas supernatant Pcp activity was significantly decreased only in presence of Ca2+. The general inhibitory effect of chronic EtOH intake on Pcp activity suggests an inhibition of TRH metabolism and an enhancement of TRH neurotransmitter/neuromodulator functions, which could be related to putative processes of tolerance to EtOH in which TRH has been involved. Our data may also indicate that active peptides and their degrading peptidases are released together to the synaptic cleft to regulate the neurotransmitter/neuromodulator functions of these peptides, through a Ca2+ -dependent mechanism.