Associations between Aging and Vitamin D Status with Whole-Body Nitric Oxide Production and Markers of Endothelial Function.

BACKGROUND: Aging and vitamin D deficiency have been associated with reduced nitric oxide (NO) synthesis and impaired endothelial function (EF) but the evidence in humans remains weak. OBJECTIVES: Two independent cross-sectional studies were designed to evaluate the association between age, sex, and plasma vitamin D concentrations with physiological and biochemical biomarkers of NO synthesis and EF in young and older healthy participants (Study 1) and in overweight and obese postmenopausal females (Study 2). METHODS: In Study 1, 40 young (20-49 y) and older (50-75 y) males and females (10 participants per age and sex group) were included. Resting blood pressure and ear-to-finger peripheral pulse wave velocity (PWV) were measured. A stable-isotopic method was used to determine whole-body NO production. Plasma 25-hydroxyvitamin D (25(OH)D), nitrate, nitrite, and asymmetric dimethylarginine (ADMA) concentrations were determined. In Study 2, 80 older overweight and obese females (age 61.2 ± 6.2 y, body mass index 29.5 ± 4.4 kg/m2) were recruited. Postocclusion reactive hyperemia (PORH) and peripheral PWV were measured. Plasma concentrations of 25(OH)D, nitrate, cyclic guanosine monophosphate, 3-nitrotyrosine (3-NT), endothelin-1, vascular endothelial growth factor, and ADMA were determined. RESULTS: In Study 1, whole-body NO production was significantly greater in young compared with older participants (0.61 ± 0.30 µmol·h-1·kg-1 compared with 0.39 ± 0.10 µmol·h-1·kg-1, P = 0.01) but there was no evidence of a sex difference (P = 0.81). Plasma 25(OH)D concentration was not associated with PWV (r = 0.18, P = 0.28) or whole-body NO production (r = -0.20, P = 0.22). Plasma ADMA concentration was associated positively with age (r = 0.35, P = 0.03) and negatively with whole-body NO production (r = -0.33, P = 0.04). In Study 2, age was associated with lower PORH (r = -0.28, P = 0.02) and greater ADMA concentrations (r = 0.22, P = 0.04). Plasma 25(OH)D concentration was inversely associated with 3-NT concentrations (r = -0.31, P = 0.004). CONCLUSIONS: Older age was associated with lower whole-body NO production. Plasma vitamin D concentrations were not associated with NO production or markers of EF but showed a weak, significant correlation with oxidative stress in postmenopausal overweight females.

New Forms of Neuroactive Phospholipids for DHA Enrichment in Brain.

Low levels of docosahexaenoic acid (DHA) in the brain have been related to neurological disorders, like Alzheimer's disease (AD). After ingestion, dietary DHA must cross the blood-brain barrier, where it is absorbed as lysophosphatidylcholine (LPC), due to its role as a preferential DHA carrier in the brain. This work aimed at the production of LPC-DHA extracts to be used in supplementation/food fortification intended neural enrichment in DHA. As it is rich in DHA, especially its phospholipids (PL), Atlantic mackerel (Scomber scombrus, caught in Spring/2022) was used as a raw material. The polar lipids fraction was separated and hydrolysed with Rhizomucor miehei lipase, to enzymatically convert phosphatidylcholine (PC) into LPC. The fish (muscle and by-products) lipids fraction was used for total lipids (TL) content, lipid classes (LC) and fatty acid (FA) profile evaluation, whilst polar lipids extracts were studied for LC production and FA analysis. Muscle TL ranged between 1.45 and 4.64 g/100 g (WW), while by-products accounted for 7.56-8.96 g/100 g, with the highest contents being found in March. However, PL were more abundant in muscle (22.46-32.20% of TL). For polar lipids extracts, PL represented 50.79% of TL, among which PC corresponded to 57.76% and phosphatidylethanolamine to 42.24%. After hydrolysis, nearly half of this PC was converted into LPC. When compared to the initial PC, DHA relative content (33.6% of total FA) was significantly higher after hydrolysis: 55.6% in PC and 73.6% in LPC. Such extract, obtained from this undervalued species, may represent a promising strategy to increase DHA uptake into brain cells while allowing this species to upgrade.

The meaning in loss protocol: A clinical trial of online grief therapy.

For a minority of the bereaved, the loss of a significant other can trigger an overwhelming emotional reaction and impaired functioning across life domains, known as prolonged grief disorder (PGD). Hence, ongoing efforts have been made to refine existing treatments to increase their efficacy and to accommodate the idiosyncrasies of grief reactions. This study presents the results of an open clinical trial of the feasibility and effectiveness of the Meaning in Loss (MIL) protocol in an online format. The brief intervention of 12 to 16 sessions combines constructivist and narrative strategies to explore and work through impediments to meaning reconstruction in loss. The sample included 25 participants diagnosed with PGD who were treated by six therapists. Baseline and post-therapy comparisons showed a significant improvement in all clinical measures (grief symptomatology, depression and general distress) and an increase of meaning making regarding the loss. Meaning making was found to be a prospective mediator of symptomatic improvement in grief across the course of therapy. These findings suggest the effectiveness of the MIL protocol in decreasing grief specific and associated symptomatology and argue for the relevance of further controlled evaluations of its efficacy. Moreover, results confirm previous findings that meaning making is a relevant factor in the evolution of grief reactions, including in the context of psychotherapy.

Development of a training programme in individual case formulation skills and a scale for assessing its effectiveness.

BACKGROUND: Little is known about the skills involved in clinical formulation. The individual case formulation (ICF) approach, based on functional analysis, employs clinical descriptions that are theory-free and depicts formulations constructed according to a set of basic conventions. AIMS: We report a test of whether this method could be taught and if the quality of the resulting diagrams could be reliably rated. METHOD: Participants (n=40) participated in a training course in formulation. A draft rating scale was refined in the course of rating formulation diagrams and basic inter-rater reliability established. RESULTS: Results of the study support further development of the ICF approach.

How Can the Microbiome Induce Carcinogenesis and Modulate Drug Resistance in Cancer Therapy?

Over the years, cancer has been affecting the lives of many people globally and it has become one of the most studied diseases. Despite the efforts to understand the cell mechanisms behind this complex disease, not every patient seems to respond to targeted therapies or immunotherapies. Drug resistance in cancer is one of the limiting factors contributing to unsuccessful therapies; therefore, understanding how cancer cells acquire this resistance is essential to help cure individuals affected by cancer. Recently, the altered microbiome was observed to be an important hallmark of cancer and therefore it represents a promising topic of cancer research. Our review aims to provide a global perspective of some cancer hallmarks, for instance how genetic and epigenetic modifications may be caused by an altered human microbiome. We also provide information on how an altered human microbiome can lead to cancer development as well as how the microbiome can influence drug resistance and ultimately targeted therapies. This may be useful to develop alternatives for cancer treatment, i.e., future personalized medicine that can help in cases where traditional cancer treatment is unsuccessful.

Accelerated idioventricular rhythm in a healthy newborn: frightening but non-threatening.

Accelerated idioventricular rhythm is a rare but benign form of ventricular tachycardia which might be challenging to differentiate from other more worrisome forms. We present the case of a healthy newborn diagnosed with an accelerated idioventricular rhythm which is spontaneously terminated without the need for medical therapy.

Reduced plasma carotenoids in individuals suffering from metabolic diseases with disturbances in lipid metabolism: a systematic review and meta-analysis of observational studies.

This review summarises the association between serum carotenoids, serum retinoids and dietary intake outcomes with obesity/overweight and individuals with metabolic diseases with disturbances in lipid metabolism. Observational studies reporting dietary intakes and serum concentrations of carotenoids and retinol were collected from Medline and Web of Science. Mean differences were calculated between "cases" (classified as obese, overweight or having a metabolic disease with disturbances in lipid metabolism; i.e. non-alcoholic fatty liver disease, type 2 diabetes, dyslipidaemia or metabolic syndrome) and "comparator group" (classified as normal weight healthy individuals) and summarised in meta-analyses. Significant summary measures were observed for most serum provitamin A and non-provitamin A carotenoids. Studies reporting total serum carotenoids had shown the greatest decrease (-0.28 µmol/l [-0.33, -0.23], p<.001, I2=62.5%, n = 7). There were no significant summary measures for dietary outcomes, suggesting a physiological role of low serum carotenoids in the development of obesity and associated diseases.

Fluctuation in the assimilation of problematic experiences: A comparison of two contrasting cases of Emotion Focused Therapy.

The assimilation model suggests that therapeutic change occurs through a gradual assimilation of problematic experiences. Previous case studies have suggested that both good- and poor-outcome cases exhibit a fluctuating pattern of assimilation progress, characterized by advances and setbacks. Our study examined more closely how this fluctuating pattern is related to symptom change across therapy. We analyzed the longitudinal relations among assimilation ratings, instability (fluctuation) in assimilation ratings, and clinical symptom intensity in two contrasting cases of emotion-focused therapy for depression, one good and one poor outcome. We used the assimilation of problematic experiences scales (APES) to measure assimilation and the outcome- questionnaire (OQ-10) to measure clinical symptom intensity. To assess assimilation instability, we used a fluctuation measure that calculated the amplitude and the frequency of changes in assimilation levels. The results showed that in the good-outcome case, assimilation levels and instability tended to increase and symptom intensity tended to decrease, particularly in the final phase of treatment. In the poor-outcome case, assimilation levels and instability did not change much across sessions.

Mediterranean Diet Increases Endothelial Function in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The endothelium plays a key role in the maintenance of vascular health and represents a potential physiological target for dietary and other lifestyle interventions designed to reduce the risk of cardiovascular diseases (CVD) including stroke or coronary heart disease. OBJECTIVE: To conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating the effects of the Mediterranean dietary pattern (MedDiet) on endothelial function. METHODS: Medline, Embase, and Scopus databases were searched from inception until January 2019 for studies that met the following criteria: 1) RCTs including adult participants, 2) interventions promoting the MedDiet, 3) inclusion of a control group, and 4) measurements of endothelial function. A random-effects meta-analysis was conducted. Metaregression and subgroup analyses were performed to identify whether effects were modified by health status (i.e., healthy participants versus participants with existing comorbidities), type of intervention (i.e., MedDiet alone or with a cointervention), study duration, study design (i.e., parallel or crossover), BMI, and age of participants. RESULTS: Fourteen articles reporting data for 1930 participants were included in the meta-analysis. Study duration ranged from 4 wk to 2.3 y. We observed a beneficial effect of the MedDiet on endothelial function [standardized mean difference (SMD): 0.35; 95% CI: 0.17, 0.53; P <0.001; I2 = 73.68%]. MedDiet interventions improved flow-mediated dilation (FMD)-the reference method for noninvasive, clinical measurement of endothelial function-by 1.66% (absolute change; 95% CI: 1.15, 2.17; P <0.001; I2 = 0%). Effects of the MedDiet on endothelial function were not modified by health status, type of intervention, study duration, study design, BMI, or age of participants (P >0.05). CONCLUSIONS: MedDiet interventions improve endothelial function in adults, suggesting that the protective effects of the MedDiet are evident at early stages of the atherosclerotic process with important implications for the early prevention of CVD. This study has the PROSPERO registration number: CRD42018106188.

A sudden turner of events.

The authors report the case of an 18-year-old woman with Turner Syndrome and aortic coarctation, who developed aortic dissection after percutaneous stenting. Surgical treatment was necessary as the lesion progressed. This case highlights both the importance of awareness as well as multidisciplinary management of this potential complication.

Differentiation of Saccharomyces cerevisiae populations from vineyards of the Azores Archipelago: Geography vs Ecology.

Aiming to elucidate the roles that ecology and geography play in shaping the differentiation of fermentative grape-associated Saccharomyces cerevisiae populations, several locations on six islands of the Azores Archipelago were surveyed. A total of 249 strains were isolated from spontaneous fermentations of grape samples from several varieties of two distinct grapevine species (Vitis vinifera L. and Vitis labrusca L.), in vineyards that are under regular cultivation or in abandoned vineyards. Strains were genetically analyzed using a set of nine microsatellite loci, and also phenotypically characterized using relevant physiological/biotechnological tests. Results showed that genetic divergence among populations of the same island was lower than from populations from different islands. Phenotypic comparison of the populations from each of the islands revealed significant differences between them. Strains isolated from the islands with more intensive viticultural activity - Pico, Terceira and Graciosa - showed higher levels of SO2 tolerance, possibly resulting from selection by human activity. The percentage of strains producing low levels of H2S was higher in S. Jorge (60%). Our findings were supported both by genetic and phenotypic data and provide clear evidence for the prevailing role of the geography over ecology in the differentiation of S. cerevisiae populations in the Azores Archipelago.

Integrating transcriptomics and metabolomics for the analysis of the aroma profiles of Saccharomyces cerevisiae strains from diverse origins.

BACKGROUND: During must fermentation thousands of volatile aroma compounds are formed, with higher alcohols, acetate esters and ethyl esters being the main aromatic compounds contributing to floral and fruity aromas. The action of yeast, in particular Saccharomyces cerevisiae, on the must components will build the architecture of the wine flavour and its fermentation bouquet. The objective of the present work was to better understand the molecular and metabolic bases of aroma production during a fermentation process. For such, comparative transcriptomic and metabolic analysis was performed at two time points (5 and 50 g/L of CO2 released) in fermentations conducted by four yeast strains from different origins and/or technological applications (cachaça, sake, wine, and laboratory), and multivariate factorial analyses were used to rationally identify new targets for improving aroma production. RESULTS: Results showed that strains from cachaça, sake and wine produced higher amounts of acetate esters, ethyl esters, acids and higher alcohols, in comparison with the laboratory strain. At fermentation time T1 (5 g/L CO2 released), comparative transcriptomics of the three S. cerevisiae strains from different fermentative environments in comparison with the laboratory yeast S288c, showed an increased expression of genes related with tetracyclic and pentacyclic triterpenes metabolism, involved in sterol synthesis. Sake strain also showed upregulation of genes ADH7 and AAD6, involved in the formation of higher alcohols in the Ehrlich pathway. For fermentation time point T2 (50 g/L CO2 released), again sake strain, but also VL1 strain, showed an increased expression of genes involved in formation of higher alcohols in the Ehrlich pathway, namely ADH7, ADH6 and AAD6, which is in accordance with the higher levels of methionol, isobutanol, isoamyl alcohol and phenylethanol observed. CONCLUSIONS: Our approach revealed successful to integrate data from several technologies (HPLC, GC-MS, microarrays) and using different data analysis methods (PCA, MFA). The results obtained increased our knowledge on the production of wine aroma and flavour, identifying new gene in association to the formation of flavour active compounds, mainly in the production of fatty acids, and ethyl and acetate esters.

Echocardiographic Versus Angiographic Assessment of Patent Arterial Duct in Percutaneous Closure: Towards X-ray Free Duct Occlusion?

Device selection and procedural guidance for percutaneous ductal closure strongly rely upon angiographic and echocardiographic imaging. Current literature recognises 2D echocardiography as an essential tool for diagnosis and assessment but does not define a consistent methodology to optimise ductal measurement. There is little research comparing echocardiography with gold standard angiography for ductal measurement. Proving 2D echocardiographic ductal measurement to be equivalent to angiography could pave the way for its use as the primary modality in image guidance for percutaneous closure of the ductus. This was a retrospective study of 100 consecutive paediatric patients who underwent percutaneous ductal closure. Echocardiographic images were studied to determine ductal (a) morphology (b) dimensions (length, aortic ampulla, pulmonary end, minimum diameter) (c) size of device that would be appropriate for closure. These data were compared to corresponding measurements generated by angiographic images. Inter and intra-observer ratings were calculated to assess levels of agreement. There were significant differences between the imaging methods in classifying the morphological sub-type and ductal measurements (p < 0.005), except for length which was not found to be significantly different between modalities. Prediction of device selection from angiographic images showed excellent agreement (weighted k = 0.81). Predictions based on echocardiographic images showed a poor level of agreement (weighted k = 0.14). We found poor correlation between echocardiography and angiography for measurement, morphological assessment and device selection. Based on our findings, percutaneous arterial duct occlusion without angiographic guidance in this age group cannot be advocated.

Narrative Changes Predict a Decrease in Symptoms in CBT for Depression: An Exploratory Study.

OBJECTIVE: Innovative moments (IMs) are new and more adjusted ways of thinking, acting, feeling and relating that emerge during psychotherapy. Previous research on IMs has provided sustainable evidence that IMs differentiate recovered from unchanged psychotherapy cases. However, studies with cognitive behavioural therapy (CBT) are so far absent. The present study tests whether IMs can be reliably identified in CBT and examines if IMs and symptoms' improvement are associated. METHODS: The following variables were assessed in each session from a sample of six cases of CBT for depression (a total of 111 sessions): (a) symptomatology outcomes (Outcome Questionnaire-OQ-10) and (b) IMs. Two hierarchical linear models were used: one to test whether IMs predicted a symptom decrease in the next session and a second one to test whether symptoms in one session predicted the emergence of IMs in the next session. RESULTS: Innovative moments were better predictors of symptom decrease than the reverse. A higher proportion of a specific type of IMs-reflection 2-in one session predicted a decrease in symptoms in the next session. Thus, when clients further elaborated this type of IM (in which clients describe positive contrasts or elaborate on changes processes), a reduction in symptoms was observed in the next session. DISCUSSION: A higher expression and elaboration of reflection 2 IMs appear to have a facilitative function in the reduction of depressive symptoms in this sample of CBT. Copyright © 2016 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: Elaborating innovative moments (IMs) that are new ways of thinking, feeling, behaving and relating, in the therapeutic dialogue, may facilitate change. IMs that are more predictive of amelioration of symptoms in CBT are the ones focused on contrasts between former problematic patterns and new adjusted ones; and the ones in which the clients elaborate on processes of change. Therapists may integrate these kinds of questions (centred on contrasts and centred on what allowed change from the client's perspective), in the usual CBT techniques. When elaborating these IMs successfully, therapists may expect an improvement in symptoms in the next session of psychotherapy.

Self-narrative reconstruction in emotion-focused therapy: A preliminary task analysis.

OBJECTIVE: This research explored the consolidation phase of emotion-focused therapy (EFT) for depression and studies-through a task-analysis method-how client-therapist dyads evolved from the exploration of the problem to self-narrative reconstruction. METHOD: Innovative moments (IMs) were used to situate the process of self-narrative reconstruction within sessions, particularly through reconceptualization and performing change IMs. We contrasted the observation of these occurrences with a rational model of self-narrative reconstruction, previously built. RESULTS: This study presents the rational model and the revised rational-empirical model of the self-narrative reconstruction task in three EFT dyads, suggesting nine steps necessary for task resolution: (1) Explicit recognition of differences in the present and steps in the path of change; (2) Development of a meta-perspective contrast between present self and past self; (3) Amplification of contrast in the self; (4) A positive appreciation of changes is conveyed; (5) Occurrence of feelings of empowerment, competence, and mastery; (6) Reference to difficulties still present; (7) Emphasis on the loss of centrality of the problem; (8) Perception of change as a gradual, developing process; and (9) Reference to projects, experiences of change, or elaboration of new plans. CONCLUSIONS: Central aspects of therapist activity in facilitating the client's progression along these nine steps are also elaborated.

Three narrative-based coding systems: Innovative moments, ambivalence and ambivalence resolution.

Narrative and dialogical perspectives suggest that personal meaning systems' flexibility is an important resource for change in psychotherapy. Drawn from these theoretical backgrounds, a research program focused on the identification of Innovative Moments (IMs)-exceptions to the inflexible meaning systems present in psychopathological suffering-has been carried out. For this purpose, three process-oriented coding systems were developed: The IMs Coding System, the Ambivalence Coding System, and the Ambivalence Resolution Coding System. They allow, respectively, for the study of change, ambivalence, and ambivalence resolution in therapy. This paper presents these coding systems, the main findings that resulted from their application to different samples and therapeutic models, the main current and future lines of research, as well as the clinical applications of this research program.

Catch-up growth in term and preterm infants after surgical closure of ventricular septal defect in the first year of life.

UNLABELLED: Growth impairment in infants with unrestrictive ventricular septal defects (VSD) is common, and normalisation of growth has been reported after surgical correction. Literature is inconsistent about growth velocity after surgery in term and preterm infants. We aimed to establish the pattern of catch-up growth in term and preterm infants submitted to VSD surgical correction before 1 year of age. Fifty-two infants (41 term, 11 preterm) were studied. Anthropometric data at birth, surgery and 3, 6, 12 and 24 months after surgery were collected retrospectively. Statistic analyses were performed in SPSS® version 21. At the time of surgery, growth was severely impaired in term and preterm infants. Term infants underwent a period of fast growth within the first 6 months after surgery, achieving posteriorly a normal growth pattern, as both weight and height were not significantly different from the reference population at 24 months after surgery. Preterms caught-up later than term infants but with a significant weight gain within 3 months after surgery. CONCLUSION: Early surgical repair of VSD leads to a significant acceleration of growth within 3 to 6 months after surgery, for both groups. WHAT IS KNOWN: • Growth impairment in infants with unrestrictive ventricular septal defects is well documented in literature. • Surgical correction in the first months of life is the current option for most ventricular septal defects, leading to a more favourable growth pattern. • Rapid growth during infancy may be associated with the development of insulin resistance, metabolic syndrome, obesity and cardiovascular disease later in life. What is New: • Literature is inconsistent about catch-up growth velocities after ventricular correction for term infants. • Preterm infants have never been enrolled in previous studies that aimed to establish a pattern of growth after surgery. • This group of children, who underwent a rapid post-surgery catch-up growth that follows a period of failure to thrive, may be at a higher risk of insulin resistance, metabolic syndrome, obesity and cardiovascular disease.

Percutaneous valve implantation in "tricuspid" position after a Fontan-Björk operation.

BACKGROUND: A 30-year-old female with tricuspid valve atresia, ventricular septal defect, and atrial septal defect had a neonatal modified Blalock Taussig shunt and a Fontan-Björk operation performed at five years of age. She did well initially but progressively developed signs of systemic congestion due to severe homograft stenosis and underwent successful percutaneous implantation of a Melody® pulmonary valve (Medtronic, Minneapolis, MN, USA) in the "tricuspid" position.

Doppler Flow Pattern and Arterial Stiffness in Patients with Aortic Coarctation.

Patients with aortic coarctation (CoAo) often have a diastolic flow in the descending aorta. The effect of arterial stiffness on CoAo flow pattern was described in vitro and with computer models. Study of Doppler flow patterns and arterial stiffness may provide helpful data to support the decision of CoAo treatment. Fifty studies were obtained in 31 patients (14 women, 21.5 ± 15.5 years). In 19 patients, studies were performed before and after percutaneous intervention. Systolic invasive gradients were measured (Sgrad). Doppler parameters included Doppler corrected gradient (Dgrad), diastolic velocity at end of T wave (DVT), end diastolic velocity (DVQ), systolic and diastolic half pressure times (SHPTc and DHPTc) and velocity runoff (VRc). In 19 patients, before intervention, arterial stiffness was assessed by measuring pulsed wave velocity (PWV) between right carotid and radial arteries. Sgrad showed correlation with Dgrad, DVT, DVQ, SHPTc, DHPTc and VRc (p < 0.01). Using multiple regression models, Sgrad variability was best explained by combining the variables Dgrad and DHPTc (R 2 = 0.766). A variable named DTail was obtained with DTail = 1 if DHPTc > 0. In the group with Sgrad below 30 mmHg, a negative correlation was found between DTail and PWV (p = 0.024), suggesting that low aortic stiffness contributes to persistent diastolic flow in the descending aorta. Doppler systolic and diastolic parameters correlated well with severity of CoAo. In mild to moderate CoAo, Doppler diastolic flow in the descending aorta was more likely in patients with lower arterial stiffness.