Influence of gender on right ventricle adaptation to endurance exercise: an ultrasound two-dimensional speckle-tracking stress study.

BACKGROUND: Characteristic right ventricle (RV) remodelling is related to endurance exercise in male athletes (MAs), but data in female athletes (FAs) are scarce. Our aim was to evaluate sex-related influence on exercise-induced RV remodelling and on RV performance during exercise. METHODS: Forty endurance athletes (>10 training hours/week, 50% female) and 40 age-matched controls (<3 h moderate exercise/week, 50% female) were included. Echocardiography was performed at rest and at maximum cycle-ergometer effort. Both ventricles were analysed by standard and speckle-tracking echocardiography. RESULTS: Endurance training induced similar structural and functional cardiac remodelling in MAs and FAs, characterized by bi-ventricular dilatation [~34%, left ventricle (LV); 29%, RV] and normal bi-ventricular function. However, males had larger RV size (p < 0.01), compared to females: RV end-diastolic area (cm2/m2): 15.6 ± 2.2 vs 11.6 ± 1.7 in athletes; 12.2 ± 2.7 vs 8.6 ± 1.6 in controls, respectively, and lower bi-ventricular deformation (RV global longitudinal strain (GLS) (%): -24.0 ± 3.6 vs -29.2 ± 3.1 in athletes; -24.9 ± 2.5 vs -30.0 ± 1.9 in controls, and LVGLS: -17.5 ± 1.4 vs -21.9 ± 1.9 in athletes; -18.7 ± 1.2 vs -22.5 ± 1.5 in controls, respectively, p < 0.01). During exercise, the increase in LV function was positively correlated (p < 0.01) with increased cardiac output (∆%LV ejection fraction, r = +0.46 and ∆%LVGLS, r = +0.36). Improvement in RV performance was blunted at high workloads, especially in MAs. CONCLUSION: Long-term endurance training induced similar bi-ventricular remodelling in MAs and FAs. Independently of training load, males had larger RV size and lower bi-ventricular deformation. Improvement in RV performance during exercise was blunted at high workloads, especially in MAs. The potential mechanisms underlying these findings warrant further investigation.

Sex-Dependent Metabolic Effects in Diet-Induced Obese Rats following Intermittent Fasting Compared with Continuous Food Restriction.

Recently, intermittent fasting has gained relevance as a strategy to lose weight and improve health as an alternative to continuous caloric restriction. However, the metabolic impact and the sex-related differences are not fully understood. The study aimed to compare the response to a continuous or intermittent caloric restriction in male and female rats following a previous induction of obesity through a cafeteria diet by assessing changes in body weight, energy intake, metabolic parameters, and gene expression in liver hepatic and adipose tissue. The continuous restriction reduced the energy available by 30% and the intermittent restriction consisted of a 75% energy reduction on two non-consecutive days per week. The interventions reduced body weight and body fat in both sexes, but the loss of WAT in females was more marked in both models of caloric restriction, continuous and intermittent. Both caloric restrictions improved insulin sensitivity, but more markedly in females, which showed a more pronounced decrease in HOMA-IR score and an upregulation of hepatic IRS2 and Sirt1 gene expression that was not observed in males. These findings suggest the fact that females are more sensitive than males to reduced caloric content in the diet.

Study protocol for a three-arm randomized controlled trial investigating the effectiveness, cost-utility, and physiological effects of a fully self-guided digital Acceptance and Commitment Therapy for Spanish patients with fibromyalgia.

Objective: Fibromyalgia (FM) is a prevalent pain syndrome with significant healthcare and societal costs. The aim of the SMART-FM-SP study is to determine the effectiveness, cost-utility, and physiological effects in patients with FM of a digital intervention (STANZA®) currently marketed in the United States, which delivers smartphone-based, fully self-guided Acceptance and Commitment Therapy (Digital ACT) for treating FM-related symptoms. Methods: A single-site, parallel-group, superiority, randomized controlled trial (RCT) will be conducted, including a total of 360 adults diagnosed with FM. Individuals will be randomly allocated (1:1:1) to treatment as usual (TAU), to TAU plus 12 weeks of treatment with Digital ACT, or to TAU plus 12 weeks of treatment with digital symptom tracking (i.e. FibroST). Participants will be assessed at baseline, post-treatment, and 6-month follow-up. An intention-to-treat analysis using linear mixed models will be computed to analyze the effects of Digital ACT on functional impairment (primary outcome), as measured by the Fibromyalgia Impact Questionnaire Revised at 6 months from the inception of the treatment. Secondary outcomes include impression of change, symptoms of distress, pain catastrophising, quality of life, cost-utility, and selected biomarkers (cortisol and cortisone, immune-inflammatory markers, and FKBP5 gene polymorphisms). The role of ACT-related processes of change will be tested with path analyses. Conclusions: This study is the first RCT that tests Digital ACT for Spanish patients with FM. Results will be important not only for patients and clinicians, but also for policy makers by examining the cost-utility of the app in a public healthcare context.

Immune-inflammatory and hypothalamic-pituitary-adrenal axis biomarkers are altered in patients with non-specific low back pain: A systematic review.

This systematic review aimed to investigate immune-inflammatory and hypothalamic-pituitary-adrenal (HPA) axis biomarkers in individuals with non-specific low back pain (NSLBP) compared to healthy control. The search was performed in five databases until 4 November 2021. Two reviewers independently conducted screenings, data extraction, risk of bias, and methodological quality assessment of 14 unique studies. All studies reported the source of the fluid analyzed: nine studies used serum, two used plasma, one used serum and plasma, and two studies used salivary cortisol. We found preliminary and limited evidence (only one study for each biomarker) of increased levels in growth differentiation factor 15 (GDF-15), interleukin-23 (IL-23), transforming growth factor-beta (TGF-ß), and soluble tumor necrosis factor receptor 1 (sTNF-R1) in NSLBP. Inconsistent and limited evidence was identified for interleukin-10 (IL-10). Although C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels appear to increase in NSLBP, only one study per each biomarker reported statistically significant differences. Interleukin-1 beta (IL-1ß), interleukin-17 (IL-17), interferon gamma (IFN-γ), and high-sensitivity CRP (hsCRP) showed no significant differences. Regarding cortisol, one study showed a significant increase and another a significant decrease. More robust evidence between GDF-15, IL-23, TGF-ß, and sTNF-R1 with NSLBP is needed. Moreover, contrary to the findings reported in previous studies, when comparing results exclusively with healthy control, insufficient robust evidence for IL-6, TNF-α, and CRP was found in NSLBP. In addition, cortisol response (HPA-related biomarker) showed a dysregulated functioning in NSLBP, with incongruent evidence regarding its directionality. Therefore, our effort is to find adjusted evidence to conclude which immune-inflammatory and HPA axis biomarkers are altered in NSLBP and how much their levels are affected. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020176153, identifier CRD42020176153.

[Theory of change implemented in the program to promote physical activity "La Ribera Camina"]. / Teoría del cambio aplicada al programa de promoción de la actividad física «La Ribera Camina¼.

OBJECTIVE: To develop a theory of change of a program to promote physical activity in eleven health districts, in order to improve its design and plan its evaluation. METHOD: Four focus groups were carried out, to develop a participatory theory of change, to identify the expected changes (long, medium and short term) of "La Ribera Camina" program, according to the following stakeholders: primary healthcare professionals, local government representatives and community members. A thematic analysis was used to identify the actions to be taken to achieve these changes, as well as the difficulties and facilitators to enhance the sustainability of the program. RESULTS: The identified changes were classified into four themes: 1) changes in physical and social health (improved physical condition, healthy habits, self-esteem and perceived well-being); 2) organizational and relational changes (better coordination between institutions); 3) specific changes to the program (incorporation of more "assets" and local associations, especially male participants, more trails and schedules); and 4) changes in the environment (improved trails' infrastructures and safety). CONCLUSIONS: The theory of change allows to identify and classify the changes that are expected, the actions to be carried out and the links between elements of the program. This will serve as the basis for its evaluation. This methodology could be applied to other programs interested in incorporating intersectorality and community engagement in their design and evaluation.

Corticosteroid-binding-globulin (CBG)-deficient mice show high pY216-GSK3ß and phosphorylated-Tau levels in the hippocampus.

Corticosteroid-binding globulin (CBG) is the specific carrier of circulating glucocorticoids, but evidence suggests that it also plays an active role in modulating tissue glucocorticoid activity. CBG polymorphisms affecting its expression or affinity for glucocorticoids are associated with chronic pain, chronic fatigue, headaches, depression, hypotension, and obesity with an altered hypothalamic pituitary adrenal axis. CBG has been localized in hippocampus of humans and rodents, a brain area where glucocorticoids have an important regulatory role. However, the specific CBG function in the hippocampus is yet to be established. The aim of this study was to investigate the effect of the absence of CBG on hippocampal glucocorticoid levels and determine whether pathways regulated by glucocorticoids would be altered. We used cbg-/- mice, which display low total-corticosterone and high free-corticosterone blood levels at the nadir of corticosterone secretion (morning) and at rest to evaluate the hippocampus for total- and free-corticosterone levels; 11ß-hydroxysteroid dehydrogenase expression and activity; the expression of key proteins involved in glucocorticoid activity and insulin signaling; microtubule-associated protein tau phosphorylation, and neuronal and synaptic function markers. Our results revealed that at the nadir of corticosterone secretion in the resting state the cbg-/- mouse hippocampus exhibited slightly elevated levels of free-corticosterone, diminished FK506 binding protein 5 expression, increased corticosterone downstream effectors and altered MAPK and PI3K pathway with increased pY216-GSK3ß and phosphorylated tau. Taken together, these results indicate that CBG deficiency triggers metabolic imbalance which could lead to damage and long-term neurological pathologies.

Mechanisms Underlying Biological Effects of Cruciferous Glucosinolate-Derived Isothiocyanates/Indoles: A Focus on Metabolic Syndrome.

An inverse correlation between vegetable consumption and the incidence of cancer has long been described. This protective effect is stronger when cruciferous vegetables are specifically consumed. The beneficial properties of vegetables are attributed to their bioactive components like fiber, antioxidants vitamins, antioxidants, minerals, and phenolic compounds. Cruciferous vegetables contain all these molecules; however, what makes them different are their sulfurous components, called glucosinolates, responsible for their special smell and taste. Glucosinolates are inactive biologically in the organism but are hydrolyzed by the enzyme myrosinase released as a result of chewing, leading to the formation of active derivatives such as isothiocyanates and indoles. A considerable number of in vitro and in vivo studies have reported that isothiocyanates and indoles elicit chemopreventive potency through multiple mechanisms that include modulation of phases I and II detoxification pathway enzymes, regulation of cell cycle arrest, and control of cell growth, induction of apoptosis, antioxidant activity, anti-angiogenic effects, and epigenetic regulation. Nuclear erythroid 2-related factor 2 (Nrf2) and Nuclear factor-κB (NF-κB) are key and central regulators in all these processes with a main role in oxidative stress and inflammation control. It has been described that isothiocyanates and indoles regulate their activity directly and indirectly. Today, the metabolic syndrome (central obesity, insulin resistance, hyperlipidemia, and hypertension) is responsible for a majority of deaths worldwide. All components of metabolic syndrome are characterized by chronic inflammation with deregulation of the PI3K/AKT/mTOR, MAPK/EKR/JNK, Nrf2, and NF-κB signaling pathways. The effects of GLSs derivatives controlling these pathways have been widely described in relation to cancer. Changes in food consumption patterns observed in the last decades to higher consumption of ultra-processed foods, with elevation in simple sugar and saturated fat contents and lower consumption of vegetables and fruits have been directly correlated with metabolic syndrome prevalence. In this review, it is summarized the knowledge regarding the mechanisms by which cruciferous glucosinolate derivatives (isothiocyanates and indoles) directly and indirectly regulate these pathways. However, the review places a special focus on the knowledge of the effects of glucosinolates derivatives in metabolic syndrome, since this has not been reviewed before.

Efficacy, cost-utility and physiological effects of Acceptance and Commitment Therapy (ACT) and Behavioural Activation Treatment for Depression (BATD) in patients with chronic low back pain and depression: study protocol of a randomised, controlled trial including mobile-technology-based ecological momentary assessment (IMPACT study).

INTRODUCTION: The IMPACT study focuses on chronic low back pain (CLBP) and depression symptoms, a prevalent and complex problem that represents a challenge for health professionals. Acceptance and Commitment Therapy (ACT) and Brief Behavioural Activation Treatment for Depression (BATD) are effective treatments for patients with persistent pain and depression, respectively. The objectives of this 12 month, multicentre, randomised, controlled trial (RCT) are (i) to examine the efficacy and cost-utility of adding a group-based form of ACT or BATD to treatment-as-usual (TAU) for patients with CLBP and moderate to severe levels of depressive symptoms; (ii) identify pre-post differences in levels of some physiological variables and (iii) analyse the role of polymorphisms in the FKBP5 gene, psychological process measures and physiological variables as mediators or moderators of long-term clinical changes. METHODS AND ANALYSIS: Participants will be 225 patients with CLBP and moderate to severe depression symptoms recruited at Parc Sanitari Sant Joan de Déu (St. Boi de Llobregat, Spain) and Hospital del Mar (Barcelona, Spain), randomly allocated to one of the three study arms: TAU vs TAU+ACT versus TAU+BATD. A comprehensive assessment to collect clinical variables and costs will be conducted pretreatment, post-treatment and at 12 months follow-up, being pain interference the primary outcome measure. The following physiological variables will be considered at pretreatment and post-treatment assessments in 50% of the sample: immune-inflammatory markers, hair cortisol and cortisone, serum cortisol, corticosteroid-binding globulin and vitamin D. Polymorphisms in the FKBP5 gene (rs3800373, rs9296158, rs1360780, rs9470080 and rs4713916) will be analysed at baseline assessment. Moreover, we will include mobile-technology-based ecological momentary assessment, through the Pain Monitor app, to track ongoing clinical status during ACT and BATD treatments. Linear mixed-effects models using restricted maximum likelihood, and a full economic evaluation applying bootstrapping techniques, acceptability curves and sensitivity analyses will be computed. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of the Fundació Sant Joan de Déu and Hospital del Mar. The results will be actively disseminated through peer-reviewed journals, conference presentations, social media and various community engagement activities. TRIAL REGISTRATION NUMBER: NCT04140838.

Different modulation by dietary restriction of adipokine expression in white adipose tissue sites in the rat.

BACKGROUND: White adipose tissue (WAT) is a disperse organ acting as energy storage depot and endocrine/paracrine controlling factor in the management of energy availability and inflammation. WAT sites response under energy-related stress is not uniform. In the present study we have analyzed how different WAT sites respond to limited food restriction as a way to better understand the role of WAT in the pathogenesis of the metabolic syndrome. METHODS: Overweight male rats had their food intake reduced a 40% compared with free-feeding controls. On day ten, the rats were killed; circulating glucose, insulin, leptin, adiponectin, triacylglycerols and other parameters were measured. The main WAT sites were dissected: mesenteric, retroperitoneal, epididymal and subcutaneous inguinal, which were weighed and frozen. Later all subcutaneous WAT was also dissected and weighed. Samples were used for DNA (cellularity) analysis and mRNA extraction and semiquantitarive RT-PCR analysis of specific cytokine gene expressions. RESULTS: There was a good correlation between serum leptin and cumulative WAT leptin gene mRNA, but not for adiponectin. Food restriction reduced WAT size, but not its DNA content (except for epididymal WAT). Most cytokines were correlated to WAT site weight, but not to DNA. There was WAT site specialization in the differential expression (and probably secretion) of adipokines: subcutaneous WAT showed the highest concentration for leptin, CD68 and MCP-1, mesenteric WAT for TNFalpha (and both tissues for the interleukins 1beta and 6); resistin was highly expressed in subcutaneous and retroperitoneal WAT. CONCLUSION: Food restriction induced different patterns for mesenteric and the other WAT sites, which may be directly related to both the response to intestine-derived energy availability, and an inflammatory-related response. However, retroperitoneal WAT, and to a lower extent, subcutaneous and epididymal, reacted decreasing the expression of inflammatory markers and the signaling of decreased energy availability in their stores. The varying cytokine expression patterns highlight the fact that WAT sites show different inflammatory and signaling responses to energy availability; they are too much different to simply extend to the whole-body WAT the findings of one or even a couple of sites.

Site-related white adipose tissue lipid-handling response to oleoyl-estrone treatment in overweight male rats.

BACKGROUND: Oleoyl-estrone (OE) decreases energy intake while maintaining glucose homeostasis, and energy expenditure at the expense of body fat. White adipose tissue (WAT) depots behave differently under starvation, postprandial state and pharmacologically induced lipolysis. AIM OF THE STUDY: To understand the mechanism of massive lipid loss from WAT elicited by OE treatment. METHODS: We used overweight male rats. Rats receiving OE (10 nmol/g) gavages were compared with controls and a pair-fed group. Whole fat pads from the mesenteric, retroperitoneal, epididymal and inguinal subcutaneous sites were excised and analyzed for lipid, DNA, mRNA and the expression of lipogenic, fatty acid transporters and lipase genes. RESULTS: In OE and pair-fed rats, WAT weights decreased, with the limited loss of cells. Patterns of gene expression in most WAT sites were similar for OE and PF, suggesting a shared mechanism of fat mobilization, but in mesenteric WAT, PF increased lipogenic and fatty acid transporter gene expressions. However, OE inhibited lipogenic expressions more deeply than PF. CONCLUSIONS: White adipose tissue sites showed different expression patterns, hinting at relatively specialized functions in fat storage; thus, single site analyses cannot be extrapolated to whole WAT. Differences between mesenteric and the other sites suggest that 'visceral fat' should be reserved for this site only, and not applied to other abdominal fat depots (epididymal, retroperitoneal).

Corticosteroid-Binding Globulin is expressed in the adrenal gland and its absence impairs corticosterone synthesis and secretion in a sex-dependent manner.

Corticosteroid-binding globulin (CBG) is synthesized by the liver and secreted into the bloodstream where binds to glucocorticoids. Thus CBG has the role of glucocorticoid transport and free hormone control. In addition, CBG has been detected in some extrahepatic tissues without a known role. CBG-deficient mice show decreased total corticosterone levels with missing of classical sexual dimorphism, increased free corticosterone, higher adrenal gland size and altered HPA axis response to stress. Our aim was to ascertain whether CBG deficiency could affect the endocrine synthetic activity of adrenal gland and if the adrenal gland produces CBG. We determined the expression in adrenal gland of proteins involved in the cholesterol uptake and its transport to mitochondria and the main enzymes involved in the corticosterone, aldosterone and catecholamine synthesis. The results showed that CBG is synthesized in the adrenal gland. CBG-deficiency reduced the expression of ACTH receptor, SRB1 and the main genes involved in the adrenal hormones synthesis, stronger in females resulting in the loss of sexual dimorphism in corticosteroid adrenal synthesis, despite corticosterone content in adrenal glands from CBG-deficient females was similar to wildtype ones. In conclusion, these results point to an unexplored and relevant role of CBG in the adrenal gland functionality related to corticosterone production and release.

Short-term oleoyl-estrone treatment affects capacity to manage lipids in rat adipose tissue.

BACKGROUND: Short-term OE (oleoyl-estrone) treatment causes significant decreases in rat weight mainly due to adipose tissue loss. The aim of this work was to determine if OE treatment affects the expression of genes that regulate lipid metabolism in white adipose tissue. RESULTS: Gene expression in adipose tissue from female treated rats (48 hours) was analysed by hybridization to cDNA arrays and levels of specific mRNAs were determined by real-time PCR. Treatment with OE decreased the expression of 232 genes and up-regulated 75 other genes in mesenteric white adipose tissue. The use of real-time PCR validate that, in mesenteric white adipose tissue, mRNA levels for Lipoprotein Lipase (LPL) were decreased by 52%, those of Fatty Acid Synthase (FAS) by 95%, those of Hormone Sensible Lipase (HSL) by 32%, those of Acetyl CoA Carboxylase (ACC) by 92%, those of Carnitine Palmitoyltransferase 1b (CPT1b) by 45%, and those of Fatty Acid Transport Protein 1 (FATP1) and Adipocyte Fatty Acid Binding Protein (FABP4) by 52% and 49%, respectively. Conversely, Tumour Necrosis Factor (TNFalpha) values showed overexpression (198%). CONCLUSION: Short-term treatment with OE affects adipose tissue capacity to extract fatty acids from lipoproteins and to deal with fatty acid transport and metabolism.

Oleoyl-estrone treatment activates apoptotic mechanisms in white adipose tissue.

To determine whether lipid mobilization in white adipose tissue caused by oleoyl-estrone (OE) treatment leads to activation of apoptosis, female Wistar rats were given a daily oral gavage of 10 micromol/kg of OE in 0.2 ml of sunflower oil and DNA fragmentation in different adipose tissues was assessed by ligation-mediated PCR after 6, 24, 48, or 240 h. Expression of selected apoptotic target genes was analysed by RT-PCR in adipose tissue from animals treated for 2 days. The response of adipose tissue to OE treatment was not the same in all locations. In mesenteric adipose tissue, a significant increase in the expression of Bid, Bax, caspase 3 and caspase 8 was detected, whereas in periovaric adipose tissue, only Bax and caspase 3 expression showed significant increases. No effect was detected in subcutaneous or retroperitoneal adipose tissue. The increased expression of apoptotic factors suggests that this pathway could be activated by OE treatment.

Paseos grupales. Evaluación cualitativa, más allá de los números / Walking groups. Qualitative evaluation, beyond the numbers

Objetivo: Indagar sobre los efectos percibidos anivel emocional, actitudinal y social, además defísicos, de un programa de promoción de la actividad física consistente en paseos grupales, desdeun centro de Atención Primaria.Método. Estudio de evaluación cualitativa mediante la realización de dos grupos focales conlos participantes habituales del programa. Se hizouna entrevista por cada grupo. Cada sesión fuegrabada y transcrita.Resultados. Se llevó a cabo un análisis temáticomediante codificación de los contenidos. Los códigos fueron agrupados dando lugar a diferentescategorías y subcategorías. Se identificaron 8 categorías: 1. Beneficios percibidos: físicos, emocionales y sociales; 2. Ventajas del grupo: inclusión,adhesión y motivación; 3. Difusión: conocimientode la actividad, visibilización; 4. Actitudes suscitadas: valoración general, disciplina, motivación, adhesión; 5. Sugerencias de mejora: ampliación de horarios, diversificación 6. Participación:asimetría de género; 7. Papel de los monitores:capacidad de liderazgo, dinamización de la actividad; 8. Condiciones de la ruta: trazado, alternativas, seguridad.Conclusiones. Los participantes identifican beneficios autopercibidos en la salud física, en formade mejoría de parámetros biológicos, mayor movilidad y menor temor a caídas; beneficios de tipoemocional, descarga de tensiones, incremento dela autoestima, sentimientos de alegría propia ydeseo de transmitirla a otras personas, y beneficios de tipo social, gracias al establecimiento denuevas relaciones interpersonales y al refuerzo delas preexistentes. Destacan las ventajas del grupo,el papel de los dinamizadores y ofrecen sugerencias de mejora del programa. (AU)

Objective: Inquire about the perceived emotional,attitudinal, social and physical effects of a program topromote physical activity in a health district.Method. Qualitative study. Two focus groups werecarried out with participants of the program. An interview was conducted for each group. The sessions wereaudio recorded with previous consent, and transcribed.Results. A thematic analysis was performed by coding the contents. Eight categories were identified:1. Perceived benefits: physical, emotional and social;2. Advantages of the group: inclusion, adherence andmotivation; 3. Diffusion: knowledge of the activity,visibility; 4. Attitudes: general assessment, discipline,motivation, adherence; 5. Suggestions for improvement: extension of hours, diversification 6. Participation: gender asymmetry; 7. Role of the facilitators: leadership capacity, dynamization of the activity; 8. Routeconditions: layout, alternatives, safety.Conclusions. The participants identify benefits inphysical health: improvement of biological parameters, greater mobility and less fear of falls; emotionalbenefits, release of tensions, increased self-esteem,feelings of joy; and social benefits: establishment ofnew relationships and reinforcement of existing ones.They highlight the advantages of the group, the roleof facilitators and offer suggestions for improving theprogram. (AU)

Atención Primaria y redes comunitarias en tiempos COVID-19: una aproximación a lo que está pasando y qué podemos hacer / Primary care and community partnerships during the COVID19 pandemic: an approach to what has been done so far and ways to improve it

Objetivo. Identificar las redes y acciones comunitarias realizadas en la Comunidad Valenciana durante la situación de la pandemia por COVID-19 y describir las fortalezas y amenazas para el desarrollo de la salud comunitaria. Diseño. Estudio cuantitativo descriptivo y cualitativo, incluyendo un cuestionario remitido por correo y análisis DAFO. Emplazamiento. Equipos de Atención Primaria (EAP) de la Comunidad Valenciana. Participantes y contexto. El ámbito de estudio son los miembros de la Societat Valenciana de Medicina Familiar i Comunitària (SoVaMFiC). Método. 1) Constitución de un grupo de trabajo; 2) diseño de un cuestionario ad hoc para la identificación de redes comunitarias, acciones o iniciativas durante la pandemia por COVID-19, y de aspectos positivos y negativos del impacto de la pandemia sobre la salud comunitaria; 3) envío del cuestionario a través de correo electrónico; 4) análisis DAFO, y 5) elaboración de recomendaciones. Resultados. Se obtuvieron un total de 56 respuestas (3,3% de participación) identificándose 32 acciones o redes comunitarias de las cuales, 19 existían previamente a la crisis de la COVID-19. Se realizó un análisis DAFO y se identificaron 6 debilidades, 9 amenazas, 5 fortalezas y 8 oportunidades. Este análisis permitió la elaboración de un decálogo de recomendaciones para promover la atención comunitaria en tiempos de la COVID-19. Conclusiones. Las acciones y redes comunitarias surgidas durante la pandemia tienen como objetivo principal responder a las necesidades que han ido apareciendo. Los EAP han participado poco en estas iniciativas. (AU)

Objective: To identify community partnerships, actions or initiatives carried out in the Valencian Community during the Covid19 pandemic and to describe the strengths and challenges to supporting community health during this situation. Design: Mixed method study using survey with closed and open-ended questions and SWOT analysis. Setting: Primary Health are teams of the Valencian Community. Participants and context: Members of the Valencian Society of Family and Community Medicine (SoVaMFiC). Method: (1) Development of a working group. (2) Design of an ad hoc questionnaire to identify community partnerships, actions or initiatives during the Covid19 pandemic, and positive and negative aspects of the impact of the pandemic on community health. (3) Launch of the questionnaire via email; (4) SWOT analysis and (5) development of recommendations. Results: A total of 56 responses were obtained (3.3% response rate), identifying 32 actions or community networks, of which 19 existed prior to the Covid19 crisis. A SWOT analysis was carried out, and six weaknesses, nine threats, five strengths and eight opportunities were identified. This analysis informed the development of a set of 10 recommendations for community care in the time of Covid19. Conclusions: The community partnerships, actions or initiatives developed during the pandemic have the main objective of responding to the needs that have been emerging. The Primary Health Care teams have shown limited engagement in these initiatives. (AU)

Modulation of SHBG binding to testosterone and estradiol by sex and morbid obesity.

OBJECTIVE: Sex hormone-binding globulin (SHBG) binds and transports testosterone and estradiol in plasma. The possibility that SHBG is a mixture of transporting proteins has been postulated. We analyzed in parallel the effects of obesity status on the levels and binding capacity of circulating SHBG and their relationship with testosterone and estradiol. DESIGN: Anthropometric measures and plasma were obtained from apparently healthy young (i.e. 35 ± 7 years) premenopausal women (n = 32) and men (n = 30), with normal weight and obesity (BMI >30 kg/m2). METHODS: SHBG protein (Western blot), as well as the plasma levels of testosterone, estradiol, cortisol and insulin (ELISA) were measured. Specific binding of estradiol and testosterone to plasma SHBG was analyzed using tritium-labeled hormones. RESULTS: Significant differences in SHBG were observed within the obesity status and gender, with discordant patterns of change in testosterone and estradiol. In men, testosterone occupied most of the binding sites. Estrogen binding was much lower in all subjects. Lower SHBG of morbidly obese (BMI >40 kg/m2) subjects affected testosterone but not estradiol. The ratio of binding sites to SHBG protein levels was constant for testosterone, but not for estradiol. The influence of gender was maximal in morbid obesity, with men showing the highest binding/SHBG ratios. CONCLUSIONS: The results reported here are compatible with SHBG being a mixture of at least two functionally different hormone-binding globulins, being affected by obesity and gender and showing different structure, affinities for testosterone and estradiol and also different immunoreactivity.

Teoría del cambio aplicada al programa de promoción de la actividad física «La Ribera Camina» / Theory of change implemented in the program to promote physical activity “La Ribera Camina”

Objetivo: Aplicar la teoría del cambio al diseño y la evaluación de un programa para promover la actividad física en 11 zonas básicas de salud. Método: Realización de cuatro grupos focales siguiendo la metodología de la teoría del cambio. Se identifican los cambios (a largo, medio y corto plazo) que se pretende alcanzar con el programa «La Ribera Camina» según la opinión de los agentes de interés: profesionales de atención primaria, concejalas/es y personal técnico municipal deportivo, y ciudadanía participante. A través de un análisis temático se identifican las acciones que se deben realizar para alcanzar estos cambios, y las dificultades y los facilitadores para la sostenibilidad del programa. Resultados: Los cambios identificados se clasificaron en cuatro apartados: 1) cambios en la salud física y social (mejoría en la condición física, hábitos saludables, autoestima y sensación de bienestar); 2) cambios organizativos y relacionales (mejor coordinación entre instituciones); 3) cambios específicos del programa (incorporación de más «activos» y asociaciones, sobre todo de hombres, y ampliación de rutas y horarios); y 4) cambios en el entorno (mejora de infraestructuras y seguridad de las rutas). Conclusiones: La teoría del cambio permite identificar y clasificar los cambios que se esperan, las acciones que deben realizarse y los vínculos entre elementos del programa. Esto servirá de base para la evaluación del programa. Dicha metodología podría aplicarse en otros programas que deseen incorporar la intersectorialidad y la participación comunitaria en su diseño y evaluación. (AU)

Objective: To develop a theory of change of a program to promote physical activity in eleven health districts, in order to improve its design and plan its evaluation. Method: Four focus groups were carried out, to develop a participatory theory of change, to identify the expected changes (long, medium and short term) of “La Ribera Camina” program, according to the following stakeholders: primary healthcare professionals, local government representatives and community members. A thematic analysis was used to identify the actions to be taken to achieve these changes, as well as the difficulties and facilitators to enhance the sustainability of the program. Results: The identified changes were classified into four themes: 1) changes in physical and social health (improved physical condition, healthy habits, self-esteem and perceived well-being); 2) organizational and relational changes (better coordination between institutions); 3) specific changes to the program (incorporation of more “assets” and local associations, especially male participants, more trails and schedules); and 4) changes in the environment (improved trails’ infrastructures and safety). Conclusions: The theory of change allows to identify and classify the changes that are expected, the actions to be carried out and the links between elements of the program. This will serve as the basis for its evaluation. This methodology could be applied to other programs interested in incorporating intersectorality and community engagement in their design and evaluation. (AU)

Altered lipid partitioning and glucocorticoid availability in CBG-deficient male mice with diet-induced obesity.

OBJECTIVE: To evaluate how deficiency in corticosteroid-binding globulin (CBG), the specific carrier of glucocorticoids, affects glucocorticoid availability and adipose tissue in obesity. METHODS: C57BL/6 (WT) and CBG-deficient (KO) male mice were fed during 12 weeks with standard or hyperlipidic diet (HL). Glucocorticoid availability and metabolic parameters were assessed. RESULTS: Body weight and food intake were increased in KO compared with WT mice fed a standard diet and were similar when fed a HL diet. Expression of CBG was found in white adipose tissue by immunochemistry, real-time PCR, and Western blot. In obesity, the subcutaneous depot developed less in KO mice compared with WT, which was associated with a minor adipocyte area and peroxisome proliferator-activated receptor-γ expression. Conversely, the epididymal depot displayed higher weight and adipocyte area in KO than in WT mice. CBG deficiency caused a fall of hepatic 11ß-hydroxysteroid dehydrogenase type 2 expression and an increase in epidymal adipose tissue, particularly in HL mice. CONCLUSIONS: Deficiency in CBG drives lipid partitioning from subcutaneous to visceral adipose depot under a context of lipid excess and differentially modulates 11ß-hydroxysteroid dehydrogenase type 2 expression.

New Roles for Corticosteroid Binding Globulin and Opposite Expression Profiles in Lung and Liver.

Corticosteroid-binding globulin (CBG) is the specific plasma transport glycoprotein for glucocorticoids. Circulating CBG is mainly synthesized in liver but, its synthesis has been located also in other organs as placenta, kidney and adipose tissue with unknown role. Using an experimental model of acute pancreatitis in cbg-/- mice we investigated whether changes in CBG affect the progression of the disease as well as the metabolism of glucocorticoids in the lung. Lack of CBG does not modify the progression of inflammation associated to pancreatitis but resulted in the loss of gender differences in corticosterone serum levels. In the lung, CBG expression and protein level were detected, and it is noteworthy that these showed a sexual dimorphism opposite to the liver, i.e. with higher levels in males. Reduced expression of 11ß-HSD2, the enzyme involved in the deactivation of corticosterone, was also observed. Our results indicate that, in addition to glucocorticoids transporter, CBG is involved in the gender differences observed in corticosteroids circulating levels and plays a role in the local regulation of corticosteroids availability in organs like lung.

Decreased OxLDL uptake and cholesterol efflux in THP1 cells elicited by cortisol and by cortisone through 11ß-hydroxysteroid dehydrogenase type 1.

BACKGROUND AND AIMS: Data about glucocorticoids role in the development of atherosclerosis are controversial showing different effects in human than in experimental animal models. Atherosclerosis is the result of a chronic inflammatory response to an injured endothelium where an uncontrolled uptake of OxLDL by macrophages triggers the development of foam cells, the main component of fatty streaks in atherosclerotic plaque. There are few data about the direct effect of glucocorticoids in macrophages of atherosclerotic plaque. The aim of the study was to elucidate the role of glucocorticoids in the development of foam cells in atherosclerosis initiation. METHODS: For this purpose we used THP1 cells differentiated to macrophages with phorbol esters and incubated with OxLDL alone or with cortisol or cortisone. THP1 cells were also incubated with cortisone plus an inhibitor of 11ß-hydroxysteroid dehydrogenase 1 (11ßHSD1) activity to determine the role of this enzyme on glucocorticoid action in this process. RESULTS: Ours results showed that cortisol and cortisone decreased significantly the inflammation promoted by OxLDL, and also diminished the expression of genes involved in influx and efflux of cholesterol resulting in a reduced lipid accumulation. Likewise cortisol and cortisone decreased 11ßHSD1 expression in THP1 cells. The presence of the inhibitor of 11ßHSD1 abolished all the effects elicited by cortisone. CONCLUSION: Our results indicate a direct effect of glucocorticoids on macrophages braking atherosclerosis initiation, reducing pro-inflammatory markers and OxLDL uptake and cholesterol re-esterification, but also inhibiting cholesterol output. These effects appear to be mediated, at least in part, by 11ßHSD1 activity.