Circulating serotonin and dopamine concentrations in osteoarthritis patients: a pilot study on the effect of pelotherapy.

Balneotherapy has demonstrated clinical efficacy in the management of pathologies involving low-grade inflammation and stress. In rheumatic conditions such as osteoarthritis (OA), this therapy presents anti-inflammatory properties and potential to improve psychological well-being. Although the neurohormones serotonin and dopamine are known to be involved in these processes, surprisingly they have not been studied in this context. The objective was to evaluate the effect of a cycle of balneotherapy with peloids (pelotherapy) on circulating serotonin and dopamine concentrations in a group of aged individuals with OA, after comparing their basal state to that of an age-matched control group. In our pilot study, a pelotherapy program (10 days) was carried out in a group of 16 elderly patients with OA, evaluating its effects on circulating serotonin and dopamine concentrations (measured by ELISA). Individuals with OA showed higher levels of serotonin and lower dopamine levels, in line with the inflammatory roles of these mediators. After pelotherapy, serotonin concentrations significantly decreased, potentially contributing to the previously reported anti-inflammatory effects of balneotherapy.

Spa therapy and peripheral serotonin and dopamine function: a systematic review.

Spa therapy consists of multiple techniques based on the healing effects of water, including hydrotherapy, balneotherapy, and mud therapy, often combined with therapeutic exercises, massage, or physical therapy. Balneotherapy is a clinically effective complementary approach in the treatment of low-grade inflammation- and stress-related pathologies, especially rheumatic conditions due to its anti-inflammatory properties. The main objective of this investigation was to conduct a systematic review analyzing the available evidence on the effect of spa therapy on serotonin and dopamine function. The databases PubMed, Web of Science, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL) were used from June to July 2023. Exclusion criteria were (1) articles not written in English, (2) full text not available, (3) article not related to the objective of the review. JADAD scale was used for methodological quality evaluation. Four studies were included in the systematic review. Two studies were related to serotonin in healthy individuals, one to serotonin in fibromyalgia, and one to dopamine in healthy individuals. One of the studies evaluated hydrotherapy, another one balneotherapy and mud-bath therapy, and the other two assessed balneotherapy interventions. Studies were very heterogeneous, and their methodological quality was low, making it difficult to draw clear conclusions regarding the effect of spa therapy on peripheral serotonin and dopamine function. The findings of this review highlight the lack of studies evaluating these neurotransmitters and hormones in the context of spa therapy. Further research is needed to evaluate the potential effects of these therapies on serotonin or dopamine function.

Subjective Sleep Quality Versus Objective Accelerometric Measures of Sleep and Systemic Concentrations of Sleep-Related Hormones as Objective Biomarkers in Fibromyalgia Patients.

Poor quality of sleep leads to an increase in severity of the symptoms associated with fibromyalgia (FM) syndrome and vice versa. The aim of this study was to determine if the poor perceived sleep quality in FM patients could be corroborated by objective physiological determinations. Perceived sleep quality was evaluated (through the Pittsburgh Sleep Quality Index) in 68 FM patients compared to an age-matched reference group of 68 women without FM. Objective sleep quality (measured using accelerometry), and systemic concentrations of sleep-related hormones (catecholamines, oxytocin, serotonin, and melatonin) were evaluated in two representative groups from the reference control group (n = 11) and FM patients (n = 11). FM patients reported poorer subjective sleep quality compared to the reference group. However, no significant differences were found in accelerometry parameters, except for a delay in getting in and out of bed. In addition, FM patients showed no significant differences in oxytocin concentration and adrenaline/noradrenaline ratio, as well as a lower serotonin/melatonin ratio. Poor perception of sleep quality in FM patients does not correspond to objective determinations. A dysregulation of the stress response could be associated with the delay in their resting circadian rhythm and difficulty falling asleep. This would be the cause that justifies the perceived lack of rest and the fatigue they feel when waking up.

The anti-inflammatory and bioregulatory effects of habitual exercise in high-fat diet-induced obesity involve crown-like structures and MCP-1 in white adipose tissue.

Macrophage accumulation in the adipose tissue and changes in their inflammatory phenotype is a hallmark of obesity-induced inflammation, notably forming inflammatory structures known as "crown-like structures (CLS)". Exercise can be a key strategy to improve inflammation-related complications, but it is crucial to consider that, although exercise generally exerts systemic and local anti-inflammatory effects, this depends on the basal inflammatory status and exercise modality. In this context, the "bioregulatory effect of exercise" implies to achieve the reduction or prevention of an excessive inflammatory response and also the preservation or stimulation of the innate response. In the present work, our aim was to evaluate the effect of regular exercise on adipose tissue inflammation in high-fat diet-induced obesity in mice, as reflected by macrophage infiltration and phenotype, and CLS formation, together with a potential role for the chemokine MCP-1 in this process. Results showed that obesity is associated with greater MCP-1 expression (p<0.05), macrophage accumulation (p<0.05), and CLS presence (p<0.001). Regular exercise reduced macrophage accumulation (p<0.05), MCP-1 expression (p<0.01), and CLS presence (p<0.05) in obese mice; while it increased macrophage and CLS presence (p<0.01), MCP-1 expression (p<0.05), and M2 polarization (p<0.05) in lean mice. MCP-1 was associated with the proliferation of CLS, showing the first image demonstrating a potential role of this chemokine in the development of these structures. Altogether, these results confirm, for the first time, the "bioregulatory effect of exercise" in the adipose tissue: reducing inflammation in individuals with an elevated inflammatory setpoint, but stimulating this response of the immune system in healthy individuals.

Influence of Chronic Fatigue Syndrome Codiagnosis on the Relationship between Perceived and Objective Psychoneuro-Immunoendocrine Disorders in Women with Fibromyalgia.

Although the predominant symptom in fibromyalgia (FM) is muscle pain, and fatigue in chronic fatigue syndrome (CFS), differential diagnosis is very difficult. This research investigates the psychoneuroimmunoendocrine disorders of FM patients and ascertains whether a previous CFS diagnosis affected them. Through accelerometry objective parameters, physical activity/sedentarism levels in relation to fatigue are studied, as well as whether perceived levels of stress, anxiety, and pain correspond to objective biomarkers, all of these with respect to a reference group (RG) of women without FM. FM patients have a worse psychological state and perceived quality of life than those with RG. These perceived outcomes are consistent with impaired objective levels of a sedentary lifestyle, higher systemic levels of cortisol and noradrenaline, and lower levels of serotonin. However, FM patients with a previous CFS diagnosis had lower systemic levels of IL-8, cortisol, oxytocin, and higher levels of adrenaline and serotonin than FM patients without diagnosed CFS. In conclusion, while perceived health parameters do not detect differences, when objective neuroimmunoendocrine parameters related to stress, inflammation, pain, and fatigue are used, people with CFS could be overdiagnosed with FM. This reinforces the need for objective biomarker assessment of these patients for better diagnostic discrimination between both syndromes.

Synbiotic Supplementation Improves Quality of Life and Inmunoneuroendocrine Response in Patients with Fibromyalgia: Influence of Codiagnosis with Chronic Fatigue Syndrome.

Fibromyalgia (FM) and chronic fatigue syndrome (CFS) are two medical conditions in which pain, fatigue, immune/inflammatory dysregulation, as well as various mental health disorders predominate in the diagnosis, without evidence of a clear consensus on the treatment of FM and CFS. The main aim of this research was to analyse the possible effects of a synbiotic (Synbiotic, Gasteel Plus® (Heel España S.A.U.), through the study of pro-inflammatory/anti-inflammatory cytokines (IL-8/IL-10) and neuroendocrine biomarkers (cortisol and DHEA), in order to evaluate the interaction between inflammatory and stress responses mediated by the cytokine-HPA (hypothalamic-pituitary-adrenal) axis, as well as mental and physical health using body composition analysis, accelerometry and previously validated questionnaires. The participants were women diagnosed with FM with or without a diagnostic of CFS. Each participant was evaluated at baseline and after the intervention, which lasted one month. Synbiotic intervention decreased levels of perceived stress, anxiety and depression, as well as improved quality of life during daily activities. In addition, the synbiotic generated an activation of HPA axis (physiological cortisol release) that can compensate the increased inflammatory status (elevated IL-8) observed at baseline in FM patients. There were no detrimental changes in body composition or sleep parameters, as well as in the most of the activity/sedentarism-related parameters studied by accelerometry. It is concluded that synbiotic nutritional supplements can improve the dysregulated immunoneuroendocrine interaction involving inflammatory and stress responses in women diagnosed with FM, particularly in those without a previous CFS diagnostic; as well as their perceived of levels stress, anxiety, depression and quality of life.

Influence of Codiagnosis of Chronic Fatigue Syndrome and Habitual Physical Exercise on the Psychological Status and Quality of Life of Patients with Fibromyalgia.

Fibromyalgia (FM) and Chronic Fatigue Syndrome (CFS) are two diseases that are frequently codiagnosed and present many similarities, such as poor tolerance to physical exercise. Although exercise is recommended in their daily routine to improve quality of life, little is known about how CFS codiagnosis affects that. Using scientifically validated questionnaires, we evaluated the psychological state and quality of life of patients with FM (n = 70) and how habitual physical exercise (HPE) reported by patients with only FM (FM-only n = 38) or codiagnosed with CFS (FM + CFS, n = 32) influences those aspects. An age-matched reference group of "healthy" women without FM (RG, n = 70) was used. The FM-only group presented a worse psychological state and quality of life compared to RG, with no influence of CFS codiagnosis. The patients of the FM-only and FM + CFS groups who perform HPE presented better levels of stress and state anxiety, but with no differences between them. Depression and trait anxiety improved only in women with just FM. CFS codiagnosis does not worsen the psychological and quality of life impairment of FM patients and does not have a great influence on the positive effect of HPE.

The Influence of Obesity and Weight Loss on the Bioregulation of Innate/Inflammatory Responses: Macrophages and Immunometabolism.

Obesity is characterized by low-grade inflammation and more susceptibility to infection, particularly viral infections, as clearly demonstrated in COVID-19. In this context, immunometabolism and metabolic flexibility of macrophages play an important role. Since inflammation is an inherent part of the innate response, strategies for decreasing the inflammatory response must avoid immunocompromise the innate defenses against pathogen challenges. The concept "bioregulation of inflammatory/innate responses" was coined in the context of the effects of exercise on these responses, implying a reduction in excessive inflammatory response, together with the preservation or stimulation of the innate response, with good transitions between pro- and anti-inflammatory macrophages adapted to each individual's inflammatory set-point in inflammatory diseases, particularly in obesity. The question now is whether these responses can be obtained in the context of weight loss by dietary interventions (low-fat diet or abandonment of the high-fat diet) in the absence of exercise, which can be especially relevant for obese individuals with difficulties exercising such as those suffering from persistent COVID-19. Results from recent studies are controversial and do not point to a clear anti-inflammatory effect of these dietary interventions, particularly in the adipose tissue. Further research focusing on the innate response is also necessary.

Balneotherapy year in review 2021: focus on the mechanisms of action of balneotherapy in rheumatic diseases.

Balneotherapy (BT) is one of the most commonly used non-pharmacologic complementary therapies for different rheumatic diseases. Its beneficial properties probably derived from a combination of mechanical, thermal, and chemical effects, but the exact mechanism of action is not elucidated. This review aimed at summarizing the current knowledge about the effects of BT, and identifying its possible mechanism of action in different rheumatic diseases. Pubmed and Scopus were used to perform a search of the literature to extract articles including terms related to BT and rheumatic diseases published in the period from 2010 to 2021. We selected pre-clinical studies, randomized controlled trials, and clinical trials. The results of clinical studies confirmed the beneficial properties on different mediators and factors of inflammation, oxidative stress, cartilage metabolism, and humoral and cellular immune responses in patients affected by chronic degenerative musculoskeletal disorders. The data derived from OA and RA-induced murine models revealed the efficacy of different BT treatments in decreasing pain, inflammation, and improving mobility, as well as in reducing the expression of matrix-degrading enzymes and markers of oxidative stress damage. Different in vitro studies analyzed the potential effect of a mineral water, as a whole, or of a mineral element, demonstrating their anti-inflammatory, antioxidant, and chondroprotective properties in OA cartilage, synoviocytes and chondrocytes, and osteoblast and osteoclast cultures. The presented data are promising and confirm BT as an effective complementary approach in the management of several low-grade inflammation, degenerative, and stress-related pathologies, as rheumatic diseases.

Differential Health Effects on Inflammatory, Immunological and Stress Parameters in Professional Soccer Players and Sedentary Individuals after Consuming a Synbiotic. A Triple-Blinded, Randomized, Placebo-Controlled Pilot Study.

The main objective of this research was to carry out an experimental study, triple-blind, on the possible immunophysiological effects of a nutritional supplement (synbiotic, Gasteel Plus®, Heel España S.A.U.), containing a mixture of probiotic strains, such as Bifidobacterium lactis CBP-001010, Lactobacillus rhamnosus CNCM I-4036, and Bifidobacterium longum ES1, as well as the prebiotic fructooligosaccharides, on both professional athletes and sedentary people. The effects on some inflammatory/immune (IL-1ß, IL-10, and immunoglobulin A) and stress (epinephrine, norepinephrine, dopamine, serotonin, corticotropin-releasing hormone (CRH), Adrenocorticotropic hormone (ACTH), and cortisol) biomarkers were evaluated, determined by flow cytometer and ELISA. The effects on metabolic profile and physical activity, as well as on various parameters that could affect physical and mental health, were also evaluated via the use of accelerometry and validated questionnaires. The participants were professional soccer players in the Second Division B of the Spanish League and sedentary students of the same sex and age range. Both study groups were randomly divided into two groups: a control group-administered with placebo, and an experimental group-administered with the synbiotic. Each participant was evaluated at baseline, as well as after the intervention, which lasted one month. Only in the athlete group did the synbiotic intervention clearly improve objective physical activity and sleep quality, as well as perceived general health, stress, and anxiety levels. Furthermore, the synbiotic induced an immunophysiological bioregulatory effect, depending on the basal situation of each experimental group, particularly in the systemic levels of IL-1ß (increased significantly only in the sedentary group), CRH (decreased significantly only in the sedentary group), and dopamine (increased significantly only in the athlete group). There were no significant differences between groups in the levels of immunoglobulin A or in the metabolic profile as a result of the intervention. It is concluded that synbiotic nutritional supplements can improve anxiety, stress, and sleep quality, particularly in sportspeople, which appears to be linked to an improved immuno-neuroendocrine response in which IL-1ß, CRH, and dopamine are clearly involved.

Influence of Obesity and Exercise on ß2-Adrenergic-Mediated Anti-Inflammatory Effects in Peritoneal Murine Macrophages.

Obesity is a chronic low-grade inflammatory condition, and ß2-adrenergic agonists as well as exercise have been proposed as anti-inflammatory strategies in obesity, so it is critical to accurately determine the effects of ß2-adrenergic stimulation, especially when combined with other non-pharmacological therapies. The aim of this investigation was to determine the effect of ß2-adrenergic activation on the inflammatory profile and phenotype of macrophages, and whether these effects could be affected by obesity and exercise in this condition. High-fat diet-induced obese and lean C57BL/6J mice were allocated to sedentary or exercised groups. The inflammatory profiles and phenotypes of their peritoneal macrophages were assessed by flow cytometry in the presence or absence of the selective ß2-adrenergic receptor agonist terbutaline. ß2-adrenergic activation caused global phenotypic anti-inflammatory effects in lean and obese sedentary mice, which were more drastic (also including anti-inflammatory effects on the cytokine profile) in obese animals. In exercised lean and obese animals, this anti-inflammatory effect is weaker and only evident by decreased iNOS and IL-8 expression, without changes in the anti-inflammatory markers. Therefore, ß2-adrenergic activation leads to anti-inflammatory effects, but these effects are modulated by obesity in sedentary conditions, as well as by regular exercise; but not by obesity in trained conditions.

ß2 Adrenergic Regulation of the Phagocytic and Microbicide Capacity of Circulating Monocytes: Influence of Obesity and Exercise.

Obese individuals present anomalous immune/inflammatory responses with dysregulations in neuroendocrine responses and immune/stress feedback mechanisms. In this context, exercise and ß2 adrenergic activation present monocyte-mediated anti-inflammatory effects that are modulated by obesity. However, these anti-inflammatory effects could immunocompromise the monocyte-mediated innate response against a pathogen challenge. Thus, the objective of this work was to evaluate the effect of obesity, and exercise in this condition, on the ß2 adrenergic regulation of the phagocytic and microbicide capacity of circulating monocytes. C57BL/6J mice were allocated to different sedentary or exercised, lean or obese groups. Obese mice showed a lower monocyte-mediated innate response than that of lean mice. Globally, selective ß2 adrenergic receptor agonist terbutaline decreased the innate response of monocytes from lean and obese sedentary animals, whereas exercise stimulated it. Exercise modulates ß2 adrenergic regulation of the innate response in lean and obese animals, with a global stimulatory or neutral effect, thus abolishing the inhibitory effect of terbutaline occurring in sedentary animals. These effects cannot be explained only by changes in the surface expression of toll-like receptors. Therefore, in general, terbutaline does not hinder the effects of regular exercise, but regular exercise does abolish the effects of terbutaline in sedentary individuals.

Optimizing Shotgun Proteomics Analysis for a Confident Protein Identification and Quantitation in Orphan Plant Species: The Case of Holm Oak (Quercus ilex).

The proteomics of orphan, unsequenced, and recalcitrant organisms is highly challenging. This is the case of the typical Mediterranean forest tree Holm oak (Quercus ilex). Proteomics has moved on quite fast from the classical 2DE-MS to shotgun or gel-free/label-free approaches, with the latter possessing a series of advantages over the gel-based ones. Before translating proteomics data into biological knowledge, a few questions as to the analysis technique itself have to be answered including its confidence in protein identification and quantification. It is important to clearly differentiate a hit from an ortholog and gene product identification, with the difference depending on the database and the confidence parameters (score, number of peptides, and coverage). With respect to quantification and for comparative purposes it is important to make sure that we are within the linear dynamic range. For that, a calibration curve based on mass spectrometry analysis of a serial dilution of the extracts should be performed. Thus, just by validating our data with the aim of improving the quality of the analysis enables us to give a correct interpretation of our results. We show a method that aims to improve the confidence in protein identification and quantification in the orphan species Q. ilex using a shotgun proteomics approach.

Gestación gemelar en paciente con epidermolisis bullosa distrófica recesiva severa: revisión de la bibliografía en base a un caso clínico / Twin pregnancy in woman affected by severe recessive dystrophic epidermolysis bullosa: a case report and a literature review

La epidermolisis bullosa distrófica es un grupo de trastornos hereditarios de muy baja prevalencia que se caracterizan por una extrema fragilidad cutánea como consecuencia de una alteración de la cohesión de la unión epidermodérmica. Sin embargo, las manifestaciones clínicas van más allá de las lesiones cutáneas, habiéndose descrito afectación de la mayoría de aparatos y sistemas y siendo frecuente también cierto grado de desnutrición y anemia de origen multifactorial. Presentamos el caso de una paciente de 34 años, secundigesta, con epidermólisis bullosa distrófica recesiva severa, gestante gemelar bicorial y biamniótica, que seguimos durante todo el embarazo y su finalización. La baja prevalencia de la enfermedad hace que el manejo de la gestación suponga un reto para el ginecobstetra. A pesar de que los casos publicados hacen creer que la gestación no modifica el curso natural de la enfermedad, lo cierto es que se recomienda que el embarazo sea seguido por un equipo multidisciplinar. Existen publicados casos en los que se finaliza la gestación por vía vaginal, sin embargo, no existe evidencia suficiente para considerar ésta como la vía de elección.

Dystrophic epidermolysis bullosa is a group of hereditary disorders that has very low prevalence. It is characterized by an extreme cutaneous fragility as a consequence of a cohesion alteration of the epidermis and dermis junction. However, the clinical manifestations also affect other systems and organs, being able to cause malnutrition and anemia. We present the case of a 34-year-old woman affected by severe recessive dystrophic epidermolysis bullosa, with a bichorial and biamniotic twin pregnancy, whom we have followed throughout the pregnancy. The low prevalence of this disease makes the management of the pregnancy a challenge for the obstetrician. Although the published cases suggest that gestation does not modify the natural course of the disease, it is recommended that these pregnancies are monitored by a multidisciplinary team. Some published cases describe vaginal delivery. Nevertheless, it is not clear that this should be the first choice.

Association between sexual dysfunction and avulsion of the levator ani muscle after instrumental vaginal delivery.

INTRODUCTION: The effects of levator ani muscle (LAM) avulsion after instrumental delivery on the sexual function of patients are currently unknown. Therefore, the objective of our study was to use a validated questionnaire, namely, the Female Sexual Function Index (FSFI), to compare the sexual function in patients with and without LAM avulsion after instrumental vaginal delivery. MATERIAL AND METHODS: This was a prospective observational study of 112 primiparous women after instrumental (vacuum or forceps) vaginal delivery. The obstetric and general characteristics of the population were studied. At 6 months postpartum, the contraceptive method used and the occurrence of LAM avulsion (using four-dimensional transperineal ultrasound) were determined, and the FSFI was administered. RESULTS: A total of 100 patients (62 without avulsion and 38 with avulsion) completed the study. Thirty-eight (38%) were diagnosed with avulsion (42.1% after Kielland forceps delivery, 57.9% after Malmström vacuum delivery; P = .837). Women with LAM avulsion had significantly lower scores for desire (2.9 ± 1.2 vs 3.4 ± 1.1; P = .049), arousal (2.8 ± 1.7 vs 3.6 ± 1.4; P = .014), lubrication (2.3 ± 1.4 vs 3.0 ± 1.2; P = .011), orgasm (2.6 ± 1.6 vs 3.3 ± 1.2; P = .006) and satisfaction (3.1 ± 1.8 vs 3.9 ± 1.5; P = .051) than did women without LAM avulsion. The overall FSFI score was lower in patients with avulsion (16.7 ± 8.9 vs 20.7 ± 6.9, P = .033). These results were obtained after controlling for confounders (delivery mode, induced labor, birthweight, perineal tears, avulsion degree, contraceptive method and group assignment for the parent study) in the multivariate analysis (F = 4.974, P = .001). CONCLUSIONS: Patients with LAM avulsion present a higher degree of sexual dysfunction compared wiith patients without avulsion at 6 months after instrumental vaginal delivery.

Effect of mud-bath therapy on the innate/inflammatory responses in elderly patients with osteoarthritis: a discussion of recent results and a pilot study on the role of the innate function of monocytes.

Recent findings from our laboratory highlight the role of the modulation of the innate immune function and systemic inflammatory response in the effectiveness of balneotherapy in rheumatic diseases, specifically in elderly patients with osteoarthritis. Immune-neuroendocrine and stress mediators are involved in these effects. The 'bioregulatory effect of balneotherapy' has also been recently proposed as a mechanism of effectiveness that consists of a reduction in systemic pro-inflammatory mediators together with the achievement of an optimal innate response through stimulation (or at least lack of impairment) of the innate defences against pathogens (i.e. phagocytosis, microbicide activity) mediated by neutrophils, also generating immunophysiological adaptations through an optimal balance between the pro- and the anti-inflammatory responses in which regulatory T cells seem to have a crucial role. In the present paper, we aim to analyse the main conclusions related to how balneotherapy with the use of peloids (pelotherapy) affects the innate and inflammatory responses, constituting an immunophysiological mechanism underlying the proven clinical benefits of this intervention. We also introduce novel results regarding the innate response (phagocytic process) of monocytes in this therapy, an inflammatory cell that has not yet been studied in this context. Increased chemotaxis together with a decline in oxidative burst, without changes in phagocytosis, could be the main response induced by this modality of balneological intervention.

Papel de la ansiedad preoperatoria en la percepción de dolor en pacientes sometidas a histeroscopia quirurgica en consulta / Impact of preprocedural anxiety levels on pain perception in patients undergoing office surgical hysteroscopy

OBJETIVO: Determinar si la ansiedad preoperatoria supone un factor de riesgo independiente para la percepción de dolor severo durante la realización de una histeroscopia quirúrgica ambulatoria. MATERIAL Y MÉTODOS: Estudio de cohortes en el que incluimos179 pacientes. Se ha aplicado el formulario STAI-S para valorar la ansiedad preoperatoria de las pacientes y distribuirlas en dos cohortes: Pacientes con ansiedad (STAI-S >50) y pacientes sin ansiedad (STAI-S7. Se ha calculado la asociación y el riesgo entre ambas variables mediante el Test X2 y el Riesgo Relativo (RR). Se ha utilizado el test de correlación de Pearson para valorar la correlación entre ambas variables. Se ha considerado estadísticamente significativo un valor de p<0.05. RESULTADOS: Las pacientes que percibieron dolor severo durante la entrada a la cavidad uterina (78,3% vs 29,5%; p<0,001) y durante la realización del proceso quirúrgico (78,8% vs 26,2%; p<0,001) fueron en su mayoría pacientes con ansiedad preoperatoria. El RR de las pacientes con ansiedad para percibir dolor severo es de 6,46 (IC 95%; 2,52 -16,60) durante la entrada y de 6,61 (IC 95%; 3,04 -14,38) durante la resección. Existe una correlación moderada y positiva entre las puntuaciones obtenida en la escala STAI-S y la puntuación EVA, tanto durante la entrada a la cavidad (r = 0,629; p = 0,042) como durante el proceso quirúrgico (r = 0'661; p =0'021). CONCLUSIONES: Las pacientes con ansiedad preoperatoria tienen más riesgo de percibir dolor severo durante la entrada en la cavidad uterina y durante la realización de la intervención histeroscópica.

OBJECTIVE: Determine if preprocedural anxiety is an independent risk factor for the perception of severe pain during an outpatient surgical hysteroscopy. MATERIAL AND METHODS: There were 179 patients included in this cohort study. The STAI-S questionnaire has been applied to assess the preoperative anxiety of the patients and distribute them into two cohorts: Patients with anxiety (STAI-S>50) and patients without anxiety (STAI-S 7. The association and the risk between both variables have been calculated using X2 test and relative risk (RR). Pearson's correlation test was used to assess the correlation between both variables. A p value < 0,05 has been considered statistically significant. RESULTS: Patients who perceived severe pain during access to the uterine cavity (78,3% vs 29,5%; p<0,001) and during the surgical procedure (78,8% vs 26,2%; p<0,001) were mostly patients with preoperative anxiety. The RR of patients with anxiety to perceive severe pain is 6.46 (95% CI; 2,52-16,60) during access to the uterine cavity and 6,61 (95% CI; 3,04-14,38) during resection. We have found a moderate and positive correlation between the scores obtained on the STAI-S questionnaire and VAS score during access to the uterine cavity (r=0,629; p=0,042) and during the surgical process (r=0,661; p=0,021) CONCLUSIONS: Patients with preprocedural anxiety are more at risk of perceiving severe pain during access into the uterine cavity and during the hysteroscopic intervention.

Obesity Affects ß2 Adrenergic Regulation of the Inflammatory Profile and Phenotype of Circulating Monocytes from Exercised Animals.

Anomalous immune/inflammatory responses in obesity take place along with alterations in the neuroendocrine responses and dysregulation in the immune/stress feedback mechanisms. Exercise is a potential anti-inflammatory strategy in this context, but the influence of exercise on the ß2 adrenergic regulation of the monocyte-mediated inflammatory response in obesity remains completely unknown. The first objective of this study was to analyze the effect of exercise on the inflammatory profile and phenotype of monocytes from obese and lean animals, and the second aim was to determine whether obesity could affect monocytes' inflammatory response to ß2 adrenergic activation in exercised animals. C57BL/6J mice were allocated to different lean or obese groups: sedentary, with acute exercise, or with regular exercise. The inflammatory profile and phenotype of their circulating monocytes were evaluated by flow cytometry in the presence or absence of the selective ß2 adrenergic receptor agonist terbutaline. Exercise caused an anti-inflammatory effect in obese individuals and a pro-inflammatory effect in lean individuals. ß2 adrenergic receptor stimulation exerted a global pro-inflammatory effect in monocytes from exercised obese animals and an anti-inflammatory effect in monocytes from exercised lean animals. Thus, ß2 adrenergic regulation of inflammation in monocytes from exercised animals seems to depend on the inflammatory basal set-point.

ß2 Adrenergic Regulation of the Phagocytic and Microbicide Capacity of Macrophages from Obese and Lean Mice: Effects of Exercise.

Macrophages are crucial in the inflammation associated with obesity. Exercise is the main non-pharmacological strategy against obesity, not only for improving metabolic impairment, but also because of its anti-inflammatory effects, particularly those mediated by ß2 adrenergic receptors (ß2-AR). Nevertheless, these anti-inflammatory effects could immunocompromise the innate response against pathogen challenge. Thus, the objective of this work was to evaluate the effect of obesity, and of exercise in this condition, on the ß2 adrenergic regulation of the innate function of macrophages. High fat diet-induced obese C57BL/6J mice were used to evaluate the effects of acute and regular exercise on the phagocytic and microbicide capacities of peritoneal macrophages. Selective ß2-AR agonist terbutaline (1 µM) decreased the phagocytic and microbicide activities of macrophages from control lean and obese sedentary animals. While acute exercise did not modify the inhibitory capacity of terbutaline, regular exercise abolished this inhibitory effect. These effects cannot be explained only by changes in the surface expression of ß2-AR. In conclusion, (1) obesity does not alter the ß2-AR-mediated decrease of the innate response of macrophages and (2) regular exercise can revert the inhibitory effect of terbutaline on the phagocytic activity of macrophages, although obesity seems to hinder this immunophysiological adaptation.

Anti-inflammatory effect of ß2 adrenergic stimulation on circulating monocytes with a pro-inflammatory state in high-fat diet-induced obesity.

Obesity is a chronic condition associated with low-grade inflammation, and it also involves alterations of the function of the hypothalamic-pituitaryadrenal axis and the sympathetic nervous system. Adrenergic agonists such as catecholamines are important immunoregulatory molecules that are involved in modulating both metabolism and most of the mechanisms of the immune response. The first objective of this study was to determine whether the systemic inflammatory state associated with obesity is also manifested in the inflammatory profile and phenotype of circulating monocytes; and the second objective was to evaluate the effects of ß2 adrenergic stimulation on the inflammatory profile and phenotype of monocytes in obesity, and whether this response could be different from that in lean individuals. C57BL/6J mice were randomly allocated to one of two diets for 18 weeks: high-fat diet in order to obtain an experimental model of obesity, and standard diet in the control lean group. Circulating monocyte expression of inflammatory cytokines (MCP-1, TNF-α, IL-8, IL-6, IL-10, and TGF-ß), surface membrane marker Ly6C, inducible nitric oxide synthase and arginase-1, and Toll-like receptor 4 were evaluated through flow cytometry in the presence or absence of selective ß2 adrenergic receptor agonist terbutaline. Monocytes from high-fat diet-induced obese animals presented higher expression levels of all pro-inflammatory cytokines and a higher percentage of monocytes with a pro-inflammatory phenotype than those from lean animals. ß2 adrenergic stimulation induced a shift towards an anti-inflammatory activity profile and phenotype in obese mice, whereas it induced a shift towards a pro-inflammatory activity profile and phenotype in lean mice. In conclusion, ß2 adrenergic stimulation in monocytes was anti-inflammatory only in obese animals, which presented a pro-inflammatory state at baseline.