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.

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.

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.

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.

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.

Adrenergic Regulation of Macrophage-Mediated Innate/Inflammatory Responses in Obesity and Exercise in this Condition: Role of ß2 Adrenergic Receptors.

BACKGROUND: The effects of exercise on the innate/inflammatory immune responses are crucially mediated by catecholamines and adrenoreceptors; and mediations in both stimulatory and anti-inflammatory responses have been attributed to them. Obesity and metabolic syndrome are included among low-grade chronic inflammatory pathologies; particularly because patients have a dysregulation of the inflammatory and stress responses, which can lead to high levels of inflammatory cytokines that induce insulin resistance, contributing to the onset or exacerbation of type 2 diabetes. Macrophages play a crucial role in this obesity-induced inflammation. Although most of the antiinflammatory effects of catecholamines are mediated by ß adrenergic receptors (particularly ß2), it is not known whether in altered homeostatic conditions, such as obesity and during exercise, innate/ inflammatory responses of macrophages to ß2 adrenergic stimulation are similar to those in cells of healthy organisms at baseline. OBJECTIVE: This review aims to emphasize that there could be possible different responses to ß2 adrenergic stimulation in obesity, and exercise in this condition. METHODS: A revision of the literature based on the hypothesis that obesity affects ß2 adrenergic regulation of macrophage-mediated innate/inflammatory responses, as well as the effect of exercise in this context. CONCLUSION: The inflammatory responses mediated by ß2 adrenoreceptors are different in obese individuals with altered inflammatory states at baseline compared to healthy individuals, and exercise can also interfere with these responses. Nevertheless, it is clearly necessary to develop more studies that contribute to widening the knowledge of the neuroimmune regulation process in obesity, particularly in this context.

Innate/inflammatory bioregulation and clinical effectiveness of whole-body hyperthermia (balneotherapy) in elderly patients with osteoarthritis.

OBJECTIVES: Balneotherapy with mud application (mud therapy) is a common hydrothermal intervention for the treatment and rehabilitation of elderly patients with osteoarthritis, leading to anti-inflammatory effects. The main purpose of this investigation was to study a role for regulatory T cells in these anti-inflammatory effects. The second objective was to assess whether the neutrophil-mediated innate response is affected by these anti-inflammatory effects. METHODS: Thirty-six elderly patients with knee osteoarthritis underwent a 10-day cycle of balneotherapy at a spa center. They received daily sessions of whole-body mud therapy at 40-42 °C, using mineral-medicinal water and mud. IL-8 and TGF-ß serum concentrations, percentage of circulating CD4+ CD25+ FOXP3+ and CD8+ CD28- regulatory T cells, and neutrophil phagocytic capacity were evaluated at baseline and at the end of the intervention. Clinical assessments included knee flexion and extension angle, pain, stiffness, physical function and health-related quality of life. RESULTS: All clinical outcomes significantly improved. Circulating concentrations of IL-8 and TGF-ß decreased, which correlated with decreased pain and improved knee flexion, respectively. Percentage of CD4+ regulatory T cells decreased, whereas CD8+ regulatory T cells increased. Neutrophil functional capacity increased. CONCLUSIONS: Balneotherapy with mud application was effective in the management of osteoarthritis symptoms. The anti-inflammatory effect mediated by cytokines contributed to the improvement in pain and joint function; and changes in the circulating percentage of regulatory T cells seem to be involved in the anti-inflammatory effects. Improvement in neutrophil function after mud therapy reflects an optimal bioregulatory effect on the inflammatory and innate responses.