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Background: Autism spectrum disorder (ASD) is one of the most prevalent neurodevelopmental disorders. Many patients with ASD often show behavioral problems at mealtimes, including food selectivity and atypical feeding behaviors. The Mediterranean diet (MD) has a beneficial effect on mental health for the general population across different ages. There is evidence that good adherence to the MD is effective in reducing peripheral inflammatory markers, such as the cytokine interleukin-6 (IL-6). The present study was designed to evaluate adherence to the MD in children with ASD using age- and sex-matched, typically developing individuals (TDs) as a control group and to determine whether differences in adherence to the MD are associated with salivary IL-6 and IL-6 receptor concentration., Methods: Twenty children and adolescents with ASD (mean age 9.95 ± 0.65 years) and twenty TDs (mean age: 9.85 ± 0.59 years) participated in this study (N = 16 males and N = 4 females in each group). Participants with ASD were enrolled in a psychiatric consultation in Valencia (Spain), and TDs were recruited from two public schools in Valencia. The parents of both ASD and TD groups answered the items in a validated Mediterranean Diet Quality Index for children and adolescents (KIDMED) questionnaire on their children's adherence to the MD., Results: The mean adherence to MD score was significantly lower in the ASD group (9.10 ± 0.42) (range 6-12) than in the TD group (10.35 ± 0.31) (range 8-12) ( p = 0.02, Mann-Whitney U test). There was no statistically significant association between adherence to the MD and age or sex in both groups, but there was a significant correlation between the total KIDMED score and body mass index (BMI) in the ASD group. Regarding the concentration of Il-6 and the Il-6 receptor in saliva samples, there were no significant differences between the two groups; however, linear regression analysis by group revealed significant associations between the adherence to MD score and the concentration of IL-6 and its receptor in saliva in the ASD group ( p = 0.003, OR = 0.68, 95% CI 0.007 to -0.02; p = 0.009, OR = -0.64, 95% CI -0.01 to -0.00). In contrast, no significant associations were observed between the adherence to MD score and the concentration of IL-6 and its receptor in saliva in the TD group., Conclusions: Children and adolescents with ASD showed significantly lower adherence to the MD, which can contribute to nutritional deficits described in ASD, and the role of BMI composition (fat versus lean mass) needs to be further investigated in this group. The concentration of IL-6 and its receptor in saliva is associated with adherence to the MD, suggesting a possible link between IL-6 and diet in ASD. Further studies to clarify the associations between IL-6, psychiatric alterations, and diet in ASD are needed.

Introduction: Recent evidence reported mental health issues in university students such as anxiety and depressive symptoms and poor sleep quality. Decreased plasma brain-derived neurotrophic factor (BDNF) levels have been proposed as a biomarker of depressive symptoms, whereas cortisol levels are an index of energy mobilization and stress and have been linked to sleep quality. Given that salivary biomarkers represent an interesting new field of research, the aim of this cross-sectional study was to evaluate salivary BDNF and cortisol levels in university students to assess whether they have associations with psychological disturbances such as anxiety and depressive symptoms, sleep quality, and stress level., Methods: Salivary BDNF and cortisol levels were measured by specific immunoassays in 70 students whose mental health was also evaluated on the same day through the evaluation of anxiety and depression symptoms (Goldberg scale), sleep quality (Pittsburg Sleep Quality Index and Athens Insomnia Scale), and stress (self-perceived stress scale) and healthy lifestyle habits (alcohol consumption, smoking, regular exercise, and body mass index) were also measured. Multivariate regression analyses were performed in order to identify the strengths of associations between psychological alterations and the concentrations of BDNF, cortisol, and other variables., Results: Salivary BDNF levels were significantly higher in students with more depressive symptoms, whereas no significant differences were found for cortisol levels. When performing the binary logistic regression model, BDNF levels are included as a predictor variable for a high-depressive-symptoms burden ( p < 0.05). Students with worse sleep quality on the Pittsburg Scale had higher cortisol levels ( p < 0.05). The subdomains of sleep latency and sleep medication were those significantly associated with salivary cortisol levels in logistic regression analyses (OR = 15.150, p = 0.028). Sleep medication only appeared to be related to cortisol levels (OR = 185.142, p = 0.019). Perceived stress levels and anxiety symptoms were not associated with BDNF or cortisol levels., Conclusions: BDNF could play a key role in the pathophysiology of mood-related disorders, and elevation of its peripheral levels could contribute to protecting neurons from the development of mental illness. Higher salivary cortisol levels measured in the morning are accompanied by poorer sleep quality. More research is needed, focusing on salivary biomarkers of disorders related to depressive symptoms and poor sleep quality as a potential tool for the diagnosis and prevention of mental illness.

Background: Poor sleep quality is prevalent in older people and impairs their quality of life. Various studies show an association between sleep disorders and altered levels of inflammatory cytokines. The cytokine IL-1β has been shown to display both somnogenic and insomnia-promoting effects in experimental animals. Objectives: to evaluate the relationship between insomnia and salivary IL-1β concentration and the role of associated factors such as the symptoms of depression, use of hypnotics, intake of caffeinated beverages, smoking, and alcohol use in older individuals. An analytical, cross-sectional, observational research was carried out with a population of community-dwelling individuals over 60 years of age in Valencia (Spain). Sleep quality was measured with the Athens insomnia scale (AIS) and depressive symptoms with Geriatric Depression Scale (GDS). Results: 287 individuals participated in the study (mean age 74.08 years (76.7% women). 41.5% of the participants had insomnia, 36.9% took drugs for sleep problems, and 32.4% had relevant depressive symptoms. There was a significant inverse correlation between the IL-1β and total AIS score (rho = -0.302, p < 0.001), the sleep difficulty subdomain (rho = -0.259, p < 0.001), and the daytime sleepiness subdomain (rho = -0.322, p < 0.001). No significant correlation was observed between GDS and salivary IL-1β concentration. The IL-1β concentration was significantly lower in individuals taking drugs for sleeping compared with those not taking those drugs (1.11 ± 0.09 and 1.48 ± 0.08, respectively; p = 0.001). Regarding the AIS score, there was no significant difference in marital status, smoking, or the number of cups of tea or cola drinks, but there was a significant association with alcohol intake ( p = 0.019) and in the number of daily intakes of coffee ( p = 0.030). The receiver operating characteristic (ROC) curve analysis of IL-1β for diagnosis of moderate-severe insomnia showed an area under the curve (AUC) value of 0.78 (95% confidence interval 0.71-0.85). At the cut-off of 0.83 pg/µL of Il-1β, it had a sensitivity of 70.3% and a specificity of 69.8%., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Objectives: Type 1 diabetes mellitus (T1DM) is one of the most common chronic diseases in children and adolescents, and is associated with stress and other psychological alterations. This study aims to assess psychological and sleep disorders and health-related quality of life in young people with T1DM and to determine the relationship between these parameters and levels of salivary cortisol, a hormone widely associated with stress and several psychological symptoms. Materials and Methods: In our cross-sectional study performed in 60 Moroccan children and adolescents with T1DM, detailed psychological evaluations were performed to assess symptoms of anxiety, attention-deficit hyperactivity disorder (ADHD), sleep quality and diabetes-specific quality of life (using the RCMAS-2, ADHD rating scale, Pittsburgh scale and the DQoL scale, respectively), and cortisol concentration was measured from saliva samples taken mid-morning. Results: A total of 60 children and adolescents with T1DM were recruited. The mean age was 11.05 ± 0.35 (6-17). The mean salivary cortisol level in ng/mL was 4.7 ± 0.49 (0.7-20.2) and was significantly associated with an anxiety RCMAS2 score for the Worry subdomain and DQoL subdomain "Anxiety". Linear regression analysis showed that salivary cortisol was significantly higher in girls compared to boys ( p = 0.004) (beta coefficient: 3.384 CI95%: 1.137-5.630) and with Hb1AC level as a continuous variable ( p = 0.0001) (beta coefficient: 1.135 CI95%: 0.509-1.760). The other variables included in the model were not significant ( p > 0.05). There was an association between salivary cortisol concentration with anxiety RCMAS2 score for Worry subdomain and QoL sub-domain "Anxiety". Still, a significant ( p = 0.018) association emerged for anxiety RCMAS2 score Worry subdomain and QoL anxiety subdomain ( p = 0.044). Conclusions: Children and adolescents with T1DM experienced significantly elevated symptoms of anxiety and sleep disturbances, particularly in girls, and frequent symptoms of ADHD, particularly in boys. Salivary cortisol concentration collected in the morning is associated with anxiety burden but not with other psychological alterations. Further studies are needed to clarify the associations between salivary cortisol concentration and anxiety in type 1 diabetes in order to propose the hormone as a biomarker for interventions aimed to reduce anxiety levels in these patients.

Background: Androgen deprivation therapy (ADT) is a mainstay of prostate cancer in both adjuvant and palliative settings. Since androgens are crucial for functional status and psychological functions, we evaluated whether blood testosterone, androstenedione, or DHEA concentrations were associated with functional status and psychological alterations in patients with localised (PCa) or metastatic prostate cancer (mPCa) receiving ADT with analogues of luteinising hormone-releasing hormone (LHRH)., Methods: The five Fried criteria were considered to identify frailty syndrome. In addition, complementary evaluations were carried out to measure other variables of interest. Sleep quality was assessed using the Athens Insomnia Scale, cognitive functions were assessed using the Mini-Mental State Examination, and symptoms of depression were measured using the Yesavage Geriatric Depression Scale. Logistic regression analysis was performed to determine if the androgens level could be related to frailty syndrome, sleep impairment, depressive symptoms, and cognitive functions., Results: The results of the multivariate analyses show that high concentrations of androstenedione were significantly associated with frailty syndrome in both groups ( p = 0.018; odds ratio = 4.66, 95% confidence interval [1.30-16.6]). There were significant relationships between frailty syndrome and the systemic concentration of androstenedione ( p = 0.01), but not the concentration of testosterone ( p = 0.60) or DHEA ( p = 0.42). In addition, the results of the non-parametric tests show significant results between a decreased gait speed in the two groups (metastatic and localised) and the concentration of androstenedione ( p = 0.015). High androstenedione levels were associated with a slow walking speed in the mCaP group ( p = 0.016), while high testosterone levels were associated with a better walking speed in the localised CaP group ( p = 0.03). For the concentration of androstenedione in plasma, the area under the curve was 0.72, with a 95% CI of 0.55-0.88 with acceptable values, and with a cut-off point of 4.51 pg/mL, a sensitivity of 82.9%, and specificity of 53.8%. No relationships between the concentration of androgens in plasma and sleep quality, cognitive functions, or symptoms of depression suggest that the changes were specific to frailty syndrome., Conclusions: Further research into the role of androstenedione should be evaluated in follow-up studies in order to recommend its use as a suitable biomarker of frailty syndrome in prostate cancer patients.

Poor sleep quality is a major public health concern for all ages. In particular, university students often face stress levels and changes in social life habits that negatively influence their quality of sleep. This could be associated with psychological well-being in terms of anxiety and depressive symptoms, stress levels, and a poor self-perceived health status. The increases in the pro-inflammatory cytokine interleukin 6 (IL-6), IL-1 beta (IL-1β), and tumor necrosis factor alpha (TNFα), in blood have been linked to poor sleep quality in many diseases, but data on salivary cytokine levels in students are missing or are seldom analyzed. In this study we determined the quality of sleep in a sample of university students and the role of psychological assessment and factors affecting sleep (alcohol intake, tobacco, consumption of stimulant drinks, exercise, and body mass index). We also aimed to shed new light on the associations between sleep quality and salivary inflammatory cytokines (IL-1β, IL-6, and TNFα). Sleep quality was measured with the Athens Insomnia Scale (AIS) and Pittsburgh Sleep Quality Index (PSQI). Perceived stress was assessed using Cohen's Perceived Stress Scale (PSS), and the Goldberg Anxiety and Depression Scale (GADS) was used to assess the level of anxiety or depression. Perceived health status was measured with a visual analogue. Saliva samples was taken in the morning and the inflammatory cytokines was measured via enzyme-linked immunoassay. There was a direct and significant association between the salivary IL-1β concentration and AIS score (r = 0.248; p = 0.038, Pearson correlation) and Pittsburgh scale score (r = 0.274; p = 0.022, Pearson correlation). The relationship between IL-1β and AIS controlling for sex, age, and chronic disease, is still significant (r = 0.260; p = 0.033). The relationship between IL-1β and PSQI controlling for the influence of these variables is also significant (r = 0.279; p = 0.022). Salivary IL-1β concentrations were not significantly associated with any of the scores of the other psychological assessments (PSS, anxiety, depression symptoms, or self-perceived health). Salivary TNFα was significantly and inversely associated with self-perceived health (r = -0.259; p = 0.033, Pearson correlation), but the salivary IL-6 concentration was not associated with any of the sleep quality scale or psychological assessment scores. Our results provide a novel relationship between pro-inflammatory cytokine IL-1β in saliva and poor sleep quality. However, the role of inflammation in poor sleep quality requires further study to identify strategies that could lower inflammation and thus, likely improve sleep quality.

Stress, depressive symptoms and sleep quality are important and modifiable determinant of health and their association with hair cortisol concentrations (HCC) in breast cancer survivors has not been evaluated. We selected a random sample of 65 participants (mean age 57.9 years old, range 44-75 years) recruited from local patients' associations of breast cancer survivors. Each provided a hair sample at enrollment and basic clinical data and psychological evaluation regarding self-perceived stress (PSS-scale), depressive (GDS scale) and insomnia symptoms (Athens scale). We observed a direct and significant (p = 0.001) association between HCC and stress-levels. Depressive symptoms associated significantly (p < 0.01) with stress levels but not with HCC. There were also a significant and direct correlation between hair cortisol concentration and totals core of insomnia symptoms (p = 0.002), and the subdimension of sleep difficulty symptoms (p = 0.002), and with daytime sleepiness symptoms (p = 0.016). Further investigations into the association between stress and insomnia and changes in HCC in breast cancer survivors are warranted in order to validate this biomarker for diagnosis of psychological alterations and to tailor the effects of interventions aimed to reduced stress and improve sleep quality in these women., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Sleep disorders are common in older individuals and are most prevalent in those who are institutionalized. Sleep complaints are often comorbid with medical and neuro-psychiatric illness and associated with polypharmacy. Various studies show an association between sleep disorders and altered levels of inflammatory cytokines, especially IL-6. In this study, an objective sleep analysis was performed using actigraphy, and IL-6 measurements in saliva in 61 older people residing in long-term nursing homes (72.1% women). Almost half (49.2%) of the people had no or mild cognitive impairment, and the rest suffered from moderate to severe dementia, mainly due to Alzheimer's disease (25 out of 31 individuals). A significant correlation was found between salivary IL6 and sleep parameters; e.g., less salivary IL-6 had significantly ( p < 0.05) worse sleep efficiency and more night awakenings. In turn, actigraphy detected alterations in people with dementia in average sleep time, daily bedtime, and average daily time out of bed. There was no significant correlation between these sleep patterns and the total number of psychotropic drugs. No significant differences were found in salivary IL-6 between individuals with or without dementia. These results should be considered in future research with institutionalized people to detect sleep disturbances and to establish interventions aimed to improve sleep quality.

Background: Prostate cancer (PCa) is considered one of the most important medical problems in the male population, with a very high incidence after the age of 65. Frailty represents one of the most critical issues facing healthcare due to its inherent relationship with poor healthcare outcomes. The physical phenotype of frailty syndrome based on Fried criteria has been associated with poor outcomes, morbidity, and premature mortality. To date, there are few studies that have analyzed frailty syndrome in patients with localized and advanced (mPCa) disease under androgen-deprivation therapy., Objective: Our goal was to assess whether there are differences in frailty criteria between mPCa and localized PCa. We also evaluated the role of other geriatric variables such as depressive and insomnia symptoms, which are frequently reported in cancer patients., Methods: In this cross-sectional study, frailty syndrome was evaluated in both groups, as well as its possible relationship with cognitive functions, depressive and insomnia symptoms, and other clinical variables related to PCa and its treatment. Frailty was defined on Fried's criteria: low lean mass, weakness, self-reported exhaustion, low activity level, and slow walking speed; prefrailty was defined as having one or two of those criteria and frailty as having three or more, depressive symptoms were defined by the Yesavage scale, cognitive functions with the Mini-Mental examination test, and insomnia symptoms by the Athens scale and self-reported health status., Results: The prevalence of prefrailty/frailty was slightly higher in mPCa compared to localized PCa (81.5% versus 72.3%, respectively), however by analyzing each of the frailty criteria, two of them were significantly reduced in mPCa compared to localized PCa patients, e.g., gait speed ( p = 0.001) and muscle strength ( p = 0.04). The reduced gait speed and muscle strength in mPCa were not due to the increased age in mPCa group, or to an increase in comorbidities or shorter time under androgen-deprivation therapy. The symptoms of insomnia were significantly higher in mPCa patients compared to those with localized PCa ( p < 0.05) whereas cognitive functions or depressive symptoms were not significantly different between the two groups., Conclusion: Patients with mPCa under androgen-deprivation therapy display higher alterations in gait speed and muscular strength and insomnia symptoms, thus interventions should be aimed to reduce these alterations in order to limit adverse outcomes related to them and to improve quality of life in these patients.

Most patients with metastatic prostate cancer (mPCa) are older. In addition, current geriatric oncology guidelines suggest that all cancer patients aged over 70 years should undergo a comprehensive geriatric assessment (CGA), with the identification of frailty syndrome being crucial for clinical decisions. Frailty can be associated with lower quality of life (QoL) and interfere with the feasibility or side effects of oncology treatments., Methods: We performed a systematic literature search to evaluate frailty syndrome and associated alterations related to CGA impairment by searching in different academic databases (PubMed, Embase, and Scopus). The identified articles were reviewed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines., Results: Of the 165 articles consulted, 7 met our inclusion criteria. Analysis of data related to frailty syndrome in patients with mPCa showed a prevalence between 30-70% depending on the tool used. Additionally, frailty was associated with other CGA assessments and QoL evaluation outcomes. In general terms, CGA scores for patients with mPCa were lower than those for patients without metastasis. Furthermore, functional QoL appeared to be worse for patients with metastasis, and global QoL (burden) was more strongly associated with frailty., Conclusion: Frailty syndrome was related to a poorer QoL in patients with mPCa and its evaluation should be considered in clinical decision-making and when choosing the most appropriate active treatment, if any, to increase survival.

Recent scientific evidence supports the idea that foot plantar stimulation increases the functional connectivity of brain regions involved in visuo-spatial and sensory-motor integration. In this before−after, non-randomised intervention study we assessed the change in several gait and postural parameters using inertial sensor measurements after acute plantar stimulation using custom 3D-printed insoles. The pilot study was performed on 22 institutionalised, older individuals with a high comorbidity burden who either walked autonomously or with the help of a cane. The intensity of the effects in the first mechanical plantar stimulation session (at one week) strongly predicted a change in the 180° turn duration (p < 0.05) and the standard deviation of the step duration (p < 0.05) during the timed up-and-go test. Based on these effects, researchers also predicted decreases in some postural parameters such as the root mean square of displacement on the anterior−posterior axis (p < 0.01). Thus, these preliminary findings provide a strong rationale for performing controlled clinical trials with larger samples to investigate the efficacy and mechanisms of mechanical plantar stimulation in frail elderly individuals.

The Mediterranean diet (MD), a well-established quality diet model, and regular physical activity are associated with reducing the appearance or progression of several chronic diseases and reducing morbidity and mortality. However, reduction of these goals, adherence to the MD, and regular physical activity occur at all ages, including older individuals in Mediterranean countries such as Spain, where at least adherence to the MD is culturally rooted. Objective: To evaluate the degree of adherence to the MD and physical activity in older individuals. Methods: The sample comprises 679 older adults aged 60 and over who attended activities in municipal centers for older adults in Valencia. Adherence to the Mediterranean diet, frequency of physical activity, and anthropometric assessment were used. Results: High adherence (score ≥ 9) to MD was observed only in 23.7% of the study sample. Smoking habits or having meals in fast-food restaurants on a weekly basis were significantly (p < 0.05) associated with lower MD adherence. Age, BMI, marital status, and physical activity were not significantly associated with MD adherence. Physical activity was significantly (p < 0.05) lower in individuals who were divorced or widow/ers and in those taking care of their grandchildren several times a week. Conclusions: Adherence to the MD in a big Spanish city is low among older individuals. Socio-family factors seem to play a role. Public health and governmental strategies should reinforce adherence to the MD among older individuals as a gold standard for nutrition.

First-line treatment in postmenopausal women with estrogen- and/or progesterone-positive breast cancer consists of aromatase inhibitors (AROi). The ability of AROi to promote or worsen cognitive function, depressive symptoms, sleep quality and performance in basic activities of daily life as primary and concomitant outcomes in long longitudinal studies in post-menopausal women has been seldom investigated. This study is a cohort trial which aimed to determine if there were differences in cognitive function assessment, depressive symptoms, and sleep quality after 1 year under AROi treatment and to determine the interrelations between these symptoms., Methods: A prospective 1-year longitudinal study was performed in a representative sample of tertiary hospital. Women with localized breast cancer newly treated with AROi therapy were evaluated for cognitive functions, depressive symptoms, sleep problems and ability to perform basic activities of the daily life at baseline and after 6 months and 12 months under adjuvant AROi treatment., Results: Analysis of cognitive functions by the Mini-Mental State Examination (MMSE) scores did not show significantly worsening under AROi treatment after 6 months and 12 months of treatment compared to the baseline. Analysis of depressive symptoms with the Geriatric Depression Scale and sleep quality with the Athens Insomnia Scale (AIS) scores showed significant (p < 0.05) changes after 6 and 12 months of treatment with AROi, with women describing more depressive symptoms and more sleep disturbances., Conclusions: Our study found impairments in sleep quality and an increase in depressive symptoms, which has important implications for clinicians as they impair quality of life and adherence to treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The standard treatment in postmenopausal women with estrogen- and progesterone-positive localized breast cancer consists of aromatase inhibitors (AROi). The ability of AROi to promote or worsen frailty syndrome over time and the relationship with changes in gonadal hormones concentration in blood have not been investigated. Methods: A prospective study to evaluate the relationship between frailty syndrome and gonadal hormones concentrations in blood at baseline (prior to AROi treatment) and after 6 and 12 months under AROi treatment in post-menopausal women with breast cancer. Frailty syndrome was evaluated by the Fried’ criteria. We evaluated whether hormone concentration at baseline could predict frailty syndrome at follow-up. Results: Multinomial regression analysis showed that of the different hormones, those significantly (p < 0.05) associated to the worsening of frailty syndrome were high androstenedione levels and low follicle-stimulating hormone (FSH) levels in blood. Receiver operating characteristic curve analysis showed both androstenedione and FSH significantly (p < 0.05) discriminate patients who developed or presented worsening of frailty syndrome over time, with acceptable sensitivity (approximately 80% in both cases) but low specificity (40%). Conclusion: Hormonal concentrations before AROi treatment constitute possible biomarkers to predict the progression of frailty syndrome.