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Many previous studies have indicated that hair cortisol constitutes a valuable tool to further supplement existing data on salivary, plasma, or urinary cortisol concentrations in patients with sleep disorders. There are numerous biological, psychological, and social factors that have a more or less prominent impact on the mental health of older adults. 33113995 4 Montoro Pazzini Watfe G., Fajersztajn L., Ribeiro E., Rossi Menezes P., Scazufca M. Prevalence of Older Adult Disability and Primary Health Care Responsiveness in Low-Income Communities. [Extracted from the article]

Background: Epitestosterone [E] has for a long time been considered as a biologically inactive androgen. However, recently a distinct antiandrogenic activity of this naturally occurring endogenous epimer of Testosterone has been demonstrated. Especially the ratios of testosterone/epitestosterone (T/E) seem to be key as inhibition of epitestosterone on androgen activity was postulated. As in autism, a higher androgen activity was implied. We, therefore, suggested higher levels of T/E ratios of children with autism versus children with typical development. Methods: Urine probes of 22 girls with autism (BMI 18.7 ± 4.3; average age 12.3 ± 3.8 years) and a sample of 51 controls (BMI 17.0 ± 2.6; average age 11.9 ± 4 years), as well as 61 boys with autism (BMI 17.04 ± 2. average age 11.9 ± 2.5 years) and 61 control boys (BMI 17.0 ± 2.6; average age 11.1 ± 3.0 years), were analyzed with gas chromatography mass spectrometry. RESULTS: The average T/E ratio of all boys with autism was 2.5 ± 1.8 versus 2.4 ± 1.3 in boys with typical development, respectively. No significant difference between boys with autism versus boys with typical development could be detected (p = 0.977). In girls with autism, the average T/E ratio was 1.4 ± 0.9 versus 2.0 ± 1.4 in girls with typical development, whereby a significant difference could be detected (p = 0.0285). Further, polynomial analysis of the third degree were conducted, showing a dependence from age with reasonable coefficients of determination (0.075 < R2 < 0.22, all samples). Discussion: As encompassing steroid hormone analysis are expensive and work-intensive, we hoped to find an easily applicable biomarker to support diagnostics in autism. However, as a relatively small sample of only 22 girls with autism were analyzed and menstrual cycle and pubertal status were only partly controllable through the matching of BMI and age, the question arises if it was an incidental finding. Nevertheless, one suggestion might be that epitestosterone has the effect of a competitive inhibition on the androgen receptor, which would probably help to explain the higher prevalence of autism in boys as compared to girls. Presumably, as no significant difference was detected in boys, this effect might not be as relevant from a steroid hormone perspective, and other effects such as altered 17/20-hydroxylase activity as previously shown in boys and girls with autism seem to have more relevance. Analysis of larger samples, including plenty of metabolites and enzymatic cascades, as well as the role of backdoor pathway activity of androgen synthesis of girls with autism, are demanded in order to validate current findings of altered steroid hormones in autism. [ABSTRACT FROM AUTHOR]

Background and Objective: Diabetes mellitus (DM) is a common long-term disease which can be related with salivary amylase levels. DM has recently been associated with salivary amylase diagnostics that could further impair diagnoses in the diabetic population, as well as being an interesting alternative to traditional methods of determine glucose levels. The main advantage of this method is related to the fact that it is a fast diagnostic method. The DM population experiences changes to their metabolism which affects their salivary parameters, making this an alternative procedure for diagnosis and follow-up of the illness due to the non-invasive nature of salivary analyzes. The objective of this review is to summarize the evidence regarding the changes in salivary amylase and glucose levels, and their relationship with blood markers of glycemic control used in clinical settings such as blood glucose and glycated hemoglobin. The differences in salivary amylase levels depending on the method of saliva collection under fasting or non-fasting conditions. The changes in salivary amylase depends on the type of diabetes, the type of insulin treatment or the quality of glycemic control. Conclusions: Salivary amylase concentration is increased in diabetic patients in most of the studies and salivary glucose concentration in all studies in both fasting and non-fasting (post-prandial) conditions. Salivary amylase and glucose concentration represent potential non-invasive biomarkers to evaluate glycemic control and clinical management of diabetic patients, although it is necessary to evaluate the influence of potential modulating factors such as age, duration diseases, sex and the effects of pharmacological treatments in these outcomes which remained to be elucidated. [ABSTRACT FROM AUTHOR]

Depression is a psychiatric disorder that has a significant health burden on patients and their families. Unfortunately, the current antidepressant medications that mainly target monoamine neurotransmitters have limited efficacy. Recent evidence has indicated that neuroinflammation participates in the genesis and development of depression, and interacts with other factors involved in depression. Therefore, exploring effective anti-inflammatory medications could be beneficial for the development of new treatment options for depression. Sirtuins are a unique class of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases, which have seven members that can affect multiple downstream targets by deacetylation activity. Among these seven members, SIRT1 and SIRT2 have been shown to participate in the pathophysiology of inflammation in numerous studies. Thus, in this short article, we review the association of SIRT1 and SIRT2 activity and depression, and evidence of the effects of SIRT1 and SIRT2 modulators on inflammation in vitro and depressive-like behaviours in vivo. [ABSTRACT FROM AUTHOR]

The relationship between cognitive decline and androgen deprivation therapy (ADT) under luteinizing hormone-releasing hormone (LHRH) analogues is unclear, and there is a scarcity of longitudinal studies considering the interaction between cognition, depressive symptoms and sleep quality in men with prostate cancer (PCa) treated with ADT. This study aimed to determine if there were differences in the scores obtained in cognitive assessment, depressive symptoms, and sleep quality after one year of ADT and determine the interrelations between sleep, mood, and cognitive status. A prospective longitudinal observational study was designed, in which a cohort of men (mean age was 70.8 years) newly treated with androgen-deprivation therapy was assessed in the first six months of treatment and 12 months later. Analysis of cognitive function by the Mini-Mental State Examination (MMSE) scores indicated a significant (p < 0.05) increase after one year of treatment and by the Brief Scale for Cognitive Evaluation (BCog) scores indicated no changes in the scores before and after one year of treatment. 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 one year of treatment with ADT, with men describing more depressive symptoms and more sleep disturbances. No statistically significant differences were found in the cognitive performance between men with impaired sleep or depression results and those without them. Our study showed no clinical evidence of the relationship between ADT under luteinizing hormone-releasing hormone (LHRH) analogues and cognitive deterioration in 1-year follow-up, but there are impairments in the sleep quality in men with PCa undergoing ADT and an increase in depressive symptoms which has important implications for clinicians as they would impair quality of life and adherence to treatment. [ABSTRACT FROM AUTHOR]

Background: Diabetic neuropathy is defined as the dysfunction of the peripheral nervous system in diabetic patients. It is considered a microvascular complication of diabetes mellitus. Its presence is associated with increased morbidity and mortality. Although several studies have found alterations at somatic motor, sensory levels and at the level of autonomic nervous system in diabetic patients, there is not a systematic approach regarding the differences in neuropathy between the major variants of diabetes, e.g., type 1 and 2 diabetes at both neurological and molecular level. Data sources: we systematically (Medline, Scopus, and Cochrane databases) evaluated the literature related to the difference of neuropathy in type 1 and 2 diabetes, differences in molecular biomarkers. Study characteristics: seventeen articles were selected based on pre-defined eligibility criteria. Conclusions: both superficial sensitivity (primarily thermal sensitivity to cold) and deep sensitivity (such as vibratory sensitivity), have been reported mainly in type 2 diabetes. Cardiac autonomic neuropathy is one of the diabetic complications with the greatest impact at a clinical level but is nevertheless one of the most underdiagnosed. While for type 1 diabetes patients most neuropathy alterations have been reported for the Valsalva maneuver and for the lying-to-standing test, for type 2 diabetes patients, alterations have been reported for deep-breathing test and the Valsalva test. In addition, there is a greater sympathetic than parasympathetic impairment, as indicated by the screening tests for autonomic cardiac neuropathy. Regarding subclinical inflammation markers, patients with type 2 diabetes showed higher blood levels of inflammatory markers such as high-sensitivity C-reactive protein, proinflammatory cytokines IL-6, IL-18, soluble cell adhesion molecules and E-selectin and ICAM-1, than in type 1 diabetes patients. By contrast, the blood levels of adiponectin, an adipocyte-derived protein with multiple paracrine and endocrine activities (anti-inflammatory, insulin-sensitizing and proangiogenic effects) are higher in type 1 than in type 2 diabetic patients. This review provides new insights into the clinical differences in type 1 and 2 diabetes and provide future directions in this research field. [ABSTRACT FROM AUTHOR]

Many neurodegenerative diseases present with progressive neuronal degeneration, which can lead to cognitive and motor impairment. Early screening and diagnosis of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD) are necessary to begin treatment before the onset of clinical symptoms and slow down the progression of the disease. Biomarkers have shown great potential as a diagnostic tool in the early diagnosis of many diseases, including AD and PD. However, screening for these biomarkers usually includes invasive, complex and expensive methods such as cerebrospinal fluid (CSF) sampling through a lumbar puncture. Researchers are continuously seeking to find a simpler and more reliable diagnostic tool that would be less invasive than CSF sampling. Saliva has been studied as a potential biological fluid that could be used in the diagnosis and early screening of neurodegenerative diseases. This review aims to provide an insight into the current literature concerning salivary biomarkers used in the diagnosis of AD and PD. The most commonly studied salivary biomarkers in AD are β-amyloid1-42/1-40 and TAU protein, as well as α-synuclein and protein deglycase (DJ-1) in PD. Studies continue to be conducted on this subject and researchers are attempting to find correlations between specific biomarkers and early clinical symptoms, which could be key in creating new treatments for patients before the onset of symptoms. [ABSTRACT FROM AUTHOR]

Poor sleep quality and sleep disorders are the most common problems in people, affecting health-related quality of life. Various studies show an association between sleep disorders and altered levels of stress hormones and inflammatory cytokines measured in saliva. The main objective of this article is to provide an analysis of the current evidence related to changes in inflammatory markers in the saliva and their associations with sleep quality measurement (both objective and subjective methods) in healthy subjects and in sleep-related disorders. To that end, a scoping review was carried out, following the PRISMA criteria in the bibliographic search in several databases: PubMed, EBSCO, and SCOPUS. Eleven of the articles are from the adult population and two from the child-youth population. They mainly measure the relationship between sleep and interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFα) alpha, as well as other inflammatory markers such as myeloperoxidase (MPO) and prostaglandin-endoperoxide synthase 2. An analysis shows the relationship between these salivary biomarkers and sleep quality, especially in the case of IL-6 in both healthy subjects and several pathologies associated with sleep-disorders. The results for TNFα and IL-1β measurements are still inconclusive and the difference with IL-6 was assessed. Two studies reported interventions that result in sleep improvement and are accompanied by the normalization of inflammatory changes detected in the saliva. As it is an easy-to-apply and non-invasive method, the measurement of salivary cytokines can be very useful in chronobiology studies. Further studies are required to determine the sensitivity of salivary inflammatory markers in monitoring biological rhythms and acting as biomarkers in the detection of sleep disorders and sleep interventions. [ABSTRACT FROM AUTHOR]

Cortisol is the end product of the hypothalamic-pituitary-adrenal (HPA) axis, and its production is increased mainly in stressful situations or in chronic disorders accompanied by stress enhancement. Altered cortisol concentrations have been reported in a number of neuropsychiatric diseases and sleep disorders. Cortisol concentrations have been measured using several methods, and in several matrixes, such as blood, saliva, and urine. However, lately, hair cortisol, for several reasons, has emerged as a promising biomarker of long-term retrospective HPA activation. Several experimental approaches for cortisol measurement with the corresponding concentration reference ranges and a summary of findings from scientific literature on this field are presented. There is evidence of a close relationship between HPA functional alteration and the development of neuropsychiatric disorders. Sleep disorders are the most common manifestation in several neuropsychiatric conditions, and have also been associated to cortisol alterations in both adults and children. Many studies indicate that hair cortisol constitutes a valuable tool for further contributing to existing data on salivary, plasma, or urinary cortisol concentrations in patients with sleep disorders. [ABSTRACT FROM AUTHOR]

There is continuous and growing interest in research into new alternatives to standard biomarkers to detect and follow-up disease, reducing physical and psychological stress in patients needing regular and invasive medical examinations for the evaluation of pathologies, including inflammatory bowel diseases (IBD). Saliva is one of the most promising body fluids in the research of new biomarkers, thanks to the large number of molecules it contains. Many molecules present in saliva are often directly correlated to their concentration in the blood but may be affected by the condition of the oral cavity. This means that a careful selection of a specific biomarker is required for each pathology, especially pathologies such as IBD, which may induce inflammation in the oral cavity. Here, we analyze the currently used and the proposed new salivary biomarkers (i.e., calprotectin, cytokines, IgA, cortisol, and oxidative stress markers) for the detection and follow-up of the main subtypes of IBD, known as ulcerative colitis and Crohn's disease. [ABSTRACT FROM AUTHOR]

Omega-3 long-chain polyunsaturated fatty acids play a central role in neuronal growth and in the development of the human brain, since they are essential elements which depend on intake through diet to ensure an adequate amount. Fish and seafood are the main dietary sources of these fatty acids in Spain and in other countries. In order to assess the effect of the intake of common foods containing high amounts of omega-3 polyunsaturated fatty acids, a food frequency questionnaire was administered to parents of children and adolescents attending a primary school in Valencia (Spain), and the intake of dietary omega-3 such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) was estimated based on their fish/seafood consumption. Low frequencies of intake were significantly (p < 0.05) lower for many types of fish/seafood in children compared to adolescents. 27.5% of children/adolescents did not eat lean fish or other types (19.8% of the sample did not eat fatty fish, and 71.8% did not eat smoked fish) and 20–60% of the sample consumed seafood only once–three times a month, leading to a reduced estimated intake of EPA+DHA below that recommended for both groups by public health agencies. Social aspects, such as the type of work done by mothers and their educational levels are significant factors (p < 0.05 in both cases) affecting children's/adolescents' intake of DHA+EPA. Dietary interventions to increase the consumption of fish and seafood are strongly advised, and health promotion strategies should be aimed at the family level and fight against gender disparities. [ABSTRACT FROM AUTHOR]

Background: Sleep disorders are common in youths with autism spectrum disorders. Inflammatory cytokines such as Il-1 beta and Il-6 in saliva have been associated with alterations in sleep quality in various conditions. We assessed whether there were associations between the salivary concentration of IL-1 beta and IL-6 and sleep quality in youths with ASD versus typically developing (TD) age- and gender-matched youths. Method: Forty children and adolescents with ASD or TD participated in this study (20% females). Their parents answered the items of a validated questionnaire on sleep quality (Pittsburgh Sleep Quality Index). Results: The mean Pittsburgh score was significantly higher (i.e., the quality of sleep was poorer) in the ASD group (8.68 ± 0.35 (SEM), ranging from 7 to 12 points), compared to the TD group (7.35 ± 0.54 (SEM), ranging from 2 to 12 points) (p = 0.02, Mann–Whitney U test). There were no significant differences in the salivary concentration of Il-1 beta and IL-6 receptor between the two groups, but salivary IL-1 beta concentration was inversely associated with poor sleep quality in the ASD group. No associations between the salivary Il-6 concentration and sleep quality were found in either group. Linear regression analysis by separate groups revealed significant associations between the sleep quality score and the concentration of IL-1 beta in the ASD group (p = 0.01, OR = −0.53, 95% CI −0.008–0.001). In contrast, no significant associations were observed in the TD group, or for IL-6 in either group. No significant effects of sex, age, or use of psychotropic medications were found. Conclusions: Children and adolescents with ASD showed significantly poorer sleep quality based on their parents' reports compared to the TD group, and the salivary IL-1 beta concentration was inversely associated with sleep quality only in the ASD group. Further studies on the associations between inflammatory cytokines and sleep in ASD are needed. [ABSTRACT FROM AUTHOR]

Background: Lung cancer carries a high burden of systemic symptoms, including in survivors, leading to a reduced quality of life (QoL). We assessed whether a 12-week multicomponent supervised exercise programme, including muscular strength and aerobic training, was beneficial in patients who had undergone surgery for early non-small cell lung cancer (NSCLC) in terms of physical performance, QoL, and metabolic and nutritional analytical parameters. Methods: Physical performance was measured by gait speed, handgrip strength, 30 s sit-to-stand (30s-STS) test repetitions, distance covered in the 6 min walk test (6MWT), and the Short Physical Performance Battery (SPPB) score. QoL was assessed with the EORTC-QLQ-C30 questionnaire. Blood glucose, cholesterol, triglycerides, total proteins, albumin, pre-albumin, creatinine, c-reactive protein, insulin-growth factor 1 (IGF-1), and the haemoglobin and hematocrit percentages were measured before and after the intervention in order to observe any beneficial effects related to metabolic markers. Results: After the intervention, the mean scores for the 6MWT (p < 0.001), STS (p < 0.001), 6MWT (p < 0.01), and SPPB (p < 0.01) had significantly improved. However, handgrip strength and nutritional analytical were unchanged. The EORTC-QLQ-C30 functions and symptoms significantly improved after the intervention (p < 0.05 and p < 0.01, respectively). A significant decrease in cholesterol, triglycerides, and IGF-1 and a significant increase in pre-albumin in blood was also observed post-intervention (p < 0.05). Conclusions: This supervised, community-based 12-week multicomponent was feasible (adherence rate 70.35%) and provided benefits not only to physical performance but also to the quality of life of patients with NSCLC. [ABSTRACT FROM AUTHOR]

Fatigue is characterized by reduced energy level, decreased muscle strength, and a variable degree of cognitive impairment. Recent evidences seem to link vitamin D deficiency to fatigue. The aim of this study was to assess and compare vitamin D status in a cohort of older subjects with and without fatigue. We recruited a total of 480 subjects, 240 patients with fatigue and 240 controls without fatigue, from the Cannizzaro Hospital of Catania (Italy). Fatigue severity was measured by the fatigue severity scale, whereas mental and physical fatigue were measured through the Wessely and Powell fatigue scale, respectively. We also measured several blood parameters and 25-OH vitamin D. Subjects with fatigue showed lower levels of vitamin D as compared with those without fatigue. Blood levels of parameters related to fatigue were normal in both groups of subjects, however, platelet, hemoglobin, hematocrit (p < 0.05), mean corpuscular volume, C-reactive protein (CRP), iron, vitamin B12, and folic acid (p < 0.001) were significantly higher in the fatigue group with respect to the control group. Moreover, compared to controls, patients showed higher scores in the physical (p < 0.001), mental (p < 0.001), and severity (p < 0.001) fatigue scales. Finally, vitamin D inversely correlated with fatigue severity (r = −0.428, p < 0.01), whereas creatine kinase and CRP levels did not correlate with vitamin D. In conclusion, our data showed a direct link between vitamin D and fatigue in older subjects, suggesting translational implications in the diagnosis and management of these patients. [ABSTRACT FROM AUTHOR]

Objective: Treating sarcopenia remains a challenge, and nutritional interventions present promising approaches. We summarize the effects of leucine supplementation in treating older individuals with sarcopenia associated with aging or to specific disorders, and we focus on the effect of leucine supplementation on various sarcopenia criteria, e.g., muscular strength, lean mass, and physical performance. Methods: A literature search for articles related to this topic was performed on the relevant databases, e.g., the PubMed/Medline, Embase, EBSCO, Cochrane, Lilacs, and Dialnet. The identified articles were reviewed according to Preferred Reporting Items for Systematic reviews and meta-analyses (PRISMA) guidelines. Results: Of the 163 articles we consulted, 23 met our inclusion criteria, analysing the effect of leucine or leucine-enriched protein in the treatment of sarcopenia, and 13 of these studies were based on randomized and placebo-controlled trials (RCTs). In overall terms, the published results show that administration of leucine or leucine-enriched proteins (range 1.2–6 g leucine/day) is well-tolerated and significantly improves sarcopenia in elderly individuals, mainly by improving lean muscle-mass content and in this case most protocols also include vitamin D co-administration. The effect of muscular strength showed mix results, and the effect on physical performance has seldom been studied. For sarcopenia-associated with specific disorders, the most promising effects of leucine supplementation are reported for the rehabilitation of post-stroke patients and in those with liver cirrhosis. Further placebo-controlled trials will be necessary to determine the effects of leucine and to evaluate sarcopenia with the criteria recommended by official Working Groups, thereby limiting the variability of methodological issues for sarcopenia measurement across studies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses various reports within the issue on topics including chlorhexidine gluconate bathing on health care-associated infections, music intervention on stress and anxiety, and acupressure for lung cancer patients.

Although cancer and diabetes are common diseases, the relationship between diabetes, neuropathy and the risk of developing peripheral sensory neuropathy while or after receiving chemotherapy is uncertain. In this review, we highlight the effects of chemotherapy on the onset or progression of neuropathy in diabetic patients. We searched the literature in Medline and Scopus, covering all entries until 31 January 2021. The inclusion and exclusion criteria were: (1) original article (2) full text published in English or Spanish; (3) neuropathy was specifically assessed (4) the authors separately analyzed the outcomes in diabetic patients. A total of 259 papers were retrieved. Finally, eight articles fulfilled the criteria, and four more articles were retrieved from the references of the selected articles. The analysis of the studies covered the information about neuropathy recorded in 768 cancer patients with diabetes and 5247 control cases (non-diabetic patients). The drugs investigated are chemotherapy drugs with high potential to induce neuropathy, such as platinum derivatives and taxanes, which are currently the mainstay of treatment of various cancers. The predisposing effect of co-morbid diabetes on chemotherapy-induced peripheral neuropathy depends on the type of symptoms and drug used, but manifest at any drug regimen dosage, although greater neuropathic signs are also observed at higher dosages in diabetic patients. The deleterious effects of chemotherapy on diabetic patients seem to last longer, since peripheral neuropathy persisted in a higher proportion of diabetic patients than non-diabetic patients for up to two years after treatment. Future studies investigating the risk of developing peripheral neuropathy in cancer patients with comorbid diabetes need to consider the duration of diabetes, cancer-induced neuropathic effects per se (prior chemotherapy administration), and the effects of previous cancer management strategies such as radiotherapy and surgery. [ABSTRACT FROM AUTHOR]

Abstract: Parkinson's disease (PD) is a progressive neurodegenerative disorder. Gait impairments are common among people with PD. Wearable sensor systems can be used for gait analysis by providing spatio-temporal parameters useful to investigate the progression of gait problems in Parkinson disease. However, various methods and tools with very high variability have been developed. The aim of this study is to review published articles of the last 10 years (from 2008 to 2018) concerning the application of wearable sensors to assess spatio-temporal parameters of gait in patients with PD. We focus on inertial sensors used for gait analysis in the clinical environment (i.e., we do not cover the use of inertial sensors to monitor walking or general activities at home, in unsupervised environments). Materials and Methods: Relevant articles were searched in the Medline database using Pubmed. Results and Discussion: Two hundred ninety-four articles were initially identified while searching the scientific literature regarding this topic. Thirty-six articles were selected and included in this review. Conclusion: Wearable motion sensors are useful, non-invasive, low-cost, and objective tools that are being extensively used to perform gait analysis on PD patients. Being able to diagnose and monitor the progression of PD patients makes wearable sensors very useful to evaluate clinical efficacy before and after therapeutic interventions. However, there is no uniformity in the use of wearable sensors in terms of: number of sensors, positioning, chosen parameters, and other characteristics. Future research should focus on standardizing the measurement setup and selecting which spatio-temporal parameters are the most informative to analyze gait in PD. These parameters should be provided as standard assessments in all studies to increase replicability and comparability of results. [ABSTRACT FROM AUTHOR]

Compared with elderly people who have not experienced falls, those who have were reported to have a shortened step length, large fluctuations in their pace, and a slow walking speed. The purpose of this study was to elucidate the step length required to maintain a walking speed of 1.0 m/s in patients aged 75 years or older. We measured the 10 m maximum walking speed in patients aged 75 years or older and divided them into the following two groups: Those who could walk 1.0 m/s or faster (fast group) and those who could not (slow group). Step length was determined from the number of steps taken during the 10 m-maximum walking speed test, and the step length-to-height ratio was calculated. Isometric knee extension muscle force (kgf), modified functional reach (cm), and one-leg standing time (s) were also measured. We included 261 patients (average age: 82.1 years, 50.6% men) in this study. The fast group included 119 participants, and the slow group included 142 participants. In a regression logistic analysis, knee extension muscle force (p = 0.03) and step length-to-height ratio (p < 0.01) were determined as factors significantly related to the fast group. As a result of ROC curve analysis, a step length-to-height ratio of 31.0% could discriminate between the two walking speed groups. The results suggest that the step length-to-height ratio required to maintain a walking speed of 1.0 m/s is 31.0% in patients aged 75 years or older. [ABSTRACT FROM AUTHOR]

The article discusses the use of virtual reality teaching material Brainstorm Edison Pro 4.1.13 software in 2023. Topics covered include the importance of visual contact between teacher and students and of motivating visual material on the students to maintain their attention. Also noted are the contents of the virtual reality nursing education software and their implementation.

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. [ABSTRACT FROM AUTHOR]

Peripheral inflammation and gait speed alterations are common in several neurological disorders and in the aging process, but the association between the two is not well established. The aim of this systematic literary review is to determine whether proinflammatory markers are a positive predictor for gait impairments and their complications, such as falls in older adults, and may represent a risk factor for slow gait speed and its complications. The systematic review was performed in line with the Preferred Report Items for Systematic Review and Meta-Analyses (PRISMA). A protocol for literature searches was structured a priori and designed according to the International Perspective Register of Systemic Review (PROSPERO: CRD42023451108). Peer-reviewed original articles were identified by searching seven electronic databases: Excerpta Medica Database (EMBASE), SciVerse (ScienceDirect), Scopus, PubMed, Medline, Web of Science, and the Cochrane Library. The search strategy was formulated based on a combination of controlled descriptors and/or keywords related to the topic and a manual search was conducted of the reference lists from the initially selected studies to identify other eligible studies. The studies were thoroughly screened using the following inclusion criteria: older adults, spatiotemporal gait characteristics, and proinflammatory markers. A meta-analysis was not performed due to the heterogeneity of the studies, and the results were narratively synthesized. Due to the clinical and methodological heterogeneity, the studies were combined in a narrative synthesis, grouped by the type of biomarkers evaluated. A standardized data extraction form was used to collect the following methodological outcome variables from each of the included studies: author, year, population, age, sample size, spatiotemporal gait parameters such as gait velocity, and proinflammatory markers such as TNF-α, high sensitivity C-reactive (CRP) proteins, and IL-6. We included 21 out of 51 studies in our review, which examined the association between inflammatory biomarkers and gait impairment. This review highlights the role of TNF-α, CRP, and IL-6 in gait impairment. Biomarkers play an important role in the decision-making process, and IL-6 can be an effective biomarker in establishing the diagnosis of slow gait speed. Further longitudinal research is needed to establish the use of molecular biomarkers in monitoring gait impairment. [ABSTRACT FROM AUTHOR]

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%. [ABSTRACT FROM AUTHOR]

Patients with a neurodevelopmental disorder such as Rett syndrome (RS), as well as their families, have complex needs that affect their quality of life (QoL). Therefore, both families and patients with RS must be provided with multidisciplinary health care that can identify the clinical features that most affect their QoL and mental health risks. The main objective of this paper is to provide a comprehensive overview of the QoL subdimensions of families affected by RS, including both the parents and children. We conducted a systematic review, following PRISMA criteria, of the data in the PubMed, PsycINFO, Cuiden, and LILACS databases. The results indicated that when considering the family as a whole, RS equally affects the physical and psychological QoL dimensions; the next most affected was the social dimension. According to parents’ reports, seizures are one of the main factors that decreases their QoL. Thus, from a clinical point of view, controlling seizure activity of children with RS is the main way of improving the QoL of their parents. Interventions in patients affected by RS should be based on the improvement of visual contact and concentration, reducing somnolence, and increasing mobility. The subdimensions of QoL that were most affected in parents of girls with RS were those related to mental health and feelings of well-being. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Sleep assessment is a fundamental part of health evaluation. In fact, many diseases (such as obesity, diabetes, or hypertension, as well as psychiatric, neurological, and cardiovascular diseases) produce sleep disorders that are often used as indicators, diagnosis (symptoms), or even as predictors (eg, for depression) of health. For this reason, many efforts have been devoted to designing methods to control and report on sleep quality. Two of the most used sleep assessment tools are sleep questionnaires and sleep diaries. Both methods have a very low cost are easy to administer do not require a sleep centre (unlike, eg, polysomnography), and can be self-administered. Most important, as it has been shown in recent studies, their accuracy is relatively high. In this survey, we systematically review and compare these tools. We examine the evolution of sleep questionnaires and diaries over time, and compare their structure and usage. We also review the validation studies and comparatives performed in previous studies. This allows us to compare the relative sensitivities and specificities of these methods. Modern sleep diaries come in the form of an app. Therefore, we also present the most advanced and used apps, and discuss their advantages over classical paper diaries. [ABSTRACT FROM AUTHOR]

Purpose Treating constipation in elderly people remains a challenge; the administration of probiotics may be a valid therapy for this problem as an alternative to traditional drug-based treatments. The objective of this systematic review was to evaluate the efficiency of probiotics in treating constipation in elderly people. Methods Articles related to this topic and published, without any time limitations, in the Medline, Embase, Scopus, Lilacs, or Cochrane databases were systematically reviewed according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The primary search terms were ‘constipation’ and ‘probiotics’. The main inclusion criteria were: 1) the article was original and the whole text was published in English or Spanish and 2) included the primary search terms in the title, summary, or body text; 3) the studies had to have included 60 or more participants defined as ‘elderly’ and 4) have specifically evaluated the effect of the administration of probiotics. Results Of the 475 articles consulted, 9 met the inclusion criteria. Among the selected studies, there were four randomised and placebo-controlled trials and the remaining five reports were observational. Overall, our analysis of the randomised and placebo-controlled trials suggests that administration of probiotics significantly improved constipation in elderly individuals by 10–40% compared to placebo controls in which no probiotic was administered. The strain of bacteria most commonly tested was Bifidobacterium longum . However, caution is needed when interpreting these reports because of the heterogeneity of the original study designs, populations, and the risk of bias. Therefore, further placebo-controlled trials are necessary to determine the most efficient strains, doses, and the optimal treatment duration. [ABSTRACT FROM AUTHOR]

Aging is an inevitable process that impacts the peripheral and central nervous systems and is considered one of the strongest risk factors for neurodegenerative diseases. In addition, when it also presents with diabetes mellitus, the risk of neurological damage may be further increased. This current study aimed to explore the relationships between peripheral sensory system decline and cognitive functions, the symptoms of depression, and quality of life (QoL) as metrics of central nervous system impairment in institutionalized older adults. A total of 95 individuals participated in this case-control study, which included diabetics and non-diabetics. The superficial sensory pathway was assessed in terms of thermal sensation, nociception, and non-discriminative touch, and the deep sensory pathway was evaluated by assessing vibration and light touch-pressure sensations. To assess function at the intellectual level, the Mini-Mental State Examination (MMSE) and Trail Making Test (TMT) cognitive functional tests were used, while the symptoms of depression and QoL were explored by employing the Yesavage Geriatric Depression Scale and EuroQol 5D questionnaire (EQ-5D), respectively. In the overall population analyses, altered thermal sensation was significantly associated with cognitive impairment (CI; p < 0.05). In turn, bivariate analyses and a binary logistic regression showed that the symptoms of depression and QoL were significantly related to altered vibratory sensation when assessed using a medical tuning fork (p < 0.05). In the group of diabetic patients, those with CI also had significantly lower thermal sensation (p < 0.05) and non-discriminative touch sensation, although this was only a trend (p = 0.055). Diabetics with depression had a significantly worse non-discriminative touch (p < 0.05) and vibratory sensation when tested with a tuning fork (p < 0.05). In addition, poorer QoL was associated with reduced sensitivity to heat (p < 0.05), light touch pressure (p < 0.05), and vibrations when assessed either with a tuning fork (p < 0.05) or a biothesiometer (p < 0.05). In contrast, no relationships were found between sensory functions and cognitive assessments in non-diabetic patients. These findings indicate that superficial sensitivity damage was related to CI, while deep sensation alterations were related to depression and poor QoL, with diabetes apparently further strengthening these relationships. [ABSTRACT FROM AUTHOR]

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. • Psychological symptoms are frequent in breast cancer survivors even many years ago from cancer diagnosis. • Chronic stress stimulated cortisol production which accumulated in hair (HCC). • High HCC is accompanied by high stress level and high insomnia symptoms. • HCC represents a suitable biomarker to evaluate these psychological alterations in breast cancer. [ABSTRACT FROM AUTHOR]

Background & Aims: GABAA receptors modulate the function of the glutamate-nitric oxide-guanosine 3′,5′-cyclic monophosphate (cGMP) pathway, which is reduced in cerebellum in hyperammonemic rats. It has been proposed that hyperammonemia-induced increases in γ-aminobutyric acid “(GABAergic) tone” contribute to the pathogenesis of hepatic encephalopathy (HE), although this has not been assessed in vivo in animal models. We studied whether chronic hyperammonemia in rats increases GABAergic tone in the cerebellum and/or cerebral cortex and whether this increase contributes to cognitive impairment. Methods: We blocked GABAA receptors of rats with bicuculline and analyzed the function of this pathway in cerebellum and effects on learning ability. Results: Hyperammonemia increased GABAergic tone in cerebellum but decreased it in the cerebral cortex of rats. Increased GABAergic tone in the cerebellum of rats with hyperammonemia could have been caused by increases in extracellular GABA; tetrahydrodeoxy-corticosterone (a neurosteroid that enhances GABAA receptor activation); or amounts of the α1, α6, and γ2 subunits of GABAA receptors. The decrease in GABAergic tone observed in the cortex could have resulted from the reduced amount of GABAA receptors δ and γ2 subunits or increased levels of pregnanolone (5-fold), which selectively reduces activation of GABAA receptors that contain α4 subunits (widely expressed in cortex but not in cerebellum). Treatment with bicuculline normalized GABAergic tone and restored the increase in cGMP that was induced by activation of N-methyl-d-aspartate receptors and learning ability in hyperammonemic rats. Conclusions: Increased GABAergic tone in the cerebellum contributes to cognitive impairment in hyperammonemic rats. [Copyright &y& Elsevier]

Dicarboxylic acids are an important source of information about metabolism and potential physiopathological alterations in children with autism spectrum disorders (ASDs). We measured the concentration between dicarboxylic adipic and suberic acids in children with an ASD and typically-developing (TD) children and analyzed any relationships between the severity of the core symptoms of ASDs and other clinical features (drugs, supplements, drugs, or diet). The core symptoms of autism were evaluated using the DSM-IV criteria, and adipic acid and suberic acid were measured in urine samples. Overall, no increase in the concentration of adipic acid in children with ASDs compared to TD children, however when considering vitamin B supplementation in ASD there were significantly increased level of urinary adipic acid in children with an ASD not taking vitamin B supplementation compared to supplemented children or to TD children. No significant difference were observed in suberic acid. Interestingly, the increase in adipic acid concentration was significantly and indirectly correlated with the severity of the deficit in socialization and communication skills in children with an ASD. Therefore, therapeutic treatments aimed at decreasing adipic acid concentration might not be beneficial for treating the core symptoms of ASDs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This mini-review focus on our studies on alterations in glutamatergic neurotransmission and their role in neurological alterations in rat models of chronic hyperammonemia and hepatic encephalopathy (HE). Hyperammonemia impairs the glutamate-nitric oxide (NO)-cGMP pathway in cerebellum, which is responsible for reduced learning ability. We studied the underlying mechanisms and designed treatments to restore the pathway and learning. This was achieved by treatment with: phosphodiesterase 5 inhibitors, cGMP, anti-inflammatories (ibuprofen), p38 inhibitors or GABA receptor antagonists (bicuculline). Hyperammonemia alters signal transduction associated to metabotropic glutamate receptors (mGluRs). Hypokinesia in hyperammonemia and HE is due to increased extracellular glutamate and mGluR1 activation in substantia nigra; blocking this receptor restores motor activity. The motor responses to mGluRs activation in nucleus accumbens (NAcc) are altered in hyperammonemia and HE, with reduced dopamine and increased glutamate release. This leads to activation of different neuronal circuits and enhanced motor responses. These studies show that altered responses to activation of NMDA receptors and mGluRs play essential roles in cognitive and motor alterations in hyperammonemia and HE and provide new treatments restoring cognitive and motor function. [ABSTRACT FROM AUTHOR]

Abstract: Hepatic encephalopathy is a complex neuropsychiatric syndrome present in patients with chronic or acute liver disease. We review here some recent advances in the study, in animal models, of the mechanisms involved in the impairment in intellectual function in hepatic encephalopathy. These studies show that the function of the glutamate–nitric oxide–cGMP pathway is impaired in brain in vivo in rats with chronic hyperammonemia or liver failure and from patients died in hepatic encephalopathy. This impairment leads to a reduced extracellular concentration of cGMP in the cerebellum and is associated with reduced learning ability in these animal models. Moreover, learning ability of hyperammonemic rats was restored by increasing cGMP by: (1) continuous intracerebral administration of zaprinast, an inhibitor of the cGMP-degrading phosphodiesterase, (2) chronic oral administration of sildenafil, an inhibitor of the phosphodiesterase that crosses the blood–brain barrier and (3) continuous intracerebral administration of cGMP. The data summarized indicate that impairment of learning ability in rats with chronic liver failure or hyperammonemia is due to impairment of the glutamate–nitric oxide–cGMP pathway. Moreover, increasing extracellular cGMP by pharmacological means may be a new therapeutic approach to improve cognitive function in patients with hepatic encephalopathy. [Copyright &y& Elsevier]

Background: In clinical practice, specific customization is needed to address foot pathology, which must be disease and patient-specific. To date, the traditional methods for manufacturing custom functional Foot Orthoses (FO) are based on plaster casting and manual manufacturing, hence orthotic therapy depends entirely on the skills and expertise of individual practitioners. This makes the procedures difficult to standardize and replicate, as well as expensive, time-consuming and material-wasting, as well as difficult to standardize and replicate. 3D printing offers new perspectives in the development of patient-specific orthoses, as it permits addressing all the limitations of currently available technologies, but has been so far scarcely explored for the podiatric field, so many aspects remain unmet, especially for what regards customization, which requires the definition of a protocol that entails all stages from patient scanning to manufacturing. Methods: A feasibility study was carried out involving interdisciplinary cooperation between industrial engineers and podiatrists. To that end: (i) For patient-specific data acquisition, 3D scanning of the foot is compared to traditional casting. (ii) a modelling GD workflow is first created to design a process permitting easy creations of customized shapes, enabling the end user (the podiatrist) to interactively customize the orthoses. Then, (iii) a comparison is made between different printing materials, in order to reproduce the same mechanical behavior shown by standard orthoses. To do this, the mechanical properties of standard materials (Polycarbonate sheets), cut and hand-shaped, are compared with four groups of 3D printed samples: poly(ethylene glycol) (PETG), poly(acrylonitrile-butadiene.styrene) (ABS), polycarbonate (PC) and poly(lactic acid) (PLA) obtained by Fused Filament Fabrication (FFF). Results: Differences found between the foot plaster model obtained with the plaster slipper cast in a neutral position and the model of the real foot obtained with 3D scanning in the same position can be ascribed to the non-stationarity of the patient during the acquisition process, and were limited by a locking system with which no substantial differences in the almost entire sole of the foot scan were observed. Conclusions: Using the designed GD workflow, podiatrists with limited CAD skills can easily design and interactively customize foot orthoses to adapt them to the patients' clinical needs. 3D printing enables the complex shape of the orthoses to be reproduced easily and quickly. Compared to Polycarbonate sheets (gold standard), all the printed materials were less deformable and reached lower yield stress for comparable deformation. No modifications in any of the materials as a result of printing process were observed. [ABSTRACT FROM AUTHOR]

Frailty syndrome is associated with poor outcomes, morbidity and premature mortality. We performed a cross-sectional study to evaluate the presence of frailty syndrome based on Fried's frailty phenotype in post-menopausal women with breast cancer. We further analyzed the association between frailty syndrome with geriatric assessments and the association with the concentration of gonadotropins LH and FSH, estrogens, androgens and the aromatase activity index in the blood. We enrolled 47 post-menopausal women with localized breast cancer (mean age 66.8 ± 1.3 years (range 52–83)) prior to the starting of adjuvant endocrine therapy. Patients were identified as "non-frail" (robust) or "prefrail/frail" if they fulfilled at least one frailty criteria. In order to determine associations among variables and to control for other variables potentially affecting frailty syndrome (age, comorbidity index and previous chemotherapy treatment), we performed a logistic regression analysis. The receiver operating characteristic curve was performed to assess the sensitivity and specificity of the hormonal concentration to discriminate prefrail/frail versus non-frail individuals. Significant positive associations were observed between the severity of frailty syndrome and estrone, FSH and LH concentrations and the aromatase activity index in the blood (p < 0.05). Further research into the role of hormonal biomarkers should be evaluated in follow-up studies in order to recommend their use as suitable biomarkers of frailty syndrome in breast cancer patients. [ABSTRACT FROM AUTHOR]

• Exposure to phthalates in pregnant women decreases the scores of the offspring in cognitive tests. • Both sexes are affected, but statistical association is higher in boys. • For many phthalates there are no statistical association, or even some positive associations. Phthalates are chemicals widely used in packaging and consumer products, which have been shown to interfere with normal hormonal function and development in some human and animal studies. In recent decades, pregnant women's exposure to phthalates has been shown to alter the cognitive outcomes of their babies, and some studies have found delays in motor development. Methods: electronic databases including PubMed/MEDLINE and Scopus were searched from their inception to March 2021, using the keywords "phthalate", "cognitive" and "motor". Results: most studies find statistically significant inverse relationships between maternal urinary phthalate concentration during pregnancy and subsequent outcomes in children's cognitive and motor scales, especially in boys rather than girls. However, many associations are not significant, and there were even positive associations, especially in the third trimester. Conclusion: the relationship between exposure to phthalates during pregnancy and low results on neurocognitive scales is sufficiently clear to adopt policies to reduce exposure. Further studies are needed to analyze sex differences, coordination and motor scales, and phthalate levels during breastfeeding. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is associated with impairment in cognitive functions which can complicate adherence to self-care behaviors. We evaluated the incidence of cognitive impairment in patients with diabetes mellitus to determine the strength of the association between diabetic foot (a complication that occurs in about 10% of diabetic patients), adherence to the clinician's recommendations, glycemic control, and cognitive function. A prospective study was carried out in a probabilistic sample of older patients with diabetic foot living in three nursing homes. Cognitive functions were evaluated by the MMSE (Mini-Mental State Examination), the Trail Making test (TMT), and the Michigan neuropathy screening instrument (MNSI). There were no significant associations between cognitive function and neuropathy or foot alterations, although glycated hemoglobin (HB1Ac > 7%) significantly (p < 0.05) associated with MMSE and adherence to treatment in the 1 month follow-up visit. Receiver operating characteristic curve analysis showed that both HB1Ac and the MNSI score significantly (p < 0.05) discriminate subsequent adherence to treatment for foot complication, with a sensitivity of 80.0–73.3% and specificity 70.6–64.7%, respectively. Proper control of foot complications in diabetic patients involves appropriate glycemic control and less severe neuropathy, and seems to be unrelated to cognitive dysfunction, and warrants further studies in order to tailor appropriate treatments to central and peripheral nervous system disorders. Poor glycemic control (Hb1Ac level > 7%) and a neuropathy score of 5.5 in the MNSI are the best-cut off points to discriminate poor adherence to the clinician's recommendations for self-care behaviors in people with diabetic foot complication. In this study, we observed that foot disorders were associated with impaired global cognitive function in elderly patients (aged ≥ 65). Podiatrists and physicians should consider cognitive dysfunction as an important chronic complication in the management of diabetic foot. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the role of peripheral inflammation (leukocyte differential count, the proinflammatory cytokines IL-beta, TNF-α, IL-6, IL-8, and the inflammatory markers fibrinogen and C-reactive protein [CRP]) in frailty syndrome in patients with prostate cancer (CaP) undergoing antiandrogen therapy (ADT).Methods: A total of 46 men between 51 and 92 years of age with CaP and receiving ADT were classified as frail, prefrail or robust according to the Fried scale. A geriatric assessment was performed, based on the Minimental State Examination for cognitive function, the Barthel index for basic activities of daily living, the Yesavage scale for geriatric depression, and the Athens insomnia scale. In addition, blood samples were collected to assess peripheral inflammation biomarkers including proinflammatory cytokines, fibrinogen, CRP and leukocyte differential count, as well as other biochemical and hematological parameters.Results: A significant negative correlation between the severity of frailty syndrome and lymphocyte count was observed (P < 0.01). The concentration of IL-6 (P < 0.05), CRP (P < 0.05), and fibrinogen (P < 0.01) were significantly associated with frailty syndrome, but not of TNF-α, IL-beta, or IL-8. The severity of frailty syndrome was not dependent upon the clinical disease stage at diagnosis, the time elapsed since CaP diagnosis, the presence of metastases, or prostatectomy.Conclusions: Further research into the role of leukocyte subtypes and peripheral inflammation and the associated adverse outcomes in patients with CaP under ADT is warranted in order to tailor interventions aimed at reducing symptoms of frailty syndrome, such as loss of muscle strength and low physical activity. [ABSTRACT FROM AUTHOR]

Opioid-induced neuroinflammation and the nitric oxide (NO) signal-transduction pathway are involved in the development of opioid analgesic tolerance. The antidepressant venlafaxine (VLF) modulates NO in nervous tissues, and so we investigated its effect on induced tolerance to morphine, neuroinflammation, and oxidative stress in mice. Tolerance to the analgesic effects of morphine were induced by injecting mice with morphine (50 mg/kg) once a day for three consecutive days; the effect of co-administration of VLF (5 or 40 mg/kg) with morphine was similarly tested in a separate group. To determine if the NO precursor l -arginine hydrochloride ( l -arg) or NO are involved in the effects rendered by VLF, animals were pre-treated with l -arg (200 mg/kg), or the NO synthesis inhibitors N(ω)-nitro- l -arginine methyl ester (L-NAME; 30 mg/kg) or aminoguanidine hydrochloride (AG; 100 mg/kg), along with VLF (40 mg/kg) for three days before receiving morphine for another three days. Nociception was assessed with a hot-plate test on the fourth day, and the concentration of tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β), interleukin-6 (IL-6), interleukin-10, brain-derived neurotrophic factor, NO, and oxidative stress factors such as total thiol, malondialdehyde content, and glutathione peroxidase (GPx) activity in the brain was also determined. Co-administration of VLF with morphine attenuated morphine-induced analgesic tolerance and prevented the upregulation of proinflammatory cytokines (TNF-α, IL-1β, and IL-6), NO, and malondialdehyde in brains of mice with induced morphine tolerance; chronic VLF administration inhibited this decrease in brain-derived neurotrophic factor, total thiol, and GPx levels. Moreover, repeated administration of l -arg before receipt of VLF antagonized the effects induced by VLF, while L-NAME and AG potentiated these effects. VLF attenuates morphine-induced analgesic tolerance, at least partly because of its anti-inflammatory and antioxidative properties. VLF also appears to suppress the development of morphine-induced analgesic tolerance through an l -arg–NO-mediated mechanism. [ABSTRACT FROM AUTHOR]

Aging affects sleep and sleep problems are common in older individuals. However, the relationship between objective and subjective tools for analysing sleep and psycho-geriatric variables have not been tested in institutionalised older individuals. This work analyses sleep quality by using actigraphy as an objective tool and validates the Athens and Oviedo sleep questionnaires in octogenarian elderly individuals as subjective scales of sleep perception. All patients wore an actigraph device for one week and then completed the Athens and Oviedo clinical sleep-evaluation questionnaires. Morning cortisol levels in blood plasma and saliva samples were also measured to assess the association between objective and reported sleep patterns. Age, gender, and psycho-geriatric evaluations, including Barthel, Tinetti, and Mini-Mental scale measurements were analysed as variables with the potential to confound the strength of any such associations. There was a significant inverse correlation between the number of awakenings and the time spent awake during night assessed by actigraphy and the total Oviedo questionnaire score, but no significant associations for the other parameters. The blood cortisol concentration appears to be a marker of insomnia related to sleep times of less than four hours and diagnosis of insomnia based on Athens scale and thus, represents a potential marker for sleep interventions. [ABSTRACT FROM AUTHOR]

Alteration in the immune system such as the number of white blood cells count (WBC) has been associated with frailty syndrome but their role in institutionalized older individuals have been rarely investigated. We evaluated the relationships between white blood cell subtypes, geriatric assessment, depression and frailty syndrome based on the criteria of physical phenotype. In particular, we aimed to analyze by a two-year follow-up and prospective study the predictive value of alterations in WBC, frailty and functional impairment in terms of hospitalizations and all-cause mortality in institutionalized older women. There was a significant and inverse correlation between the frailty score and lymphocyte count at baseline but it did not display any predictive effect for the outcomes (hospitalizations and mortality). In contrast, monocytes count was significantly correlated with number of hospital stays and predicted hospitalizations in the follow-up. High frailty score directly and better functional status (Barthel score) inversely predicted mortality in the follow-up with an HR of 1.87 (95%CI: 1.04–3.35), and 0.97 (95% CI: 0.96–0.99) (p < .05 in both cases). Further investigation into the role of white blood cell subtypes in aging and its associated adverse outcomes in older adults is warranted. Physical phenotype of frailty besides general population, also predicted mortality in older institutionalized women and deserves specific intervention in this subgroup of older individuals. [ABSTRACT FROM AUTHOR]

Aims Changes in serum cytokines and altered neutrophin concentration have been associated with bipolar disorder (BD). Our aim here was to analyze peripheral blood biomarkers according to the clinical stages of BD. Method Euthymic BD-I patients were grouped according to their level of functioning in early-stage (n = 25) and late-stage (n = 23), and compared to healthy siblings (n = 23) and genetically unrelated healthy controls (n = 21). Neurotrophin (neurotrophin-3 and BDNF) concentration and biomarkers of inflammation, including cytokines (IL-6, IL-10 and TNF-α), leukocytes count and acute phase proteins, were measured. Results IL-10 concentration was significantly increased in early-stage patients compared to late-stage patients, healthy siblings and controls whereas TNF-α concentration was significantly increased in late-stage patients compared to controls. Total leukocytes, neutrophil and monocyte count were significantly increased in late-stage patients compared to healthy siblings and controls. The concentration of IL-6, neurotrophin-3 and BDNF was unchanged in euthymia. Healthy siblings did not show significant changes in any biomarker. Conclusions The concentration of IL-10, TNF-α, neutrophil and monocytes subtype count in blood is altered in patients with BD during euthymic state. The link between peripheral inflammation and different stages in BD deserves further studies. [ABSTRACT FROM AUTHOR]

We used a complete battery of geriatric and psychometric tests to evaluate whether plasma-borne brain-derived neurotrophic factor (BDNF), a master molecule in neuroplasticity, is associated with the severity of functional and cognitive impairment in non-disabled older individuals. There was a significant positive correlation between BDNF plasma concentrations and the Barthel index, a measurement of the ability of individuals to perform the activities of daily living ( p = 0.03) and the concentration subcategory measured with the mini mental state examination (MMSE) test ( p = 0.01). Furthermore, plasma BDNF inversely and significantly correlated with the blood eosinophil count ( p = 0.01), the total cholesterol concentration ( p = 0.04), and high-density lipoprotein cholesterol ( p = 0.04). However, BDNF did not correlate with any other socio-demographic or clinical characteristics, other analytical parameters measured in the blood, or any other geriatric assessment scales. Our results suggest that BDNF may play a role in the pathophysiology of functional impairment in the elderly and in some aspects of cognitive function. However, more studies are needed to understand the relationship between circulating BDNF and functional impairment to determine if BDNF represents a candidate biomarker for this type of cognitive impairment. [ABSTRACT FROM AUTHOR]

Background Frailty is a geriatric syndrome characterized by the clinical presentation of identifiable physical alterations and decreased physiological reserve. The assessment of frailty syndrome has been recently related with post-surgical outcomes and overall mortality in older individuals. Design and data sources We performed searches in Pubmed, Embase, Scopus, SCIELO and IME (Spanish medical index) databases from their start dates to February 2014 for original papers about the identification of the relationship between frailty and pre-operative risk evaluation in people aged 65 and over. Review methods We followed criteria of systematic PRISMA guidelines. Two independent reviewers extracted descriptive information on frailty criteria and outcomes from the selected papers: of the 77 articles retrieved from the searches, 32 met the study inclusion criteria. Results Severity of frailty syndrome significantly correlated with post-surgical mortality rates and with many although not all post-surgical complications. These relationships emerge in different type of surgical procedures and patients' features. The comparison of diagnostic tools to assess frailty in pre-operative risk evaluation are very few and to date, no recommendation can be made about the best scale to measure it. Conclusion Assessment of frailty syndrome should be added in the pre-operative risk assessment in older individuals. [ABSTRACT FROM AUTHOR]