Thyroid hormones, metabolic syndrome and Vitamin D in middle-aged and older euthyroid subjects: a preliminary study.

AIM: To explore the relationship between thyroid hormones, Vitamin D (Vit.D) serum concentrations and metabolic syndrome (MetS) in euthyroid subjects. METHODS: 123 community-dwelling subjects were enrolled. According to thyroid-stimulating hormone (TSH) values the sample was divided into: (1) group 1 (TSH ≤ 2 mU/L); (2) group 2 (TSH > 2 mU/L). RESULTS: Group 2 showed higher percentage of subjects with MetS (p = 0.003) and hypertension (p = 0.031), higher values of waist circumference (WC) (p = 0.007), parathyroid hormone (p = 0.016), glycaemia (p = 0.045), triglycerides (p = 0.034) and free T4 (fT4) (p = 0.013). Correlation analysis showed several weak significant correlations: MetS with TSH (r = 0.202, p = 0.031) and fT3 (r = - 0.206, p = 0.028); THS with body mass index (r = 0.187, p = 0.047) and hypertension (r = 0.199, p = 0.034); Vit.D with WC (r = - 0.185, p = 0.04). CONCLUSIONS: Our results showed a possible association between thyroid hormones and MetS. Visceral fat and insulin resistance may be an interesting link between Vit.D and TSH levels.

The development of a new tool for the evaluation of handicap in elderly: the Geriatric Handicap Scale (GHS).

BACKGROUND: To date, the comprehensive geriatric assessment (CGA) does not include an evaluation tool for handicap. AIM: To develop a new instrument for assessing handicap in the elderly: the Geriatric Handicap Scale (GHS). METHODS: 656 community-dwelling elderly were enrolled in this study. We identified the thematic areas investigated by the CGA which showed a significant correlation with the handicap condition (handicap yes/not) to be included in our scale (Phase 1). Afterwards, we evaluated the possible correlations between: (1) the score obtained in each area of GHS and those obtained in CGA tests investigating similar dimensions, (2) GHS total score and the Multidimensional Prognostic Index (MPI) total score (Phase 2). RESULTS: In Phase 1, data analysis showed several significant correlations between the handicap condition and the scores obtained to the CGA tests exploring cognition, mood, functional impairment, comorbidity, social and environmental variables. Thus, we developed a tool considering five variables: (1) cognition and mood; (2) functional impairment; (3) hearing/visual impairment; (4) any additional comorbidity factors; (5) environmental/social risk factors. In Phase 2, data analysis showed significant correlations between the score obtained in each area of GHS and those obtained in the CGA tests investigating similar dimensions. A positive correlation between GHS total score and MPI total score (r = 68; p = 0.001) was also reported. Cut-off score for the GHS was established. Psychometric properties of GHS were also investigated and adequate estimates of internal reliability were demonstrated. CONCLUSIONS: Our tool could prove useful to correctly categorize the disadvantageous condition related to patient's disability.

The Mozart Effect: A quantitative EEG study.

The aim of this study is to investigate the influence of Mozart's music on brain activity through spectral analysis of the EEG in young healthy adults (Adults), in healthy elderly (Elderly) and in elderly with Mild Cognitive Impairment (MCI). EEG recording was performed at basal rest conditions and after listening to Mozart's K448 or "Fur Elise" Beethoven's sonatas. After listening to Mozart, an increase of alpha band and median frequency index of background alpha rhythm activity (a pattern of brain wave activity linked to memory, cognition and open mind to problem solving) was observed both in Adults and in Elderly. No changes were observed in MCI. After listening to Beethoven, no changes in EEG activity were detected. This results may be representative of the fact that said Mozart's music is able to "activate" neuronal cortical circuits related to attentive and cognitive functions.

[Physical and psychological stress in a group of Italian caregivers: a new medical emergency? A pilot study]. / Stress psicofisici in un gruppo di operatori sanitari italiani; nuova emergenza medica? Uno studio pilota.

INTRODUCTION: this study aimed to evaluate physical and psychological stress in a group of italian caregivers. METHODS: 20 subjects were enrolled in the study and divided into 2 groups: 10 healthy controls and 10 caregivers. Every subject underwent an cognitive, clinical and instrumental assessment. RESULTS: the statistical analysis showed an increased presence of pathological alterations in caregivers group such as decreased ejection fraction, cognitive impairment and depressed mood. CONCLUSIONS: the study shows the figure of a elderly caregiver, predominantly women, who spend many hours in patient care. The caregiver-type takes about four drugs a day and is not involved in screening programs offered by the health service for his age group. Results a high risk of social isolation, emotional fragility and an increased risk of cardiovascular events and cognitive impairment.

The effects of the glycaemic control on the severity of the delirium in the advanced phase of Alzheimer's disease.

BACKGROUND: Behavioral and psychological symptoms of dementia (BPSD) and delirium are common in advanced phases of Alzheimer's disease (AD). METHODS: Thirty-eight moderate-severe AD patients were enrolled (n=16 affected by type 2 diabetes). Each patient received a comprehensive geriatric assessment (CGA) (including evaluation of BPSD and frailty), and a complete metabolic evaluation (including the measurement of the glycated hemoglobin, HbA1c). RESULTS: Both the hyper- and hypo-glycemic extremes of the glycemic spectrum worsened BPSD, but delirium was more susceptible to hypoglycemic events. The severity of delirium was significantly related to cognitive function (r = -0.585, p<0.001) and frailty (r = +0.440, p<0.05). CONCLUSIONS: The measurement of HbA1c was useful for evaluating the risk of delirium in relationship to glycemic control and nutritional status.

Antimicrobial Peptides and their Multiple Effects at Sub-Inhibitory Concentrations.

The frequent occurrence of multidrug-resistant strains to conventional antimicrobials has led to a clear decline in antibiotic therapies. Therefore, new molecules with different mechanisms of action are extremely necessary. Due to their unique properties, antimicrobial peptides (AMPs) represent a valid alternative to conventional antibiotics and many of them have been characterized for their activity and cytotoxicity. However, the effects that these peptides cause at concentrations below the minimum growth inhibitory concentration (MIC) have yet to be fully analyzed along with the underlying molecular mechanism. In this mini-review, the ability of AMPs to synergize with different antibiotic classes or different natural compounds is examined. Furthermore, data on microbial resistance induction are reported to highlight the importance of antibiotic resistance in the fight against infections. Finally, the effects that sub-MIC levels of AMPs can have on the bacterial pathogenicity are summarized while showing how signaling pathways can be valid therapeutic targets for the treatment of infectious diseases. All these aspects support the high potential of AMPs as lead compounds for the development of new drugs with antibacterial and immunomodulatory activities.

Adherence to Mediterranean diet moderates the association between multimorbidity and depressive symptoms in older adults.

AIM: Adherence to Mediterranean Diet (Med-Diet) has been associated with a lower incidence of chronic diseases and may be associated with lower risk for depression. The aim of the present study was to investigate (i) the association of adherence to Med-Diet with depressive symptoms and multimorbidity in a cohort of geriatric medical outpatients, and (ii) the role of Med-Diet in mediating the association between depressive symptoms and multimorbidity. METHODS: A total of 143 geriatric patients (mean age: 73.1 ± 8.35) were included. Adherence to Med-Diet was evaluated using a validated 14-item questionnaire; depressive and cognitive symptoms were assessed through the 15-item Geriatric Depression Scale (GDS) and Mini Mental State Examination (MMSE) respectively; multimorbidity was evaluated using the Cumulative Illness Rating Scale for Geriatrics (CIRSG-SI). RESULTS: Significant associations were found between MDQ score, GDS and CIRSG-SI (MDQ score and GDS: r= -0.206, p = 0.014; MDQ score and CIRSG-SI: r= -0.247, p = 0.003; GDS and CIRSG-SI: r = 0.251; p = 0.003). These associations remained significant after adjusting for potential confounding factors. A mediational model analysis showed that the direct effect of CIRSG-SI on GDS was significant (b = 1.330; se = 0.59; p = 0.028) with this effect being counterbalanced by higher MDQ scores (indirect effect of CIRS-G on GDS through MDQ: b = 0.382; se = 0.19; p = 0.048). CONCLUSION: These findings (i) add to the accumulating evidence that Med-Diet may have a positive impact on mental health in the elderly, and (ii) suggest that Med-Diet may contribute, at least in part, to protect geriatric patients with multimorbidity from the development of depressive symptoms, ultimately promoting healthy aging.

Oxidative Stress and Gut-Derived Lipopolysaccharides in Neurodegenerative Disease: Role of NOX2.

BACKGROUND: Neurodegenerative diseases (ND) as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis represent a growing cause of disability in the developed countries. The underlying physiopathology is still unclear. Several lines of evidence suggest a role for oxidative stress and NADPH oxidase 2 (NOX2) in the neuropathological pathways that lead to ND. Furthermore, recent studies hypothesized a role for gut microbiota in the neuroinflammation; in particular, lipopolysaccharide (LPS) derived from Gram-negative bacteria in the gut is believed to play a role in causing ND by increase of oxidative stress and inflammation. The aim of this study was to assess NOX2 activity as well as serum 8-iso-prostaglandin F2α (8-iso-PGF2α (8-iso-PGF2. METHODS: One hundred and twenty-eight consecutive subjects, including 64 ND patients and 64 controls (CT) matched for age and gender, were recruited. A cross-sectional study was performed to compare serum activity of soluble NOX2-dp (sNOX2-dp), blood levels of isoprostanes, serum H2O2, and LPS in these two groups. Serum zonulin was used to assess gut permeability. RESULTS: Compared with CT, ND patients had higher values of sNOX2-dp, 8-iso-PGF2α (8-iso-PGF2p < 0.001), zonulin (Rs = 0.411; p < 0.001), zonulin (Rs = 0.411; p < 0.001), zonulin (Rs = 0.411; α (8-iso-PGF2p < 0.001), zonulin (Rs = 0.411; p < 0.001), zonulin (Rs = 0.411; α (8-iso-PGF2p < 0.001), zonulin (Rs = 0.411; ß, 0.459; p < 0.001), zonulin (Rs = 0.411; α (8-iso-PGF2ß, 0.459; p < 0.001), zonulin (Rs = 0.411; R 2 = 57%). CONCLUSION: This study provides the first report attesting that patients with ND have high NOX2 activation that could be potentially implicated in the process of neuroinflammation.

Association between epicardial fat thickness and cognitive function in elderly. A preliminary study.

BACKGROUND: Recent studies suggested that the visceral fat could exert a predictive role in the pathogenesis of dementia. The aims of the present study were to evaluate: i) possible differences between groups with different epicardial adipose tissue (EAT) thickness on the included variables; ii) the possible predictive role of the EAT levels on cognitive functioning. METHODS: 65 community-dwelling subjects were enrolled and divided into two groups: EAT < 7 mm (n = 36); EAT > 7 mm (n = 29). The metabolic profile was assessed through the evaluation of the biochemical parameters whereas the EAT thickness was measured through the transthoracic echocardiography. The Mini Mental State Examination (MMSE) was also administered. RESULTS: The two EAT groups reported several significant differences, included on the MMSE scores. The multiple linear regression analysis showed that the EAT thickness levels and the hypertension had a predictive effect on the MMSE scores. CONCLUSIONS: These preliminary findings support the association between EAT thickness levels and cognitive impairment.

Esculentin-1a Derived Antipseudomonal Peptides: Limited Induction of Resistance and Synergy with Aztreonam.

BACKGROUND: The massive use of antibiotics has led to the selection of resistant bacterial strains that are difficult to eradicate. Among these, Pseudomonas aeruginosa most frequently colonizes and infects the airways of cystic fibrosis patients. Cationic Antimicrobial Peptides (AMPs) represent interesting molecules for the development of new antimicrobial agents. Thanks to their mechanism of action that involves the permeabilization of the bacterial cytoplasmic membrane, the induction of resistance is quite limited. OBJECTIVE: The evaluation of the capability of two frog-skin derived AMPs, i.e. Esc(1-21) and its diastereomer Esc(1-21)-1c, to induce resistance in P. aeruginosa and synergize with aztreonam. METHOD: The induction of resistance was evaluated after 15 cycles of exposure to non-inhibitory growth concentrations of antibiotics and peptides. Subsequently, the Minimal Inhibitory Concentration (MIC) was calculated and compared to that obtained before drug exposure. Furthermore, MICs of AMPs and antibiotics were evaluated in Artificial Sputum Medium (ASM). Finally, the ability of the two peptides to synergize with aztreonam was determined by the checkerboard titration method. RESULTS: Pseudomonas aeruginosa acquired resistance to antibiotics, as evidenced by the increased MICs compared to the initial ones (from 8 to 128-fold higher), while no change in MICs was observed after multiple treatments with the Esc-peptides. In addition, both peptides showed significantly lower MICs than aztreonam in ASM. Finally, the diastereomer Esc(1-21)-1c had the ability to synergize with aztreonam in inhibiting growth and in killing Pseudomonas cells. CONCLUSION: Both peptides represent promising candidates for the development of new antipseudomonal compounds, which do not induce resistance.

A new tool for the evaluation of the rehabilitation outcomes in older persons: a machine learning model to predict functional status 1 year ahead.

PURPOSE: To date, the assessment of disability in older people is obtained utilizing a Comprehensive Geriatric Assessment (CGA). However, it is often difficult to understand which areas of CGA are most predictive of the disability. The aim of this study is to evaluate the possibility to early predict-1 year ahead-the disability level of a patient using machine leaning models. METHODS: Community-dwelling older people were enrolled in this study. CGA was made at baseline and at 1 year follow-up. After collecting input/independent variables (i.e., age, gender, schooling followed, body mass index, information on smoking, polypharmacy, functional status, cognitive performance, depression, nutritional status), we performed two distinct Support Vector Machine models (SVMs) able to predict functional status 1 year ahead. To validate the choice of the model, the results achieved with the SVMs were compared with the output produced by simple linear regression models. RESULTS: 218 patients (mean age = 78.01; SD = 7.85; male = 39%) were recruited. The combination of the two SVMs is able to achieve a higher prediction accuracy (exceeding 80% instances correctly classified vs 67% instances correctly classified by the combination of the two linear regression models). Furthermore, SVMs are able to classify both the three categories, self sufficiently, disability risk and disability, while linear regression model separates the population only in two groups (self-sufficiency and disability) without identifying the intermediate category (disability risk) which turns out to be the most critical one. CONCLUSIONS: The development of such a model can contribute to the early detection of patients at risk of self-sufficiency loss.

Event related brain potentials in elderly patients with recently diagnosed isolated systolic hypertension.

OBJECTIVE: Isolated Systolic Hypertension (ISH) is a known risk factor for cognitive impairment, but the time of onset of neurocognitive changes relative to the onset of ISH has yet to be established. The purpose of this study was to investigate the relationship between systolic BP values and neurocognitive function in the early stages of ISH. METHODS: Twenty elderly patients with recently (< 2 years) diagnosed ISH and 10 elderly normotensive controls underwent Ambulatory Blood Pressure Monitoring (ABPM) and neurocognitive assessment, performed using the Mini Mental State Examination (MMSE), and the recording of ERPs with an odd ball acoustic paradigm. RESULTS: There were no significant differences in MMSE scores or in the P300 latency between ISH patients and controls. The N2 latency was significantly higher in ISH patients vs. controls (p<0.0001), and showed a significant association with both clinical and ambulatory systolic BP and pulse pressure values in the overall study population. CONCLUSIONS: These findings suggest the existence of early subclinical alterations in neurocognitive function in early ISH, detectable through ERPs. SIGNIFICANCE: Our findings underscore the ISH may constitute a threat to neurocognitive health in the elderly.

Promising Approaches to Optimize the Biological Properties of the Antimicrobial Peptide Esculentin-1a(1-21)NH2: Amino Acids Substitution and Conjugation to Nanoparticles.

Antimicrobial peptides (AMPs) represent an interesting class of molecules with expanding biological properties which make them a viable alternative for the development of future antibiotic drugs. However, for this purpose, some limitations must be overcome: (i) the poor biostability due to enzymatic degradation; (ii) the cytotoxicity at concentrations slightly higher than the therapeutic dosages; and (iii) the inefficient delivery to the target site at effective concentrations. Recently, a derivative of the frog skin AMP esculentin-1a, named esculentin-1a(1-21)NH2, [Esc(1-21): GIFSKLAGKKIKNLLISGLKG-NH2] has been found to have a potent activity against the Gram-negative bacterium Pseudomonas aeruginosa; a slightly weaker activity against Gram-positive bacteria and interesting immunomodulatory properties. With the aim to optimize the antimicrobial features of Esc(1-21) and to circumvent the limitations described above, two different approaches were followed: (i) substitutions by non-coded amino acids, i.e., α-aminoisobutyric acid or d-amino acids; and (ii) peptide conjugation to gold nanoparticles. In this mini-review, we summarized the structural and functional properties of the resulting Esc(1-21)-derived compounds. Overall, our data may assist researchers in the rational design and optimization of AMPs for the development of future drugs to fight the worldwide problem of antibiotic resistance.

[Resistant hypertension in the elderly.] / L'ipertensione arteriosa resistente nell'anziano.

Actually, in literature there are no epidemiologic studies on the prevalence of resistant hypertension in the elderly; however the National Health and Nutrition Examination Survey observed in the adult population prevalence of 12.8% to clinical measurement. But, especially in elderly, it's necessary exclude pseudoresistance forms due to white coat hypertension, arterial stiffness, poor patient compliance to therapy, excessive salt intake, abuse of non-steroidal ant-inflammatory drugs and the forms of secondary hypertension. Arterial hypertension, which is really resistant, it is a greater cardiovascular risk and thus the need to implement adherence to healthy lifestyle and therapy and to implement a pharmacological therapy to block the renin-angiotensin system or a dihydropyridine calcium channel, if they are not already present in the therapy and/or aldosterone antagonists. Currently experimental clinical therapeutic studies are examining such methods as renal denervation and the stimulation of the baroreflex.

Association between serum vitamin D and metabolic syndrome in middle-aged and older adults and role of supplementation therapy with vitamin D.

OBJECTIVES: To evaluate i) the correlation between vitamin D (vit. D) serum concentrations and metabolic syndrome (MetS); ii) the efficacy of 6 months supplementation therapy with vit. D. METHOD: 200 patients were enrolled. Blood analyses and anthropometric measurements were carried out. Patients with hypovitaminosis D received an oral supplement therapy. RESULTS: 81% of the sample shows vit. D levels < 30 ng/mL. Rate of MetS was significantly higher in vit. D deficiency group than in vit D insufficiency (p = 0.009) and sufficiency (p = 0.002) groups. Vit. D shows a significant negative correlation with both waist circumference (WC) (ρ - 0.202 p = 0.004) and glycaemia values (FBG) (ρ -0.185 p = 0.009). After the supplementation therapy in a group of 60 subjects a significant increase in vit. D levels (p = 0.001) and a significant reduction in WC values (p = 0.001) were observed. CONCLUSIONS: MetS, WC and FBG appeared to be associated vit. D status and it is well-known that central obesity, with the inflammatory alterations thereto correlated that determine insulin resistance, can be considered the "primum movens" for the development of MetS.

Efficacy and safety of spinning exercise in middle-aged and older adults with metabolic syndrome: randomized control trial.

BACKGROUND: Few studies have been conducted to investigate the effects of spinning exercise on cardio-vascular weal. AIM: To assess whether a 6 months spinning training, combined with proper diet, is more effective than standard training programs and diet alone in improving metabolic abnormalities in middle-aged and older adults. DESIGN: Randomized clinical trial. SETTING: Rehabilitation Unit of our Department. POPULATION: Patients with Metabolic Syndrome (MetS) according to the National Cholesterol Education Program Adult Treatment Panel III diagnostic criteria. METHODS: Patients were randomly assigned to receive treatment with diet (group A, n = 10), with diet and general gymnastics program (group B, n = 10), with diet and spinning physical training program (group C, n = 10). RESULTS: During the study period we observed a significant reduction in blood pressure (group C: systolic blood pressure p = 0.03; diastolic blood pressure p = 0.004 / group B: systolic blood pressure p = 0.001), in lipid profile (group B: plasma total cholesterol p = 0.001; triglycerides p = 0.001 / group C: plasma total cholesterol p = 0.04); in fasting blood glucose (group B: p = 0.01; group C: p = 0.008); in Homeostatic Model Assessment of Insulin Resistance (group B: p = 0.01; group C: p = 0.001); in waist circumference (group C: p = 0.005; group A: p = 0.02; group B: p = 0.04). No patients reported adverse events during follow-up. CONCLUSION: Our results confirm the effectiveness of spinning training combined with diet in the management of MetS. CLINICAL REHABILITATION IMPACT: The findings provide a preliminary evidence to support that spinning training may represent a useful and safe intervention also in middle-aged and older adults geriatric with multiple CV risk factors.

Relationship between vitamin D and body fat distribution evaluated by DXA in postmenopausal women.

OBJECTIVE: The aim of this study was to explore the relationship between 25-hydroxyvitamin D (25[OH]D) serum concentrations and body fat distribution in a sample of postmenopausal women. METHODS: We enrolled sixty-two postmenopausal women; 25(OH)D serum concentrations, serum intact parathyroid hormone, blood analyses, and anthropometric measurements were carried out. Body fat composition was evaluated by dual-energy X-ray absorptiometry. Insulin resistance was estimated by homeostatic model assessment of insulin resistance (HOMA-IR) calculation. RESULTS: Low levels of vitamin D (<30 ng/mL) were found in 77.4% of the population studied. There was a correlation (P < 0.0001) between 25(OH)D and waist circumference (r = -0.543), android fat to gynoid fat (A/G) ratio (r = -0.554), high-density lipoprotein cholesterol (r = 0.498), and HOMA-IR (r = -0.520). A/G fat ratio (B = -34.90; 95% confidence interval [-55.30, -14.1]; P = 0.019), HOMA-IR (B = -3.17; 95% confidence interval [-5.99, -0.351]; P = 0.028), and high-density lipoprotein cholesterol (B = 0.361; 95% confidence interval [0.033, 0.698]; P = 0.032), were found to be independent predictors of lower 25(OH)D by multilogistic regression analysis. Except for waist circumference, both these results were maintained when correlations were adjusted for age, onset of menopause, serum intact parathyroid hormone, and medications, and when body mass index was added as covariate. CONCLUSIONS: Vitamin D deficiency and insufficiency are common conditions. A/G ratio appeared to be associated with 25(OH)D concentrations and it is well-known that the android disposition of body fat is more closely associated with the onset of metabolic syndrome. Longitudinal studies are needed to better characterize the direction and the causal links of this association.