My Mind Project: the effects of cognitive training for elderly-the study protocol of a prospective randomized intervention study.

BACKGROUND: Cognitive decline and dementia represent a key problem for public health as they heavily impair social functioning and independent living. The development of new strategies to support recommendations for patients and their caregivers may represent an outstanding step forward. AIMS: To describe the study protocol and methods of "My Mind Project: the effect of cognitive training for elderly" (Grant No. 154/GR-2009-1584108), which investigates, by the use of a multidisciplinary approach, the effects of a comprehensive cognitive training programme on performances in aged subjects with mild-moderate Alzheimer's disease, mild cognitive impairment and normal cognitive functioning. METHODS: The study is a prospective randomized intervention for the assessment of cognitive training effects in three groups of elderly subjects with different cognitive status. A total of 321 elderly people were enrolled in Marche Region, Italy. Each subject was randomly assigned to an experimental group or to a control group. Cognitive performances and biochemical blood markers have also been analysed before cognitive training (baseline), immediately after termination (follow-up 1), after 6 months (follow-up 2) and after 2 years (follow-up 3). DISCUSSION: The results will be useful to identify some efficient programmes for the enhancement of cognitive performance in elderly with and without cognitive decline. CONCLUSION: The application of a non-pharmacological approach in the treatment of elderly with cognitive disorders could have a profound impact on National Health Service.

Management of paediatric maxillofacial fractures: conventional methods and resorbable materials.

AIM: To compare the outcomes between the use of resorbable plates and screws and the conventional methods in children with paediatric maxillofacial fractures. STUDY DESIGN: a retrospective observational study was designed reviewing the clinical records from June 2007 and June 2011. Data collected included aepidemiological data, type of treatment, outcome and satisfaction questionnaire. Descriptive statistics and bivariate analysis were performed. RESULTS: A total of 1122 children (0-17 years old) were studied. Children treated by conventional methods were 912, while children treated by resorbable materials were 210. The frequency of complications during recovery was similar and no statistically significant difference was noted. The satisfaction questionnaire revealed similar percentages of satisfaction, with a high degree of satisfaction. CONCLUSION: Our experience suggests that resorbable devices should be considered as a treatment option, which avoids the need of further surgery to remove metallic fixation, limits hospital spending and increases children's quality of life.

Use of Ceftolozane-Tazobactam in Patient with Severe Medium Chronic Purulent Otitis by XDR Pseudomonas aeruginosa.

We present a case of a male Italian patient of 66 years with a history of kidney transplantation in treatment with cyclosporine and methylprednisolone. He visited an ENT clinic and was diagnosed as chronic left purulent otitis media. He began at-home antibiotic therapy with poor benefit. On 09/13/18, he was admitted to the hospital "S. Maria "of Terni for persistence of left ear pain and complete hearing loss. Magnetic resonance imaging (MRI) of the brain showed "in correspondence of the petrous rock and the mastoid…presence of flogistic tissue." Auricular swabs and later surgical drainage of the purulent material were performed and both were positive for extensively drug-resistant (XDR) Pseudomonas aeruginosa sensitive only to colistin in absence of synergism with rifampin. The patient underwent antibiotic therapy with ceftolozane-tazobactam, a new generation cephalosporin with anti-Pseudomonas activity and a ß-lactamase inhibitor, that currently is indicated for the treatment of complicated urinary tract infections and complicated intra-abdominal infections, with complete healing. In literature, it is described a series of 12 patients with severe MDR (multidrug-resistant) Pseudomonas aeruginosa infections (6 pneumonia) who received salvage therapy with ceftolozane-tazobactam after inappropriate empirical and/or suboptimal treatment. This study included a case of a male patient of 45 years, affected by Burkitt lymphoma and severe neutropenia, who presented with otitis and mastoiditis, and isolation of Pseudomonas aeruginosa in surgical drainage of the purulent material of the ear (blood cultures were negative). He underwent antibiotic therapy with ceftolozane-tazobactam at a dosage of 3 g/8 h for 21.3 days. The patient was healed, but a late recurrence was described because of isolation of ceftolozane-tazobactam-resistant Pseudomonas after therapy. The possibility of acquiring resistance to ceftolozane-tazobactam should be considered in patients with previous exposure to beta-lactams and with poor response to these antibiotics.

Acetylcholinesterase inhibitors in Alzheimer's disease influence Zinc and Copper homeostasis.

BACKGROUND: Alzheimer's disease (AD) is the most common age-related neurodegenerative disease. An altered homeostasis of Zinc (Zn) and Copper (Cu), as well as a dysregulated expression of Zn-regulatory proteins have been previously described in AD. Acetylcholinesterase inhibitors (AChEI) are commonly used as AD treatment to improve cognitive function, but their effect on Zn homeostasis is still unexplored. OBJECTIVES: The aims of this study were to define the metal dyshomeostasis in AD patients, to investigate AChEI influence on Zn homeostasis and inflammation, and to analyze the relationship between cognitive impairment at two-year follow-up and metal concentrations, considering AChEI use. METHODS AND RESULTS: 84 Healthy Elderly (HE) and 95 AD patients were enrolled (62 AchEI user and 33 AchEI naïve). HE showed similar plasma Zn and Cu concentrations and Cu/Zn ratio in comparison to AChEI users, but significantly higher Zn level, as well as lower Cu amount and Cu/Zn ratio than AChEI naïve patients. Moreover, AChEI users had increased Zn plasma level, reduced Cu amount, Cu/Zn ratio, and IL1ß concentration and lower Zip2 lymphocytic expression vs. naïve patients. A multiple linear regression analysis showed that the MMSE score decline after two-year follow-up was reduced by AChEI therapy and was positively associated with plasma Zn decrease over time. CONCLUSION: Our data revealed that AChEI use may affect peripheral Zn and Cu homeostasis in AD patients, decrease Cu/Zn ratio demonstrating a general reduction of inflammatory status in patients under AChEI treatment. Finally, AChEI influence on circulating Zn could be implicated in the drug-related slowdown of cognitive decline.

Clinical evaluation of TRCReady M.TB for rapid automated detection of M. tuberculosis complex in respiratory samples.

SETTING: Timely diagnosis of tuberculosis (TB) is essential for effectively controlling and managing the disease. Although international guidelines recommend acid-fast bacilli staining and culture as the 'gold standard', new molecular methods are available to safely and rapidly identify positive samples. OBJECTIVE: To evaluate the performance of the newer and fully automated version of a molecular assay for rRNA amplification (TRCReady® M.TB) on 1028 respiratory samples collected from 378 patients for its possible use as a reliable screening method. Results were evaluated using culture as the reference test. RESULTS: Of four diagnostic protocols employed, best results were obtained when TRCReady M.TB was used together with microscopy on the first respiratory sample, followed by microscopy alone on a second one. The sensitivity and specificity were respectively 97% and 100%, with a turnaround time of 24 h. We propose a possible laboratory algorithm for rapid identification of patients with TB. CONCLUSIONS: TRCReady offers the advantages of full automation and avoidance of cross-contamination. As such, it should be considered as a more economical option for TB screening than other commercial assays that are currently available.

Psychosocial and biochemical interactions in aging: preliminary results from an Italian old sample of "Zincage" project.

The study of the interactions among biological factors and psychosocial conditions is a very innovative field, because data are lacking in the scientific literature. Among biological aspects, zinc is an essential element in the elderly, especially in relation to one of the proteins, such as albumin, involved in zinc transport into the cells. In this study, the aim is the assessment of the interrelationship between albumin value (used as an index of the body zinc status) and some psychosocial dimensions in elderly Italian sample recruited for ZINCAGE project, supported by the European Commission in the "Sixth Framework Programme". Some tests and questionnaires were administered to older people included in the trial: the "life-style questionnaire"; the mini mental state examination (MMSE); the geriatric depression scale (GDS-15 items). On the basis of the Senieur Protocol for gerontological studies, a sample of 291 Italian healthy old subjects has been recruited in Central Italy and divided into 3 age groups: (a) 125 subjects aged from 65 to 74 years, (b) 89 subjects aged from 75 to 84 years, (c) 77 subjects aged >or=85 years (classified like successful old people). No cognitive impairment assessed by MMSE was observed in 67.5% of the sample; 64.0% had GDS score less than 5, indicating no depression, whereas the prevalence of biological albumin deficiency (<3.5 g/dl) found in Italian old people was 21.0%. Sixty one percent of subjects with albumin deficiency displayed higher values of GDS (>or=5). These preliminary results showed an interrelationship among serum albumin value and psychosocial aspects in Italian old population, suggesting that low albumin values may be involved in impaired psychological dimensions.

Morphometric studies on synapses of the cerebellar glomerulus: the effect of centrophenoxine treatment in old rats.

Young, adult and old female Wistar rats (3, 18 and 28 months of age, respectively), were studied using electron-microscopic stereology. Synaptic parameters of the cerebellar glomerulus were calculated and compared with similar data obtained from old Wistar rats of the same breed treated with centrophenoxine (CPH; HelferginR, Promonta, Hamburg) in the form of intraperitoneal injections (100 mg/kg body weight) for 40 days. This treatment resulted in a sort of "rejuvenation" of synaptic structures. Namely, the surface density and the total length of synaptic contact zones were markedly reduced in the untreated old group, but in the treated animals these parameters returned to the values found in the young and adult animals. At the same time the numerical density of synapses remained unaltered in the treated group, while the average synaptic length displayed some further increase. The results are interpreted in terms of the age-dependent decrease in reactive synaptogenesis, suggesting that CPH stimulates the metabolism of the nervous elements persisting in old brain. The possible mechanism of CPH effect is also discussed.

Effect of chronic vitamin E deficiency on the synapses of cerebellar glomeruli in young rats.

A morphometric investigation has been carried out on the synaptic junctions in the cerebellar glomeruli of young-adult rats chronically deprived of vitamin E for 10 months and control animals of the same age. The following parameters were evaluated: the average length of the synapses (L), the numerical (NV) as well as the surface (SV) density of the synaptic contact zones. The results from these experimental groups were compared with data from young, adult and old rats. The results obtained show a significant decrease of the surface density of the synaptic contact zones in old and alpha-tocopherol deprived young-adult (11-month-old) rats as compared to younger and normally fed animals. This reduction of the synaptic contact area seems to be due to the marked decline in the number of synapses found in both cases. The average size (L) of the synaptic junctions, on the other hand, was increased in alpha-tocopherol deficient rats as compared to normally fed littermates. The significant reduction of the synaptic contact area in old and vitamin E deprived young rats supports the hypothesis that a common denominator may be responsible to explain this alteration. Because of the recognized protective role of alpha-tocopherol against free radical attacks on plasma membranes, the present findings support an involvement of membrane structural alterations in aging as well as in vitamin E deficiency.

Electron-microscopic morphometric analysis of mouse liver. I. Experimental studies on the morphogenetic significance of the thymus in nude and normal mice.

Haired, nude, thymus-grafted nude and haired thymectomized Balb/c-nu mice 2 months of age were studied by electron-microscopic stereology. Each group consisted of 5 animals and a complete morphometric analysis was carried out on their livers. In the absence of the thymus there is a slowing down of the development of the whole organism. Among the liver parameters especially the nuclear ones displayed alterations. Namely, the volume of hepatocyte nuclei increased above the normal level and this phenomenon was reversed by thymus graft into the nude mice. The hepatocyte volume also increased significantly in the surgically thymectomized group, influencing all the morphometric parameters regarding mitochondria and endoplasmic reticulum, when measured per hepatocyte. On the basis of the results obtained, one can conclude that the thymus has a regulatory role in the development of hepatocyte morphology. The findings agree with the biochemical observations demonstrating non-immunological effects of the thymus on cellular development.

Chronic dietary choline modulates synaptic plasticity in the cerebellar glomeruli of aging mice.

A morphometric investigation was carried out on ethanolic phosphotungstic acid (E-PTA) stained synaptic junctions in the cerebellar glomeruli of adult, old, old choline-deficient and old choline-supplemented mice. Numerical (Nv) and surface (Sv) density as well as average length (L) of the synapses were calculated on 100 pictures per group. A significant reduction of Nv and Sv, as well as an increase of L was found during aging. Choline deficient animals did not show any change as compared to old animals of the same age. In choline supplemented mice Nv and Sv were significantly increased and L significantly decreased, respectively, as compared to old control littermates. No difference was found between adult and choline supplemented mice. In the cerebellar glomeruli only a small fraction of fibers are cholinergic, therefore the present findings support the idea that dietary choline can influence systems other than cholinergic. The possible role of choline supplementation in the modulation of synaptic plasticity via the synthesis and/or turnover of neuronal membrane choline phospholipids, is discussed.

In vivo effects of vitamin E deficiency on the intracellular monovalent electrolyte concentrations in brain and liver of rat. An energy dispersive X-ray microanalytic study.

Vitamin E is known to play a protective role for cell membranes against free-radical attacks. Vitamin E deficiency causes a rapid macroscopic ageing of rats. On the other hand, during normal ageing, cell membranes undergo functional alterations resulting in an increased intracellular potassium concentration in brain and liver cells. Therefore, is was of interest to study whether vitamin E deficiency produces similar alterations in young rats. Female Wistar rats were fed with a vitamin E deficient diet from 1 month of age for 10 months. The parietal brain cortex and the liver were analyzed by means of a quantitative energy dispersive X-ray microanalytic method using a JEOL JSM-35C-EDAX-711-NOVA-3 system. Monovalent electrolyte contents as well as the water content of the cells were determined in 5 treated and 5 control animals. Water content was measured by analyzing the potassium content in aqueous, frozen state, and again in the dry mass of the cells. On the basis of these data, a computer program calculated the water proportions. Average values for 200 or more cells of each organ per group revealed a significant increase in the intracellular potassium content of the brain cells, whereas the sodium and chloride contents increased to a much lower extent. There was a 2.6% loss of intracellular water in the brain cells in the vitamin E deficient group. The liver monovalent ions and water content remained unchanged. The results obtained are discussed in terms of the membrane hypothesis of ageing.

Electron-microscopic morphometric analysis of mouse liver. II. Effect of ageing and thymus transplantation in old animals.

The influence of age and thymus on liver cells has been investigated by performing a complete morphometric analysis. The age-dependence was tested in three groups of mice aged 2, 12, and 24 months, while the action of the thymus was studied on 24-month-old mice grafted with neonatal thymus 30 days before the analysis was performed. Among the investigated parameters, the most considerable changes were found in the mean nuclear volume, which displayed a significant increase during ageing. The thymus was capable of reversing such an age-dependent increase when grafted into old animals. The volume of single hepatocytes also displayed an age-dependent increase which was not corrected by thymus grafting. The data presented suggest that the thymus influences the mitotic activity of the hepatocytes and further support the hypothesis that the thymus also plays an important role in non-immunological processes of ageing.

Quantitative investigation of the morphological plasticity of synaptic junctions in rat dentate gyrus during aging.

The morphological plasticity of synaptic junctions was investigated by means of quantitative stereology in the dentate gyrus supragranular layer of young (3 months), adult (12 months) and old (30 months) female Fisher 344 rats. The numerical (Nv) and surface (Sv) density and the average surface area (S) of EPTA-stained synaptic junctions were calculated on 100 EM pictures per age group. We found that Nv significantly increased between the young and adult group and decreased in old animals when compared both to 3 and 12 months of age. Sv was unchanged in young and adult rats, whereas it underwent a significant reduction in the old group. The percentage distribution of S showed that at 3 months of age the majority of the synaptic population had an average size ranging between 0.12 and 0.20 micron 2, whereas during adulthood and aging there was a shift towards smaller and larger synaptic contacts, respectively. Taking into account Nv, Sv and S all together per age group, the present findings demonstrate that the morphological aspect of synaptic plasticity is markedly influenced by time and that during aging it undergoes a serious impairment. The possible involvement in memory and learning processes of these synaptic age-related morphological adaptations and the fact that the investigated junctions are supposed to be cholinergic is discussed.

In vitro block of murine L 1210 leukemia cell growth by amiloride, an inhibitor of passive Na+ influx.

The present study was aimed to decide whether Na+ influx can be involved in regulation of murine L 1210 leukemia cell growth. Cells were cultivated in the presence of different concentrations of amiloride and cellular growth was monitored by 3H-thymidine incorporation/10(5) cells. This drug inhibited cell growth in concentrations ranging from 1 X 10(-5) to 1 X 10(-3) mmol/ml. Even short time treatments with amiloride caused irreversible alterations: the cells, although survived, lost their ability to divide. The results support the hypothesis that Na+ influx is necessary for the duplication of tumor cells.

Chronic dietary choline influences the permeability of nerve cell membranes as revealed by in vivo Rb+ uptake and release.

The effect of chronic choline supplementation on the in vivo Rb+ uptake and release of rat brain cortical cells was investigated. Adult (11 months old) and old (22 months old) controls as well as old (22 months old) female rats treated with choline (approximately 100 mg/day in the drinking water) by the age of 11 months, were used. All the animals received a daily dose of 30 mg RbCl/100 g body weight for 14 days, given intraperitoneally, half in the morning, half in the evening. After discontinuation of the RbCl treatment, the animals were killed at intervals of 2, 4, 9 and 16 days, respectively. The intracellular Rb+ and K+ contents were analyzed by energy dispersive X-ray microanalysis, whereas concentrations of these two elements were determined by atomic absorption spectrophotometry in the cerebrospinal fluid. Old animals accumulate more Rb+ than the adult ones at any time taken into account. Choline treatment was able to reduce the amount of accumulated Rb+ in the old rats. Rb+-discrimination ratios calculated on the basis of Rb+ and K+ contents of both cortical cells and cerebrospinal fluid, is higher in old rats as compared to both adult and old choline treated rats. Present findings support that chronic choline treatment is effective improving the passive membrane permeability of nerve cells for Rb+ (and K+) in the old animals.

Age-dependence of the stimulatory effect of triiodothyronine on the DNA synthesis of rat hepatocytes.

The effect of a single subcutaneous injection of triiodothyronine (T3) on DNA synthesis rate and liver growth was studied in young and old female Wistar rats. The hormonal treatment was effective in stimulating DNA synthesis, resulting in an increase of the specific liver volume as well as volume and numerical density of nuclei/100 g body wt. in young animals. In the old animals T3 injection induced a reduced and delayed synthesis of DNA, which did not affect the morphometric parameters of liver/100 g body wt.

The effect of acute and chronic centrophenoxine treatment on the synaptic plasticity of old rats.

The cerebellar glomerulus was studied by electron microscopic morphometry in female Wistar rats. Age-dependent alterations have been revealed from 3 to 28 mth of age, and the effect of centrophenoxine (CPH) was analyzed in two different patterns of administration. First, 27-mth-old rats were treated daily for 6 wk (acute treatment), and second, 18-mth-old rats were treated 3 times per week for 5 months (chronic treatment). The dose was 100 mg CPH/kg body weight, injected intraperitoneally. The surface density (SV), the numerical density (NV) and the average length (L) of the synaptic junctions were calculated from data obtained on ethanol-phosphotungstic acid stained ultrathin sections. An age-dependent reduction of SV and NV of the synaptic contact zones was found, and the L increased in the oldest animals. CPH-treatment resulted in a marked increase of SV in both types of application, whereas the other two parameters behaved differently in the two groups. The chronic treatment resulted in a significant slowing down of the decrease of NV, whereas L remained invariate. On the contrary, the acute treatment increased L but did not alter significantly NV. The results and the differences between the treatment types are discussed in terms of synaptic plasticity and are interpreted as different manifestations of the same reactive synaptogenetic process.

Age-related morphological rearrangements of synaptic junctions in the rat cerebellum and hippocampus.

A quantitative investigation has been carried out on the age-related morphological changes of the synaptic junctions in the cerebellar glomeruli and in the supragranular layer of the hippocampal dentate gyrus of young (3 months), adult (12 months) and old (28-30 months) rats. The numerical (Nv) and surface (Sv) density as well as the average length (L) of E-PTA stained synapses was calculated by means of morphometric methods. The results we obtained showed a similar trend in both these areas of the CNS. Nv significantly increased between young and adult rats and significantly decreased in the old group, when compared both to young and adult animals. Sv appeared to be unchanged comparing young and adult animals, whereas it was significantly reduced in the old group. L showed a decrease between 3 and 12 months of age and appeared to be markedly increased in the old animals when compared to adult values. From the present findings it can be inferred that number (Nv) and size (L) of the synapses are in a close inverse relationship which, through the organism's life span, aims to maintain the constancy of the surface contact area (Sv) among the dendritic network. By considering Nv, L and Sv altogether per age group, we were able to obtain a reliable measurement of the morphological aspect of synaptic plasticity through different periods of the life. With regard to aging we found that, despite the 'compensative synaptogenesis' brought about by the increased size (L) of the synaptic appositions, the reactive capacity of old nerve cells is seriously impaired.

Vitamin E deficiency alters the in vivo Rb+ discrimination of rat brain cortical cells.

The in vivo Rb+ uptake and release of rat brain cortical cells of 11-months-old rats fed with a vitamin E deficient diet was investigated. The animals were treated with a daily dose of 30 mg RbCl/100 g body weight for 14 days. After discontinuation of the RbCl treatment the animals were killed at intervals of 2, 4, 9 and 15 days, respectively. The intracellular Rb+ and K+ contents were analyzed by energy dispersive X-ray microanalysis, whereas concentrations of these two ions were determined by atomic absorbtion spectrophotometry in the serum and cerebrospinal fluid. Vitamin E deficient rats accumulate more Rb+ than age-matched normally fed animals at any time taken into account. Rb+-discrimination ratios calculated on the basis of Rb+ and K+ contents of both, cortical cell cytoplasm and cerebrospinal fluid, are higher in vitamin E deficient rats than in the controls (+20%), which supports the view that the enhanced membrane lipid peroxidation induced by vitamin E deficiency impairs the passive membrane permeability for Rb+ (and K+).

Dietary habits and ageing in a sample of Italian older people.

OBJECTIVES: To analyse dietary habits and explore the role of socioeconomic status in a sample of elderly Italians. STUDY DESIGN: Observational. PARTICIPANTS AND SETTING: 306 elderly subjects aged 65 and over living in the Marche Region (Italy). MEASUREMENTS: Assessment of dietary habits and life-style characteristics using a "Life-style questionnaire". Nutritional data collected by means of a 53-item "Frequency food questionnaire". RESULTS: The study revealed differences in dietary patterns and food consumption. Age was negatively related to all food categories. Some socio-economic characteristics (level of education and economic status) were correlated with consumption of many foods, such ad Fish, Red Meat and Diary products. Between-the-sexes differences were also documented. CONCLUSION: Our findings showed that the nutritional and dietary habits varied greatly within the sample investigated. The mapping of these dietary and nutritional patterns may be of value for future research in elderly populations, particularly those with low educational status and poor economic means. Conclusively, greater promotion of healthy dietary habits should be targeted towards elderly populations.