Hyperlysinemia, an ultrarare inborn error of metabolism: Review and update.

Familial hyperlysinemia is a rare autosomal recessive disorder due to defects of the AASS (α-aminoadipate δ-semialdehyde synthase) gene, which encodes for a bifunctional enzyme. Two types of hyperlysinemia have been identified namely type 1, due to the deficit of the alfa-ketoglutarate activity, and type 2, due to the deficit of the saccharopine dehydrogenase activity. METHODS: To better characterize the phenotypic spectrum of familial hyperlysinemia type 1, we conducted a systematic review of cases in the literature following PRISMA guidelines. We selected 16 articles describing 23 patients with hyperlysinemia type 1, twelve of whom with homozygous or compound heterozygous mutations in AASS gene. We also included a novel patient with a homozygous c.799C>T; p.(Arg267Cys) mutation in AASS gene. We collected genetic, clinical, brain imaging and electroencephalogram (EEG) features when available. RESULTS: The phenotype of this disease is heterogeneous, ranging from more severe forms with spastic tetraparesis, intellectual disability and epilepsy and mild-moderate forms with only intellectual disability or behavioural problem and/or epilepsy to normal clinical conditions. Only our patient has neuropathy unrelated to infectious event. CONCLUSIONS: We described the heterogeneous phenotypic spectrum of familial hyperlysinemia type 1 and we identified a new symptom, axonal neuropathy, never before described in this condition.

Neuroinflammation and status epilepticus: a narrative review unraveling a complex interplay.

Status epilepticus (SE) is a medical emergency resulting from the failure of the mechanisms involved in seizure termination or from the initiation of pathways involved in abnormally prolonged seizures, potentially leading to long-term consequences, including neuronal death and impaired neuronal networks. It can eventually evolve to refractory status epilepticus (RSE), in which the administration of a benzodiazepine and another anti-seizure medications (ASMs) had been ineffective, and super-refractory status epilepticus (SRSE), which persists for more than 24 h after the administration of general anesthesia. Objective of the present review is to highlight the link between inflammation and SE. Several preclinical and clinical studies have shown that neuroinflammation can contribute to seizure onset and recurrence by increasing neuronal excitability. Notably, microglia and astrocytes can promote neuroinflammation and seizure susceptibility. In fact, inflammatory mediators released by glial cells might enhance neuronal excitation and cause drug resistance and seizure recurrence. Understanding the molecular mechanisms of neuroinflammation could be crucial for improving SE treatment, wich is currently mainly addressed with benzodiazepines and eventually phenytoin, valproic acid, or levetiracetam. IL-1ß signal blockade with Anakinra has shown promising results in avoiding seizure recurrence and generalization in inflammatory refractory epilepsy. Inhibiting the IL-1ß converting enzyme (ICE)/caspase-1 is also being investigated as a possible target for managing drug-resistant epilepsies. Targeting the ATP-P2X7R signal, which activates the NLRP3 inflammasome and triggers inflammatory molecule release, is another avenue of research. Interestingly, astaxanthin has shown promise in attenuating neuroinflammation in SE by inhibiting the ATP-P2X7R signal. Furthermore, IL-6 blockade using tocilizumab has been effective in RSE and in reducing seizures in patients with febrile infection-related epilepsy syndrome (FIRES). Other potential approaches include the ketogenic diet, which may modulate pro-inflammatory cytokine production, and the use of cannabidiol (CBD), which has demonstrated antiepileptic, neuroprotective, and anti-inflammatory properties, and targeting HMGB1-TLR4 axis. Clinical experience with anti-cytokine agents such as Anakinra and Tocilizumab in SE is currently limited, although promising. Nonetheless, Etanercept and Rituximab have shown efficacy only in specific etiologies of SE, such as autoimmune encephalitis. Overall, targeting inflammatory pathways and cytokines shows potential as an innovative therapeutic option for drug-resistant epilepsies and SE, providing the chance of directly addressing its underlying mechanisms, rather than solely focusing on symptom control.

Design and performance simulation studies of a breast PET insert integrable into a clinical whole-body PET/MRI scanner.

Objective. Three different breast positron emission tomography (PET) insert geometries are proposed for integration into an existing magnetic resonance imaging (MRI) breast coil (Breast Biopsy Coil, NORAS MRI products) to be used inside a whole-body PET/MRI scanner (Biograph mMR, Siemens Healthineers) to enhance the sensitivity and spatial resolution of imaging inside the breast.Approach. Monte Carlo simulations were performed to predict and compare the performance characteristics of the three geometries in terms of the sensitivity, spatial resolution, scatter fraction, and noise equivalent count rate (NECR). In addition, the background single count rate due to organ uptake in a clinical scan scenario was predicted using a realistic anthropomorphic phantom.Main results. In the center of the field of view (cFOV), absolute sensitivities of 3.1%, 2.7%, and 2.2% were found for Geometry A (detectors arranged in two cylinders), Geometry B (detectors arranged in two partial cylinders), and Geometry C (detectors arranged in two half cylinders combined with two plates), respectively. The full width at half maximum spatial resolution was determined to be 1.7 mm (Geometry A), 1.8 mm (Geometry B) and 2.0 mm (Geometry C) at 5 mm from the cFOV. Designs with multiple scintillation-crystal layers capable of determining the depth of interaction (DOI) strongly improved the spatial resolution at larger distances from the transaxial cFOV. The system scatter fractions were 33.1% (Geometries A and B) and 32.3% (Geometry C). The peak NECRs occurred at source activities of 300 MBq (Geometry A), 310 MBq (Geometry B) and 340 MBq (Geometry C). The background single-event count rates were 17.1 × 106cps (Geometry A), 15.3 × 106cps (Geometry B) and 14.8 × 106cps (Geometry C). Geometry A in the three-layer DOI variant exhibited the best PET performance characteristics but could be challenging to manufacture. Geometry C had the lowest impact on the spatial resolution and the lowest sensitivity among the investigated geometries.Significance. Geometry B in the two-layer DOI variant represented an effective compromise between the PET performance and manufacturing difficulty and was found to be a promising candidate for the future breast PET insert.

Multi-center observational study on occurrence and related clinical factors of neurogenic heterotopic ossification in patients with disorders of consciousness.

Aims: to assess occurrence and clinical correlates of neurogenic heterotopic ossifications (NHO) in patients with prolonged disorder of consciousness (DoC).Design: multi-center cross-sectional observational study.Setting: 23 intensive neurorehabilitation units.Subjects: 287 patients with prolonged disorder of consciousness (DoC; 150 in vegetative state, VS, and 128 in minimally conscious state, MCS) of different etiology (vascular = 125, traumatic = 83, anoxic = 56, others = 14).Main Measures: clinical evidence of NHO confirmed by standard radiological and/or sonographic evaluation; Coma Recovery Scale-Revised; Disability Rating Scale (DRS); Early Rehabilitation Barthel Index; presence of ventilator support, spasticity, bone fractures and paroxysmal sympathetic hyperactivity.Results: 31 patients (11.2%) presented NHO. Univariate analyses showed that NHO was associated with VS diagnosis, traumatic etiology, high DRS category and total score, and high occurrence of limb spasticity and bone fractures. A cluster-corrected binary logistic regression model (excluding spasticity available in a subset of patients) showed that only lower DRS total score and presence of bone fractures were independently associated with NHO.Conclusions: NHO are relatively frequent in patients with DoC, and are independently associated with functional disability, bone fractures and spasticity. These findings contribute to identifying patients with DoC prone to develop NHO and requiring special interventions to improve functional recovery.

Post-traumatic stress, anxiety, and depressive symptoms in caregivers of children tested for COVID-19 in the acute phase of the Italian outbreak.

BACKGROUND: The recent COVID-19 pandemic pointed out new burdens for researchers on mental health and that evidence-based (EB) studies on vulnerable populations are timely needed. The present paper aims at analysing the impact of suspicious of SARS-COV-2 infection in a cohort of parents presented at 3 major hospitals (spread between north and center of Italy) during the Italian COVID-19 pandemic phase 1. METHODS: Participants of the present cross-sectional, multicenter study were parental couples of children suspected to have COVID-19 who underwent testing with nasopharyngeal swabbing. All subjects were assessed by means of the: Impact of Event Scale-Revised (IES-R), Generalized Anxiety Disorder 7-Item (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) in order to evaluate Post-traumatic stress (PTSS), anxiety, and depressive symptoms, respectively. OUTCOMES: Results evidenced that parents whose children tested positive for COVID-19 were more prone to developing PTSS, anxiety and depressive symptoms. The same results emerged for parents who had quarantined as opposed to those who had not. Moreover, patients who suffered economic damage showed a higher prevalence of anxiety and depressive symptoms, whereas PTSS was more common among unemployed subjects and among mothers. INTERPRETATION: This study identified a mental health strain represented by parenting a child who tested positive for SARS-CoV-2 infection. Further EB research is needed to develop evidence-driven strategies to reduce adverse psychological impacts and related psychiatric symptoms in caregivers of COVID-19 infected children during the next phases of the pandemic.

Multi-center study on overall clinical complexity of patients with prolonged disorders of consciousness of different etiologies.

Aim: to assess overall clinical complexity of patients with acquired disorders of consciousness (DoC) in vegetative state/unresponsive wakefulness syndrome (VS/UWS) vs. minimally conscious state- MCS) and in different etiologies..Design: Multi-center cross-sectional observational study.Setting: 23 intensive neurorehabilitation units.Subjects: 264 patients with DoC in the post-acute phase: VS/UWS = 141, and MCS = 123 due to vascular (n = 125), traumatic (n = 83) or anoxic (n = 56) brain injury.Main Measures: Coma Recovery Scale-Revised, and Disability Rating Scale (DRS); presence of medical devices (e.g., for eating or breathing); occurrence and severity of medical complications.Results: patients in DoC, and particularly those in VS/UWS, showed severe overall clinical complexity. Anoxic patients had higher overall clinical complexity, lower level of responsiveness/consciousness, higher functional disability, and higher needs of medical devices. Vascular patients had worse premorbid clinical comorbidities. The two etiologies showed a comparable rate of MC, higher than that observed in traumatic etiology.Conclusion: overall clinical complexity is significantly higher in VS/UWS than in MCS, and in non-traumatic vs. traumatic etiology. These findings could explain the worse clinical evolution reported in anoxic and vascular etiologies and in VS/UWS patients and contribute to plan patient-tailored care and rehabilitation programmes.

Trait Anxiety Mediated by Amygdala Serotonin Transporter in the Common Marmoset.

High trait anxiety is associated with altered activity across emotion regulation circuitry and a higher risk of developing anxiety disorders and depression. This circuitry is extensively modulated by serotonin. Here, to understand why some people may be more vulnerable to developing affective disorders, we investigated whether serotonin-related gene expression across the brain's emotion regulation circuitry may underlie individual differences in trait anxiety using the common marmoset (Callithrix jacchus, mixed sexes) as a model. First, we assessed the association of region-specific expression of the serotonin transporter (SLC6A4) and serotonin receptor (HTR1A, HTR2A, HTR2C) genes with anxiety-like behavior; and second, we investigated their causal role in two key features of the high trait anxious phenotype: high responsivity to anxiety-provoking stimuli and an exaggerated conditioned threat response. While the expression of the serotonin receptors did not show a significant relationship with anxiety-like behavior in any of the targeted brain regions, serotonin transporter expression, specifically within the right ventrolateral prefrontal cortex (vlPFC) and most strongly in the right amygdala, was associated positively with anxiety-like behavior. The causal relationship between amygdala serotonin levels and an animal's sensitivity to threat was confirmed via direct amygdala infusions of a selective serotonin reuptake inhibitor (SSRI), citalopram. Both anxiety-like behaviors, and conditioned threat-induced responses were reduced by the blockade of serotonin reuptake in the amygdala. Together, these findings provide evidence that high amygdala serotonin transporter expression contributes to the high trait anxious phenotype and suggest that reduction of threat reactivity by SSRIs may be mediated by their actions in the amygdala.SIGNIFICANCE STATEMENT Findings here contribute to our understanding of how the serotonin system underlies an individual's expression of threat-elicited negative emotions such as anxiety and fear within nonhuman primates. Exploration of serotonergic gene expression across brain regions implicated in emotion regulation revealed that serotonin transporter gene expression in the ventrolateral prefrontal cortex (vlPFC) and most strongly in the amygdala, but none of the serotonin receptor genes, were predictive of interindividual differences in anxiety-like behavior. Targeting of amygdala serotonin reuptake with selective serotonin reuptake inhibitors (SSRIs) confirmed the causal relationship between amygdala serotonin transporter and an animal's sensitivity to threat by reversing expression of two key features of the high trait-like anxiety phenotype: high responsivity to anxiety-provoking uncertain threat and responsivity to certain conditioned threat.

Chronic inflammation: A key role in degeneration of bicuspid aortic valve.

INTRODUCTION: Bicuspid aortic valve (BAV) is the most common congenital valvular heart defect resulting from abnormal aortic cusp formation during heart development, where two of the three normal and equal sized cusps fuse into a single large cusp resulting in a two cusps aortic valve. Over the past years, much interest has been given in understanding the pathogenesis of BAV and its complications. In this review, we focused on the role of inflammation, involved in the degeneration of BAV and the development of its complications. ROLE OF INFLAMMATION: From a pathophysiological point of view, BAV may rapidly progress into aortic stenosis (AS) and is related to aortopathy. Several histopathologic studies have demonstrated that the development and progression of alterations in bicuspid aortic valve are related to an active process that includes: oxidative stress, shear stress, endothelial dysfunction, disorganized tissue architecture, inflammatory cells and cytokines. These factors are closely related one to each other, constituting the basis of the structural and functional alterations of the BAV. CONCLUSION: Chronic inflammation plays a key role in the degeneration of BAV. Severe aortic stenosis in bicuspid aortic valves is associated with a more aggressive inflammatory process, increased inflammatory cells infiltration and neovascularization when compared to tricuspid AS. These findings might help to explain the more frequent onset and rapid progression of AS and the heavy aortic valve calcification seen in patients with BAV.

Trajectories and Milestones of Cortical and Subcortical Development of the Marmoset Brain From Infancy to Adulthood.

With increasing attention on the developmental causes of neuropsychiatric disorders, appropriate animal models are crucial to identifying causes and assessing potential interventions. The common marmoset is an ideal model as it has sophisticated social/emotional behavior, reaching adulthood within 2 years of birth. Magnetic resonance imaging was used in an accelerated longitudinal cohort (n = 41; aged 3-27 months; scanned 2-7 times over 2 years). Splines were used to model nonlinear trajectories of grey matter volume development in 53 cortical areas and 16 subcortical nuclei. Generally, volumes increased before puberty, peaked, and declined into adulthood. We identified 3 milestones of grey matter development: I) age at peak volume; II) age at onset of volume decline; and III) age at maximum rate of volume decline. These milestones differentiated growth trajectories of primary sensory/motor cortical areas from those of association cortex but also revealed distinct trajectories between association cortices. Cluster analysis of trajectories showed that prefrontal cortex was the most heterogenous of association regions, comprising areas with distinct milestones and developmental trajectories. These results highlight the potential of high-field structural MRI to define the dynamics of primate brain development and importantly to identify when specific prefrontal circuits may be most vulnerable to environmental impact.

T-pattern detection and analysis for the discovery of hidden features of behaviour.

BACKGROUND: The behaviour of all living beings consists of hidden patterns in time; consequently, its nature and its underlying dynamics are intrinsically difficult to be perceived and detected by the unaided observer. METHOD: Such a scientific challenge calls for improved means of detection, data handling and analysis. By using a powerful and versatile technique known as T-pattern detection and analysis (TPA) it is possible to unveil hidden relationships among the behavioural events in time. RESULTS: TPA is demonstrated to be a solid and versatile tool to study the deep structure of behaviour in different experimental contexts, both in human and non human subjects. CONCLUSION: This review deepens and extends contents recently published by adding new concepts and examples concerning the applications of TPA in the study of behaviour both in human and non-human subjects.

Temporal patterns of rat behaviour in the central platform of the elevated plus maze. Comparative analysis between male subjects of strains with different basal levels of emotionality.

We have analyzed the temporal patterns of behaviour of male rats of the Wistar and DA/Han strains on the central platform of the elevated plus maze. The ethogram encompassed 10 behavioural elements. Durations, frequencies and latencies showed quantitative differences as to walking and sniffing activities. Wistar rats displayed significantly lower latency and significantly higher durations and frequencies of walking activities. DA/Han rats showed a significant increase of sniffing duration. In addition, DA/Han rats showed a significantly higher amount of time spent in the central platform. Multivariate T-pattern analysis revealed differences in the temporal organization of behaviour of the two rat strains. DA/Han rats showed (a) higher behavioural complexity and variability and (b) a significantly higher mean number of T-patterns than Wistar rats. Taken together, T-pattern analysis of behaviour in the centre of the elevated plus maze can noticeably improve the detection of subtle features of anxiety related behaviour. We suggest that T-pattern analysis could be used as sensitive tool to test the action of anxiolytic and anxiogenic manipulations.

Multivariate temporal pattern analysis applied to the study of rat behavior in the elevated plus maze: methodological and conceptual highlights.

Aim of this article is to illustrate the application of a multivariate approach known as t-pattern analysis in the study of rat behavior in elevated plus maze. By means of this multivariate approach, significant relationships among behavioral events in the course of time can be described. Both quantitative and t-pattern analyses were utilized to analyze data obtained from fifteen male Wistar rats following a trial 1-trial 2 protocol. In trial 2, in comparison with the initial exposure, mean occurrences of behavioral elements performed in protected zones of the maze showed a significant increase counterbalanced by a significant decrease of mean occurrences of behavioral elements in unprotected zones. Multivariate t-pattern analysis, in trial 1, revealed the presence of 134 t-patterns of different composition. In trial 2, the temporal structure of behavior become more simple, being present only 32 different t-patterns. Behavioral strings and stripes (i.e. graphical representation of each t-pattern onset) of all t-patterns were presented both for trial 1 and trial 2 as well. Finally, percent distributions in the three zones of the maze show a clear-cut increase of t-patterns in closed arm and a significant reduction in the remaining zones. Results show that previous experience deeply modifies the temporal structure of rat behavior in the elevated plus maze. In addition, this article, by highlighting several conceptual, methodological and illustrative aspects on the utilization of t-pattern analysis, could represent a useful background to employ such a refined approach in the study of rat behavior in elevated plus maze.

Significant divergences between the temporal structure of the behavior in Wistar and in the spontaneously more anxious DA/Han strain of rats tested in elevated plus maze.

The aim of present research is to study the temporal structure of the behavior in two strains of rats with different basal level of emotionality. To this purpose, the temporal profile of the behavior in Wistar rat and in the spontaneously more anxious DA/Han strain was analyzed in the Elevated Plus Maze. Both quantitative and multivariate t-pattern analyses were carried out. In comparison with Wistar, DA/Han subjects showed a significant reduction of the permanence in open arm and a significant increase of the time spent in the central platform of the maze. Mean frequencies of each behavioral element showed significant modifications both in open and in closed arm. Multivariate t-pattern analyses demonstrated a very different temporal profile of behavior in the two strains: Wistar rats presented 197 t-patterns of different composition, whereas DA/Han rats only 26; as to the mean number of t-patterns, Wistar presented a value of 698.90, whereas DA/Han only 92.80. Similar clear-cut differences were detected for the mean number of t-patterns in the two arms and for the time course of such t-patterns. Present study has evidenced that the temporal organization of the bahavior in Elevated Plus Maze is differently structured in two strains of rats with different basal level of emotionality.

Temporal structure of the rat's behavior in elevated plus maze test.

Aim of the research was to evaluate, by means of quantitative and multivariate temporal pattern analyses, the behavior of Wistar rat in elevated plus maze (EPM) test. On the basis of an ethogram encompassing 24 behavioral elements, quantitative results showed that 130.14 ± 8.01 behavioral elements occurred in central platform and in closed arms (protected zones), whereas 88.62 ± 6.04 occurred in open arms (unprotected zones). Percent distribution was characterized by a prevalence of sniffing, walking and vertical exploration. Analysis of minute-by-minute duration evidenced a decrease for time spent in open arms and central platform and an increase for time spent in closed arms. As to multivariate t-pattern analysis, 126 different temporal patterns were detected. Behavioral stripes, summarizing distribution of such t-patterns along time, showed that several t-patterns were not homogeneously distributed along the test observational period: t-patterns encompassing behavioral events occurring prevalently in central platform-open arms were observed during the first minutes, whereas t-patterns structured on the basis of events occurring mainly in central platform-closed arms were detected during the last minutes. Therefore, during the observation in elevated plus maze, rat's behavior undergoes significant rearrangements of its temporal features. Present research demonstrates, for the first time, the existence of complex and significantly timed behavioral sequences in the activity of Wistar rats tested in elevated plus maze. Application of t-pattern analysis can provide useful tools to characterize the behavioral dynamics of anxiety-related rodent behavior and differentiate the effect of various anxioselective substances.

Adjuvant radiotherapy on older and oldest elderly rectal cancer patients.

The purpose of this study was to evaluate the impact of radiotherapy in terms of feasibility and activity in the patients aged > or = 75 with advanced rectal cancer. From January 2002 to December 2006, 41 consecutive patients (27 men and 14 women) aged > or = 75 received radiotherapy for local advanced rectal cancer, 9 in a pre-operative and 22 in a post-operative setting. Sixteen patients received concomitant chemotherapy. Variables considered were age, co-morbidities, evaluated according to the adult co-morbidity evaluation index (ACE-27), surgery versus no surgery, and timing of radiotherapy. The median age was 80.5 years (range 75-90). A total of 19.5% of the patients had no co-morbidity, 48.8% mild, 17.1% moderate, and 14.6% had severe co-morbidities. Thirty-nine subjects (95.1%) were submitted to surgery. All patients but one completed the planned radiation schedule. At a median follow-up of 23.1 months, the 2- and 4-year overall survival rates were 71.8% and 61.6%, respectively. There was a better survival for patients with no or mild co-morbidities (p=0.002) and a good performance status (p=0.003). The cancer-free survival at 2 and 4 years was 78.9% and 26.4%, respectively. No difference in acute and late toxicity rates was found between patients with different ACE-27 indexes. We conclude that compliance with radiotherapy is good and rate of toxicity is acceptable in elderly patients. Patients with no or mild co-morbidities have a significantly better survival. Increasing severity of co-morbidity may sufficiently shorten remaining life expectancy to cancel gains with adjuvant radiotherapy. Further prospective trials are needed to confirm these results.

[HPV infection: comparison between morphological studies and molecular biology]. / L'infezione da HPV: confronto diagnostico tra indagini morfologiche e biologia molecolare.

Human Papilloma Virus plays an essential role in the development of cervical cancer. We investigated the global prevalence of Human Papilloma Virus infection in a population of 699 women recruited at the Ospedali Riuniti in Foggia for gynaecological controls from September 2005 to March 2007, and compared with a group of 90 women, selected on clinical aspects for Human Papilloma Virus features. The observed prevalence was 27.4%, which is higher that that reported in the literature. In the study group, the most frequent viral type was 16, while type 18 was considerably less frequent compared with other emergent viral types (39, 52, 56, 58, 59). The high prevalence of Human Papilloma Virus-DNA in women with negative cytology or inflammatory changes raises doubts about the utility of the Human Papilloma Virus-DNA method as a primary screening test because of the low cost/benefit ratio. The absence of uniform and standardised reports does not allow objective comparison between different methods of analysis (cytology, colposcopy and molecular biology), pointing out the need for a unique centre for collection and data analysis.

Cardiovascular aging and psychometric performances: correlations in a group of ultraseptagenarian elderly.

Aging of the Italian population resulted in a net increase of the cardiovascular pathologies, and the correlated disabilities. In addition, the cardiovascular diseases represent actually in Italy the most frequent cause of death. With advancing age, both the heart and the blood vessels undergo numerous morphological and functional modifications, which are reducing the functional reserves of these organs. The present study looked for correlation between the cardiac functionality and the cognitive, as well as affective functions. Furthermore, we evaluated the functional variations of the autonomy and autosufficiency of the same patients. We had 171 enrolled subjects (108 women and 63 men), all above the age of 70 years. Based on the classification of the New York Heart Association (NYHA), 85 of these patients (35 men and 50 women) had a II class (Group A), and 86 of them (28 men and 58 women) a III NYHA class of heart function (Group B). We included only patients who did not have any cerebrovascular event yet, and were not bed-ridden. The psychometric performance has been evaluated by using the mini-mental state examination (MMSE), the geriatric depression scale (GDS), the activities of daily living (ADL) and the instrumental activities of daily living (IADL) scales. Cardiac functions have been measured by Doppler echocardiography, in M-mode. The Group A (of mean age 71 +/- 3 years) displayed ventricular ejection fraction (VEF) values in average of 43 +/- 4%, MMSE scores 27 +/- 2; GDS scores 14 +/- 3; IADL 6 +/- 1, and ADL = 6, i.e., maintained a complete autosufficiency. The Group B (mean age 74 +/- 4 years) displayed VEF values in average of 26 +/- 3%, MMSE scores 23 +/- 4; GDS scores 22 +/- 3; IADL 4 +/- 2, and ADL = 4 +/- 1, i.e., had a reduced autosufficiency. These results confirm that also the heart pays a toll for aging: the myocardial contractility becomes significantly altered, meaning the loss of cardiac functions itself. These morpho-functional heart alterations are accompanied by decreased psychometric performances during aging, with consequent reductions of cognitivity, affectivity, autosufficiency and autonomy, involving a complex decrease of the quality of life.

Antiresorption therapy and reduction in fracture susceptibility in the osteoporotic elderly patient: open study.

The identification of risk factors for osteoporosis has been an essential step towards the understanding of the onset of the disease as well as of the osteoporosis-related fractures due to bone fragility. The present study has been aimed at assessing whether a correlation may exist between the increment in bone mass, consequent to an antiresorption therapy, and the reduction in the incidence of fractures. Moreover, the possibility that such a reduction might result from the action of other factors, such as the changes in bone microstructure, has been investigated. A total of 2,000 osteoporotic women (mean age: 68 +/- 9 years) were enrolled in the study and divided at random into 4 treatment groups. Each group received one of the following treatments: Alendronate 10 mg/daily (1,000 patients), Clodronate 100 mg/weekly i.m. (800 patients), Risedronate 5 mg/dailt (100 patients), and Raloxifene 60 mg/daily (100 patients). Clinical evaluation was based on bone mineral density (BMD) assay on lumbar vertebrae (L1-L4) by means of a DEXA (Lunar DPX) mineralometer, as well as on the incidence of fractures following both 12- and 24-month treatment periods. The results showed an overlapping pattern in patients treated with Alendronate or Risedronate, namely a significant increment in BMD after a 24-month treatment period, whereas such an increment in BMD was less evident in patients receiving either Clodronate or Risedronate after a 24-month treatment period. In addition, a total of 18 osteoporosis-related fractures were observed during the entire study period; 10 out of 18 fractures occurred in the Alendronate treated group, whereas the remaining 8 fractures were observed in the Clodronate treated group. Fourteen fractures were detected in patients over 80-year old, whereas the remaining 4 occurred in patients aged from 70 to 79 years and appeared to be independent of both the T-score assigned and the BMD increment obtained as a result of the therapy. Such findings suggest that the plain monitoring of BMD appears not to be adequate to anticipate clearly the danger of the probable onset of additional fractures, while the higher incidence of fractures in patients over 80-year old evidences that "old age" has to be considered the most serious risk factor for osteoporosis, since it is also the real responsible factor for changes taking place in bone microstructure.

Oxidative stress and aging: studies on an East-Sicilian, ultraoctagenarian population living in institutes or at home.

The role of the free radicals in aging has been in center of research for long years. It is assumed that with advancing age, damaging effects of oxygen free radicals might be accumulated in the organisms on all components, especially on the DNA and the mitochondria. In addition, because of the decreased efficiency of the antioxidant systems, the oxidative mechanisms prevail in numerous age-dependent diseases, such as the arterio -sclerosis, Parkinson and Alzheimer diseases. The present study was aimed at revealing an eventual correlation between the free radical levels and the psychophysical health state of an ultraoctagenarian East-Sicilian population living in institutes or at home. Our study population consisted of 125 ultraoctagenarian subjects, 62 of them were institutionalized and 63 living outside the institutes. The free radical effects were measured by using the free radical analytical system (FRAS) assessing the derivatives of reactive oxygen metabolites(D-ROMs). The results are expressed in units of Caratelli (U-CARR). The psycho-physical state of the subjects was estimated by means of the mini mental state examination(MMSE), geriatric depression scale (GDS), activities of daily living (ADL) and instrumental activities of daily living (IADL). The nutritional state and the physical activity of the subjects were evaluated through the mini nutritional assessment (MNA) and the physical performance test (PPT). All studied parameters underwent a correlation analysis of Pearson. Statistically significant negative correlation was found between the free radical levels and the cognitive performance (p < 0.0001), as well as the levels of autonomy and autosufficiency,the physical activity in the total population (p < 0.01). These correlations were even more expressed in the institutionalized subjects. Statistically significant positive correlation seems to exist between the free radical levels and the nutritional status (p < 0.001). These studies revealed some important differences between the institutionalized and noninstitutionalized population. The levels of oxygen free radicals were higher in the former group, indicating a stronger oxidative stress, influencing the psychophysical state of the elderly subjects. This may have negative consequences on the quality and duration of the life. It is difficult to define the exact role of free radicals in the determination of aging pattern,but they may be considered without any doubt as true "markers" of an enhanced oxidative stress, accompanying a non-successful aging process.

The leptin, a new hormone of adipose tissue: clinical findings and perspectives in geriatrics.

Obesity has gained a great importance during the last decades, and this fact stimulated numerous studies regarding the genetic causes of this disease. A recently discovered new molecule, called leptin, raised a wide interest. It is a product of the adipocytes, it exerts inhibitory effects on the center of appetite and increases the energy expenditure of the organism. The present study evaluated blood leptin levels in 57 elderly subjects and searched for eventual correlations between this parameter and the age, the body mass index (BMI), the fat body mass (fat%), the waist (W) and hip (H) circumference, as well as the ratio (R) of these latter two values (WHR). Blood leptin levels do not correlate with age, body height and the WHR, but display significant positive correlations with the body weight, the BMI, the fat%, the W, H and WHR. A deeper knowledge on leptin and the correlations of this hormone with other body parameters might be helpful in a better understanding of several pathogenetic mechanisms related to aging and involved in a deterioration of the quality of life in elderly, like multiple atherosclerotic and metabolic diseases (diabetes, dyslipidemias).