Effect of two different parts of CGF on post-extractive alveolar ridge preservation: a preliminary histomorphometric analysis in a Split-Mouth design.

Tooth extraction produces alveolar bone resorption and soft tissue remodelling, so identification of adequate technique for alveolar ridge preservation after tooth extraction is fundamental for all specific cases. Among the several biomaterials, CGF can represent an ideal alternative considering its and its mechanical and biological properties. In this preliminary study we compared the effectiveness of the use of two different parts of CGF (WP-White Part and BC-Buffy Coat) versus natural healing (CTR) by a split-mouth randomized clinical design. Four healthy patients who needed extraction of three teeth were selected. Post-extractive alveolar sockets were filled randomly with CGF-WP, CGF-BC or nothing for CTR. After 60 days, before implant placement, a biopsy for each alveola was obtained for quantitative histomorphometric analysis. The data obtained showed that the use of CGF-WP could achieve good regenerative results, supporting the use of this part for the preservation of the post-extractive alveolar socket.

Spatial entanglement of bosons in optical lattices.

Entanglement is a fundamental resource for quantum information processing, occurring naturally in many-body systems at low temperatures. The presence of entanglement and, in particular, its scaling with the size of system partitions underlies the complexity of quantum many-body states. The quantitative estimation of entanglement in many-body systems represents a major challenge, as it requires either full-state tomography, scaling exponentially in the system size, or the assumption of unverified system characteristics such as its Hamiltonian or temperature. Here we adopt recently developed approaches for the determination of rigorous lower entanglement bounds from readily accessible measurements and apply them in an experiment of ultracold interacting bosons in optical lattices of ~10(5) sites. We then study the behaviour of spatial entanglement between the sites when crossing the superfluid-Mott insulator transition and when varying temperature. This constitutes the first rigorous experimental large-scale entanglement quantification in a scalable quantum simulator.

Accuracy of hippocampal network activity is disrupted by neuroinflammation: rescue by memantine.

Understanding how the hippocampus processes episodic memory information during neuropathological conditions is important for treatment and prevention applications. Previous data have shown that during chronic neuroinflammation the expression of the plasticity related behaviourally-induced immediate early gene Arc is altered within the CA3 and the dentate gyrus; both of these hippocampal regions show a pronounced increase in activated microglia. Low doses of memantine, a low to moderate affinity open channel uncompetitive N-Methyl-d-aspartate receptor antagonist, reduce neuroinflammation, return Arc expression to control levels and attenuate cognitive deficits induced by lipopolysaccharide. Here we investigate whether neuroinflammation affects the accuracy of information processing in the CA3 and CA1 hippocampal regions and if this is modified by memantine treatment. Using the immediate early gene-based brain-imaging method called cellular analysis of temporal activity by fluorescence in situ hybridization, it is possible to detect primary transcripts at the genomic alleles; this provides exceptional temporal and cellular resolution and facilitates the mapping of neuronal activity. Here, we use this method to compare the neuronal populations activated by two separate experiences in CA1 and CA3 and evaluate the accuracy of information processing during chronic neuroinflammation. Our results show that the CA3 pyramidal neuron activity is not stable between two exposures to the same environment context or two different contexts. CA1 networks, however, do not differ from control conditions. These data suggest that during chronic neuroinflammation, the CA3 networks show a disrupted ability to encode spatial information, and that CA1 neurons can work independently of CA3. Importantly, memantine treatment is able to partially normalize information processing in the hippocampus, suggesting that when given early during the development of the pathology memantine confers neuronal and cognitive protection while indirectly prevents pathological microglial activation.

Anti-inflammatory property of the cannabinoid agonist WIN-55212-2 in a rodent model of chronic brain inflammation.

Cannabinoid receptors (CBr) stimulation induces numerous central and peripheral effects. A growing interest in the beneficial properties of manipulating the endocannabinoid system has led to the possible involvement of CBr in the control of brain inflammation. In the present study we examined the effect of the CBr agonist, (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)-pyrrolo[1,2,3-de]-1,4benzoxazin-6-yl]-1-naphthalenyl-methanone mesylate (WIN-55212-2), on microglial activation and spatial memory performance, using a well-characterized animal model of chronic brain inflammation produced by the infusion of lipopolysaccharide (LPS, 250 ng/h for 3 weeks) into the fourth ventricle of young rats. WIN-55212-2 (0.5 or 1.0 mg/kg/day, i.p.) was administered for 3 weeks. During the third week of treatment, spatial memory ability was examined using the Morris water-maze task. We found that 0.5 and 1 mg/kg WIN-55212-2 reduced the number of LPS-activated microglia, while 1 mg/kg WIN-55212-2 potentiated the LPS-induced impairment of performance in the water maze task. Cannabinoid receptors 1 were not expressed by microglia and astrocytes, suggesting an indirect effect of WIN-55212-2 on microglia activation and memory impairment. Our results emphasize the potential use of CBr agonists in the regulation of inflammatory processes within the brain; this knowledge may lead to the use of CBr agonists in the treatment of neurodegenerative diseases associated with chronic neuroinflammation, such as Alzheimer disease.

Memantine protects against LPS-induced neuroinflammation, restores behaviorally-induced gene expression and spatial learning in the rat.

Neuroinflammation is reliably associated with the pathogenesis of a number of neurodegenerative diseases, and can be detected by the presence of activated microglia. Neuroinflammation can be induced by chronic lipopolysaccharide (LPS) infusion into the 4th ventricle of the rat resulting in region-selective microglia activation and impaired hippocampal-dependent memory. Furthermore, this treatment results in altered behaviorally-induced expression of the immediate early gene Arc, indicating altered network activity. LPS is known to activate microglia directly, leading to increased glutamate release, and in enhanced N-methyl-d-aspartate (NMDA) -dependent signaling. Taken together, the foregoing suggests that decreasing NMDA receptor activation during early stages of chronic neuroinflammation should reduce a) microglia activation, b) overexpression of Arc, and c) spatial memory deficits. Memantine, a low to moderate affinity open channel uncompetitive NMDA receptor antagonist, at low doses was used here to test these hypotheses. Rats were chronically infused into the 4th ventricle for 28 days with LPS alone, vehicle alone (via osmotic minipump) or LPS and memantine (10 mg/kg/day memantine s.c.). The results reported here demonstrate that memantine reduces OX6-immunolabeling for activated microglia, spares resident microglia, returns Arc (activity-regulated cytoskeletal associated protein, protein) -expressing neuronal populations to control levels (as revealed by Arc immunolabeling and fluorescence in situ hybridization), and ameliorates the spatial memory impairments produced by LPS alone. These data indicate that memantine therapy at low doses, recreating plasma levels similar to those of therapeutic doses in human, acts in part through its ability to reduce the effects of neuroinflammation, resulting in normal gene expression patterns and spatial learning. Combined, these findings suggest that low, therapeutically relevant doses of memantine delivered early in the development of neuroinflammation-influenced diseases may confer neural and cognitive protection.

Chemokine receptor 5 antagonist D-Ala-peptide T-amide reduces microglia and astrocyte activation within the hippocampus in a neuroinflammatory rat model of Alzheimer's disease.

Chronic neuroinflammation plays a prominent role in the progression of Alzheimer's disease. Reactive microglia and astrocytes are observed within the hippocampus during the early stages of the disease. Epidemiological findings suggest that anti-inflammatory therapies may slow the onset of Alzheimer's disease. Chemokine receptor 5 (CCR5) up-regulation may influence the recruitment and accumulation of glia near senile plaques; activated microglia express CCR5 and reactive astrocytes express chemokines. We have previously shown that neuroinflammation induced by chronic infusion of lipopolysaccharide into the 4th ventricle reproduces many of the behavioral, neurochemical, electrophysiological and neuropathological changes associated with Alzheimer's disease. The current study investigated the ability of D-Ala-peptide T-amide (DAPTA), a chemokine receptor 5 chemokine receptor antagonist of monocyte chemotaxis, to influence the consequences of chronic infusion of lipopolysaccharide. DAPTA (0.01 mg/kg, s.c., for 14 days) dramatically reduced the number of activated microglia and astrocytes, as compared with lipopolysaccharide-infused rats treated with vehicle. DAPTA treatment also reduced the number of immunoreactive cells expressing nuclear factor kappa binding protein, a prominent component of the proinflammatory cytokine signaling pathway. The present study suggests that DAPTA and other CCR5 antagonists may attenuate critical aspects of the neuroinflammation associated with Alzheimer's disease.

The epidemiology of panic disorder and agoraphobia in Europe.

A literature search, in addition to expert survey, was performed to estimate the size and burden of panic disorder in the European Union (EU). Epidemiologic data from EU countries were critically reviewed to determine the consistency of prevalence estimates across studies and to identify the most pressing questions for future research. A comprehensive literature search focusing on epidemiological studies in community and clinical settings in European countries since 1980 was conducted (Medline, Web of Science, Psychinfo). Only studies using established diagnostic instruments on the basis of DSM-III-R or DSM-IV, or ICD-10 were considered. Thirteen studies from a total of 14 countries were identified. Epidemiological findings are relatively consistent across the EU. The 12-month prevalence of panic disorder and agoraphobia without history of panic were estimated to be 1.8% (0.7-2.2) and 1.3% (0.7-2.0) respectively across studies. Rates are twice as high in females and age of first onset for both disorders is in adolescence or early adulthood. In addition to comorbidity with agoraphobia, panic disorder is strongly associated with other anxiety disorders, and a wide range of somatoform, affective and substance use disorders. Even subclinical forms of panic disorder (i.e., panic attacks) are associated with substantial distress, psychiatric comorbidity and functional impairment. In general health primary care settings, there appears to be substantial underdiagnosis and undertreatment of panic disorder. Moreover, panic disorder and agoraphobia are poorly recognized and rarely treated in mental health settings, despite high health care utilization rates and substantial long-term disability.

Adaptation of the structured clinical interview for DSM-IV disorders for assessing depression in women during pregnancy and post-partum across countries and cultures.

BACKGROUND: To date, no study has used standardised diagnostic assessment procedures to determine whether rates of perinatal depression vary across cultures. AIMS: To adapt the Structured Clinical Interview for DSM-IV Disorders (SCID) for assessing depression and other non-psychotic psychiatric illness perinatally and to pilot the instrument in different centres and cultures. METHOD: Assessments using the adapted SCID and the Edinburgh Postnatal Depression Scale were conducted during the third trimester of pregnancy and at 6 months postpartum with 296 women from ten sites in eight countries. Point prevalence rates during pregnancy and the postnatal period and adjusted 6-month period prevalence rates were computed for caseness, depression and major depression. RESULTS: The third trimester and 6-month point prevalence rates for perinatal depression were 6.9% and 8.0%, respectively. Postnatal 6-month period prevalence rates for perinatal depression ranged from 2.1% to 31.6% across centres and there were significant differences in these rates between centres. CONCLUSIONS: Study findings suggest that the SCID was successfully adapted for this context. Further research on determinants of differences in prevalence of depression across cultures is needed.

The toxicity of tumor necrosis factor-alpha upon cholinergic neurons within the nucleus basalis and the role of norepinephrine in the regulation of inflammation: implications for Alzheimer's disease.

Inflammation and reduced forebrain norepinephrine are features of Alzheimer's disease that may interact to contribute to the degeneration of specific neural systems. We reproduced these conditions within the basal forebrain cholinergic system, a region that is vulnerable to degeneration in Alzheimer's disease. Tumor necrosis factor-alpha was infused into the basal forebrain of young mice pretreated with a norepinephrine neuronal toxin, N-(2-chloroethyl)-N-ethyl-2 bromobenzylamine (DSP4), with the expectation that the loss of noradrenergic input would enhance the loss of cholinergic neurons. The results indicate that chronic infusion of tumor necrosis factor-alpha alone significantly decreased cortical choline acetyltransferase activity and increased the number of activated microglia and astrocytes within the basal forebrain. The loss of forebrain norepinephrine following systemic treatment with DSP4 did not alter the level of cortical choline acetyltransferase activity or activate microglia but significantly activated astrocytes within the basal forebrain. Infusion of tumor necrosis factor-alpha into DSP4-pretreated mice also reduced cortical choline acetyltransferase activity on the side of the infusion; however, the decline was not significantly greater than that produced by the infusion of tumor necrosis factor-alpha alone. The neurodegeneration seen may be indirect since a double-immunofluorescence investigation did not find evidence for the co-existence of tumor necrosis factor-alpha type I receptors on choline acetyltransferase-positive cells in the basal forebrain. The results suggest that noradrenergic cell loss in Alzheimer's disease does not augment the consequences of the chronic neuroinflammation and does not enhance neurodegeneration of forebrain cholinergic neurons.

Epidemiology of social phobia: a clinical approach.

The recent epidemiologic studies report extremely varied rates for social phobia (SP). One of the reasons for this may be the difficulty in diagnosing SP, the boundaries of which are uncertain. A community survey was carried out using doctors with experience in clinical psychiatry as interviewers, and a clinical diagnostic instrument. Two thousand three hundred and fifty-five people (out of the 2,500 randomly selected from the population) living in Sesto Fiorentino, a suburb of Florence, Italy, were interviewed by their own general practitioner, using the MINI plus six additional questions. Six hundred and ten of the 623 subjects that were found positive for any form of psychopathology at the screening interview, and 57 negative subjects, were re-interviewed by residents in psychiatry using the Florence Psychiatric Interview (FPI). The FPI is a validated composite instrument that has the format of a structured clinical research record. It was found that 6.58% of subjects showed social anxiety not attributable to other psychiatric or medical conditions during their life. Social or occupational impairments meeting DSM-IV diagnostic requirements for SP was detected in 76 subjects (lifetime prevalence = 3.27%). Correction for age raises the lifetime expected prevalence to 4%. Sex ratio was approximately (F:M) 2:1. The most common fear was speaking in public (89.4%), followed by entering a room occupied by others (63.1%) and meeting with strangers (47.3%). Eighty-six point nine percent of subjects with SP complained of more than one fear. The mean age of onset (when the subjects first fully met DSM-IV criteria for SP) was 28.8 years, but the first symptoms of SP usually occurred much earlier, with a mean age of onset at 15.5 years. Ninety-two percent of cases with SP also showed at least one other co-morbid psychiatric disorder during their life. Lifetime prevalence of avoidant personality disorder (APD) was 3.6%. Forty-two point nine percent of cases with SP also had APD, whereas 37.9% of cases with APD developed SP.

[The recrudescence of spondylodiscitis due to migratory flows. The role of magnetic resonance as a method of first instance in diagnosis and follow-up]. / Recrudescenza della spondilodiscite da incremento dei flussi migratori. Ruolo della Risonanza Magnetica come metodica di prima istanza nella diagnosi e nei controlli.

PURPOSE: We report 15 cases of spondylodiscitis due to infective processes of different etiology and stress the role of MRI in the diagnosis and follow-up of this condition, whose high epidemiologic recrudescence is probably related to an increased westward migratory flow. PATIENT AND METHODS: February through December, 1996, fifteen patients with acute spinal pain were submitted to MRI (1.0 T superconductive magnet, Magnetom SP42E, Siemens, Erlangen, Germany). In all cases both the painful spinal tract and the rest of the spine were studied to detect any infiltrative processes elsewhere in the spine. All patients underwent MR follow-up, according to the evolution of subjective symptoms, until complete recovery of the infections. RESULTS: MRI always permitted the correct diagnosis to be made and the correct evaluation of infection evolution, allowing adequate (medical and/or surgical) treatment to be carried out in the early stage of infections. DISCUSSION: MRI can be considered the best diagnostic tool study osteomedullary inflammations and, particularly, to diagnose and follow-up spondylodiscitis. This technique permits clear differentiation between the different evolution stages of the infections, as well as the evaluation of bone, disks, epidural spaces and spinal cord involvement. Moreover the MR findings permit adequate treatment choices, which results in much fewer complications and therefore better prognosis. CONCLUSIONS: The role of MRI in the diagnosis and follow-up of spondylodiscitis has been fully discussed in the literature. Our report is aimed at stressing the important role of MRI as the technique of choice for the diagnosis of suspected spondylodiscitis, especially considering the high recrudescence of this condition in Western populations which is probably related to increased westward migrations.

Follow-up of colorectal cancer resected for cure. An experience with CEA, TPA, Ca 19-9 analysis and second-look surgery.

Sixty-four consecutive patients who had undergone curative resection for colorectal carcinoma were studied prospectively to evaluate the roles of sequential CEA determinations and independent instrumental follow-up in the early detection of resectable recurrences. Fifty-two of these patients also were submitted to sequential determinations of other tumor antigens: TPA (tissue polypeptide antigen) and Ca 19-9 (colon cancer antigen detected with a monoclonal antibody), for a retrospective evaluation of their utility as markers of recurrent tumors. Twenty-two recurrences were detected in a period ranging from 12 to 72 months (median, 47 months). CEA was the best predictor of recurrence (sensitivity, 90 percent) when compared with the other two markers (TPA sensitivity, 60 percent; Ca 19-9 sensitivity, 20 percent). When compared with the instrumental or biochemical examinations of the follow-up, CEA was still the most sensitive indicator of relapse although the specificity was quite low (78 percent) if minimal significative increases were considered. History and physical examination were more useful than CEA in detecting local recurrences in rectal cancer where the preoperative CEA level was low. A few second-look explorations based solely on small CEA increases failed to demonstrate recurrence or revealed peritoneal carcinomatosis. Selected second-look surgery based on demonstrated recurrences resulted in a resectability rate of 57 percent. A follow-up program based on frequent CEA assays, history, and physical examinations, including rectal, vaginal, and perineal exploration, is proposed. Extensive instrumental investigations should follow when a minimal significative CEA rise is observed, or when history and physical examinations suggest a possible recurrence. Second-look surgery should be evaluated after confirmed or highly suspected diagnosis of recurrence, on the basis of instrumental or clinical examinations.