Photonic paper: Multiscale assembly of reflective cellulose sheets in Lunaria annua.

Bright, iridescent colors observed in nature are often caused by light interference within nanoscale periodic lattices, inspiring numerous strategies for coloration devoid of inorganic pigments. Here, we describe and characterize the septum of the Lunaria annua plant that generates large (multicentimeter), freestanding iridescent sheets, with distinctive silvery-white reflective appearance. This originates from the thin-film assembly of cellulose fibers in the cells of the septum that induce thin-film interference-like colors at the microscale, thus accounting for the structure's overall silvery-white reflectance at the macroscale. These cells further assemble into two thin layers, resulting in a mechanically robust, iridescent septum, which is also significantly light due to its high air porosity (>70%) arising from the cells' hollow-core structure. This combination of hierarchical structure comprising mechanical and optical function can inspire technological classes of devices and interfaces based on robust, light, and spectrally responsive natural substrates.

Report from a Consensus Conference on the treatment of Ménière's disease with betahistine: rationale, methodology and results.

Ménière's disease is a disorder of the inner ear that causes vertigo, tinnitus, fullness and hearing loss. Although several treatments are available, the success rate is reported to be around 70%, similar to placebo. Betahistine, a weak H1 receptor agonist and an effective H3 receptor antagonist, is frequently prescribed for Ménière's disease, especially to reduce recurrent vertigo attacks. The effects of this drug on hearing and other audiological symptoms remains unclear. Given the inconclusive reports in the literature, we proposed a consensus conference on the use of betahistine in Ménière's disease. The aim was to define best practice criteria for therapy for Ménière's disease, improve clinical suitability and reduce heterogeneity of the therapeutic approach. The consensus conference on betahistine for Ménière's disease involved a group of Italian experts in vestibular disorders who were asked a series of questions prepared by opinion leaders. The Delphi method, an iterative investigation method, was used to increase consensus. Via a tele-voting system, each participant anonymously evaluated all statements using a Likert 5-point scale. Betahistine was considered useful for the treatment of dizziness and vertigo during the intercritical phase of the disease (87% agreeing answers). However, during the acute phase of the disease betahistine was considered less effective and useful only when associated with other drugs (71% agreement). Similarly, the efficacy of the drug was considered low when used to reduce progressive hearing loss, tinnitus, and ear fullness. The experts advocated the use of betahistine during the intercritical phase of Ménière's disease to reduce the number and severity of vertigo attacks. Its use seems to be at low risk of major side effects.

Endovascular and surgical approaches of ethmoidal dural fistulas: a multicenter experience and a literature review.

Ethmoidal dural arteriovenous fistulae are rare vascular malformations associated with a high risk of bleeding. We present a multicenter contemporary series of patients treated with microsurgical and endovascular techniques. Sixteen consecutive patients were evaluated and/or treated between 2008 and 2015 at four centers with large experience in the endovascular and surgical treatment of cerebrovascular diseases. We analyzed demographic and clinical data, risk factors for dural fistulas, treatment type, peri- and post-operative morbidity, clinical and radiological outcomes, rates of occlusion, and long-term neurological outcome. Sixteen patients (81 % men, mean age of 58 years) with ethmoidal dural fistulas were included in the analysis. Seven patients had suffered an intracranial hemorrhage; the remaining presenting with neurological signs and symptoms or the fistula was an incidental finding. Three patients were managed conservatively. Among patients who underwent intervention (n = 13), 46.1 % were treated with endovascular therapy and 53.9 % were treated surgically. Complete angiographic obliteration was achieved in 100 % immediately after treatment and at last follow-up evaluation. All patients experienced a favorable neurological recovery (mRS 0-2) at the last follow-up visit (12 months). Ethmoidal dural AVFs are found mostly in male patients. Nowadays, due to wider use of non-invasive imaging, AVFs are discovered with increasing frequency in patients with minimal or no symptoms. Traditionally, these fistulas were considered "surgical." However, in the modern endovascular era, selected patients can be effectively and safely treated with embolization although surgical ligation continues to have an important role in their management.

Italian survey on benign paroxysmal positional vertigo.

Benign paroxysmal positional vertigo (BPPV) is the most common type of peripheral vertigo. BPPV often relapses after the first episode, with a recurrence rate between 15% and 50%. To date both the aetiopathogenetic processes that lead to otoconia detachment and the factors that make BPPV a relapsing disease are still unclear, but recent epidemiological studies have shown a possible association with cardiovascular risk factors. The aim of the present study (Sesto Senso Survey) was to evaluate in the Italian population through an observational survey, the main demographic and clinical characteristics of patients with BPPV (first episode or recurrent) with particular focus on the potential cardiovascular risk factors. The survey was conducted in 158 vestibology centres across Italy on 2,682 patients (mean age 59.3 ± 15.0 years; 39.1% males and 60.9% females) suffering from BPPV, from January 2013 to December 2014. The results showed a high prevalence of cardiovascular risk factors such as high blood pressure (55.8%), hypercholesterolaemia (38.6%) and diabetes (17.7%), as well as a family history of cardiovascular disease (49.4%). A high percentage of patients also had hearing loss (42.9%), tinnitus (41.2%), or both (26.8%). The presence of hypertension, dyslipidaemia and pre-existing cardiovascular comorbidities were significantly related to recurrent BPPV episodes (OR range between 1.84 and 2.31). In addition, the association with diabetes and thyroid/autoimmune disease (OR range between 1.73 and 1.89) was relevant. The survey results confirm the significant association between cardiovascular comorbidities and recurrent BPPV and identify them as a potential important risk factor for recurrence of BPPV in the Italian population, paving the way for the evaluation of new therapeutic strategies in the treatment of this disease.

Clinical efficacy of nutraceutical diet for cats with clinical signs of cutaneus adverse food reaction (CAFR).

Food allergies and food intolerances are clinically difficult to discriminate. Most often, along with cutaneous adverse food reactions or CAFR, they are classified as adverse food reactions, whose causes are numerous, including toxic compounds. Eighteen indoor-housed domestic cats with evident clinical symptoms related to CAFR (drooling, back and neck intense itching, neck eczema, chronic conjunctivitis and stomatitis) involving skin lesions were studied. Cytological evaluations of ear, skin and gingival swabs revealed an increased turnover of keratinocytes while the oxytetracycline ELISA determination showed an unexpected high amount of oxytetracycline in all cats at the first visit. All cats were then randomly assigned to receive a standard (SD group) or a nutraceutical diet (ND group) for 60 days. In the ND group a significant reduction of the mean serum concentration of oxytetracycline, pruritus intensity and skin lesion severity (**p<0.01, ***p<0.001, and ***p<0.001, respectively) was observed after 60 days, and associated with a significant improvement in the clinical picture. Although a direct correlation between oxytetracycline presence within cat sera and CAFR-related symptoms has never been described, this study highlights the benefit of a specific nutraceutical diet supplementation in improving clinical symptoms and skin lesions in cats with CARF.

Protective factors for work ability in preschool teachers.

BACKGROUND: Work ability (WA) describes the physical and intellectual resources on which individuals can rely to respond to work demands. While several studies have investigated the protective role of work-related psychosocial factors on WA, only a few have examined differences across age cohorts. Moreover, few studies have investigated WA in the educational context and most of those did not consider preschool teachers. AIMS: To examine the role of psychosocial factors (support from colleagues, support from supervisors, work meaning, reward, skill discretion and autonomy) in sustaining WA among preschool teachers in different age cohorts. METHODS: A cross-sectional study of preschool teachers employed in the municipal educational services of a city in northwest Italy. Study subjects completed a self-reported questionnaire. RESULTS: Among the 706 study subjects, in the 35-44 age cohort, support from colleagues was positively associated with WA. In the 45-54 age cohort, WA was found to be associated with reward and skill discretion while in the 55-63 age cohort, work meaning was significantly associated with WA. CONCLUSIONS: Our findings indicate that potential protective factors for WA may differ between age cohorts. They also suggest that in order to sustain WA effectively, interventions in working populations should be tailored to employees' ages.

Effects in dogs with behavioural disorders of a commercial nutraceutical diet on stress and neuroendocrine parameters.

The well-being of dogs can be affected by changes in human lifestyle, eating habits and increased stressors that lead to behavioural disorders including fear, hyperactivity and anxiety, followed by negative affective moods and poor welfare. This randomised, controlled clinical evaluation involved 69 dogs, 38 males and 31 females, of different breeds, with behavioural disorders related to anxiety and chronic stress. They were fed a control diet or a nutraceutical diet (ND group) for 45 days. Neuroendocrine (serotonin, dopamine, ß-endorphins, noradrenaline and cortisol) and stress (derivatives of reactive oxygen metabolites (dROMs) and biological antioxidant potential (BAP)) parameters related to behavioural disorders were evaluated at the beginning and end of the study period. Results showed a significant increase in serotonin, dopamine and ß-endorphins plasma concentrations (*P<0.05, *P<0.05 and **P<0.01, respectively) and a significant decrease in noradrenaline and cortisol plasma concentrations in the ND group (*P<0.05). dROMs significantly decreased in the ND group (*P<0.05) while BAP was not affected. This study demonstrated for the first time that a specific diet significantly and positively affected neuroendocrine parameters and dROMs. These results open significant perspectives concerning the use of diet and nutraceuticals in the treatment of behavioural disorders.

Fe3O4@SiO2 core-shell nanoparticles for biomedical purposes: adverse effects on blood cells.

Magnetite nanoparticles coated with silica, obtained by a sol-gel process in the reverse micelle microemulsion, were characterized and homogeneously suspended in water in order to assay their biocompatibility toward blood cells, in view of a potential medical use of this material. Their hemolytic, pro-thrombotic and pro-inflammatory properties were observed.

Tracking graphene by fluorescence imaging: a tool for detecting multiple populations of graphene in solution.

Most methods used for the characterization of graphene produced by liquid phase exfoliation require the deposition of the liquid sample on a substrate and subsequent drying. Because of this or other post-synthetic treatments, the reliability of the data in describing the actual features of the graphene particles in the pristine solution becomes questionable. Hence there is a need for new methods that permit the study of graphene directly in solution. Fluorescence imaging is at present the most convenient and sensitive method to visualize nanosized objects in solution. Here we report the development of a new method for visualizing and tracking exfoliated graphene directly in solution using a conventional set-up for fluorescence microscopy. We functionalized a fluorescent surfactant typically used for exfoliating graphite in aqueous phase (Pluronic P123) with two different fluorophores, in order to make graphene detectable by fluorescence microscopy. The photophysical interactions between the fluorescent surfactant and graphene were investigated at the bulk level. Finally, fluorescence microscopy allowed us to track the carbon particles produced and to identify two different populations of particles with sizes of 265 ± 25 and 1100 ± 200 nm respectively. The correlation of these results with TEM and DLS data is discussed.

Toxicological Implications and Inflammatory Response in Human Lymphocytes Challenged with Oxytetracycline.

Antibiotics are widely used in zoo technical and veterinary practices as feed supplementation to ensure wellness of farmed animals and livestock. Several evidences have been suggesting both the toxic role for tetracyclines, particularly for oxytetracycline (OTC). This potential toxicity appears of great relevance for human nutrition and for domestic animals. This study aimed to extend the evaluation of such toxicity. The biologic impact of the drug was assessed by evaluating the proinflammatory effect of OTC and their bone residues on cytokine secretion by in vitro human peripheral blood lymphocytes. Our results showed that both OTC and OTC-bone residues significantly induced the T lymphocyte and non-T cell secretion of interferon (IFN)-γ, as cytokine involved in inflammatory responses in humans as well as in animals. These results may suggest a possible implication for new potential human and animal health risks depending on the entry of tetracyclines in the food-processing chain.

Cytotoxic effects of oxytetracycline residues in the bones of broiler chickens following therapeutic oral administration of a water formulation.

Tetracyclines, which represent one of the most commonly used antibiotics for poultry, are known to be deposited in bones, where they can remain, despite the observation of appropriate withdrawal times. The aim of the study was to determine the concentration of oxytretracycline (OTC) residues in the bone and muscle of chickens, following the oral administration of a commercially available liquid formulation, and to test their cytotoxic effects on an in vitro cell culture model. Seventy-two 1-day-old broiler chickens were randomly allotted into 2 groups (control and treated animals). OTC (40 mg/kg BW) was administered via drinking water during the 1 to 5 and 20 to 25 days of life periods. At the end of the trial, the birds were slaughtered and the OTC residues in the target tissues were measured by means of liquid chromatography (LC) - tandem mass spectrometry (MS/MS). Cytotoxicity was assessed by evaluating the pro-apoptotic effect of the bone residues on the K562 erythroleukemic line and on the peripheral blood mononuclear cells (PBMC). In all the animals, the OTC residues in the muscle were far below the established MRL of 100 µg/kg. The OTC levels in the bones of the treated animals were instead found in the parts per million (ppm) range. Cell cytotoxicity was assessed by evaluating the pro-apoptotic effect of OTC bone residues on the haematopoietic cell system. This in vitro system has revealed a significant pro-apoptotic effect on both the K562 cell line and PBMC cultures. This result suggests potential human and animal health risks due to the entry of tetracycline residues contained in the bones of treated livestock into the food-chain. This could be of concern, particularly for canine and feline diets, as meat, bone meal, and poultry by-products represent some of the main ingredients of pet foods, especially in the case of dry pet food. Further studies are needed to define the underlying mechanisms of cytotoxicity and to evaluate the in vivo toxicological implications due to the observed in vitro effects.

Blister-like aneurysms of middle cerebral artery: a multicenter retrospective review of diagnosis and treatment in three patients.

Blood blister-like aneurysms (BBA) were described for the first time in the 1990s, as small hemispherical bulges arising from a very fragile arterial wall. Until 2008, it was thought that this type of aneurysm almost exclusively affected the internal carotid artery, in particular, its dorsal portion. Subsequently, it was discovered that a BBA may also be present on the anterior communicating artery and on the vessels of the posterior cranial fossa. However, we found no reports in English-language literature of BBA arising from the middle cerebral artery (MCA). In this article, we present three cases of MCA BBA and discuss the unique diagnostic and therapeutic aspects of this vascular lesion. In our retrospective, multicenter review of 1330 patients with non-traumatic subarachnoid hemorrhage admitted to our services from 2000 to 2013, we found three cases (all in men) of MCA BBA. The patients' outcome was assessed using the modified Rankin scale. All three patients underwent angio-computed tomography, which did not reveal any aneurysms. Digital subtraction angiography performed within 24-48 h after admission, in all cases, demonstrated a very small aneurysm (<2 mm), with a triangular shape and abroad base, at non-branching sites of MCA. All the aneurysms were treated: one by wrapping + clipping, one by wrapping + flow-diverter stent, and one with coils. At the time of surgery, the aneurysms appeared on the surface of the parent artery without any involvement of the branches. All presented as blister-like aneurysms that were thin-walled and lacked a surgical neck. At the time of discharge, the outcome was good in one patient and poor in the other two. Our cases demonstrate that BBA can also arise from the MCA, despite the lack of previous reports of this occurrence; a BBA should be suspected, particularly in cases of non-perimesencephalic subarachnoid hemorrhage in which the presence of a MCA aneurysm is suspected but not revealed by digital subtraction angiography or angio-computed tomography.

The proline-rich tyrosine kinase Pyk2 regulates platelet integrin αIIbß3 outside-in signaling.

BACKGROUND: The proline-rich tyrosine kinase Pyk2 is a focal adhesion kinase expressed in blood platelets, and is activated downstream of G-protein coupled receptors as well as integrin α2ß1. OBJECTIVE: In this study we have investigated the involvement of Pyk2 in integrin αIIbß3 outside-in signaling in human and murine platelets. METHODS: We analyzed the stimulation of intracellular signaling pathways in platelets from Pyk2 knockout mice adherent to immobilized fibrinogen. RESULTS: Pyk2 was rapidly phosphorylated and activated in human and murine platelets adherent to fibrinogen through integrin αIIbß3. Activation of Pyk2 was Src-dependent, but did not require phospholipase Cγ2 activity. Platelets from Pyk2 knockout mice showed a defective ability to adhere and spread on fibrinogen, in association with a dramatic reduction of phosphatidylinositol 3-kinase (PI3K) activation and Akt phosphorylation. Pharmacological and genetic analysis demonstrated that integrin αIIbß3 engagement selectively stimulated the ß-isoform of PI3K (PI3Kß), and that, as for Pyk2, PI3Kß activation required Src family kinases activity, but not phospholipase Cγ2. In fibrinogen-adherent platelets, both Pyk2 and PI3Kß were necessary for stimulation of the small GTPase Rap1b, a regulator of cell adhesion and spreading. Integrin αIIbß3 engagement triggered the association of the PI3Kß regulatory subunit p85 with the adaptor protein c-Cbl, which was mediated by the p85 SH3 domain, and was independent of c-Cbl tyrosine phosphorylation. However, p85-associated c-Cbl was tyrosine phosphorylated by activated Pyk2 in fibrinogen adherent platelets. CONCLUSIONS: These results identify a novel pathway of integrin αIIbß3 outside-in signaling and recognize the tyrosine kinase Pyk2 as a major regulator of platelet adhesion and spreading on fibrinogen.

Dissecting aneurysm of the middle cerebral artery treated with heparin infusion in a 6-year-old child; neurological recovery with delayed spontaneous thrombosis: case illustration and literature review.

Aneurysms in the pediatric population are a rare pathology with specific features which requires a deep knowledge of their pathogenesis for the best therapeutic choice; the authors report their experience with a patient presenting aneurysm of the middle cerebral artery (MCA) associated with proximal stenosis of the vessel. A six-year-old girl came to our observation after sudden onset of headache and left hemiparesis. Angio-MRI and angio-CT scan showed a right MCA dissecting aneurysms associated with proximal stenosis of the vessel. Patient started a therapy with low molecular weight heparin (LMWH), replaced, 15 days later, with acetyl-salicylic acid (ASA). Patient showed a rapid and almost complete neurological recovery, despite several radiological exams confirmed a complete occlusion of the right MCA. As many other authors noted, dissecting aneurysms in the pediatric population are probably due to a defect of the entire arterial wall. Combination of stenosis, turbulence and partial thrombosis of the aneurysm led to a complete occlusion of artery involved, leading to the formation of collateral circles. In our case, complete thrombosis was probably delayed with anticoagulant therapy and the progressive reinforcement of collateral circles lead to the patient's neurological recovery.

Integrin alpha2beta1 induces phosphorylation-dependent and phosphorylation-independent activation of phospholipase Cgamma2 in platelets: role of Src kinase and Rac GTPase.

BACKGROUND: Platelet adhesion promoted by integrin alpha2beta1 induces integrin alpha(IIb)beta3 activation through the phospholipase C (PLC)-dependent stimulation of the small GTPase Rap1b. OBJECTIVE: To analyze the mechanism of PLC activation downstream of alpha2beta1 that is required for regulation of Rap1b and alpha(IIb)beta3. METHODS: Human and murine platelets were allowed to adhere to immobilized type I monomeric collagen through alpha2beta1. Tyrosine phosphorylation of PLCgamma2, PLC activation, accumulation of GTP-bound Rap1b and fibrinogen binding were measured and compared. RESULTS: Integrin alpha2beta1 recruitment induced an evident PLC activation that was concomitant with robust tyrosine phosphorylation of PLCgamma2, and was suppressed in platelets from PLCgamma2-knockout mice. Moreover, PLCgamma2(-/-) platelets were unable to accumulate active Rap1b and to activate alpha(IIb)beta3 upon adhesion through alpha2beta1. Inhibition of Src kinases completely prevented tyrosine phosphorylation of PLCgamma2 in adherent platelets, but did not affect its activation, and both Rap1b and alpha(IIb)beta3 stimulation occurred normally. Importantly, alpha(IIb)beta3-induced phosphorylation and activation of PLCgamma2, as well as accumulation of active Rap1b, were totally suppressed by Src inhibition. Integrin alpha2beta1 recruitment triggered the Src kinase-independent activation of the small GTPase Rac1, and activation of Rac1 was not required for PLCgamma2 phosphorylation. However, when phosphorylation of PLCgamma2 was blocked by the Src kinase inhibitor PP2, prevention of Rac1 activation significantly reduced PLCgamma2 activation, GTP-Rap1b accumulation, and alpha(IIb)beta3 stimulation. CONCLUSIONS: Src kinases and the Rac GTPases mediate independent pathways for PLCgamma2 activation downstream of alpha2beta1.

Impaired navigation skills in patients with psychological distress and chronic peripheral vestibular hypofunction without vertigo.

Few studies have focused on the role of the vestibular system for navigation and spatial memory functions in humans, with controversial results. Since most experimental settings were based on magnetic resonance imaging volumetry of the hippocampus and virtual navigation task on a PC, aim of this study was to investigate whether a well-compensated unilateral peripheral vestibular hypofunction in humans could interfere with navigation tasks while walking on memorized routes. A series of 50 unilateral labyrinthine-defective patients, without vertigo at the time of examination, and 50 controls were invited to visually memorize 3 different routes (a triangle, a circle and a square) on a grey carpet and then to walk along them clockwise and counter-clockwise (mental map navigation) with eyes closed. The same test was then repeated with eyes open (actual navigation) and a second time with eyes closed (mental navigation). Execution time was recorded in each test. In the same session, working spatial memory was assessed by the Corsi block test and all subjects completed the Symptom Check List (SCL-90) to assess depression and anxiety levels. Results showed that labyrinthine-defective patients presented higher levels of anxiety and depression and performed the Corsi block test with more difficulties than controls. All differences reached statistically significant level (p < 0.05). Moreover, patients needed more time than controls in the first and third navigation tasks (eyes closed). No difference was observed between clockwise and counter-clockwise walking, on all routes, either in patients or controls. Patients showed a greater improvement in the third navigation task, with respect to the first test, than controls, with no side-effect in relation to labyrinthine hypofunction. These data demonstrate that walking along memorized routes without vision is impaired by peripheral vestibular damage even if vestibular compensation prevents patients from suffering from vertigo and balance disturbances. This impairment could be due to a permanent deficit of visuo-spatial short-term memory as suggested by the Corsi block test results even if a residual sensori-motor impairment and/or an interference of psychological distress could not be excluded.

[Peripheral vestibular damage causes impaired navigation tasks on memorized routes in humans].

OBJECTIVES: To investigate if a well-compensated unilateral peripheral vestibular hypofunction could interfere with navigation tasks on memorized routes in humans. METHODS: After a complete otoneurological investigation, fifty labyrinthine-defective patients and fifty controls were invited to visually memorize three different routes (a triangle, a circle and a square) on a grey carpet and then to walk along them with eye closed clockwise and counter-clockwise (mental map navigation). The same test was then repeated with eye open (actual navigation) and again with eye closed (mental navigation). Execution time was recorded in each test. Corsi block test and a psychiatric questionnaire completed the neuropsychological examination. RESULTS: Labyrinthine-defective patients showed higher levels of anxiety and depression and performed Corsi block test with more difficulties than controls. Patients spent more time than controls in the first and third session (eye closed). No difference was recorded between clockwise and counter-clockwise navigation tasks both in patients and in controls. Patients showed a greater improvement in the third navigation task than controls. CONCLUSION: Walking on memorized routes in non-visual condition is impaired by a peripheral vestibular damage, even if patients are well compensated. This impairment could be due to a defect of the visuospatial short-term memory, as supported by Corsi block tests, but a residual sensorimotor impairment and/or an interference of psychological distress could not be definitively excluded.

Clinical examination of labyrinthine-defective patients out of the vertigo attack: sensitivity and specificity of three low-cost methods.

Many reports have appeared in the medical literature concerning the clinical examination at the bedside of patients with vertigo and, even if few controversial opinions exist, the observation of one or more kinds of nystagmus is generally regarded as suggesting an organic aetiology. So far, the presence of nystagmus has been generally considered to be crucially important for clinicians who are daily asked to differentiate between an "organic" cause of vertigo (for example, a labyrinthine dysfunction) and a "non-organic" cause of vertigo, such as a panic disorder. Albeit, it should not be forgotten that the central nervous system is able to resolve the asymmetry of vestibulo-ocular reflexes, due to a peripheral vestibular failure, by means of compensatory mechanisms so that nystagmus is rapidly abolished after the acute attack of vertigo. In addition, visual fixation elicits sub-cortical inhibitory pathways to the vestibular nuclei so that spontaneous nystagmus is remarkably reduced by light. In order to more easily detect nystagmus, attempts have been made to minimize the interference of visual fixation by means of positive lenses (Frenzel's glasses) and light occluding masks with infrared cameras (videonystagmoscopy) which have in part replaced direct observation of the patient's eyes, albeit no systematic validation of the advantages has been reported yet. To investigate the usefulness of these 3 low-cost methods to detect nystagmus, 528 outpatients presenting peripheral vestibular hypofunction, diagnosed by a complete audiological and vestibular examination, including caloric tests, were enrolled in the present study, while 133 subjects with normal vestibular function acted as a control group. All patients and control subjects underwent a standardized clinical examination based on search for spontaneous, positioning and head-shaking nystagmus detected by direct observation of patient's eyes, Frenzel's glasses and videonystagmoscopy. Specificity of the three techniques were 35.6, 43.7 and 91.6, whilst sensitivity was 88.7, 88.7 and 84.2, respectively. Finally, discriminant analysis based on the presence/absence of at least one kind of nystagmus was computed for each technique and showed that videonystagmoscopy allowed the examiner to correctly classify both pathological and normal subjects more frequently (> 77% of cases) than the other two methods (about 50%). It is concluded that only videonystagmoscopy is an acceptable technique for screening a labyrinth defect in a population of outpatients with vertigo.

Betahistine in the treatment of vertiginous syndromes: a meta-analysis.

Vertigo is a very frequent disorder, associated with highly disabling symptomatology. Since the aetiology cannot always be easily identified, treatment is often addressed to the symptoms. Betahistine, a drug characterized by a multi-factorial mode of action of the modulatory type, has been widely employed in the management of various vertiginous syndromes. Its use in Italy is, currently, authorized to treat the vertiginous symptoms related to Ménière's disease. A meta-analysis has, therefore, been carried out to assess, the efficacy of betahistine in the treatment of other vertiginous syndromes, such as positional paroxysmal vertigo (cupulo-canalolithiasis) and vertigo secondary to arterial deficiency of the vertebrobasilar area, regardless of the specific cause. A review has been made of the literature concerning clinical trials performed with betahistine versus placebo in a randomised double-blind, parallel-group or cross-over design. Only studies evaluating betahistine in patients with vertiginous symptomatology not related to Ménière's disease were selected. Of the 104 publications, obtained from an analysis of "Medline", "EMBASE" and "CINAHL" databases, 7 clinical studies, which met the selection criteria, for a total of 367 patients, were extrapolated and analysed. The meta-analysis was conducted using the "Cochrane Collaboration's Review Manager" software in all the case series and in the sub-groups identified by the experimental design (parallel or crossover design), range of dosages (32-48 mg/day) and range of treatment duration (from 3 weeks to 4 months). The various parameters used to evaluate efficacy, adopted in the trials, and taken into account in the metaanalysis, as overall judgement of the patient or physician, number of vertiginous episodes and their duration, were classified according to the binary classification of "improved" and "not improved". The results of the meta-analysis confirm the therapeutic benefit of betahistine versus placebo. In particular, the investigation carried out on the overall sample shows an odds ratio of 3.52 (95% confidence interval 2.40-5.18) and a relative risk of 1.78 (95% confidence interval 1.48-2.13), while the analysis of the sub-groups denotes a maximum efficacy after doses of 32 to 36 mg and with a period of treatment of 3-8 weeks. The present meta-analysis confirms the benefit of drug treatment with betahistine for the vertiginous symptomatology related to cupulo-canalolithiasis and vertebro-basilar arterial insufficiency.