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Background and Purpose: To evaluate the 1‐year effectiveness and tolerability of galcanezumab in real life and the prognostic indicators of persistent response. Methods: High‐frequency episodic migraine (HFEM) and chronic migraine (CM) patients treated with galcanezumab who completed a 1‐year observation were enrolled. The primary outcomes assessed during the 12 months (V1–V12) were the change in monthly migraine days (MMDs) from baseline and the response rates ≥50% in MMDs (MMD ≥50% RR). The secondary outcomes were changes in pain intensity (numerical rating scale [NRS]) and in monthly acute medication intake (MAMI). Results: We enrolled 191 patients (77.5% CM). Twenty‐three patients (12%) dropped out, two for nonserious adverse events. At least 40% of patients took add‐on standard preventives from baseline to V12. At V12, MMDs were reduced by 6.0 days in HFEM and by 11.9 days in CM patients (both p < 0.00001); NRS and MAMI were also decreased in both groups (p < 0.00001). One‐hundred eight (56.5%) patients presented MMD ≥50% RR for 9 cumulative months (interquartile range=8): we defined this value as the cutoff for a persistent response. Persistent responders were less likely to have a higher body mass index (BMI) (p = 0.007) but more frequently had a good response to triptans (p = 0.005) and MMD ≥50% RR at V1 (p < 0.0000001). Patients without a persistent response were on add‐on therapy for longer periods of time (p < 0.001). Conclusions: Galcanezumab was effective and well‐tolerated in the 1‐year term, with most patients presenting MMD ≥50% RR for at least 9 months. Triptan response, lower BMI, and MMD ≥50% RR in the first month emerged as predictive factors for a persistent response. [ABSTRACT FROM AUTHOR]

Background and purpose: A rapid response to preventive therapy is of pivotal importance in severely disabled patients with chronic migraine (CM) and diverse preventive treatment failures. This prospective, observational, multicenter real‐life study aimed at investigating the effectiveness of galcanezumab in the first 3 months of treatment of CM patients at 14 Italian headache centers. Methods: All consecutive adult patients with CM diagnosis with the clinical indication for galcanezumab were considered. We collected patients' baseline characteristics, monthly headache days, monthly painkiller intake, migraine clinical characteristics, and disability scale scores during a 1‐month run‐in period (baseline) and the first 3 months of therapy. Possible predictive factors of treatment were considered. Results: A total of 156 patients (82.4% female, aged 47.3 ± 12.3 years) were enrolled. The 65 (41.7%) patients with a consecutive ≥50% response rate (RR) in the 3 months of therapy presented a lower body mass index (p = 0.004) and more frequently presented unilateral migraine pain (p = 0.002) and good response to triptans (p = 0.003). Persistent conversion from CM to episodic migraine was observed in 55.8% (87/156) of patients. They more frequently presented a good response to triptans (p = 0.003) and unilateral pain (p = 0.046). At baseline, 131 of 156 (83.9%) patients presented medication overuse (MO). Of these, 61.8% (81/131) no longer displayed MO consistently during the 3 months. These patients were more frequently responders to triptans (p = 0.002) and less frequently suffered from gastrointestinal comorbidity (p = 0.007). Conclusions: Unilateral pain, good response to triptans, and normal weight may be associated with a persistent positive response in the first 3 months of therapy with galcanezumab in CM patients. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the long‐term effectiveness, safety, and tolerability of erenumab in a real‐world migraine population, looking for putative predictors of responsiveness. Background: Erenumab proved to be effective, safe, and well tolerated in the prevention of episodic migraine (EM) and chronic migraine (CM) in long‐term extension studies of double‐blind, placebo‐controlled trials in patients with no more than two (EM) or three (CM) prior preventive treatment failures. Methods: A 48‐week, multicenter, longitudinal cohort real‐life study was conducted at 15 headache centers across eight Italian regions between December 20, 2018 and July 31, 2020. We considered all consecutive patients with high‐frequency episodic migraine (HFEM) or CM aged 18–65 years. Each patient was treated with erenumab 70 mg, administered monthly. The dose was switched to 140 mg in nonresponders and in responders who had become nonresponders for at least 4 weeks. Change in monthly migraine days (MMDs) or monthly headache days (MHDs) at Weeks 45–48 compared with baseline was the primary efficacy endpoint. Secondary endpoints encompassed variation in monthly analgesic intake, achievement of a ≥50%, ≥75%, or 100% reduction in migraine or headache days, and any change in the Visual Analogue Scale (VAS) and Headache Impact Test‐6 scores (HIT‐6) during the same time interval. Results: A total of 242 patients with migraine received at least one dose of erenumab 70 mg and were considered for safety analysis, whereas 221 received a monthly erenumab dose for ≥48 weeks and were included in the effectiveness and safety analysis set. All patients had previously been treated unsuccessfully with ≥3 migraine‐preventive medication classes. From baseline to Weeks 45–48, erenumab treatment reduced MMD by 4.3 ± 5.3 (mean ± SD) in patients with HFEM, and MHD by 12.8 ± 8.9 (mean ± SD) in subjects with CM. VAS and HIT‐6 scores were decreased by 1.8 ± 1.9 (mean ± SD) and 12.3 ± 11 (mean ± SD) in HFEM, and by 3.0 ± 2.2 (mean ± SD) and 13.1 ± 11.2 (mean ± SD) in CM. Median monthly analgesic intake passed from 11.0 (interquartile range [IQR] 10.0–13.0) to 5 (IQR 2.0–8.0) in HFEM and from 20.0 (IQR 15.0–30.0) to 6.0 (IQR 3.8–10.0) in CM. The ≥50% responders were 56.1% (32/57) in HFEM and 75.6% (124/164) in CM; ≥75% responders were 31.6% (18/57) and 44.5% (73/164); and 100% responders were 8.8% (5/57) and 1.2% (2/164), respectively. At Week 48, 83.6% (137/164) of patients with CM had reverted to EM. Erenumab was safe and well tolerated. Responsiveness to erenumab was positively associated with cutaneous allodynia (OR: 5.44, 95% CI: 1.52–19.41; p = 0.009) in HFEM. In patients with CM, ≥50% responsiveness was positively associated with male sex (OR: 2.99, 95% CI: 1.03–8.7; p = 0.044) and baseline migraine frequency (OR: 1.12, 95% CI: 1.05–1.20; p = 0.001) and negatively associated with psychiatric comorbidities (OR: 0.37, 95% CI: 0.15–0.87; p = 0.023) and prior treatment failures (OR: 0.77, 95% CI: 0.64–0.92; p = 0.004). Conclusions: Long‐term (48‐week) erenumab treatment provides sustained effectiveness, safety, and tolerability in real‐life patients with HFEM or CM with ≥3 prior preventive treatment failures. The dose of 140 mg was required in most patients along the study and should be taken into consideration as the starting dose. Allodynia (in HFEM), male sex, and baseline migraine frequency (in CM) might represent positive responsiveness predictors. Conversely, psychiatric comorbidities and multiple prior preventive treatment failures could be negative predictors in patients with CM. [ABSTRACT FROM AUTHOR]

Objective: To develop a dedicated Italian chronic migraine (CM) database (IRON project) to overcome disease misconceptions, improve clinical administration, reduce patients' burden, and rationalize economic resource allotment. Background: Proper CM management requires a comprehensive appraisal of its full clinical, social, and economic complexity. Methods: In this cross‐sectional study, CM patients were screened in 24 certified headache centers with face‐to‐face interviews. Information on sociodemographic factors, medical history, characteristics of CM, and of prior episodic migraine (EM), and healthcare resource use was gathered using a semistructured web‐based questionnaire. Results: A total of 866 CM patients were enrolled. CM started ~20 years after EM onset (age at EM onset 17.4 ± 9.1 vs. age at CM onset 35.3 ± 12.5 [mean ± SD]). CM prophylaxis, used by 430/866 (49.6%) of the patients, was often ineffective, not tolerated, and prematurely discontinued. Medications and diagnostic workup, frequently inappropriate, were mostly subsidized by the Italian national health service. CM patients with ≥25 headache days/month revealed substantial clinical differences and heavier disability and economic burden compared with those with <25 headache days/month. Conclusions: CM is a heterogeneous headache disorder deserving more in‐depth clinical characterization, sharper diagnostic criteria, and tailored treatments. CM registries are expected to improve clinical management, resulting in increased disease awareness, better healthcare resource allocation, and reduced economic burden. [ABSTRACT FROM AUTHOR]

Objective: To assess the effectiveness, safety, and tolerability of erenumab in a real‐life migraine population, while trying to identify responsiveness predictors. Background: Erenumab is a fully human Ig‐2 monoclonal antibody blocking the calcitonin gene‐related peptide receptor, indicated for migraine prophylaxis. Phase II and III trials demonstrated that erenumab is effective, safe, and well tolerated in the prevention of episodic and chronic migraine (CM), showing an early onset of action. Methods: This is a multicenter, prospective, cohort, and real‐life study. We considered for enrolment all consecutive patients aged 18–65 affected by high‐frequency episodic migraine (HFEM) or CM, with or without medication overuse, visited at nine Italian Headache Centers from December 20, 2018 to September 30, 2019. Each patient was treated with erenumab 70 mg, administered subcutaneously every 4 weeks. Treatment duration was planned to last from 6 to 12 months, depending on the patient's response. The primary endpoint was the change in monthly migraine days (MMDs) at weeks 9–12 compared to baseline. Secondary endpoints included changes in monthly analgesics intake, ≥50%, ≥75%, and 100% responder rates and any variation in the Visual Analog Scale (VAS) and Headache Impact Test scores (HIT). Results: In total, 372 migraine patients were treated with at least one dose of erenumab 70 mg. At weeks 9–12, erenumab decreased MMDs by 4.5 ± 4.1 days (mean ± SD) in patients with HFEM and by 9.3 ± 9.1 (mean ± SD) days in those with CM compared to baseline. At weeks 9–12 VAS score was reduced by 1.9 ± 1.9 (mean ± SD), HIT score by 10.7 ± 8.8 (mean ± SD), and median monthly analgesics intake passed from 12.0 (interquartile range [IQR] 10.0–14.0) to 5.0 (IQR 3.0–7.0) in HFEM. In CM patients, VAS was reduced by 1.7 ± 2.0 (mean ± SD), HIT by 9.7 ± 10.4 (mean ± SD), and median monthly analgesics intake passed from 20.0 (IQR 15.0–30.0) to 8.0 (IQR 5.0–15.0). At week 12, ≥50% responders were 60/101 (59.4%) for HFEM and 146/263 (55.5%) for CM, ≥75% responders were 17/101 (16.8%) and 59/263 (22.4%) and 100% responders 1/101 (1.0%) and 3/263 (1.1%), respectively. Erenumab responsiveness in HFEM was positively associated with unilateral pain localization (OR: 3.03, 95% CI: 1.24–7.40; p = 0.015), whereas in CM responsiveness was positively associated with and baseline migraine frequency (OR: 1.06, 95% CI:1.02–1.11; p = 0.031), dopaminergic symptoms (OR: 2.01, 95% CI: 1.14–3.52; p = 0.015), and negatively associated with psychiatric comorbidities (OR: 0.43, 95% CI: 0.20–0.93; p = 0.003). Conclusions: Erenumab 70 mg is effective, safe, and well tolerated in real life. Easily obtainable clinical features might be of help in predicting patient's responsiveness. [ABSTRACT FROM AUTHOR]

Plants, including cocoa bean, are the main source of metabolites with multiple biological functions. Polyphenol extracts are widely used as a nutraceutical supplement for their well‐known health‐promoting role. In this paper, a preliminary untargeted metabolic screening was carried out by matrix‐assisted laser desorption/ionization (MALDI)‐time of flight (TOF)/TOF on a pool of chocolate samples made by cocoa beans of different geographical areas. Then, a targeted approach was developed for polyphenol quantification by an optimized Liquid chromatography (LC)–tandem mass spectrometry (MS/MS) method multiple reaction monitoring (MRM) ion mode. Detection limit of polyphenol standard ranged between 1 and 25 pg/μl with variation coefficient lower than 15%. External calibration curves were used for quantification of polyphenols in 18 samples. Fifty polyphenols were detected in a single LC–MRM/MS run and quantified by monitoring almost 90 transitions in a 5‐minute run. The polyphenols content of different cocoa beans from several countries was finally compared by principal component analysis (PCA) statistical analysis suggesting that the chocolate made by Ecuador cocoa beans showed the highest level of polyphenols. [ABSTRACT FROM AUTHOR]

Objective: This article reviews current headache disability measures and clinical need, as well as presenting the rationale for a new measure addressing work‐related disability in migraine patients and the steps devoted to this aim. Background: Episodic and chronic migraine (EM and CM) constitute an enormous economic burden to societies, and the vast majority of this burden is attributable to indirect costs, ie those associated with productivity loss. A measure of work‐related disability is therefore needed to quantify the impact of EM and CM on patients' ability to carry out work tasks. Methods: We briefly present the advantages and disadvantages of the disability measures that have been most commonly used for this purpose and the rationale for developing a new measure. Results: The entire process of development of HEADWORK, a questionnaire designed to assess work‐related disability, is presented together with short‐term sensitivity to change. Conclusions: Current headache disability measures need improvement. HEADWORK is a valid, reliable, and sensitive questionnaire to address the amount and severity of work‐related difficulties and of the factors contributing to such difficulties. HEADWORK is suitable for daily clinical practice, epidemiological research and for clinical trials, and potentially to define work‐related disability weights for the calculation of migraine indirect costs. [ABSTRACT FROM AUTHOR]

Dissipative mechanisms occurring at the interface between multiwall nanotubes (MWCNT) and an elastomeric matrix are investigated and quantitatively predicted through analytical equations derived from a micromechanical model. The effects of MWCNT aspect ratio on dissipative properties of the reinforced system are investigated at high strains (100-300%). Cyclic tensile tests illustrate that the fraction of dissipated strain energy increases with the amount of MWCNT and varies with their aspect ratio. Lower mean diameter MWCNT are able to dissipate a higher amount of strain energy. The model developed on the basis of the shear lag theory correctly predicts the dissipated strain energy at high strains, taking into account the different contributions to the mechanical behavior of nanotubes' different aspect ratios. [ABSTRACT FROM AUTHOR]

Prion protein, a sialoglycoprotein with neuroprotective properties on oxidative stress damage, has been related with the mechanisms leading to migraine. In the present case-control study, we investigated the correlation between the common methionine/valine polymorphism at codon 129 within the prion protein gene ( PRNP) and migraine. Genotyping of PRNP V129M variant was performed in 384 migraine patients and 185 age-, sex-, and race-ethnicity-matched healthy controls. The frequencies of the PRNP V129M genotype did not differ significantly between migraineurs and controls. The frequencies of 129VV genotype were significantly higher in patients with earlier age at migraine onset. No correlation was found between PRNP 129 genotype and demographics, and other clinical migraine features. Our data suggest that the PRNP 129VV polymorphism is not a direct migraine risk factor but is significantly associated with an earlier onset of the disease. [ABSTRACT FROM AUTHOR]

We propose a quantum gravity-extended form of the classical length contraction law obtained in special relativity. More specifically, the framework of our discussion is the UV self-complete theory of quantum gravity. We show how our results are consistent with (i) the generalized form of the uncertainty principle (GUP), (ii) the so-called hoop-conjecture, and (iii) the intriguing notion of "classicalization" of trans-Planckian physics. We argue that there is a physical limit to the Lorentz contraction rule in the form of some minimal universal length determined by quantum gravity, say the Planck Length, or any of its current embodiments such as the string length, or the TeV quantum gravity length scale. In the latter case, we determine the critical boost that separates the ordinary "particle phase," characterized by the Compton wavelength, from the "black hole phase," characterized by the effective Schwarzschild radius of the colliding system. [ABSTRACT FROM AUTHOR]

Objective.- To clarify the frequency and characteristics of altered transverse sinus morphology in a series of consecutive patients with chronic migraine. Background.- As terminology, neuroradiological techniques and patient selection differ widely across various studies, reliable, reproducible information is lacking on the frequency of cerebral transverse sinus asymmetry as measured by cerebral magnetic resonance venography in patients with chronic migraine. Methods.- We assessed the frequency and characteristics of transverse sinus asymmetries and their correlation with the chronic migraine phenotype in a blind, cross-sectional magnetic resonance venographic study in a series of 83 consecutive patients with chronic migraine. Results.- After excluding mild (≤10%) physiological differences in transverse sinus diameter, we found magnetic resonance venographic evidence of altered transverse sinus morphology in 50.6% of the patients: 16.9% had moderate transverse sinus asymmetry (≤50%), 24.1% severe asymmetry (>50%), and 9.6% aplasia. Among the tested risk factors for migraine chronification, analgesic consumption, anxiety, and high systolic blood pressure were more frequent in patients with transverse sinus aplasia than in those without. Conclusions.- Advanced magnetic resonance venographic techniques used in strictly selected subjects disclose transverse sinus asymmetries in as many as 50.6% of patients with chronic migraine, even when mild differences in physiological caliber are excluded. The unexpected correlation between transverse sinus aplasia and some risk factors for migraine chronification requires confirmation in larger studies. [ABSTRACT FROM AUTHOR]

The foaming processes of nanocomposites based on high-performance thermoplastic polymers, namely, poly(ether sulfone) (PES; amorphous) and poly (ethylene-2,6-naphthalate) (PEN; semicrystalline), reinforced by two nanofiller types (expanded graphite and SiO2 nanopowder), were investigated. Matrices were prepared by melt blending through extrusion, and a good dispersion of particles was achieved, as confirmed by microscopic and X-ray diffraction analyses. A solid-state foaming technique was used to prepare the foams; the samples were solubilized with carbon dioxide and quickly heated in an oil bath to the selected foaming temperature. The effects of both the type and concentration of the filler and the polymer type (amorphous and semicrystalline) on the cellular morphology were analyzed. Foams prepared from PES-based nanocomposites showed microcellular morphologies and higher numbers of nucleated cells (up to 1011 cells/cm3), but low expansion ratios were achieved compared to PEN-based foams. Both SiO2 and graphite nanoparticles acted as cell nucleating agents in the PES nanocomposites, but the latter gave better results, increasing the cell number by two orders of magnitude with respect to the neat polymer. This behavior was attributed to either the heterogeneous nucleation of cells or the improved barrier to gas diffusion of the graphite nanoplatelets with respect to SiO2 nanoparticles. The PEN nanocomposite foams exhibited low foam densities, but fewer cells were nucleated with respect to the PES nanocomposites. The increase in the crystallization rate related to the presence of fillers, in particular when graphite was used, affected the expansion ratio at high foaming temperatures. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011 [ABSTRACT FROM AUTHOR]

Reinforced foams were prepared by exposing a polyurethane matrix filled with iron particles to a magnetic field during the foaming process. The magnetic field induced an alignment of the iron particles along the field direction, giving rise to columnar structures similar to fibrils, as observed by SEM and microtomographic 3D reconstructions. The anisotropic reinforcement induced by the fibrils improved the mechanical performances, yielding a threefold increase of both elastic modulus and yield stress in the alignment direction, whereas minor effects were observed in the transversal direction. In this case, the mechanical properties were comparable with those of randomly filled foams or, in some cases, of unfilled foam. The reinforcing efficiency of fibrils was evaluated through a theoretical model, based on the combination of the mechanics of foams with two micromechanical models for aligned short fibers composites (Halpin-Tsai and Cox-Krenchel). The theoretical predictions based on the Halpin-Tsai equations showed a good agreement with the experimental data, whereas the model derived from Cox-Krenchel equations overestimated data. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011 [ABSTRACT FROM AUTHOR]

The trehalose/maltose-binding protein (MalE1) is one component of trehalose and maltose uptake system in the thermophilic organism Thermus thermophilus. MalE1 is a monomeric 48 kDa protein predominantly organized in α-helix conformation with a minor content of β-structure. In this work, we used Fourier-infrared spectroscopy and in silico methodologies for investigating the structural stability properties of MalE1. The protein was studied in the absence and in the presence of maltose as well as in the absence and in the presence of SDS at different p2H values (neutral p2H and at p2H 9.8). In the absence of SDS, the results pointed out a high thermostability of the MalE1 α-helices, maintained also at basic p2H values. However, the obtained data also showed that at high temperatures the MalE1 β-sheets underwent to structural rearrangements that were totally reversible when the temperature was lowered. At room temperature, the addition of SDS to the protein solution slightly modified the MalE1 secondary structure content by decreasing the protein thermostability. The infrared data, corroborated by molecular dynamics simulation experiments performed on the structure of MalE1, indicated that the protein hydrophobic interactions have an important role in the MalE1 high thermostability. Finally, the results obtained on MalE1 are also discussed in comparison with the data on similar thermostable proteins already studied in our laboratories. Proteins 2008. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Our objective was to report the clinical characteristics and to investigate the role of SLITRK1 gene in a large Italian family with Tourette syndrome (TS). The diagnosis of TS and chronic motor tics (CMT) was made according to 'The Tourette Syndrome Classification Study Group' (1993). Psychiatric diagnoses were made by administering the Structured Clinical Interview for DSM and the Yale-Brown Obsessive Compulsive Scale. Genetic study included direct sequencing and copy number analysis of the SLITRK1 gene, and haplotype analysis. We found tics or other behavioral manifestations in 15 subjects. Of these, 5 received a diagnosis of definite TS, 5 were classified as having definite CMT, 2 had definite nonspecific tic disorder, and 3 patients had obsessive-compulsive disorder without motor or phonic tics. Tics mainly involved the craniocervical district. Many patients with tics had coexisting psychiatric disorders, especially obsessive-compulsive disorder, performed poorly at school and had social problems. Direct sequencing and copy number analysis of the SLITRK1 gene, and haplotype analysis suggested that the SLITRK1 locus was not involved in this family. In conclusion, the distinctive clinical features in this family are the motor tics mainly involving the face and the neck and the severe coexisting psychiatric disorders. The negative results of the SLITRK1 analysis point to genetic heterogeneity in TS. © 2007 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Human skin is continuously exposed to internal and external influences that may alter its condition and functioning. As a consequence, the skin may undergo alterations leading to immune dysfunction, imbalanced epidermal homeostasis, or other skin disorders. New theories are developing that link food intake and health. The objective of this review is to evaluate current knowledge about the interrelation of food and skin, particularly the effect of nutrients on some cutaneous immune disorders and therapeutic actions of nutrients in skin disorders.

Abstract Background Patients with type III Ehlers–Danlos syndrome show hypermobile joints, luxation, and minimal atrophic scars. The disease has an incidence of 9–16% and the molecular defect that underlies this subtype is unknown. In order to widen diagnostic investigations in type III Ehlers–Danlos syndrome, skin and articular areas were studied by ultrasound (US) test. Methods Thirty-five patients, 20 women and 15 men, aged from 18 to 25 years, with type III Ehlers–Danlos syndrome were enrolled in this study. Patients showed hypermobile joints (35 cases), minimal atrophic wrinkled scars (35 cases), and a few ice-pick acne scars. Hypermobility of phalangeal joints was studied by means of the Beighton scoring system and by a US test (performed by Sonora Logic 400 MD unit with 10 MHz probe). The following US parameters were considered: the distance of the intra-articular space and the thicknesses of the extensor tendon and of the overhanging dermis and subcutis. Result US reports showed an increase in distance of the intra-articular space and a reduction in the thickness of the extensor tendon and of the dermis and subcutis covering it. The dermis showed high and homogeneous echogenicity with irregular hyperechogenic lines. Conclusion The Beighton scoring system, the US findings, and the aspect and diameter of the scars suggested that the disease can be divided into three different stages which allow the correlation, over progressive intervals of values, of the articular hypermobility and atrophic wrinkled scars. Our results showed that US test is able to confirm the clinical diagnosis and to evaluate the seriousness of hypermobile joints. [ABSTRACT FROM AUTHOR]

A member of the laccase multigene family in Pleurotus ostreatus been cloned and sequenced The gene structure has been determined by comparison with the corresponding cDNA, synthesized by reverse transcription/PCR amplification. The gene encode a laccase isoenzyme of 533 amino acids which has already been purified and characterized [Palmieri, G., Giardina, P., Marzullo, L., Desiderio, B., Nitti, G., Cannio, R. & Sannia, G. (1993) Appl. Microbiol. Biotechnol. 39, 632–636]. More than 92% of the protein sequence, including the N and C termini, has been verified by fast-atom-bombardment mass spectrometry, thus confirming the correspondence between the gene and its protein, product. The protein wan N-glycosylated at Asn444. Glycan analysis showed the presence of only a high- mannose structure containing varying numbers of mannose residues. The presence of O-linked oligosaccharides as well as other post-translational modification could be ruled out by the mass analysis. [ABSTRACT FROM AUTHOR]

The progressive ageing of the population will produce an increase of those neuropsychiatric disturbances (late onset psychosis, behavioural disturbances of dementia, psychosis in Parkinson's disease) which may require treatment with antipsychotics. However, aged individuals are at higher risk for the development of adverse events from these drugs, namely extrapyramidal disturbances and tardive dyskinesias (TD). TD are a complex disorder, and despite much work done both in basic science and in clinical studies, many issues are still unresolved, such as risk factors, natural history and response to treatment. Although TD may be a mild disorder, it may become debilitating in a proportion of patients. As treatment is often quite disappointing, efforts are directed to its prevention. In this respect, atypical antipsychotics, with their peculiar mixed dopamine–serotonin antagonism, present a clear advantage over classic neuroleptics in young schizophrenic patients, with a lower incidence of TD during chronic treatment. Data are accumulating to show that this is likely to be true also in older patients. Copyright © 2001 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]