Are NSAIDs Useful to Treat Alzheimer's Disease or Mild Cognitive Impairment?

Several epidemiological studies suggest that long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) may protect subjects carrying one or more ε4 allele of the apolipoprotein E (APOE ε4) against the onset of Alzheimer's disease (AD). The biological mechanism of this protection is not completely understood and may involve the anti-inflammatory properties of NSAIDs or their ability of interfering with the β-amyloid (Aβ) cascade. Unfortunately, long-term, placebo-controlled clinical trials with both non-selective and cyclooxygenase-2 (COX-2) selective inhibitors in mild-to-moderate AD patients produced negative results. A secondary prevention study with rofecoxib, a COX-2 selective inhibitor, in patients with mild cognitive impairment was also negative. A primary prevention study (ADAPT trial) of naproxen (a non-selective COX inhibitor) and celecoxib (a COX-2 selective inhibitor) in cognitively normal elderly subjects with a family history of AD was prematurely interrupted for safety reasons after a median period of treatment of 2 years. Although both drugs did not reduce the incidence of dementia after 2 years of treatment, a 4-year follow-up assessment surprisingly revealed that subjects previously exposed to naproxen were protected from the onset of AD by 67% compared to placebo. Thus, it could be hypothesized that the chronic use of NSAIDs may be beneficial only in the very early stages of the AD process in coincidence of initial Aβ deposition, microglia activation and consequent release of pro-inflammatory mediators. When the Aβ deposition process is already started, NSAIDs are no longer effective and may even be detrimental because of their inhibitory activity on chronically activated microglia that on long-term may mediate Aβ clearance. The research community should conduct long-term trials with NSAIDs in cognitively normal APOE ε4 carriers

Pastiches in laboratorio

in libro multimediale promosso da Istituto centrale per la grafica Real Academia di San Fernando, Ministero della cultur

Numerical and Experimental Acoustic Performance Investigations of a High-Speed Train Composite Sandwich Panel

Present work focuses on the implementation of numerical and experimental analyses aimed to acoustic performances characterization of a composite sandwich panel used for a high-speed train. Firstly, an experimental and a numerical modal analyses are presented. Starting from both FE simulation and impact testing outcomes, it has been possible to carry out a correlation study through the computation of the Modal Assurance Criterion (MAC). Good agreement between numerical and experimental analyses has been found, therefore the definition of a reliable FE model has been obtained without the necessity of implementing a sensitivity and updating procedure. In this paper, to find a convenient and accurate mean for predicting the panel Transmission Loss parameter, the panel is modeled as a composite sandwich panel, and its TL is predicted with the hybrid FE&SEA (Statistical Energy Analysis) method. The TL result is then compared to the experimental one, carried out through the employment of an intensity sound probe. A very good accordance has been found allowing to use such numerical procedure for further acoustic performances improvements. Hence, future developments could regard the possibility to implement a Reverse Engineering procedure, in order to realize an optimization process by considering different materials and stratifications or different panel thicknesses, to improve the acoustic attenuation properties at those frequencies at which a worse acoustic behavior of the panel, is present

Alternative pharmacological treatment options for agitation in Alzheimer's disease

In patients with dementia and Alzheimer's disease (AD), treatment of neuropsychiatric symptoms (NPS) is a major concern in the management of these devastating diseases. Among NPS in AD, agitation and aggression are common with earlier institutionalization, increased morbidity and mortality, and greater caregiver burden. Pharmacological treatments for AD-related agitation, specifically off-label use of atypical antipsychotics, showed only modest improvements, with increased side-effect burden and risk of mortality. Non-pharmacological treatment approaches have become the preferred firstline option. However, when such treatments fail, pharmacological options are often used. Therefore, there is an urgent need to identify effective and safe pharmacological treatments for agitation/aggression in AD and dementia. Unfortunately, progresses have been slow, with a small number of methodologically heterogeneous randomized controlled trials (RCTs), with disappointing results. However, evidence coming from recently completed RCTs on novel or repositioned drugs (mibampator, dextromethorphan/ quinidine, cannabinoids, and citalopram) showed some promise in treating agitation in AD, but still with safety concerns. Further evidence will come from ongoing Phase II and III trials on promising novel drugs for treating these distressing symptoms in patients with AD and dementia

effectiveness of switching therapy from complexing protein containing botulinum toxin type a to a formulation with low immunogenicity in spasticity after stroke a case report

Objective: some patients receiving botulinum toxin type a therapy develop immunological resistance due to the production of neutralizing antibodies against the neurotoxin, thus partially or completely reducing the therapeutic effect. Case report: We report here neurophysiological and clinical findings for a 58-year-old man treated with botulinum toxin type A for spasticity after ischaemic stroke, who became a secondary non-responder patient. subsequent treatment with a different preparation of botulinum toxin type A had a great therapeutic effect on his spasticity. the muscles injected and the dosages were the same for each treatment, but evaluation with the Modified Ashworth Scale after treatment with the second preparation showed a reduction of approximately 2 points compared with the first examination. The clinical results were also supported by extensor digitorum brevis testing of the right muscle, which showed a reduction in compound muscle action potential, whereas it was unchanged in the non-injected muscle. No side-effects were reported, and after 1 year of treatment with this formulation clinical benefits were still evident. Conclusion: the neurophysiological and clinical results obtained in this patient suggest that switching therapy from a complexing protein-containing product to a product potentially free of complexing proteins, which has low immunogenicity, may be a viable therapeutic option in secondary non-responder patients

Variability in Ejection Fraction Measured By Echocardiography, Gated Single-Photon Emission Computed Tomography, and Cardiac Magnetic Resonance in Patients With Coronary Artery Disease and Left Ventricular Dysfunction

Importance: Clinical decisions are frequently based on measurement of left ventricular ejection fraction (LVEF). Limited information exists regarding inconsistencies in LVEF measurements when determined by various imaging modalities and the potential impact of such variability. Objective: To determine the intermodality variability of LVEF measured by echocardiography, gated single-photon emission computed tomography (SPECT), and cardiovascular magnetic resonance (CMR) in patients with left ventricular dysfunction. Design, Setting, and Participants: International multicenter diagnostic study with LVEF imaging performed at 127 clinical sites in 26 countries from July 24, 2002, to May 5, 2007, and measured by core laboratories. Secondary study of clinical diagnostic measurements of LVEF in the Surgical Treatment for Ischemic Heart Failure (STICH), a randomized trial to identify the optimal treatment strategy for patients with LVEF of 35% or less and coronary artery disease. Data analysis was conducted from March 19, 2016, to May 29, 2018. Main Outcomes and Measures: At baseline, most patients had an echocardiogram and subsets of patients underwent SPECT and/or CMR. Left ventricular ejection fraction was measured by a core laboratory for each modality independent of the results of other modalities, and measurements were compared among imaging methods using correlation, Bland-Altman plots, and coverage probability methods. Association of LVEF by each method and death was assessed. Results: A total of 2032 patients (mean [SD] age, 60.9 [9.6] years; 1759 [86.6%] male) with baseline LVEF data were included. Correlation of LVEF between modalities was r = 0.601 (for biplane echocardiography and SPECT [n = 385]), r = 0.493 (for biplane echocardiography and CMR [n = 204]), and r = 0.660 (for CMR and SPECT [n = 134]). Bland-Altman plots showed only moderate agreement in LVEF measurements from all 3 core laboratories with no substantial overestimation or underestimation of LVEF by any modality. The percentage of observations that fell within a range of 5% ranged from 43% to 54% between different imaging modalities. Conclusions and Relevance: In this international multicenter study of patients with coronary artery disease and reduced LVEF, there was substantial variation between modalities in LVEF determination by core laboratories. This variability should be considered in clinical management and trial design. Trial Registration: Clinicaltrials.gov Identifier: NCT00023595

ACOUSTIC ANALYSIS OF SWALLOWING SOUNDS: A NEW TECHNIQUE FOR ASSESSING DYSPHAGIA

Objective: To perform acoustic analysis of swallowing sounds, using a microphone and a notebook computer system, in healthy subjects and patients with dysphagia affected by neurological diseases, testing the positive/negative predictive value of a pathological pattern of swallowing sounds for penetration/aspiration. Design: Diagnostic test study, prospective, not blinded, with the penetration/aspiration evaluated by fibreoptic endo scopy of swallowing as criterion standard. Subjects: Data from a previously recorded database of normal swallowing sounds for 60 healthy subjects according to gender, age, and bolus consistency was compared with those of 15 patients with dysphagia from a university hospital referral centre who were affected by various neurological diseases. Methods: Mean duration of the swallowing sounds and postswallowing apnoea were recorded. Penetration/aspiration was verified by fibreoptic endoscopy of swallowing in all patients with dysphagia. Results: The mean duration of swallowing sounds for a liquid bolus of 10 ml water was significantly different between patients with dysphagia and healthy patients. We also described patterns of swallowing sounds and tested the negative/positive predictive values of post-swallowing apnoea for penetration/aspiration verified by fibreoptic endoscopy of swallowing (sensitivity 0.67 (95% confidence interval 0.24–0.94); specificity 1.00 (95% confidence interval 0.56–1.00)). Conclusion: The proposed technique for recording and measuring swallowing sounds could be incorporated into the bedside evaluation, but it should not replace the use of more diagnostic and valuable measures

effect of intrathecal baclofen botulinum toxin type a and a rehabilitation programme on locomotor function after spinal cord injury a case report

Objective: a few studies have reported the use of botulinum toxin injections after spinal cord injury, as this is the gold standard to treat focal spasticity. We report such a case here. Case report: a 38-year-old woman who had become paraplegic and care-dependent secondary to cervico-thoracic intramedullary ependymoma, presented 8 months later with painful lower limb spasticity, which was being treated with oral anti-spastic and benzodiazepine drugs with no therapeutic effect. We treated the patient with intrathecal baclofen to reduce her spasticity and in order to avoid the major side-effects of high dosages of oral baclofen. after motor rehabilitation programmes, which included functional ele

Engineering robust next-generation networks

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