Presbycusis and balance disorders in the elderly. Bibliographical review of ethiopathogenic aspects, consequences on quality of life and positive effects of its treatment.

At this time, we still do not have adequate knowledge and awareness of the consequences of hearing loss in the elderly on quality of life. Similarly, there is also insufficient information on the relationship of presbycusis and balance disorders with other comorbidities. Such knowledge can contribute to improve both prevention and treatment of these pathologies, to reduce their impact on other areas such as cognition or autonomy, as well as to have more accurate information on the economic impact they generate in society and in the health system.

New Drug and Biologics Approvals in 2019: A Systematic Analysis of Patient Experience Data in FDA Drug Approval Packages and Product Labels.

Background: The FDA Patient-Focused Drug Development Initiative was launched to ensure the incorporation of the patient voice into drug development and evaluation. Since 2017, the FDA must publish a statement outlining patient experience data (PED) considered in the approval of new drugs. This study investigated the presence and role of PED in drug approval and translation into product label claims.

US, EU, and Japanese Regulatory Guidelines for Development of Drugs for Treatment of Alzheimer's Disease: Implications for Global Drug Development.

Drug development guidelines from regulatory authorities provide important information to sponsors on requirements for clinical evidence needed to support approval of new drugs. In the field of Alzheimer's disease (AD), recently published guidelines are available from EU, US, and Japanese regulatory authorities. In this review, these three guidelines are compared and discussed with emphasis on the recommendations provided for demonstration of efficacy in pivotal clinical trials conducted in predementia stages of AD.

Labeling of Disease-Modifying Therapies for Neurodegenerative Disorders.

Neurodegenerative disorders are characterized by progressive degeneration of nerve cells resulting in functional decline of cognition and/or movement. As the prevalence of many of these disorders increases with the aging global population, there is an urgent need for disease-modifying drugs that will halt or slow the progression of these devastating diseases. A summary of the scientific information needed to guide the safe and effective use of a drug is provided in the product label in which the indication section should clearly state the treatment concept, e.

Characteristics of Single Pivotal Trials Supporting Regulatory Approvals of Novel Non-orphan, Non-oncology Drugs in the European Union and United States from 2012-2016.

For regulatory approval of a new medicine, the gold standard for demonstration of efficacy has traditionally been a minimum of two positive, adequate, and well-controlled clinical trials. Nevertheless, drugs to treat cancer and rare diseases are usually approved based on a single and often uncontrolled pivotal trial. In contrast, little is known about single pivotal trial approvals for non-orphan, non-oncology drugs.

Technology-Enabled Assessment of Functional Health.

The maturation of pervasive computing technologies has dramatically altered the face of healthcare. With the introduction of mobile devices, body area networks, and embedded computing systems, care providers can use continuous, ecologically valid information to overcome geographic and temporal barriers and thus provide more effective and timely health assessments. In this paper, we review recent technological developments that can be harnessed to replicate, enhance, or create methods for assessment of functional performance.

European Marketing Authorizations Granted Based on a Single Pivotal Clinical Trial: The Rule or the Exception?

A minimum of two positive, adequate, and well-controlled clinical trials has historically been the gold standard for providing substantial evidence to support regulatory approval of a new medicine. Nevertheless, the present analysis of European Marketing Authorizations granted between 2012 and 2016 showed that 45% of new active substances were approved based on a single pivotal clinical trial. For therapeutic areas such as oncology and cardiovascular diseases, approvals based on a single pivotal trial are the rule rather than the exception, whereas new medicines within the nervous system area were generally supported by two or more pivotal trials.

Active engagement in a web-based tutorial to prevent obesity grounded in Fuzzy-Trace Theory predicts higher knowledge and gist comprehension.

We used Sharable Knowledge Objects (SKOs) to create an Intelligent Tutoring System (ITS) grounded in Fuzzy-Trace Theory to teach women about obesity prevention: GistFit, getting the gist of healthy eating and exercise. The theory predicts that reliance on gist mental representations (as opposed to verbatim) is more effective in reducing health risks and improving decision making. Technical information was translated into decision-relevant gist representations and gist principles (i.

Abnormalities of motor function, transcription and cerebellar structure in mouse models of THAP1 dystonia.

DYT6 dystonia is caused by mutations in THAP1 [Thanatos-associated (THAP) domain-containing apoptosis-associated protein] and is autosomal dominant and partially penetrant. Like other genetic primary dystonias, DYT6 patients have no characteristic neuropathology, and mechanisms by which mutations in THAP1 cause dystonia are unknown. Thap1 is a zinc-finger transcription factor, and most pathogenic THAP1 mutations are missense and are located in the DNA-binding domain.

Evidence that small molecule enhancement of β-hexosaminidase activity corrects the behavioral phenotype in Dutch APP(E693Q) mice through reduction of ganglioside-bound Aβ.

Certain mutant Alzheimer's amyloid-β (Aβ) peptides (that is, Dutch mutant APP(E693Q)) form complexes with gangliosides (GAβ). These mutant Aβ peptides may also undergo accelerated aggregation and accumulation upon exposure to GM2 and GM3. We hypothesized that increasing β-hexosaminidase (β-hex) activity would lead to a reduction in GM2 levels, which in turn, would cause a reduction in Aβ aggregation and accumulation.

Dystonia type 6 gene product Thap1: identification of a 50 kDa DNA-binding species in neuronal nuclear fractions.

Mutations in THAP1 result in dystonia type 6, with partial penetrance and variable phenotype. The goal of this study was to examine the nature and expression pattern of the protein product(s) of the Thap1 transcription factor (DYT6 gene) in mouse neurons, and to study the regional and developmental distribution, and subcellular localization of Thap1 protein. The goal was accomplished via overexpression and knock-down of Thap1 in the HEK293T cell line and in mouse striatal primary cultures and western blotting of embryonic Thap1-null tissue.

Induction of DARPP-32 by brain-derived neurotrophic factor in striatal neurons in vitro is modified by histone deacetylase inhibitors and Nab2.

Neurotrophins and modifiers of chromatin acetylation and deacetylation participate in regulation of transcription during neuronal maturation and maintenance. The striatal medium spiny neuron is supported by cortically-derived brain derived neurotrophic factor and is the most vulnerable neuron in Huntington's disease, in which growth factor and histone deacetylase activity are both disrupted. We examined the ability of three histone deacetylase inhibitors, trichostatin A, valproic acid and Compound 4 b, alone and combined with brain derived neurotrophic factor (BDNF), to promote phenotypic maturation of striatal medium spiny neurons in vitro.

Benefits of the HiRes 120 coding strategy combined with the Harmony processor in an adult European multicentre study.

Conclusion: The Harmony processor was found to be reliable, comfortable and offered a substantially increased battery life compared with the previous generation processor. No significant improvement in speech understanding with HiRes was demonstrated from objective measures, but the majority of subjects showed a clear subjective preference for the combination HiRes 120/Harmony processor.

Objectives: To evaluate experience with the Harmony™ sound processor, together with the HiRes 120 strategy.

Psychosis and silent celiac disease in a down syndrome adolescent: a case report.

Celiac disease is an autoimmune systemic disorder. It presents gastrointestinal and nongastrointestinal manifestations as well as associated conditions. We report a 16-year-old Down syndrome girl who presented psychosis symptomatology, and she was diagnosed as having silent celiac disease.

[Cochlear implant complications and failures].

Introduction: Cochlear implantation is a relatively safe surgery performed on profound bilateral hearing loss patients. Its surgical indications have increased and the age of implantation has decreased over the last years. As with any other surgery, it presents complications; device failure is one of the most important, given its potential risk for the need to explant and reimplant the device.

[Paediatric cochlear implantation in the critical period of the auditory pathway, our experience].

Introduction: Numerous experimental and clinical studies have suggested a critical or sensitive period in which the auditory pathway develops its greatest potential in terms of plasticity and learning. Early cochlear implantation performed in prelingual deaf children in this period provides a better prognosis for language acquisition. The aim of this study is to show the importance of cochlear implantation before this critical period ends.

beta-Glucosidases as detonators of plant chemical defense.

Some plant secondary metabolites are classified as phytoanticipins. When plant tissue in which they are present is disrupted, the phytoanticipins are bio-activated by the action of beta-glucosidases. These binary systems--two sets of components that when separated are relatively inert--provide plants with an immediate chemical defense against protruding herbivores and pathogens.

The beta-glucosidases responsible for bioactivation of hydroxynitrile glucosides in Lotus japonicus.

Lotus japonicus accumulates the hydroxynitrile glucosides lotaustralin, linamarin, and rhodiocyanosides A and D. Upon tissue disruption, the hydroxynitrile glucosides are bioactivated by hydrolysis by specific beta-glucosidases. A mixture of two hydroxynitrile glucoside-cleaving beta-glucosidases was isolated from L.

The magnitude of the antibody and memory B cell responses during priming with a protein-polysaccharide conjugate vaccine in human infants is associated with the persistence of antibody and the intensity of booster response.

Rapid waning of anti-polysaccharide bactericidal Ab and vaccine effectiveness is observed following infant immunization with the serogroup C meningococcal (MenC) glycoconjugate vaccine. This is despite the demonstrable presence of immunological memory. Persistence of functional Ab, therefore, appears to be the key determinant of MenC conjugate vaccine effectiveness.

Paralytic ileus: a complication after intrathecal baclofen therapy.

Introduction: Baclofen is frequently used in the management of spasticity. When the therapeutic benefit of oral baclofen is not satisfactory, intrathecal administration should be considered. This method reduces side effects due to a reduction in dosage compared to oral administration.

Risk factors for invasive disease among children in Spain.

Objective: To identify the risk factors related to invasive disease caused by Haemophilus influenzae type b (Hib), Neisseria meningitidis, and Streptococcus pneumoniae.

Methods: Case-control study. All hospitals of the region of Valencia in Spain (covering 95% of the population of Valencia).

Auditory neuropathy in patients carrying mutations in the otoferlin gene (OTOF).

Inherited hearing impairment affects one in 2,000 newborns. Nonsyndromic prelingual forms are inherited mainly as autosomal recessive traits, for which 16 genes are currently known. Mutations in the genes encoding connexins 26 and 30 account for up to 50% of these cases.