Female Sexual Function Index Adaptation for Breast Cancer Patients (FSFI-BC): Brazilian Portuguese Translation and Cultural Adaptation.

BACKGROUND: The assessment of female sexual function after diagnosis and treatment of breast cancer is relevant, as cancer can negatively affect sexuality and, therefore, quality of life. Instruments assessing female sexuality can be useful in clinical practice. However, there are few validated instruments available for this purpose. This study aimed to translate the Female Sexual Function Index Adaptation for Breast Cancer Patients (FSFI-BC) into Brazilian Portuguese and culturally adapt it for use in Brazil. PATIENTS AND METHODS: Translation and cross-cultural adaptation followed the linguistic validation process, according to international guidelines. The instrument was translated and back-translated by independent translators. Sixty women aged 25 to 70 years who had been diagnosed and surgically treated for breast cancer at least 6 months previously participated in the cultural adaptation process. Participants were stratified into sexually active or inactive. Internal consistency was analyzed using Cronbach's alpha coefficient. RESULTS: Mean participant age was 52.5 years. For sexually active women, reliability analysis (Cronbach's alpha) showed excellent internal consistency between the items of the subscales 'Desire/Arousal' (α = 0.912) and 'Orgasm' (α = 0.904), and good internal consistency for 'Lubrication' (α = 0.814) and 'Pain' (α = 0.839). For sexually inactive women, excellent internal consistency was observed between the items of the subscale 'Reason for Inactivity - difficulty lubricating' (α = 0.930), and good internal consistency for the other subscales. The instrument had face and content validity. CONCLUSIONS: FSFI-BC was translated and culturally adapted to the context of the Brazilian population.

Spectrum and frequency of GJB2 mutations in a cohort of 264 Portuguese nonsyndromic sensorineural hearing loss patients.

OBJECTIVE: To assess the spectrum and prevalence of mutations in the GJB2 gene in Portuguese nonsyndromic sensorineural hearing loss (NSSHL) patients. DESIGN: Sequencing of the coding region, basal promoter, exon 1, and donor splice site of the GJB2 gene; screening for the presence of the two common GJB6 deletions. STUDY SAMPLE: A cohort of 264 Portuguese NSSHL patients. RESULTS: At least one out of 21 different GJB2 variants was identified in 80 (30.2%) of the 264 patients analysed. Two mutant alleles were found in 53 (20%) of these probands, of which 83% (44/53) harboured at least one c.35delG allele. Twenty-seven (10.2%) of the probands harboured only one mutant allele. Subsequent analysis revealed that the GJB6 deletion del(GJB6-D13S1854) was present in at least 7.4% (2/27) of the patients carrying only one mutant GJB2 allele. Overall, one in five (55/264) of the patients were diagnosed as having DFNB1-related NSSHL, of which the vast majority (53/55) harboured only GJB2 mutations. CONCLUSIONS: This study provides clear demonstration that mutations in the GJB2 gene are an important cause of NSSHL in Portugal, thus representing a valuable indicator as regards therapeutical and rehabilitation options, as well as genetic counseling of these patients and their families.

The global hearing therapeutic pipeline: 2021.

Hearing loss is a serious condition affecting more than 1.5 billion people globally. Many affected people benefit from the use of devices, such as hearing aids, but these do not restore natural hearing, and many users still struggle to follow speech in the presence of background noise. Consequently, there is rapid growth in work to discover therapeutics to address this need. Our analysis of the therapeutic pipeline for inner ear and central processing disorders identified 23 assets in clinical trials and 56 in preclinical development, of which 25% have entered the pipeline in the past three years. The innovative potential of this pipeline is encouraging, but there are translational hurdles to be overcome. We highlight challenges for the pipeline and comment on opportunities to support and strengthen it.

Targeted deletion of the RNA-binding protein Caprin1 leads to progressive hearing loss and impairs recovery from noise exposure in mice.

Cell cycle associated protein 1 (Caprin1) is an RNA-binding protein that can regulate the cellular post-transcriptional response to stress. It is a component of both stress granules and neuronal RNA granules and is implicated in neurodegenerative disease, synaptic plasticity and long-term memory formation. Our previous work suggested that Caprin1 also plays a role in the response of the cochlea to stress. Here, targeted inner ear-deletion of Caprin1 in mice leads to an early onset, progressive hearing loss. Auditory brainstem responses from Caprin1-deficient mice show reduced thresholds, with a significant reduction in wave-I amplitudes compared to wildtype. Whilst hair cell structure and numbers were normal, the inner hair cell-spiral ganglion neuron (IHC-SGN) synapse revealed abnormally large post-synaptic GluA2 receptor puncta, a defect consistent with the observed wave-I reduction. Unlike wildtype mice, mild-noise-induced hearing threshold shifts in Caprin1-deficient mice did not recover. Oxidative stress triggered TIA-1/HuR-positive stress granule formation in ex-vivo cochlear explants from Caprin1-deficient mice, showing that stress granules could still be induced. Taken together, these findings suggest that Caprin1 plays a key role in maintenance of auditory function, where it regulates the normal status of the IHC-SGN synapse.

Drug-induced Stress Granule Formation Protects Sensory Hair Cells in Mouse Cochlear Explants During Ototoxicity.

Stress granules regulate RNA translation during cellular stress, a mechanism that is generally presumed to be protective, since stress granule dysregulation caused by mutation or ageing is associated with neurodegenerative disease. Here, we investigate whether pharmacological manipulation of the stress granule pathway in the auditory organ, the cochlea, affects the survival of sensory hair cells during aminoglycoside ototoxicity, a common cause of acquired hearing loss. We show that hydroxamate (-)-9, a silvestrol analogue that inhibits eIF4A, induces stress granule formation in both an auditory cell line and ex-vivo cochlear cultures and that it prevents ototoxin-induced hair-cell death. In contrast, preventing stress granule formation using the small molecule inhibitor ISRIB increases hair-cell death. Furthermore, we provide the first evidence of stress granule formation in mammalian hair cells in-vivo triggered by aminoglycoside treatment. Our results demonstrate that pharmacological induction of stress granules enhances cell survival in native-tissue, in a clinically-relevant context. This establishes stress granules as a viable therapeutic target not only for hearing loss but also other neurodegenerative diseases.

The controversial p.Met34Thr variant in GJB2 gene: Two siblings, one genotype, two phenotypes.

INTRODUCTION: Recent advances in molecular genetics have increased the identification of genes and mutations responsible for inherited forms of hearing loss (HL), enabling early detection of these cases. Approximately, 60% of early-onset HL cases are due to genetic causes, of which 70% are non-syndromic. Of these, 75-80% are inherited in an autosomal recessive pattern (DFNB). Mutations in GJB2 gene, coding for connexin 26 (Cx26), are the major cause of autosomal recessive hereditary HL, but some GJB2 mutations are yet of unclear or controversial significance. OBJECTIVES: The aim of the present study was to identify the etiology of hearing loss, and correlate genotype-phenotype, in two Portuguese siblings with profound and moderate non-syndromic sensorineural bilateral HL. MATERIAL AND METHODS: The affected subjects and their parents underwent audiological and genetic study. Molecular analysis of GJB2 gene was performed, searching for mutations in the coding region and receptor splicing site by automated sequencing. RESULTS: The onset and the degree of HL were different in the two affected subjects. However, the same GJB2 genotype [p.Met34Thr]+[p.Arg184Pro] was identified in both siblings. The c.551G>C (p.Arg184Pro) and c.101T>C (p.Met34Thr) missense variants were inherited from the father and mother, respectively, both heterozygous carriers of these variants. CONCLUSION: The clinical and genetic data here presented suggest that the non-syndromic sensorineural HL of these two Portuguese siblings might be due to the presence of p.Met34Thr and p.Arg184Pro variants in compound heterozygosity. If so, p.Met34Thr variant could have function as a hypomorphic allele that may cause HL depending on the opposing GJB2 allele. The observed phenotypic variability may not, however, be solely explained by variable expression of this genotype. A putative modifier gene or mutations in another HL-associated gene could probably be contributing to the severe HL in one of the siblings.

Avaliação microbiológica do pirarucu (Arapaima gigas) manejado nas Reservas de Desenvolvimento Sustentável Mamirauá e Amanã (resultados preliminares) / Microbiological evaluation of pirarucu (Arapaima gigas) managed in Mamirauá and Amanã Sustainable Development Reserves (preliminary results)

O pirarucu (Arapaima gigas) é um peixe carnívoro da Amazônia e é considerado um dos peixes mais importantes da região. Ele é manejado de forma sustentável por Acordos de Pesca da Reserva de Desenvolvimento sustentável Mamirauá. Dados microbiológicos são necessários para verificar a qualidade higiênico-sanitária dos peixes manejados nessa região. Devido a essa importância o presente trabalho teve como objetivo avaliar a qualidade microbiológica do pirarucu manejado nas Reservas de Desenvolvimento Sustentável Mamirauá e Amanã. Foram avaliados 16 amostras no total, provenientes de dois Acordos de Pesca diferentes (AP1 e AP2). Os microrganismos analisados foram Mesófilos, Staphylococcus aureus, Coliformes Totais e Escherichia coli. As amostras dos dois Acordos de Pesca tiveram presença para todas as bactérias e grupos de bactérias analisados, com valores mais elevados para o AP1. Tendo assim a partir desses resultados a necessidade de um controle maior das condições higiênico-sanitária no fluxograma de beneficiamento dos locais estudados.

A novel p.Leu213X mutation in GJB2 gene in a Portuguese family.

INTRODUCTION: Hearing loss is the most common sensory disability and is present in about 1.9 per 1000 infants at birth. The DFNB1 locus (13q11-q12) includes the genes GJB2, coding for connexin 26, and GJB6, encoding connexin 30. More than 100 mutations have been identified associated with autosomal dominant and recessive hearing loss in the GJB2 gene. OBJECTIVES: The aim of the present study was to identify the genetic aetiology of deafness in two Portuguese individuals, presenting nonsyndromic sensorineural moderate and severe hearing loss, respectively. PATIENTS AND METHODS: The individuals were evaluated in both ears by pure tone audiometry and blood samples were collected after written informed consent was signed. DNA extraction and PCR amplification of GJB2 coding region followed standard methodologies. PCR products were automatically sequenced in both directions. RESULTS: We identified a novel mutation, c.638T>A (p.Leu213X), in GJB2 gene. This nonsense mutation was found in both siblings, and was inherited from their hearing father. Molecular analysis showed that the two siblings were also heterozygous for c.333-334delAA, a previously described GJB2 deletion. This novel mutation was not found in a random control sample of 480 individuals that were screened for coding region of GJB2 gene. p.Leu213X mutation identified in this study for the first time changes the codon 213, coding for a highly conserved and slowly evolving residue of connexin 26, localised to the C-terminus domain of the protein, to a STOP codon, leading to the deletion of the last 14 amino acids of the protein. CONCLUSION: We can conclude that the aetiology of deafness in these individuals is due to the GJB2 genotype involving the c.333-334delAA deletion and the novel p.Leu213X mutation in compound heterozygosity.

Infarto cerebelar. Considerações sobre 12 casos / Cerebellar infarction. Considerations about 12 cases

Trata-se de estudo retrospectivo sobre 12 casos de infarto cerebelar. Sete pacientes eram do sexo masculino e cinco, do feminino. A idade variou entre 46 e 76 anos, com média de 54 anos. As causas foram hipertensão arterial sistêmica em seis, endocardite bacteriana em três e desconhecida em outros três. A cefaléia foi sintoma presente em dez pacientes, vômitos em oito, tonteira em oito, ataxia da marcha em sete e vertigem em quatro. A tomografia do crânio foi útil no diagnóstico e conduta. Onze pacientes foram submetidos a tratamento conservador. Derivação ventricular externa e craniectomia suboccipital foram realizadas em um paciente. Houve quatro óbitos. O prognóstico esteve diretamente relacionado ao nível de consciência por ocasião da admissão, da extensão do infarto e da idade do paciente.

Doença de Rosai-Dorfman

A doença de Rosai-Dorfman ou Histiocitose Sinusal com Linfadenomegalia Maciça é uma desorganização histiocitária proliferativa rara. Tem como principal manifestação clínica Linfonodomegalia cervical, mas pode atingir outros linfonodos e órgãos extranodais. A etiologia ainda não é bem conhecida, porém há estudos associando com patógenos infecciosos e imunodeficiência...The Rosai-Dorfman or Sinus Histiocytosis with Massive adenomegaly clutter is a rare histiocytic proliferative. Its main clinical manifestation of cervical Lymph node enlargement, but may spread to other lymph nodes and extranodal organs. The etiology is not well known, but there are reports of associated with infectious pathogens and immunodeficiency ...