Hearing and vision:the age old problem

Opticians and audiologists tend to see the same people. Many factors that are associated with poorer vision, whether hereditary, pre-natal, or post-natal, are also associated with poorer hearing. The most common factor is simply old age. According to the Royal National Institute for Deaf People (RNID), more than half of all people aged over 60 have some degree of hearing loss and are gradually losing their hearing as part of the ageing process – a process known as presbycusis.

Mechanisms of tumour-induced cachexia

The effect of cancer cachexia on host metabolism has been studied in mice transplanted with either the MAC16 adenocarcinoma which induces profound loss of host body weight and depletion of lipid stores or, the MAC13 adenocarcinoma which is of the same histological type, but which grows without an effect on host body weight. Oxidation of D-[U-14C]glucose was elevated in both tumour-bearing states irrespective of cachexia, when compared with non tumour-bearing controls. Both the MAC16 and MAC13 tumours in vivo utilised glucose at the expense of the brain, where its use was partially replaced by 3-hydroxybutyrate, a ketone body. Oxidation of both [U-14C]palmitic acid and [1-14C]triolein was significantly increased in MAC16 tumour-bearing animals and decreased in MAC13 tumour-bearing animals when compared with non tumour-bearing controls, suggesting that in cachectic tumour-bearing animals, mobilisation of body lipids is accompanied by an increased utilisation by the host. Weight loss in MAC16 tumour-bearing animals is associated with the production of a lipolytic factor. Injection of this partially purified lipolytic factor induced weight loss in recipient animals which could be maintained over time in tumour-bearing animals. This suggests that the tumour acts as a sink for the free fatty acids liberated as a result of the mobilisatation of adipose stores. Lipids are important as an energy source in cachectic animals because of their high calorific value and because glucose is being diverted away from host tissues to support tumour growth. Their importance is further demonstrated by the evidence of a MAC16 tumour-associated lipolytic factor. This lipolytic factor is the key to understanding the alterations in host metabolism that occur in tumour-induced cachexia, and may provide future alternatives for the reversal of cachexia and the treatment of cancer itself.

Help-seeking for medically unexplained hearing difficulties:a qualitative study

Aims - Up to 10% of audiology patients report diffi culties hearing speech in noise even though clinical investigation reveals normal hearing thresholds, in other words, no evidence of physical pathology. The diagnostic category applied to these patients is known as King-Kopetzky Syndrome (KKS). This study aimed to gather descriptions of patients' experiences of the clinical encounter involving their KKS diagnosis and analyse the themes of help-seeking, as part of a larger study into the process of coping with medically unexplained hearing diffi culties. Method - A qualitative approach was employed, comprising unstructured interviews in the homes of 25 patients who had attended audiology services (and received a diagnosis of KKS) in Bath and Cardiff. Thematic analysis of transcripts was undertaken, infl uenced by grounded theory techniques. Findings - Informants characterized the clinical encounter as either negative or positive. Negative consultations were those in which patients' illness claims were dismissed and as such not validated. Positive encounters were typifi ed by the provision of meaningful information that reconciled clinical information with the patients' experiences of hearing loss. Conclusion - Successful management of medically unexplained illnesses requires the adoption of a patient-centred approach, rather than focusing on the absence of observable pathology

An exploration of the perspectives of help-seekers prescribed hearing aids

Aim - This pilot study uses qualitative methods to learn about the psycho-social needs of people who seek help with hearing loss. Background - There has been some emphasis in health policy to reduce the number of appointments required between assessment of hearing loss and fitting of hearing aids. This may respond to audiological needs but may not address the psycho-social needs. This study piloted a phenomenological approach to identify the patient's perspective. Methods - A phenomenological approach was taken to provide description of patient perspectives. Findings - Six patients reported that help-seeking was primarily influenced by the need to appease social partners and to improve hearing performance. Hearing aids were not regarded as acceptable treatments. Conclusions - Service providers need to consider the psycho-social consequences of hearing-aid issue alongside audiological needs.

Effects of real -time captioning and sign language interpreting on the learning of college students who are deaf or hard of hearing

College personnel are required to provide accommodations for students who are deaf and hard of hearing (D/HoH), but few empirical studies have been conducted on D/HoH students as they learn under the various accommodation conditions (sign language interpreting, SLI, real-time captioning, RTC, and both). Guided by the experiences of students who are D/HoH at Miami-Dade College (MDC) who requested RTC in addition to SLI as accommodations, the researcher adopted Merten’s transformative-emancipatory theoretical framework that values perceptions and voice of students who are D/HoH. A mixed methods design addressed two research questions: Did student learning differ for each accommodation? What did students experience while learning through accommodations? Participants included 30 students who were D/HoH (60% women). They represented MDC’s majority minority population: 10% White (non-Hispanic), 20% Black (non-Hispanic, including Haitian/Caribbean), 67% Hispanic, and 3% other. Hearing loss, ranged from severe-profound (70%) to mild-moderate (30%). All were able to communicate with American Sign Language: Learning was measured while students who were D/HoH viewed three lectures under three accommodation conditions (SLI, RTC, SLI+RTC). The learning measure was defined as the difference in pre- and post-test scores on tests of the content presented in the lectures. Using repeated measure ANOVA and ANCOVA, confounding variables of fluency in American Sign Language and literacy skills were treated as covariates. Perceptions were obtained through interviews and verbal protocol analysis that were signed, videotaped, transcribed, coded, and examined for common themes and metacognitive strategies. No statistically significant differences were found among the three accommodations on the learning measure. Students who were D/HoH expressed thoughts about five different aspects of their learning while they viewed lectures: (a) comprehending the information, (b) feeling a part of the classroom environment, (c) past experiences with an accommodation, (d) individual preferences for an accommodation, (e) suggestions for improving an accommodation. They exhibited three metacognitive strategies: (a) constructing knowledge, (b) monitoring comprehension, and (c) evaluating information. No patterns were found in the types of metacognitive strategies used for any particular accommodation. The researcher offers recommendations for flexible applications of the standard accommodations used with students who are D/HoH.

Development of test-based wind-driven rain intrusion model for hurricane-induced building interior and contents damage

Major portion of hurricane-induced economic loss originates from damages to building structures. The damages on building structures are typically grouped into three main categories: exterior, interior, and contents damage. Although the latter two types of damages, in most cases, cause more than 50% of the total loss, little has been done to investigate the physical damage process and unveil the interdependence of interior damage parameters. Building interior and contents damages are mainly due to wind-driven rain (WDR) intrusion through building envelope defects, breaches, and other functional openings. The limitation of research works and subsequent knowledge gaps, are in most part due to the complexity of damage phenomena during hurricanes and lack of established measurement methodologies to quantify rainwater intrusion. This dissertation focuses on devising methodologies for large-scale experimental simulation of tropical cyclone WDR and measurements of rainwater intrusion to acquire benchmark test-based data for the development of hurricane-induced building interior and contents damage model. Target WDR parameters derived from tropical cyclone rainfall data were used to simulate the WDR characteristics at the Wall of Wind (WOW) facility. The proposed WDR simulation methodology presents detailed procedures for selection of type and number of nozzles formulated based on tropical cyclone WDR study. The simulated WDR was later used to experimentally investigate the mechanisms of rainwater deposition/intrusion in buildings. Test-based dataset of two rainwater intrusion parameters that quantify the distribution of direct impinging raindrops and surface runoff rainwater over building surface — rain admittance factor (RAF) and surface runoff coefficient (SRC), respectively —were developed using common shapes of low-rise buildings. The dataset was applied to a newly formulated WDR estimation model to predict the volume of rainwater ingress through envelope openings such as wall and roof deck breaches and window sill cracks. The validation of the new model using experimental data indicated reasonable estimation of rainwater ingress through envelope defects and breaches during tropical cyclones. The WDR estimation model and experimental dataset of WDR parameters developed in this dissertation work can be used to enhance the prediction capabilities of existing interior damage models such as the Florida Public Hurricane Loss Model (FPHLM).^

Studies of the role of nf-κb in controlling osteoclast differentiation and bone loss

Increased osteoclast (OC) bone resorption and/or decreased osteoblast (OB) bone formation contribute to bone loss in osteoporosis and rheumatoid arthritis (RA). Findings of the basic and translational research presented in this thesis demonstrate a number of mechanisms by which cytokine-induced NF-κB activation controls bone resorption and formation: 1) Tumour necrosis factor-α (TNF) expands pool of OC precursors (OCPs) by promoting their proliferation through stimulation of the expression of macrophage colony stimulating factor (M-CSF) receptor, c-Fms, and switching M-CSF-induced resident (M2) to inflammatory (M1) macrophages with enhanced OC forming potential and increased production of inflammatory factors through induction of NF-κB RelB; 2) Similar to RANKL, TNF sequentially activates transcriptional factors NF-κB p50 and p52 followed by c-Fos and then NFATc1 to induce OC differentiation. However, TNF alone induces very limited OC differentiation. In contrast, it pre-activates OCPs to express cFos which cooperates with interleukin-1 (IL-1) produced by these OCPs in an autocrine mechanism by interacting with bone matrix to mediate the OC terminal differentiation and bone resorption from these pre-activated OCPs. 3) TNF-induced OC formation is independent of RANKL but it also induces NF-κB2 p100 to limit OC formation and bone resorption, and thus p100 deletion accelerates joint destruction and systemic bone loss in TNF-induced RA; 4) TNF receptor associated factor-3 (TRAF3) limits OC differentiation by negatively regulating non-canonical NF-κB activation and RANKL induces TRAF3 ubiquitination and lysosomal degradation to promote OC differentiation. Importantly, a lysosomal inhibitor that inhibits TRAF3 degradation prevents ovariectomy-induced bone loss; 5) RelB and Notch NICD bind RUNX2 to inhibit OB differentiation and RelB:p52 dimer association with NICD inhibit OB differentiation by enhancing the binding of RBPjκ to Hes1. These findings suggest that non-canonical NF- κB signaling could be targets to develop new therapies for RA or osteoporosis. For example 1) Agents that degrade TNF-induced RelB could block M1 macrophage differentiation to inhibit inflammation and joint destruction for the therapy of RA; 2)Agents that prevent p100 processing or TRAF3 degradation could inhibit bone resorption and also stimulate bone formation simultaneously for the therapy of osteoporosis.

Stapedotomy and its effect on hearing – our experience with 54 cases.

Introduction: This study reviews the cases of stapedotomy and evaluates its effectiveness at improving hearing loss in patients with otosclerosis. Materials and methods: Retrospective review of patients’ records who had clinical and audiometric diagnosis of otosclerosis from January to December 2012. Results: A total of 54 stapedotomy surgeries (52 unilateral and 1 bilateral surgeries) were received. Average post-operative ABG for 0.5, 1, 2 and 4 KHz showed that 61.1% had complete closure of ABG (ABG < 10 dB) compared with 1.6% preoperatively and 85.2% had closure of ABG to within 20dB compared with 4.7% preoperatively (t – 13.89, p = 0.000). More than 94% had hearing improvement and 81.5% had ABG closure greater than 10 dB postoperatively (mean gain 23.38 ± 12.37, t = 13.89, p = 0.000). A total of 13% complications were recorded with TM perforation (5.6%) being the commonest complication. Conclusion: Stapedotomy is an effective surgical procedure for the treatment of otosclerosis which leads to improvement in patients’ quality of life. A favorable hearing outcome can be obtained by the combination of experienced hands with minimal surgical trauma and appropriate surgical technique.

Association of SNPs in LCP1 and CTIF with hearing in 11 year old children:findings from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort and the G-EAR consortium

BACKGROUND: The genetic basis of hearing loss in humans is relatively poorly understood. In recent years, experimental approaches including laboratory studies of early onset hearing loss in inbred mouse strains, or proteomic analyses of hair cells or hair bundles, have suggested new candidate molecules involved in hearing function. However, the relevance of these genes/gene products to hearing function in humans remains unknown. We investigated whether single nucleotide polymorphisms (SNPs) in the human orthologues of genes of interest arising from the above-mentioned studies correlate with hearing function in children. METHODS: 577 SNPs from 13 genes were each analysed by linear regression against averaged high (3, 4 and 8 kHz) or low frequency (0.5, 1 and 2 kHz) audiometry data from 4970 children in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth-cohort at age eleven years. Genes found to contain SNPs with low p-values were then investigated in 3417 adults in the G-EAR study of hearing. RESULTS: Genotypic data were available in ALSPAC for a total of 577 SNPs from 13 genes of interest. Two SNPs approached sample-wide significance (pre-specified at p = 0.00014): rs12959910 in CBP80/20-dependent translation initiation factor (CTIF) for averaged high frequency hearing (p = 0.00079, β = 0.61 dB per minor allele); and rs10492452 in L-plastin (LCP1) for averaged low frequency hearing (p = 0.00056, β = 0.45 dB). For low frequencies, rs9567638 in LCP1 also enhanced hearing in females (p = 0.0011, β = -1.76 dB; males p = 0.23, β = 0.61 dB, likelihood-ratio test p = 0.006). SNPs in LCP1 and CTIF were then examined against low and high frequency hearing data for adults in G-EAR. Although the ALSPAC results were not replicated, a SNP in LCP1, rs17601960, is in strong LD with rs9967638, and was associated with enhanced low frequency hearing in adult females in G-EAR (p = 0.00084). CONCLUSIONS: There was evidence to suggest that multiple SNPs in CTIF may contribute a small detrimental effect to hearing, and that a sex-specific locus in LCP1 is protective of hearing. No individual SNPs reached sample-wide significance in both ALSPAC and G-EAR. This is the first report of a possible association between LCP1 and hearing function.

Ruolo della proteina OPA3 nella patogenesi di malattie neurodegenerative

OPA3 è una proteina codificata dal genoma nucleare che, grazie a una sequenza di targeting mitocondriale, viene indirizzata ai mitocondri dopo la sua sintesi. Le mutazioni nel gene OPA3 sono associate a due patologie neurodegenerative: la Sindrome di Costeff, causata da mutazioni recessive, e una forma di atrofia ottica dominante che si manifesta con cataratta e spesso sordità. L’esatta funzione e regolazione della proteina non sono ancora state completamente chiarite, così come la sua localizzazione nella membrana mitocondriale esterna o interna. Lo scopo di questa tesi era quello di fare luce sulla funzione della proteina OPA3, con particolare interesse alla dinamica mitocondriale e all’autofagia, sulla sua localizzazione subcellulare ed infine di definire il meccanismo patogenetico nelle patologie neurodegenerative causate da mutazioni in questo gene. A questo scopo abbiamo utilizzato sia una linea di neuroblastoma silenziata stabilmente per OPA3 che linee cellulari primarie derivate da pazienti. I risultati del presente studio dimostrano che la riduzione di OPA3, indotta nelle cellule del neuroblastoma e presente nei fibroblasti derivati dai pazienti, produce alterazioni nel network mitocondriale con uno sbilanciamento a favore della fusione. Questo fenomeno è probabilmente dovuto all’aumento della forma long della proteina OPA1 che è stato riscontrato in entrambi i modelli cellulari. Inoltre, seppur con direzione apparentemente opposta, in entrambi i modelli abbiamo osservato un’alterata regolazione dell’autofagia. Infine, abbiamo confermato che OPA3 localizza nella membrana mitocondriale interna ed è esposta per gran parte nella matrice. Inoltre, un segnale della proteina è stato trovato anche nelle mitochondrial associated membranes, suggerendo un possibile ruolo di OPA3 nel trasferimento dei lipidi tra i mitocondri e il reticolo endoplasmatico. Abbiamo rilevato un’interazione della proteina OPA3 con l’acido fosfatidico che non era mai stata evidenziata fino ad oggi. Queste osservazioni sono compatibili con le alterazioni della dinamica mitocondriale e la disregolazione dell’autofagia documentate nei modelli studiati.

Caracterização do jogo simbólico em deficientes auditivos: estudo de casos e controles

TEMA: crianças deficientes auditivas não adquirem linguagem no mesmo período e velocidade de uma criança normo-ouvinte, pois o aprendizado da linguagem oral é um evento essencialmente auditivo. O desenvolvimento da criança consiste na aquisição progressiva de habilidades motoras e psicocognitivas, e a entrada no mundo simbólico é fator preponderante para que a criança possa atingir os níveis de maior complexidade no domínio da linguagem. OBJETIVO: relacionar o jogo simbólico e aspectos do desenvolvimento infantil em crianças deficientes auditivas com seus pares ouvintes. MÉTODO: 32 crianças, de ambos os sexos, de 2 a 6 anos de idade, pareadas por idade, foram submetidas à Avaliação da Maturidade Simbólica e ao Teste de Triagem do Desenvolvimento de Denver II, sendo 16 deficientes auditivas neurossensorial de grau moderado a profundo (grupo pesquisa - GP) e 16 normo-ouvintes (grupo controle - GC). RESULTADOS: observou-se simbolismo na brincadeira de 81,25% do GP, enquanto que no GC isto ocorreu em 87,5%. No Teste de Denver II 100% do GP foi classificado como risco, e o GC apresentou 94% de crianças normais e 6% de risco (p < 0,001). CONCLUSÃO: observou-se desempenho semelhante nos dois grupos quanto ao jogo simbólico. Entretanto, numa análise qualitativa, o GP apresentou brincadeiras menos complexas que o GC. Observou-se que o GP apresentou desempenho no jogo simbólico compatível ao seu desempenho nos aspectos pessoal-social, motor fino-adaptativo e motor grosseiro do Teste de Denver II.

Contribuições para análise da política de saúde auditiva no Brasil

OBJETIVO: Realizar o levantamento do quantitativo dos procedimentos relacionados à adaptação de aparelho de amplificação sonora individual (AASI) incluídos na Tabela do Sistema Único de Saúde (Tabela SUS). MÉTODOS: Os dados sobre os procedimentos relacionados à adaptação de AASI incluídos na Tabela SUS foram levantados no site www.datasus.gov.br. Após o levantamento desses dados, foi realizada a organização e a análise descritiva da produção dos atendimentos ambulatoriais registrados pelos serviços de saúde auditiva do Brasil, durante o período de novembro de 2004 a julho de 2010. Os dados foram analisados estatisticamente. RESULTADOS: Quanto aos procedimentos relacionados à dispensação de AASI no território nacional no âmbito da saúde auditiva, em 2006, a terapia fonoaudiológica ultrapassou o quantitativo obtido pela adaptação de AASI e, o acompanhamento fonoaudiológico, por sua vez, foi pouco realizado no país. Os AASI com tecnologias B e C vem sendo mais adaptados do que os AASI de tecnologia A e a realização de medida com microfone sonda ou acoplador de 2cc na adaptação dos AASI é pouco realizada em comparação ao ganho funcional. CONCLUSÃO: Houve grandes avanços na atenção ao deficiente auditivo no país, mas é necessário aprimorar o acompanhamento dos usuários de AASI, e revisar procedimentos como medidas com microfone sonda e tecnologias dos AASI.