Down-Regulation of Tinnitus Negative Valence via Concurrent HD-tDCS and PEI Technique: A Pilot Study.

Around 30% of the general population experience subjective tinnitus, characterized by conscious attended awareness perception of sound without an external source. Clinical distress tinnitus is more than just experiencing a phantom sound, as it can be highly disruptive and debilitating, leading those affected to seek clinical help. Effective tinnitus treatments are crucial for psychological well-being, but our limited understanding of the underlying neural mechanisms and a lack of a universal cure necessitate further treatment development. In light of the neurofunctional tinnitus model predictions and transcranial electrical stimulation, we conducted an open-label, single-arm, pilot study that utilized high-definition transcranial direct current stimulation (HD-tDCS) concurrent with positive emotion induction (PEI) techniques for ten consecutive sessions to down-regulate tinnitus negative valence in patients with clinical distress tinnitus. We acquired resting-state functional magnetic resonance imaging scans of 12 tinnitus patients (7 females, mean age = 51.25 ± 12.90 years) before and after the intervention to examine resting-state functional connectivity (rsFC) alterations in specific seed regions. The results showed reduced rsFC at post-intervention between the attention and emotion processing regions as follows: (1) bilateral amygdala and left superior parietal lobule (SPL), (2) left amygdala and right SPL, (3) bilateral dorsolateral prefrontal cortex (dlPFC) and bilateral pregenual anterior cingulate cortex (pgACC), and (4) left dlPFC and bilateral pgACC (FWE corrected p < 0.05). Furthermore, the post-intervention tinnitus handicap inventory scores were significantly lower than the pre-intervention scores (p < 0.05). We concluded that concurrent HD-tDCS and PEI might be effective in reducing tinnitus negative valence, thus alleviating tinnitus distress.

Dose-Response Transcranial Electrical Stimulation Study Design: A Well-Controlled Adaptive Seamless Bayesian Method to Illuminate Negative Valence Role in Tinnitus Perception.

The use of transcranial Electrical Stimulation (tES) in the modulation of cognitive brain functions to improve neuropsychiatric conditions has extensively increased over the decades. tES techniques have also raised new challenges associated with study design, stimulation protocol, functional specificity, and dose-response relationship. In this paper, we addressed challenges through the emerging methodology to investigate the dose-response relationship of High Definition-transcranial Direct Current Stimulation (HD tDCS), identifying the role of negative valence in tinnitus perception. In light of the neurofunctional testable framework and tES application, hypotheses were formulated to measure clinical and surrogate endpoints. We posited that conscious pairing adequately pleasant stimuli with tinnitus perception results in correction of the loudness misperception and would be reinforced by concurrent active HD-tDCS on the left Dorsolateral Prefrontal Cortex (dlPFC). The dose-response relationship between HD-tDCS specificity and the loudness perception is also modeled. We conducted a double-blind, randomized crossover pilot study with six recruited tinnitus patients. Accrued data was utilized to design a well-controlled adaptive seamless Bayesian dose-response study. The sample size (n = 47, for 90% power and 95% confidence) and optimum interims were anticipated for adaptive decision-making about efficacy, safety, and single session dose parameters. Furthermore, preliminary pilot study results were sufficient to show a significant difference (90% power, 99% confidence) within the longitudinally detected self-report tinnitus loudness between before and under positive emotion induction. This study demonstrated a research methodology used to improve emotion regulation in tinnitus patients. In the projected method, positive emotion induction is essential for promoting functional targeting under HD-tDCS anatomical specificity to indicate the efficacy and facilitate the dose-finding process. The continuous updating of prior knowledge about efficacy and dose during the exploratory stage adapts the anticipated dose-response model. Consequently, the effective dose range to make superiority neuromodulation in correcting loudness misperception of tinnitus will be redefined. Highly effective dose adapts the study to a standard randomized trial and transforms it into the confirmatory stage in which active HD-tDCS protocol is compared with a sham trial (placebo-like). Establishing the HD-tDCS intervention protocols relying on this novel method provides reliable evidence for regulatory agencies to approve or reject the efficacy and safety. Furthermore, this paper supports a technical report for designing multimodality data-driven complementary investigations in emotion regulation, including EEG-driven neuro markers, Stroop-driven attention biases, and neuroimaging-driven brain network dynamics.

Cochlear turns measurements in patients with meningitis: A histopathological study.

OBJECTIVE: To demonstrate the cochlear turns area changes among patients with a history of meningitis, through otopatologic study. METHODS: We performed an analysis of the area of the bony cochlear turns and the cochlear lumen of the horizontal sections containing the modiolus and the area of the basal turn at the level of round window, in temporal bones obtained from patients with a history of meningitis and compared to a nondiseased control group. RESULTS: The mean area of the bony walls and the lumen of all cochlear turns are reduced within the meningitis group. Patients who presented a time from the diagnosis of meningitis to death longer than 30 days had a significant reduction in the cochlear turns area, as compared to the control group. CONCLUSION: Future studies may further correlate audiologic outcomes, cochlear volume, and cochlear area among patients with meningitis.

Morphological and molecular correlates of altered hearing sensitivity in the genetically audiogenic seizure-prone hamster GASH/Sal.

Rodent models of audiogenic seizures, in which seizures are precipitated by an abnormal response of the brain to auditory stimuli, are crucial to investigate the neural bases underlying ictogenesis. Despite significant advances in understanding seizure generation in the inferior colliculus, namely the epileptogenic nucleus, little is known about the contribution of lower auditory stations to the seizure-prone network. Here, we examined the cochlea and cochlear nucleus of the genetic audiogenic seizure hamster from Salamanca (GASH/Sal), a model of reflex epilepsy that exhibits generalized tonic-clonic seizures in response to loud sound. GASH/Sal animals under seizure-free conditions were compared with matched control hamsters in a multi-technical approach that includes auditory brainstem responses (ABR) testing, histology, scanning electron microscopy analysis, immunohistochemistry, quantitative morphometry and gene expression analysis (RT-qPCR). The cochlear histopathology of the GASH/Sal showed preservation of the sensory hair cells, but a significant loss of spiral ganglion neurons and mild atrophy of the stria vascularis. At the electron microscopy level, the reticular lamina exhibited disarray of stereociliary tufts with blebs, loss or elongated stereocilia as well as non-parallel rows of outer hair cells due to protrusions of Deiters' cells. At the molecular level, the abnormal gene expression patterns of prestin, cadherin 23, protocadherin 15, vesicular glutamate transporters 1 (Vglut1) and -2 (Vglut2) indicated that the hair-cell mechanotransduction and cochlear amplification were markedly altered. These were manifestations of a cochlear neuropathy that correlated to ABR waveform I alterations and elevated auditory thresholds. In the cochlear nucleus, the distribution of VGLUT2-immunolabeled puncta was differently affected in each subdivision, showing significant increases in magnocellular regions of the ventral cochlear nucleus and drastic reductions in the granule cell domain. This modified inputs lead to disruption of Vglut1 and Vglut2 gene expression in the cochlear nucleus. In sum, our study provides insight into the morphological and molecular traits associated with audiogenic seizure susceptibility in the GASH/Sal, suggesting an upward spread of abnormal glutamatergic transmission throughout the primary acoustic pathway to the epileptogenic region.

Histopathological changes to the peripheral vestibular system following meningitic labyrinthitis.

OBJECTIVE: While cochlear ossification is a common sequalae of meningitic labyrinthitis, less is known about the effects of meningitis on peripheral vestibular end organs. Herein, we investigate histopathologic changes in the peripheral vestibular system and cochlea in patients with a history of meningitic labyrinthitis. METHODS: Temporal bone (TB) specimens from patients with a history of meningitis were evaluated and compared to age-matched controls. Specimens were evaluated by light microscopy and assessed for qualitative changes, including the presence of vestibular and/or cochlear endolymphatic hydrops, presence and location of inflammatory cells, new bone formation, and labyrinthitis ossificans; and quantitative changes, including Scarpa's ganglion neuron (ScGN) and spiral ganglion neuron (SGN) counts. RESULTS: Fifteen TB from 10 individuals met inclusion and exclusion criteria. Presence of inflammatory cells and fibrous tissue was found in 5 TB. Of these, evidence of labyrinthitis ossificans was found in 2 TB. In the peripheral vestibular system, mild to severe degeneration of the vestibular membranous labyrinth was identified in 60% of cases (n = 9 TBs). There was a 21.2% decrease (range, 3%-64%) in the mean total count of ScGN in patients with meningitis, compared to age-matched controls. In the cochlea, there was a 45% decrease (range, 25.3%-80.9%) in the mean total count of SGN compared to age-matched controls (n = 14 TBs). CONCLUSIONS: Otopathologic analysis of TB from patients with a history of meningitic labyrinthitis demonstrated distinct peripheral vestibular changes. Future research may help to delineate potential mechanisms for the observed otopathologic changes following meningitis. LEVEL OF EVIDENCE: N/A.

Analysis of postural control and muscular performance in young and elderly women in different age groups.

BACKGROUND: muscle strength and power are two factors affecting balance. The impact of muscle strength and power on postural control has not been fully explored among different age strata over sixty. OBJECTIVES: the aim of the present study was to assess the muscle strength and power of elderly women in different age groups and determine their correlation with postural control. METHOD: eighty women were divided into four groups: the young 18-30 age group (n=20); the 60-64 age group (n=20); the 65-69 age group (n=20); and the 70-74 age group (n=20). The participants underwent maximum strength (one repetition maximum or 1-RM) and muscle power tests to assess the knee extensor and flexor muscles at 40%, 70%, and 90% 1-RM intensity. The time required by participants to recover their balance after disturbing their base of support was also assessed. RESULTS: the elderly women in the 60-64, 65-69, and 70-74 age groups exhibited similar muscle strength, power, and postural control (p>0.05); however, these values were lower than those of the young group (p<0.05) as expected. There was a correlation between muscle strength and power and the postural control performance (p<0.05). CONCLUSION: despite the age difference, elderly women aged 60 to 74 years exhibited similar abilities to generate strength and power with their lower limbs, and this ability could be one factor that explains the similar postural control shown by these women.

Macroscopic description of the external and middle ear of paca (Cuniculus paca Linnaeus, 1766) / Descrição macroscópica da orelha externa e media da paca (Cuniculus paca Linnaeus, 1766)

Paca (Cuniculus paca), one of the largest rodents of the Brazilian fauna, has inherent characteristics of its species which can conribute as a new option for animal experimantation. As there is a growing demand for suitable experimental models in audiologic and otologic surgical research, the gross anatomy and ultrastructural ear of this rodent have been analyzed and described in detail. Fifteen adult pacas from the Wild Animals Sector herd of Faculdade de Ciências Agrárias e Veterinárias, Unesp-Jaboticabal, were used in this study. After anesthesia and euthanasia, we evaluated the entire composition of the external ear, registering and ddescribing the details; the temporal region was often dissected for a better view and detailing of the tympanic bulla which was removed and opened to expose the ear structures analyzed mascroscopically and ultrastructurally. The ear pinna has a triangular and concave shape with irregular ridges and sharp apex. The external auditory canal is winding in its path to the tympanic mebrane. The tympanic bulla is is on the back-bottom of the skull. The middle ear is formed by a cavity region filled with bone and membranous structures bounded by the tympanic membrane and the oval and round windows. The tympanic membrane is flat and seals the ear canal. The anatomy of the paca ear is similar to the guinea pig and from the viewpoint of experimental model has major advantages compared with the mouse ear.

A paca (Cuniculus paca), um dos maiores roedores da fauna brasileira, possui características inerentes à sua espécie que podem contribuir como uma nova opção de animal experimental; assim, considerando-se que há crescente busca por modelos experimentais apropriados para pesquisas audiológicas e otológica cirúrgicas foram analisados e descritos em detalhes a anatomia macroscópica e ultraestrutural da orelha desse roedor. Para o estudo, utilizaram-se 15 animais adultos provenientes do plantel do Setor de Animais Silvestres da Faculdade de Ciências Agrárias e Veterinárias, Unesp-Jaboticabal, Jaboticabal/SP. Após anestesia e eutanásia, avaliou-se toda a composição da orelha externa, registrando-se e descrevendo-se os detalhes, também se dissecou a região temporal para melhor visibilização e detalhamento da bula timpânica e estas foram removidas e abertas a fim de expor as estruturas da orelha, as quais foram analisadas, macroscopicamente e ultraestruturalmente. O pavilhão auricular apresenta forma triangular e côncava com cristas irregulares e ápice pontiagudo; o conduto auditivo externo é sinuoso em seu trajeto até a membrana timpânica; a bula timpânica encontra-se na parte posterior-inferior do crânio; a orelha média é formada por uma região cavitária preenchida por estruturas ósseas e membranosas. É delimitada pela membrana timpânica e as janelas redonda e oval, sendo a membrana timpânica de forma plana e que veda todo o conduto auditivo. A anatomia da orelha da paca é semelhante à da cobaia e do ponto de vista de modelo experimental apresenta grandes vantagens em comparação com a orelha do rato.

Analysis of postural control and muscular performance in young and elderly women in different age groups

BACKGROUND: muscle strength and power are two factors affecting balance. The impact of muscle strength and power on postural control has not been fully explored among different age strata over sixty. OBJECTIVES: the aim of the present study was to assess the muscle strength and power of elderly women in different age groups and determine their correlation with postural control. METHOD: eighty women were divided into four groups: the young 18-30 age group (n=20); the 60-64 age group (n=20); the 65-69 age group (n=20); and the 70-74 age group (n=20). The participants underwent maximum strength (one repetition maximum or 1-RM) and muscle power tests to assess the knee extensor and flexor muscles at 40%, 70%, and 90% 1-RM intensity. The time required by participants to recover their balance after disturbing their base of support was also assessed. RESULTS: the elderly women in the 60-64, 65-69, and 70-74 age groups exhibited similar muscle strength, power, and postural control (p>0.05); however, these values were lower than those of the young group (p<0.05) as expected. There was a correlation between muscle strength and power and the postural control performance (p<0.05). CONCLUSION: despite the age difference, elderly women aged 60 to 74 years exhibited similar abilities to generate strength and power with their lower limbs, and this ability could be one factor that explains the similar postural control shown by these women. .

Aminoglycoside antibiotic derivatives: preparation and evaluation of toxicity on cochlea and vestibular tissues and antimicrobial activity.

Aminoglycoside antibiotic derivatives such as neamine, methyl neobiosaminide B, 2-deoxystreptamine, tetra-azidoneamine, tetra-N-acetylneamine, tetra-N-carboxy-benzylneamine, tetra-N-carboxy-methylneamine and tetra-p-methoxy-benzyliminoneamine were prepared and evaluated as to their cochlear and vestibular toxicity. Methyl neobiosaminide B, the most promising derivative in the series showed selective, cochlea-dissociated vestibulotoxic activity and was considered to be a potential lead compound for the treatment of Ménière's disease. Antimicrobial properties of the compounds, qualitatively evaluated against a group of pathogenic bacteria, indicated that neomycin B sulfate, neamine as a free base and methyl-neobiosaminide B dihydrochloride show a broader range of activity when compared to the other derivatives.

Rinossinusite em pacientes infectados pelo vírus da imunodeficiência humana (hiv): estudo clínico e microbiológico / Rhinosinusitis in Patients with Human Immunodeficiency Virus (HIV): Clinical and Microbiological Aspects

Estudos recentes têm apresentado o crescente aumento na incidência de rinossinusite crônica e recorrente em pacientes infectados pelo vírus da imunodeficiência humana (HIV), relacionando-o à gravidade do quadro e dificuldade do tratamento, buscando definir sua etiologia infecciosa para a terapêutica antimicrobiana mais adequada. Objetivos: Buscar a positividade de amostras obtidas de punção dos seios maxilares em pacientes HIV com rinossinusite crônica, definindo o agente etiológico infeccioso quando presente, e contribuir para o tratamento antimicrobiano mais adequado nestes casos. Material e método: 21 pacientes HIV e 14 pacientes não HIV com diagnóstico de rinossinusite crônica e recorrente foram submetidos a coleta de amostras do antro maxilar por punção via fossa canina ou no ato cirúrgico. As amostras foram submetidas a exame microbiológico para bactérias aeróbias, anaeróbias e micobactérias e cultura para fungos. Foram analisados dados clínicos e exames laboratoriais e de imagem. Resultado: observamos ausência de crescimento em 33,32% dos pacientes HIV e 28,57% dos não HIV. No grupo de pacientes HIV encontramos predomínio do Staphylococcus aureus (16,65%), seguido do Staphylococcus epidermidis, Streptococcus pneumoniae e Peptostreptococcus sp. (11,10%). No grupo de pacientes não HIV encontramos predomínio da Pseudomonas aeruginosa e Klebsiella pneumoniae (18,18%). Conclusão: Os dados mostram a prevalência de bactérias aeróbias, cocos gram positivos na rinossinusite crônica de pacientes HIV, seguidos de anaeróbios e sem especial destaque para a Pseudomonasaeruginosa, como propõem diversos trabalhos. No grupo dos não HIV encontramos predomínio de bacilos gram negativos. Os índices de negatividade foram altos, podendo se questionar se estas bactérias não seriam contaminantes de uma mucosa predisposta por alterações estruturais irreversíveis, podendo esses agentes contribuir para aumentar o dano estrutural. Devido à possibilidade da presença de germes atípicos em pacientes HIV com rinossinusite crônica, e pela própria característica de recorrência dos quadros nessa população, a utilização dos antibióticos de segunda escolha para rinossinusites, bem como de antifúngicos, deve ser considerada.

Studies have been reported a increase in chronic and recurrent rinossinusitis in human virus immunodeficiency (HIV) infected patients and this account with severity and difficult to treat, trying to define the etyology and correct antimicrobial treatment. Purpose: Available positive cultures with antral maxilary sinus puncture through oral cavity in HIV patients with chronic rinossinusitis get infectious agent, when present and to contribute adequating antimicrobial treatment in this population. Material and methods: 21 HIV patients and 14 normal patients with chronic and recurrent rinossinusitis were going through antral maxilary puncture to canine dimple or during endonasal surgery. This material was examined by microbiologyst to aerobic, anaerobic, micobacterial and fungus agents. Clinical, laboratory and radiologycal features was available. Results: Negativity was observed in 33,32% and 28,57% of the antimicrobial cultures on HIV and NON-HIV patients, respectivelly. On HIV patients the Stbaphilococcus aureus becoming positive in 16,65%, Stapbilococcus epidermidis, Streptococcus pneumoniae and Peptostreptococcus sp. get positive in 11.10%. In NON-HIV patients, Pseudomonas aeruginosa, Klebsiella pneumoniae becoming positive in 18.18%. Conclusion: It was observed most positivity to aerobic gram positive cocos and anaerobic agents in HIV patients with chronic rinossinusitis, without special positivity to Pseudomonas aeruginosa like some other studies. In NON-HIV patients, the gram negative roads was most frequent. The increased negativity can do we think abouth this bacterial agents can be contamination to the sinus mucosa with irreversible structural damage and this contribute to increase this structural damage. For the possibility of atipical antimicrobial agents on HIV patients with chronic rinossinusitis and caracteristic recurrential on this population, the antimicrobial terapy with second choice drugs to rinossinusitis, as well antifungi drugs most be considered.

Perdas auditivas condutivas / Conductive hearing loss

O sistema auditivo é constituído pelas orelhas externa, média e interna e pelas vias auditivas no sistema nervoso central. A membrana timpânica tem como função amplificar a pressão sonora, permitindo uma amplificação de sons. A orelha média compreende a cavidade timpânica composta pela membrana timpânica (camadas intermediária e interna), cadeia ossicular com seus músculos e ligamentos, a tuba auditiva, o adito, o antro e as células mastóideas. Conhecendo-se as estruturas das orelhas externa e média e sua fisiologia na transmissão sonora, pode-se reconhecer o que alterações neste sistema trazem de prejuízos para a função auditiva no ser humano, constituindo assim quadros clínicos diversos que cursam com perdas auditivas condutivas.