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Research Square May 2024Stereocilia are unidirectional F-actin-based cylindrical protrusions on the apical surface of inner ear hair cells and function as biological mechanosensors of sound and...
Live-cell single-molecule fluorescence microscopy for protruding organelles reveals regulatory mechanisms of MYO7A-driven cargo transport in stereocilia of inner ear hair cells.
Stereocilia are unidirectional F-actin-based cylindrical protrusions on the apical surface of inner ear hair cells and function as biological mechanosensors of sound and acceleration. Development of functional stereocilia requires motor activities of unconventional myosins to transport proteins necessary for elongating the F-actin cores and to assemble the mechanoelectrical transduction (MET) channel complex. However, how each myosin localizes in stereocilia using the energy from ATP hydrolysis is only partially understood. In this study, we develop a methodology for live-cell single-molecule fluorescence microscopy of organelles protruding from the apical surface using a dual-view light-sheet microscope, diSPIM. We demonstrate that MYO7A, a component of the MET machinery, traffics as a dimer in stereocilia. Movements of MYO7A are restricted when scaffolded by the plasma membrane and F-actin as mediated by MYO7A's interacting partners. Here, we discuss the technical details of our methodology and its future applications including analyses of cargo transportation in various organelles.
PubMed: 38826223
DOI: 10.21203/rs.3.rs-4369958/v1 -
PloS One 2024Since the early 2000's, digital reading applications have enhanced the language and literacy skills of typically hearing young children; however, no digital storybook... (Clinical Trial)
Clinical Trial
Since the early 2000's, digital reading applications have enhanced the language and literacy skills of typically hearing young children; however, no digital storybook intervention currently exists to scaffold the early language and literacy skills of their peers who are deaf or hard of hearing. To address this gap, our research team developed a novel digital storybook intervention called Hear Me Read with the aim of enhancing the therapeutic, language, and literacy benefits of speech-language therapy. This prospective clinical trial (registered at clinicaltrials.gov, NCT#: 05245799) aims to determine the efficacy of adding Hear Me Read to in-person speech-language therapy for children aged three to five years who are deaf or hard of hearing. Fifty caregivers, their child, and their child's treating speech-language pathologist participate in the trial for 12 months. In the first six months, children attend standard-of-care speech-language therapy sessions. In the second six months, children continue to attend standard-of-care speech-language therapy sessions and use the Hear Me Read application, via a study supplied iPad. The primary outcome of this trial is that, compared to in-person speech-language therapy alone, in-person speech-language therapy with Hear Me Read will improve vocabulary, speech, and language outcomes in children aged three to five years who are deaf or hard of hearing. The secondary outcome is that, compared to in-person speech-language therapy alone, in-person speech-language therapy with Hear Me Read will improve literacy outcomes in children aged three to five years who are deaf or hard of hearing. The goal of this intervention is to help children who are deaf or hard of hearing achieve their vocabulary, speech, language, and literacy goals through interactive digital storybook reading.
Topics: Humans; Child, Preschool; Reading; Prospective Studies; Deafness; Male; Female; Literacy; Hearing Loss; Language Therapy; Speech Therapy
PubMed: 38820413
DOI: 10.1371/journal.pone.0302734 -
Frontiers in Genetics 2024Cross-sectional data allow the investigation of how genetics influence health at a single time point, but to understand how the genome impacts phenotype development, one...
Cross-sectional data allow the investigation of how genetics influence health at a single time point, but to understand how the genome impacts phenotype development, one must use repeated measures data. Ignoring the dependency inherent in repeated measures can exacerbate false positives and requires the utilization of methods other than general or generalized linear models. Many methods can accommodate longitudinal data, including the commonly used linear mixed model and generalized estimating equation, as well as the less popular fixed-effects model, cluster-robust standard error adjustment, and aggregate regression. We simulated longitudinal data and applied these five methods alongside naïve linear regression, which ignored the dependency and served as a baseline, to compare their power, false positive rate, estimation accuracy, and precision. The results showed that the naïve linear regression and fixed-effects models incurred high false positive rates when analyzing a predictor that is fixed over time, making them unviable for studying time-invariant genetic effects. The linear mixed models maintained low false positive rates and unbiased estimation. The generalized estimating equation was similar to the former in terms of power and estimation, but it had increased false positives when the sample size was low, as did cluster-robust standard error adjustment. Aggregate regression produced biased estimates when predictor effects varied over time. To show how the method choice affects downstream results, we performed longitudinal analyses in an adolescent cohort of African and European ancestry. We examined how developing post-traumatic stress symptoms were predicted by polygenic risk, traumatic events, exposure to sexual abuse, and income using four approaches-linear mixed models, generalized estimating equations, cluster-robust standard error adjustment, and aggregate regression. While the directions of effect were generally consistent, coefficient magnitudes and statistical significance differed across methods. Our in-depth comparison of longitudinal methods showed that linear mixed models and generalized estimating equations were applicable in most scenarios requiring longitudinal modeling, but no approach produced identical results even if fit to the same data. Since result discrepancies can result from methodological choices, it is crucial that researchers determine their model , refrain from testing multiple approaches to obtain favorable results, and utilize as similar as possible methods when seeking to replicate results.
PubMed: 38818035
DOI: 10.3389/fgene.2024.1203577 -
Health Services Management Research May 2024The sharing of information and feedback directly from service-providing staff to healthcare organisational management is vital for organisational culture and service...
The sharing of information and feedback directly from service-providing staff to healthcare organisational management is vital for organisational culture and service improvement. However, hospital doctors report feeling unable to communicate effectively with management to provide evidence and affect improvement, and this can impact job satisfaction, workplace relations, service delivery and ultimately patient safety. In this paper, we draw on data elicited from a Mobile Instant Messaging Ethnography (MIME) study involving 28 hospital doctors working in Irish hospitals, to explore the barriers preventing them from speaking up and effecting change, and the impact of this on staff morale and services. We identify three major barriers, consistent with previous literature, to effective feedback and communication: (1) organisational deafness, (2) disconnect between managers and frontline staff, and (3) denial of the narratives and issues raised. We draw these together to identify key implications from these findings for healthcare managers, and suggest policy and practice improvements.
PubMed: 38817143
DOI: 10.1177/09514848241254929 -
Nature Communications May 2024Our limited understanding of the pathophysiological mechanisms that operate during sepsis is an obstacle to rational treatment and clinical trial design. There is a...
Our limited understanding of the pathophysiological mechanisms that operate during sepsis is an obstacle to rational treatment and clinical trial design. There is a critical lack of data from low- and middle-income countries where the sepsis burden is increased which inhibits generalized strategies for therapeutic intervention. Here we perform RNA sequencing of whole blood to investigate longitudinal host response to sepsis in a Ghanaian cohort. Data dimensional reduction reveals dynamic gene expression patterns that describe cell type-specific molecular phenotypes including a dysregulated myeloid compartment shared between sepsis and COVID-19. The gene expression signatures reported here define a landscape of host response to sepsis that supports interventions via targeting immunophenotypes to improve outcomes.
Topics: Humans; Sepsis; COVID-19; Ghana; Transcriptome; Phenotype; Male; Cohort Studies; SARS-CoV-2; Female; Adult; Middle Aged; Gene Expression Profiling; Sequence Analysis, RNA
PubMed: 38816375
DOI: 10.1038/s41467-024-48821-0 -
"Congenital cytomegalovirus in Sub-Saharan Africa-a narrative review with practice recommendations".Frontiers in Public Health 2024Cytomegalovirus (CMV) is the most common cause of congenital infection internationally, occurring in 0.67% of births, and increasingly recognised as a major public... (Review)
Review
Cytomegalovirus (CMV) is the most common cause of congenital infection internationally, occurring in 0.67% of births, and increasingly recognised as a major public health burden due to the potential for long-term neurodevelopmental and hearing impairment. This burden includes estimates of 10% of childhood cerebral palsy and up to 25% of childhood deafness. In Sub-Saharan Africa, where CMV-seroprevalence is almost ubiquitous, prevalence of congenital CMV (cCMV) is higher than the global average, and yet there is a dearth of research and initiatives to improve recognition, diagnosis and treatment. This narrative review outlines the epidemiology and clinical presentation of cCMV, discusses issues of case identification and treatment in Sub-Saharan Africa, and recommends a framework of strategies to address these challenges. Considering the significant burden of cCMV disease in this setting, it is undoubtably time we embark upon improving diagnosis and care for these infants.
Topics: Humans; Cytomegalovirus Infections; Africa South of the Sahara; Cytomegalovirus; Infant, Newborn; Prevalence; Female; Pregnancy
PubMed: 38813410
DOI: 10.3389/fpubh.2024.1359663 -
Frontiers in Public Health 2024is one of the porcine pathogens that have recently emerged as a pathogen capable of causing zoonoses in some humans. Patients infected with can present with sepsis,...
INTRODUCTION
is one of the porcine pathogens that have recently emerged as a pathogen capable of causing zoonoses in some humans. Patients infected with can present with sepsis, meningitis, or arthritis. Compared to common pathogens, such as , , and , infections in humans have been reported only rarely.
METHODS
This case report described a 57-year-old man who presented with impaired consciousness and fever following several days of backache. He was a butcher who worked in an abattoir and had wounded his hands 2 weeks prior. The patient was dependent on alcohol for almost 40 years. was detected in the cerebrospinal fluid by metagenomic next-generation sequencing. Although he received adequate meropenem and low-dose steroid therapy, the patient suffered from bilateral sudden deafness after 5 days of the infection. The final diagnosis was meningitis and sepsis.
RESULTS
The patient survived with hearing loss in both ears and dizziness at the 60-day follow-up.
DISCUSSION
We reported a case of infection manifested as purulent meningitis and sepsis. Based on literature published worldwide, human meningitis shows an acute onset and rapid progression in the nervous system. Similar to bacterial meningitis, effective antibiotics, and low-dose steroids play important roles in the treatment of human meningitis.
Topics: Humans; Streptococcus suis; Male; Middle Aged; Streptococcal Infections; China; Meningitis, Bacterial; Anti-Bacterial Agents; Sepsis; Hearing Loss, Sudden
PubMed: 38808002
DOI: 10.3389/fpubh.2024.1369703 -
Ear, Nose, & Throat Journal May 2024Paradoxical embolism from right-to-left shunting is a common cause of cryptogenic stroke in the young. Circulatory ischemia of the cochlea is closely connected with...
Paradoxical embolism from right-to-left shunting is a common cause of cryptogenic stroke in the young. Circulatory ischemia of the cochlea is closely connected with severe-to-profound sudden sensorineural hearing loss. This study aimed to explore the role of paradoxical embolism in severe-to-profound sudden sensorineural hearing loss in juveniles and young adults. From August 2021 to September 2022, consecutive outpatients under 35 years of age with severe-to-profound sudden hearing loss were included in the study. Routine auditory electrophysiological testing and contrast transcranial Doppler ultrasonography (c-TCD) were conducted, and the results were retrospectively analyzed. Seven patients (age: 19.4 ± 6.5 years) were enrolled, including 5 juveniles and 2 young adults. Three patients had severe deafness, and 4 patients had profound deafness. Right-to-left shunting was detected in all patients through c-TCD. Patent foramen ovale was found in 2 patients while pulmonary arteriovenous fistula was found in 1 patient through contrast transthoracic echocardiography or cardiac catheterization. No patients had precipitating factors for sudden sensorineural hearing loss, and none had abnormalities on head magnetic resonance imaging. Six patients underwent wholeexome sequencing, and no known deafness gene variant was detected. After standard treatment for 1 month, 2, 3, and 2 patients had complete, slight, and no hearing recovery, respectively. Paradoxical embolism is a possible cause of severe-to-profound sudden sensorineural hearing loss in juveniles and young adults. In young patients, c-TCD is an effective screening tool to detect right-to-left shunting, while contrast transthoracic echocardiography is a complementary examination to c-TCD.
PubMed: 38801178
DOI: 10.1177/01455613241250185 -
Frontiers in Psychology 2024The impact of deafness on visual attention has been widely discussed in previous research. It has been noted that deficiencies and strengths of previous research can be...
The impact of deafness on visual attention has been widely discussed in previous research. It has been noted that deficiencies and strengths of previous research can be attributed to temporal or spatial aspects of attention, as well as variations in development and clinical characteristics. Visual attention is categorized into three networks: orienting (exogenous and endogenous), alerting (phasic and tonic), and executive control. This study aims to contribute new neuroscientific evidence supporting this hypothesis. This paper presents a systematic review of the international literature from the past 15 years focused on visual attention in the deaf population. The final review included 24 articles. The function of the orienting network is found to be enhanced in deaf adults and children, primarily observed in native signers without cochlear implants, while endogenous orienting is observed only in the context of gaze cues in children, with no differences found in adults. Results regarding alerting and executive function vary depending on clinical characteristics and paradigms used. Implications for future research on visual attention in the deaf population are discussed.
PubMed: 38800679
DOI: 10.3389/fpsyg.2024.1369941 -
Hearing Research Aug 2024Neurons within a neuronal network can be grouped by bottom-up and top-down influences using synchrony in neuronal oscillations. This creates the representation of...
Neurons within a neuronal network can be grouped by bottom-up and top-down influences using synchrony in neuronal oscillations. This creates the representation of perceptual objects from sensory features. Oscillatory activity can be differentiated into stimulus-phase-locked (evoked) and non-phase-locked (induced). The former is mainly determined by sensory input, the latter by higher-level (cortical) processing. Effects of auditory deprivation on cortical oscillations have been studied in congenitally deaf cats (CDCs) using cochlear implant (CI) stimulation. CI-induced alpha, beta, and gamma activity were compromised in the auditory cortex of CDCs. Furthermore, top-down information flow between secondary and primary auditory areas in hearing cats, conveyed by induced alpha oscillations, was lost in CDCs. Here we used the matching pursuit algorithm to assess components of such oscillatory activity in local field potentials recorded in primary field A1. Additionally to the loss of induced alpha oscillations, we also found a loss of evoked theta activity in CDCs. The loss of theta and alpha activity in CDCs can be directly related to reduced high-frequency (gamma-band) activity due to cross-frequency coupling. Here we quantified such cross-frequency coupling in adult 1) hearing-experienced, acoustically stimulated cats (aHCs), 2) hearing-experienced cats following acute pharmacological deafening and subsequent CIs, thus in electrically stimulated cats (eHCs), and 3) electrically stimulated CDCs. We found significant cross-frequency coupling in all animal groups in > 70% of auditory-responsive sites. The predominant coupling in aHCs and eHCs was between theta/alpha phase and gamma power. In CDCs such coupling was lost and replaced by alpha oscillations coupling to delta/theta phase. Thus, alpha/theta oscillations synchronize high-frequency gamma activity only in hearing-experienced cats. The absence of induced alpha and theta oscillations contributes to the loss of induced gamma power in CDCs, thereby signifying impaired local network activity.
Topics: Animals; Cats; Auditory Cortex; Deafness; Acoustic Stimulation; Gamma Rhythm; Cochlear Implants; Alpha Rhythm; Evoked Potentials, Auditory; Algorithms; Auditory Pathways; Disease Models, Animal; Theta Rhythm
PubMed: 38797035
DOI: 10.1016/j.heares.2024.109032