Lhx3, a LIM domain transcription factor, is regulated by Pou4f3 in the auditory but not in the vestibular system

A dominant mutation of the gene encoding the POU4F3 transcription factor underlies human non-syndromic progressive hearing loss DFNA15. Using oligonucleotide microarrays to generate expression profiles of inner ears of Pou4f3 ddl/ ddl mutant and wild-type mice, we have identified and validated Lhx3, a LIM domain transcription factor, as an in vivo target gene regulated by Pou4f3. Lhx3 is a hair cell-specific gene expressed in all hair cells of the auditory and vestibular system as early as embryonic day 16. The level of Lhx3 mRNA is greatly reduced in the inner ears of embryonic Pou4f3 mutant mice. Our data also show that the expression of Lhx3 is regulated differently in auditory and vestibular hair cells. This is the first example of a hair cell-specific gene expressed both in auditory and in vestibular hair cells, with differential regulation of expression in these two closely related systems.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72019/1/j.1460-9568.2007.05332.x.pd

CLRN1 Is Nonessential in the Mouse Retina but Is Required for Cochlear Hair Cell Development

Mutations in the CLRN1 gene cause Usher syndrome type 3 (USH3), a human disease characterized by progressive blindness and deafness. Clarin 1, the protein product of CLRN1, is a four-transmembrane protein predicted to be associated with ribbon synapses of photoreceptors and cochlear hair cells, and recently demonstrated to be associated with the cytoskeleton. To study Clrn1, we created a Clrn1 knockout (KO) mouse and characterized the histological and functional consequences of Clrn1 deletion in the retina and cochlea. Clrn1 KO mice do not develop a retinal degeneration phenotype, but exhibit progressive loss of sensory hair cells in the cochlea and deterioration of the organ of Corti by 4 months. Hair cell stereocilia in KO animals were longer and disorganized by 4 months, and some Clrn1 KO mice exhibited circling behavior by 5–6 months of age. Clrn1 mRNA expression was localized in the retina using in situ hybridization (ISH), laser capture microdissection (LCM), and RT–PCR. Retinal Clrn1 transcripts were found throughout development and adulthood by RT–PCR, although expression peaked at P7 and declined to undetectable levels in adult retina by ISH. LCM localized Clrn1 transcripts to the retinas inner nuclear layer, and WT levels of retinal Clrn1 expression were observed in photoreceptor-less retinas. Examination of Clrn1 KO mice suggests that CLRN1 is unnecessary in the murine retina but essential for normal cochlear development and function. This may reflect a redundancy in the mouse retina not present in human retina. In contrast to mouse KO models of USH1 and USH2, our data indicate that Clrn1 expression in the retina is restricted to the Müller glia. This is a novel finding, as most retinal degeneration associated proteins are expressed in photoreceptors, not in glia. If CLRN1 expression in humans is comparable to the expression pattern observed in mice, this is the first report of an inner retinal protein that, when mutated, causes retinal degeneration

Integration of Transcriptomics, Proteomics, and MicroRNA Analyses Reveals Novel MicroRNA Regulation of Targets in the Mammalian Inner Ear

We have employed a novel approach for the identification of functionally important microRNA (miRNA)-target interactions, integrating miRNA, transcriptome and proteome profiles and advanced in silico analysis using the FAME algorithm. Since miRNAs play a crucial role in the inner ear, demonstrated by the discovery of mutations in a miRNA leading to human and mouse deafness, we applied this approach to microdissected auditory and vestibular sensory epithelia. We detected the expression of 157 miRNAs in the inner ear sensory epithelia, with 53 miRNAs differentially expressed between the cochlea and vestibule. Functionally important miRNAs were determined by searching for enriched or depleted targets in the transcript and protein datasets with an expression consistent with the dogma of miRNA regulation. Importantly, quite a few of the targets were detected only in the protein datasets, attributable to regulation by translational suppression. We identified and experimentally validated the regulation of PSIP1-P75, a transcriptional co-activator previously unknown in the inner ear, by miR-135b, in vestibular hair cells. Our findings suggest that miR-135b serves as a cellular effector, involved in regulating some of the differences between the cochlear and vestibular hair cells

A Myo6 Mutation Destroys Coordination between the Myosin Heads, Revealing New Functions of Myosin VI in the Stereocilia of Mammalian Inner Ear Hair Cells

Myosin VI, found in organisms from Caenorhabditis elegans to humans, is essential for auditory and vestibular function in mammals, since genetic mutations lead to hearing impairment and vestibular dysfunction in both humans and mice. Here, we show that a missense mutation in this molecular motor in an ENU-generated mouse model, Tailchaser, disrupts myosin VI function. Structural changes in the Tailchaser hair bundles include mislocalization of the kinocilia and branching of stereocilia. Transfection of GFP-labeled myosin VI into epithelial cells and delivery of endocytic vesicles to the early endosome revealed that the mutant phenotype displays disrupted motor function. The actin-activated ATPase rates measured for the D179Y mutation are decreased, and indicate loss of coordination of the myosin VI heads or ‘gating’ in the dimer form. Proper coordination is required for walking processively along, or anchoring to, actin filaments, and is apparently destroyed by the proximity of the mutation to the nucleotide-binding pocket. This loss of myosin VI function may not allow myosin VI to transport its cargoes appropriately at the base and within the stereocilia, or to anchor the membrane of stereocilia to actin filaments via its cargos, both of which lead to structural changes in the stereocilia of myosin VI–impaired hair cells, and ultimately leading to deafness

Exacerbation of chronic myofascial pain during COVID-19

Objective: The COVID-19 pandemic-related restrictions on the public have led to changes in occupation status and societal behavior which may be linked with adverse effects on mental health. We hypothesized that elevated personal stress induced by COVID-19 may underlie pain exacerbation among individuals with chronic myofascial pain. Methods: Comprehensive myofascial pain questionnaire among 319 patients registered in our pain clinic. In total, 78 patients with TMD-associated pain responded and 113 patients with pain in other orofacial regions responded. Results: Patients with chronic TMD pain reported a higher self-rated stress level, which correlated with significantly increased pain intensity, and analgesic consumption. In contrast, patients experiencing non-TMD pain did not report of any increase pain, regardless of their stress levels. Conclusion: Significant correlation between self-perceived psychosocial stress levels and chronic myofascial pain exacerbation. Patients may benefit from early education and conservative intervention, and avoid uncontrolled increases in consumption of pain relief medication

Reasons underlying the intention to vaccinate children aged 5-11 against COVID-19: A cross-sectional study of parents in Israel, November 2021

Vaccination is a key tool to mitigate impacts of the COVID-19 pandemic. In Israel, COVID-19 vaccines became available to adults in December 2020 and to 5–11-year-old children in November 2021. Ahead of the vaccine roll-out in children, we aimed to determine whether surveyed parents intended to vaccinate their children and describe reasons for their intentions. We collected information on parental socio-demographic characteristics, COVID-19 vaccine history, intention to vaccinate their children against COVID-19, and reasons for parental decisions using an anonymous online survey. We identified associations between parental characteristics and plans to vaccinate children using a logistic regression model and described reasons for intentions to vaccinate or not. Parental non-vaccination and having experienced major vaccination side effects were strongly associated with non-intention to vaccinate their children (OR 0.09 and 0.18 respectively, p < .001). Parents who were younger, lived in the socio-economically deprived periphery, and belonged to the Arab population had lower intentions to vaccinate their children. Reasons for non-intention to vaccinate included concerns about vaccine safety and efficacy (53%, 95%CI 50–56) and the belief that COVID-19 is a mild disease (73%, 95%CI 73–79), while a frequent motive for vaccination was the return to normal social and educational life (89%, 95%CI 87–91). Understanding rationales for COVID-19 vaccine rejection or acceptance, as well as parental demographic data, can pave the way for intentional educational campaigns to encourage not only vaccination against COVID-19, but also regular childhood vaccine programming

Rapid implementation of teledentistry during the Covid-19 lockdown

Introduction: The current corona virus disease 2019 (COVID-19) outbreak set new challenges to nearly all health plans and large health organizations worldwide, including movement restrictions, strict limitations in healthcare services, especially in the dental profession, and patient fears regarding potential infection. Telehealth can serve as an effective platform for remote connection between dental healthcare providers and patients, and can help reduce the risk of infection when social distancing is required. Objective: The current study aimed to evaluate the quality of treatment provided via teledentistry, as perceived by patients using the service, as well as their willingness to use online distant medical consultation in the future. Methods: Since March 2020, a new online service was implemented in the Oral Medicine Unit and Oral and Maxillofacial Surgery Department in the Galilee Medical Center, to expand the range of services beyond merely emergency treatments. Results: The current study examined the quality of teledentistry services as perceived by 89 patients participating in at least one teleconsultation, and their acceptance of remote healthcare. Satisfaction rates were high in patients who received both full and partial solution to their chief complaint. Moreover, acceptance of the teledentistry platform was high, even in the older age groups. Conclusions: We propose to implement teledentistry services in current and future pandemics, as well as during routine times, to strengthen our health care system with digital technologies

The impact of delayed surgical intervention following high velocity maxillofacial injuries

Abstract Our study compares the number of postoperative complications of Syrian patients admitted to the Galilee Medical Center (GMC) over a 5-year period (May 2013–May 2018) for treatment after initial high-velocity maxillofacial injuries sustained during the Syrian civil war. Specifically, we evaluated complication rates of patients arriving “early,” within 24 h, to the GMC versus those who arrived “late,” or 14–28 days following high-velocity maxillofacial injuries. Both groups of patients received definitive surgical treatment within 48 h of admission to our hospital with a total of 60 patients included in this study. The mean age was 26 ± 8 years (range: 9–50) and all except one were male. Postoperative complications in the early group were found to be significantly higher compared to the delayed arrival group (p = 0.006). We found that unintentionally delayed treatment may have contributed to a critical revascularization period resulting in improved healing and decreased postoperative morbidity and complications. We discuss potential mechanisms for complication rate variations, including critical vascularization periods. Our study may add to a growing body of work demonstrating the potential benefit of delayed surgical treatment for high-velocity maxillofacial injuries

COVID-19 Vaccine Acceptance Among Dental Professionals Based on Employment Status During the Pandemic

The COVID-19 pandemic spread rapidly across the globe, leading governments to impose prolonged lockdowns on both movement and commerce. Although lockdowns decrease the rates of novel infections, they can have devastating consequences on the economy and employment levels. One of the most severely affected sectors during this crisis has been dental medicine. Dental professionals are uniquely exposed to environments with high levels of occupational hazards, conferring additional risks of viral exposure and transmission. We analyzed 506 anonymous questionnaires completed by dentists and residents regarding acceptance of a future potential SARS-CoV-2 vaccine. Our results demonstrate a statistically significant correlation between the individual's unemployment rate and their willingness to inoculate with a SARS-CoV-2 vaccine when it becomes available. This information can be used to predict trends of vaccine acceptance or rejection based on economic burden during the COVID-19 pandemic by different sectors as part of the preparedness toward global vaccination programs