Repair of surviving hair cells in the damaged mouse utricle.

Sensory hair cells (HCs) in the utricle are mechanoreceptors required to detect linear acceleration. After damage, the mammalian utricle partially restores the HC population and organ function, although regenerated HCs are primarily type II and immature. Whether native, surviving HCs can repair and contribute to this recovery is unclear. Here, we generated the Pou4f3DTR/+; Atoh1CreERTM/+; Rosa26RtdTomato/+ mouse to fate map HCs prior to ablation. After HC ablation, vestibular evoked potentials were abolished in all animals, with ∼57% later recovering responses. Relative to nonrecovery mice, recovery animals harbored more Atoh1-tdTomato+ surviving HCs. In both groups, surviving HCs displayed markers of both type I and type II subtypes and afferent synapses, despite distorted lamination and morphology. Surviving type II HCs remained innervated in both groups, whereas surviving type I HCs first lacked and later regained calyces in the recovery, but not the nonrecovery, group. Finally, surviving HCs initially displayed immature and subsequently mature-appearing bundles in the recovery group. These results demonstrate that surviving HCs are capable of self-repair and may contribute to the recovery of vestibular function.

Every 2-month belatacept maintenance therapy in kidney transplant recipients greater than 1-year posttransplant: A randomized, noninferiority trial.

Belatacept results in improved kidney transplant outcomes, but utilization has been limited by logistical barriers related to monthly (q1m) intravenous infusions. Every 2-month (q2m) belatacept has potential to increase utilization, therefore we conducted a randomized noninferiority trial in low immunologic risk renal transplant recipients greater than 1-year posttransplant. Patients on belatacept were randomly assigned to q1m or q2m therapy. The primary objective was a noninferiority comparison of renal function (eGFR) at 12 months with a noninferiority margin (NIM) of 6.0 ml/min/1.73 m2 . One hundred and sixty-six participants were randomized to q1m (n = 82) or q2m (n = 84) belatacept, 163 patients received treatment, and 76 q1m and 77 q2m subjects completed the 12-month study period. Every 2-month belatacept was noninferior to q1m, as the difference in mean eGFR adjusted for baseline renal function did not exceed the NIM. Two-month dosing was safe and well tolerated, with no patient deaths or graft losses. Four rejection episodes and three cases of donor-specific antibodies (DSAs) occurred among q2m subjects; however, only one rejection and one instance of DSA were observed in subjects adherent to the study protocol. Every 2-month belatacept therapy may facilitate long-term utilization of costimulation blockade, but future multicenter studies with long-term follow-up will further elucidate immunologic risk. (ClinicalTrials.gov NCT02560558).

Methylomic profiles reveal sex-specific differences in leukocyte composition associated with post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a debilitating mental disorder precipitated by trauma exposure. However, only some persons exposed to trauma develop PTSD. There are sex differences in risk; twice as many women as men develop a lifetime diagnosis of PTSD. Methylomic profiles derived from peripheral blood are well-suited for investigating PTSD because DNA methylation (DNAm) encodes individual response to trauma and may play a key role in the immune dysregulation characteristic of PTSD pathophysiology. In the current study, we leveraged recent methodological advances to investigate sex-specific differences in DNAm-based leukocyte composition that are associated with lifetime PTSD. We estimated leukocyte composition on a combined methylation array dataset (483 participants, ∼450 k CpG sites) consisting of two civilian cohorts, the Detroit Neighborhood Health Study and Grady Trauma Project. Sex-stratified Mann-Whitney U test and two-way ANCOVA revealed that lifetime PTSD was associated with significantly higher monocyte proportions in males, but not in females (Holm-adjusted p-val < 0.05). No difference in monocyte proportions was observed between current and remitted PTSD cases in males, suggesting that this sex-specific difference may reflect a long-standing trait of lifetime history of PTSD, rather than current state of PTSD. Associations with lifetime PTSD or PTSD status were not observed in any other leukocyte subtype and our finding in monocytes was confirmed using cell estimates based on a different deconvolution algorithm, suggesting that our sex-specific findings are robust across cell estimation approaches. Overall, our main finding of elevated monocyte proportions in males, but not in females with lifetime history of PTSD provides evidence for a sex-specific difference in peripheral blood leukocyte composition that is detectable in methylomic profiles and that may reflect long-standing changes associated with PTSD diagnosis.

The safety and efficacy of radiofrequency ablation in benign pediatric thyroid disease in the US: An initial case series.

Objective: To evaluate the efficacy and safety of radiofrequency ablation (RFA) for benign nonfunctional thyroid nodules or functional lingual thyroid gland in a pediatric population. Methods: Four pediatric patients (four female; mean age 13.50 ± 4.04, range 8-17 years) with either benign thyroid nodules or mildly obstructive lingual thyroid glands were treated with RFA from 2020 to 2021 were evaluated. The inclusion criteria for RFA therapy were (i) age < 18 years; (ii) benign cytopathological results on ultrasound guided fine needle aspiration; (iii) pressure or pain symptoms caused by the thyroid nodules; (iv) dysphagia or obstruction caused by the lingual thyroid tissue; (v) follow up for >6 months with otolaryngology or endocrinology. Results: Two patients had benign non-functioning thyroid nodules and two had mildly obstructive functioning lingual thyroid glands. Mean follow up was 10.75 ± 4.79 months. Each patient underwent one RFA session with no complications. For the patients with thyroid nodules, there was >74% reduction in nodule size at last follow up with improvement in neck swelling and pain. For the patients with lingual thyroid glands, both did not have any other functional thyroid gland identified. Both had visible decrease in size of the gland as visualized transorally with improvement in dysphagia and obstructive symptoms when lying flat. Conclusion: RFA is a safe and effective option for managing benign thyroid nodules and lingual thyroid glands in a pediatric patient population. Level of evidence: 4.

Effect of vicarious discrimination on race-based stress symptoms among Asian American young adults during the COVID-19 pandemic.

OBJECTIVE: The COVID-19 pandemic has led to a rise in anti-Asian hate crimes in the United States. Previous work has established that experiencing racism increases one's dysfunctional anxiety and avoidance actions-key symptoms of race-based stress symptoms. However, the psychological impact of vicarious, or secondhand, discrimination (witnessing racism targeting one's own race group) remains less understood. METHOD: We tested the hypothesis that higher reported vicarious discrimination would be associated with higher levels of race-based stress symptoms reported by Asian American young adults (n = 135) during the pandemic using a cross-sectional analysis of the COVID-19 Adult Resilience Experiences Study (CARES). Starting in April 2020, CARES assessed sociodemographic characteristics and key psychometric scales in young adults through three waves of online surveys. RESULTS: Our multiple regression analysis showed vicarious discrimination significantly predicted race-based stress symptoms, even after controlling for direct discrimination (p < .01). This association remained significant after controlling for age, gender, subjective childhood family social status, and preexisting psychiatric disorders (p < .01). Our results demonstrate that regardless of the effect that direct discrimination might have on race-based stress symptoms, witnessing discrimination against members of one's own racial group is significantly associated with increased race-based stress symptoms (b = 2.68, p < .01). Social media was the most common source of vicarious discrimination, with one out of three participants in our sample reporting nearly daily exposure. CONCLUSION: Providers should intentionally create a space within the therapeutic setting to discuss the effects of vicarious discrimination. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Single-cell transcriptomic atlas reveals increased regeneration in diseased human inner ear balance organs.

Mammalian inner ear hair cell loss leads to permanent hearing and balance dysfunction. In contrast to the cochlea, vestibular hair cells of the murine utricle have some regenerative capacity. Whether human utricular hair cells regenerate in vivo remains unknown. Here we procured live, mature utricles from organ donors and vestibular schwannoma patients, and present a validated single-cell transcriptomic atlas at unprecedented resolution. We describe markers of 13 sensory and non-sensory cell types, with partial overlap and correlation between transcriptomes of human and mouse hair cells and supporting cells. We further uncover transcriptomes unique to hair cell precursors, which are unexpectedly 14-fold more abundant in vestibular schwannoma utricles, demonstrating the existence of ongoing regeneration in humans. Lastly, supporting cell-to-hair cell trajectory analysis revealed 5 distinct patterns of dynamic gene expression and associated pathways, including Wnt and IGF-1 signaling. Our dataset constitutes a foundational resource, accessible via a web-based interface, serving to advance knowledge of the normal and diseased human inner ear.

Promoting Surgeon-Scientists in Otolaryngology-Head and Neck Surgery-From Bench to Bedside.

Importance: Surgeon-scientists (defined as principal investigators [PIs] with a Doctor of Medicine [MD] degree or a combined MD and Doctor of Philosophy [PhD] degree) in otolaryngology-head and neck surgery (OHNS) are imperative for achieving clinical translation in the OHNS field. Objective: To (1) raise awareness about the current state of surgeon-scientists in OHNS, (2) contextualize the landscape of surgeon-scientists in OHNS by comparing it to those of neurosurgery and ophthalmology, and (3) identify strategies for attracting and retaining surgeon-scientists in OHNS. Evidence Review: Research funding data from fiscal years 2015 to 2021 among surgeon-scientists in OHNS, neurosurgery, and ophthalmology were obtained from the National Institutes of Health (NIH) Research Portfolio Online Reporting Tools Expenditures and Results and the US Department of Defense (DOD) Congressionally Directed Medical Research Programs awards database. The Association of American Medical Colleges provided the total number of active physicians in each specialty per year and the number and percentage of residents with an MD-PhD degree in each specialty per year. Cohen d was used to express the standardized value of the magnitude of the mean difference between compared groups. Findings: From 2015 to 2021, on average, there were 9566 active physicians in OHNS, 5559.8 in neurosurgery, and 18908.8 in ophthalmology. In OHNS, a greater number of NIH K (research career development) grants were held by surgeon-scientists than by PIs with a PhD degree (21.4 vs 5.1; mean difference, 16.3; 95% CI, 14.3-18.3; Cohen d = 9.6), whereas most NIH R (research) and U (cooperative agreement) grants (144.1 vs 81.6; mean difference, 62.6; 95% CI, 46.3-78.9; Cohen d = 4.5) and DOD grants (9.9 vs 4.1; mean difference, 5.7; 95% CI, 1.0-10.4; Cohen d = 1.4) were held by PIs with a PhD degree. In a comparison of OHNS to neurosurgery and ophthalmology, after the number of R and U grants was scaled by the number of physicians in each field, neurosurgery had a much greater number of grants per surgeon than OHNS (0.02 vs 0.01; mean difference, 0.01; 95% CI, 0.01-0.02; Cohen d = 4.2). Additionally, neurosurgeons received a much larger R and U grant amount per physician than otolaryngologists ($10 630.20 vs $4511.80; mean difference, $6118.40; 95% CI, $2625.90-$9610.80; Cohen d = 2.0). For the R and U grant metrics, there were no meaningful differences between OHNS and ophthalmology. Conclusions and Relevance: Results of this database study showed that from 2015 to 2021, the number of governmental grants held by surgeon-scientists in OHNS increased, but there is room for improvement given the metrics of neurosurgeons, a population smaller than otolaryngologists. Possible strategies include intramural research grants, surgeon-scientist training programs, and partnerships between specialty societies and NIH administering institutes and centers.

Omeprazole-induced Visual Hallucinations: A Case Report.

Proton pump inhibitors (PPIs) are medications that are frequently prescribed for gastroesophageal reflux disease. However, a few case reports have described neuropsychiatric symptoms following PPI use. In this report, we present a case of visual hallucinations secondary to PPI usage and propose possible mechanisms. In this case, a 65-year-old man with no psychiatric history developed acute visual hallucinations following initiation of omeprazole, in the absence of delusions, paranoia, and other psychotic symptoms. The visual hallucinations began after the patient started treatment with omeprazole and resolved almost immediately upon discontinuation of omeprazole. To treat symptoms of gastroesophageal reflux disease, omeprazole was replaced with famotidine, and the visual hallucinations did not recur after the omeprazole had been discontinued. No other psychotic signs or symptoms were present in this patient throughout the duration of his hospitalization. Although the scientific literature provides limited information on psychosis related to PPI use, a growing number of case reports and studies in recent years have suggested that neuropsychiatric symptoms may occur after PPI use. It is our hope that this case report adds to the scientific and medical knowledge in this area.

Associations between childhood family emotional health, fronto-limbic grey matter volume, and saliva 5mC in young adulthood.

BACKGROUND: Poor family emotional health (FEH) during childhood is prevalent and impactful, and likely confers similar neurodevelopmental risks as other adverse social environments. Pointed FEH study efforts are underdeveloped, and the mechanisms by which poor FEH are biologically embedded are unclear. The current exploratory study examined whether variability in 5-methyl-cytosine (5mC) and fronto-limbic grey matter volume may represent pathways through which FEH may become biologically embedded. RESULTS: In 98 university students aged 18-22 years, retrospective self-reported childhood FEH was associated with right hemisphere hippocampus (b = 10.4, p = 0.005), left hemisphere amygdala (b = 5.3, p = 0.009), and right hemisphere amygdala (b = 5.8, p = 0.016) volumes. After pre-processing and filtering to 5mC probes correlated between saliva and brain, analyses showed that childhood FEH was associated with 49 5mC principal components (module eigengenes; MEs) (prange = 3 × 10-6 to 0.047). Saliva-derived 5mC MEs partially mediated the association between FEH and right hippocampal volume (Burlywood ME indirect effect b = - 111, p = 0.014), and fully mediated the FEH and right amygdala volume relationship (Pink4 ME indirect effect b = - 48, p = 0.026). Modules were enriched with probes falling in genes with immune, central nervous system (CNS), cellular development/differentiation, and metabolic functions. CONCLUSIONS: Findings extend work highlighting neurodevelopmental variability associated with adverse social environment exposure during childhood by specifically implicating poor FEH, while informing a mechanism of biological embedding. FEH-associated epigenetic signatures could function as proxies of altered fronto-limbic grey matter volume associated with poor childhood FEH and inform further investigation into primarily affected tissues such as endocrine, immune, and CNS cell types.

The impact of psychopathology, social adversity and stress-relevant DNA methylation on prospective risk for post-traumatic stress: A machine learning approach.

BACKGROUND: A range of factors have been identified that contribute to greater incidence, severity, and prolonged course of post-traumatic stress disorder (PTSD), including: comorbid and/or prior psychopathology; social adversity such as low socioeconomic position, perceived discrimination, and isolation; and biological factors such as genomic variation at glucocorticoid receptor regulatory network (GRRN) genes. This complex etiology and clinical course make identification of people at higher risk of PTSD challenging. Here we leverage machine learning (ML) approaches to identify a core set of factors that may together predispose persons to PTSD. METHODS: We used multiple ML approaches to assess the relationship among DNA methylation (DNAm) at GRRN genes, prior psychopathology, social adversity, and prospective risk for PTS severity (PTSS). RESULTS: ML models predicted prospective risk of PTSS with high accuracy. The Gradient Boost approach was the top-performing model with mean absolute error of 0.135, mean square error of 0.047, root mean square error of 0.217, and R2 of 95.29%. Prior PTSS ranked highest in predicting the prospective risk of PTSS, accounting for >88% of the prediction. The top ranked GRRN CpG site was cg05616442, in AKT1, and the top ranked social adversity feature was loneliness. CONCLUSION: Multiple factors including prior PTSS, social adversity, and DNAm play a role in predicting prospective risk of PTSS. ML models identified factors accounting for increased PTSS risk with high accuracy, which may help to target risk factors that reduce the likelihood or course of PTSD, potentially pointing to approaches that can lead to early intervention. LIMITATION: One of the limitations of this study is small sample size.

Sense of belonging, sense of exclusion, and racial and ethnic identities in Korean transracial adoptees.

Although many Korean transracial adoptees (KTAs) have White European American (WEA) family members, their racial features place them in the minority group. Thus, they navigate the meanings of race and culture from two reference groups: the majority WEA group and the Korean American group. This study explored the processes through which perceptions of group meanings and sense of belonging and exclusion related to the development of racial and ethnic identities. Fourteen adult KTAs in the Northeast participated in interviews analyzed using grounded theory methodology. Results indicated that KTAs' racial and ethnic identities were coconstructed in relation to experiences of belonging and exclusion with their families and both WEA and Korean American groups.

Sex-specific and shared expression profiles of vulnerability and resilience to trauma in brain and blood.

BACKGROUND: While post-traumatic stress disorder (PTSD) is defined by behavioral/cognitive symptoms most directly relevant to brain function, it can be considered a systemic disorder characterized by a distinct inability to reinstate homeostasis after trauma. METHODS: In this study, we conducted a secondary analysis of gene expression profiles in key PTSD-relevant tissues, namely blood, amygdala, and hippocampus, from a rat model of PTSD, to identify sex-specific and shared processes associated with individual differences in response to recent trauma exposure. RESULTS: Our findings suggest both shared and sex-specific mechanisms underlying individual differences associated with vulnerability and resilience to trauma in hippocampus, amygdala, and blood. By disentangling cell composition from transcriptional changes, we found higher proportions of hippocampal oligodendrocytes in the PTSD-like, extreme behavioral response (EBR) group for both sexes and also identified modules for transcriptional activity associated with group differences (i.e., response to trauma) in the hippocampus that appeared to be sex-specific. By contrast, we found prominent sex differences, but no group differences, in amygdalar cell composition, and both shared and sex-specific modules representing PTSD-relevant transcriptional activity in the amygdala. Across amygdala and hippocampus, both sex-specific and shared processes were relevant to an overarching framework for EBR implicating disrupted TNFα/NFκΒ signaling and excitatory/inhibitory imbalance in dysregulated synaptic/structural plasticity with important implications for fear learning and memory. Our main finding in peripheral blood was consistent with the human literature and identified wound healing processes and hemostasis to be upregulated in the resilient, minimal behavioral response (MBR) group across sexes, but disrupted in a sexually dimorphic manner in the EBR group. CONCLUSION: In contrast to the varied characterization of the PTSD-like EBR group, characterization of MBR across blood, amygdala, and hippocampus suggests a common theme of upregulated wound healing and extracellular matrix (ECM) remodeling shared between sexes. In all, we identified differential oligodendrocyte proportions in hippocampus between PTSD-like EBR and resilient MBR, and identified processes and pathways that characterize the EBR and MBR-associated transcriptional changes across hippocampus, amygdala, and blood. The sex-specific mechanisms involved in EBR may contribute to the pronounced disparity in risk for PTSD, with women much more likely to develop PTSD.

Advances in Inner Ear Therapeutics for Hearing Loss in Children.

Purpose of review: Hearing loss is a common congenital sensory disorder with various underlying causes. Here, we review and focus on genetic, infectious, and ototoxic causes and recent advances in inner ear therapeutics. Recent findings: While hearing aids and cochlear implantation are the mainstay of treatment for pediatric hearing loss, novel biological therapeutics are being explored. Recent preclinical studies report positive results in viral-mediated gene transfer techniques and surgical approaches to the inner ear for genetic hearing loss. Novel pharmacologic agents, on the other hand, show promising results in reducing aminoglycoside and cisplatin ototoxicity. Clinical trials are underway to evaluate the efficacy of antivirals for cytomegalovirus-related hearing loss, and its pathogenesis and other potential therapeutics are currently under investigation. Summary: Individualized therapies for genetic and infectious causes of sensorineural hearing loss in animal models as well as pediatric patients show promising results, with their potential efficacy being active areas of research.

Major complications after tongue-tie release: A case report and systematic review.

INTRODUCTION: The diagnosis of ankyloglossia, or tongue-tie, and the number of frenotomies performed has increased over 10-fold from 1997 to 2012 in the United States. The sharpest increase has been in neonates. For parents considering frenotomy for their breastfeeding newborn, there is controversy surrounding the evaluation of tongue-tie and the benefit of a frenotomy. Complications from tongue-tie procedures are thought to be low, though it is not well reported nor studied. OBJECTIVES: The aim of this study is to describe a case of a sublingual mucocele after laser frenotomy in a neonate with tongue-tie and to investigate major complications reported after tongue-tie release in pediatric patients through a systematic review of the literature. CASE REPORT: We present a 6-week-old female who underwent a laser frenotomy procedure performed by a dentist who presented with a new cyst under her tongue. MATERIAL AND METHODS: A systematic literature search of articles published from 1965 to April 2020 was conducted in Ovid MEDLINE(R), Ovid EMBASE, and Scopus. Citations were uploaded into a systematic review software program (DistillerSR, Ottawa, ON, Canada), followed by full text screening. RESULTS: 47 major complications were reported in 34 patients, including our patient. Most of the cases were located in the United States and Europe. The most frequent indications for the procedure were breastfeeding problems (n = 18) and speech impediment (n = 4). The procedure was performed by dentists (n = 6), lactation consultants (n = 5), and otolaryngologists (n = 4). The bulk of the major complications after frenotomy included poor feeding (n = 7), hypovolemic shock (n = 4), apnea (n = 4), acute airway obstruction (n = 4), and Ludwig angina (n = 2). CONCLUSIONS: Reporting of complications after frenotomy is lacking. Risks to neonates may be different than risks to older children and adults. Practitioners across different specialties should be monitoring and studying this more rigorously to better guide patients and families on the risks and benefits of this procedure.

Prevalence and significance of cranial nerve imaging abnormalities in patients with hereditary neuropathies: Clinical implications at the skull base.

OBJECTIVE: To estimate the prevalence and significance of cranial nerve (CN) imaging abnormalities in patients with hereditary neuropathy and discuss clinical implications. METHODS: We retrospectively analyzed data from patients at four tertiary academic medical centers with hereditary neuropathy diagnoses who had undergone gadolinium-enhanced magnetic resonance imaging (MRI) of the brain or skull base between 2004 and 2018. MRI scans, as well as computed tomography imaging when available, were reviewed and bivariable analysis was performed to identify predictors of CN abnormalities on imaging. RESULTS: Among 39 patients meeting study criteria, 11 had clinical CN deficits (28%) and 8 had CN abnormalities on imaging (21%). Of the patients with CN abnormalities on imaging, half had CN deficits (4/8) and only a quarter had imaging abnormalities of the CNs with the deficits (2/8). Imaging abnormalities were found in varied CNs, including CNs III, V, VII, and the VII/VIII complex in the internal auditory canal. MRI obtained for the purpose of evaluating CN deficits had a statistically significant increased likelihood of containing CN imaging abnormalities. However, CN deficits themselves were not predictive of imaging abnormalities. CONCLUSION: Thickening and enhancement of CNs on MRI may be found in approximately 1/5 of patients with hereditary neuropathies and are inconsistently associated with clinical deficits. These imaging findings should not be mistaken for neoplastic and infectious processes as they may be manifestations of the patients' underlying genetic neuropathy. LEVEL OF EVIDENCE: 4.

Direct cellular reprogramming and inner ear regeneration.

INTRODUCTION: Sound is integral to communication and connects us to the world through speech and music. Cochlear hair cells are essential for converting sounds into neural impulses. However, these cells are highly susceptible to damage from an array of factors, resulting in degeneration and ultimately irreversible hearing loss in humans. Since the discovery of hair cell regeneration in birds, there have been tremendous efforts to identify therapies that could promote hair cell regeneration in mammals. AREAS COVERED: Here, we will review recent studies describing spontaneous hair cell regeneration and direct cellular reprograming as well as other factors that mediate mammalian hair cell regeneration. EXPERT OPINION: Numerous combinatorial approaches have successfully reprogrammed non-sensory supporting cells to form hair cells, albeit with limited efficacy and maturation. Studies on epigenetic regulation and transcriptional network of hair cell progenitors may accelerate discovery of more promising reprogramming regimens.

Molecular therapy for genetic and degenerative vestibular disorders.

PURPOSE OF REVIEW: The primary purpose of this review is to summarize current literature in the field of vestibular regeneration with a focus on recent developments in molecular and gene therapies. RECENT FINDINGS: Since the discovery of limited vestibular hair cell regeneration in mammals in the 1990s, many elegant studies have improved our knowledge of mechanisms of development and regeneration of the vestibular system. A better understanding of the developmental pathways of the vestibular organs has fueled various biological strategies to enhance regeneration, including novel techniques in deriving vestibular hair cells from embryonic and induced pluripotent stem cells. In addition, the identification of specific genetic mutations responsible for vestibular disorders has opened various opportunities for gene replacement therapy. SUMMARY: Vestibular dysfunction is a significant clinical problem with limited therapeutic options, warranting research on biological strategies to repair/regenerate the vestibular organs to restore function. The use of gene therapy appears promising in animal models of vestibular dysfunction.

Neuroepigenetics of Post-Traumatic Stress Disorder.

While diagnosis of PTSD is based on behavioral symptom clusters that are most directly associated with brain function, epigenetic studies of PTSD in humans to date have been limited to peripheral tissues. Animal models of PTSD have been key for understanding the epigenetic alterations in the brain most directly relevant to endophenotypes of PTSD, in particular those pertaining to fear memory and stress response. This chapter provides an overview of neuroepigenetic studies based on animal models of PTSD, with an emphasis on the effect of stress on fear memory. Where relevant, we also describe human-based studies with relevance to neuroepigenetic insights gleaned from animal work and suggest promising directions for future studies of PTSD neuroepigenetics in living humans that combine peripheral epigenetic measures with measures of central nervous system activity, structure and function.

Outcomes of chronic frontal sinusitis treated with ethmoidectomy: a prospective study.

BACKGROUND: In medically refractory chronic frontal sinusitis, ethmoidectomy without instrumentation of the frontal ostium may resolve frontal disease. Our aim was to determine the efficacy of ethmoidectomy alone for the treatment of chronic frontal sinusitis. METHODS: Adults with chronic rhinosinusitis prospectively enrolled in a multicenter study who demonstrated frontal sinusitis on computed tomography were divided into 2 groups: (1) endoscopic sinus surgery (ESS) incorporating ethmoidectomy, but excluding frontal sinusotomy; and (2) ESS incorporating frontal sinusotomy. The primary outcome was improvement in 22-item Sino-Nasal Outcome Test (SNOT-22) scores. Secondary outcomes included endoscopic scores and use of corticosteroids and antibiotics. RESULTS: A total of 196 cases undergoing frontal sinusotomy and 30 cases treated with ethmoidectomy without frontal sinusotomy were analyzed and were comparable demographically. The prevalence of nasal polyps, previous ESS, asthma, and aspirin intolerance was more common in the frontal sinusotomy group (p < 0.050). Preoperative endoscopy and computed tomography scores were higher in the frontal sinusotomy group (p ≤ 0.001). Postoperatively, both groups showed comparable SNOT-22 scores with worse endoscopy scores in the frontal sinusotomy group (p = 0.038). Postoperative improvement in SNOT-22 total and subdomain scores was comparable between groups. Nasal endoscopy scores improved to a greater degree in the frontal sinusotomy group (p = 0.023). Duration of postoperative topical steroid use was higher in the frontal sinusotomy group (p = 0.007). Revision surgery was needed in 2.6% of frontal sinusotomy patients and 0% of patients without frontal sinusotomy. CONCLUSION: The treatment of chronic frontal sinusitis through ethmoidectomy is a potential alternative to frontal sinusotomy achieving similar quality of life (QOL) improvements in patients manifesting less severe sinus disease.