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Background Exposure to adverse childhood experiences (ACEs) and being female are distinct risk factors for having a major depressive episode (MDE) or an anxiety disorder (AD) in adulthood, but it is unclear whether these two risk factors are synergistic. The purpose of this study was to determine whether exposure to ACEs and being female are more than additive (synergistic) in their association with MDE and AD in US adults. Methods We pooled cross-sectional survey data in the Midlife in the United States study from two nationally-representative cohorts of English-speaking US adults. Data from the first cohort were collected in 2004–2006 and from the second in 2011–2014. Data from both cohorts included the 12-month prevalence of MDE and AD (generalized anxiety disorder or panic disorder) assessed with the Composite International Diagnostic Interview Short Form, gender (here termed female and male), and the count of five categories of exposure to ACEs: physical, sexual, or emotional abuse; household alcohol or substance abuse; and parental separation or divorce. Results Of the 5834 survey respondents, 4344 (74.5%) with complete data on ACEs were included in the analysis. Mean (SD) age was 54.1 (13.8) years and 53.9% were female. The prevalences of MDE, AD, and exposure to 3–5 categories of ACEs were 13.7, 10.0, and 12.5%, respectively. After adjusting for covariates (age, race, and current and childhood socioeconomic disadvantage), for those with both risk factors (female and 3–5 ACEs) the prevalence of MDE was 26.9%. This was 10.2% (95% CI: 1.8, 18.5%) higher than the expected prevalence based on the additive associations of the two risk factors. The adjusted prevalence of AD among females with 3–5 ACEs was 21.9%, which was 11.4% (95% CI: 4.0, 18.9%) higher than the expected prevalence. Conclusions For both MDE and AD, there was synergy between the two risk factors of exposure to ACEs and being female. Identification and treatment of MDE and AD may benefit from understanding the mechanisms involved in the synergistic interaction of gender with ACEs.

The epigenomic reader Brd4 is an important drug target for cancers. However, its role in cell differentiation and animal development remains largely unclear. Using two conditional knockout mouse strains and derived cells, we demonstrate that Brd4 controls cell identity gene induction and is essential for adipogenesis and myogenesis. Brd4 co-localizes with lineage-determining transcription factors (LDTFs) on active enhancers during differentiation. LDTFs coordinate with H3K4 mono-methyltransferases MLL3/MLL4 (KMT2C/KMT2D) and H3K27 acetyltransferases CBP/p300 to recruit Brd4 to enhancers activated during differentiation. Brd4 deletion prevents the enrichment of Mediator and RNA polymerase II transcription machinery, but not that of LDTFs, MLL3/MLL4-mediated H3K4me1, and CBP/p300-mediated H3K27ac, on enhancers. Consequently, Brd4 deletion prevents enhancer RNA production, cell identity gene induction and cell differentiation. Interestingly, Brd4 is dispensable for maintaining cell identity genes in differentiated cells. These findings identify Brd4 as an enhancer epigenomic reader that links active enhancers with cell identity gene induction in differentiation. Despite being an important cancer drug target, the role of epigenetic reader Brd4 in cell differentiation and development remains unclear. Here, the authors provide evidence that Brd4 plays an important role in adipogenesis and myogenesis by binding to active enhancers to regulate gene expression.

COVID-19 induces both acute and chronic neurological changes. Existing evidence suggests that chemosensory changes, particularly olfactory loss, may reflect central neurological dysfunction in neurodegenerative diseases and mark progression from mild cognitive impairment to Alzheimer's. This scoping review summarizes the available literature to evaluate the relationship between neurocognition and olfaction in young to middle-aged adults with minimal comorbidities following COVID-19 infection. A literature search of PubMed, Ovid Embase, Web of Science, and Cochrane Library was conducted. Studies underwent title/abstract and full text screening by two reviewers, with a third reviewer resolving any conflicts. Remaining studies underwent data extraction. Seventeen studies were eligible for data extraction after the review process, where 12 studies found significantly poorer cognition in those suffering from olfactory dysfunction, four studies showed no association between cognition and olfaction, and one study reported lower anosmia prevalence among patients with cognitive impairment. The majority of studies in this review find that olfactory dysfunction is associated with poorer cognition. More rigorous studies are needed to further elucidate the relationship between olfaction and cognition after COVID-19.

Introduction Strong evidence suggests that olfactory dysfunction (OD) can predict additional neurocognitive decline in neurodegenerative conditions such as Alzheimer’s and Parkinson’s diseases. However, research exploring olfaction and cognition in younger populations is limited. The aim of this review is to evaluate cognitive changes among non-elderly adults with non-COVID-19-related OD. Methods We performed a structured comprehensive literature search of PubMed, Ovid Embase, Web of Science, and Cochrane Library in developing this scoping review. The primary outcome of interest was the association between OD and cognitive functioning in adults less than 60 years of age. Results We identified 2878 studies for title and abstract review, with 167 undergoing full text review, and 54 selected for data extraction. Of these, 34 studies reported on populations of individuals restricted to the ages of 18–60, whereas the remaining 20 studies included a more heterogeneous population with the majority of individuals in this target age range in addition to some above the age of 60. The etiologies for smell loss among the included studies were neuropsychiatric disorders (37%), idiopathic cause (25%), type 2 diabetes (7%), trauma (5%), infection (4%), intellectual disability (4%), and other (18%). Some studies reported numerous associations and at times mixed, resulting in a total number of associations greater than the included number of 54 studies. Overall, 21/54 studies demonstrated a positive association between olfaction and cognition, 7/54 demonstrated no association, 25/54 reported mixed results, and only 1/54 demonstrated a negative association. Conclusion Most studies demonstrate a positive correlation between OD and cognition, but the data are mixed with associations less robust in this young adult population compared to elderly adults. Despite the heterogeneity in study populations and outcomes, this scoping review serves as a starting point for further investigation on this topic. Notably, as many studies in this review involved disorders that may have confounding effects on both olfaction and cognition, future research should control for these confounders and incorporate non-elderly individuals with non-psychiatric causes of smell loss.

Background Sheep have been proposed as a large-animal model for studying cochlear implantation. However, prior sheep studies report that the facial nerve (FN) obscures the round window membrane (RWM), requiring FN sacrifice or a retrofacial opening to access the middle-ear cavity posterior to the FN for cochlear implantation. We investigated surgical access to the RWM in Hampshire sheep compared to Suffolk-Dorset sheep and the feasibility of Hampshire sheep for cochlear implantation via a facial recess approach. Methods Sixteen temporal bones from cadaveric sheep heads (ten Hampshire and six Suffolk-Dorset) were dissected to gain surgical access to the RWM via an extended facial recess approach. RWM visibility was graded using St. Thomas’ Hospital (STH) classification. Cochlear implant (CI) electrode array insertion was performed in two Hampshire specimens. Micro-CT scans were obtained for each temporal bone, with confirmation of appropriate electrode array placement and segmentation of the inner ear structures. Results Visibility of the RWM on average was 83% in Hampshire specimens and 59% in Suffolk-Dorset specimens ( p  = 0.0262). Hampshire RWM visibility was Type I (100% visibility) for three specimens and Type IIa (> 50% visibility) for seven specimens. Suffolk-Dorset RWM visibility was Type IIa for four specimens and Type IIb (< 50% visibility) for two specimens. FN appeared to course more anterolaterally in Suffolk-Dorset specimens. Micro-CT confirmed appropriate CI electrode array placement in the scala tympani without apparent basilar membrane rupture. Conclusions Hampshire sheep appear to be a suitable large-animal model for CI electrode insertion via an extended facial recess approach without sacrificing the FN. In this small sample, Hampshire specimens had improved RWM visibility compared to Suffolk-Dorset. Thus, Hampshire sheep may be superior to other breeds for ease of cochlear implantation, with FN and facial recess anatomy more similar to humans.

Purpose Sheep are used as a large-animal model for otology research and can be used to study implantable hearing devices. However, a method for temporal bone extraction in sheep, which enables various experiments, has not been described, and literature on middle ear access is limited. We describe a method for temporal bone extraction and an extended facial recess surgical approach to the middle ear in sheep. Methods Ten temporal bones from five Hampshire sheep head cadavers were extracted using an oscillating saw. After craniotomy and removal of the brain, a coronal cut was made at the posterior aspect of the orbit followed by a midsagittal cut of the occipital bone and disarticulation of the atlanto-occipital joint. Temporal bones were surgically prepared with an extended facial recess approach. Micro-CT scans of each temporal bone were obtained, and anatomic dimensions were measured. Results Temporal bone extraction was successful in 10/10 temporal bones. Extended facial recess approach exposed the malleus, incus, stapes, and round window while preserving the facial nerve, with the following surgical considerations: minimally pneumatized mastoid; tegmen (superior limit of mastoid cavity) is low-lying and sits below temporal artery; chorda tympani sacrificed to optimize middle ear exposure; incus buttress does not obscure view of middle ear. Distance between the superior aspect of external auditory canal and tegmen was 2.7 (SD 0.9) mm. Conclusion We identified anatomic landmarks for temporal bone extraction and describe an extended facial recess approach in sheep that exposes the ossicles and round window. This approach is feasible for studying implantable hearing devices.

Objective This study sought to quantify the deep venous thrombosis (DVT) incidence in head and neck cancer (HNC) patients undergoing free tissue transfer and to identify independent predictors of postoperative DVT. Materials and Methods This is a cross‐sectional study of the National Surgical Quality Improvement Program database from 2010 through 2020. The sample included all HNC surgical patients treated with free flap reconstruction. The study outcome was the presence of a DVT requiring treatment within 30 days of surgery. Univariate analyses were performed using chi‐squared and independent t‐tests. A multiple logistic regression model was created using all significant univariate predictors. Results A total of 3954 patients were identified, of whom 53 (1.3%) experienced a postoperative DVT. The only medical comorbidity associated with DVT was COPD (RR = 2.7 [1.3, 5.4]; p < .01). Operative time longer than 9 hours (RR = 1.9 [1.0, 3.2]; p = .04) and length of stay longer than 10 days (RR = 1.9 [1.1, 3.2]; p = .02) were associated with greater DVT rates. In the multivariate analysis, only COPD (p < .01) and operative time (p = .02) were independently associated with DVT risk. The presence of a DVT was found to increase the relative risk of readmission (RR = 2.1 [1.2, 3.6]; p < .01) and non‐home disposition (RR = 2.4 [1.7, 3.5]; p < .01). Conclusions The incidence of DVT in HNC free flap patients was comparable to what has been reported in the general population of HNC surgery patients. Operative time >9 h and COPD history were independent risk factors for DVT in this subset of patients. Symptomatic DVTs necessitating treatment were accompanied by poorer post‐hospitalization outcomes. Level of Evidence Level 3. The American College of Surgeons National Surgical Quality Improvement Program database was analyzed for factors associated with postoperative deep venous thrombosis (DVT) in head and neck cancer patients undergoing free flap reconstruction. Out of 3954 patients, 1.3% experienced postoperative DVT requiring treatment. COPD and operative time >9 h were independent risk factors for this adverse outcome.

Abstract Ultrasound-guided ethanol ablation (EA) is a less invasive alternative to surgical resection for the management of thyroglossal duct cysts (TGDCs). However, to date, EA is rarely used in the United States to treat TGDCs. We present a case of TGDC successfully treated with EA in the United States. A 66-year-old man presented with a mobile anterior neck mass. Neck ultrasonography revealed a complex cystic mass in the midline directly anterior to the trachea, measuring 52 × 41 × 50 mm. Fine needle aspiration revealed no malignant cells, and pathology was consistent with TGDC. The patient had no contraindications to surgical resection. The patient's pretreatment symptom score was 7 and cosmetic score was 3. One month after EA, volume reduction ratio was 40%, symptom score was 1, and cosmetic score was 3. Four months after EA, the TGDC was resolved without need for an additional procedure. The volume reduction ratio was 96.8%, and symptom score and cosmetic score were both 1. In summary, EA is a viable alternative to surgical resection, even in patients who are surgical candidates. EA is attractive due to its simplicity, cost effectiveness, and tolerable side effect profile. Further studies are needed to evaluate long-term safety and efficacy, particularly in United States patients.