Flow Analysis of Central Venous Outflow Tract: A New Approach to Understanding Pulse-Synchronous Tinnitus.

OBJECTIVE: Pulse-synchronous tinnitus (PST) has been linked to multiple anatomical variants of the central venous outflow tract (CVOT) including sigmoid sinus (SS) dehiscence and diverticulum. This study investigates flow turbulence, pressure, and wall shear stress along the CVOT and proposes a mechanism that results in SS dehiscence and PST. STUDY DESIGN: Case series. SETTING: Tertiary Academic Center. METHODS: Venous models were reconstructed from computed tomography scans of 3 patients with unilateral PST. Two models for each patient are obtained: a symptomatic and contralateral asymptomatic side. A turbulent model-enabled commercial flow solver was used to simulate the pulsatile blood flow over the cardiac cycle through the models. Fluid flow through the transverse and SS junction was analyzed to observe the velocity, pressure, turbulent kinetic energy (TKE), and shear stress over a simulated cardiac cycle. RESULTS: Fluid flow on the symptomatic side showed increased vorticity in the presence of an SS diverticulum. Higher TKE with periodicity following the cardiac cycle was observed on the symptomatic side, and a sharp increase was observed if SS diverticulum was present. Shear stress was highest near the narrowest segments of the vessel. Pressure was observed to be lower on the symptomatic side at the transverse-SS junction for all 3 patients. CONCLUSION: Computational fluid dynamics modeling of blood flow through the CVOT in PST suggests that low pressure may be the cause of dehiscence, and tinnitus may result from periodic increases in TKE.

Epidemiology, management, and treatment outcomes of metastatic spinal melanoma.

Metastatic spinal melanoma is a rare and aggressive disease process with poor prognosis. We review the literature on metastatic spinal melanoma, focusing on its epidemiology, management, and treatment outcomes. Demographics of metastatic spinal melanoma are similar to those for cutaneous melanoma, and cutaneous primary tumors tend to be most common. Decompressive surgical intervention and radiotherapy have traditionally been considered mainstays of treatment, and stereotactic radiosurgery has emerged as a promising approach in the operative management of metastatic spinal melanoma. While survival outcomes for metastatic spinal melanoma remain poor, they have improved in recent years with the advent of immune checkpoint inhibition, used in conjunction with surgery and radiotherapy. New treatment options remain under investigation, especially for patients with disease refractory to immunotherapy. We additionally explore several of these promising future directions. Nevertheless, further investigation of treatment outcomes, ideally incorporating high-quality prospective data from randomized controlled trials, is needed to identify optimal management of metastatic spinal melanoma.

Systematic review of cochlear implantation in patients with inner ear malformations.

OBJECTIVES: To evaluate the outcomes of cochlear implantation in patients with severe to profound sensorineural hearing loss due to inner ear malformations (IEMs) when compared to patients without IEMs. We discussed audiological outcomes such as open-set testing, closed-set testing, CAP score, and SIR score as well as postoperative outcomes such as cerebrospinal fluid gusher and incomplete insertion rate associated with cochlear implantation in individuals with IEMs. DATA SOURCES: PubMed, Science Direct, Web of Science, Scopus, and EMBASE databases. REVIEW METHODS: After screening a total of 222 studies, twelve eligible original articles were included in the review to analyze the speech and hearing outcomes of implanted patients with IEMs. Five reviewers independently screened, selected, and extracted data. The "Tool to Assess Risk of Bias in Cohort Studies" published by the CLARITY group was used to perform quality assessment on eligible studies. Systematic review registration number: CRD42021237489. RESULTS: IEMs are more likely to be associated with abnormal position of the facial nerve, raising the risk of intraoperative complications. These patients may benefit from cochlear implantation, but audiological outcomes may also be less favorable than in individuals without IEMs. Furthermore, due to the risk of cerebrospinal fluid gusher, incomplete insertion of electrodes, and postoperative facial nerve stimulation, surgeons can employ precautionary measures such as preoperative imaging and proper counseling. Postoperative imaging is suggested to be beneficial in ensuring proper electrode placement. CONCLUSIONS: Cochlear implants (CIs) have the potential to provide auditory rehabilitation to individuals with IEMs. Precise classification of the malformation, preoperative imaging and anatomical mapping, appropriate electrode selection, intra-operative techniques, and postoperative imaging are recommended in this population.

Association Between Tinnitus and Hypertension: A Cross-Sectional Analysis of the National Health and Nutrition Examination Survey.

OBJECTIVE: Evaluating the association between arterial hypertension and tinnitus while controlling for gender, race, diabetes, hearing loss, and depression as potential confounders. STUDY DESIGN: The present study employed a cross-sectional design. SETTING: Health interviews were conducted in the respondents' homes. PATIENTS: Respondents represent a nationwide sample of the noninstitutionalized civilian population of the United States. A total of 5,735 adults were identified by the NHANES 2015 to 2016 questionnaires. INTERVENTIONS: Questionnaires were administered to each participant. MAIN OUTCOME MEASURES: Participants' responses regarding tinnitus, hypertension, hearing loss, depression, diabetes, and demographics were used to evaluate potential associations. Multivariate logistic regression analyses were conducted on different age groups with the presence of hypertension as the response variable. RESULTS: Participants aged 20 to 39 with tinnitus were significantly more likely to be diagnosed with hypertension (OR = 2.49; p = 0.024) after adjusting for potential confounding. No significant association between tinnitus and hypertension was found for older age groups. The diagnosis of diabetes was associated with hypertension in ages 20 to 39 (OR = 7.11; p = 0.001), 40 to 59 (OR = 3.45; p = 0.020), and 60 to 69 (OR = 3.89; p = 0.032). CONCLUSIONS: Tinnitus is associated with hypertension in younger age groups of 20 to 39 years of age but not in age groups greater than 40 years. Diabetes is also associated with hypertension in individuals aged 20 to 69 years. This finding of tinnitus as a risk factor for hypertension in younger populations may inform better clinical practice and lead to earlier detection of hypertension in at-risk patients.

Laryngotracheal stenosis: Mechanistic review.

BACKGROUND: The purpose of this review article is to summarize the existing literature surrounding wound healing mechanisms in laryngotracheal stenosis. METHODS: A review of general wound healing pathophysiology, followed by a focused review of iatrogenic laryngotracheal stenosis (iLTS) and idiopathic subglottic stenosis (iSGS) as conditions of aberrant wound healing. RESULTS: iLTS is the scarring of the laryngotracheal complex, coming secondary to injury from prolonged intubation. iSGS is a chronic fibroinflammatory scarring and narrowing of the subglottic airway in the absence of any obvious preceding injury or trauma. They are both thought to result from a prolonged and dysregulated wound healing response that promotes the deposition of pathologic scar in the airway. CONCLUSIONS: Understanding the mechanisms that underlie wound healing will help identify and intervene on the process early in its development and discover future therapies that target individual wound healing mechanisms limiting the incidence of this recalcitrant disease process.

Recent advancements in cell-based models for auditory disorders.

Introduction: Cell-based models play an important role in understanding the pathophysiology and etiology of auditory disorders. For the auditory system, models have primarily focused on restoring inner and outer hair cells. However, they have largely underrepresented the surrounding structures and cells that support the function of the hair cells. Methods: In this article, we will review recent advancements in the evolution of cell-based models of auditory disorders in their progression towards three dimensional (3D) models and organoids that more closely mimic the pathophysiology in vivo. Results: With the elucidation of the molecular targets and transcription factors required to generate diverse cell lines of the components of inner ear, research is starting to progress from two dimensional (2D) models to a greater 3D approach. Of note, the 3D models of the inner ear, including organoids, are relatively new and emerging in the field. As 3D models of the inner ear continue to evolve in complexity, their role in modeling disease will grow as they bridge the gap between cell culture and in vivo models. Conclusion: Using 3D cell models to understand the etiology and molecular mechanisms underlying auditory disorders holds great potential for developing more targeted and effective novel therapeutics.

Unraveling pathological mechanisms in neurological disorders: the impact of cell-based and organoid models.

Cell-based models are a promising tool in deciphering the molecular mechanisms underlying the pathogenesis of neurological disorders as well as aiding in the discovery and development of future drug therapies. The greatest challenge is creating cell-based models that encapsulate the vast phenotypic presentations as well as the underlying genotypic etiology of these conditions. In this article, we discuss the recent advancements in cell-based models for understanding the pathophysiology of neurological disorders. We reviewed studies discussing the progression of cell-based models to the advancement of three-dimensional models and organoids that provide a more accurate model of the pathophysiology of neurological disorders in vivo. The better we understand how to create more precise models of the neurological system, the sooner we will be able to create patient-specific models and large libraries of these neurological disorders. While three-dimensional models can be used to discover the linking factors to connect the varying phenotypes, such models will also help to understand the early pathophysiology of these neurological disorders and how they are affected by their environment. The three-dimensional cell models will allow us to create more specific treatments and uncover potentially preventative measures in neurological disorders such as autism spectrum disorder, Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis.

Cutaneous Neurocristic Hamartoma Mimicking Basal Cell Carcinoma in a Patient With Xeroderma Pigmentosum.

ABSTRACT: Neurocristic hamartomas (NCH) of cutaneous origin are especially rare congenital or acquired neoplasms that often arise through aberrant embryologic development of pluripotent neural crest cells. Clinically, they often present as pigmented macules or papules on the scalp with associated alopecia. NCHs are characterized histopathologically by dermal melanocytic, fibroblastic, and neurosustentacular components. Correct identification of this etiology is critical because of potential for malignant transformation, particularly in acquired NCHs. Our patient was a 6-year-old girl with xeroderma pigmentosum and confirmed XPC mutation followed in our dermatology clinic since the age of 3. She had a history of multiple actinic keratoses but no prior skin cancers. A 4-mm homogenous pink papule on the left frontal scalp concerning for basal cell carcinoma was noted during routine skin examination. After a 3-month course of 3 times weekly topical imiquimod, the lesion had grown to a 6 mm diameter. The patient was then referred to plastic surgery for definitive excision. Histologically, the lesion showed a well-circumscribed proliferation of spindle cells with a trabecular and nested growth pattern. Perivascular pseudorosettes were identified, as were areas that resembled well-differentiated neural tissue. The spindle cells diffusely expressed S100 protein, SOX10, and CD34, with patchy expression of Melan-A and HMB-45. PRAME was negative, and p16 was retained. Array comparative genomic hybridization was performed, and no clinically significant copy number or single nucleotide variants were detected. To the best of our knowledge, this is the first documented case in the literature of a cutaneous neurocristic hamartoma arising in a patient with xeroderma pigmentosum.

Implications of Transcranial Magnetic Stimulation as a Treatment Modality for Tinnitus.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive, neuromodulating technique for brain hyperexcitability disorders. The objective of this paper is to discuss the mechanism of action of rTMS as well as to investigate the literature involving the application of rTMS in the treatment of tinnitus. The reviewed aspects of the protocols included baseline evaluation, the total number of sessions, frequency and the total number of stimuli, the location of treatment, and the outcome measures. Even with heterogeneous protocols, most studies utilized validated tinnitus questionnaires as baseline and outcome measures. Low frequency (1 Hz) stimulation throughout 10 consecutive sessions was the most widely used frequency and treatment duration; however, there was no consensus on the total number of stimuli necessary to achieve significant results. The auditory cortex (AC) was the most targeted location, with most studies supporting changes in neural activity with multi-site stimulation to areas in the frontal cortex (FC), particularly the dorsolateral prefrontal cortex (DLPFC). The overall efficacy across most of the reviewed trials reveals positive statistically significant results. Though rTMS has proven to impact neuroplasticity at the microscopic and clinical level, further studies are warranted to demonstrate and support the clinical use of rTMS in tinnitus treatment with a standardized protocol.

Hawai'i Physician Workforce Assessment 2016: Improvement in Physician Numbers but Physician Suicides of Concern.

Hawai'i's Physician Workforce Assessment project was launched in 2010. Over the past 5 years the State has experienced decreases and increases in physician workforce. This current article describes the status of the physician workforce, past trends and anticipated projections as well as recent insights into why people leave Hawai'i. Survey data, internet searches and direct dialing methodologies were utilized to clarify and elucidate practice location, full time equivalency of time providing patient care and specialty of non-military physicians caring for Hawai'i's population. A proprietary microsimulation modeling methodology from the company the US Health Resources and Services Administration employs is utilized to assess demand. The current shortage of physicians is estimated to be between 455 and 707 full time equivalents with the greatest percentage of shortages on neighbor islands. Numerically the greatest total shortage of physicians is on O'ahu and the specialty in greatest demand is primary care with a shortage of 228 Full Time Equivalents (FTEs). Physician average age in Hawai'i is 54.9 compared to a national average of 51. There was an increase in the number of physicians who report using telehealth, from 2% to 15%. Initial improvements in the size of Hawai'i's physician workforce are promising, but we note two reported suicides in the intervening year. More attention must be paid to support practicing physicians in addition to our efforts to recruit new physicians.

Presence of the Paternal Pronucleus Assists Embryo in Overcoming Cycloheximide Induced Abnormalities in Zygotic Mitosis.

After fertilization, the maternal and paternal chromosomes independently proceed through pronuclear formation. These chromatin reconfigurations occur within a shared cytoplasm thus exposing both gametes to the same factors. Here, we report that continuous cycloheximide [40 µg/mL] treatment of parthenogenotes, androgenotes, and ICSI embryos reveals ORC2 pronuclear instability in the maternal (MPN) but not the paternal pronucleus (PPN). When released from CHX after 8 h, the MPN can recover ORC2 and proceed through replication, however, parthenogenotes encounter severe mitotic defects while both ICSI embryos and androgenotes are able to recover and develop at significantly higher rates. Taken together, these data suggest cycloheximide treatment promotes an environment that asymmetrically affects the stability of ORC2 on the MPN, and the ability of the MPN to develop. Furthermore, the presence of the PPN in the zygote can ameliorate both effects. These data suggest further evidence for crosstalk between the two pronuclei during the first cell cycle of the embryo. J. Cell. Biochem. 117: 1806-1812, 2016. © 2016 Wiley Periodicals, Inc.