Molecular Insights into α-Synuclein Fibrillation: A Raman Spectroscopy and Machine Learning Approach.

The aggregation of α-synuclein is crucial to the development of Lewy body diseases, including Parkinson's disease and dementia with Lewy bodies. The aggregation pathway of α-synuclein typically involves a defined sequence of nucleation, elongation, and secondary nucleation, exhibiting prion-like spreading. This study employed Raman spectroscopy and machine learning analysis, alongside complementary techniques, to characterize the biomolecular changes during the fibrillation of purified recombinant wild-type α-synuclein protein.

Considering the Costs: Resin 3D Printing for a Temporal Bone Dissection Course.

Significant costs associated with obtaining cadaveric temporal bones (TBs) have led many to seek more cost-effective alternatives for TB surgical simulation. Multiple studies support the face validity of resin 3-dimensional (3D)-printed TBs as high-fidelity, useful alternatives for simulating TB dissection. However, a paucity of literature describes the cost or time associated with in-house manufacturing of resin TBs at scale.

Intratumoral CXCL12 Gradients Contextualize Tumor Cell Invasion, Migration and Immune Suppression in Breast Cancer.

Although the CXCL12/CXCR4 pathway has been prior investigated for its prometastatic and immuno- suppressive roles in the tumor microenvironment, evidence on the spatiotemporal regulation of these hallmarks has been lacking. Here, we demonstrate that CXCL12 forms a gradient specifically around cancer cell intravasation doorways, also known as Tumor Microenvironment of Metastasis (TMEM) doorways, thus facilitating the chemotactic translocation of prometastatic tumor cells expressing CXCR4 toward the perivascular TMEM doorways for subsequent entry into peripheral circulation. Fur- thermore, we demonstrate that the CXCL12-rich micro-environment around TMEM doorways may cre- ate immunosuppressive niches, whereby CD8 T cells, despite being attracted to these regions, often exhibit reduced effector functions, limiting their efficacy.

A prospective comparison of WALANT technique and general anesthesia in forefoot surgery.

Introduction: Wide Awake Local Anesthesia No Tourniquet (WALANT) technique has been widely used in hand surgery, but there are few prospective data on its use in forefoot surgery.

Hypothesis: The WALANT technique reduces pain compared to general anesthesia for bone surgery on the first ray of forefoot.

Methods: This was a prospective, longitudinal, comparative, non-randomized cohort study in adult patients undergoing bone surgery on the first ray of forefoot.

Worldwide differences in surgeon intraoperative practices for cochlear implantation.

Objective: To characterize practice patterns of intraoperative imaging and/or functional confirmation of cochlear implant electrode location worldwide.

Methods: A cross-sectional survey of otolaryngologists performing cochlear implantation was conducted between March 1 and May 6, 2023. Participants were recruited worldwide using an international otologic society membership email list and at professional meetings.

Delayed hearing loss after cochlear implantation: Re-evaluating the role of hair cell degeneration.

Delayed loss of residual acoustic hearing after cochlear implantation is a common but poorly understood phenomenon due to the scarcity of relevant temporal bone tissues. Prior histopathological analysis of one case of post-implantation hearing loss suggested there were no interaural differences in hair cell or neural degeneration to explain the profound loss of low-frequency hearing on the implanted side (Quesnel et al., 2016) and attributed the threshold elevation to neo-ossification and fibrosis around the implant.

Intracochlear Trauma and Local Ossification Patterns Differ Between Straight and Precurved Cochlear Implant Electrodes.

Hypothesis: Trauma to the osseous spiral lamina (OSL) or spiral ligament (SL) during cochlear implant (CI) insertion segregates with electrode type and induces localized intracochlear ossification and fibrosis.

Background: The goal of atraumatic CI insertion is to preserve intracochlear structures, limit reactive intracochlear tissue formation, and preserve residual hearing. Previous qualitative studies hypothesized a localized effect of trauma on intracochlear tissue formation; however, quantitative studies failed to confirm this.

Initial Experience With Robotic-Assisted Otologic and Lateral Skull Base Surgery.

Robotic-assisted surgery has gained popularity for otolaryngology procedures. It provides high-definition images and surgical precision to perform diverse procedures. It is an alternative to the operating microscope, endoscope, or exoscope when reaching hidden anatomical structures in the ear.

Uncovering potential diagnostic and pathophysiological roles of α-synuclein and DJ-1 in melanoma.

Background: Melanoma, the most lethal skin cancer type, occurs more frequently in Parkinson's disease (PD), and PD is more frequent in melanoma patients, suggesting disease mechanisms overlap. α-synuclein, a protein that accumulates in PD brain, and the oncogene DJ-1, which is associated with PD autosomal recessive forms, are both elevated in melanoma cells. Whether this indicates melanoma progression or constitutes a protective response remains unclear.

An emerging paradigm of CXCL12 involvement in the metastatic cascade.

The chemokine CXCL12, also known as stromal cell-derived factor 1 (SDF1), has emerged as a pivotal regulator in the intricate molecular networks driving cancer progression. As an influential factor in the tumor microenvironment, CXCL12 plays a multifaceted role that spans beyond its traditional role as a chemokine inducing invasion and metastasis. Indeed, CXCL12 has been assigned functions related to epithelial-to-mesenchymal transition, cancer cell stemness, angiogenesis, and immunosuppression, all of which are currently viewed as specialized biological programs contributing to the "metastatic cascade" among other cancer hallmarks.

Incomplete Partition Type II Cochlear Malformations: Delineating the Three-Dimensional Structure from Digitized Human Histopathological Specimens.

Hypothesis: There are clinically relevant differences in scalae anatomy and spiral ganglion neuron (SGN) quantity between incomplete partition type II (IP-II) and normal cochleae.

Background: IP-II is a commonly implanted cochlear malformation. Detailed knowledge of intracochlear three-dimensional (3D) morphology may assist with cochlear implant (CI) electrode selection/design and enable optimization of audiologic programming based on SGN maps.

Human Histology after Structure Preservation Cochlear Implantation via Round Window Insertion.

Objectives: Current surgical techniques aim to preserve intracochlear structures during cochlear implant (CI) insertion to maintain residual cochlear function. The optimal technique to minimize damage, however, is still under debate. The aim of this study is to histologically compare insertional trauma and intracochlear tissue formation in humans with a CI implanted via different insertion techniques.

Cochlear Ossification After Vestibular Schwannoma Surgery: A Temporal Bone Study.

Objective: This study aims to investigate patterns of cochlear ossification (CO) in cadaveric temporal bones of patients who underwent vestibular schwannoma (VS) surgery via the translabyrinthine (TL), middle cranial fossa (MF), or retrosigmoid (RS) approaches.

Study Design: Histopathologic analysis of cadaveric temporal bones.

Setting: Multi-institutional national temporal bone repository.

Glycosylation spectral signatures for glioma grade discrimination using Raman spectroscopy.

Background: Gliomas are the most common brain tumours with the high-grade glioblastoma representing the most aggressive and lethal form. Currently, there is a lack of specific glioma biomarkers that would aid tumour subtyping and minimally invasive early diagnosis. Aberrant glycosylation is an important post-translational modification in cancer and is implicated in glioma progression.

Three-dimensional quantification of fibrosis and ossification after cochlear implantation via virtual re-sectioning: Potential implications for residual hearing.

Hearing preservation may be achieved initially in the majority of patients after cochlear implantation, however, a significant proportion of these patients experience delayed hearing loss months or years later. A prior histological report in a case of delayed hearing loss suggested a potential cochlear mechanical origin of this hearing loss due to tissue fibrosis, and older case series highlight the frequent findings of post-implantation fibrosis and neoosteogenesis though without a focus on the impact on residual hearing. Here we present the largest series (N = 20) of 3-dimensionally reconstructed cochleae based on digitally scanned histologic sections from patients who were implanted during their lifetime.

Development of an interdisciplinary microtia-atresia care model: A single-center 20-year experience.

Objectives: Microtia and aural atresia are congenital ear anomalies with a wide-ranging spectrum of phenotypes and varied functional and psychosocial consequences for patients. This study seeks to analyze the management of microtia-atresia patients at our center over a 20-year period and to propose recommendations for advancing microtia-atresia care at a national level.

Methods: We performed a retrospective analysis of data from patients presenting to the Massachusetts Eye and Ear (Boston, MA) for initial otolaryngology consultation for congenital microtia and/or aural atresia between 1999 and 2018.

The diagnostic and prognostic potential of the EGFR/MUC4/MMP9 axis in glioma patients.

Glioblastoma is the most aggressive form of brain cancer, presenting poor prognosis despite current advances in treatment. There is therefore an urgent need for novel biomarkers and therapeutic targets. Interactions between mucin 4 (MUC4) and the epidermal growth factor receptor (EGFR) are involved in carcinogenesis, and may lead to matrix metalloproteinase-9 (MMP9) overexpression, exacerbating cancer cell invasiveness.

Voluntary Field Recall of Advanced Bionics HiRes Cochlear Implants: A Single-Institution Experience.

Objectives: In 2020, Advanced Bionics (AB) announced a recall of two cochlear implant (CI) models, the "HiRes Ultra" and "HiRes Ultra 3D", because of reports of hearing degradation. The present study examines clinical parameters and patient features in cases of device failure and evaluates outcomes after reimplantation.

Materials And Methods: A series of 52 patients implanted with the recalled devices experienced suspected device failure and subsequently underwent revision CI placement at a tertiary academic medical center between December 2019 and November 2021.

Otopathologic and Computed Tomography Correlation of Internal Auditory Canal Diverticula in Otosclerosis.

Introduction: Internal auditory canal (IAC) diverticula, also known as IAC cavitary lesions or anterior cupping of the IAC, observed in otopathologic specimens and high-resolution computed tomography (CT) scans of the temporal bone are thought to be related to otosclerosis. Herein, we examined the usefulness of CT scans in identifying diverticula and determined whether IAC diverticula are associated with otosclerosis on otopathology.

Methods: One hundred five consecutive specimens were identified from the National Temporal Bone Hearing and Balance Pathology Resource Registry.

Computed Tomography Density as a Bio-marker for Histologic Grade of Otosclerosis: A Human Temporal Bone Pathology Study.

Hypothesis: Computed tomography (CT) density measurement can be used to objectively distinguish otosclerosis from normal bone and to determine histologic grades of otosclerosis.

Background: Otosclerosis can be seen on CT as subtle radiolucent areas. An objective radiologic measurement that corresponds to known otosclerosis pathology may improve diagnostic accuracy, and could be used as a radiologic biomarker for otosclerosis grade.

Cochlear implants: Causes, effects and mitigation strategies for the foreign body response and inflammation.

Cochlear implants provide effective auditory rehabilitation for patients with severe to profound sensorineural hearing loss. Recent advances in cochlear implant technology and surgical approaches have enabled a greater number of patients to benefit from this technology, including those with significant residual low frequency acoustic hearing. Nearly all cochleae implanted with a cochlear implant electrode array develop an inflammatory and fibrotic response.

Message in the bottle: regulation of the tumor microenvironment via exosome-driven proteolysis.

Exosomes comprise a subtype of extracellular vesicles involved in cell-to-cell communication, specifically by transporting biological molecules, such as proteins and nucleic acids, to either local or more distant recipient cells, thus triggering distinct biological behaviors. Included in the exosome cargo is frequently a wide range of proteolytic enzymes, such as the matrix metalloproteinases (MMPs), the disintegrin and metalloproteinases (ADAMs), and the ADAM with thrombospondin-like motifs (ADAMTSs), whose functions contribute to the development and progression of cancer. In recent years, extensive research on the potential use of exosomes in diagnostic and therapeutic applications for personalized medicine has emerged, but the targeting of the proteolytic cargo of exosomes has not been fully exploited in this direction.