Predictive Factors for Subjective Vertigo Following Cochlear Implantation: A Regional Multicenter Cohort Study of 395 Patients.

INTRODUCTION: Cochlear implantation (CI) is generally accepted as having a low rate of postoperative complications, but between 9.3% and 13% of cases experience vertigo postoperatively. This study aimed to examine patient, surgical, and device factors contributing toward the risk of postoperative vertigo. METHODOLOGY: A retrospective review was conducted of adult patients who underwent cochlear implant in a regional area of New South Wales from 2007 to 2018. A total of 395 cochlear implant cases were included in the final study. RESULTS: The overall incidence of vertigo at 3 months of follow-up was 7.1% (n = 28/395). No difference was identified in this study between rates of postoperative vertigo between device factors, including implant make (Cochlear vs. Med-El), electrode shape (perimodiolar vs. straight), and electrode model. No significant difference was found also for surgical factors such as the number of electrode rings inserted, side of implantation, or surgical approach of tympanic ramp (round window insertion vs. cochleostomy).A higher percentage of patients with preoperative vertigo experienced vertigo postoperatively (18.4%, n = 7/38), compared with the population without preoperative vertigo (6.0%, n = 21/352) ( p = 0.005). Patients with previous mastoid surgery also reported a higher rate of postoperative vertigo (20%, n = 9/45) compared with those who had not had mastoid surgery (5.43%, n = 19/350) ( p = 0.006). The mean age of patients experiencing postoperative vertigo was higher than the population without postoperative symptoms (67 vs. 63). CONCLUSION: This study of a large multicenter population outlines that patient factors are more critical than surgical or device factors when considering risk factors for vertigo post-cochlear implant.

Simultaneous cochlear implantation during resection of a cerebellopontine angle meningioma: case report.

Cerebellopontine angle (CPA) meningiomas commonly involve the internal auditory canal (IAC). We report a case of a 68-year-old lady with idiopathic profound bilateral deafness with a meningioma which was discovered on workup for cochlear implantation. We performed simultaneous excision of her CPA and IAC meningioma with insertion of a cochlear implant (CI). She regained functional hearing with marked improvement in quality of life. Intraoperative electrophysiological testing can be used to confirm preservation of the cochlear nerve enabling simultaneous implantation which is preferable for clinical and logistical reasons. This creates an option for hearing rehabilitation at the time of IAC/CPA tumour surgery in appropriate patients.

H-Bonds in Crambin: Coherence in an α-Helix.

We applied coherence analysis-used by engineers to identify linear interactions in stochastic systems-to molecular dynamics simulations of crambin, a thionin storage protein found in Abyssinian cabbage. A key advantage of coherence over other analyses is that it is robust, independent of the properties, or even the existence of probability distributions often relied on in statistical mechanics. For frequencies between 0.391 and 5.08 GHz (corresponding reciprocally to times of 2.56 and 0.197 ns), the displacements of oxygen and nitrogen atoms across α-helix H-bonds are strongly correlated, with a coherence greater than 0.9; the secondary structure causes the H-bonds to effectively act as a spring. Similar coherence behavior is observed for covalent bonds and other noncovalent interactions including H-bonds in ß-sheets and salt bridges. In contrast, arbitrary pairs of atoms that are physically distant have uncorrelated motions and negligible coherence. These results suggest that coherence may be used to objectively identify atomic interactions without subjective thresholds such as H-bond lengths angles and angles. Strong coherence is also observed between the average position of adjacent leaves (groups of atoms) in an α-helix, suggesting that the harmonic analysis of classical molecular dynamics can successfully describe the propagation of allosteric interactions through the structure.

Systematic Review and Meta-Analysis on the Incidence of Level-Specific Cervical Nodal Metastasis in Primary Parotid Malignancies.

OBJECTIVE: In primary parotid gland malignancies, the incidence of level-specific cervical lymph node metastasis in clinically node-positive necks remains unclear. This study aimed to determine the incidence of level-specific cervical node metastasis in clinically node-negative (cN0) and node-positive (cN+) patients who presented with primary parotid malignancies. DATA SOURCES: Electronic databases (MEDLINE, EMBASE, PubMed, Cochrane). REVIEW METHODS: Random-effects meta-analysis was used to calculate pooled estimate incidence of level-specific nodal metastasis for parotid malignancies with 95% confidence intervals (CIs). Subgroup analyses of cN0 and cN+ were performed. RESULTS: Thirteen publications consisting of 818 patients were included. The overall incidence of cervical nodal involvement in all neck dissections was 47% (95% CI, 31%-63%). Among those who were cN+, the incidence of nodal positivity was 89% (95% CI, 75%-98%). Those who were cN0 had an incidence of 32% (95% CI, 14%-53%). In cN+ patients, the incidence of nodal metastasis was high at all levels (level I 33%, level II 73%, level III 48%, level IV 39%, and level V 37%). In cN0 patients, the incidence of nodal metastasis was highest at levels II (28%) and III (11%). CONCLUSION: For primary parotid malignancies, the incidence of occult metastases was 32% compared to 89% in a clinically positive neck. It is recommended that individuals with a primary parotid malignancy requiring elective treatment of the neck have a selective neck dissection which involves levels II to III, with the inclusion of level IV based on clinical judgment. Those undergoing a therapeutic neck dissection should undergo a comprehensive neck dissection (levels I-V).

Comparison of postoperative complications in early versus delayed tracheostomy decannulation in patients undergoing oral cancer surgery with microvascular reconstruction.

The purpose of this study was to determine the relationship of early and delayed tracheostomy decannulation protocols on the length of stay, time to oral feeding and incidence of postoperative complications in patients undergoing microvascular reconstruction for oral cancer. A review of all patients who underwent surgical management of oral squamous cell carcinoma (OSCC) over the study period from 01/07/2017 to 31/06/2021 was performed. Patients who underwent elective tracheostomy as part of their microvascular reconstruction were included. Two cohorts were identified based on distinct postoperative tracheostomy decannulation protocols; early (Within 7 days) and delayed (≥7 days). Time to oral feeding, length of stay and complication rates was determined for both groups for statistical analysis. A total of 103 patients with OSCC were included in the study. The overall complication rate was 35.9% and were more likely in node positive patients (53.7% vs 23.2%; p = 0.003) and in cases where the geniohyoid muscle complex was disrupted during tumour resection (66.7% vs 31.9%; p = 0.026). Early decannulation was significantly associated with shorter length of hospital stay (10 days vs 15 days) and earlier removal of nasogastric feeding tubes (7 vs 10 days). There was no difference in the overall complication rate between the two groups (33.3% vs 37.5%; p = 0.833). Early decannulation in appropriately selected patients is recommended as it significantly reduces the length of hospital stay and aids in early resumption of oral intake. Furthermore, this approach is not associated with increased rates of complications.

Coupled chemical reactions: Effects of electric field, diffusion, and boundary control.

Chemical reactions involve the movement of charges, and this paper presents a mathematical model for describing chemical reactions in electrolytes. The model is developed using an energy variational method that aligns with classical thermodynamics principles. It encompasses both electrostatics and chemical reactions within consistently defined energetic and dissipative functionals. Furthermore, the energy variation method is extended to account for open systems that involve the input and output of charge and mass. Such open systems have the capability to convert one form of input energy into another form of output energy. In particular, a two-domain model is developed to study a reaction system with self-regulation and internal switching, which plays a vital role in the electron transport chain of mitochondria responsible for ATP generation-a crucial process for sustaining life. Simulations are conducted to explore the influence of electric potential on reaction rates and switching dynamics within the two-domain system. It shows that the electric potential inhibits the oxidation reaction while accelerating the reduction reaction.

Late Free Flap Failure in Head and Neck Reconstruction: Unusual Etiology in Two Case Studies and Literature Review.

The development of modern microvascular surgical techniques has enabled the reliable transfer of free vascularized tissue. This allowed for predictable reconstruction outcomes with excellent surgical success rates. However, devastating consequences of partial or total flap failure and subsequent loss may occur. This usually occurs in the first 48-72 h post-operatively. It is rare for flaps to fail in the late post-operative period and it remains poorly understood why flaps fail after day seven. We presented two patients in whom flap failure occurred after the seventh post-operative day (POD). Complete flap failure occurred after POD 9 and 27 in our cases. During the postoperative period, there was no evidence of early occlusion or insult to the vascular integrity such as venous/arterial compression. The cause of late flap failure was due to thrombophlebitis secondary to infection from the tracheostomy-neck fistula. This assumption was supported by recurrent failure of anastomoses revision.

Gating current noise produced by Brownian models of a voltage sensor.

The activation of voltage-dependent ion channels is associated with the movement of gating charges, which give rise to gating currents. Although gating currents from a single channel are too small to be detected, analysis of the fluctuations of macroscopic gating currents from a population of channels allows a good guess of their magnitude. The analysis of experimental gating current fluctuations, when interpreted in terms of a rate model of channel activation and assuming sufficiently high bandwidth, is in accordance with the presence of a main step along the activation pathway carrying a charge of 2.3-2.4 e0. To give a physical interpretation to these results and to relate them to the known atomic structure of the voltage sensor domain, we used a Brownian model of voltage-dependent gating based on atomic detail structure, that follows the laws of electrodynamics. The model predicts gating currents and gating current fluctuations essentially similar to those experimentally observed. The detailed study of the model output, also performed by making several simplifications aimed at understanding the basic dependencies of the gating current fluctuations, suggests that in real channels the voltage sensor moves along a sequence of intermediate states separated by relatively low (<5 kT) energy barriers. As a consequence, crossings of successive gating charges through the gating pore become very frequent, and the corresponding current shots are often seen to overlap because of the relatively high filtering. Notably, this limited bandwidth effect is at the origin of the relatively high single-step charge experimentally detected.

A tridomain model for potassium clearance in optic nerve of Necturus.

Complex fluids flow in complex ways in complex structures. Transport of water and various organic and inorganic molecules in the central nervous system are important in a wide range of biological and medical processes. However, the exact driving mechanisms are often not known. In this work, we investigate flows induced by action potentials in an optic nerve as a prototype of the central nervous system. Different from traditional fluid dynamics problems, flows in biological tissues such as the central nervous system are coupled with ion transport. They are driven by osmosis created by concentration gradient of ionic solutions, which in turn influence the transport of ions. Our mathematical model is based on the known structural and biophysical properties of the experimental system used by the Harvard group Orkand et al. Asymptotic analysis and numerical computation show the significant role of water in convective ion transport. The full model (including water) and the electrodiffusion model (excluding water) are compared in detail to reveal an interesting interplay between water and ion transport. In the full model, convection due to water flow dominates inside the glial domain. This water flow in the glia contributes significantly to the spatial buffering of potassium in the extracellular space. Convection in the extracellular domain does not contribute significantly to spatial buffering. Electrodiffusion is the dominant mechanism for flows confined to the extracellular domain.

Maxwell Equations without a Polarization Field, Using a Paradigm from Biophysics.

When forces are applied to matter, the distribution of mass changes. Similarly, when an electric field is applied to matter with charge, the distribution of charge changes. The change in the distribution of charge (when a local electric field is applied) might in general be called the induced charge. When the change in charge is simply related to the applied local electric field, the polarization field P is widely used to describe the induced charge. This approach does not allow electrical measurements (in themselves) to determine the structure of the polarization fields. Many polarization fields will produce the same electrical forces because only the divergence of polarization enters Maxwell's first equation, relating charge and electric forces and field. The curl of any function can be added to a polarization field P without changing the electric field at all. The divergence of the curl is always zero. Additional information is needed to specify the curl and thus the structure of the P field. When the structure of charge changes substantially with the local electric field, the induced charge is a nonlinear and time dependent function of the field and P is not a useful framework to describe either the electrical or structural basis-induced charge. In the nonlinear, time dependent case, models must describe the charge distribution and how it varies as the field changes. One class of models has been used widely in biophysics to describe field dependent charge, i.e., the phenomenon of nonlinear time dependent induced charge, called 'gating current' in the biophysical literature. The operational definition of gating current has worked well in biophysics for fifty years, where it has been found to makes neurons respond sensitively to voltage. Theoretical estimates of polarization computed with this definition fit experimental data. I propose that the operational definition of gating current be used to define voltage and time dependent induced charge, although other definitions may be needed as well, for example if the induced charge is fundamentally current dependent. Gating currents involve substantial changes in structure and so need to be computed from a combination of electrodynamics and mechanics because everything charged interacts with everything charged as well as most things mechanical. It may be useful to separate the classical polarization field as a component of the total induced charge, as it is in biophysics. When nothing is known about polarization, it is necessary to use an approximate representation of polarization with a dielectric constant that is a single real positive number. This approximation allows important results in some cases, e.g., design of integrated circuits in silicon semiconductors, but can be seriously misleading in other cases, e.g., ionic solutions.

Diagnostics for SARS-CoV-2 infections.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to nearly every corner of the globe, causing societal instability. The resultant coronavirus disease 2019 (COVID-19) leads to fever, sore throat, cough, chest and muscle pain, dyspnoea, confusion, anosmia, ageusia and headache. These can progress to life-threatening respiratory insufficiency, also affecting the heart, kidney, liver and nervous systems. The diagnosis of SARS-CoV-2 infection is often confused with that of influenza and seasonal upper respiratory tract viral infections. Due to available treatment strategies and required containments, rapid diagnosis is mandated. This Review brings clarity to the rapidly growing body of available and in-development diagnostic tests, including nanomaterial-based tools. It serves as a resource guide for scientists, physicians, students and the public at large.

Multiscale modeling shows that dielectric differences make NaV channels faster than KV channels.

The generation of action potentials in excitable cells requires different activation kinetics of voltage-gated Na (NaV) and K (KV) channels. NaV channels activate much faster and allow the initial Na+ influx that generates the depolarizing phase and propagates the signal. Recent experimental results suggest that the molecular basis for this kinetic difference is an amino acid side chain located in the gating pore of the voltage sensor domain, which is a highly conserved isoleucine in KV channels but an equally highly conserved threonine in NaV channels. Mutagenesis suggests that the hydrophobicity of this side chain in Shaker KV channels regulates the energetic barrier that gating charges cross as they move through the gating pore and control the rate of channel opening. We use a multiscale modeling approach to test this hypothesis. We use high-resolution molecular dynamics to study the effect of the mutation on polarization charge within the gating pore. We then incorporate these results in a lower-resolution model of voltage gating to predict the effect of the mutation on the movement of gating charges. The predictions of our hierarchical model are fully consistent with the tested hypothesis, thus suggesting that the faster activation kinetics of NaV channels comes from a stronger dielectric polarization by threonine (NaV channel) produced as the first gating charge enters the gating pore compared with isoleucine (KV channel).

Pharmacotherapeutics of SARS-CoV-2 Infections.

The COVID-19 pandemic has affected more than 38 million people world-wide by person to person transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therapeutic and preventative strategies for SARS-CoV-2 remains a significant challenge. Within the past several months, effective treatment options have emerged and now include repurposed antivirals, corticosteroids and virus-specific antibodies. The latter has included convalescence plasma and monoclonal antibodies. Complete viral eradication will be achieved through an effective, safe and preventative vaccine. To now provide a comprehensive summary for each of the pharmacotherapeutics and preventative strategies being offered or soon to be developed for SARS-CoV-2.

On the polarization of ligands by proteins.

Although ligand-binding sites in many proteins contain a high number density of charged side chains that can polarize small organic molecules and influence binding, the magnitude of this effect has not been studied in many systems. Here, we use a quantum mechanics/molecular mechanics (QM/MM) approach, in which the ligand is the QM region, to compute the ligand polarization energy of 286 protein-ligand complexes from the PDBBind Core Set (release 2016). Calculations were performed both with and without implicit solvent based on the domain decomposition Conductor-like Screening Model. We observe that the ligand polarization energy is linearly correlated with the magnitude of the electric field acting on the ligand, the magnitude of the induced dipole moment, and the classical polarization energy. The influence of protein and cation charges on the ligand polarization diminishes with the distance and is below 2 kcal mol-1 at 9 Å and 1 kcal mol-1 at 12 Å. Compared to these embedding field charges, implicit solvent has a relatively minor effect on ligand polarization. Considering both polarization and solvation appears essential to computing negative binding energies in some crystallographic complexes. Solvation, but not polarization, is essential for achieving moderate correlation with experimental binding free energies.

A Bidomain Model for Lens Microcirculation.

There exists a large body of research on the lens of the mammalian eye over the past several decades. The objective of this work is to provide a link between the most recent computational models and some of the pioneering work in the 1970s and 80s. We introduce a general nonelectroneutral model to study the microcirculation in the lens of the eye. It describes the steady-state relationships among ion fluxes, between water flow and electric field inside cells, and in the narrow extracellular spaces between cells in the lens. Using asymptotic analysis, we derive a simplified model based on physiological data and compare our results with those in the literature. We show that our simplified model can be reduced further to the first-generation models, whereas our full model is consistent with the most recent computational models. In addition, our simplified model captures in its equations the main features of the full computational models. Our results serve as a useful link intermediate between the computational models and the first-generation analytical models. Simplified models of this sort may be particularly helpful as the roles of similar osmotic pumps of microcirculation are examined in other tissues with narrow extracellular spaces, such as cardiac and skeletal muscle, liver, kidney, epithelia in general, and the narrow extracellular spaces of the central nervous system, the "brain." Simplified models may reveal the general functional plan of these systems before full computational models become feasible and specific.

Continuum Gating Current Models Computed with Consistent Interactions.

The action potential of nerve and muscle is produced by voltage-sensitive channels that include a specialized device to sense voltage. The voltage sensor depends on the movement of charges in the changing electric field as suggested by Hodgkin and Huxley. Gating currents of the voltage sensor are now known to depend on the movements of positively charged arginines through the hydrophobic plug of a voltage sensor domain. Transient movements of these permanently charged arginines, caused by the change of transmembrane potential V, further drag the S4 segment and induce opening/closing of the ion conduction pore by moving the S4-S5 linker. This moving permanent charge induces capacitive current flow everywhere. Everything interacts with everything else in the voltage sensor and protein, and so it must also happen in its mathematical model. A Poisson-Nernst-Planck (PNP)-steric model of arginines and a mechanical model for the S4 segment are combined using energy variational methods in which all densities and movements of charge satisfy conservation laws, which are expressed as partial differential equations in space and time. The model computes gating current flowing in the baths produced by arginines moving in the voltage sensor. The model also captures the capacitive pile up of ions in the vestibules that link the bulk solution to the hydrophobic plug. Our model reproduces the signature properties of gating current: 1) equality of ON and OFF charge Q in integrals of gating current, 2) saturating voltage dependence in the Q(charge)-voltage curve, and 3) many (but not all) details of the shape of gating current as a function of voltage. Our results agree qualitatively with experiments and can be improved by adding more details of the structure and its correlated movements. The proposed continuum model is a promising tool to explore the dynamics and mechanism of the voltage sensor.

Idiopathic pretracheal deep neck space infection with mediastinal extension: A series of 3 cases and review of the literature.

Idiopathic pretracheal deep neck space infection is an extremely rare condition with potentially devastating complications. We present a series of 3 cases of pretracheal deep neck space infection that arose in the absence of trauma or a congenital lesion and that exhibited mediastinal spread. To the best of our knowledge, these cases represent the first reported series of this rare condition to be published in the English-language literature. All cultures grew Streptococcus milleri, and all patients had a favorable outcome. A high index of suspicion for a deep neck space infection is warranted in view of the devastating complications of this condition. Computed tomography is the investigation of choice. Treatment with intravenous antibiotics and surgical drainage, particularly when mediastinitis is present, is recommended. This rare presentation warrants a thorough investigation to identify the source of infection.