COVID-19-related chemosensory changes: Findings from a prospective national database.

Objective: The aim of this study was to review findings from a large prospective national database of chemosensory disturbances associated with coronavirus disease 2019 (COVID-19) infection. Data Sources: The Virginia Commonwealth University Smell and Taste Center national database of COVID-19 chemosensory disturbances. Methods: A series of online surveys, first opened on April 10, 2020, was made accessible nationwide to any adult with sudden chemosensory dysfunction since January 2020. Participants received subsequent follow-up surveys 14 days, 1 month, 3 months, and 6 months after enrollment. An additional survey was sent to all participants on May 28, 2022 to assess long-term outcomes. Information pertaining to demographics, symptoms, comorbidities, treatments, and life impact was collected. Results: Of 363 participants who reported complete smell recovery, 51.2% recovered within 1 month, 70% within 3 months, and 79% within 6 months, while 8.8% took over 1 year to completely recover. Among all participants, 7.5% had no smell recovery. Positive predictors of recovery included age <40, male gender, and the presence of nasal congestion. Negative predictors included difficulty breathing and prior head injury. Many participants reported a decrease in quality of life and the presence of potential safety hazards associated with decreased smell loss. Conclusions: Most subjects with COVID-19-related chemosensory dysfunction recover, with the majority noting complete recovery within weeks of infection. Those aged over 40 years and female gender were associated with lower rates of recovery. A considerable number of participants reported significant impact on quality of life and safety.

Comprehensive Analysis of Adverse Events Associated With Hypoglossal Nerve Stimulators: Insights From the MAUDE Database.

OBJECTIVE: This study aims to examine the adverse events associated with hypoglossal nerve stimulator (HNS) implantation for treating obstructive sleep apnea (OSA), drawing data from the Manufacturer and User Facility Device Experience (MAUDE) database. We aim to provide a comprehensive and updated account of these adverse events. STUDY DESIGN: Retrospective analysis. SETTING: MAUDE Database review. METHODS: A retrospective analysis was performed on the MAUDE database to collect all HNS-related reports from May 2014 to December 2023. Variables collected included date of event, event description, nature of event, iatrogenic injuries, required interventions, and, if available, root causes. Each event description was analyzed to classify the adverse event, the postevent intervention, and device model number. RESULTS: Out of 1178 reports fulfilling the inclusion criteria, 1312 adverse events were identified. Common adverse events included infection (24.0%), pain (19.7%), and hematoma/seroma (10.2%). Approximately 83.1% of these adverse events necessitated medical and/or surgical intervention. The most frequent procedures included explantation (29.4%) and device repositioning (15.8%). Pneumothorax was reported in 50 cases, with 41 (82.0%) requiring a chest tube to be inserted. Three adverse events described overstimulation in the setting of magnetic resonance imaging (MRI) despite the implantation of MRI-compatible second-generation internal pulse generators. CONCLUSION: While HNS implantation has been established as a reliable intervention for OSA in cases of continuous positive airway pressure failure or intolerance, this study highlights several perioperative and postoperative difficulties and complications. Understanding these challenges is essential for refining surgical practices and enhancing patient consent processes, ultimately aiming to improve therapeutic outcomes.

Conductance-based dendrites perform Bayes-optimal cue integration.

A fundamental function of cortical circuits is the integration of information from different sources to form a reliable basis for behavior. While animals behave as if they optimally integrate information according to Bayesian probability theory, the implementation of the required computations in the biological substrate remains unclear. We propose a novel, Bayesian view on the dynamics of conductance-based neurons and synapses which suggests that they are naturally equipped to optimally perform information integration. In our approach apical dendrites represent prior expectations over somatic potentials, while basal dendrites represent likelihoods of somatic potentials. These are parametrized by local quantities, the effective reversal potentials and membrane conductances. We formally demonstrate that under these assumptions the somatic compartment naturally computes the corresponding posterior. We derive a gradient-based plasticity rule, allowing neurons to learn desired target distributions and weight synaptic inputs by their relative reliabilities. Our theory explains various experimental findings on the system and single-cell level related to multi-sensory integration, which we illustrate with simulations. Furthermore, we make experimentally testable predictions on Bayesian dendritic integration and synaptic plasticity.

Are There Hidden Adverse Events in Hypoglossal Nerve Stimulation: Comparing Social Media and a Federal Database.

OBJECTIVE: Hypoglossal nerve stimulation (HNS) can be an effective treatment for moderate to severe obstructive sleep apnea (OSA) in positive airway pressure (PAP) intolerant patients. To better understand patient experiences with HNS therapy, we explored reported events from HNS-related Facebook groups and the Manufacturer and User Facility Device Experience (MAUDE) database. METHODS: A retrospective analysis of HNS-related Facebook posts from three groups pertaining to HNS therapy, from October 1, 2022 to October 1, 2023, was performed. Posts were analyzed for patient-reported adverse events. Concurrently, the MAUDE database was reviewed for HNS-related events during the same timeframe. RESULTS: From 737 Facebook posts, 132 (17.55%) adverse events were identified. Adverse events included pain (34.85%), stimulation discomfort (14.39%), lip weakness (6.82%) and issues related to lead tethering or tight leads around the neck (3.79%). Analysis of the MAUDE database found 428 adverse events, including pain (24.07%), lip weakness (0.44%), and lead tethering (1.64%). CONCLUSION: Facebook group members reported higher rates of lip weakness and lead tethering than recorded in the MAUDE database. These findings illustrate how diverse data sources, such as social media, can enhance our understanding of patient experiences and identify gaps in patient education with HNS therapy. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

Modular-integrative modeling: a new framework for building brain models that blend biological realism and functional performance.

This Perspective presents the Modular-Integrative Modeling approach, a novel framework in neuroscience for developing brain models that blend biological realism with functional performance to provide a holistic view on brain function in interaction with the body and environment.

Bioglass/ceria nanoparticle hybrids for the treatment of seroma: a comparative long-term study in rats.

Background: Seroma formation is a common postoperative complication. Fibrin-based glues are typically employed in an attempt to seal the cavity. Recently, the first nanoparticle (NP)-based treatment approaches have emerged. Nanoparticle dispersions can be used as tissue glues, capitalizing on a phenomenon known as 'nanobridging'. In this process, macromolecules such as proteins physically adsorb onto the NP surface, leading to macroscopic adhesion. Although significant early seroma reduction has been shown, little is known about long-term efficacy of NPs. The aim of this study was to assess the long-term effects of NPs in reducing seroma formation, and to understand their underlying mechanism. Methods: Seroma was surgically induced bilaterally in 20 Lewis rats. On postoperative day (POD) 7, seromas were aspirated on both sides. In 10 rats, one side was treated with NPs, while the contralateral side received only NP carrier solution. In the other 10 rats, one side was treated with fibrin glue, while the other was left untreated. Seroma fluid, blood and tissue samples were obtained at defined time points. Biochemical, histopathological and immunohistochemical assessments were made. Results: NP-treated sides showed no macroscopically visible seroma formation after application on POD 7, in stark contrast to the fibrin-treated sides, where 60% of the rats had seromas on POD 14, and 50% on POD 21. At the endpoint (POD 42), sides treated with nanoparticles (NPs) exhibited significant macroscopic differences compared to other groups, including the absence of a cavity, and increased fibrous adhesions. Histologically, there were more macrophage groupings and collagen type 1 (COL1) deposits in the superficial capsule on NP-treated sides. Conclusion: NPs not only significantly reduced early manifestations of seroma and demonstrated an anti-inflammatory response, but they also led to increased adhesion formation over the long term, suggesting a decreased risk of seroma recurrence. These findings highlight both the adhesive properties of NPs and their potential for clinical therapy.

Gun shot injuries to the temporal bone: Anatomic predictors of mortality.

PURPOSE: To explore anatomic predictors of mortality from gunshot wounds involving the temporal bone. METHODS: A retrospective search of radiology reports was performed for all patients with CT reports suggestive of gunshot wounds (GSW) to the TB (2000-2020). All cases were reviewed by the senior author to confirm injury to the temporal bone. Detailed demographic and radiographic data were collected. MAIN FINDINGS: A total of 120 patients met inclusion criteria. The majority of patients were male (n = 101) and the average age was 32.9. The squamosa was the most commonly involved subsite (n = 90), followed by the mastoid (n = 43). Squamosal entry site had the highest associated mortality (89.7 %). For those with known disposition, 65.8 % (79 of 120) expired on the same hospital admission. Inpatient otolaryngology consultation was noted in 18.3 % (n = 22) of patients, with poor outpatient follow-up. CONCLUSIONS: This series represents the largest survey of GSW to the temporal bone to date. Although associated mortality is high and outpatient follow-up poor, otolaryngologists should be aware of associated morbidities to facilitate both inpatient and subsequent outpatient management.

Learning beyond sensations: How dreams organize neuronal representations.

Semantic representations in higher sensory cortices form the basis for robust, yet flexible behavior. These representations are acquired over the course of development in an unsupervised fashion and continuously maintained over an organism's lifespan. Predictive processing theories propose that these representations emerge from predicting or reconstructing sensory inputs. However, brains are known to generate virtual experiences, such as during imagination and dreaming, that go beyond previously experienced inputs. Here, we suggest that virtual experiences may be just as relevant as actual sensory inputs in shaping cortical representations. In particular, we discuss two complementary learning principles that organize representations through the generation of virtual experiences. First, "adversarial dreaming" proposes that creative dreams support a cortical implementation of adversarial learning in which feedback and feedforward pathways engage in a productive game of trying to fool each other. Second, "contrastive dreaming" proposes that the invariance of neuronal representations to irrelevant factors of variation is acquired by trying to map similar virtual experiences together via a contrastive learning process. These principles are compatible with known cortical structure and dynamics and the phenomenology of sleep thus providing promising directions to explain cortical learning beyond the classical predictive processing paradigm.

Earth's field NMR relaxation of pre-polarised water protons for real-time detection of free-radical formation.

Real-time imaging of free-radical formation is important in physical chemistry, biochemistry, and radiobiology, especially for the study of radiation dose-rate effects. Herein, we show for the first time that the formation of free radicals during the time course of a chemical reaction can be imaged through NMR relaxation measurements of water protons in the Earth's magnetic field, in an open-coil spectrometer. The relaxation rate constants of water magnetisation are enhanced as reactions leading to the formation of hydroxyl radicals and oxygen proceed on the timescale of tens of minutes. The reaction rate of iodide-catalysed H2O2 decay was followed by Earth-field 1H NMR relaxation in real time. The relaxivities of the reaction product and several other paramagnetic compounds were determined. Spin-trap molecules were then used to capture ˙OH radical species, thus altering the reaction rate in proportion to the formation of new paramagnetic compounds. Thereby, a new experimental method for magnetic resonance imaging of the formation of intermediate and stable radical species in water is proposed.

A general Monte Carlo method for sample size analysis in the context of network models.

We introduce a general method for sample size computations in the context of cross-sectional network models. The method takes the form of an automated Monte Carlo algorithm, designed to find an optimal sample size while iteratively concentrating the computations on the sample sizes that seem most relevant. The method requires three inputs: (1) a hypothesized network structure or desired characteristics of that structure, (2) an estimation performance measure and its corresponding target value (e.g., a sensitivity of 0.6), and (3) a statistic and its corresponding target value that determines how the target value for the performance measure be reached (e.g., reaching a sensitivity of 0.6 with a probability of 0.8). The method consists of a Monte Carlo simulation step for computing the performance measure and the statistic for several sample sizes selected from an initial candidate sample size range, a curve-fitting step for interpolating the statistic across the entire candidate range, and a stratified bootstrapping step to quantify the uncertainty around the recommendation provided. We evaluated the performance of the method for the Gaussian Graphical Model, but it can easily extend to other models. The method displayed good performance, providing sample size recommendations that were, on average, within three observations of a benchmark sample size, with the highest standard deviation of 25.87 observations. The method discussed is implemented in the form of an R package called powerly, available on GitHub and CRAN. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Multiple Stroboscopic Detection of Long-Lived Nuclear Magnetization for Glutathione Oxidation Kinetics.

Imaging the molecular kinetics of antioxidants by magnetic resonance can contribute to the mechanistic understanding of therapeutic approaches. Magnetic resonance detection of the response to flashes of oxidative stress requires sequential spectroscopy on the same time scale on which reactive oxygen species are generated. To this effect, we propose a single-polarization multiple-detection stroboscopic experiment. We demonstrate this experiment for the follow-up of glutathione oxidation kinetics. On-the-fly stroboscopic detection minimizes the durations necessary for single acquisitions yet necessitates sustaining of magnetization lifetimes. Long-lived proton spin states (LLS) in the cysteine and glycine residues of glutathione with TLLS up to 16 s are reached. Based on 1H LLS, we followed fast oxidation kinetics in the glutathione redox pair GSH/GSSG. This new detection method allows sampling of long-lived spin order multiple times via small flip-angle excitations. This establishes the ground for the follow-up of redox processes detecting GSH/GSSG kinetics as magnetic-resonance biomarker of FLASH oxidative processes on time scales of tens of seconds.

Vascular injury arising from lateral skull base fractures.

PURPOSE: Although uncommon, vascular injury can be seen in patients with lateral skull base fractures (LSBF). However, little is known about this potentially life-threatening comorbidity. The objective of this study is to better characterize the vascular injuries associated with temporal and lateral sphenoid bone fractures. BASIC PROCEDURES: Retrospective review of all patients with computed tomography angiography (CTA) performed specifically to evaluate for vascular injury following LSBF. In addition to patient demographics (age, gender, race), the mechanism of injury, the location of fracture(s), and the nature of vascular injury diagnosed by CTA was recorded. Two-way ANOVA was performed to determine if any variables were predictive of vascular injury. MAIN FINDINGS: From 2011 to 2021, 143 patients with 333 subsite fractures met inclusion criteria. Of all patients, 46 (32.2 %) had CTA evidence of at least one vascular injury, the most common type being venous thrombosis/filling defect (41.7 %). Evidence of vascular injury was unclear in 14 patients (9.8 %). Fractures most associated with vascular injury ranged from 0.7 % (otic capsule fractures) to 26.7 % (mastoid, lateral sphenoid fractures). Risk of vascular injury was no different between patients with single vs multiple fractures. There were no fracture locations that could reliably predict specific vascular injury. CONCLUSIONS: Over 40 % of all CTAs ordered following LSBF identified were suspicious for associated vascular injury. Yet fracture location and number cannot reliably predict vascular injury. Until such determinants can be better identified, clinicians should have a low threshold to obtain CTA to rule out associated vascular injury.

The osteocutaneous SCIP flap: A detailed description of the surgical technique and retrospective cohort study of consecutive cases in a tertiary European centre.

INTRODUCTION: In the era of increasing popularity of the superficial circumflex iliac perforator (SCIP) flap, osteocutaneous variants of the flap have been described as well. Despite their benefits such as customizability and low donor site morbidity, these flaps have not yet gained broad acceptance. By reviewing our case series, we aim to promote the safe application of this promising new tool in osteoplastic reconstructions. PATIENTS AND METHODS: We performed a single-centre, retrospective chart review of all cases in which osteocutaneous SCIP-flaps were used. We describe our surgical technique and present the surgical, functional and aesthetic outcomes of the patients in our cohort. RESULTS: Since September 2019, we have used osteocutaneous SCIP flaps in six patients, five in the extremities and one for the head and neck region. The vascularised bone segment was measured on average 4.9 cm (range 4-7 cm) x 3 cm (range 1.5-4 cm) and was combined with a skin paddle of a mean length of 14.3 cm (range 8-20 cm) and width of 6.3 cm (range 5-8 cm). One flap underwent emergency revision due to venous congestion. All flaps survived and healed uneventfully. Long-term follow-up shows adequate bony integration and stable soft tissue coverage with good functional restoration and minimal donor site morbidity. CONCLUSION: The osteocutaneous SCIP flap provides a large and thin skin island and a "moderately sized" vascularised bone segment with minimal donor site morbidity and can be successfully used in selected cases of osteoplastic reconstruction.

Using a Double Syringe Sterile System for MSK Aspiration/Injection Procedures Eliminates Risk of Iatrogenic Infection.

Introduction: Diverse musculo-skeletal pathology can be treated conservatively by different types of injections and in most cases, results are significantly better if the existing inflammatory fluid is aspirated prior to injection of medication solutions. The present study analyses an original technique which uses infusion therapy accessories to create two types of closed sterile double syringe systems, and compares the benefits of using such a system in aspiration/injection procedures to classic aspiration injection technique that implies changing and connecting multiple syringes to the same needle, thus increasing the risk for septic complications. The aim of the present study is to minimize therapeutic risk of iatrogenic septic complications during aspiration/injection procedures. Methods: 1024 patients underwent aspiration/injection procedures in our clinic using the double syringe system between 2015 and 2020. During the early stages of the study, the second type of assembly was rendered impractical so the study continued with analyzing a single type of double syringe system using a three way infusion therapy device which is readily available, and allows the assembly of a closed sterile system with a single, two-step procedure technique. Iatrogenic local septic complications were followed by means of a six week clinical follow-up evaluation with additional investigations only if necessary. Results: In 1024 procedures we report 0% incidence of iatrogenic septic complications, or other types of complications and recommend this technique in a vast array of rheumatic, orthopedic or traumatic conditions that require aspiration/injection procedures. Discussion: The double syringe system is practical, easy to use, it completely eliminates the risk of iatrogenic infection due to manipulation errors, and significantly simplifies the technique for sonography guided aspiration/injection procedures for musculo-skeletal pathology.

Transcutaneous sentinel lymph node detection in cutaneous melanoma with indocyanine green and near-infrared fluorescence: A diagnostic sensitivity study.

Sentinel lymph node (SLN) biopsy with preoperative radiocolloid-based lymphoscintigraphy and blue dye injection is considered the standard procedure for staging nodal metastases in early-stage cutaneous melanoma patients with clinically uninvolved lymph nodes. While this combination renders good accuracy in SLN detection, radiation exposure and the frequent allergic reactions to the blue dye are considered drawbacks of this technique. Indocyanine green (ICG) is a water-soluble fluorescent dye that can be identified through near-infrared fluorescence imaging (NIRFI). The aim of this prospective diagnostic sensitivity study was to assess the feasibility of ICG and NIRFI to identify SLNs in melanoma transcutaneously ("before skin incision") and to analyze the various factors influencing detection rate, in comparison to lymphoscintigraphy. This study included 93 patients undergoing SLN biopsy for cutaneous melanoma. The region and the number of the SLNs identified with lymphoscintigraphy and with ICG were recorded. Patients' characteristics, as well as tumor details were also recorded preoperatively. One hundred and ninety-four SLNs were identified through lymphoscintigraphy. The sensitivity of ICG for transcutaneous identification of the location of the SLNs was 96.1% overall, while the sensitivity rate for the number of SLNs was 79.4%. Gender and age did not seem to influence detection rate, but a body mass index >30 kg/m2 was associated with a lower identification rate of the number of SLNs (P = .045). Transcutaneous identification of SLNs through ICG and NIRFI technology is a feasible technique that could potentially replace in selected patients the standard SLN detection methodology in cutaneous melanoma.

Variational learning of quantum ground states on spiking neuromorphic hardware.

Recent research has demonstrated the usefulness of neural networks as variational ansatz functions for quantum many-body states. However, high-dimensional sampling spaces and transient autocorrelations confront these approaches with a challenging computational bottleneck. Compared to conventional neural networks, physical model devices offer a fast, efficient and inherently parallel substrate capable of related forms of Markov chain Monte Carlo sampling. Here, we demonstrate the ability of a neuromorphic chip to represent the ground states of quantum spin models by variational energy minimization. We develop a training algorithm and apply it to the transverse field Ising model, showing good performance at moderate system sizes ( N ≤ 10 ). A systematic hyperparameter study shows that performance depends on sample quality, which is limited by temporal parameter variations on the analog neuromorphic chip. Our work thus provides an important step towards harnessing the capabilities of neuromorphic hardware for tackling the curse of dimensionality in quantum many-body problems.

Natural-gradient learning for spiking neurons.

In many normative theories of synaptic plasticity, weight updates implicitly depend on the chosen parametrization of the weights. This problem relates, for example, to neuronal morphology: synapses which are functionally equivalent in terms of their impact on somatic firing can differ substantially in spine size due to their different positions along the dendritic tree. Classical theories based on Euclidean-gradient descent can easily lead to inconsistencies due to such parametrization dependence. The issues are solved in the framework of Riemannian geometry, in which we propose that plasticity instead follows natural-gradient descent. Under this hypothesis, we derive a synaptic learning rule for spiking neurons that couples functional efficiency with the explanation of several well-documented biological phenomena such as dendritic democracy, multiplicative scaling, and heterosynaptic plasticity. We therefore suggest that in its search for functional synaptic plasticity, evolution might have come up with its own version of natural-gradient descent.

Learning cortical representations through perturbed and adversarial dreaming.

Humans and other animals learn to extract general concepts from sensory experience without extensive teaching. This ability is thought to be facilitated by offline states like sleep where previous experiences are systemically replayed. However, the characteristic creative nature of dreams suggests that learning semantic representations may go beyond merely replaying previous experiences. We support this hypothesis by implementing a cortical architecture inspired by generative adversarial networks (GANs). Learning in our model is organized across three different global brain states mimicking wakefulness, non-rapid eye movement (NREM), and REM sleep, optimizing different, but complementary, objective functions. We train the model on standard datasets of natural images and evaluate the quality of the learned representations. Our results suggest that generating new, virtual sensory inputs via adversarial dreaming during REM sleep is essential for extracting semantic concepts, while replaying episodic memories via perturbed dreaming during NREM sleep improves the robustness of latent representations. The model provides a new computational perspective on sleep states, memory replay, and dreams, and suggests a cortical implementation of GANs.

Cortical oscillations support sampling-based computations in spiking neural networks.

Being permanently confronted with an uncertain world, brains have faced evolutionary pressure to represent this uncertainty in order to respond appropriately. Often, this requires visiting multiple interpretations of the available information or multiple solutions to an encountered problem. This gives rise to the so-called mixing problem: since all of these "valid" states represent powerful attractors, but between themselves can be very dissimilar, switching between such states can be difficult. We propose that cortical oscillations can be effectively used to overcome this challenge. By acting as an effective temperature, background spiking activity modulates exploration. Rhythmic changes induced by cortical oscillations can then be interpreted as a form of simulated tempering. We provide a rigorous mathematical discussion of this link and study some of its phenomenological implications in computer simulations. This identifies a new computational role of cortical oscillations and connects them to various phenomena in the brain, such as sampling-based probabilistic inference, memory replay, multisensory cue combination, and place cell flickering.