Seasickness susceptibility and the vestibular time constant: a prospective study.

Human passive motion during boat, car or airplane travel may trigger motion sickness. Seasickness is the most provoking manifestation of motion sickness. It imposes major constraints on quality of life and human performance. Based on seasickness susceptibility the population is usually categorized into susceptible (S) and non-susceptible (NS). During repeated exposure some susceptible individuals undergo habituation and obtain symptoms relief, reflecting a third group of habituating (H) individuals. Recently, accumulative evidence suggests that the vestibular time constant (Tc) is associated with motion sickness susceptibility and attenuation of symptoms. These studies demonstrated that repeated passive motion stimuli lead to temporary short-term (days) changes in Tc, whereas sea sickness habituation process lasts 3 to 6 months. Therefore, the goal of the present study was to examine the behavior of Tc during the entire span of the seasickness habituation process between the H, S and NS groups to find an objective test for seasickness severity prediction. Tc of 30 subjects was prospectively evaluated pre, 3 and 6 months post exposure to sea environment using a computerized rotatory chair system protocol. Seasickness severity was evaluated by Wiker questionnaire. Significantly shorter Tc was found in the S group compared with the NS and H groups. Further analysis revealed lower maximal Slow Phase Velocity (mSPV) and nystagmus frequency (total number of beats/second) in the S group. Our results suggest that Tc, mSPV and nystagmus frequency might serve as a prediction for seasickness severity. This study was retrospectively registered on December 7th 2022 and assigned the identifier number NCT05640258.

The Vestibular Time Constant and Clinical Response to Antimotion Sickness Medication.

OBJECTIVE: The therapeutic effects of antimotion sickness medications involve suppression of several components along the vestibular system. Scopolamine-based medications have proved to be the most effective anti-seasickness agents. However, there is high variability in individual responses. The vestibular nuclei, in which the vestibular time constant is modulated, contain acetylcholine receptors which are affected by scopolamine. The hypothesis of the study was that successful seasickness prevention by scopolamine requires vestibular suppression to be reflected by the shortening of the vestibular time constant. DESIGN: Subjects were 30 naval crew members suffering from severe seasickness and were treated with oral scopolamine. The study participants were defined as responsive or non-responsive to the anti-seasickness medication according to the clinical outcome: successful response to scopolamine was defined as a reduction of seasickness severity from the highest score of 7 according to the Wiker scale to 4 or less. Scopolamine and placebo were assigned to each subject in a crossover, double-blind design. The horizontal semicircular canal time constant was evaluated by a computerized rotatory chair before, 1 and 2 hours after drug or placebo administration. RESULTS: The vestibular time constant was significantly shortened from 16.01 ± 3.43 seconds to 12.55 ± 2.40 seconds ( p < 0.001) in the scopolamine-responsive group but not in the nonresponsive group. In contrast, vestibular time constant values were 13.73 ± 4.08 and 12.89 ± 4.48 for baseline and 2 hours measurements, respectively. This change was not statistically significant. CONCLUSIONS: Reduction in the vestibular time constant after scopolamine administration can be used to predict whether motion sickness alleviation will occur. This will enable the administration of appropriate pharmaceutical treatment without the need for prior exposure to sea conditions.

Galvanic vestibular stimulation as a novel treatment for seasickness.

Motion sickness is the cause of major physical discomfort and impaired performance in many susceptible individuals. Some habituate to sea conditions, whereas others remain chronically susceptible, requiring lifelong pharmaceutical treatment. The present study sets out to investigate whether galvanic vestibular stimulation (GVS) coupled with rotatory chair stimulation could mimic sea conditions and alleviate motion sickness symptoms in individuals deemed chronically susceptible. Thirty seasickness susceptible subjects, after at least six months of regular sailing, were enrolled in a prospective, single-blind, randomised controlled study. The treatment group underwent GVS coupled with inverse phase rotatory chair impulse in sinusoidal harmonic acceleration protocol. The control group underwent a sham procedure. All subjects performed repeated velocity step tests to determine the vestibular time constant (Tc) and completed a seasickness questionnaire. The GVS rotatory chair procedure decreased the prevalence of severe seasickness. The number of motion sickness clinic visits and anti-motion sickness drug consumption were reduced in the treatment group three-month post intervention as compared to control. In addition, there was significant reduction of Tc in the treatment group. GVS coupled with rotatory chair impulse could decrease motion sickness severity, induce neurophysiological learning processes and promote habituation to seasickness in chronic susceptible subjects. This is a novel and promising non-pharmacological method to treat motion sickness susceptible individuals. Furthermore, the investigation demonstrated that adaptation to sea conditions may take place even after years of susceptibility to seasickness. This study was retrospectively registered on August 10th 2021 and assigned the identifier number NCT05004818.

SARS-CoV-2 variant evolution in the United States: High accumulation of viral mutations over time likely through serial Founder Events and mutational bursts.

Since the first case of COVID-19 in December 2019 in Wuhan, China, SARS-CoV-2 has spread worldwide and within a year and a half has caused 3.56 million deaths globally. With dramatically increasing infection numbers, and the arrival of new variants with increased infectivity, tracking the evolution of its genome is crucial for effectively controlling the pandemic and informing vaccine platform development. Our study explores evolution of SARS-CoV-2 in a representative cohort of sequences covering the entire genome in the United States, through all of 2020 and early 2021. Strikingly, we detected many accumulating Single Nucleotide Variations (SNVs) encoding amino acid changes in the SARS-CoV-2 genome, with a pattern indicative of RNA editing enzymes as major mutators of SARS-CoV-2 genomes. We report three major variants through October of 2020. These revealed 14 key mutations that were found in various combinations among 14 distinct predominant signatures. These signatures likely represent evolutionary lineages of SARS-CoV-2 in the U.S. and reveal clues to its evolution such as a mutational burst in the summer of 2020 likely leading to a homegrown new variant, and a trend towards higher mutational load among viral isolates, but with occasional mutation loss. The last quartile of 2020 revealed a concerning accumulation of mostly novel low frequency replacement mutations in the Spike protein, and a hypermutable glutamine residue near the putative furin cleavage site. Finally, end of the year data and 2021 revealed the gradual increase to prevalence of known variants of concern, particularly B.1.1.7, that have acquired additional Spike mutations. Overall, our results suggest that predominant viral genomes are dynamically evolving over time, with periods of mutational bursts and unabated mutation accumulation. This high level of existing variation, even at low frequencies and especially in the Spike-encoding region may become problematic when super-spreader events, akin to serial Founder Events in evolution, drive these rare mutations to prominence.