Longer Latency Research Articles

0192 Effects of emerging alcohol use on developmental trajectories of functional sleep measures in adolescents

Abstract Introduction Adolescence is characterized by developmental changes in sleep timing and architecture as well as alcohol use initiation. While the effects of acute and chronic alcohol use on sleep in adults are well-documented, much less is known in adolescents. We used longitudinal data from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) to examine how emerging alcohol use affected sleep architecture in adolescents. Methods Overnight polysomnographic recordings were made each year, for 4 years, in 94 adolescents (12–21 years at baseline, 43% female) from the NCANDA cohort. All participants were no or low (youth adjusted Cahalan score of zero) alcohol users at baseline. These data were used to examine developmental trajectories of sleep macro-architecture and sleep electroencephalographic (EEG) measures using linear mixed effect models (LMMs), considering age, sex, family history of alcohol use, body mass index, ethnicity, and alcohol use class (i.e., no-to-low, moderate or heavy) at each annual assessment. Results There were strong developmental changes in sleep macro-structure and EEG, most notably, a decrease in slow wave sleep percentage and slow wave (delta) EEG activity with advancing age (p=0.02)​. Compared to those who remained no-to-low drinkers, participants who became moderate/heavy drinkers during the follow-up period, had different sleep trajectories, especially those older at baseline at baseline, including higher slow wave activity (p = 0.04), higher REM sleep percentage (p = 0.03), poorer sleep efficiency​ (p=0.003), and longer latency to sustained sleep (p = 0.03). The effects of alcohol use depended on sex, with male heavy drinkers having more REM sleep than female heavy drinkers (p = 0.04). Overall, a positive family history of alcohol use was associated with less NREM sleep and shorter sleep duration. Conclusion Our results present novel findings showing that emerging alcohol use during adolescence exerts complex effects on sleep macro- and micro-structure, over and above normal developmental changes in sleep. These effects could, in part, be alcohol effects on brain maturation processes underlying sleep regulation. Support (If Any) AA021696, AA021690

FOCAL EPILEPSY AND EXECUTIVE DYSFUNCTION IN AUTISM SPECTRUM DISORDER (ASD)

Recent advances in neuroscience have allowed researchers to introduce functional neuromarkers of autism spectrum disorders (ASD) into clinical practice. Most promising are studies of brain work in milliseconds, such as quantitative EEGs, event-related potentials (ERPs), low resolution electromagnetic tomography(sLORETA), especially when it is possible to use Human Brain Index (HBI) methodology to compare test results obtained by a child with ASD with the normative database. The use of HBI methodology make possible to determine functional neuromarkers of ASD and comorbidities, such as epilepsy, impaired cognitive and emotional control or executive function (FF) disorders. Such procedure can contribute to more effective diagnosis, as well as provide personalized care for patients with ASD. In this case study we use the HBI methodology for more effective diagnosis of the child with ASD (level 2) with focal epilepsy and EF dysfunction in hope that we can provide more effective therapies which might improve her quality of life. We present the case of a 11-years-old girl with an initial diagnosis of ASD with focal epilepsy and EF dysfunction. The patient was sent to the Teaching-Reintegration Centre in Kraków with remarks that she simply could not function in everyday life. A neuropsychological examination using standardized batteries to assess the girl's cognitive, emotional and social functioning confirmed the presence of ASD (level 2), and co-occurring executive function disorders (EF). She was also analyzed from the clinical EEG perspective as well as from the QEEG/ERPs perspective and current coexistence of 3 Hz Spike-Wave Discharges on EEG and focal epilepsy was found. In the examination several episodes of 3 Hz paroxysms were found in the ventro-lateral prefrontal cortex (BA 11) in 40 min EEG recoding in Eyes open, Eyes closed as well as in task conditions. The patient’s ERPs showed that to the first stimulus (continue cue) temporal P2 wave with larger duration and longer latency was elicited in comparison to the average of the norm for her age from the Human Brain Index (HBI) normative database at Chur, Switzerland. The P30 cue was smaller in the patient than in the healthy controls from HBI and statistically significant deviations from the average were found. Also in response to NOGO stimulus no positive parietal-central P3 was observed, which appears in the ERPs of ealthy controls from HBI. The ERPs differences in the VCPT show statistically significant deviations in the patient’s brain function when compared to the ealthy controls from HBI. It should be stressed that the number of trials for the first stimulus presentation and NOGO condition were large enough for computing reliable ERPs, as it was indicated by Kropotov (2009; 2016). HBI methodology was helpful in finding functional neuromarkers of co-existence of 3 Hz Spike-Wave Discharges on EEG with focal epilepsy and EF disorder in girl with ASD (level 2). Therefore, it was possible to offer more effective rehabilitation of the disorders, which will contribute to the integration of the self system and better quality of her life.

Acoustic change complex using short duration stimuli in normal hearing children: temporal resolution and frequency discrimination

Objective Acoustic Change Complex (ACC) is a cortical auditory evoked potential elicited in response to a change in an ongoing sound. Since it is supposed to reflect auditory discrimination at the cortical level, recording of this potential has recently gained much attention. From a technical standpoint, the stimulus used should be long enough to accommodate the needed change. This research addresses the development and standardization of short duration tonal stimuli which can be implemented in most of the Evoked Potential (EP) equipment used in regular Audiology clinics. Methods Short duration tonal stimuli (500 msec.) were generated and edited using Audacity software. Temporal change was done using gap-in-tones stimuli (6, 10, 30 and 50 msec. in 1000 Hz tone). Frequency change was represented by frequency pairs (2%, 4%, 10% and 25% change from 1000 Hz base frequency). The developed stimuli were then used to generate ACC potential in 41 normal hearing children ranging in age from 2 to 10 years. A comparison was held between ACC response recorded using the different stimuli in reference to percent identifiability, morphology, latency and amplitude measures. Results Gap-in-tones at 10 msec. and 4% frequency change could elicit ACC response in 100% of subjects. ACC had the same morphology of the onset response in the majority of subjects, with longer latency and smaller amplitude. ACC amplitude was consistently affected by magnitude of change. Conclusion ACC was successfully recorded in 100% of normal hearing children using the developed short duration tonal stimuli for temporal change (10 msec.) and frequency change (4%). These stimuli can be uploaded in clinical EP equipment. ACC amplitude could be a better indicator of cortical discrimination compared to latency.

The Spatial Leaky Competing Accumulator Model

The Leaky Competing Accumulator model (LCA) of Usher and McClelland is able to simulate the time course of perceptual decision making between an arbitrary number of stimuli. Reaction times, such as saccadic latencies, produce a typical distribution that is skewed toward longer latencies and accumulator models have shown excellent fit to these distributions. We propose a new implementation called the Spatial Leaky Competing Accumulator (SLCA), which can be used to predict the timing of subsequent fixation durations during a visual task. SLCA uses a pre-existing saliency map as input and represents accumulation neurons as a two-dimensional grid to generate predictions in visual space. The SLCA builds on several biologically motivated parameters: leakage, recurrent self-excitation, randomness and non-linearity, and we also test two implementations of lateral inhibition. A global lateral inhibition, as implemented in the original model of Usher and McClelland, is applied to all competing neurons, while a local implementation allows only inhibition of immediate neighbors. We trained and compared versions of the SLCA with both global and local lateral inhibition with use of a genetic algorithm, and compared their performance in simulating human fixation latency distribution in a foraging task. Although both implementations were able to produce a positively skewed latency distribution, only the local SLCA was able to match the human data distribution from the foraging task. Our model is discussed for its potential in models of salience and priority, and its benefits as compared to other models like the Leaky integrate and fire network.

Non‐invasive, Spatiotemporal Characterization of Muscle Activation Patterns from Vagus Nerve Stimulation in Human Subjects

Background and HypothesisVagus nerve stimulation (VNS) is used for treatment of epilepsy in over 100,000 patients worldwide and is a potential treatment for inflammatory disorders such as rheumatoid arthritis, diabetes, and sepsis. VNS‐evoked compound nerve action potentials (CNAPs) may have applications as a biomarker of VNS treatment efficacy, but transcutaneous measurement of this activity is obscured by laryngeal muscle artifacts during cervical VNS. Our objective is to develop a more precise understanding of muscle activation patterns that could improve recording and analysis protocols for isolating the vagus nerve (VN) CNAP from EMG artifacts. We hypothesize that analyzing multi‐electrode array (MEA) surface recordings overlying the VN will allow us to characterize this muscle artifact.MethodsTwelve patients undergoing VNS therapy for epilepsy were enrolled in a clinical study at Indiana University School of Medicine (IRB #2006075899). The anatomical dimensions of the neck were recorded for seven of the twelve subjects. A custom‐made MEA with a grid of 32 soft foam electrodes was placed on the skin overlying the VN on each side of the neck with the short axis parallel to the sternocleidomastoid muscle and the midpoint at the level of the laryngeal prominence. Surface potentials were recorded for approximately 20 minutes at the patient’s established device settings.ResultsVNS‐evoked potentials were visualized in nine subjects (three subjects were excluded due to insufficient data). Two probable muscle artifacts were identified, defined as non‐propagating features in the mean response to n > 600 pulses of VNS. The first had an onset latency of ~1‐3 ms, and the second had a latency of ~7‐10 ms. Both artifacts appeared primarily in the electrodes overlying the laryngeal muscles. In one subject, propagating activity at an approximate velocity of 70‐110 m/s was visualized between 1‐2 ms latency.ConclusionThe short latency of the first muscle artifact suggests stimulus signal leakage activating the superior laryngeal nerve. The propagating activity visualized in one subject may show the activity of the external branch of the superior laryngeal nerve, which stimulates the cricothyroid muscle to contract, creating the first muscle artifact. The second artifact with longer latency is likely caused by the recurrent laryngeal nerve, which causes contraction of intrinsic laryngeal muscles such as the posterior cricoarytenoids. Previous analyses may have mischaracterized the first muscle artifact as nerve activity [Usami, K., Kawai, K., Sonoo, M., and Saito, N. (2013). Brain Stimul. 6(4), 615‐623]. The use of MEA‐based recordings clarifies our understanding of the VN’s response to VNS, which may lead to better treatment efficacy and the eventual development of personalized VNS therapies for epilepsy and a range of inflammatory disorders.

Anti-saccade as a Tool to Evaluate Neurocognitive Impairment in Alcohol Use Disorder.

It has been widely shown that chronic alcohol use leads to cognitive dysfunctions, especially inhibitory control. In an extension of the traditional approach, this research field has benefited from the emergence of innovative measures, among which is an anti-saccade, allowing direct and sensitive measure of the eye movements indexing attention bias to alcohol-related cues and the capability of inhibiting the reflexive saccades to the cues. During the past decade, there are numerous reports showing that drinkers make more unwanted reflexive saccades and longer latency in the anti-saccade task. These increased errors are usually explained by the deficits in inhibitory control. It has been demonstrated that inhibitory control on eye movement may be one of the earliest biomarkers of the onset of alcohol-related cognitive impairments. This review summarizes how an anti-saccade task can be used as a tool to investigate and assess the cognitive dysfunctions and the early detection of relapsing risk of alcohol dependence.

Oral magnesium sulphate administration in rats with minimal hepatic encephalopathy: NMR-based metabolic characterization of the brain

To investigate the metabolic changes in rats with minimal hepatic encephalopathy (MHE) treated with oral magnesium sulphate administration. A total of 30 Sprague-Dawley rats were divided into a control group and MHE group (further divided into an MHE group and an MHE-Mg group treated with oral administration of 124 mg/kg/day magnesium sulphate). Morris water maze (MWM), Y maze and narrow beam walking (NBW) were used to evaluate cognitive and motor functions. Brain manganese and magnesium content were measured. The metabolic changes in rats with MHE were investigated using hydrogen-nuclear magnetic resonance. Metabolomic signatures were identified with enrichment and pathway analysis. A significantly decreased number of entries into the MWM within the range of interest, longer latency and total time during NBW, and higher brain manganese content were found in rats with MHE. After magnesium sulphate treatment, the rats with MHE had better behavioural performance and lower brain manganese content. The 25 and 26 metabolomic signatures were identified in the cortex and striatum of rats with MHE. The pathway analysis revealed alanine, aspartate and glutamate metabolism as the major abnormal metabolic pathways associated with these metabolomic signatures. Alanine, aspartate and glutamate metabolism are major abnormal metabolic pathways in rats with MHE, which could be restored by magnesium sulphate treatment.

Determining Candidate Hypobaric Hypoxia Profiles for Humane Killing of Laboratory Mice.

Millions of mice are used annually in scientific research and must be humanely killed. Despite significant welfare concerns, carbon dioxide exposure remains the most common killing method, primarily because there is no practical and humane alternative. We explored whether hypobaric hypoxia via gradual decompression could induce a non-recovery state in anesthetized male C57BL/6 and Balb/c laboratory mice. We aimed to determine if this was possible in a feasible timescale with minimal pathological consequences, as a proof-of-principle step. Systematic evaluation of two decompression rates (75, 150 ms−1) and three profile shapes (accelerated, linear, gradual) in a factorial design revealed that hypobaric hypoxia effectively induced a non-recovery state in anesthetized laboratory mice, irrespective of decompression rate and shape. Mice took longer to reach a non-recovery state with the 75 ms−1 decompression rate (75 ms−1: 257 ± 8.96 vs. 150 ms−1: 214 ± 7.26 s), with longer latencies in gradual and linear shaped profiles. Accelerated shaped profiles were least susceptible to meaningful refinement via rate. The only pathological changes of concern were moderate middle ear congestion and hemorrhage. These findings suggest that hypobaric hypoxia has potential, and subsequent work will evaluate the welfare consequences of gradual decompression in conscious mice, to identify decompression profiles that minimize welfare harms associated with ear barotrauma.

Motor preparation impairment in multiple sclerosis: Evidence from the Bereitschaftspotential in simple and complex motor tasks

ObjectivesMultiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, characterized by the accumulation of demyelinating lesions and axonal loss over its course. This study aimed to increase current knowledge of motor preparation in this condition, by assessing the two components of the Bereitschaftspotential (BP1 and BP2), also known as the readiness potential. MethodsTwelve patients with MS and ten age- and gender-matched healthy controls (HC) were included. Patients’ demographic and clinical data were collected. Participants were asked to perform two different tasks, a simple index extension and a Luria sequence. BP1 and BP2 values were obtained from 18 central electroencephalography electrodes and were compared between the two groups. ResultsCompared to HC, patients with MS showed earlier BP1 onset (i.e., longer latency) in almost all the analyzed scalp regions during index extension. This was also observed during the Luria sequence, but only in the centro-parietal regions. As for BP2 latency, no significant difference was noted between groups during either task. With regard to amplitudes, patients with MS had larger BP1 amplitudes in the right fronto-central area during index extension and greater BP1 and BP2 amplitudes in bilateral centro-parietal and left central regions during the Luria task. BP1 latency was also found to be significantly correlated with disease duration and performance on executive function tests (Trail Making Test). ConclusionsThis study showed, for the first time, changes in the Bereitschaftspotential in patients with MS. These data reflect prolonged movement preparation in this population and may suggest global alteration of the premotor scheme.

Eye-hand coordination during online reach corrections is task dependent.

To produce accurate movements, the human motor system needs to deal with errors that can occur due to inherent noise, changes in the body, or disturbances in the environment. Here, we investigated the temporal coupling of rapid corrections of the eye and hand in response to a change in visual target location during the movement. In addition to a "classic" double-step task in which the target stepped to a new position, participants performed a set of modified double-step tasks in which the change in movement goal was indicated by the appearance of an additional target, or by a spatial or symbolic cue. We found that both the absolute correction latencies of the eye and hand and the relative eye-hand correction latencies were dependent on the visual characteristics of the target change, with increasingly longer latencies in tasks that required more visual and cognitive processing. Typically, the hand started correcting slightly earlier than the eye, especially when the target change was indicated by a symbolic cue, and in conditions where visual feedback of the hand position was provided during the reach. Our results indicate that the oculomotor and limb-motor system can be differentially influenced by processing requirements of the task and emphasize that temporal eye-hand coupling is flexible rather than rigid.NEW & NOTEWORTHY Eye movements support hand movements in many situations. Here, we used variations of a double-step task to investigate temporal coupling of corrective hand and eye movements in response to target displacements. Correction latency coupling depended on the visual and cognitive processing demands of the task. The hand started correcting before the eye, especially when the task required decoding a symbolic cue. These findings highlight the flexibility and task dependency of eye-hand coordination.

Effectiveness of galvanic vestibular evoked myogenic potential for evaluation of Meniere’s disease

ObjectivesAlthough the cause of Meniere’s disease (MD) is not fully understood, endolymphatic hydrops is widely believed to be responsible for MD. Previous studies have used Air-Conducted Sound (ACS)-induced Vestibular Evoked Myogenic Potentials (VEMPs) to evaluate otolithic function in patients with MD. However, the use of Galvanic Vestibular Stimulation-VEMPs (GVS-VEMPs) with other vestibular tests in MD has been rare. This study aimed to explore the application of galvanic VEMPs in assessing MD. MethodsNormal individuals and patients with unilateral definite MD were included in this retrospective study. All participants underwent pure tone audiometry. Ocular and cervical VEMPs induced by GVS, and ACS were recorded. The characteristic parameters of VEMPs (n1 latency, p1 latency, amplitude, and AR) were analyzed. ResultsThe provocation rates of GVS-VEMPs did not differ between MD patients and control individuals. Compared with ACS, GVS could evoke potentials with longer latencies. MD patients presented GVS-VEMPs with lower amplitudes and ACS-cVEMP with shorter latencies and had a higher response rate in GVS-oVEMP. However, no differences or correlations were found in the characteristic parameters of GVS-VEMPs among the different stages of MD. ConclusionsGVS is as effective as ACS for inducing VEMP, and GVS-VEMP recording can detect retrolabyrinthine degeneration in MD. Further research is needed to assess the utility of GVS-VEMP in the evaluation of MD severity. Level of evidenceLevel 4.

Increased risk of high-grade prostate cancer among testicular cancer survivors.

IntroductionTesticular cancer survivors (TCS) have an increased risk of additional cancers, including prostate cancer. Our understanding of the natural history of prostate cancer in testicular cancer survivors is very limited due to its rare incidence.MethodsUsing the Surveillance, Epidemiology, and End Results (SEER) Registry from 1978 to 2011, we identified 282 TCS with subsequent prostate cancer and examined the tumor grade and clinical outcomes in contrast to men with primary prostate cancer in the general population.ResultsTCS with a subsequent prostate cancer diagnosis were more likely to be diagnosed at a younger age than men with primary prostate cancer (65.2% vs. 37.6% for age ≤65, 34.8% vs. 62.4% for age >65, p<0.001) and were more likely to have grade III/IV tumors (46.2% vs. 37.0%, p<0.002). Longer latency between testicular and prostate cancer diagnoses was associated with a higher risk of grade III/IV (p<0.001) cancer. Despite the increased risk for high-grade tumors, 10-year prostate cancer-specific survival and overall survival were not significantly different between TCS and men with primary prostate cancer. Based on the available information in SEER, we found that prior history of radiotherapy for testicular cancer had no impact on tumor grade or survival outcomes.ConclusionsProstate cancer in TCS was more likely to be diagnosed at a younger age and with higher grades. Risks of grade III/IV disease increased with longer latency between testicular and prostate cancer diagnoses. Radiotherapy for testicular cancer did not appear to have a significant impact on the outcome of subsequent prostate cancer.

MRNA Covid-19 vaccines in pregnancy: A systematic review.

Pregnancy is a known risk factor for severe Coronavirus disease 2019. It is important to develop safe vaccines that elicit strong maternal and fetal antibody responses. Registries (ClinicalTrials.gov, the WHO Clinical Trial Registry, and the European Union Clinical Trial Registry) and databases (MEDLINE, ScienceDirect, Cochrane Library, Proquest, Springer, medRxiv, and bioRxiv) were systematically searched in June 20-22, 2021, for research articles pertaining to Covid-19 and pregnancy. Manual searches of bioRxiv and medRxiv were also conducted. Inclusion criteria were studies that focused on Covid-19 vaccination among pregnant women, while review articles and non-human studies were excluded. Infection rate, maternal antibody response, transplacental antibody transfer, and adverse events were described. There were 13 observational studies with a total of 48,039 pregnant women who received mRNA vaccines. Of those, three studies investigated infection rate, six studies investigated maternal antibody response, seven studies investigated antibody transfer, three studies reported local adverse events, and five studies reported systemic adverse events. The available data suggested that the mRNA-based vaccines (Pfizer-BioNTech and Moderna) can prevent future SARS-CoV-2 infection. These vaccines did not show clear harm in pregnancy. The most commonly encountered adverse reactions were pain at the injection site, fatigue, and headache, but these were transient. Antibody responses were rapid after the first vaccine dose. After the booster, antibody responses were stronger and associated with better transplacental antibody transfer. Longer intervals between first vaccination dose and delivery were also associated with higher antibody fetal IgG and a better antibody transfer ratio. The SARS-CoV-2 mRNA vaccines are encouraged for pregnancy. These vaccines can be a safe option for pregnant women and their fetuses. Two vaccine doses are recommended for more robust maternal and fetal antibody responses. Longer latency is associated with higher fetal antibody responses. Further research about its long-term effect on pregnancy is needed. PROSPERO (CRD42021261684).

Overexpression of Foxc1 ameliorates sepsis‑associated encephalopathy by inhibiting microglial migration and neuroinflammation through the IκBα/NF‑κB pathway.

Sepsis-associated encephalopathy (SAE) is a common and severe complication of sepsis. The cognitive dysfunction that ensues during SAE has been reported to be caused by impairments of the hippocampus. Microglia serves a key role in neuroinflammation during SAE through migration. Forkhead box C1 (Foxc1) is a member of the forkhead transcription factor family that has been found to regulate in cell migration. However, the role of Foxc1 in neuroinflammation during SAE remains unknown. In the present study, the mechanistic role of Foxc1 on microglial migration, neuroinflammation and neuronal apoptosis during the occurrence of cognitive dysfunction in SAE was investigated. A microglia-mediated inflammation model was induced by LPS in BV-2 microglial cells in vitro, whilst a SAE-related cognitive impairment model was established in mice using cecal ligation and perforation (CLP) surgery. Cognitive function in mice was evaluated using the Morris Water Maze (MWM) trial. Lipopolysaccharide (LPS) treatment was found to trigger BV-2 cell migration, inflammation and neuronal apoptosis. In addition, CLP surgery induced cognitive injury, which was indicated by longer latencies and shorter dwell times in the goal quadrant compared with those in the Sham group in the MWM trial. LPS treatment or CLP induction decreased the expression of Foxc1 and inhibitor of NF-κB (IκΒα) whilst increasing that of p65, IL-1β and TNF-α. After Foxc1 was overexpressed, the cognitive dysfunction of mice that underwent CLP surgery was improved, with the expression of IκBα also increased, microglial cell migration, the expression of p65, IL-1β and TNF-α and neuronal apoptosis were all decreased in vivo and in vitro, which were in turn reversed by the inhibition of IκBα in vitro. Overall, these results suggest that the overexpression of Foxc1 inhibited microglial migration whilst suppressing the inflammatory response and neuronal apoptosis by regulating the IκBα/NF-κB pathway, thereby improving cognitive dysfunction during SAE.

Active Middle Ear Implant Evoked Auditory Brainstem Response Intensity-Latency Characteristics.

ObjectiveTo analyze intensity-latency functions of intraoperative auditory evoked brainstem responses (ABRs) to stimulation by the Vibrant Soundbridge (VSB) active middle ear implant with respect to coupling efficiency, VSB evoked ABR thresholds, and coupling modality [oval window (OW) placement vs. Incus placement and vs. round window (RW) placement].Study DesignExploratory study.SettingBi-centric study at tertiary referral centers.PatientsTwenty-four patients (10 female, 14 male, mean age: 58 years) who received a VSB.Outcome MeasuresWave-V intensity-latency functions of intraoperative VSB evoked ABRs using a modified audio processor programmed to preoperative bone conduction thresholds for stimulation. Threshold level correction to coupling efficiency and ABR thresholds. Individual plots and exponential function fits.ResultsAfter ABR threshold level correction, the latency functions could be aligned. A large variance of latencies was observed at individual threshold level. Wave-V latency was longest in the Incus placement subgroup (9.73 ms, SD: 1.04) as compared to OW placement subgroup (9.47 ms, SD: 1.05), with the shortest latency in the RW placement subgroup (8.99 ms, SD: 0.68). For increasing stimulation levels, the variance decreased with intensity-latency function slopes converging toward a steady-state (saturation) latency caused by saturation of audio processor (stimulation) gain. Latency saturation was reached at a stimulation level of 50 dB nHL for the OW placement subgroup, 35 dB nHL for the Incus placement subgroup, and 30 dB nHL for the RW placement subgroup. The latency and saturation results indicated decreased dynamic range for RW placement, i.e., reverse stimulation.ConclusionsVSB evoked ABR wave-V intensity-latency function slopes were similar to acoustic stimulation at high stimulation levels with a shift toward longer latencies caused by audio processor signal delay. Saturation of latencies occurred for higher stimulation levels due to saturation of audio processor gain. Thus, the analysis of VSB evoked intensity-latency functions appears to allow for the objective assessment of a patient's individual dynamic range. This can further improve diagnostics as well as intraoperative and postoperative quality control.

Adverse drug reaction profile of daily regimen antituberculosis treatment.

The objective was to estimate the proportion of adverse drug reactions (ADRs) to daily regimen antituberculosis treatment (ATT) among the ADRs received in the ADR monitoring center (AMC) of the institution and to describe its pattern. This was a descriptive study conducted in the Department of Pharmacology of a Government Medical College in Central Kerala and the period under study was October 2017-June 2020. The data on ADR were entered into a structured pro forma and data were analyzed using SPSS for Windows Version 16.0 (SPSS Inc., Chicago, USA). Of the 643 ADRs, 98 (15.24%) were suspected to be due to the daily regimen of ATT. The most common organ system affected was hepatobiliary 46 (46.9%) namely hepatitis in 35 and asymptomatic elevated liver enzymes in 11 followed by eye with 26 reports of decreased vision. In 96 (97.95%), the suspected ADR had probable causality and in 2 (2.04%) it was possible. Seventy-seven (78.6%) ADR reports were serious as well as moderate-level 4b in severity and 57 (58.16%) were probably preventable. The mean days of onset of ADR after starting the ATT regimen were 56.40 ± 58.29 days (range 1-180). Decrease in vision with a mean duration of 125.23 ± 55.46 days had the longest latency in onset among all the ADRs. Of all the ADRs reported to AMC 15.24% were due to the daily regimen of ATT. Hepatitis was the most common ADR encountered followed by decrease in vision. The majority of the ADRs were probable in causality, serious, moderate-level 4b in severity, and probably preventable.

Lateral semicircular canal-BPPV: Prospective randomized study on the efficacy of four repositioning maneuvers

IntroductionMultiple repositioning maneuvers have been described to treat lateral semi-circular canal Benign Paroxysmal Positional Vertigo (LC-BPPV) patients. In this study, we compare efficacy of four therapeutic repositioning maneuvers for LC-BPPV patients and aim to identify clinical variables associated with persistent disease. Material and methodsA prospective study was conducted at a tertiary center, between January 2017 and September 2019. Patients diagnosed with LC-BPPV were randomly treated with Gufoni or barbecue-roll maneuvers (for the geotropic variant) and Gufoni-Appiani, barbecue-roll or Zuma-e-Maia maneuvers (for the apogeotropic form). Efficacy was compared and statistical analysis was performed to find clinical factors associated with no response. ResultsForty-eight patients and 82 maneuvers were included. Female patients and right side were more commonly affected. The mean age was 67 years. Seven cases (14.6%) resulted from a canal-switch. One single maneuver resolved 23 cases (47.9%) and the success rate rose to 75% at the end of the first visit (after up to 4 maneuvers) and to 93.8% after a-week of follow-up. Success rates were significantly better with Gufoni (68%) than with barbecue roll (34.8%; p=0.021) in geotropic LC-BPPV and better with Gufoni-Appiani (71.4%) than barbecue roll and Zuma-e-Maia maneuvers (33.3%; p=0.239) in apogeotropic LC-BPPV. Higher rates of persistent disease after first visit were found with older patients, left side and apogeotropic LC-BPPV and with longer latency and duration diagnostic nystagmus. ConclusionOur study suggests that Gufoni and Gufoni-Appiani maneuvers may be the most efficacious treatment for geotropic and apogeotropic LC-BPPV, respectively, compared to barbecue-roll and Zuma-e-Maia maneuvers.

Inhalation Administration of Agarwood Incense Rescues Scopolamine-Induced Learning and Memory Impairment in Mice.

Background: Agarwood, a type of herbal medicine widely used in Asian countries, is noted in traditional medicine for its intelligence-enhancing effects. Agarwood incense is traditionally administered by oral and nasal inhalation. To verify whether agarwood incense can exert its intelligence-enhancing effects in this way to rescue learning and memory impairment, typical clinical manifestations of dementia, we conducted a set of behavioral tests related to learning and memory. Methods: C57BL/6 mice were divided into six groups. In addition to the control and model groups, we added a donepezil treatment group to evaluate the effect of three different agarwood administration doses. After a week of administration, scopolamine was injected 30 min before each behavioral test to create a learning and memory impairment model. A series of behavioral tests [the Morris water maze test (MWM), the novel object recognition test (NOR), and the step-down test (SDT)] were used to assess their learning ability, as well as their spatial and recognition memory. Results: After scopolamine injection, the model group showed significant learning and memory impairment (i.e., longer latencies, lower crossing times, and lesser distance travelled in the target quadrant in MWM; a lower recognition index in NOR; and longer latencies and higher error times in SDT). The other four treatment groups all showed improvements in these indicators, and the overall therapeutic effect of agarwood was superior. Conclusion: The inhalation administration of agarwood can significantly improve the learning and memory impairment caused by scopolamine in mice, and the therapeutic effect varied between doses.

Factors associated with longer latency in expectant management of severe pre-eclampsia

Expectant management of pre-eclampsia with severe features (SPREX) is often considered if diagnosed < 34 weeks. We sought to identify antepartum factors associated with latency of ≥7 days (long latency) and latency ≥14 days (very-long latency) among patients undergoing expectant management of SPREX.

Intracorporeal Cortical Telemetry as a Step to Automatic Closed-Loop EEG-Based CI Fitting: A Proof of Concept.

Electrically evoked auditory potentials have been used to predict auditory thresholds in patients with a cochlear implant (CI). However, with exception of electrically evoked compound action potentials (eCAP), conventional extracorporeal EEG recording devices are still needed. Until now, built-in (intracorporeal) back-telemetry options are limited to eCAPs. Intracorporeal recording of auditory responses beyond the cochlea is still lacking. This study describes the feasibility of obtaining longer latency cortical responses by concatenating interleaved short recording time windows used for eCAP recordings. Extracochlear reference electrodes were dedicated to record cortical responses, while intracochlear electrodes were used for stimulation, enabling intracorporeal telemetry (i.e., without an EEG device) to assess higher cortical processing in CI recipients. Simultaneous extra- and intra-corporeal recordings showed that it is feasible to obtain intracorporeal slow vertex potentials with a CI similar to those obtained by conventional extracorporeal EEG recordings. Our data demonstrate a proof of concept of closed-loop intracorporeal auditory cortical response telemetry (ICT) with a cochlear implant device. This research breaks new ground for next generation CI devices to assess higher cortical neural processing based on acute or continuous EEG telemetry to enable individualized automatic and/or adaptive CI fitting with only a CI.