Changes In Threshold Research Articles

Perception of vibration threshold potential with tuning fork and pure tone audiometry assessment for early detection of diabetic polyneuropathy

Background: Diabetes mellitus (DM), a multisystem disorder, is a known etiological entity, leading to several neurological disorders. Among them, nervous system is more commonly affected. In most of the diabetic polyneuropathy cases, sensory symptoms involving both general and special senses predominate. Due to gradual and non-homogenous manifestations, it is not easy to detect its onset. Till now no accepted gold standard has been available for its assessment and diagnosis. In this study, changes in vibration perception threshold (VPT) at different frequencies and auditory perception threshold have been investigated in diabetes patients and healthy controls. Aims and objectives: Determination of perception threshold of a general sense-vibration sense and a special sense-hearing in normal human subjects and patients of DM and evaluation of perception threshold of the human sensory system by VPT test and pure tone audiometry (PTA) as a diagnostic, prognostic and research tool for diabetic neuropathy. Materials and Methods: A case–control study, conducted in the department of physiology at medical college, Kolkata, after obtaining approval by the institutional research and ethics committee on 100 cases and 40 control subjects. Testing of vibration sensitivity was performed with the help of tuning forks of frequencies of 128 Hz, 256 Hz, and 512 Hz. Assessment of auditory perception threshold was done by Siemens SD 28 diagnostic audiometer. Results: All data obtained by the methods described here are tabulated. Graphs and charts are drawn and analyzed by standard statistical methods using Statistical Packages for the Social Sciences (version-16) and MATLAB (version-9). A P < 0.05 was considered as significant. A partial negative correlation was observed between the vibration sensitivity and fasting blood sugar and postprandial blood sugar level of the patient population of DM cases, with a “r” value (Pearson’s correlation coefficient was around −0.5. By PTA, it was found the percentage of rise in auditory threshold is around 92–93% in 8000 Hz frequency, and the results of the t-test yield a very highly significant difference (P < 0.0001) between cases and controls. It was found that 128 Hz and 256 Hz vibration stimuli applied over maxillary prominence are highly sensitive and efficient tools for perception analysis. Pure tone auditory threshold evaluation showed preservation of the right-sided advantage of auditory sensitivity and frequency-dependent loss of hearing in the diabetic study population. Conclusion: Determination of perception threshold of vibration sense by tuning fork and auditory perception by PTA may be used as an effective, easily performed, and low-cost bedside and also outpatient department-based diagnostic tool in patients with DM.

Assessment of orofacial nociceptive behaviors of mice with the sheltering tube method: Oxaliplatin-induced mechanical and cold allodynia in orofacial regions.

Preclinical studies on pathological pain rely on the von Frey test to examine changes in mechanical thresholds and the acetone spray test to determine alterations in cold sensitivity in rodents. These tests are typically conducted on rodent hindpaws, where animals with pathological pain show reliable nocifensive responses to von Frey filaments and acetone drops applied to the hindpaws. Pathological pain in orofacial regions is also an important clinical problem and has been investigated with rodents. However, performing the von Frey and acetone spray tests in the orofacial region has been challenging, largely due to the high mobility of the head of testing animals. To solve this problem, we implemented a sheltering tube method to assess orofacial nociception in mice. In experiments, mice were sheltered in elevated tubes, where they were well accommodated because the tubes provided safe shelters for mice. Examiners could reliably apply mechanical stimuli with von Frey filament, cold stimuli with acetone spray, and light stimuli with a laser beam to the orofacial regions. We validated this method in Nav1.8-ChR2 mice treated with oxaliplatin that induced peripheral neuropathy. Using the von Frey test, orofacial response frequencies and nociceptive response scores were significantly increased in Nav1.8-ChR2 mice treated with oxaliplatin. In the acetone spray test, the duration of orofacial responses was significantly prolonged in oxaliplatin-treated mice. The response frequencies to laser light stimulation were significantly increased in Nav1.8-ChR2 mice treated with oxaliplatin. Our sheltering tube method allows us to reliably perform the von Frey, acetone spray, and optogenetic tests in orofacial regions to investigate orofacial pain.

Temporal summation does not predict the acupuncture response in patients with chronic non-specific low back pain.

Previously, we had observed that immediate pain reduction after one acupuncture treatment was associated with high temporal summation of pain (TS) at a pain free control site and younger age in a mixed population of chronic pain patients. The aim of the present study was to verify these results in chronic non-specific low back pain (LBP) and to collect pilot data on the association between TS and the response to an acupuncture series. TS at a pain free control site (back of dominant hand) and at the pain site was quantified by the pin-prick induced wind-up ratio (WUR) in 60 LBP patients aged 50 years or younger. Response to one acupuncture treatment was assessed by change in pain intensity and pressure pain threshold (PPT) at the pain site. The primary hypothesis was that a high TS (WUR > 2.5) would be associated with a clinically relevant reduction in pain intensity of at least 30%. In study part two, 26 patients received nine additional treatments. Response to the acupuncture series was assessed by the pain intensity during the last week, the PPT and the Hannover functional ability questionnaire (FFbH-R). An immediate reduction in pain intensity of at least 30% was frequent irrespective of TS at the control site (low vs. high TS 58% vs. 72%, p = 0.266). High TS at the pain site was also not significantly associated with a clinically relevant immediate reduction in pain intensity (low vs. high TS 46% vs. 73%, p = 0.064). The PPT was not changed after one acupuncture treatment. Study part two did not reveal a consistent association between TS at the control site and any of the outcome measures but also a trend toward a higher chance for a clinically relevant response along with low TS at the pain site. Our results do not suggest an important role of TS for predicting a clinically important acupuncture effect or the response to a series of 10 acupuncture treatments in patients with chronic non-specific LBP. Overall high response rates imply that acupuncture is a suitable treatment option for LBP patients irrespective of their TS.

Methylphenidate attenuates signs of evoked neuropathic pain in animal model.

Methylphenidate is a psychostimulant that increases dopamine and noradrenaline levels. Recent studies have shown that methylphenidate potentiates the effect of morphine and together suppress acute and chronic pain. In clinical practice, methylphenidate has been used as a treatment for ADHD and changes of pain threshold have been noted in these patients. The aim of this study was to determine the effect of methylphenidate in an animal model of peripheral neuropathic pain. Neuropathic pain was modeled by the chronic constriction of the sciatic nerve (CCI) in Wistar rats. We evaluated the effect of methylphenidate (1 mg/kg, s.c.) on evoked pain (reflex tests - plantar test, vonFrey test and operant test - thermal place preference) and on spontaneous pain (conditioned place preference). CCI induced thermal, mechanical and cold hyperalgesia/allodynia. Methyphenidate suppressed mechanical and cold hyperalgesia/allodynia, while had no effect on thermal one. Therefore, methylphenidate seems to be a new potential pharmacotherapy for the treatment of neuropathic pain.

High-Dose Glucocorticoids for the Treatment of Sudden Hearing Loss

BackgroundSystemic glucocorticoids are commonly used for primary therapy of idiopathic sudden sensorineural hearing loss (ISSNHL). However, the comparative effectiveness and risk profiles of high-dose over lower-dose regimens remain unknown.MethodsWe randomly assigned patients with sudden hearing loss of greater than or equal to 50 dB within 7 days from onset to receive either 5 days of high-dose intravenous prednisolone at 250 mg/d (HD-Pred), 5 days of high-dose oral dexamethasone at 40 mg/d (HD-Dex), or, as a control, 5 days of oral prednisolone (Pred-Control) at 60 mg/d followed by 5 days of tapering doses. The primary outcome was the change in hearing threshold (pure tone average) in the three most affected contiguous frequencies from baseline to day 30. Secondary outcomes included speech understanding, tinnitus, communication competence, quality of life, hypertension, and insulin resistance.ResultsA total of 325 patients were randomly assigned. Mean change in 3PTAmost affected hearing threshold from baseline to 30 days was 34.2 dB (95% CI, 28.4 to 40.0) in the HD-Pred group, 41.4 dB (95% CI, 35.6 to 47.2) in the HD-Dex group, and 41.0 dB (95% CI, 35.2 to 46.8) in the Pred-Control group (P=0.09 for analysis of variance). There were more adverse events related to trial medication in the HD-Pred (n=73) and HD-Dex (n=76) groups than in the Pred-Control group (n=46).ConclusionsSystemic high-dose glucocorticoid therapy was not superior to a lower-dose regimen in patients with ISSNHL, and it was associated with a higher risk of side effects. (Funded by the Federal Ministry of Education and Research [BMBF]; EudraCT number, 2015‐002602‐36.)

Features of professional hearing loss with combined exposure to noise and vibration

For most modern industries, there is characteristic the simultaneous impact of noise with other factors aggravating its effect.
 The purpose of the study is to determine the features of occupational hearing loss in the combined effects 
 of noise and vibration.
 Materials and methods. A comparative assessment of the level of occupational risk and audiometric indicators was carried out in three groups of employees: 1st group (210 people) — is exposed to noise, 2nd group 
 (170 people) — to noise and local vibration, 3rd group (200 people) — to noise and general vibration.
 Results. In group 1 workers exposed to isolated noise, occupational hearing loss was diagnosed significantly less frequently compared to group 2 and 3 including workers exposed to combined noise and vibration 
 (7% vs. 14 and 13%, respectively, p < 0.05). Combined exposure to noise and vibration increases the risk of occupational hearing loss by 1.82–1.85 times (RR = 1.82–1.85; EF = 45–46%). Audiological features 
 of the lesion of the auditory analyzer have been revealed depending on the presence and nature of the affecting vibration, manifested by changes in hearing thresholds in certain frequency spectra and their combination. According to the data of speech audiometry, a violation of speech intelligibility with the presence of speech-tonal dissociation was revealed in workers of groups 2 and 3, indicating violations in the central department 
 of the auditory analyzer.
 Limitations of the study. The study is limited to the study of the features of occupational hearing loss in the combined effects of noise and vibration in mining workers according to audiometric indicators.
 Conclusion. The conducted studies have shown the need to develop individual programs for the preservation of hearing, taking into account the degree of risk and the identified features of the formation of occupational hearing loss. The topic of research on the effects of noise and vibration on hearing loss requires in-depth research, taking into account the intensity and duration of vibration exposure, the type of vibration generating equipment.

Electrochemical Framework for Dynamic Tracking of Soil Organic Matter (SOM)

Soil Health parameters serve as excellent surrogate measures towards assessing environmental quality and understanding effects of climate change mitigation via carbon sequestration. Soil health monitoring in the near past has been highly qualitative and speculative with more recent advancements still trying to fill the void of determining a holistic soil profile through phantom based measurements. In fields and crop-circles, testing methods to perform in-situ profiling however from one lab is likely to vary with another and hence results are not universally compatible. Additionally, these normalized techniques ideally involve empirical approaches, extensive sample preparation which adds on to a temporal factor along with equipment for extraction and subsequently-analysis. Even with the upcoming research breakthroughs in non-destructive approaches like spectroscopy and tomography-based models, there is a barrier in-terms of equipment complexity and availability as well as high costs and high logistical overhead.There are a wide number of redox systems present in soil that exist in reduced state under ideal conditions (submerged). While Carbon monitoring would be highly beneficial in the field, an overall sense of the organic matter nutrients present in soil denoted as soil organic matter understanding would offer a wholistic manner of surveying soil and environmental health. In this work, faradaic and non-faradaic measurements are utilized to determine threshold changes in soil electrochemical activity due to presence of various electroactive substances present in the matrix. First, a galvanostatic approach using the chronopotentiometry modality was applied to a soil slurry system- ‘test’ sample to which different levels (w/v %) of the following amendments were added to see how the effective charge modulation can be visualized. Utilizing this experimental framework as preliminary information- A hypothesized mechanism of interaction between the RTIL (Room Temperature Ionic-Liquid) modified electrode and the OM functional moieties based on hydrogen bonding and pi-pi interactions captured using charge-based (chronocoulometry) and interfacial mapping-based (electrochemical impedance spectroscopy) method is utilized to design and test a first-of-a-kind electrochemical soil organic matter (SOM) sensor. Figure 1. Chronopotentiometric characterization of soil organic matter using an RTIL modified electrode. Figure 1

Clinical Outcomes of Endolymphatic Sac Decompression Surgery in Menière’s Disease

Objectives: Endolymphatic sac decompression surgery (ESDS) is one of the surgical methods for intractable Menière’s disease (MD), and it is known as a relatively safe treatment that does not cause hearing loss. However, the effectiveness and the degree of vertigo control rate of ESDS are still controversial. In this study, we aimed to evaluate the clinical outcomes of ESDS in intractable MD.Methods: We retrospectively reviewed 33 patients who underwent ESDS for intractable MD from January 2002 to March 2022. Clinical characteristics of patients, pure tone threshold, medical treatment method, and number of vertigo attacks before and after surgery were assessed. The improvement of hearing and vertigo was evaluated according to the 1995 American Academy of Otolaryngology-Head and Neck Surgery criteria.Results: Of the 33 patients, the average follow-up period was 21.2 months, with immediate follow-up within 2 months (28 patients), short term between 2 and 6 months (27 patients), and long term at 12 months or later (29 patients). In the immediate hearing threshold, both air conduction and bone conduction showed slight deterioration, but there was no significant change in the long-term hearing threshold. At long-term follow-up, 12 patients (41.4%) were able to live without medication, and 18 patients (62.1%) showed improvement in their vertigo symptoms. In addition, patients who showed improvement in hearing also showed improvement in vertigo at the same time.Conclusions: ESDS in intractable MD is a relatively safe and effective treatment method for reducing vertigo attack without worsening hearing threshold.

Study of Proximity Effect in Projection based Micro Vat Photopolymerization Process

Micro Projection-based Stereolithography (µPSL), also known as micro vat photopolymerization, is a promising technology that could revolutionize microfabrication by providing benefits similar to traditional lithography while reducing production time and cost. However, it faces a significant challenge in the form of the "proximity effect." This effect occurs when adjacent features are too close together, causing undesirable artifacts and limiting the achievable fabrication resolution. The proximity effect is caused by interactions between adjacent pixels of light and affects both the spatial and temporal domains of the fabrication process. Although researchers have been aware of this issue for some time, there has been little progress in understanding and addressing the proximity effect in micro vat photopolymerization. Existing models developed for laser-based systems can explain the effect to some extent, but they do not fully account for the impact of large area projection or explain how local threshold changes affect part size. This research aims to fill this knowledge gap by using in-situ observation systems to experimentally study the spatial and temporal proximity effects in single-shot vat photopolymerization microfabrication. We also investigate the role of oxygen in the proximity effect and lay the groundwork for better understanding how the effect impacts periodic structures with micronic inter-feature distances. In conclusion, while micro vat photopolymerization offers significant advantages over traditional lithography, the proximity effect remains a significant obstacle. This research represents an important step forward in addressing this challenge and improving the accuracy and resolution of vat photopolymerization in microfabrication.

Topical and oral steroids for otitis media with effusion (OME) in children.

Topical and oral steroids for otitis media with effusion (OME) in children.

Neurofibromin 1 mediates sleep depth in Drosophila.

Neural regulation of sleep and metabolic homeostasis are critical in many aspects of human health. Despite extensive epidemiological evidence linking sleep dysregulation with obesity, diabetes, and metabolic syndrome, little is known about the neural and molecular basis for the integration of sleep and metabolic function. The RAS GTPase-activating gene Neurofibromin (Nf1) has been implicated in the regulation of sleep and metabolic rate, raising the possibility that it serves to integrate these processes, but the effects on sleep consolidation and physiology remain poorly understood. A key hallmark of sleep depth in mammals and flies is a reduction in metabolic rate during sleep. Here, we examine multiple measures of sleep quality to determine the effects of Nf1 on sleep-dependent changes in arousal threshold and metabolic rate. Flies lacking Nf1 fail to suppress metabolic rate during sleep, raising the possibility that loss of Nf1 prevents flies from integrating sleep and metabolic state. Sleep of Nf1 mutant flies is fragmented with a reduced arousal threshold in Nf1 mutants, suggesting Nf1 flies fail to enter deep sleep. The effects of Nf1 on sleep can be localized to a subset of neurons expressing the GABAA receptor Rdl. Sleep loss has been associated with changes in gut homeostasis in flies and mammals. Selective knockdown of Nf1 in Rdl-expressing neurons within the nervous system increases gut permeability and reactive oxygen species (ROS) in the gut, raising the possibility that loss of sleep quality contributes to gut dysregulation. Together, these findings suggest Nf1 acts in GABA-sensitive neurons to modulate sleep depth in Drosophila.

The effectiveness of using pulsed electromagnetic fields for osteoarthritis of the knee joint

BACKGROUND: Osteoarthritis is one of the most common forms of pathology of the musculoskeletal system with significant impairment of motor function, which is one of the main causes of disability in the population.
 AIM: This study was aimed at testing the effectiveness of the portable device "ALMAG+" with pulsed electromagnetic fields in the treatment of pain in patients with osteoarthritis of the knee joint.
 MATERIALS AND METHODS: This randomized, double-blind, placebo-controlled clinical trial included patients with radiographic evidence of knee osteoarthritis and persistent pain greater than 40 mm on a visual analogue scale (VAS). The study included daily treatment with pulsed electromagnetic fields from the ALMAG+ device for 1 month in 60 patients with knee osteoarthritis. The primary outcome measure was reduction in pain intensity assessed by VAS and WOMAC scales. Secondary outcomes included the 36-item Short Form Medical Outcomes Study version 2 (SF-36 v2) quality of life, pressure pain threshold, and changes in non-steroidal anti-inflammatory drug/analgesic use.
 RESULTS: Sixty-six patients were enrolled in the study, and 60 completed the study. After 1 month of treatment, pulsed electromagnetic fields caused a significant reduction in pain VAS and WOMAC scores compared to placebo. In addition, patients receiving pulsed electromagnetic fields improved pain tolerance, which was reflected in changes in pain threshold, and physical condition. We obtained a significant and statistically significant effect of the organized pulsed electromagnetic fields factor on VAS pain scores (F=47.6; p=0.00006); assessments of the severity of pain, joint function and stiffness on the scales of the WOMAC questionnaire also significantly changed under the influence of the pulsed electromagnetic fields factor (F=14.7; p=0.001). 26% of patients in the pulsed electromagnetic fields group discontinued non-steroidal anti-inflammatory drug/analgesic therapy. No adverse events were identified during treatment.
 CONCLUSION: These results suggest that pulsed electromagnetic fields therapy is effective in relieving pain in patients with knee osteoarthritis and also affects pain threshold, stiffness, and physical functioning. In the future, it is desirable to conduct larger studies, including those comparing the effectiveness of pulsed electromagnetic fields therapy with standard pharmacological approaches for osteoarthritis.

Hearing Loss and Risk Factors in Very Low Birth Weight Infants.

The incidence of sensorineural hearing loss (SNHL) is still high in very low birth weight (VLBW) infants. The purpose of our study was to provide the prevalence rates of SNHL and to analyze the risk factors of hearing impairment and changes in hearing thresholds in a cohort of VLBW infants. A retrospective observational study was conducted in our neonatal intensive care unit (NICU) from 2012 to 2016. All VLBW infants included were screened by transient evoked otoacoustic emissions (TEOAEs) and diagnostic auditory brainstem response (ABR). In total, we enrolled 316 infants and SNHL was diagnosed in 68, leading to an early incidence of 21.5% as 36 infants out of 68 improved. Finally, SNHL was confirmed in 20 patients (6.3%) who needed hearing aids. They were significantly smaller, sicker, had longer hospitalizations, and received more ototoxic therapies. Logistic regression analysis showed that gestational age (GA) influenced the association between drugs and SNHL. The results underlined how the total exposure to antibiotics is significantly associated with SNHL, even after GA correction. In conclusion, GA, birth weight and, above all, the length and complexity of NICU stay quantify the risk of SNHL and should be considered at the individual level for parent counseling.

Strategic insight into the thresholds & barriers to uptake of Electronic Repeat Dispensing (eRD) by therapeutic area

Abstract Introduction The use of eRD offers a simplified process compared to paper based repeat dispensing and electronic repeat prescribing, and has several benefits for GP practices, community pharmacies and patients. It is estimated that up to 80% of all repeat prescriptions could be replaced with repeat dispensing potentially saving 2.7 million hours of GP and practice time. eRD also has the benefit of reduced medicines and can contribute towards reducing overprescribing and supporting the NHS sustainability agenda. Aim To determine if there are specific thresholds of eRD implementation by GP practices at which barriers to uptake occur. Subsequently to understand if these thresholds are associated with specific therapeutics and if the difficulty in increasing uptake is related to drug specific requirements or differing prescription management processes needed. Methods Dispensed medicines data (Oct-Dec 22, ePACT2) was analysed at practice level nationally to test the hypothesis that there are multiple thresholds of eRD implementation uptake. The percentage of practices achieving less than or equal to each incremental %eRD value was plotted against % eRD implementation. Thresholds were identified by a change in the rate of implementation uptake. Prescribing data was then analysed by BNF chapter at the identified thresholds to determine how this variation was represented clinically. Dispensed medicines data (Jul-Sept 21, North of England (NoE)) was also reviewed by pharmacists at presentation level for appropriateness as an eRD item (excludes patient level considerations). The items considered prescribable by eRD were tagged and the data re-run to estimate the maximum %eRD that might have been achieved. Ethical approval was not required for this study as it utilised non-patient identifiable population level primary care prescribing data. Results There were 8 thresholds (changes in rate of implementation) identified from the national data; occurring at 3, 9, 35, 42, 50, 57, 64 and 72% eRD. There is consistency in three of the most prescribed drug groups for eRD across all the NoE Integrated Care Systems (ICSs), which includes: lipid regulating drugs, proton pump inhibitors and renin-angiotensin system; readily implemented as eRD from the 3% threshold. The other most commonly prescribed drugs by eRD were: Beta-blockers, calcium channel blockers, antiplatelets and antidiabetics. Retrospective data analysis by pharmacists determined that a maximum of 66.6% of items Jul-Sept 21 in the NoE could have been prescribed by eRD if patient factors at individual review had also considered it appropriate. Discussion/Conclusion Further clinical review and guidance on the appropriateness and requirements of specific therapeutics to be prescribed by eRD is required. For instance, rheumatic disease suppressant drugs, which require GP practices to establish monitoring arrangements in conjunction with eRD, increase from the 9% threshold. Whereas adrenoceptor agonists, requiring respiratory/inhaler reviews, increase from the 35% threshold. Further qualitative analysis is ongoing to understand the barriers occurring at different thresholds of eRD uptake. The maximum percentage of eRD achievable in the snapshot data was significantly lower than expected. This work is limited by the volume of items at presentation level that could potentially be prescribed.

Effect of granule sizes on magneto-optical spectra of nanocomposites

The magneto-optical transverse Kerr effect (TKE) spectroscopy allows non-contact investigation of nanostructures, giving valuable information about the microstructure of samples. In this paper, within the framework of effective medium approach we analyze the effect of granule size on the magneto-optical spectra of magnetic nanocomposites. We consider the influence of various microscopic parameters such as plasma frequency, relaxation time, the coefficient of the anomalous Hall effect inside the granule and on its surface on the amplitude and profile of the TKE spectrum. Three main mechanisms are considered: the quasi-classical size effect, spin–orbit interaction enhancement at the granule surface and change of the percolation threshold.

Escitalopram-induced QTc prolongation and its relationship with KCNQ1, KCNE1, and KCNH2 gene polymorphisms

BackgroundEscitalopram can cause prolongation of the QT interval on the electrocardiogram (ECG). However, only some patients get pathological QTc prolongation in clinic. We investigated the influence of KCNQ1, KCNE1, and KCNH2 gene polymorphisms along with clinical factors on escitalopram-induced QTc prolongation. MethodsA total of 713 patients prescribed escitalopram were identified and had at least one ECG recording in this retrospective study. 472 patients with two or more ECG data were divided into QTc prolongation (n = 119) and non-prolongation (n = 353) groups depending on the threshold change in QTc of 30 ms above baseline value (∆QTc ≥ 30 ms). 45 patients in the QTc prolongation group and 90 patients in the QTc non-prolongation group were genotyped for 43 single nucleotide polymorphisms (SNPs) of KCNQ1, KCNE1, and KCNH2 genes. ResultsPatients with QTc prolongation (∆QTc ≥ 30 ms) got higher escitalopram dose (10.3 mg) than patients without QTc prolongation (9.4 mg), although no significant relationship was found between QTc interval and escitalopram dose in the linear mixed model. Patients who were older/coronary disease/hypertension or carried with KCNE1 rs1805127 C allele, KCNE1 rs4817668 C allele, KCNH2 rs3807372 AG/GG genotype were significantly at risk for QTc prolongation (∆QTc ≥ 30 ms). Concomitant antipsychotic treatment was associated with a longer QTc interval. LimitationsA relatively small sample size and lack of the blood concentration of escitalopram restricted the accurate relationship between escitalopram dose and QTc interval. ConclusionOur study revealed that KCNQ1, KCNE1, and KCNH2 gene polymorphisms along with clinical factors provide a complementary effect in escitalopram-induced QTc prolongation.

Age-related changes of auditory sensitivity across the life span of CBA/CaJ mice

The inbred mouse strain CBA/CaJ is a frequently used animal model of age-related hearing loss in humans. These mice display significant hearing loss at a relatively advanced age, similar to most humans, with progressive loss of hearing as the mouse continues to age. While important descriptions of hearing loss in this mouse strain at multiple ages have previously been published, shortcomings persist in the data for hearing over the lifespan of the mouse. Therefore, we analyzed auditory brainstem response threshold data from records maintained by our research group to yield an extensive database of thresholds over nearly the entire life span of the CBA/CaJ mouse (from 79 to 1085 days). Data was collected from in-house bred mice of CBA/CaJ stock, initially from The Jackson Laboratory. Data was collected using BiosigRZ software and TDT System III hardware. Thresholds were routinely measured in conjunction with behavioral and electrophysiological experiments; only responses from baseline or experimentally naïve animals were analyzed. The resulting data set comprised 376 female mice and 441 males. At the lowest and highest frequencies (8 & 32 kHz), initial thresholds were just under 30 dB SPL and increased slowly until they were significantly different at 16-18 months compared to 1-3 months age, with the difference increasing over subsequent ages. At the middle frequencies (12 & 16 kHz), initial thresholds were just under 20 dB SPL and increased until they became different from initial at 16-18 months. At 24 kHz, initial thresholds were just above 20 dB and became different from initial at 13-16 months of age. The rate of change of thresholds with age were similar for all frequencies until about 30 months of age, when 32 kHz threshold changes lagged behind other frequencies. Generally, CBA/CaJ mice in our colony display relatively low thresholds until approximately 16 months of age, depending on frequency. After 16-18 months, thresholds become significantly worse. After approximately 20-22 months thresholds increase linearly with age.

Clinical effects of different virtual reality presentation content on anxiety and pain: a randomized controlled trial

Many patients are frightened of or anxious about dental treatment. We have recently reported our use of virtual reality (VR) to alleviate the fear and anxiety experienced during oral surgical procedures However, the effectiveness of VR in alleviating anxiety varies greatly between individuals. We therefore investigated whether the content of the VR presentation made any difference to its effect in alleviating anxiety, and whether it had any analgesic effect. The study subjects experienced one of two different types of VR presentation and were asked to complete a questionnaire about any changes in their anxiety during the procedure, including a visual analog scale (VAS) score. As an objective evaluation, changes in pain threshold during the VR presentation were investigated using PainVision. For those patients who experienced a presentation showing a natural landscape, the change in VAS score was − 13.3 ± 28.7 mm, whereas for those who experienced a presentation showing a video game the change was − 22.2 ± 32.1 mm, an even greater reduction. In a pain questionnaire completed by individuals who had experienced the video game presentations, approximately 70% reported that their pain had diminished. An objective evaluation of pain threshold also showed that the pain threshold of individuals increased by around 3% while experiencing the natural landscape VR presentation, but that while experiencing the video game presentation, it increased significantly by around 15% compared with baseline. These results show that the content of the presentation affected not only the rate of decrease in anxiety, but also the pain threshold.

The hypoalgesic effects of wrist extensors training with blood flow restriction in patients with lateral elbow tendinopathy: a study protocol for a cross-over randomized controlled trial

Background: Lateral elbow tendinopathy (LET) is a disabling overuse injury with a significant healthcare burden. Despite the fact that exercise interventions are considered the best recommended treatment option of LET, their effectiveness in reducing pain and improving function remains debatable. The aim of our study is to evaluate the immediate effects of a new method of exercise using blood flow restriction (BFR) on pain perception and pain-free grip strength in patients with LET. Methods: This study was designed as a cross-over randomized controlled trial. We will compare an intervention using wrist extensors training with (WET-BFR) to a control intervention using WET-without-BFR in patients with LET. All measurements will be taken by a blinded assessor pre- and post-intervention. Primary outcome measures will be the changes in pressure pain thresholds at the lateral epicondyle, extensor carpi radialis brevis, C4 vertebra and tibialis anterior. Secondary outcome measure will be the changes in pain-free grip strength ratio. Conclusions: New approaches are needed to improve the treatment outcomes in LET. Although BFR training was found more effective in improving function and treatment success than conventional training, the effects on pain intensity were poor. Our hypothesis is that using the best BFR practice guidelines for wrist extensors training might be more effective to reduce pain sensitivity compared with non-BFR training in patients with LET. The trial will provide new research data to inform clinical practice regarding the effects of using BFR training in the current patient group. Trial registration: University of West Attica ethics committee: 9150/01-02-2023, ClinicalTrials.gov: NCT05919914

OGC P15 Analysing the Impact of Prehabilitation on Patient Outcomes in Oesophagogastric Cancer Surgery: Combined Data from Four prospective Clinical Trials performed across the UK and Ireland

Abstract Background Prehabilitation is increasingly being used in patients undergoing multi-modality treatment for oesophago-gastric (OG) cancer. Most studies to date have been small, single centre trials lacking statistical power. The results of larger randomised trials are still awaited. There remain considerable uncertainties regarding the outcome measures that may benefit from prehabilitation, the exact nature of the intervention and the mechanisms behind any observed benefit. This collaborative study sought to combine data from four prospective clinical prehabilitation trials performed in the UK and Ireland to determine the overall impact of the intervention on patient outcomes following oesophagogastric cancer surgery. Methods Anonymised data from four prospective prehabilitation trials conducted in the UK and Ireland (Southampton, Guildford, Dublin, and St Thomas’, London) in patients undergoing multi-modality treatment for oesophagogastric cancer was combined. The studies included two randomized and two non-randomized clinical trials. The primary outcome measures were differences in complications and length of stay. Secondary outcomes were changes in BMI, fitness (VO2 max), chemotherapy completion rates and tumour regression. In total, 180 patients were included from four studies, with 93 patients in the prehabilitation group and 87 patients in the control group. Results Severe complications (Clavien Dindo >=3) were observed less frequently in the prehabilitation group (19% vs 34%; p=0.038). Hospital length of stay also favoured prehabilitation (10 vs 11 days) albeit not statistically significant. Chemotherapy completion rates were significantly higher following prehabilitation (96% vs 63%; p<0.001). There were non-significant improvements in VO2 max change following neo-adjuvant therapy (delta 1.35 vs 2.39; p=0.25), anaerobic threshold change (delta 1.20 vs 2.20; p=0.11) and chemotherapy response (Mandard 1-3 57% vs 44%; p=0.178). Conclusions Despite some limitations in terms of heterogeneity of study methodology and prehabilitation interventions, this study has highlighted a willingness of individual units to collaborate and tangible clinical benefits across a range of outcome measures in a larger OG patient population. Current initiatives to agree national standards for delivering prehabilitation and the results of on-going trials will help to further refine this important intervention and expand the evidence base to support the widespread adoption and implementation of prehabilitation programs.