Testing Paradigm Research Articles

Conceptualization and standardization of a non-invasive closed head injury model using directed shockwave to mice

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide, with closed head injury (CHI) being one of the most common forms of TBI. Preclinical modeling of TBI is challenging due to confounding factors like craniectomy and poorly controlled injury severity. This study proposes a non-invasive CHI model using directed shockwaves. The mice heads were exposed to the shockwave and accommodated together following the implantation of RFID tags for automated neurocognitive assessment. Following a 13-day paradigm, mice underwent a digital gait analysis and subsequent classical behavioral test paradigms for affective, cognitive, and locomotor functions. Qualitative and quantitative histopathological assessment was carried out for shockwave pulses-dependent changes in terms of lesion volume, neuronal death, dendritic complexity, and spine density. Studies showed shockwave pulses-dependent differences in survivability, righting reflex, neural damage, and death. Shockwave-exposed mice showed significantly impaired learning and cognitive flexibility. Interestingly, exposed mice showed locomotor hyperactivity and risk-taking behavior (lack of anxiety) along with depression-like phenotypes. Our result suggests that the shockwave-based CHI models result in the clinically relevant phenotype and are precisely controlled for reproducibility.

Mapping common and distinct brain correlates among cognitive flexibility tasks: concordant evidence from meta-analyses.

Cognitive flexibility allows individuals to switch between different tasks, strategies, or ideas; an ability that is important for everyday life. The Wisconsin card sorting test (WCST) and task switching paradigm (TSP) are popular measures of cognitive flexibility. Although both tasks require switching, the TSP requires participants to memorize switching rules and retrieve them when they view a cue (rule-retrieval), whereas the classic WCST requires participants to discover the switching rule via trial-and-error (rule-discovery). Many functional magnetic resonance imaging studies have examined brain responses to these tasks. Extant meta-analyses show concordance in activation in a widespread set of areas including frontal, parietal, and cingulate cortices. Critically, past meta-analyses have not specifically examined brain correlates associated with rule derivation (i.e., rule-discovery vs. rule-retrieval) in cognitive flexibility tasks. We examine for the first time common and distinct concordance in brain responses to rule-discovery (i.e., WCST) and rule-retrieval (i.e., TSP), as well as TSP subtypes using quantitative meta-analyses. We analyzed data from 69 eligible articles with a total of 1617 young-adult participants. Conjunction results show concordance in common fronto-parietal areas predominantly in the left hemisphere. Contrast analyses show that rule-discovery required increased involvement in multiple cortical and subcortical regions such as frontopolar (Brodmann Area 10), parietal, insular cortex, thalamus and caudate nucleus predominantly in the right hemisphere. No significant differences in concordance were observed among the three, task switching paradigm sub-types. We propose a neuroanatomical model of cognitive flexibility and discuss theoretical and practical applications.

Social contagion of pain and fear results in opposite social behaviors in rodents: meta- analysis of experimental studies.

The study aimed to explore the key factors influencing emotional valence in rodents, focusing on the critical elements that distinguish the contagion processes of fear and pain. Through a systematic review and meta-analysis, we examined behavioral outcomes of rodents exposed to painful or fearful catastrophes to see whether they are prosocial or antisocial through three-chamber test and dyadic social interaction paradigm. Fear contagion, particularly when witnessed, leads to social avoidance behavior, unaffected by sex difference but more pronounced with age. In contrast, pain contagion promotes social approach and caring/helping behaviors. The present study demonstrates that the emotional valence induced by pain contagion is quite different from fear contagion and this difference may result in different motivations and social behaviors, namely, social contagion of pain is likely to be more associated with prosocial behaviors, however, social contagion of fear is likely to be more associated with antisocial behaviors. PROSPERO (CRD42024566326).

Review: Diagnostic Potential for Collaborative Pharyngitis Biomarkers.

Pharyngitis is an inflammatory condition of the pharynx and/or tonsils commonly seen in both children and adults. Viruses and bacteria represent the most common encountered etiologic agents-yeast/fungi and parasites are infrequently implicated. Some of these are predominantly observed in unique populations (eg, immunocompromised or unvaccinated individuals). This manuscript (part 3 of 3) summarizes the current state of biomarker diagnostic testing and highlights the expanding role they will likely play in the expedited diagnosis and management of patients with acute pharyngitis. Biomarkers, in conjunction with rapid antigen and/or nucleic acid amplification testing, will likely become the standard of care to accurately diagnose the etiologic agent(s) of pharyngitis. This novel testing paradigm has the potential to guide appropriate patient management and antibiotic stewardship by accurately determining if the cause of pharyngitis is due to a viral or bacterial etiology.

Size sound symbolism in mothers' speech to their infants.

Six-month-olds infer object size based on pitch: they map high-pitched vowels onto smaller objects and low-pitched vowels onto larger objects (Peña et al., 2011). The 'sound symbolism bootstrapping hypothesis' (Imai & Kita, 2014) proposes that this may support understanding of word-meaning correspondences; by drawing on iconic pairings between linguistic cues and corresponding referents (e.g., higher pitch for smaller objects), infants develop understanding of word-referent associations. Here we analyse mother-child interactions, testing whether sound-symbolic pitch-size correspondences occur in infant-directed speech. 40 dyads engaged in (semi-)naturalistic interaction around picture books containing images of toys of varying sizes. We compare mothers' pitch when referring to small versus large toys, analysing i) actual size (bigger vs. smaller toys); ii) relative toy size congruence (i.e., congruent vs. incongruent with real-world expectation); and iii) transparency of the test paradigm as regards its focus on size contrastiveness (non-transparent, moderately transparent, highly transparent) to observe the nuances of size sound symbolism in infant-directed speech.

Multi-channel portable odor delivery device for self-administered and rapid smell testing

To improve our understanding of the perception of odors, researchers are often required to undertake experimental procedures with users exposed to multiple odors in a variety of settings, including to diagnose smell loss in clinics and care homes. Existing smell tests are typically administered using multiple sniffing pens, manually presented to patients by a highly specialized nurse using a time-consuming and complex testing paradigm. Automated odor delivery devices, such as olfactometer systems, exist but are expensive, bulky and typically lab based, making them difficult to use for on the ground odor delivery. Here we have developed a portable, affordable, odor delivery device that can deliver 24 odors through individual channels with high temporal precision and without cross-contamination. The device allows for the rapid, flexible sequencing of odors via digital control using a mobile application and has been experimentally validated in the lab, as well as tested on patients. The design provides several advantages for investigating olfactory perception and offers the possibility that users can one day self-administer smell tests in a range of settings, including at home, allowing smell healthcare services to evolve and become part of a routine practice and self-care culture.

Organoid intelligence for developmental neurotoxicity testing.

The increasing prevalence of neurodevelopmental disorders has highlighted the need for improved testing methods to determine developmental neurotoxicity (DNT) hazard for thousands of chemicals. This paper proposes the integration of organoid intelligence (OI); leveraging brain organoids to study neuroplasticity in vitro, into the DNT testing paradigm. OI brings a new approach to measure the impacts of xenobiotics on plasticity mechanisms - a critical biological process that is not adequately covered in current DNT in vitro assays. Finally, the integration of artificial intelligence (AI) techniques will further facilitate the analysis of complex brain organoid data to study these plasticity mechanisms.

A Comparison of European Union and Turkish Reports on the Statistics of Experimental Animal Use in Toxicity Testing.

The data on the number of animals used for experimental purposes, with a particular focus on regulatory toxicity studies, in Turkey and EU member states plus Norway (EU+), were compared for the period 2015 to 2020 (UK data after Brexit for 2020 were included too). The total number of listed vertebrates used for regulatory toxicity testing in the full 6-year reporting period in Turkey was 3.6% of that reported for the EU+. However, these numbers showed an increasing trend over the reporting period in Turkey, while the trend decreased in the EU+. In the top three most-used species for regulatory toxicology purposes in Turkey, 41% were fish (68,758 animals), followed by rats (29%; 49,975 animals), and then mice (20%; 33,292 animals). Turkey used low numbers of cats and dogs, while the corresponding number for the EU+ was more than 70-fold higher. Non-human primates were not used at all in Turkey, whereas about 34,000 were used in EU+ laboratories. The majority of toxicity tests (57%) performed in Turkey were categorised as 'Other' toxicity tests, and 27% were acute and sub-acute toxicity tests. Successful replacement alternatives (e.g. in vitro and in silico approaches) are already used in a wide range of research areas. However, although this new research and testing paradigm is underpinned by scientific evidence, the legislation and pace of acceptance of these new techniques in Turkey is considerably lagging behind other countries.

A-323 Advancing Point-of-Care Testing: Independent Evaluation of the Truvian Platform

Abstract Background To address the deficiencies of long turnaround time, increased cost and delayed medical intervention in the current paradigm of routine blood testing, Truvian has developed an automated blood testing platform that provides timely and lab-accurate results at the point of care. With 300 µL from a single Lithium Heparin blood sample, the Truvian solution generates 34 test results, including CMP, Lipid, HbA1c, TSH and CBC in under 30 minutes (TruWellness PanelTM).The present study focused on rigorous evaluation of the reliability and accuracy of Truvian's platform in a real-world clinical setting by untrained operators. Platform precision was measured over time on multiple Truvian instruments under standardized protocol. Accuracy and reliability were assessed independently at the UC San Diego Anti-Viral Research Center (AVRC) by testing samples from donors with chronic medical conditions and comparing against FDA cleared devices, Roche Cobas and Sysmex-XN. Methods Precision was assessed using the control workflow where three commercially available controls, were loaded as sample inputs into the Truvian consumables to perform the TruWellness Panel(TM). Three levels of controls were run in quadruplicate daily on 4 instruments (N > 100 per instrument). Within and between run, day, instrument, and consumable lot variance components were assessed.Accuracy was assessed as part of an IRB-approved method comparison study at AVRC by untrained operators. A total of 50 unique donors representing various disease states were consented and enrolled. Three 4-mL blood samples were collected from each donor: one Lithium Heparin (LiHep) sample for the Truvian System's TruWellness PanelTM, another LiHep gel tube for Roche Cobas clinical chemistry and TSH assays, and an EDTA sample for the Sysmex complete blood count with 3-part differential and HbA1c. All samples were tested on the Truvian System within an hour of collection or processed for central lab testing. Concordance to comparator devices was assessed via relative difference plots, Passing-Bablok and/or Deming regression analyses. Results Our results indicated that the performance of Truvian's instrument met pre-specified reliability, precision and accuracy criteria (per preliminary analysis of the first 50 patients). Reproducibility results showed 100% (69/69) of all tests met specifications. Interim analysis of the first 50 patients in the method comparison study indicates a robust concordance with predicate devices with 20 out of 23 tests showing a correlation coefficient of ≥ 0.9. During donor testing, the instrument demonstrated 96% (48/50) run reliability with only a single operator-induced error where the blood tube was not loaded correctly, highlighting the robustness and ease of use of the platform. Conclusions The present evaluation underscores Truvian's instrument as an easy-to-operate platform that can be run by untrained operators, maintain reliability in real-world clinical settings, and deliver accurate and precise results. Enrollment and sample testing are ongoing, with plans to expand the sample size to 200 donors and study completion planned for May 2024. Broadening the study to encompass a wider range of analyte measurements among chronic disease patients is expected to enhance performance data. This independent evaluation provided confidence in Truvian Platform’s performance and suitability for practical healthcare applications.

Role of the video head impulse test in the evaluation of vestibulo-ocular reflex in individuals with Parkinson's disease.

<p>Parkinson&rsquo;s disease (PD) is the most common movement disorder and the second most common neu&shy;rodegenerative disease of the central ner&shy;vous system. Dizziness is frequently reported by PD patients, yet there is a paucity of research focusing on the vestibulo-ocular reflex (VOR) in this population using high-frequency vestibular testing. This study aims to investigate the VOR in individuals with PD using the video head thrust test with and without suppression.&nbsp;</p>. <p>Forty individuals with PD and 40 healthy individuals were included in the study. According to the Hoehn-Yahr Scale, individuals with PD were defined as early stage with a score of 1&ndash;2.5 and middle to late stage with a score of 3 to 5. The Head Impulse Testing Paradigm (HIMP) and Suppression Head Impulse Testing Paradigm (SHIMP) were applied to all individuals.</p>. <p>No statistically significant difference was observed between the PD group and the control group in terms of semicircular canal (SCC) gains in both HIMP and SHIMP tests. No catch-up saccades were observed in the right anterior, right posterior, left anterior, and left posterior SCC planes in the PD and control groups. However, in the right lateral SCC plane 32 patients in the PD group had saccades, while 8 patients in the control group had saccades. In the left lateral SCC plane, 32 patients in the PD group and 9 patients in the control group had catch-up saccades. A statistically significant difference was observed in the number and amplitude of saccades in the right and left lateral SCC planes compared to the control group (p&lt;0.05). In addition, in the PD group, the amplitude, peak velocity, and latency of the anticompensatory saccades seen in SHIMP showed a statistically significant difference compared to the control group (p&lt;0.05).</p>. <p>VOR in the vertical SCC plane was not affected in individuals with PD. However, VOR in the lateral SCC plane was affected. It was concluded that when evaluating VOR with both HIMP and SHIMP in individuals with PD, the presence of catch-up saccades should be focused on and evaluated for possible vestibular dysfunction, even though SCC gains are normal. This study will contribute to a deeper understanding of vestibular function in PD, potentially informing better management strategies for dizziness in this population.&nbsp;</p>.

Early Electrophysiology in Suspected Acute Guillain-Barré Syndrome: A Prospective Study of Comprehensive Testing.

Electrophysiologic changes in early Guillain-Barré Syndrome (GBS) can be nondiagnostic. Improved testing paradigms may improve hyperacute treatment. This work prospectively evaluated consecutive patients admitted to a metropolitan teaching hospital in Melbourne, Australia, with suspected acute GBS. We performed extensive neurophysiology at three different time points. Novel tests, including cutaneous silent periods, long latency reflexes, and contraction-induced H reflexes, were assessed. Twenty-three participants were studied, including 13 cases of acute GBS. In total, 69% of acute cases of GBS were accurately diagnosed on the first nerve conduction study using published neurophysiologic criteria, with serial studies rarely altering the GBS subtype classification. Antidromic and orthodromic upper limb sensory studies were diagnostically equivalent. A sural sparing pattern was seen in 77% of cases of GBS at the first test. Long latency reflexes and contraction-induced H reflexes testing were abnormal in most participants but were limited by muscle weakness in some. Cutaneous silent periods testing was unobtainable in approximately 50% of cases because of weakness and did not discriminate from mimic disorders. Abnormalities of long latency reflexes and contraction-induced H reflexes may be helpful where initial electrophysiology is nondiagnostic but are nonspecific. Cutaneous silent periods testing seems of limited value. Comprehensive testing provides diagnostic certainty in most cases of GBS from the very first study.

Cumulative risk predicting differential effectiveness of the incredible years parent-training

The evidence on whether socioeconomic status moderates the effectiveness of parent-training programs for disruptive child behaviors is inconclusive. These varied results may stem from differences in the programs or the studies themselves. We applied an equivalence test paradigm to test the hypothesis of equal benefit from the Incredible Years Parent-Training (IYPT) across family risk on disruptive child behaviors. During the Danish roll-out of the IYPT, 1203 families were recruited across 20 different municipalities. The isolated and cumulative effect of five markers of low socioeconomic status, specifically single parent household, parental unemployment, low family income, low parental educational level, and teen parenthood, were analyzed as predictors of pre-to-post treatment response. Results showed equal benefit among families experiencing from zero to four accumulated socioeconomic risks (99 % of our sample). Our findings suggest that the IYPT brings equal benefit across socioeconomic backgrounds and risk levels in Danish community settings.

Updated Risk Score Algorithms for Acute HIV Infection Detection at a Sexually Transmitted Infections Clinic in Lilongwe, Malawi

Background: Detection of acute (pre-seroconversion) HIV infection (AHI), the phase of highest transmission risk, requires resource-intensive RNA- or antigen-based detection methods that can be infeasible for routine use. Risk score algorithms can improve the efficiency of AHI detection by identifying persons at highest risk of AHI for prioritized RNA/antigen testing, but prior algorithms have not considered geospatial information, potential differences by sex, or current antibody testing paradigms. Methods: We used elastic net models to develop sex-stratified risk score algorithms in a case-control study of persons (136 with AHI, 250 without HIV) attending a sexually transmitted infections (STI) clinic in Lilongwe, Malawi from 2015 to 2019. We designed algorithms for varying clinical contexts according to three levels of data availability: 1) routine demographic and clinical information, 2) behavioral and occupational data obtainable through patient interview, and 3) geospatial variables requiring external datasets or field data collection. We calculated sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) to assess model performance and developed a web application to support implementation. Results: The highest-performing AHI risk score algorithm for men (AUC=0.74) contained five variables (condom use, body aches, fever, rash, genital sores/ulcers) from the first two levels of data availability. The highest-performing algorithm for women (AUC=0.81) contained fifteen variables from all three levels of data availability. A risk score cut-point of 0.26 had an AHI detection sensitivity of 93% and specificity of 27% for males, and a cut-point of 0.15 had 97% sensitivity and 44% specificity for females. Additional models are available in the web application. Conclusion: Risk score algorithms can facilitate efficient AHI detection in STI clinic settings, creating opportunities for HIV transmission prevention interventions during this critical period of elevated transmission risk.

Economic Evaluation of Population-Based BRCA1 and BRCA2 Testing in Canada

Population-based BRCA testing can identify many more BRCA carriers who will be missed by the current practice of BRCA testing based on family history (FH) and clinical criteria. These carriers can benefit from screening and prevention, potentially preventing many more breast and ovarian cancers and deaths than the current practice. To estimate the incremental lifetime health outcomes, costs, and cost-effectiveness associated with population-based BRCA testing compared with FH-based testing in Canada. For this economic evaluation, a Markov model was developed to compare the lifetime costs and outcomes of BRCA1/BRCA2 testing for all general population women aged 30 years compared with FH-based testing. BRCA carriers are offered risk-reducing salpingo-oophorectomy to reduce their ovarian cancer risk and magnetic resonance imaging (MRI) and mammography screening, medical prevention, and risk-reducing mastectomy to reduce their breast cancer risk. The analyses were conducted from both payer and societal perspectives. This study was conducted from October 1, 2022, to February 20, 2024. Outcomes of interest were ovarian cancer, breast cancer, additional heart disease deaths, and incremental cost-effectiveness ratio ICER per quality-adjusted life-year (QALY). One-way and probabilistic-sensitivity-analyses (PSA) were undertaken to explore the uncertainty. In the simulated cohort of 1 000 000 women aged 30 years in Canada, the base case ICERs of population-based BRCA testing were CAD $32 276 (US $23 402.84) per QALY from the payer perspective or CAD $16 416 (US $11 903.00) per QALY from the societal perspective compared with FH-based testing, well below the established Canadian cost-effectiveness thresholds. Population testing remained cost-effective for ages 40 to 60 years but not at age 70 years. The results were robust for multiple scenarios, 1-way sensitivity, and PSA. More than 99% of simulations from payer and societal perspectives were cost-effective on PSA (5000 simulations) at the CAD $50 000 (US $36 254.25) per QALY willingness-to-pay threshold. Population-based BRCA testing could potentially prevent an additional 2555 breast cancers and 485 ovarian cancers in the Canadian population, corresponding to averting 196 breast cancer deaths and 163 ovarian cancer deaths per 1 000 000 population. In this economic evaluation, population-based BRCA testing was cost-effective compared with FH-based testing in Canada from payer and societal perspectives. These findings suggest that changing the genetic testing paradigm to population-based testing could prevent thousands of breast and ovarian cancers.

Chemicals regulation and non-animal methods: displacing the gold standard.

Regulating industrial chemicals in foodstuffs and consumer products is a major aspect of protecting populations against health risks. Non-animal testing methods are an essential part of the radical change to the framework for toxicity testing that is long overdue in global economies. This paper discusses reasons why the drive to reduce animal testing for chemical safety testing is so difficult to achieve, as perceived by those who are closely involved in chemicals regulations in different capacities. Progress is slow, despite the fact that the ethico-legal conditions for a move away from animal testing are largely in place, and despite scientific arguments for a radical change in the paradigm of toxicity testing, away from reliance on animal studies. I present empirical data drawn from two studies in a European Commission context promoting non-animal methods. The aim of the paper is modest. It is to foreground the voices of those who deal with the science and regulation of chemicals on a day-to-day basis, rather than to offer a theoretical framework for what I heard from them. I offer a synthesis of the main challenges faced by non-animal alternatives, as these are perceived by people in different stakeholder groups dealing with chemicals regulation. I show where there are pockets of agreement between different stakeholders, and where the main disagreements lie. In particular there is dispute and disagreement over what counts as validation of these alternative tests, and by implication of the traditional 'gold standard' of animal testing. Finally, I suggest that the shift to non-animal methods in chemicals regulation demonstrates the need for the concept of validation to be broadened from a purely techno-scientific definition, and be more explictly understood as a demand for trust and acceptance, with more attention given to the complex social, institutional and economic settings in which it operates.

Mutant induced neurons and humanized mice enable identification of Niemann-Pick type C1 proteostatic therapies.

Therapeutics that rescue folding, trafficking, and function of disease-causing missense mutants are sought for a host of human diseases, but efforts to leverage model systems to test emerging strategies have met with limited success. Such is the case for Niemann-Pick type C1 disease, a lysosomal disorder characterized by impaired intracellular cholesterol trafficking, progressive neurodegeneration, and early death. NPC1, a multipass transmembrane glycoprotein, is synthesized in the endoplasmic reticulum and traffics to late endosomes/lysosomes, but this process is often disrupted in disease. We sought to identify small molecules that promote folding and enable lysosomal localization and functional recovery of mutant NPC1. We leveraged a panel of isogenic human induced neurons expressing distinct NPC1 missense mutations. We used this panel to rescreen compounds that were reported previously to correct NPC1 folding and trafficking. We established mo56-hydroxycholesterol (mo56Hc) as a potent pharmacological chaperone for several NPC1 mutants. Furthermore, we generated mice expressing human I1061T NPC1, a common mutation in patients. We demonstrated that this model exhibited disease phenotypes and recapitulated the protein trafficking defects, lipid storage, and response to mo56Hc exhibited by human cells expressing I1061T NPC1. These tools established a paradigm for testing and validation of proteostatic therapeutics as an important step toward the development of disease-modifying therapies.

Exploring the effects of increased socket-residual limb coupling integrity via vacuum assisted suspension on prosthetic control: a preliminary study in transtibial prosthesis users.

The prosthetic socket provides the critical interface between prosthesis and residuum. The purpose of this pilot study was to explore the effect of altering socket-residuum coupling integrity on limb and body control, through the use of vacuum-assisted suspension. A secondary purpose was to explore the potential use of two measurement tools designed to assess mobility in a clinical context. Individuals with unilateral transtibial amputation performed intentional sway (n = 7) and treadmill walking (n = 6) tasks at three vacuum levels. Sway deviation from a straight-line path to peripheral targets was measured using an instrumented balance platform. Step width variability and targeting accuracy were measured using an augmented reality treadmill. There was a significant difference in intentional sway performance toward the target on the anterior diagonal toward the prosthetic side (p = 0.036); higher vacuum levels tended toward less deviation from a straight-line path. We found no group differences between total intentional sway deviation, step width variability or stepping accuracy across vacuum levels. Improved socket-residuum coupling integrity via vacuum may have measurable effects on functional control that warrant further investigation. We highlight limitations of the clinical testing paradigms to inform future work.Implications for rehabilitationThe fit of the socket is a critical factor in the success of lower limb prosthesis use.Vacuum-assisted suspension modifies the coupling between the residuum and socket.Changes in socket-residuum coupling may lead to measurable differences in control; however, these may be activity and person-specific.Clinically intended instrumented tests of movement function derived for an intact anatomy should be used with caution when assessing prosthesis users.

Effects of high-intensity chronic noise on spatial memory in male versus female rats.

The detrimental effects of high-intensity noise on the auditory system and emotional status, including the induction of anxiety, are well documented. Preclinical as well as epidemiological and clinical studies have solidly established differential responses between males and females to various stressful stimuli, including high-intensity white noise (HIWN). However, whether chronic exposure to noise affects cognitive functions and whether this effect is sex dependent has not been adequately addressed. In this study, we used two cognitive test paradigms, such as the Morris water maze (MWM) and the multi-branch maze (MBM), to test the effect of chronic HIWN on indices of spatial learning and memory in both male and female Wistar rats. Our findings indicate that daily (1 h) exposure to 100 dB of noise for 30 consecutive days induces different task-dependent responses in male versus female rats. For example, in the acquisition phase of MWM, female rats exposed to noise outperformed their male counterparts at twice the speed. Similarly, in the MBM test, noise-exposed female rats outperformed the male rats in reaching the nest box. It is clear from these studies that noise impairs cognitive functions twice as negatively in male rats as in female rats. Thus, sex-related differences in spatial learning and memory in response to HIWN must be taken into consideration when investigating the neurobiological components and/or treatment modalities.

Between Scylla and Charybdis: assessing the multidimensional aspects of pain behaviors in rats using a double avoidance place preference paradigm.

Although the behavioral response to pain is complex and involves supraspinal processes, assessment of pain symptoms in animal models still mainly relies on reflex-based nociceptive tests, which do not account for the affective-motivational nor cognitive components of pain. We introduce a double avoidance place preference paradigm, an integrated testing procedure in freely moving rats that relies on the conflict between the avoidance of a dark compartment in which a thermal ramp is activated, and the escape towards an aversive brightly lit compartment. We were able to differentiate the first nociceptive threshold from the temperature of definitive escape from the dark compartment, conveying information on the adaptive behavior of animals. Measures were repeated after an hour to evaluate the adaptive learning response upon reexposure. In naive animals, there was a significant decrease in the time spent in the dark compartment at all stages of the testing paradigm upon reexposure, leading to a final escape before the flood had reached nociceptive values. This adaptive behavior was blunted by anxiolytic treatment. In animals exhibiting hyperalgesia following intraplantar complete Freund adjuvant injection, escape thresholds were significantly higher than that of control animals, hinting at a maladaptive affective-motivational response to noxious stimulation. However, in cuff animals, we failed to reveal any hot nociceptive hypersensitivity, but animals exhibited a strong adaptive response to cold simulation upon reexposure. Overall, the proposed paradigm allows for an integrated cortical response leading to a proactive avoidance behavior, while fully complying with ethical standards in animal experimentation.

The Audible Contrast Threshold (ACT) test: A clinical spectro-temporal modulation detection test

Over the last decade, multiple studies have shown that hearing-impaired listeners’ speech-in-noise reception ability, measured with audibility compensation, is closely associated with performance in spectro-temporal modulation (STM) detection tests. STM tests thus have the potential to provide highly relevant beyond-the-audiogram information in the clinic, but the available STM tests have not been optimized for clinical use in terms of test duration, required equipment, and procedural standardization. The present study introduces a quick-and-simple clinically viable STM test, named the Audible Contrast Threshold (ACT™) test. First, an experimenter-controlled STM measurement paradigm was developed, in which the patient is presented bilaterally with a continuous audibility-corrected noise via headphones and asked to press a pushbutton whenever they hear an STM target sound in the noise. The patient's threshold is established using a Hughson-Westlake tracking procedure with a three-out-of-five criterion and then refined by post-processing the collected data using a logistic function. Different stimulation paradigms were tested in 28 hearing-impaired participants and compared to data previously measured in the same participants with an established STM test paradigm. The best stimulation paradigm showed excellent test-retest reliability and good agreement with the established laboratory version. Second, the best stimulation paradigm with 1-second noise “waves” (windowed noise) was chosen, further optimized with respect to step size and logistic-function fitting, and tested in a population of 25 young normal-hearing participants using various types of transducers to obtain normative data. Based on these normative data, the “normalized Contrast Level” (in dB nCL) scale was defined, where 0 ± 4 dB nCL corresponds to normal performance and elevated dB nCL values indicate the degree of audible contrast loss. Overall, the results of the present study suggest that the ACT test may be considered a reliable, quick-and-simple (and thus clinically viable) test of STM sensitivity. The ACT can be measured directly after the audiogram using the same set up, adding only a few minutes to the process.