Onset Of Response Research Articles

Abstract IA014: Unraveling pancreatic tumor defenses: inside the stromal orchestra with the HOST-factor

Abstract Dive into how members of the Cukierman lab and their collaborators explore desmoplasia, the dense “shield” around tumors. Discover their groundbreaking 3D model that reveals the intricate “symphony” of fibroblasts and the interstitial extracellular matrix they produce. Learn how these elements impact cancer cells, as well as the function of immune and other tumor microenvironment cells. Central to the lab’s research is the HOST-Factor (Harmonic Output of Stromal Traits), a new tool to measure and eventually modify the microenvironment’s influence on tumors. Don’t miss this opportunity to see how the team is transforming our understanding of pancreatic cancer’s onset, progression, and treatment responses. Citation Format: Edna Cukierman. Unraveling pancreatic tumor defenses: inside the stromal orchestra with the HOST-factor [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr IA014.

Spatiotemporal hierarchies of face representation in the human ventral temporal cortex

In this study, we examined the relatively unexplored realm of face perception, investigating the activities within human brain face-selective regions during the observation of faces at both subordinate and superordinate levels. We recorded intracranial EEG signals from the ventral temporal cortex in neurosurgical patients implanted with subdural electrodes during viewing of face subcategories (human, mammal, bird, and marine faces) as well as various non-face control stimuli. The results revealed a noteworthy correlation in response patterns across all face-selective areas in the ventral temporal cortex, not only within the same face category but also extending to different face categories. Intriguingly, we observed a systematic decrease in response correlation coupled with an increased response onset time from human face to mammalian face, bird face and marine faces. Our result aligns with the notion that distinctions at the basic level category (e.g., human face versus non-human face) emerges earlier than those at the superordinate level (e.g., animate versus inanimate). This indicates response gradient in the representation of facial images within human face-sensitive regions, transitioning progressively from human faces to non-face stimuli. Our findings provide insights into spatiotemporal dynamic of face representations which varies spatially and at different timescales depending on the face subcategory represented.

Cancer-associated fibroblasts shape early myeloid cell response to chemotherapy-induced immunogenic signals in next generation tumor organoid cultures

BackgroundPatient-derived colorectal cancer (CRC) organoids (PDOs) solely consisting of malignant cells led to major advances in the understanding of cancer treatments. Yet, a major limitation is the absence of cells...

Autoimmune/Inflammatory Syndrome Induced by Adjuvants (ASIA) Related to Breast Implants: A Comprehensive Review

Autoimmune/Inflammatory Syndrome Induced by Adjuvants (ASIA) is a complex clinical entity characterized by the onset of autoimmune or inflammatory responses following exposure to adjuvants, substances that enhance immune responses. One of the most studied triggers of ASIA is breast implants, which are commonly composed of silicone. While breast implants are generally considered safe, a subset of patients may develop systemic symptoms collectively termed as "Breast Implant Illness" (BII), now recognized within the broader spectrum of ASIA. This review provides a thorough analysis of the pathophysiology, clinical presentation, diagnostic challenges, and management options for ASIA associated with breast implants. We aim to elucidate the underlying mechanisms of immune dysregulation and inflammatory responses induced by silicone and explore the latest evidence-based therapeutic approaches, including explantation surgery and immunosuppressive therapies. Our review underscores the need for heightened clinical awareness and further research into ASIA, as early recognition and intervention can significantly improve patient outcomes.

Spatiotemporal mapping of auditory onsets during speech production.

The human auditory cortex is organized according to the timing and spectral characteristics of speech sounds during speech perception. During listening, the posterior superior temporal gyrus is organized according to onset responses, which segment acoustic boundaries in speech, and sustained responses, which further process phonological content. When we speak, the auditory system is actively processing the sound of our own voice to detect and correct speech errors in real time. This manifests in neural recordings as suppression of auditory responses during speech production compared to perception, but whether this differentially affects onset and sustained temporal profiles is not known. Here we investigated this question using intracranial EEG recorded from seventeen pediatric, adolescent, and adult patients with medication-resistant epilepsy while they performed a reading/listening task. We identified onset and sustained responses to speech in bilateral auditory cortex and observed a selective suppression of onset responses during speech production. We conclude that onset responses provide a temporal landmark during speech perception that is redundant with forward prediction during speech production and are therefore suppressed. Phonological feature tuning in these "onset suppression" electrodes remained stable between perception and production. Notably, auditory onset responses and phonological feature tuning were present in the posterior insula during both speech perception and production, suggesting an anatomically and functionally separate auditory processing zone that we believe to be involved in multisensory integration during speech perception and feedback control.Significance Statement Specific neural populations in the auditory cortex preferentially respond to the onset of speech sounds. These "onset responses" aid in perceiving boundaries in continuous speech. We recorded neural responses from patients with intracranial electrodes during a speaking and listening task to investigate the role of onset responses in speech production. Onset responses were present in the auditory cortex during listening, but absent during speaking. On the other hand, onset responses were observed in the insula during both conditions, suggesting a different functional role for the insula in auditory feedback processing. These findings extend our knowledge of how different parts of the brain involved in feedback control operate during speech production by identifying two functionally and anatomically distinct patterns of activity.

Ionising radiation exposure-induced regulation of selected biomarkers and their impact in cancer and treatment.

Ionising radiation (IR) is a form of energy that travels as electromagnetic waves or particles. While it is vital in medical and occupational health settings, IR can also damage DNA, leading to mutations, chromosomal aberrations, and transcriptional changes that disrupt the functions of certain cell regulators, genes, and transcription factors. These disruptions can alter functions critical for cancer development, progression, and treatment response. Additionally, IR can affect various cellular proteins and their regulators within different cell signalling pathways, resulting in physiological changes that may promote cancer development, progression, and resistance to treatment. Understanding these impacts is crucial for developing strategies to mitigate the harmful effects of IR exposure and improve cancer treatment outcomes. This review focuses on specific genes and protein biomarkers regulated in response to chronic IR exposure, and how their regulation impacts disease onset, progression, and treatment response.

Body orientation change of neighbors leads to scale-free correlation in collective motion

Collective motion, such as milling, flocking, and collective turning, is a common and captivating phenomenon in nature, which arises in a group of many self-propelled individuals using local interaction mechanisms. Recently, vision-based mechanisms, which establish the relationship between visual inputs and motion decisions, have been applied to model and better understand the emergence of collective motion. However, previous studies often characterize the visual input as a transient Boolean-like sensory stream, which makes it challenging to capture the salient movements of neighbors. This further hinders the onset of the collective response in vision-based mechanisms and increases demands on visual sensing devices in robotic swarms. An explicit and context-related visual cue serving as the sensory input for decision-making in vision-based mechanisms is still lacking. Here, we hypothesize that body orientation change (BOC) is a significant visual cue characterizing the motion salience of neighbors, facilitating the emergence of the collective response. To test our hypothesis, we reveal the significant role of BOC during collective U-turn behaviors in fish schools by reconstructing scenes from the view of individual fish. We find that an individual with the larger BOC often takes on the leading role during U-turns. To further explore this empirical finding, we build a pairwise interaction mechanism on the basis of the BOC. Then, we conduct experiments of collective spin and collective turn with a real-time physics simulator to investigate the dynamics of information transfer in BOC-based interaction and further validate its effectiveness on 50 real miniature swarm robots. The experimental results show that BOC-based interaction not only facilitates the directional information transfer within the group but also leads to scale-free correlation within the swarm. Our study highlights the practicability of interaction governed by the neighbor’s body orientation change in swarm robotics and the effect of scale-free correlation in enhancing collective response.

Characterisation of the antibody-mediated selective pressure driving intra-host evolution of SARS-CoV-2 in prolonged infection.

Neutralising antibodies against the SARS-CoV-2 spike (S) protein are major determinants of protective immunity, though insufficient antibody responses may cause the emergence of escape mutants. We studied the humoral immune response causing intra-host evolution in a B-cell depleted, haemato-oncologic patient experiencing clinically severe, prolonged SARS-CoV-2 infection with a virus of lineage B.1.177.81. Following bamlanivimab treatment at an early stage of infection, the patient developed a bamlanivimab-resistant mutation, S:S494P. After five weeks of apparent genetic stability, the emergence of additional substitutions and deletions within the N-terminal domain (NTD) and the receptor binding domain (RBD) of S was observed. Notably, the composition and frequency of escape mutations changed in a short period with an unprecedented dynamic. The triple mutant S:Delta141-4 E484K S494P became dominant until virus elimination. Routine serology revealed no evidence of an antibody response in the patient. A detailed analysis of the variant-specific immune response by pseudotyped virus neutralisation test, surrogate virus neutralisation test, and immunoglobulin-capture enzyme immunoassay showed that the onset of an IgM-dominated antibody response coincided with the appearance of escape mutations. The formation of neutralising antibodies against S:Delta141-4 E484K S494P correlated with virus elimination. One year later, the patient experienced clinically mild re-infection with Omicron BA.1.18, which was treated with sotrovimab and resulted in an increase in Omicron-reactive antibodies. In conclusion, the onset of an IgM-dominated endogenous immune response in an immunocompromised patient coincided with the appearance of additional mutations in the NTD and RBD of S in a bamlanivimab-resistant virus. Although virus elimination was ultimately achieved, this humoral immune response escaped detection by routine diagnosis and created a situation temporarily favouring the rapid emergence of various antibody escape mutants with known epidemiological relevance.

T(11;14) with multiple myeloma: Standard risk survival but slow and poor response.

We described 790 patients with newly diagnosed multiple myeloma, including 224 (28.4%) standard risk (SR) patients without t(11;14), 99 (12.5%) patients with t(11;14)alone, 58 (7.3%) with t(11;14) + HR, and 409 (51.8%) in the high-risk cytogenetic abnormality (HRCA) group including t(4;14), t(14;16), t(14;20), C1A1 and/or del(17p) but without t(11;14), to evaluate the impact of t(11;14) in NDMM patients on response rate, response kinetics and survival. Our study showed that NDMM patients in the t(11;14)alone group had similar PFS (49.3 vs. 50.7months; P = 0.392) and OS (112.4 vs. NR months; P = 0.982) as those in the SR group. However, the t(11;14)alone group exhibited a significantly poorer depth of response compared to the SR group, particularly with a lower MRD negativity rate (60.0% vs. 76.0%, P = 0.009). In the t(11;14)alone group, MRD status did not significantly impact PFS or OS, which was in contrast to the other groups. Response kinetics analyses showed that the t(11;14)alone group had a slower response rate than the other subgroups (t(11;14)alone vs. SR vs. HRCA: median time to MRD negativity = 9.19 vs. 4.25 vs. 4.27 months; P < 0.001). Our study showed that t(11;14)alone was characterized by survival comparable to standard risk cytogenetics despite exhibiting the slowest timing of response onset and lowest plateau of remission, which suggested a relatively indolent clinical course.

Systemic neurophysiological entrainment to behaviorally relevant rhythmic stimuli.

Physiological oscillations, such as those involved in brain activity, heartbeat, and respiration, display inherent rhythmicity across various timescales. However, adaptive behavior arises from the interaction between these intrinsic rhythms and external environmental cues. In this study, we used multimodal neurophysiological recordings, simultaneously capturing signals from the central and autonomic nervous systems (CNS and ANS), to explore the dynamics of brain and body rhythms in response to rhythmic auditory stimulation across three conditions: baseline (no auditory stimulation), passive auditory processing, and active auditory processing (discrimination task). Our findings demonstrate that active engagement with auditory stimulation synchronizes both CNS and ANS rhythms with the external rhythm, unlike passive and baseline conditions, as evidenced by power spectral density (PSD) and coherence analyses. Importantly, phase angle analysis revealed a consistent alignment across participants between their physiological oscillatory phases at stimulus or response onsets. This alignment was associated with reaction times, suggesting that certain phases of physiological oscillations are spontaneously prioritized across individuals due to their adaptive role in sensorimotor behavior. These results highlight the intricate interplay between CNS and ANS rhythms in optimizing sensorimotor responses to environmental demands, suggesting a potential mechanism of embodied predictive processing.

A Review of the Vitiligo Literature to Standardize Expression of Disease Severity.

The literature on vitiligo is heterogeneous with limited standardization in vitiligo disease severity reporting. The IDEOM Vitiligo Workgroup initiated a project to develop an improved understanding of clinical reporting of vitiligo severity. A medical librarian-developed literature review identified 50 clinical trials treating vitiligo topically using topical corticosteroids or topical tacrolimus that included adult and pediatric patients, with 10 or more patients, with grading by SORT criteria. Grading systems used included body surface area scoring (BSA) clinically or via photography and mapping. Most studies create a grading system of repigmentation including G0- no change, G1- 1-25%, G2- 26-50%, G3- 51-75%, G4- 75-99%, and G5- 100%. Variations include reporting success as thresholds &gt;25% (G2-G5), &gt;50% (G3-G5), and &gt;75% (G4-G5) repigmentation. Vitiligo Area Scoring Index (VASI), Dermatology Life Quality Index (DLQI), patient satisfaction, and the vitiligo noticeability scale are all standardized scoring systems that have been used in clinical studies. Other metrics reported include onset and maintenance of response, treatment burden, side effects, and cost-effectiveness. BSA total and quartiles of improvement are the most commonly reported metrics in studies with high-level evidence. The addition of categories of no improvement, complete clearance, spontaneous improvement, and worsening appears to enhance information collection. Collection of data using photographs or computer-assisted BSA monitoring enhances data reproducibility. Thresholds of success should include 25%, 50%, 75%, and adding 90% and 100% repigmentation. VASI represents a validated collection method, which can be modified for 50%, 75%, and 90% improvement. Newer metrics including treatment burden and cost effectiveness are emerging metrics under evaluation. J Drugs Dermatol. 2024;23(10):842-846. doi:10.36849/JDD.8049.

The Role of Inducible Nitric Oxide Synthase in Assessing the Functional Level of Coronary Artery Lesions in Chronic Coronary Syndrome.

Chronic coronary syndrome (CCS) is a long-term manifestation of coronary artery disease, marked by stable but recurring chest pain and myocardial ischemia due to the gradual buildup of atherosclerotic plaques in the coronary arteries. It is a metabolic disorder of coronary arteries characterized by oxidative stress, endothelial dysfunction, inflammation, and hyperlipidemia. The imbalance in oxidative-antioxidative status contributes to stable ischemic heart disease. Oxidative stress involves reactive oxygen and nitrogen species, leading to low-density lipoprotein (LDL) oxidation. Endothelial dysfunction, marked by reduced nitric oxide (NO) bioavailability, is an early onset of CCS, affecting vasodilation, cell proliferation, and inflammatory responses. Enzyme myeloperoxidase (MPO), traditionally considered protective, plays a dual role in initiating and progressing inflammatory diseases. MPO interacts with NO, modulating its catalytic activity. Elevated NO levels inhibit MPO through a reversible complex formation, preventing NO-induced inhibition by inducible nitric oxide synthase (iNOS). MPO also inactivates endothelial nitric oxide synthase (eNOS) and reacts with L-arginine, hindering NO synthesis. The interplay between MPO and NO significantly influences inflammation sites, impacting peroxidation rates and oxidation reactions. Peroxynitrite, a reactive species, contributes to nitration of tyrosine residues and lipid peroxidation. Mechanistic pathways suggest MPO enhances iNOS catalytic activity, influencing CCS development. iNOS, implicated in inflammation and atherosclerosis, is connected to NO regulation. This review analyzes the complex interplay of MPO, iNOS, and NO that affects plaque morphology, oxidative stress, and inflammation, contributing to atherosclerosis progression. Therefore, it is possible that the phenotypes of atherosclerotic plaques, focal and diffuse coronary artery disease, could be defined by the relationship between MPO and iNOS.

Bimekizumab efficacy and safety in Korean patients with moderate to severe plaque psoriasis: A phase 3, randomized, placebo-controlled, double-blinded study.

Bimekizumab treatment has demonstrated significant improvements in clinical outcomes in patients with moderate to severe plaque psoriasis; however, studies so far have focused on predominantly White patient populations from North America and Europe, with one smaller study in a Japanese population. Here, clinical responses, safety, and tolerability of bimekizumab treatment in Korean patients are reported. Korean patients with moderate to severe plaque psoriasis were randomized to bimekizumab 320 mg every 4 weeks (Q4W) or placebo Q4W to week 16. Co-primary efficacy end points were achievement of ≥90% improvement from baseline in the Psoriasis Area and Severity Index (PASI 90) and Investigator's Global Assessment score of 0/1 (clear/almost clear) at week 16. Secondary efficacy end points included achievement of PASI 75 at week 4 and Dermatology Life Quality Index 0/1 at week 16. Safety outcomes were also assessed. Statistical analysis of the co-primary efficacy end points was performed using a type I error rate, at a two-sided α level of 0.05. Overall, 47 Korean patients were randomized to treatment (bimekizumab: 32, placebo: 15). At week 16, bimekizumab-treated patients had significantly higher clinical responses versus placebo-treated patients (PASI 90: 81.3% vs. 0%; IGA 0/1: 87.5% vs. 0%, p < 0.001 for both). Bimekizumab showed a rapid onset of clinical response, with 75.0% of patients achieving PASI 75 by week 4 (0% in placebo patients [nominal p < 0.001]). A higher proportion of bimekizumab-treated patients achieved DLQI 0/1 at week 16 (46.9% vs. 6.7% in placebo patients, nominal p = 0.007), indicating greater improvements in health-related quality of life (HRQoL) following bimekizumab treatment. Bimekizumab was well-tolerated in Korean patients, with no new safety signals identified. Treatment with bimekizumab led to rapid improvements in clinical responses and HRQoL versus placebo in Korean patients, consistent with responses in global populations. These findings suggest that bimekizumab is an effective and well-tolerated treatment option in Korean patients with psoriasis.

Innate immune cell activation by adjuvant AS01 in human lymph node explants is age independent.

Vaccine adjuvants are thought to work by stimulating innate immunity in the draining lymph node (LN), although this has not been proven in humans. To bridge the data obtained in animals to humans, we have developed an in situ human LN explant model to investigate how adjuvants initiate immunity. Slices of explanted LNs were exposed to vaccine adjuvants and revealed responses that were not detectable in LN cell suspensions. We used this model to compare the liposome-based AS01 with its components, monophosphoryl lipid A (MPL) and QS-21, and TLR ligands. Liposomes were predominantly taken up by subcapsular sinus-lining macrophages, monocytes, and DCs. AS01 induced DC maturation and a strong proinflammatory cytokine response in intact LN slices but not in dissociated cell cultures, in contrast to R848. This suggests that the onset of the immune response to AS01 required a coordinated activation of LN cells in time and space. Consistent with the robust immune response observed in older adults with AS01-adjuvanted vaccines, the AS01 response in human LNs was independent of age, unlike the response to R848. This human LN explant model is a valuable tool for studying the mechanism of action of adjuvants in humans and for screening new formulations to streamline vaccine development.

Fecal microbial transplants as investigative tools in cancer.

The gut microbiome plays a critical role in the development, progression, and treatment of cancer. As interest in microbiome-immune-cancer interactions expands, the prevalence of fecal microbial transplant (FMT) models has increased proportionally. However, current literature does not provide adequate details or consistent approaches to allow for necessary rigor and experimental reproducibility. In this review, we evaluate key studies using FMT to investigate the relationship between the gut microbiome and various types of cancer. In addition, we will discuss the common pitfalls of these experiments and methods for improved standardization and validation as the field uses FMT with greater frequency. Finally, this review focuses on the impacts of the gut and extraintestinal microbes, prebiotics, probiotics, and postbiotics in cancer risk and response to therapy across a variety of tumor types.NEW & NOTEWORTHY The microbiome impacts the onset, progression, and therapy response of certain types of cancer. Fecal microbial transplants (FMTs) are an increasingly prevalent tool to test these mechanisms that require standardization by the field.

Delayed Summer Monsoon Onset in Response to the Cold Tongue in the South China Sea

Delayed Summer Monsoon Onset in Response to the Cold Tongue in the South China Sea

Systemic inflammation following traumatic injury and its impact on neuroinflammatory gene expression in the rodent brain

BackgroundTrauma can result in systemic inflammation that leads to organ dysfunction, but the impact on the brain, particularly following extracranial insults, has been largely overlooked.MethodsBuilding upon our prior findings, we aimed to understand the impact of systemic inflammation on neuroinflammatory gene transcripts in eight brain regions in rats exposed to (1) blast overpressure exposure [BOP], (2) cutaneous thermal injury [BU], (3) complex extremity injury, 3 hours (h) of tourniquet-induced ischemia, and hind limb amputation [CEI+tI+HLA], (4) BOP+BU or (5) BOP+CEI and delayed HLA [BOP+CEI+dHLA] at 6, 24, and 168 h post-injury (hpi).ResultsGlobally, the number and magnitude of differentially expressed genes (DEGs) correlated with injury severity, systemic inflammation markers, and end-organ damage, driven by several chemokines/cytokines (Csf3, Cxcr2, Il16, and Tgfb2), neurosteroids/prostaglandins (Cyp19a1, Ptger2, and Ptger3), and markers of neurodegeneration (Gfap, Grin2b, and Homer1). Regional neuroinflammatory activity was least impacted following BOP. Non-blast trauma (in the BU and CEI+tI+HLA groups) contributed to an earlier, robust and diverse neuroinflammatory response across brain regions (up to 2–50-fold greater than that in the BOP group), while combined trauma (in the BOP+CEI+dHLA group) significantly advanced neuroinflammation in all regions except for the cerebellum. In contrast, BOP+BU resulted in differential activity of several critical neuroinflammatory-neurodegenerative markers compared to BU. t-SNE plots of DEGs demonstrated that the onset, extent, and duration of the inflammatory response are brain region dependent. Regardless of injury type, the thalamus and hypothalamus, which are critical for maintaining homeostasis, had the most DEGs. Our results indicate that neuroinflammation in all groups progressively increased or remained at peak levels over the study duration, while markers of end-organ dysfunction decreased or otherwise resolved.ConclusionsCollectively, these findings emphasize the brain's sensitivity to mediators of systemic inflammation and provide an example of immune-brain crosstalk. Follow-on molecular and behavioral investigations are warranted to understand the short- to long-term pathophysiological consequences on the brain, particularly the mechanism of blood–brain barrier breakdown, immune cell penetration–activation, and microglial activation.

Evaluating the suitability of nitrate-nitrogen levels for post-smolt Atlantic salmon Salmo salar production in RAS with assistance from heart rate bio-loggers

Previous onsite research determined that post-smolt Atlantic salmon Salmo salar growth, health, and welfare were unaffected by exposure to 99 mg/L nitrate-nitrogen (NO3-N) in freshwater recirculating aquaculture systems (RAS). A subsequent study was conducted to determine if higher concentrations negatively impact Atlantic salmon within a similar size range. Salmon production metrics were compared in triplicate RAS with NO3-N levels increasing from 100 to 250 mg/L (“high”) vs. 50–100 mg/L NO3-N (“low”). An average feed loading rate of 2.53 kg feed/m3 makeup water/day was maintained to facilitate natural NO3-N accumulation up to 75–100 mg/L, and sodium nitrate was continuously dosed to achieve higher concentrations. All-female diploid and all-female triploid Atlantic salmon were comingled in six replicated RAS, resulting in 227 fish/tank with an initial mean weight of 0.35 kg. Six diploid salmon with surgically implanted heart rate bio-loggers were included in each RAS. Continuously logged heart rates were matched with frequently measured NO3-N levels to determine the onset of a physiological response. At the end of the 6-month study, salmon exposed to the high and low NO3-N conditions weighed 1.84 ± 0.05 and 1.91 ± 0.02 kg, respectively (p > 0.05). Diploid and triploid salmon growth rates, feed conversion ratios, maturation prevalence, survival, fin condition, and cataract scores were unaffected (p > 0.05). However, salmon heart rates were generally higher in the high NO3-N treatment after concentrations exceeded 150 mg/L NO3-N. Higher plasma chloride, hematocrit, and hemoglobin levels (p < 0.05) consistent with an adaptive response to a stressor were also measured in salmon from the high NO3-N RAS during this period. These findings suggest that NO3-N concentrations < 150 mg/L do not affect post-smolt Atlantic salmon under similar operating conditions, including freshwater RAS without denitrification technologies and water hardness >300 mg/L as CaCO3. Additional research is required to determine if higher NO3-N concentrations are suitable for Atlantic salmon production over longer exposure periods and with naturally produced NO3-N levels imparted by reduced water exchange. Feed- and nitrogen-loading rates conducive to maintaining the tested NO3-N levels are reported.

Onset and Offset of Early Dupilumab Response Using Domiciliary Monitoring in Type 2 High Unified Airway Disease.

Onset and Offset of Early Dupilumab Response Using Domiciliary Monitoring in Type 2 High Unified Airway Disease.

An intense electrical stimulus can elicit a StartReact effect but with decreased incidence and later onset of the startle reflex.

Planned actions can be triggered involuntarily by a startling acoustic stimulus (SAS), resulting in very short reaction times (RT). This phenomenon, known as the StartReact effect, is thought to result from the startle-related activation of reticular structures. However, other sensory modalities also can elicit a reflexive startle response. Here, we assessed the effectiveness of an intense startling electric stimulus (SES) in eliciting the StartReact effect as compared to a SAS. We tested SES intensities at 15 and 25 times the perceptual threshold of each participant, as well as SAS intensities of 114 dB and 120 dB. The electrical stimulation electrodes were placed over short head of the biceps brachii on the arm not involved in the task. Intense electric and acoustic stimuli were presented on 20% of the trials in a simple RT paradigm requiring a targeted ballistic wrist extension movement. The proportion of trials showing short latency (≤ 120 ms) startle reflex-related activation in sternocleidomastoid was significantly lower on intense electrical stimulus trials compared to intense acoustic trials, and the startle response onset occurred significantly later on SES trials compared to SAS. However, when a startle reflex was observed, RTs related to the prepared movement were facilitated to a similar extent for both SES and SAS conditions, suggesting that the accelerated response latency associated with the StartReact effect is independent of stimulus type.