Peripheral Responses Research Articles

Building Narratives Through Empathy: The Role of Empathy Mechanisms and Associative Thinking in Creative Writing

ABSTRACTEmpathy emerges as a pivotal skill in creative writing, yet previous studies lack an understanding of empathy's multidimensionality and specific impact of its facets on the capacity to generate narrative stories. This cross‐sectional study delved into the various cognitive and affective empathy facets—that is, perspective‐taking, online simulation, emotion contagion, proximal responsivity, and peripheral responsivity—and their contributions to creative writing. Further, it examined the mediating effects of associative thinking—conceptualized as a common empathy‐creativity resource—on the relationship between empathy facets and creative writing. Two‐hundred twenty participants (university students) completed performance‐based tasks and self‐report measures of creative writing, associative thinking, and empathy. A latent mediation model implemented in Structural Equation Modeling indicated two effects of empathy facets on creative writing, with perspective‐taking emerging as a positive predictor. Additionally, peripheral responsivity (i.e., affect sharing in indirect contexts) exhibited an indirect positive influence on creative writing, mediated by associative thinking. In summary, associative thinking appears to be an important ingredient in both empathy and creative writing, while cognitive empathy, specifically intuitive perspective‐taking, contributes significantly to creative writing skills. Future studies should further explore these connections and their causalities, possibly using experimental or longitudinal approaches.

Quantitative proteomics and multi-omics analysis identifies potential biomarkers and the underlying pathological molecular networks in Chinese patients with multiple sclerosis

Multiple sclerosis (MS) is an autoimmune disorder caused by chronic inflammatory reactions in the central nervous system. Currently, little is known about the changes of plasma proteomic profiles in Chinese patients with MS (CpwMS) and its relationship with the altered profiles of multi-omics such as metabolomics and gut microbiome, as well as potential molecular networks that underlie the etiology of MS. To uncover the characteristics of proteomics landscape and potential multi-omics interaction networks in CpwMS, Plasma samples were collected from 22 CpwMS and 22 healthy controls (HCs) and analyzed using a Tandem Mass Tag (TMT)-based quantitative proteomics approach. Our results showed that the plasma proteomics pattern was significantly different in CpwMS compared to HCs. A total of 90 differentially expressed proteins (DEPs), such as LAMP1 and FCG2A, were identified in CpwMS plasma comparing to HCs. Furthermore, we also observed extensive and significant correlations between the altered proteomic profiles and the changes of metabolome, gut microbiome, as well as altered immunoinflammatory responses in MS-affected patients. For instance, the level of LAMP1 and ERN1 were significantly and positively correlated with the concentrations of metabolite L-glutamic acid and pro-inflammatory factor IL-17 (Padj < 0.05). However, they were negatively correlated with the amounts of other metabolites such as L-tyrosine and sphingosine 1-phosphate, as well as the concentrations of IL-8 and MIP-1α. This study outlined the underlying multi-omics integrated mechanisms that might regulate peripheral immunoinflammatory responses and MS progression. These findings are potentially helpful for developing new assisting diagnostic biomarker and therapeutic strategies for MS.

The role of neutrophils in pain: systematic review and meta-analysis of animal studies.

The peripheral inflammatory response is an attractive therapeutic target for pain treatment. Neutrophils are the first circulating inflammatory cells recruited to sites of injury, but their contribution to pain outcomes is unclear. We performed a systematic review and meta-analysis of original preclinical studies, which evaluated the effect of preemptive neutrophil depletion on pain outcomes (PROSPERO registration number: CRD42022364004). Literature search (PubMed, January 19, 2023) identified 49 articles, which were meta-analyzed using a random-effects model. The risk of bias was evaluated using SYRCLE's tool. The pooled effect considering all studies showed that neutrophil depletion induced a consistent pain reduction. Inflammatory, joint, neuropathic, and visceral pain showed significant pain alleviation by neutrophil depletion with medium-large effect sizes. However, muscle and postoperative pain were not significantly alleviated by neutrophil depletion. Further analysis showed a differential contribution of neutrophils to pain outcomes. Neutrophils had a higher impact on mechanical hyperalgesia, followed by nociceptive behaviors and mechanical allodynia, with a smaller contribution to thermal hyperalgesia. Interspecies (mice or rats) differences were not appreciated. Analyses regarding intervention unveiled a lower pain reduction for some commonly used methods for neutrophil depletion, such as injection of antineutrophil serum or an anti-Gr-1 antibody, than for other agents such as administration of an anti-Ly6G antibody, fucoidan, vinblastine, CXCR1/2 inhibitors, and etanercept. In conclusion, the contribution of neutrophils to pain depends on pain etiology (experimental model), pain outcome, and the neutrophil depletion strategy. Further research is needed to improve our understanding on the mechanisms of these differences.

SARS-CoV-2 XBB.1.5 mRNA booster vaccination elicits limited mucosal immunity.

Current COVID-19 vaccines provide robust protection against severe disease but minimal protection against acquisition of infection. Intramuscularly administered COVID-19 vaccines induce robust serum neutralizing antibodies (NAbs), but their ability to boost mucosal immune responses remains to be determined. In this study, we show that the XBB.1.5 messenger RNA (mRNA) boosters result in increased serum neutralization to multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in humans, including the dominant circulating variant JN.1. In contrast, we found that the XBB.1.5 mRNA booster did not augment mucosal NAbs or mucosal IgA responses, although acute SARS-CoV-2 XBB infection substantially increased mucosal antibody responses. These data demonstrate that current XBB.1.5 mRNA boosters substantially enhance peripheral antibody responses but do not robustly increase mucosal antibody responses. Our data highlight a separation between the peripheral and mucosal immune systems in humans and emphasize the importance of developing next-generation vaccines to augment mucosal immunity to protect against respiratory virus infections.

Differences in Cytokine Expression at Baseline and in Response to Mineral Stimulation by Peripheral Blood Mononuclear Cells from Podoconiosis Cases and Healthy Control Individuals

Epidemiological, histological, and immunogenetic studies suggest that podoconiosis (a non-infectious tropical lymphoedema affecting approximately 4 million people globally) is an HLA class II-associated inflammatory condition that develops in response to an unknown trigger found in volcanic red clay soils. Silicate particles of the kaolinite and aluminum types have been identified in femoral lymph node biopsy samples from endemic area residents, suggesting a possible role in the pathogenesis of podoconiosis. We measured in vitro peripheral blood mononuclear cell cytokine responses (TNF-α, IL-1β, and IFN-γ) to stimulation with the minerals kaolinite, chlorite, and beryllium sulfate (all at 100 µM) using ELISA. Real time PCR was used to measure gene expression of signature cytokines in fresh whole blood, comparing podoconiosis patients and endemic healthy controls. Our results showed that the levels of TNF-α and IL-1β from in vitro cell cultures were significantly higher in unstimulated samples from patients compared to controls (p = 0.04 and p = 0.005, respectively). The minerals kaolinite and chlorite induced two and three-fold higher levels of IL-1β following 24 h of stimulation in healthy controls compared to patients, respectively. We did not find significant differences in mRNA expression of the cytokine genes assayed, though a slight fold increment in IL-1β and TGF-β was observed. In conclusion, our data suggest that the immune system is in a state of persistent activation in vivo in podoconiosis patients, and additional studies of immune regulation and exhaustion are needed to further characterize immune dysfunction in the pathogenesis of the disease. A better understanding of the underlying processes could lead to the development of a ‘biosignature’ detectable in the early reversible stages that could ultimately contribute to the elimination of this preventable, disabling, neglected tropical disease.

Novelties on Neuroinflammation in Alzheimer's Disease-Focus on Gut and Oral Microbiota Involvement.

Recent studies underscore the role of gut and oral microbiota in influencing neuroinflammation through the microbiota-gut-brain axis, including in Alzheimer's disease (AD). This review aims to provide a comprehensive synthesis of recent findings on the involvement of gut and oral microbiota in the neuroinflammatory processes associated with AD, emphasizing novel insights and therapeutic implications. This review reveals that dysbiosis in AD patients' gut and oral microbiota is linked to heightened peripheral and central inflammatory responses. Specific bacterial taxa, such as Bacteroides and Firmicutes in the gut, as well as Porphyromonas gingivalis in the oral cavity, are notably altered in AD, leading to significant changes in microglial activation and cytokine production. Gut microbiota alterations are associated with increased intestinal permeability, facilitating the translocation of endotoxins like lipopolysaccharides (LPS) into the bloodstream and exacerbating neuroinflammation by activating the brain's toll-like receptor 4 (TLR4) pathways. Furthermore, microbiota-derived metabolites, including short-chain fatty acids (SCFAs) and amyloid peptides, can cross the blood-brain barrier and modulate neuroinflammatory responses. While microbial amyloids may contribute to amyloid-beta aggregation in the brain, certain SCFAs like butyrate exhibit anti-inflammatory properties, suggesting a potential therapeutic avenue to mitigate neuroinflammation. This review not only highlights the critical role of microbiota in AD pathology but also offers a ray of hope by suggesting that modulating gut and oral microbiota could represent a novel therapeutic strategy for reducing neuroinflammation and slowing disease progression.

Effect of Level and Frequency of Forward Masker on Auditory Brainstem Response.

Forward masking (FM) is characterized by the perception of a signal being reduced or wholly masked due to a preceding sound (masker) of the same or different frequencies that offers a challenge for the auditory system to resolve. Considering that the off-frequency masker is expected to undergo linear processing compared to the on-frequency masker at the signal place, it reflects the peripheral auditory systems' compressive response. Thus, the present study focused on employing FM electrophysiological analogous such as auditory brainstem responses (ABR) to the behavioral masking experiments to objectively measure the frequency and level of processing in the auditory system, from the periphery to the brainstem level. The study was an observational research on 21 female volunteers. ABR was obtained using a tone-on-tone FM paradigm for 1000- and 4000-Hz probe stimuli. An experiment used two forward maskers, on-frequency and off-frequency, with varying levels from 50 to 70 dB SPL. A progressive shift for Vth peak latency and reduction in response amplitude was observed in proportion to the increase of masker level for both the probe stimuli and the masking experiments. However, ABR responses in neither masking condition were observed to differ between 60 and 70 dB SPL. FM ABR experiments are an assessment tool for estimating frequency and level processing in the auditory system, providing good efficiency, reliability, and less subject bias compared to behavioral measures.

Hypoxic Effects of Heroin and Fentanyl and Their Basic Physiological Mechanisms.

Respiratory depression that diminishes oxygen delivery to the brain is the most dangerous effect of opioid drugs. While plethysmography is a valuable tool to examine drug-induced changes in respiration, the primary cause of brain abnormalities induced by opioids is the global decrease in brain oxygen levels. The primary goal of this review is to provide an overview and discussion on fluctuations in brain oxygen levels induced by opioids, with a focus on heroin and fentanyl. To evaluate fluctuations in brain oxygen levels we used oxygen sensors coupled with high-speed amperometry in awake, freely moving rats. First, we provide an overview of brain oxygen responses induced by natural physiological stimuli and discuss the mechanisms regulating oxygen entry into brain tissue. Then, we present data on brain oxygen responses induced by heroin and fentanyl and review their underlying mechanisms. These data allowed us to compare the effects of these drugs on brain oxygen regarding their latency, potency, time-dependency, and potential lethality at high doses as well as their relationships with peripheral oxygen responses. We also discuss data on the effects of naloxone on brain oxygen responses induced by heroin and fentanyl in the paradigms of both the pre-treatment and treatment, when naloxone is administered at different times after the primary opioid drug. Although most data discussed were obtained in rats, they may have clinical relevance for understanding the mechanisms underlying the physiological effects of opioids and developing rational treatment strategies to decrease acute lethality and long-term health complications of opioid misuse.

APOE4 carriers display loss of anticipatory cerebral vascular regulation over AD progression.

Maintenance of cerebral blood flow during orthostasis is impaired with aging and associated with cognitive decline, but the effect of Apolipoprotein 4-allele (APOE4) is unknown. Older adults (n=108) (APOE4 carriers, n=47; noncarriers, n=61) diagnosed as cognitively-normal (NC), MCI, or AD participated. Middle cerebral artery blood velocity (MCAv), assessed using Transcranial Doppler ultrasound, and beat-to-beat mean arterial blood pressure (MAP) were continuously recorded during a sit-to-stand transition. Anticipatory and orthostatic-induced MCAv and MAP responses were compared between genotypes and across disease progression. Cognitively-normal APOE4 carriers showed greater anticipatory MCAv increase, greater MCAv decrease with orthostasis, and shorter latency of peripheral MAP responses to orthostasis compared to noncarriers. MCAv and MAP responses were delayed and attenuated across the APOE4 disease progression, with no differences between genotypes in MCI and AD. APOE4 carriers and noncarriers present with distinct phenotypes of cerebral vascular dysfunction during hemodynamic orthostatic challenge. Unique cerebral and peripheral vascular compensation observed in APOE4 carriers may be lost as AD progresses.

Slack potassium channels in spinal dorsal horn neurons control neuropathic pain and acute itch.

The sodium-activated potassium channel Slack (KNa1.1, Kcnt1) plays a critical role in tuning neuronal excitability. Previous studies have revealed that Slack is expressed in neurons of the superficial dorsal horn of the spinal cord. However, the precise role of Slack in spinal dorsal horn neurons is unclear. In this study, we used mice in which Slack is conditionally ablated in spinal dorsal horn neurons (Lbx1-Slack-/- mice) and analyzed their behaviors in various models of pain and itch. Lbx1-Slack-/- mice exhibited increased neuropathic pain behavior after peripheral nerve injury but normal responses in a model of inflammatory pain. Unexpectedly, Lbx1-Slack-/- mice demonstrated increased scratching after intradermal injection of chloroquine, LY344864, and histamine. Moreover, neuromedin B receptors are coexpressed with Slack in the dorsal horn, and scratching after intrathecal delivery of neuromedin B was increased in Lbx1-Slack-/- mice. Our study provides in vivo evidence that Slack expressed in spinal dorsal horn neurons inhibits nerve injury-induced allodynia and acute itch induced by various pruritogens.

6415 Resistance to Thyroid Hormone -A Challenge to Manage

Abstract Disclosure: A. Altaf: None. F. Iqbal: None. E. Hamoudeh: None. C. Coyne: None. K. Anne: None. L. Buckley: None. Background: Resistance to thyroid hormone (RTH) or Refetoff syndrome was first introduced in 1967. It is an autosomal dominant or recessive genetic disease with a mutation in the thyroid hormone receptorβ (THR-β) gene or the thyroid hormone receptorα (THR-α) gene. The distinguishing biochemical feature of RTHβ is an elevated level of circulating free thyroid hormones with normal or high TSH concentration and decreased peripheral tissue response to thyroid hormone. Common signs and symptoms in patients with RTHβ are short stature, attention deficit disorder, and resting tachycardia and many patients might be asymptomatic. Case: We report a case of a 36-year-old patient with past medical history of congenital bilateral hearing loss, atrial fibrillation, CHF, and slow learning/comprehending who presented to the ER with shortness of breath and atrial fibrillation with tachycardia. Admission labs revealed elevated TSH 3.9, elevated fT4 3.28, and elevated TT3 205. He reported that for the past year, he has been on levothyroxine 50mcg for abnormal TSH. Levothyroxine was stopped and the patient was discharged on methimazole 10mg daily. Further workup revealed negative thyroglobulin and thyroid peroxidase antibodies. Thyroid ultrasound with Doppler demonstrated a mildly hypervascular thyroid gland without evidence of nodules. Brain MRI was negative for any pituitary abnormalities. HAMA testing continued to show elevated TSH. Patient was followed by cardiology and due to continued atrial fibrillation, had multiple cardioversions and was managed on a beta blocker. Due to his atrial fibrillation, endocrinology service continued his methimazole till his genetic testing came positive for an autosomal dominant heterozygous pathogenic mutation in THRB c.1373 T&amp;gt;C (p. Val458Ala). His thyroid hormones and TSH continue to be elevated. Currently, he is not on thyroid medication and getting monitored. The need for multiple cardioversions for atrial fibrillation in this patient makes resistance to thyroid hormone management challenging. Discussion: Hyperthyroidism is commonly mistaken for RTH. However, the lack of TSH suppression should be further investigated. Most patients with RTHβ are adequately compensated by the increased endogenous supply of thyroid hormone showing increased serum fT3 and fT4 levels and normal or near normal TSH levels. Beta Blockers like atenolol cannot inhibit the conversion of T4 to T3 and can be used for RTHβ with tachycardia. Triiodothyroaceticacid (TRIAC) or dextrothyroxine (DT4) have also been used to treat thyrotoxicosis. In summary, treatment for RTHβ remains a challenge for clinicians, especially in patients with atrial fibrillation and many patients are misdiagnosed and managed as hyperthyroidism. Presentation: 6/3/2024

Relationship between peripheral and intracoronary blood flow in patients with angina and nonobstructive coronary arteries.

Coronary vasomotor dysfunction, an important underlying cause of angina and nonobstructive coronary arteries (ANOCA), encompassing coronary vasospasm, coronary endothelial dysfunction, and/or coronary microvascular dysfunction, is clinically assessed by invasive coronary function testing (ICFT). As ICFT imposes a high burden on patients and carries risks, developing noninvasive alternatives is important. We evaluated whether coronary vasomotor dysfunction is a component of systemic microvascular endothelial and smooth muscle dysfunction and can be detected using laser speckle contrast analysis (LASCA). Forty-three consecutive patients with ANOCA underwent ICFT, with intracoronary acetylcholine, adenosine, and flow measurements, to assess coronary vasomotor dysfunction. Cutaneous microvascular function was assessed using LASCA in the forearm, combined with vasodilators acetylcholine, sodium nitroprusside, and insulin and using EndoPAT, by measuring the reactive hyperemia index (RHI). Of the 43 included patients with ANOCA (79% women, 59 ± 9 yr old), 38 patients had coronary vasomotor dysfunction, including 28 with coronary vasospasm, 26 with coronary endothelial dysfunction, and 18 with coronary microvascular dysfunction, with overlapping endotypes. Patients with and without coronary vasomotor dysfunction had similar peripheral flow responses to acetylcholine, insulin, and RHI. In contrast, coronary vasomotor dysfunction was associated with lower peripheral flow responses to sodium nitroprusside (P < 0.001). An absolute flow response to sodium nitroprusside of 83.95 APU resulted in 86.1% sensitivity and 80.0% specificity for coronary vasomotor dysfunction (area under the ROC curve, 0.883; P = 0.006). In conclusion, this study provides evidence of systemic vascular smooth muscle dysfunction in patients with ANOCA with coronary vasomotor dysfunction and the diagnostic value of peripheral microvascular function testing as a noninvasive tool for detecting coronary vasomotor dysfunction.NEW & NOTEWORTHY This study provides proof of concept that assessment of the peripheral vasculature, particularly vascular smooth muscle cells measured using the LASCA technology holds potential as a noninvasive tool for detecting coronary vasomotor dysfunction. This finding highlights the potential of the LASCA technology in, for example, medication studies for coronary vasomotor dysfunction, especially when investigating whether medication improves vascular function, as repeated peripheral measurements are less invasive than invasive coronary function testing, the current gold standard.

Oocyte donation pregnancies with high fetal-maternal immunogenetic dissimilarity show alterations in the maternal peripheral immunoregulatory response

Oocyte donation (OD) pregnancies result in increased fetal-maternal immunogenetic dissimilarity due to paternal and donor-derived genes. Higher fetal-maternal HLA mismatches are correlated with preeclampsia. Therefore, this study explored the maternal immune response, focusing on regulatory T cells (Tregs), during low versus high allogeneic pregnancies, and healthy versus preeclamptic OD pregnancies. Ten healthy and five preeclamptic OD pregnancies were included. Maternal peripheral blood was collected at different stages of pregnancy. Fetal-maternal HLA mismatches were determined, and immunophenotyping of peripheral blood mononuclear cells was conducted using a 22-colour spectral flow cytometry panel. Cytokines and hormones were detected in maternal plasma using ELISA and Luminex assays. The findings show similarities, but also distinct differences between low and high allogeneic healthy OD pregnancies. Early high allogeneic OD pregnancy showed reduction in Tregs, and CD8+ T cells, alongside lower percentage of effector/memory Tregs expressing PD-1 and Helios. Additionally, high allogeneic OD pregnancies showed increased IL-6 and progesterone in the first trimester. These variations suggest a different mode of immune regulation in early high allogeneic OD pregnancies, possibly to maintain healthy pregnancy. Further comparative analyses revealed reduced CD45RO+CTLA-4+ Tregs and increased latent TGF-β1 and -β2 levels in early preeclamptic compared to healthy OD pregnancy. Late-stage preeclamptic OD pregnancies exhibited higher frequencies of CD45RO+TIGIT+ Tregs and higher levels of TNFα, indicating both a regulatory and pro-inflammatory environment. Overall, this study sheds light on the course of various immunoregulatory key players in OD pregnancy, and expands knowledge on maternal tolerance in this particular type of pregnancy.

P3.08E.03 Dynamics of Peripheral Blood Inflammatory Index Predict Response of Neoadjuvant Immunotherapy in Non-Small Cell Lung Cancer

P3.08E.03 Dynamics of Peripheral Blood Inflammatory Index Predict Response of Neoadjuvant Immunotherapy in Non-Small Cell Lung Cancer

Peripheral Blood IFN Responses to Toll-Like Receptor 1/2 Signaling Associate with Longer Survival in Men with Metastatic Prostate Cancer Treated with Sipuleucel-T.

The identification of factors that determine successful cancer immunotherapy, particularly in refractory tumor types like mCRPC, is urgently needed: both to identify patients that may benefit from such therapies and to uncover routes to sensitize patients with cancer to immunotherapy. Our work links functional peripheral immune responses with race and survival after cellular immunotherapy in men with mCRPC.

Abnormal resting-state functional connectivity of hippocampal subregions in type 2 diabetes mellitus-associated cognitive decline.

Type 2 diabetes mellitus (T2DM) over time predisposes to inflammatory responses and abnormalities in functional brain networks that damage learning, memory, or executive function. The hippocampus is a key region often reporting connectivity abnormalities in memory disorders. Here, we investigated peripheral inflammatory responses and resting-state functional connectivity (RSFC) changes characterized of hippocampal subregions in type 2 diabetes-associated cognitive decline (T2DACD). The study included 16 patients with T2DM, 16 patients with T2DACD and 25 healthy controls (HCs). Subjects were assessed for cognitive performance, tested for the expression of inflammatory factors IL-6, IL-10 and TNF-α in peripheral serum, underwent resting-state functional magnetic resonance imaging scans, and analyzed for RSFC using the hippocampal subregions as seeds. We also calculated the correlation between cognitive performance and RSFC of hippocampal subregion, and analyzed the significantly altered RSFC values of T2DACD for Receiver Operating Characteristic (ROC) analysis. T2DACD patients showed a decline in their ability to complete cognitive assessment scales and experimental paradigms, and T2DM did not show abnormal cognitive performance. IL-6 expression was increased in peripheral serum in both T2DACD and T2DM. Compared with HCs, T2DACD showed abnormalities RSFC of the left anterior hippocampus with left precentral gyrus and left angular gyrus. T2DM showed abnormalities RSFC of the left middle hippocampus with right medial frontal gyrus, right anterior and middle hippocampus with left precuneus, left anterior hippocampus with right precuneus and right posterior middle temporal gyrus. Compared with T2DM, T2DACD showed abnormalities RSFC of the left posterior hippocampus and right middle hippocampus with left precuneus. In addition, RSFC in the left posterior hippocampus with left precuneus of T2DACD was positively correlated with Flanker conflict response time (r=0.766, P=0.001). In the ROC analysis, the significantly altered RSFC values of T2DACD achieved significant performance. T2DACD showed a significant decrease in attentional inhibition and working memory, peripheral pro-inflammatory response increased, and abnormalities RSFC of the hippocampal subregions with default mode network and sensory-motor network. T2DM did not show a significant cognitive decline, but peripheral pro-inflammatory response increased and abnormalities RSFC of the hippocampus subregions occurred in the brain. In addition, the left precuneus may be a key brain region in the conversion of T2DM to T2DACD. The results of this study may provide a basis for the preliminary diagnosis of T2DACD.

Exploring Adaptive Virtual Reality Systems Used in Interventions for Children With Autism Spectrum Disorder: Systematic Review.

Adaptive systems serve to personalize interventions or training based on the user's needs and performance. The adaptation techniques rely on an underlying engine responsible for processing incoming data and generating tailored responses. Adaptive virtual reality (VR) systems have proven to be efficient in data monitoring and manipulation, as well as in their ability to transfer learning outcomes to the real world. In recent years, there has been significant interest in applying these systems to improve deficits associated with autism spectrum disorder (ASD). This is driven by the heterogeneity of symptoms among the population affected, highlighting the need for early customized interventions that target each individual's specific symptom configuration. Recognizing these technology-driven therapeutic tools as efficient solutions, this systematic review aims to explore the application of adaptive VR systems in interventions for young individuals with ASD. An extensive search was conducted across 3 different databases-PubMed Central, Scopus, and Web of Science-to identify relevant studies from approximately the past decade. Each author independently screened the included studies to assess the risk of bias. Studies satisfying the following inclusion criteria were selected: (1) the experimental tasks were delivered via a VR system, (2) system adaptation was automated, (3) the VR system was designed for intervention or training of ASD symptoms, (4) participants' ages ranged from 6 to 19 years, (5) the sample included at least 1 group with ASD, and (6) the adaptation strategy was thoroughly explained. Relevant information extracted from the studies included the sample size and mean age, the study's objectives, the skill trained, the implemented device, the adaptive strategy used, the engine techniques, and the signal used to adapt the systems. Overall, a total of 10 articles were included, involving 129 participants, 76% of whom had ASD. The studies included level switching (7/10, 70%), adaptive feedback strategies (9/10, 90%), and weighing the choice between a machine learning (ML) adaptive engine (3/10, 30%) and a non-ML adaptive engine (8/10, 80%). Adaptation signals ranged from explicit behavioral indicators (6/10, 60%), such as task performance, to implicit biosignals, such as motor movements, eye gaze, speech, and peripheral physiological responses (7/10, 70%). The findings reveal promising trends in the field, suggesting that automated VR systems leveraging real-time progression level switching and verbal feedback driven by non-ML techniques using explicit or, better yet, implicit signal processing have the potential to enhance interventions for young individuals with ASD. The limitations discussed mainly stem from the fact that no technological or automated tools were used to handle data, potentially introducing bias due to human error.

Calorie restriction increases the sensitivity of progeroid Ercc1Δ/- mice to acute (neuro)inflammation.

Hospitalized elderly patients frequently suffer from delirium, especially in the context of sepsis-associated encephalopathy. Current treatments of delirium are merely symptomatic. Calorie restriction (CR) is both a promising strategy to protect against sepsis and has beneficial effects on aging-induced neurodegeneration. In this study, we investigated whether six weeks of 30% CR had protective effects on lipopolysaccharide (LPS) induced (neuro)inflammation in wild-type (WT) and progeroid mice deficient in the DNA excision-repair gene Ercc1 (Ercc1Δ/-). While CR did not affect the LPS-induced inflammatory response in WT mice, CR exaggerated the peripheral inflammatory response in Ercc1Δ/- mice, as evidenced by an increase of pro-inflammatory serum cytokines (TNF-α, IL-1β, and IFN-γ) and kidney injury marker Ngal. Neuroinflammatory effects were assessed by RNA-sequencing of isolated microglia. Similarly, CR did not affect microglia gene expression in WT mice, but increased neuroinflammation-associated gene expression in Ercc1Δ/- mice. In conclusion, CR increases the peripheral and brain inflammatory response of Ercc1Δ/- mice to a systemic inflammatory stimulus.

AGTR1 variant rs2638355 is associated with increased salt sensitivity of blood pressure: a female-specific effect in individuals from the HyperPath cohort.

Salt-sensitive hypertension (SSH) affects approximately half of the hypertensive population, increasing the risk of vascular complications. The underlying pathophysiological mechanisms of SSH remain complex and need to be fully elucidated. Our prior research has identified genetic factors contributing to the salt sensitivity of blood pressure (SSBP), particularly involving genes regulating volume and blood pressure. We also observed enhanced peripheral vascular response to angiotensin II in humans with salt-sensitive hypertension. Given the pivotal role of the angiotensin II receptor type-1 (AT1R or AGTR1) in blood pressure and intravascular volume regulation, we hypothesized a genetic association between AGTR1 and SSBP. Our study involved 240 individuals of European ancestry from the HyperPATH cohort, examined under restricted and high dietary salt conditions. We employed a tagging single nucleotide variant approach to genotype participants at AGTR1. Our regression model revealed a significant association between the rs2638355 (A/G) variant and salt-sensitive systolic blood pressure (SS-SBP), and rs2638355 increased AGTR1 gene expression. Notably, carriers of the risk-allele of the noncoding regulatory variant rs2638355 exhibited higher systolic blood pressure under high salt diet conditions than nonrisk allele individuals. A sex-stratified analysis showed this salt-driven effect on systolic blood pressure was significant only in females, underscoring the role of dietary salt in modulating genetic effects in this group. Furthermore, a restricted salt diet in these individuals diminished blood pressure and negated the blood pressure phenotype-genotype association. Overall, our findings could aid in pinpointing individuals with salt-sensitive blood pressure among hypertensive patients, especially considering dietary and sex-specific factors.

Central and peripheral physiological responses to decision making in hoarding disorder

Individuals with hoarding disorder (HD) have difficulty parting with personal possessions, which leads to the accumulation of excessive clutter. According to a proposed biphasic neurobiological model, HD is characterized by blunted central and peripheral nervous system activity at rest and during neutral (non-discarding) decisions, and exaggerated activity during decision-making about discarding personal possessions. Here, we compared the error-related negativity (ERN) and psychophysiological responses (skin conductance, heart rate and heart rate variability, and end tidal CO2) during neutral and discarding-related decisions in 26 individuals with HD, 37 control participants with anxiety disorders, and 28 healthy control participants without psychiatric diagnoses. We also compared alpha asymmetry between the HD and control groups during a baseline resting phase. Participants completed a series of Go/No Go decision-making tasks, one involving choosing certain shapes (neutral task) and the other involving choosing images of newspapers to imaginally “discard” (discarding task). While all participants showed expected increased frontal negativity to commission of an error, contrary to hypotheses, there were no group differences in the ERN or any psychophysiological measures. Alpha asymmetry at rest also did not differ between groups. The findings suggest that the ERN and psychophysiological responses may not differ in individuals with HD during simulated discarding decisions relative to control participants, although the null results may be explained by methodological challenges in using Go/No Go tasks as discarding tasks. Future replication and extension of these results will be needed using ecologically valid discarding tasks.