Somatic Responses Research Articles

High-fructose intake-induced dyslipidemia and oxidative stress accompanied by hippocampal dysfunctions in hypertensive but not hypertriacylglycerolemic rats.

A high-fructose intake is metabolically analogous to a high-fat diet. The impact of highfructose intake was investigated in spontaneously hypertensive (SHR) and hypertriacylglycerolemic (HTG) rats to find out the impact of which risk factor of metabolic syndrome - hypertension or hypertriacylglycerolemia - will cause more complications. Rats were fed a standard or a fructose diet (F60) with 60% of added fructose for 5 weeks. The F60 diet increased the total serum cholesterol content of both HTG-F60 and SHR-F60 rats. Further, in SHR-F60 it increased serum triacylglycerols, TBARS in the liver, a specific activity of NAGA in the kidney, aggravated glucose tolerance, deteriorated synaptic plasticity, and reduced somatic and dendritic responses in the hippocampus. SHR rats were more sensitive to the F60 diet, suggesting that hypertension along with a high-fructose intake result in a more pronounced disorder compared to hypertriacylglycerolemia. This work wants to draw attention to fructose-induced health risks associated with hypertension.

Influence of alternating electromagnetic field on somatic reactions of pathogens

Outbreaks of new infectious diseases are occurring with increasing frequency and consequences, including wildlife diseases and zoonoses. The increasing emergence of infectious pathogens has many causes, all related to increasing anthropogenic impacts on nature. Some studies show how exposure to fields can enhance or reduce cellular activity, with possible application implications in the field of biotechnology. The effects of magnetic fields at the cellular level in microbial cells may include cell viability and proliferation, apoptosis, morphological changes, changes in metabolic and enzymatic activities, changes in ion transport into the cell, and genotoxicity and changes in gene expression. The aim of this study was to determine the differences in the somatic response of pathogen cells used in biotechnological processes exposed to an alternating electromagnetic field with a constant frequency of 50 Hz in three variants of exposure time. It was found that stimulation with an alternating electromagnetic field affects the somatic responses of microorganisms represented by their growth. The responses of the studied microorganisms are also related to their morphology.

The genetic and somatic expressions of trauma: A review of pathology and treatment

Traumatic experiences change one’s orientation to self, others, and the environment. In the wake of trauma, survivors are besieged by powerful emotions, sensations, and memories as they adapt to a new and unwanted reality. Chronic recall of disorganized traumatic memory engenders a myriad of unpleasant psychological and somatic responses. Confrontation with an overwhelming experience from which escape is not possible will challenge and change the way the brain communicates- both with itself and other parts of the body. While quickly adapting to environment and experience, what the brain is designed to do, in the presence of trauma, the brain is concurrently trying to find a way to internally escape the external environment. The symptoms that present secondary to PTSD are compulsory and biological, making traditional psychotherapy practices limiting as they do not resolve neurological conflicts in brain synapses or brain communication. This work explores the implications of trauma, innovative treatment modalities, and the genetic expression of PTSD.

Adult T-Cell Leukemia/Lymphoma Diagnosed in North American Is Characterized By a Requirement for BCL6 and a Cell Cycle Program Associated with DNA Replication Stress

Adult T-cell leukemia/lymphoma (ATLL) is a rare and aggressive disease of malignant CD4+ T cells that develops in human T-lymphotropic virus-1 (HTLV-1) carriers. Patients diagnosed with ATLL have the worst survival among all peripheral T-cell lymphomas. At the moment, no outcome-changing targeted therapy is available for ATLL highlighting an urgent need for in-depth understanding of its pathogenesis and development of new treatment strategies. We and others have shown that ATLLs diagnosed in the Japanese (J-ATLL) and North American (NA-ATLL) patients have very different clinical behavior, with the NA-ATLL variant characterized by a higher rate of chemo-refractory disease and worse prognosis. Differences are also seen in the somatic mutation patterns and responsiveness to an immune checkpoint blockade therapy, Nivolumab. To explore additional aspects of ATLL biology where NA-ATLL and J-ATLL may exhibit distinct characteristics, we examined immunophenotypic features of 5 J-ATLL cell lines and cultures from 7 NA-ATLL patients using a panel of 17 flow cytometry markers. Our results show that, while the J-ATLL cell lines have a surface marker profile resembling classic regulatory T (Treg) cells, NA-ATLL samples are more similar to follicular T regulatory (Tfr) cells. This conclusion is also supported by GSEA analysis of of bulk RNA-seq. Consistent with a Tfr-like phenotype, NA-ATLL samples are characterized by more frequent expression of PD-1 and variable levels of BCL6. We also detected BCL6 in patient biopsy samples by IHC. Interestingly, although some J-ATLL cell lines express BCL6 as well, only NA-ATLL but not J-ATLL cell lines are sensitive to the BCL6-specific inhibitor FX1. Inactivating BCL6 by either FX1 treatment or siRNA-mediated BCL6 knock-down in NA-ATLL cells triggered rapid activation of the DNA damage response and death of S phase cells. These results suggest that in transformed NA-ATLL cells, BCL6 promotes survival by suppressing replication stress. Our experiments also demonstrate that compared to J-ATLL cell lines, NA-ATLL cell lines are more sensitive to S phase-targeting drugs including Wee1i (AZD-1775), ATRi (AZD-6738), and PARPi (Olaparib). These results support the concept that the cell cycle S phase is an Achilles’ Heel of NA-ATLL cells and an attractive therapeutic target. In summary, despite the involvement of the same HTLV-1 subtype (HTLV-1a) in ATLLs diagnosed in Japan and North America, these two ATLL variants have distinct features in clinical behavior, mutational landscape, and immunophenotype. Our experiments described here point to additional differences in the cell cycle program and roles played by BCL6. Further studies are needed to fully characterize the cellular phenotype of NA-ATLL and develop S phase-based targeting strategies to treat this devastating disease.

Pharmacotypes across the Genomic Landscape of Pediatric Acute Lymphoblastic Leukemia and Impact on Treatment Response

INTRODUCTION The current paradigm of risk stratification in childhood acute lymphoblastic leukemia (ALL) utilizes a combination of clinical features, leukemia somatic genomics and early treatment response as measured by minimal residual disease (MRD). Although ALL subtypes and MRD are strongly related to treatment outcomes, the pharmacological basis of their prognostic impact remains incompletely understood. Therefore, we sought to characterize pharmacotypes (drug sensitivities) across the complete spectrum of ALL molecular subtypes and determine their association with in vivo treatment response and survival outcomes. METHODS This was a prospective study of 805 children with newly-diagnosed ALL from Total Therapy XV, XVI, and XVII trials at St Jude Children's Research Hospital. We performed ex vivo pharmacotyping of 18 drugs on primary ALL diagnostic blasts to determine drug sensitivities (LC50 - dose required to kill 50% of leukemia cells). RNA-sequencing was performed to derive molecular subtype. We then evaluated the associations of drug LC50 with clinical features, ALL subtype, MRD, and event-free survival (Figure 1). RESULTS We analyzed 5,447 drug measurements across 23 ALL subtypes. LC50s of prednisolone, asparaginase, and mercaptopurine were associated with age, and/or with leukocyte count at diagnosis. Sensitivities to 14 of 18 drugs varied across ALL molecular subtypes. For cytotoxic agents, B-ALL subtypes with favorable prognosis (ETV6-RUNX1 and hyperdiploidy) exhibited greatest sensitivity to asparaginase and glucocorticoids, whereas high-risk subtypes (KMT2A, BCR-ABL1, and BCR-ABL1-like) were resistant. Novel subtypes DUX4 and ETV6-RUNX1-like ALL showed significant resistance to cytotoxic drugs. For targeted agents, hyperdiploid ALL was most sensitive to venetoclax, whereas TCF3-PBX1, BCR-ABL1, and T-ALL were dasatinib-sensitive. The poor-prognosis ETP-ALL was resistant to most cytotoxic drugs compared to T-ALL. Although BCR-ABL1, BCR-ABL1-like, and CRLF2 are closely related transcriptionally, these three subtypes had distinctive drug sensitivity profiles. In B-ALL, sensitivities of prednisolone, asparaginase, dexamethasone, cytarabine and thiopurines were positively correlated with MRD. By contrast, these drugs were not correlated with MRD in T-ALL. Instead, sensitivities of dasatinib and nelarabine correlated positively, and venetoclax negatively, with MRD in T-ALL. Finally, we classified patients into six functional clusters based on ALL pharmacotypes, each with distinct patterns of somatic genomic aberrations and MRD response. Drug sensitivity cluster was significantly associated with event-free survival, even after adjusting for MRD. Importantly, pharmacotyping identified a T-ALL subset with poor prognosis under conventional chemotherapy but also with unique sensitivity to targeted agents, pointing to therapeutic intervention to improve survival in this group. CONCLUSIONEx vivo drug sensitivities vary widely across ALL subtypes and strongly influence in vivo MRD. Our study comprehensively described pharmacological heterogeneity of ALL and the association of drug sensitivities with survival outcomes, providing insight into the pharmacological basis of inter-patient variability in ALL treatment outcomes and highlighting opportunities for individualizing therapy for this blood cancer. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Development of an MMPI reference group for outpatients with persisting symptoms following mild TBI

ABSTRACT Objective To develop an MMPI-2-RF reference group for persistently symptomatic patients with mTBI in order to aid interpretation and better evaluate atypical scale elevations. Method Using the Q Local MMPI-2-RF Comparison Group Generator (CGG), 200 valid MMPI-2-RF profiles were aggregated for mTBI outpatients with persisting symptoms 2–24 months post injury. Results Compared to established MMPI general population norms, individuals with persisting symptoms demonstrated elevations on several scales, primarily in cognitive and somatic domains. T scores > 60 and standard deviations > 10 were observed for the F-r (Infrequent Responses), Fs (Infrequent Somatic Responses), FBS-r (Symptom Validity), RBS (Response Bias Scale), RC1 (Somatic Complaints), MLS (Malaise), HPC (Head Pain Complaints), NUC (Neurological Complaints), and COG (Cognitive Complaints) scales. All other scales were consistent with established norms for the general population. Conclusion This study is the first to establish an empirically derived MMPI reference group for individuals with persisting symptoms following mTBI. By comparing MMPI profiles of patients with mTBI against this reference group, clinicians may be better able to identify abnormal symptomatology. Evaluating profiles within this context may allow for more accurate case conceptualization and targeted treatment recommendations for those patients who demonstrate disproportionate symptomatology outside the range of the mTBI reference group.

An Algorithm Based on a Cable-Nernst Planck Model Predicting Synaptic Activity throughout the Dendritic Arbor with Micron Specificity.

Recent technological advances have enabled the recording of neurons in intact circuits with a high spatial and temporal resolution, creating the need for modeling with the same precision. In particular, the development of ultra-fast two-photon microscopy combined with fluorescence-based genetically-encoded Ca2+-indicators allows capture of full-dendritic arbor and somatic responses associated with synaptic input and action potential output. The complexity of dendritic arbor structures and distributed patterns of activity over time results in the generation of incredibly rich 4D datasets that are challenging to analyze (Sakaki et al. in Frontiers in Neural Circuits 14:33, 2020). Interpreting neural activity from fluorescence-based Ca2+ biosensors is challenging due to non-linear interactions between several factors influencing intracellular calcium ion concentration and its binding to sensors, including the ionic dynamics driven by diffusion, electrical gradients and voltage-gated conductances. To investigate those dynamics, we designed a model based on a Cable-like equation coupled to the Nernst-Planck equations for ionic fluxes in electrolytes. We employ this model to simulate signal propagation and ionic electrodiffusion across a dendritic arbor. Using these simulation results, we then designed an algorithm to detect synapses from Ca2+ imaging datasets. We finally apply this algorithm to experimental Ca2+-indicator datasets from neurons expressing jGCaMP7s (Dana et al. in Nature Methods 16:649-657, 2019), using full-dendritic arbor sampling in vivo in the Xenopus laevis optic tectum using fast random-access two-photon microscopy. Our model reproduces the dynamics of visual stimulus-evoked jGCaMP7s-mediated calcium signals observed experimentally, and the resulting algorithm allows prediction of the location of synapses across the dendritic arbor. Our study provides a way to predict synaptic activity and location on dendritic arbors, from fluorescence data in the full dendritic arbor of a neuron recorded in the intact and awake developing vertebrate brain.

The Colleen Bawn in Her Element: Sensation, Spectatorship, Meaning

This essay considers the appeal of the ‘water cave’ scene in Boucicault's The Colleen Bawn to nineteenth-century spectators by focusing on its iconography and visual address. The written archive is of limited value on this question since contemporary commentators struggled to explain its popularity. Recent scholarly accounts have identified this and other sensation scenes as vehicles for eliciting spectator ‘affect’, meaning involuntary somatic responses, prompted in this case by the spectacle of physical danger. While this approach has been useful in seeking readings beyond those embedded in language and text, it has tended to confine the discussion to a narrow range of extreme affective states associated with anxiety and terror. This essay considers interpretations arising out of the ‘affective turn’ before proposing a new direction. Working across a range of images, I address the specific visual nature of the ‘water cave’ scene, drawing out a more subtle and multi-faceted set of ideas than those with which sensation drama is generally associated, and proposing an alternative reading to do with feminine power and transfiguration.

Unraveling Functional Diversity of Cortical Synaptic Architecture Through the Lens of Population Coding.

The synaptic inputs to single cortical neurons exhibit substantial diversity in their sensory-driven activity. What this diversity reflects is unclear, and appears counter-productive in generating selective somatic responses to specific stimuli. One possibility is that this diversity reflects the propagation of information from one neural population to another. To test this possibility, we bridge population coding theory with measurements of synaptic inputs recorded in vivo with two-photon calcium imaging. We construct a probabilistic decoder to estimate the stimulus orientation from the responses of a realistic, hypothetical input population of neurons to compare with synaptic inputs onto individual neurons of ferret primary visual cortex (V1) recorded with two-photon calcium imaging in vivo. We find that optimal decoding requires diverse input weights and provides a straightforward mapping from the decoder weights to excitatory synapses. Analytically derived weights for biologically realistic input populations closely matched the functional heterogeneity of dendritic spines imaged in vivo with two-photon calcium imaging. Our results indicate that synaptic diversity is a necessary component of information transmission and reframes studies of connectivity through the lens of probabilistic population codes. These results suggest that the mapping from synaptic inputs to somatic selectivity may not be directly interpretable without considering input covariance and highlights the importance of population codes in pursuit of the cortical connectome.

Can Physical Exercise Help Deal With the COVID-19 Stressors? Comparing Somatic and Psychological Responses.

This research aims to explore whether physical exercise can buffer the impact of the COVID-19 stressors. Based on the cross-stressor adaptation hypothesis, we proposed a moderated mediation model relating the COVID-19 stressors to sleep disorder via somatic and worry complaints, depending on the amount of physical exercise. A sample of working adults in Beijing (N = 207) filled surveys in two waves during the COVID-19 pandemic. Structural regression analysis showed that physical exercise moderates the impact of the COVID-19 stressors on sleep disorder via somatic complaints (index = −0.11, 95% CI [−0.22, −0.01]), rather than psychological worry complaints (index = −0.01, 95% CI [−0.07, 0.04]). Specifically, the COVID-19 stressors increase somatic complaints for people with a low amount of physical exercise (b = 0.17, p = 0.01]), while the COVID-19 stressors are not significantly related to somatic complaints for people with a high amount of physical exercise (b = −0.06, p = 0.33). This research extends the cross-stressor adaptation hypothesis and provides evidence on an individual intervention of physical exercise to deal with the COVID-19 pandemic.

Somatic DNA Damage Response and Homologous Repair Gene Alterations and Its Association With Tumor Variant Burden in Breast Cancer Patients With Occupational Exposure to Pesticides.

Homologous recombination is a crucial pathway that is specialized in repairing double-strand breaks; thus, alterations in genes of this pathway may lead to loss of genomic stability and cell growth suppression. Pesticide exposure potentially increases cancer risk through several mechanisms, such as the genotoxicity caused by chronic exposure, leading to gene alteration. To analyze this hypothesis, we investigated if breast cancer patients exposed to pesticides present a different mutational pattern in genes related to homologous recombination (BRCA1, BRCA2, PALB2, and RAD51D) and damage-response (TP53) concerning unexposed patients. We performed multiplex PCR-based assays and next-generation sequencing (NGS) of all coding regions and flanking splicing sites of BRCA1, BRCA2, PALB2, TP53, and RAD51D in 158 unpaired tumor samples from breast cancer patients on MiSeq (Illumina) platform. We found that exposed patients had tumors with more pathogenic and likely pathogenic variants than unexposed patients (p = 0.017). In general, tumors that harbored a pathogenic or likely pathogenic variant had a higher mutational burden (p < 0.001). We also observed that breast cancer patients exposed to pesticides had a higher mutational burden when diagnosed before 50 years old (p = 0.00978) and/or when carrying BRCA1 (p = 0.0138), BRCA2 (p = 0.0366), and/or PALB2 (p = 0.00058) variants, a result not found in the unexposed group. Our results show that pesticide exposure impacts the tumor mutational landscape and could be associated with the carcinogenesis process, therapy response, and disease progression. Further studies should increase the observation period in exposed patients to better evaluate the impact of these findings.

The Development of Somatic Symptom Disorder in Children: Psychological Characteristics and Psychiatric Comorbidity

Somatic symptom disorder (SSD) is one of the most common pediatric psychiatric disorders in adolescents, and several biological, psychological, and social factors have been considered to contribute to its development. The aim of the present study was to elucidate the link between psychological functioning (depression and anxiety), psychological characteristics (perfectionism and alexithymia), negative life events, and parental accommodation in children diagnosed with SSD. Fifty patients (age range 7-18 years) were diagnosed with SSD in an outpatient clinic and completed multiple self-report questionnaires on SSD symptoms, negative life events, and psychological factors. Linear regression models were used to indicate predictors of SSD symptoms. Cluster analysis was performed to identify gastrointestinal and abdominal complaints and their associations. Association with SSD symptoms was strongest for state anxiety (standardized β= 0.85, 95% confidence interval [CI]=0.44, 1.27, P= 0.0006), depression (β= 0.72, 95% CI=0.38, 1.06, P= 0.0006), trait anxiety (β= 0.60, 95% CI=0.22, 0.98, P= 0.0005), and family accommodation (β= 0. 49, 95% CI=0.23, 0.75, P= 0.001). These factors were associated with gastrointestinal but not with neurological complaints. Family accommodation was associated with somatic complaints among children younger than 12 years (r= 0.57, P= 0.007), while state anxiety (r= 0.69, P= 0.007) and depression (r= 0.65, P= 0.007) were significantly associated among older children. Several psychological factors may result in a somatic response. The phenotypic expression of these factors may vary among different ages. Somatic complaints were related to parental accommodation among young children, while it was strongly associated with anxiety and depression among adolescents.

Graded epidural anesthesia for fistulectomy with symptomatic obstructive hypertrophic cardiomyopathy

Hemodynamic fluctuations can occur when fistulectomy is usually done under spinal anesthesia that can cause detrimental effects for a patient with obstructive cardiomyopathy. This is a case of 51-year-old male with fistula in ano sustaining obstructive hypertrophic cardiomyopathy as suggested by chest pain, palpitation, breathlessness on exertion was scheduled for fistulectomy. Electrocardiography (ECG) showed left ventricular hypertrophy with deep narrow Q waves in V1 to V6. Echo showed asymmetrical septal hypertrophy, grade 1 diastolic dysfunction, EF – 60%. Regional anesthesia technique such as graded epidural anesthesia can be safe and cost effective by prolonging the postoperative pain relief and thus also effective in blunting autonomic, somatic, and endocrine response triggered by surgical insult.

Visual Aggression: Images of Martyrdom in Late Medieval Germany

Visual Aggression: Images of Martyrdom in Late Medieval Germany

Acute toxicity evaluation of ethanolic extract of the leaves of Anredera cordifolia in wistar rats (Rattus Norvegicus)

Anredera cordifolia (Binahong) is one of the medicinal plants that has been widely used for its properties of inhibiting the growth of microorganisms, decreasing blood uric acid, and healing wounds. This study was conducted to evaluate the acute toxicity effects of ethanolic extract of binahong to support its use as a medicinal plant. Ethanolic extracts of binahong leaves were prepared. Twenty-five white male rats (Rattus norvegicus) were divided into 5 groups and administered with a single dose of Na-CMC suspension or a dose of 300, 600, 1200, or 2400 mg/kg BW of binahong ethanolic leaf extract, respectively. Toxicity symptoms were monitored at three-time intervals: ½-1, 1½-2, and 3-6 hours after the administration. A macroscopic evaluation of the rat’s liver was carried out to identify any lesion. The rat’s liver and whole-body weights were determined to assess the weight reduction. The results showed that there was no dead rat in any of the groups, indicating that no LD50 was identified. Also, there were several toxic effects observed including a decrease in movements, somatic response, insensitivity, and stool consistency. There was no evidence of a lesion on liver macroscopy. However, the weights of rats’ livers increased in tandem with the reduction in their body weights. The findings from this study reveal that single dose of binahong ethanolic extract ranging from 300 to 2400 mg/kg BW are safe, while minimal toxic effects were observed.

Neural circuit mechanisms of hierarchical sequence learning tested on large-scale recording data.

The brain performs various cognitive functions by learning the spatiotemporal salient features of the environment. This learning requires unsupervised segmentation of hierarchically organized spike sequences, but the underlying neural mechanism is only poorly understood. Here, we show that a recurrent gated network of neurons with dendrites can efficiently solve difficult segmentation tasks. In this model, multiplicative recurrent connections learn a context-dependent gating of dendro-somatic information transfers to minimize error in the prediction of somatic responses by the dendrites. Consequently, these connections filter the redundant input features represented by the dendrites but unnecessary in the given context. The model was tested on both synthetic and real neural data. In particular, the model was successful for segmenting multiple cell assemblies repeating in large-scale calcium imaging data containing thousands of cortical neurons. Our results suggest that recurrent gating of dendro-somatic signal transfers is crucial for cortical learning of context-dependent segmentation tasks.

Abstract 3058: Characterization of the tumor microbiome in patients with locally advanced rectal cancer treated with neoadjuvant therapy

Abstract The gut microbiota is a component of the tumor microenvironment that has the potential to influence sensitivity or resistance to neoadjuvant therapy through modulation of the host immune response in patients diagnosed with locally advanced rectal cancer (LARC, stage II-III). We performed DNA and RNA sequencing of pre-treatment endoscopic biopsies from 89 LARC patients treated with neoadjuvant therapy (NAT). Our cohort included 84 microsatellite stable and 5 microsatellite unstable (MSI) patients. We identified the presence of microbial species by mapping non-human RNA read sequences to a large catalogue of viral and bacterial microorganisms. Our methodology has been validated and determined to have comparable accuracy to reference microbial tests for both viruses and bacteria. We analyzed correlations between presence of specific microbial species and (1) clinicopathological variables such as age, stage, anatomic location and MSI status, (2) genomic variables such as tumor mutational burden, chromosomal instability and somatic alterations and (3) response to NAT. We identified 152 species with at least 100 mapped reads in 10% or more of our cohort. The median number of species per patient was 37 [IQR 16-66], with only 6/89, 7% patients having no detected species at all. The most frequently detected species included well-known intestinal bacteria such as Escherichia coli, Fusobacterium nucleatum, Faecalibacterium prausnitzii and several members of the Bacteroides genus. The Parvimonas micra coccus was more often detected in tumors from the lower rectum (13/22, 59%, 0-4 cm from the anal verge) than the middle (8/36, 22%, 4-8 cm) and upper rectum (5/30, 17%, 8-12 cm) (p&amp;lt;0.01). Several species from the Gordonia and Rhodococcus genera were associated with increased tumor mutational burden (p&amp;lt;0.001) and significantly higher numbers of mapped reads in samples from the CMS1 molecular subtype (p&amp;lt;0.01), which is enriched in MSI tumors. RNA-Seq based estimates of neutrophil abundance were positively correlated with detection of several Ruminococcus and Prevotella species (p&amp;lt;0.001), highlighting the cross-talk between host immunity and microbiota. Opportunistic bacteria previously reported to benefit from a patient’s weakened immune system such as Williamsia muralis and several species of Agrobacterium were associated with lower rates of complete response (30% vs. 15%, n.s.) and significantly shorter disease free survival following NAT (3-year disease free survival was 25% in 8 Williamsia positive patients vs. 42% in 12 Agrobacterium fabrum patients vs. 87% in the rest of the cohort; pairwise log-rank p&amp;lt;0.001). Our data shows that standard RNA sequencing platforms can be used to detect microbial species in endoscopic biopsies from LARC patients and that the presence of specific species is associated with clinical and genomic features of translational relevance. Citation Format: Chad M. Vanderbilt, Walid K. Chatila, Danny N. Khalil, Chin-Tung Chen, Jin K. Kim, Fan Wu, Nikolaus Schultz, Martin R. Weiser, Julio Garcia-Aguilar, Francisco Sanchez-Vega. Characterization of the tumor microbiome in patients with locally advanced rectal cancer treated with neoadjuvant therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3058.

Mental health effects of the Gangwon wildfires

BackgroundThe April 2019 wildfires in Gangwon Province, South Korea forced the evacuation of 1500 individuals and cost more than $100 million in damages, making it the worst wildfire disaster in Korean history. The purpose of this paper was to investigate the mental health effects on survivors following the wildfires.MethodsBetween April and May 2019, outreach psychological support services were delivered to people impacted by the wildfires. Post-disaster psychological responses using a checklist and the Clinical Global Impression Scale-Severity (CGI-S) were evaluated for 206 wildfires survivors. The CGI-S was administered consequently at 1, 3, and 6 months after baseline measurement.ResultsAmong four response categories, somatic responses (76.2%) were most frequently observed among the wildfire survivors. Specifically, insomnia (59.2%), anxiety (50%), chest tightness (34%), grief (33%), flashbacks (33%), and depression (32.5%) were reported by over 30% of the participants. The mean CGI-S scores were significantly decreased at 1 month (mean score = 1.94; SE = 0.09) compared to baseline (mean score = 2.94; SE = 0.08) and remained at the decreased level until 6 months (mean score = 1.66; SE = 0.11). However, participants with flashbacks showed significantly higher CGI-S scores compared to those without flashback at 6 months.ConclusionsWildfire survivors have various post-disaster responses, especially somatic responses. While most participants’ mental health improved over time, a few of them may have experienced prolonged psychological distress after 6 months. Flashbacks were particularly associated with continuing distress. These results suggest that the characteristics of responses should be considered in early phase intervention and in follow-up plans for disaster survivors.

Development and Psychometric Evaluation of the Reactions to Somatic Stress Questionnaire (RSSQ)

Abstract. Background: Stress is a ubiquitous phenomenon in modern societies and is often accompanied by somatic sensations and symptoms, such as tension and nausea. Despite the inherent somatic component of stress, research on coping with stress has previously neglected to consider how somatic stress responses (i.e., somatic stress) may affect stress-coping behavior. Aim: To address this gap in the literature, this study introduces the concept of reactions to somatic stress (RSS). It also provides the first psychometric evaluation of the Reactions to Somatic Stress Questionnaire (RSSQ), a novel 16-item questionnaire that assesses hampering and facilitating RSS. Method: The RSSQ and a battery of questionnaires on related constructs were administered via an online survey to N = 265 participants from the general population. Results: Exploratory ( n = 133) and confirmatory ( n = 132) factor analyses yielded two dimensions of the RSSQ: Hampering RSS (RSS-H) and facilitating RSS (RSS-F). Both subscales showed good internal consistency (α = .81–.89). Correlations with body awareness, emotion regulation skills, and beliefs about stress indicated medium to high convergent and discriminant validity. The RSS-H and RSS-F scores significantly predicted maladaptive and adaptive coping behavior, respectively. This association remained stable after controlling for subjective stress and related measures. Limitations: Generalization of the obtained results is limited to healthy individuals. Conclusion: The study supports the theoretical assumptions underlying the RSS concept. The RSSQ suggests a promising way to assess reactions to somatic stress as they relate to coping with stress. The RSSQ could be used for clinical and health psychological testing or interdisciplinary research.

Whole-Brain Wiring Diagram of Oxytocin System in Adult Mice.

Oxytocin (Oxt) neurons regulate diverse physiological responses via direct connections with different neural circuits. However, the lack of comprehensive input-output wiring diagrams of Oxt neurons and their quantitative relationship with Oxt receptor (Oxtr) expression presents challenges to understanding circuit-specific Oxt functions. Here, we establish a whole-brain distribution and anatomic connectivity map of Oxt neurons, and their relationship with Oxtr expression using high-resolution 3D mapping methods in adult male and female mice. We use a flatmap to describe Oxt neuronal expression in four hypothalamic domains including under-characterized Oxt neurons in the tuberal nucleus (TU). Oxt neurons in the paraventricular hypothalamus (PVH) broadly project to nine functional circuits that control cognition, brain state, and somatic visceral response. In contrast, Oxt neurons in the supraoptic (SO) and accessory (AN) nuclei have limited central projection to a small subset of the nine circuits. Surprisingly, quantitative comparison between Oxt output and Oxtr expression showed no significant correlation across the whole brain, suggesting abundant indirect Oxt signaling in Oxtr-expressing areas. Unlike output, Oxt neurons in both the PVH and SO receive similar monosynaptic inputs from a subset of the nine circuits mainly in the thalamic, hypothalamic, and cerebral nuclei areas. Our results suggest that PVH-Oxt neurons serve as a central modulator to integrate external and internal information via largely reciprocal connection with the nine circuits while the SO-Oxt neurons act mainly as unidirectional Oxt hormonal output. In summary, our Oxt wiring diagram provides anatomic insights about distinct behavioral functions of Oxt signaling in the brain.SIGNIFICANCE STATEMENT Oxytocin (Oxt) neurons regulate diverse physiological functions from prosocial behavior to pain sensation via central projection in the brain. Thus, understanding detailed anatomic connectivity of Oxt neurons can provide insight on circuit-specific roles of Oxt signaling in regulating different physiological functions. Here, we use high-resolution mapping methods to describe the 3D distribution, monosynaptic input and long-range output of Oxt neurons, and their relationship with Oxt receptor (Oxtr) expression across the entire mouse brain. We found Oxt connections with nine functional circuits controlling cognition, brain state, and somatic visceral response. Furthermore, we identified a quantitatively unmatched Oxt-Oxtr relationship, suggesting broad indirect Oxt signaling. Together, our comprehensive Oxt wiring diagram advances our understanding of circuit-specific roles of Oxt neurons.