Elevated dementia risk, cognitive decline, and hippocampal atrophy in multisite chronic pain.

Numerous studies have investigated the impacts of common types of chronic pain (CP) on patients' cognitive function and observed that CP was associated with later dementia. More recently, there is a growing recognition that CP conditions frequently coexist at multiple body sites and may bring more burdens on patients' overall health. However, whether and how multisite CP (MCP) contributes to an increased risk of dementia, compared to single-site CP (SCP) and pain-free (PF), is largely unclear. In the current study, utilizing the UK Biobank cohort, we first investigated dementia risk in individuals (n = 354,943) with different numbers of coexisting CP sites using Cox proportional hazards regression models. We then applied generalized additive models to investigate whether MCP leads to excessive deterioration of participants' (n = 19,116) cognition and brain structure. We found that individuals with MCP were associated with significantly higher dementia risk, broader and faster cognitive impairment, and greater hippocampal atrophy than both PF individuals and those with SCP. Moreover, the detrimental effects of MCP on dementia risk and hippocampal volume aggravated along with the number of coexisting CP sites. Mediation analyses further revealed that the decline of fluid intelligence in MCP individuals was partially mediated by hippocampal atrophy. Our results suggested that cognitive decline and hippocampal atrophy interact biologically and may underlie the increased risk of dementia associated with MCP.

Role of APOE in glaucoma.

Glaucoma is a chronic blinding eye disease caused by the progressive loss of retinal ganglion cells (RGCs). Currently, no clinically approved treatment can directly improve the survival rate of RGCs. The Apolipoprotein E (APOE) gene is closely related to the genetic risk of numerous neurodegenerative diseases and has become a hot topic in the field of neurodegenerative disease research in recent years. The optic nerve and retina are extensions of the brain's nervous system. The pathogenesis of retinal degenerative diseases is closely related to the degenerative diseases of the nerves in the brain. APOE consists of three alleles, ε4, ε3, and ε2, in a single locus. They have varying degrees of risk for glaucoma. APOE4 and the APOE gene deletion (APOE-/-) can reduce RGC loss. By contrast, APOE3 and the overall presence of APOE genes (APOE+/+) result in significant loss of RGC bodies and axons, increasing the risk of glaucoma RGCs death. Currently, there is no clear literature indicating that APOE2 is beneficial or harmful to glaucoma. This study summarises the mechanism of different APOE genes in glaucoma and speculates that APOE targeted intervention may be a promising method for protecting against RGCs loss in glaucoma.

THz spectrum processing method based on optimal wavelet selection.

Terahertz spectrum is easily interfered by system noise and water-vapor absorption. In order to obtain high quality spectrum and better prediction accuracy in qualitative and quantitative analysis model, different wavelet basis functions and levels of decompositions are employed to perform denoising processing. In this study, the terahertz spectra of wheat samples are denoised using wavelet transform. The compound evaluation indicators (T) are used for systematically analyzing the quality effect of wavelet transform in terahertz spectrum preprocessing. By comparing the optimal denoising effects of different wavelet families, the wavelets of coiflets and symlets are more suitable for terahertz spectrum denoising processing than the wavelets of fejer-korovkin and daubechies, and the performance of symlets 8 wavelet basis function with 4-level decomposition is the optimum. The results show that the proposed method can select the optimal wavelet basis function and decomposition level of wavelet denoising processing in the field of terahertz spectrum analysis.

Sex difference in trait empathy is encoded in the human anterior insula.

Females are considered the more empathic sex. This conventional view, however, has been challenged in the past few decades with mixed findings. These heterogeneous findings could be caused by the fact that empathy is a complex and multifaceted construct. To clarify whether sex differences exist in certain dimensions of empathy and whether they are associated with specific neural bases, this study measured trait empathy using the interpersonal reactivity index (IRI) and collected brain structural and functional magnetic resonance imaging data in a large sample of healthy participants (206 males vs. 302 females). We found that females scored higher in the personal distress (PD) subscale than males, but they were comparable to males in other IRI subscales. Sex difference in PD was encoded by brain structural (e.g. gray matter volume in left anterior insula [AI]) and functional (e.g. resting-state functional connectivity between left AI and temporoparietal junction/inferior frontal gyrus) characteristics. Notably, the relationship between sex and PD was indirect-only and serially mediated by AI-associated structural and functional characteristics. Altogether, our results suggested that sex difference existed in self-oriented affective empathy (i.e. PD) and highlighted the importance of the AI, both structurally and functionally, in mediating the sex difference in trait empathy.

Neural processes responsible for the translation of sustained nociceptive inputs into subjective pain experience.

Tracking and predicting the temporal structure of nociceptive inputs is crucial to promote survival, as proper and immediate reactions are necessary to avoid actual or potential bodily injury. Neural activities elicited by nociceptive stimuli with different temporal structures have been described, but the neural processes responsible for translating nociception into pain perception are not fully elucidated. To tap into this issue, we recorded electroencephalographic signals from 48 healthy participants receiving thermo-nociceptive stimuli with 3 different durations and 2 different intensities. We observed that pain perception and several brain responses are modulated by stimulus duration and intensity. Crucially, we identified 2 sustained brain responses that were related to the emergence of painful percepts: a low-frequency component (LFC, < 1 Hz) originated from the insula and anterior cingulate cortex, and an alpha-band event-related desynchronization (α-ERD, 8-13 Hz) generated from the sensorimotor cortex. These 2 sustained brain responses were highly coupled, with the α-oscillation amplitude that fluctuated with the LFC phase. Furthermore, the translation of stimulus duration into pain perception was serially mediated by α-ERD and LFC. The present study reveals how brain responses elicited by nociceptive stimulation reflect the complex processes occurring during the translation of nociceptive information into pain perception.

Inter-module gap filling method for photon counting detectors based on dual acquisition.

The use of photon counting detectors in X-ray imaging missions can effectively improve the signal-to-noise ratio and image resolution. However, the stitching of photon counting detector modules leads to large-size localized information loss in the acquired projected image, which seriously affects the regional observation. In this paper, we propose a method to fill the inter-module gap based on dual acquisition, referred to as the GFDA algorithm, which is divided into three main steps: (i) acquire the main projection by short-exposure scanning, and then scan again by vertically moving the carrier table to acquire the reference projection; (ii) use the alignment method to locate the projected region of interest; (iii) use image stitching and image fusion to recover the missing information. We analyzed the gray value of the region of interest of the Siemens star projection and the reconstructed conch slice data, and proved that the proposed method can recover the information more smoothly and perfectly. The GFDA algorithm is able to achieve a better image restoration effect without additional scanning time and better retain image details. In addition, the GFDA algorithm is scalable, which is demonstrated in the task of filling the stitching of multiple types of photonic technology detectors.

Neurotrophic keratitis caused by lightning injury: a case report.

BACKGROUND: This study aimed to report a case of neurotrophic keratitis caused by lightning. CASE PRESENTATION: A 38-year-old man was hit by lightning and suffered eye injury. He eventually developed neurotrophic keratitis. RESULTS: The patient's injury history and burn site were analyzed, and it was judged that lightning directly damaged his cornea, eventually resulting in neurotrophic keratitis. Fortunately, the patient's vision improved after treatment. CONCLUSION: Lightning can cause eye damage, and the clinical manifestations are diverse. Lightning currents cause corneal nerve loss, resulting in neurotrophic keratitis. To maintain corneal integrity and prevent disease progression, early assessment and appropriate treatment are necessary.

Enhanced neural synchrony associated with long-term ballroom dance training.

Long-term dance training offers numerous benefits, including improvements in physical health, posture, body coordination, and mental health and well-being. Since dance is an art form of body-to-body communication, professional dancers may share feelings and thoughts on dance with their partners, owing to their shared training experiences. Considering this perspective, one may expect that professional dancers would demonstrate pronounced neural similarities when viewing dancing videos, which could be associated with their training duration. To test these hypotheses, we collected functional magnetic resonance imaging (fMRI) data while presenting ballroom dancing and neutral video clips with long durations (∼100 s each) to 41 professional ballroom dancers (19 pairs of dance partners) and 39 age- and sex-matched nondancers. Our findings revealed that dancers exhibited broader and stronger neural similarities across the whole brain when watching dancing video clips, as compared to the control group. These increased neural similarities could be interpreted in at least two distinct ways. First, neural similarities in certain brain regions within the motor control circuit (i.e., frontal cortical-basal ganglia-thalamic circuit) were significantly correlated with dance-related information (e.g., dance partners' cooperation duration), which reinforced the impact of long-term dance training on neural synchronization. Second, neural similarities in other brain regions (e.g., memory-related brain regions) were significantly correlated with subjects' impression of the viewed videos (i.e., whether they have watched before, familiarity, and liking), which may not necessarily be directly linked to long-term dance training. Altogether, our study provided solid evidence for synchronized neural mechanisms in professional dancers due to long-term dance training.

The association between ballroom dance training and empathic concern: Behavioral and brain evidence.

Dance is unique in that it is a sport and an art simultaneously. Beyond improving sensorimotor functions, dance training could benefit high-level emotional and cognitive functions. Duo dances also confer the possibility for dancers to develop the abilities to recognize, understand, and share the thoughts and feelings of their dance partners during the long-term dance training. To test this possibility, we collected high-resolution structural and resting-state functional magnetic resonance imaging (MRI) data from 43 expert-level ballroom dancers (a model of long-term exposure to duo dance training) and 40 age-matched and sex-matched nondancers, and measured their empathic ability using a self-report trait empathy scale. We found that ballroom dancers showed higher scores of empathic concern (EC) than controls. The EC scores were positively correlated with years with dance partners but negatively correlated with the number of dance partners for ballroom dancers. These behavioral results were supported by the structural and functional MRI data. Structurally, we observed that the gray matter volumes in the subgenual anterior cingulate cortex (ACC) and EC scores were positively correlated. Functionally, the connectivity between ACC and occipital gyrus was positively correlated with both EC scores and years with dance partners. In addition, the relationship between years with dance partners and EC scores was indirect-only mediated by the ACC-occipital gyrus functional connectivity. Therefore, our findings provided solid evidence for the close link between long-term ballroom dance training and empathy, which deepens our understanding of the neural mechanisms underlying this phenomenon.

The effect of background liked music on acute pain perception and its neural correlates.

Music shows tremendous promise in pain relief, especially when considering its non-pharmacological nature. However, our understanding of the precise mechanisms behind music-induced analgesia (MIA) remains poor. The positive emotional state induced by music is one of the key components explaining MIA. To test this possibility and reveal its neural correlates, the present study applied nociceptive laser stimuli to 28 healthy participants when their liked or disliked songs were played as background music, or when they were resting in silence. Differences among conditions were quantified by self-reports of pain intensity and unpleasantness, as well as brain activations in response to acute laser stimuli. As expected, liked music significantly lowered pain ratings to acute painful stimuli compared to disliked music and no music. Consistent with this observation, brain activations in response to acute painful stimuli were deceased within brain areas encoding sensory components of pain, such as the right precentral and postcentral gyri (PreCG/PoCG), brain areas related to affective components of pain, such as the anterior cingulate cortex and bilateral putamen, and brain areas associated with motor control and avoidance reactions to pain, such as the left cerebellum, when liked music was played in the background in comparison to disliked music. Importantly, the relationship between music listening and differences in pain ratings of two music conditions was mediated by the magnitude of right PreCG/PoCG and left cerebellum activations. These findings deepened our understanding of the analgesic benefits of background liked music, a property relevant to clinical applications.

The analgesic effects and neural oscillatory mechanisms of virtual reality scenes based on distraction and mindfulness strategies in human volunteers.

BACKGROUND: Virtual reality (VR) has been widely used as a non-pharmacological adjunct to pain management. However, there is no consensus on what type of VR content is the best for pain alleviation and by what means VR modulates pain perception. We used three experiments to explore the analgesic effect of VR scenes in healthy adult volunteers. METHODS: We first compared the effect of immersive VR on pain perception with active (i.e. non-immersive, two-dimensional video) and passive (i.e. no VR or audiovisual input) controls at both subjective perceptual (Experiment 1) and electrophysiological (electroencephalography) levels (Experiment 2), and then explored possible analgesic mechanisms responsible for VR scenes conveying different strategies (e.g. exploration or mindfulness; Experiment 3). RESULTS: The multisensory experience of the VR environment lowered pain intensity and unpleasantness induced by contact heat stimuli when compared with two control conditions (P=0.001 and P<0.001, respectively). The reduced pain intensity rating correlated with decreased P2 amplitude (r=0.433, P<0.001) and increased pre-stimulus spontaneous gamma oscillations (r=-0.339, P=0.004) by 32-channel electroencephalography. A VR exploration scene induced a strong sense of immersion that was associated with increased pre-stimulus gamma oscillations (r=0.529, P<0.001), whereas a VR mindfulness meditation scene had a minor effect on immersive feelings but induced strong pre-stimulus alpha oscillations (r=-0.550, P<0.001), which led to a comparable analgesic effect. CONCLUSIONS: Distinct neural mechanisms are responsible for VR-induced analgesia, deepening our understanding of the analgesic benefits of VR and its neural electrophysiological correlates. These findings support further development of digital healthcare.

Post-traumatic stress symptoms in COVID-19 survivors: a self-report and brain imaging follow-up study.

Previous coronavirus pandemics were associated elevated post-traumatic stress symptoms (PTSS), but the self-report and neurological basis of PTSS in patients who survived coronavirus disease 2019 (COVID-19) are largely unknown. We conducted a two-session study to record PTSS in the COVID-19 survivors discharged from hospitals for a short (i.e., about 3 months, Session 1) to a medium period (i.e., about 6 months, Session 2), as well as brain imaging data in Session 2. The control groups were non-COVID-19 locals. Session 1 was completed for 126 COVID-19 survivors and 126 controls. Session 2 was completed for 47 COVID-19 survivors and 43 controls. The total score of post-traumatic stress disorder (PTSD) checklist for DSM-5 (PCL-5) score was significantly higher in COVID-19 survivors compared with controls in both sessions. The PCL-5 score in COVID-19 survivors was positively correlated with the duration after discharge (r = 0.27, p = 0.003 for Session 1), and increased by 20% from Session 1 to Session 2 for the survivors who participated both sessions. The increase was positively correlated with individual's test-retest duration (r = 0.46, p = 0.03). Brain structural volume and functional activity in bilateral hippocampus and amygdala were significantly larger in COVID-19 survivors compared with controls. However, the volumes of the left hippocampus and amygdala were negatively correlated with the PCL-5 score for the COVID-19 survivors. Our study suggests that COVID-19 survivors might face possible PTSS deteriorations, and highlights the importance of monitoring mental wellness of COVID-19 survivors.

The role of negative emotions in sex differences in pain sensitivity.

Pain perception varies widely among individuals due to the varying degrees of biological, psychological, and social factors. Notably, sex differences in pain sensitivity have been consistently observed in various experimental and clinical investigations. However, the neuropsychological mechanism underlying sex differences in pain sensitivity remains unclear. To address this issue, we quantified pain sensitivity (i.e., pain threshold and tolerance) using the cold pressure test and negative emotions (i.e., pain-related fear, pain-related anxiety, trait anxiety, and depression) using well-established questionnaires and collected magnetic resonance imaging (MRI) data (i.e., high-resolution T1 structural images and resting-state functional images) from 450 healthy subjects. We observed that, as compared to males, females exhibited lower pain threshold and tolerance. Notably, sex differences in pain sensitivity were mediated by pain-related fear and anxiety. Specifically, pain-related fear and anxiety were the complementary mediators of the relationship between sex and pain threshold, and they were the indirect-only mediators of the relationship between sex and pain tolerance. Besides, structural MRI data revealed that the amygdala subnuclei (i.e., the lateral and basal nuclei in the left hemisphere) volumes were the complementary mediators of the relationship between sex and pain-related fear, which further influenced pain sensitivity. Altogether, our results provided a comprehensive picture of how negative emotions (especially pain-related negative emotions) and related brain structures (especially the amygdala) contribute to sex differences in pain sensitivity. These results deepen our understanding of the neuropsychological underpinnings of sex differences in pain sensitivity, which is important to tailor a personalized method for treating pain according to sex and the level of pain-related negative emotions for patients with painful conditions.

Intense pulsed light for meibomian gland dysfunction: a systematic review and meta-analysis.

BACKGROUND: Intense pulsed light therapy (IPL) is a new method being used to treat meibomian gland dysfunction (MGD) globally. With an increasing number of studies being published, it is necessary to consider additional factors related to treatment. This review aims to investigate the efficacy and safety of IPL for the treatment of MGD. METHODS: The PubMed, EMBASE, Web of Science, Cochrane Library, Google Scholar, China National Knowledge Infrastructure (CNKI), Wanfang, VIP, and SinoMed databases were searched through February 24, 2020. Randomized clinical trials and cohort studies comparing IPL+ meibomian gland expression (MGX) or IPL alone with control groups were included. The weighted mean difference (WMD) was calculated to analyze the Ocular Surface Disease Index (OSDI) score and Standard Patient Evaluation of Eye Dryness (SPEED) score, and the standard mean difference (SMD) was calculated to analyze the tear breakup time (TBUT). Heterogeneity was quantified by the I2 statistic ranging from 0 to 100%, and a random effects model was used in this meta-analysis. All analyses were performed by RevMan 5.3. All p values were calculated by the t test, and p values were regarded as statistically significant at p < 0.05. The Cochrane Collaboration's tool for assessing risk of bias was used to identify and evaluate bias in the literature. RESULTS: Nine studies with a total of 539 patients were included. Eight studies examined TBUT, six examined OSDI scores, and four examined SPEED scores. IPL combined with MGX showed superiority regarding the TBUT (SMD 2.33, 95% CI 1.04-3.61), and OSDI scores (WMD 11.93, 95% CI - 17.10 to - 6.77), with high heterogeneity. The SPEED scores were not significantly different. CONCLUSIONS: IPL combined with MGX may be an effective and safe treatment for MGD, but it cannot improve all symptoms. IPL alone is not superior to MGX. The efficacy is also affected by the number and average frequency of treatments. The efficacy of IPL may decrease within 6 months after the last treatment, so it should be considered a long-term adjuvant therapy combined with MGX. When patients receive 3 or 4 treatments (once every 3-4 weeks), a return visit at 6 months after the last treatment is required.

The linkage between first-hand pain sensitivity and empathy for others' pain: Attention matters.

Many studies suggested shared psychological and neural representations for first-hand physical pain and empathy for others' pain, both of which depend strongly upon top-down controlled mechanisms such as attention. This study aimed to assess the interindividual variation in first-hand physical pain and empathy for pain, and whether their relationship is dependent upon attention. We recruited participants exhibiting high and low sensitivity to first-hand pain (HPS and LPS), and adopted pain empathy paradigms involving attention directed toward or withdrawn from pain of another. Relative to the LPS group, participants in the HPS group estimated greater pain intensity experienced by others, felt greater unpleasantness when viewing others in pain, and exhibited greater sensitivity in discriminating others' pain. Electroencephalographic data showed that when attention was directed toward others' pain, only participants in the HPS group exhibited significant pain empathic effects on the N1 component of event-related potentials and on the α-oscillation response. These empathic neural responses mediated the linkage between first-hand pain sensitivity and empathic behavioral responses. Nevertheless, empathic responses were comparable between two groups when attention was withdrawn from others' pain. These results demonstrate a shared sensitivity to first-hand pain and empathy for pain provided that attention is directed toward pain.

Pavlov's Pain: the Effect of Classical Conditioning on Pain Perception and its Clinical Implications.

PURPOSE OF REVIEW: It has been known for decades that classical conditioning influences pain perception. However, the precise relationship between conditioning and pain remains unclear. In addition, the clinical implications of their relationship are vastly underappreciated. Thus, we aim to (a) examine how conditioning increases or decreases pain sensitivity, (b) assess how conditioning contributes to the development and maintenance of chronic pain, and (c) explore strategies to utilize conditioning to optimize pain treatment. RECENT FINDINGS: We first review studies regarding how classical conditioning alters pain perception with an emphasis on two phenomena where conditioning increases pain sensitivity (i.e., conditioned hyperalgesia) or decreases it (i.e., conditioned hypoalgesia). Specifically, we critically examine empirical studies about conditioned hyperalgesia and conditioned hypoalgesia, explore reasons why conditioning leads to these two seemingly opposite phenomena, and discuss the neural mechanisms behind them. We then highlight how conditioning contributes to the development and maintenance of chronic pain, and present neuroscientific evidence for maladaptive aversive conditioning in chronic pain patients. Moreover, we propose a framework for understanding how to exploit conditioning to optimize pain treatment, including minimizing conditioned hyperalgesia, maximizing conditioned hypoalgesia, and eliminating excessive fear and overgeneralization in chronic pain. Classical conditioning profoundly modulates the experience of pain and affects the development and maintenance of chronic pain. The relationship between them has far-reaching clinical implications in pain treatment. Further investigations should tackle crucial issues in previous studies, including the complex relationship between conditioning and explicit expectation, and a lack of relevant clinical studies. Resolving these issues, future research would advance our understanding of the nature of pain, help relieve the suffering of patients, and thus contribute to promoting human flourishing.

The influence of visual information on auditory processing in individuals with congenital amusia: An ERP study.

While most normal hearing individuals can readily use prosodic information in spoken language to interpret the moods and feelings of conversational partners, people with congenital amusia report that they often rely more on facial expressions and gestures, a strategy that may compensate for deficits in auditory processing. In this investigation, we used EEG to examine the extent to which individuals with congenital amusia draw upon visual information when making auditory or audio-visual judgments. Event-related potentials (ERP) were elicited by a change in pitch (up or down) between two sequential tones paired with a change in spatial position (up or down) between two visually presented dots. The change in dot position was either congruent or incongruent with the change in pitch. Participants were asked to judge (1) the direction of pitch change while ignoring the visual information (AV implicit task), and (2) whether the auditory and visual changes were congruent (AV explicit task). In the AV implicit task, amusic participants performed significantly worse in the incongruent condition than control participants. ERPs showed an enhanced N2-P3 response to incongruent AV pairings for control participants, but not for amusic participants. However when participants were explicitly directed to detect AV congruency, both groups exhibited enhanced N2-P3 responses to incongruent AV pairings. These findings indicate that amusics are capable of extracting information from both modalities in an AV task, but are biased to rely on visual information when it is available, presumably because they have learned that auditory information is unreliable. We conclude that amusic individuals implicitly draw upon visual information when judging auditory information, even though they have the capacity to explicitly recognize conflicts between these two sensory channels.

USP5 facilitates diabetic retinopathy development by stabilizing ROBO4 via deubiquitination.

Ubiquitin-specific proteases (USPs) have been proved to play important roles in the progression of diabetic retinopathy. In this study, we explored the role of USP5 and its possible mechanisms in diabetic retinopathy development. Cell proliferation, apoptosis, inflammation and oxidative stress were determined using CCK-8 assay, EdU staining assay, flow cytometry, and ELISA, respectively. The mRNA and protein expression of ROBO4 and USP5 were measured through RT-qPCR and western blot, respectively. Co-IP and deubiquitination assay were conducted to evaluate the interaction between ROBO4 and USP5. The results showed that high glucose (HG) stimulation significantly led to HRPE cell damage as described by suppressing proliferation, and promoting oxidative stress, inflammation and apoptosis. ROBO4 was markedly increased in diabetic retinopathy plasma samples and HG-triggered HRPE cells. Depletion of ROBO4 could alleviate HG-caused HRPE cell damage. USP5 was also significantly elevated in diabetic retinopathy plasma samples and HG-triggered HRPE cells. USP5 overexpression aggravated HG-induced HRPE cell damage. USP5 stabilized ROBO4 through deubiquitination. Moreover, USP5 knockdown decreased ROBO4 expression to mitigate HG-triggered cell damage in HRPE cells. USP5 stabilized ROBO4 via deubiquitination to repress cell proliferation, and facilitate inflammation, cell apoptosis and oxidative stress in HG-treated HRPE cells, thereby promoting the development of diabetic retinopathy.

Multimodal covarying brain patterns mediate genetic and psychological contributions to individual differences in pain sensitivity.

ABSTRACT: Individuals vary significantly in their pain sensitivity, with contributions from the brain, genes, and psychological factors. However, a multidimensional model integrating these factors is lacking due to their complex interactions. To address this, we measured pain sensitivity (ie, pain threshold and pain tolerance) using the cold pressor test, collected magnetic resonance imaging (MRI) data and genetic data, and evaluated psychological factors (ie, pain catastrophizing, pain-related fear, and pain-related anxiety) from 450 healthy participants with both sexes (160 male, 290 female). Using multimodal MRI fusion methods, we identified 2 pairs of covarying structural and functional brain patterns associated with pain threshold and tolerance, respectively. These patterns primarily involved regions related to self-awareness, sensory-discriminative, cognitive-evaluative, motion preparation and execution, and emotional aspects of pain. Notably, pain catastrophizing was negatively correlated with pain tolerance, and this relationship was mediated by the multimodal covarying brain patterns in male participants only. Furthermore, we identified an association between the single-nucleotide polymorphism rs4141964 within the fatty acid amide hydrolase gene and pain threshold, mediated by the identified multimodal covarying brain patterns across all participants. In summary, we suggested a model that integrates the brain, genes, and psychological factors to elucidate their role in shaping interindividual variations in pain sensitivity, highlighting the important contribution of the multimodal covarying brain patterns as important biological mediators in the associations between genes/psychological factors and pain sensitivity.

Intestinal Morphology and Glucose Transporter Gene Expression under a Chronic Intake of High Sucrose.

Sucrose is a disaccharide that is degraded into fructose and glucose in the small intestine. High-sucrose and high-fructose diets have been reported, using two-dimensional imaging, to alter the intestinal morphology and the expression of genes associated with sugar transport, such as sodium glucose co-transporter 1 (SGLT1), glucose transporter 2 (GLUT2), and glucose transporter 5 (GLUT5). However, it remains unclear how high-fructose and high-sucrose diets affect the expression of sugar transporters and the intestinal morphology in the whole intestine. We investigate the influence of a chronic high-sucrose diet on the expression of the genes associated with sugar transport as well as its effects on the intestinal morphology using 3D imaging. High sucrose was found to increase GLUT2 and GLUT5 mRNA levels without significant changes in the intestinal morphology using 3D imaging. On the other hand, the delay in sucrose absorption by an α-glucosidase inhibitor significantly improved the intestinal morphology and the expression levels of SGLT1, GLUT2, and GLUT5 mRNA in the distal small intestine to levels similar to those in the proximal small intestine, thereby improving glycemic control after both glucose and sucrose loading. These results reveal the effects of chronic high-sugar exposure on glucose absorption and changes in the intestinal morphology.