CRF regulates pain sensation by enhancement of corticoaccumbal excitatory synaptic transmission.

Both peripheral and central corticotropin-releasing factor (CRF) systems have been implicated in regulating pain sensation. However, compared with the peripheral, the mechanisms underlying central CRF system in pain modulation have not yet been elucidated, especially at the neural circuit level. The corticoaccumbal circuit, a structure rich in CRF receptors and CRF-positive neurons, plays an important role in behavioral responses to stressors including nociceptive stimuli. The present study was designed to investigate whether and how CRF signaling in this circuit regulated pain sensation under physiological and pathological pain conditions. Our studies employed the viral tracing and circuit-, and cell-specific electrophysiological methods to label the CRF-containing circuit from the medial prefrontal cortex to the nucleus accumbens shell (mPFCCRF-NAcS) and record its neuronal propriety. Combining optogenetic and chemogenetic manipulation, neuropharmacological methods, and behavioral tests, we were able to precisely manipulate this circuit and depict its role in regulation of pain sensation. The current study found that the CRF signaling in the NAc shell (NAcS), but not NAc core, was necessary and sufficient for the regulation of pain sensation under physiological and pathological pain conditions. This process was involved in the CRF-mediated enhancement of excitatory synaptic transmission in the NAcS. Furthermore, we demonstrated that the mPFCCRF neurons monosynaptically connected with the NAcS neurons. Chronic pain increased the protein level of CRF in NAcS, and then maintained the persistent NAcS neuronal hyperactivity through enhancement of this monosynaptic excitatory connection, and thus sustained chronic pain behavior. These findings reveal a novel cell- and circuit-based mechanistic link between chronic pain and the mPFCCRF → NAcS circuit and provide a potential new therapeutic target for chronic pain.

Lateral septum-lateral hypothalamus circuit dysfunction in comorbid pain and anxiety.

Pain and anxiety comorbidities are a common health problem, but the neural mechanisms underlying comorbidity remain unclear. We propose that comorbidity implies that similar brain regions and neural circuits, with the lateral septum (LS) as a major candidate, process pain and anxiety. From results of behavioral and neurophysiological experiments combined with selective LS manipulation in mice, we find that LS GABAergic neurons were critical for both pain and anxiety. Selective activation of LS GABAergic neurons induced hyperalgesia and anxiety-like behaviors. In contrast, selective inhibition of LS GABAergic neurons reduced nocifensive withdrawal responses and anxiety-like behaviors. This was found in two mouse models, one for chronic inflammatory pain (induced by complete Freund's adjuvant) and one for anxiety (induced by chronic restraint stress). Additionally, using TetTag chemogenetics to functionally mark LS neurons, we found that activation of LS neurons by acute pain stimulation could induce anxiety-like behaviors and vice versa. Furthermore, we show that LS GABAergic projection to the lateral hypothalamus (LH) plays an important role in the regulation of pain and anxiety comorbidities. Our study revealed that LS GABAergic neurons, and especially the LSGABAergic-LH circuit, are a critical to the modulation of pain and anxiety comorbidities.

GABAergic Neurons in the Dorsal-Intermediate Lateral Septum Regulate Sleep-Wakefulness and Anesthesia in Mice.

BACKGROUND: The γ-aminobutyric acid-mediated (GABAergic) inhibitory system in the brain is critical for regulation of sleep-wake and general anesthesia. The lateral septum contains mainly GABAergic neurons, being cytoarchitectonically divided into the dorsal, intermediate, and ventral parts. This study hypothesized that GABAergic neurons of the lateral septum participate in the control of wakefulness and promote recovery from anesthesia. METHODS: By employing fiber photometry, chemogenetic and optogenetic neuronal manipulations, anterograde tracing, in vivo electrophysiology, and electroencephalogram/electromyography recordings in adult male mice, the authors measured the role of lateral septum GABAergic neurons to the control of sleep-wake transition and anesthesia emergence and the corresponding neuron circuits in arousal and emergence control. RESULTS: The GABAergic neurons of the lateral septum exhibited high activities during the awake state by in vivo fiber photometry recordings (awake vs. non-rapid eye movement sleep: 3.3 ± 1.4% vs. -1.3 ± 1.2%, P < 0.001, n = 7 mice/group; awake vs. anesthesia: 2.6 ± 1.2% vs. -1.3 ± 0.8%, P < 0.001, n = 7 mice/group). Using chemogenetic stimulation of lateral septum GABAergic neurons resulted in a 100.5% increase in wakefulness and a 51.2% reduction in non-rapid eye movement sleep. Optogenetic activation of these GABAergic neurons promoted wakefulness from sleep (median [25th, 75th percentiles]: 153.0 [115.9, 179.7] s to 4.0 [3.4, 4.6] s, P = 0.009, n = 5 mice/group) and accelerated emergence from isoflurane anesthesia (514.4 ± 122.2 s vs. 226.5 ± 53.3 s, P < 0.001, n = 8 mice/group). Furthermore, the authors demonstrated that the lateral septum GABAergic neurons send 70.7% (228 of 323 cells) of monosynaptic projections to the ventral tegmental area GABAergic neurons, preferentially inhibiting their activities and thus regulating wakefulness and isoflurane anesthesia depth. CONCLUSIONS: The results uncover a fundamental role of the lateral septum GABAergic neurons and their circuit in maintaining awake state and promoting general anesthesia emergence time.

[Body Image and Its Clinical Implications].

Although the concept of body image was first introduced to Taiwan nursing in 1975, its application in the context of clinical nursing with regard to promoting humanistic patient-centered care has yet to be examined. This paper adopts a field-study approach to reinterpret the concept of body image with deeper and broader strength using patient vignettes, nursing case studies, and the findings of prior nursing research. The four main issues covered in this paper are: 1. The body image concept, 2. Building body schema and a postural model based on body experiences, 3. The characteristics of body image, and 4. The extended meaning of body image, including self-concept and the role function of relationship. This paper is expected to help nurses better understand the concept of body image and further apply this concept in clinical practice in order to improve the provision of humanistic patient-centered care.

Hydrogen breath test to detect small intestinal bacterial overgrowth: a prevalence case-control study in autism.

The aim of this study is to assess the prevalence of small intestinal bacterial overgrowth (SIBO) by hydrogen breath test in patients with autism spectrum disorders (ASD) with respect to a consistent control group. From 2011 to 2013, 310 children with ASD and 1240 sex- and age-matched typical children were enrolled in this study to undergo glucose breath test. The study participants were considered to exhibit SIBO when an increase in H2 of ≥20 ppm or CH4 of ≥10 ppm with respect to the fasting value was observed up to 60 min after the ingestion of glucose. Ninety-six children with autism suffered from SIBO, giving a prevalence rate of SIBO was 31.0% (95% CI 25.8-36.1%). In contrast, 9.3% of the typical children acknowledged SIBO. The difference between groups was statistically significant (P < 0.0001). The median Autism Treatment Evaluation Checklist (ATEC) score in the children with autism and with SIBO was significantly high when compared with the children without autism and without SIBO [98 (IQR, 45-120) vs. 63 (32-94), P < 0.001]. For the autism group, the 6-GI Severity Index (6-GSI) score was found to be strongly and significantly correlated with the total ATEC score (r = 0.639, P < 0.0001). SIBO was significantly associated with worse symptoms of autism, demonstrating that children with SIBO may significantly contribute to symptoms of autism.

Insights into the interactions between etheric compounds and myofibrillar proteins using multi-spectroscopy, molecular docking, and molecular dynamics simulation.

This study aimed to examine how the addition of etheric compounds (EC) affects the characteristics of myofibrillar proteins (MP) and to understand underlying interaction mechanisms. Fourier transform infrared spectroscopy confirmed that the EC-MP complex was formed through hydrogen bonding. The addition of EC resulted in an increase in the α-helix content and a decrease in the ß-sheet content of MP, which would promote the protein unfolding. The unfolding of MP led to aggregation and formation of larger and non-uniform particles. As a result, the exposure of negative charge on the MP surface was enhanced, and zeta potential was decreased from -5.33 mV to -7.45 mV. Moreover, the EC-induced modification of MP conformation resulted in a less rigid three-dimensional network structure of MP gel and enhanced the discharge of aldehyde compounds (C > 6). Moreover, the rheological characteristics of MP were enhanced by the suppression of protein-protein interactions due to the MP unfolding. Molecular dynamics simulations revealed that anethole reduced the binding capacity of myosin to decanal by raising its binding energy from -22.22 kcal/mol to -19.38 kcal/mol. In the meantime, anethole competed for the amino acid residue (PHE165) where myosin connects to decanal. This caused the hydrogen bonds and hydrophobic contacts between the two molecules to dissolve, altering myosin's conformation and releasing decanal. The results might be useful in predicting and controlling the ability of proteins to release and hold onto flavors.

Insights into flavor formation of braised chicken: Based on E-nose, GC-MS, GC-IMS, and UPLC-Q-Exactive-MS/MS.

Effects of braising duration on volatile organic compounds (VOCs) and lipids in chicken were investigated. Aroma profiles identified by an electronic nose were effective in differentiating braising stages. During braising process, a total of 25 key VOCs were detected in braised chicken, and sample braised for 210 min exhibited the highest level of key VOCs. Additionally, a gas chromatography mass spectrometry fingerprint was established to evaluate the distribution of VOCs throughout the braising process. Partial least square discriminant analysis indicated that 2-heptanone, 3-methyl-2-butanone, octanal, nonanal, butanal, (E)-2-pentenal, 1-octen-3-ol, 1-hexanol, pentanal, hexanal, and 1-pentanol significantly affected flavor characteristics of braised chicken. Furthermore, 88 differential lipids were screened, and glycerolipids metabolic was found to be main metabolic pathway during braising process. Triglycerides (TG) and phosphatidyl ethanolamine (PE), such as TG (16:0/18:1/18:2), TG (18:0/18:1/18:2), TG (18:1/18:2/18:3), TG (18:1/18:1/18:2), PE (O-18:2/18:2), PE(O-18:2/18:1), and TG (16:0/16:1/18:2), played a vital role in the generation of VOCs.

Conformational changes induced by selected flavor compounds from spices regulate the binding ability of myofibrillar proteins to aldehyde compounds.

Interactions among flavor compounds from spices (FCS) and myofibrillar proteins (MP) were investigated. Fluorescence and Fourier transform infrared spectroscopy showed that hydrogen bonding and hydrophobic interactions were the main binding forces between FCS and MP. The FCS increased the particle size and SH content of MP and caused a reduction of zeta potential from -5.23 to -6.50 mV. Furthermore, FCS could modify the binding ability of MP and aldehydes. Eugenol reduced the ability of MP to bond with aldehydes by 22.70-47.87 %. Molecular dynamics simulations demonstrated that eugenol may combat nonanal to attain binding site of amino acid residue (PHE165) and induce protein conformational changes. Electrostatic interactions and van der Waals forces within myosin-nonanal may be disrupted by these alterations, which could reduce stability of complex and cause release of nonanal. This study could provide new insights into regulating the ability of proteins to release and hold flavors.

Exploring the interaction between myofibrillar proteins and pyrazine compounds: Based on molecular docking, molecular dynamics simulation, and multi-spectroscopy techniques.

Flavor is one of the most important factors that affect consumers' preference for processed meat products. This study aimed to investigate effects of heating on interaction between myofibrillar proteins (MPs) and pyrazine compounds and understand the underlying mechanisms. A combination of multispectral, molecular docking, and molecular dynamics technologies was used to achieve study's aim. Results demonstrated that MPs underwent structural reconstruction and expansion during heating, which significantly altered surface hydrophobicity and SH content. MPs' zeta potential reduced from -7.29 to -10.47 when a short heating time. Additionally, a positive correlation was found between ß-sheet content and ability of MPs to adsorb pyrazine compounds. Molecular docking analysis revealed 13 binding sites for pyrazines and MPs. Furthermore, amino acid residues and pyrazine compounds were found to interact by four different forms of forces, primarily van der Waals forces, carbon­hydrogen bonds, alkyl groups, and π-alkyl groups. Obtained results demonstrated that adequate or optimized heat treatment could expose more binding sites, hence enhancing the binding of MPs to pyrazine compounds. This study may be used to better understand how structural changes in MPs during processing affect MPs' capacity to bind flavor substances, which can help improve flavor of processed meats to encourage their consumption.

Structural changes induced by ultrasound improve the ability of the myofibrillar protein to bind flavor compounds from spices.

Effects of ultrasound (UT) treatments on the structural, physicochemical, and functional properties of myofibrillar proteins (MPs), as well as their ability to bind to flavor compounds from spices, were investigated. The results demonstrated that UT treatment enhanced surface hydrophobicity, SH content, and absolute ζ-potential value of the MPs. Atomic force microscopy analysis displayed formation of MPs aggregates with small particle size in the UT-treated MPs samples. Meanwhile, UT treatment could improve the emulsifying properties and physical stability of MPs' emulsion. Additionally, the MPs gel network structure and stability significantly improved following UT treatment. Changes in the structural, physicochemical, and functional properties enhanced the ability of MPs to bind to flavor substances from spices depending on the duration of UT treatment. Furthermore, correlation analysis showed that the ability of myristicin, anethole, and estragole to bind to MPs was highly correlated with surface hydrophobicity, ζ-potential value, and α-helix content of MPs. The results of this study may help in understanding the relationship between the changes in MPs properties during the processing of meat products and their ability to bind to flavors from spices, thereby improving flavors retention and taste of processed meat products.

Understanding interactions among flavor compounds from spices and myofibrillar proteins by multi-spectroscopy and molecular docking simulation.

Influence of the constant heating treatment on structural and adsorption properties of myofibrillar proteins (MPs) of chicken was investigated. The results showed that heat treatment enhanced the exposure of sulfhydryl groups and improved hydrophobicity of MPs surface. Particle size distribution of MPs significantly varied depending on heat treatment duration. Also, heat treatments resulted in significant changes in the α-helix and ß-sheet structures of MPs. Besides, the MPs formed larger, irregular, and cluster-like aggregates after heat treatments. Moreover, heat treatments increased viscosity and surface roughness of MPs, while zeta potential value was reduced after heat treatments. Furhthermore, binding interactions between the MPs and spices flavors signifcanlty varied relying on nature of MPs and flavor compounds, as well as heat treatments duration. Amino acid residues were interacted with flavor compounds of spices via a variety of bonds and a stable MPs-flavors complex was performed. The obtained results provide a basis for understanding structural and physicochemical changes that occur in MPs during cooking and the interactions between MPs and flavors of spices.

Characterization of aroma profiles of chinese four most famous traditional red-cooked chickens using GC-MS, GC-IMS, and E-nose.

The aroma profile of the four most popular types of red-cooked chickens in China was analyzed using a combination of gas chromatography-mass spectrometry (GC-MS), gas chromatography-ion mobility spectrometry (GC-IMS), and electronic nose (E-nose). Principal component analysis (PCA) demonstrated that the E-nose could successfully distinguish between the four types of red-cooked chickens. Additionally, a fingerprint was created using GC-IMS to examine the variations in volatile organic compounds (VOCs) distribution in the four chicken types. A total number of 84 and 62 VOCs were identified in the four types of red-cooked chickens using GC-MS and GC-IMS, respectively. Odor activity value (OAV) showed that 1-octen-3-ol, heptanal, hexanal, nonanal, octanal, eugenol, dimethyl trisulfide, anethole, anisaldehyde, estragole, and eucalyptol were the key volatile components in all samples. Furthermore, partial least squares-discriminant analysis (PLS-DA) demonstrated that (E, E)-2,4-decadienal, dimethyl trisulfide, octanal, eugenol, hexanal, (E)-2-nonenal, 1-octen-3-ol, butanal, ethyl acetate, ethyl acetate (D), nonanal, and heptanal could be used as markers to distinguish aroma of the four types of red-cooked chickens. Also, it is worth noting that levels of VOCs varied between chicken breast muscle and skin. The obtained results offer theoretical and technological support for flavor identification and control in red-cooked chickens to enhance their quality and encourage consumer consumption, which will be advantageous for the red-cooked chicken production chain.

KCNQ Channels in the Mesolimbic Reward Circuit Regulate Nociception in Chronic Pain in Mice.

Mesocorticolimbic dopaminergic (DA) neurons have been implicated in regulating nociception in chronic pain, yet the mechanisms are barely understood. Here, we found that chronic constructive injury (CCI) in mice increased the firing activity and decreased the KCNQ channel-mediated M-currents in ventral tegmental area (VTA) DA neurons projecting to the nucleus accumbens (NAc). Chemogenetic inhibition of the VTA-to-NAc DA neurons alleviated CCI-induced thermal nociception. Opposite changes in the firing activity and M-currents were recorded in VTA DA neurons projecting to the medial prefrontal cortex (mPFC) but did not affect nociception. In addition, intra-VTA injection of retigabine, a KCNQ opener, while reversing the changes of the VTA-to-NAc DA neurons, alleviated CCI-induced nociception, and this was abolished by injecting exogenous BDNF into the NAc. Taken together, these findings highlight a vital role of KCNQ channel-mediated modulation of mesolimbic DA activity in regulating thermal nociception in the chronic pain state.

Behaviors Related to Psychiatric Disorders and Pain Perception in C57BL/6J Mice During Different Phases of Estrous Cycle.

Robust sex difference among humans regarding psychiatry- and pain-related behaviors is being researched; however, the use of female mice in preclinical research is relatively rare due to an unchecked potential behavioral variation over the estrous cycle. In the present study, a battery of psychiatry- and pain-related behaviors are examined under physiological condition in female C57BL/6J mice over different estrous cycle phases: proestrus, estrous, metestrous, diestrous. Our behavioral results reveal that there is no significant difference over different phases of the estrous cycle in social interaction test, sucrose preference test, tail suspension test, open field test, marble burying test, novelty-suppressed feeding test, Hargreaves thermal pain test, and Von Frey mechanical pain test. These findings implicate those psychiatry- and pain-related behaviors in normal female C57BL/6J mice appear to be relatively consistent throughout the estrous cycle; the estrous cycle might not be a main contributor to female C57BL/6J mice's variability of behaviors.

Discrepancy between physicians' perceptions and practices during pelvic examinations in Taiwan.

OBJECTIVE: This study explored (1) physicians' perceptions of pelvic examination (PE) procedures and (2) the discrepancy between physicians' perceptions and their practices as observed by their attending nurses. METHOD: Data were collected from 20 physician-completed questionnaires on the perceived importance of 23 PE procedures. Each physician's practice of the same 23 PE procedures was assessed by 4-6 attending nurses (100 nurse observations). Physicians and nurses were sampled by convenience from the obstetrics/gynecology outpatient departments of 3 teaching hospitals in central Taiwan. Discrepancies between physicians' perceptions and their practices as assessed by attending nurses were examined by the Mann-Whitney U test. RESULTS: Physicians' mean scores ranged from 3.15 to 4.00, indicating that PE procedures were generally perceived as important. The procedures were rank ordered according to the mean scores from highest to lowest. Physicians' 5 top-ranking procedures were wearing gloves during the PE, asking agreement for the examination, paying attention to privacy during the PE, protecting the woman's personal information, and protecting the woman's medical records. Physicians' 5 lowest ranking procedures were telling the woman before inserting the speculum that she will feel some pressure, explaining the procedure before the PE, proactively providing information, asking the woman how she feels during the PE, asking a woman's permission to examine prior to commencing the PE, and describing observations to the woman during the PE (the last two procedures were tied for 5th rank). For 15 of the 23 PE procedures, physicians' perceptions did not differ significantly from their practices as assessed by attending nurses. The remaining 8 procedures were statistically significant between physicians' perception and their practices, and were rated higher by physicians (perception) than by attending nurses (practice). CONCLUSION: The 5 top-ranking PE procedures in terms of perceived importance were related to procedural behaviors, whereas the 5 lowest ranking procedures were verbal statements with explicit affective content. During nurse-observed PEs, Taiwanese physicians consistently practiced the procedural aspects of PEs they perceived as important (e.g., communication and consultation, protection and skilled technique, and confidentiality). However, physicians' practices were less consistent in affective aspects (e.g., explanation and consent, information and instruction, and sensitivity). PRACTICE IMPLICATIONS: Our results suggest that physicians should concentrate not only on procedural behaviors, but also on affective behaviors. These findings could be incorporated in medical education, particularly for medical students training to become obstetric and gynecological physicians.

Gynecologists' perception of the patient-physician relationship in pelvic examinations in Taiwan.

OBJECTIVE: To explore the gynecologists' physical contact and their interaction with patients, as well as the patient-physicians relationship during the pelvic examination (PE). STUDY DESIGN: This qualitative study uses face-to-face, in-depth interviews with 20 gynecologists from three hospitals in central Taiwan. RESULTS: The results revealed two main categories: adopting non-gendered and desexualised strategies and acknowledging a patient's situation. The majority of gynecologists adopted strategies to reduce their embarrassment during a PE, such as the use of a PE curtain, having a nurse in attendance, the tendency to depend on an ultrasound scan and the use of minimal verbal communication. CONCLUSION: Within the social context in Taiwan, male gynecologists tend to adopt a non-gendered and desexualised attitude to lessen the embarrassment and to protect them from accusations of sexual misconduct by patients during the PE. Acknowledging a patient's situation can benefit the gynecologists and allowed them to conduct the PE more easily. The results could possibly provide the medical student with an awareness and reflection of how social interaction plays a role for the gynecologists and their patients during a PE.

Decision-making tree for women considering hysterectomy.

AIMS: This paper reports on a study carried out to establish a decision tree model to describe how women in Taiwan make the decision whether or not to have a hysterectomy. In addition, we examined the predictability of the decision-tree model. BACKGROUND: Hysterectomy is the second most common surgical procedure performed worldwide. Medical professionals believe that the operation can relieve pain and prevent cervical cancer, thus improving a woman's quality of life. While most physicians advise hysterectomy even for benign uterine conditions, feminists decry the belief that the uterus has no purpose, believing that it is an important symbol of womanhood. METHODS: The study was conducted in two phases. Phase I, the model development phase, was carried out to generalize data from a qualitative study of 14 women and to establish a tree model outlining their decision to proceed with hysterectomy. The second phase was the model prediction phase that applied inductive and deductive methods to data analysis and development of the decision-tree model. The model tree was then tested with 18 women who were deciding whether or not to undergo hysterectomy. Using the decision-making tree, we studied the women's thought processes and analysed their primary concerns. The study was carried out in 1999-2001. RESULTS: The study determined 13 criteria that Taiwanese women use when deciding about having a hysterectomy. Developed in accordance with Gladwin's methodology, the model tree successfully predicted 90% of decisions whether or not to have a hysterectomy. CONCLUSIONS: Nurses working in gynaecological services should understand how women decide to undergo hysterectomy so that the proper counselling and follow-up can be provided. With further testing, our decision tree may help in this process.