Multicenter radio-multiomic analysis for predicting breast cancer outcome and unravelling imaging-biological connection.

Radiomics offers a noninvasive avenue for predicting clinicopathological factors. However, thorough investigations into a robust breast cancer outcome-predicting model and its biological significance remain limited. This study develops a robust radiomic model for prognosis prediction, and further excavates its biological foundation and transferring prediction performance. We retrospectively collected preoperative dynamic contrast-enhanced MRI data from three distinct breast cancer patient cohorts. In FUSCC cohort (n = 466), Lasso was used to select features correlated with patient prognosis and multivariate Cox regression was utilized to integrate these features and build the radiomic risk model, while multiomic analysis was conducted to investigate the model's biological implications. DUKE cohort (n = 619) and I-SPY1 cohort (n = 128) were used to test the performance of the radiomic signature in outcome prediction. A thirteen-feature radiomic signature was identified in the FUSCC cohort training set and validated in the FUSCC cohort testing set, DUKE cohort and I-SPY1 cohort for predicting relapse-free survival (RFS) and overall survival (OS) (RFS: p = 0.013, p = 0.024 and p = 0.035; OS: p = 0.036, p = 0.005 and p = 0.027 in the three cohorts). Multiomic analysis uncovered metabolic dysregulation underlying the radiomic signature (ATP metabolic process: NES = 1.84, p-adjust = 0.02; cholesterol biosynthesis: NES = 1.79, p-adjust = 0.01). Regarding the therapeutic implications, the radiomic signature exhibited value when combining clinical factors for predicting the pathological complete response to neoadjuvant chemotherapy (DUKE cohort, AUC = 0.72; I-SPY1 cohort, AUC = 0.73). In conclusion, our study identified a breast cancer outcome-predicting radiomic signature in a multicenter radio-multiomic study, along with its correlations with multiomic features in prognostic risk assessment, laying the groundwork for future prospective clinical trials in personalized risk stratification and precision therapy.

The Beijing angle closure progression study: design and methodology.

Purpose: The purpose of this study is to summarize the design and methodology of a large-scale trial in northern China, the Beijing Angle Closure Progression Study (BAPS). This trial is designed to explore the 5-year incidence of primary angle-closure suspect (PACS) progressing to primary angle-closure (PAC) or primary angle-closure glaucoma (PACG) and to determine the possible risk factors of disease progression. Methods/design: The BAPS is a clinic-based, multicenter, noninterventional trial conducted on a sample of urban Chinese adults. Consecutive eligible patients who meet PACS diagnostic criteria will be recruited from eight participating centers, with the trial commencing on August 4, 2022. The target sample size is set at 825 subjects, with follow up planned for a minimum period of 5 years. Baseline examination will include presenting visual acuity, best corrected visual acuity, intraocular pressure (IOP), undilated slit-lamp biomicroscopy, stereoscopic evaluation of the optic disc, visual field test, optical coherence tomography evaluation of retinal nerve fiber layer, ultrasound biomicroscopy and IOLMaster. Questionnaires will also be used to collect detailed personal history. Patients are scheduled to visit the glaucoma clinic every 12 months and may visit the emergency room in case of acute attack of angle closure. Study endpoints include acute PAC episodes, elevated IOP, peripheral anterior synechiae, glaucomatous visual field defect, or glaucomatous abnormality of optic nerve. Discussion: The BAPS will provide data on the 5-year incidence of PACS progressing to PAC or PACG and determine the risk factors for disease progression. This study will also help redefine high-risk patients with PACS.

Deoxyshikonin: a promising lead drug grass against drug resistance or sensitivity to Helicobacter pylori in an acidic environment.

Helicobacter pylori (H. pylori) is closely associated with the diseases such as gastric sinusitis, peptic ulcers, and gastric adenocarcinoma. Its drug resistance is very severe, and new antibiotics are urgently needed. Nine comfrey compounds were screened by antimicrobial susceptibility testing, among which deoxyshikonin had the best inhibitory effect, with a minimum inhibitory concentration (MIC) of 0.5-1 µg/mL. In addition, deoxyshikonin also has a good antibacterial effect in an acidic environment, it is highly safe, and H. pylori does not readily develop drug resistance. Through in vivo experiments, it was proven that deoxyshikonin (7 mg/kg) had a beneficial therapeutic effect on acute gastritis in mice infected with the multidrug-resistant H. pylori BS001 strain. After treatment with desoxyshikonin, colonization of H. pylori in the gastric mucosa of mice was significantly reduced, gastric mucosal damage was repaired, inflammatory factors were reduced, and the treatment effect was better than that of standard triple therapy. Therefore, deoxyshikonin is a promising lead drug to solve the difficulty of drug resistance in H. pylori, and its antibacterial mechanism may be to destroy the biofilm and cause an oxidation reaction.

The Suprainguinal Fascia Iliaca Block Prolonging Spinal Anesthesia Duration.

Spinal anesthesia is commonly used for lower limb procedures, its duration may be limited with potential complications due to high doses of local anesthetic. This study describes the technique and experience of using suprainguinal fascia iliaca block (SIFI) as an adjunct to spinal anesthesia in an elderly patient undergoing lower extremity surgery. The case presented here involves an 81-year-old female undergoing hip surgery, where a SIFI block was performed prior to the administration of spinal anesthesia. Despite the unexpectedly prolonged surgical duration of approximately 5 hours, the patient remained comfortable, and the surgery was completed without complications. Subarachnoid block for provision of surgical anesthesia generally lasts between 2 and 3 hours with dose-dependent local anesthetic-related adverse effects. This may hinder the utility of spinal anesthesia in complex cases where extended surgical duration may be expected. The continuous spinal anesthesia and combined spinal-epidural (CSE) are useful techniques to provide consistent peri-operative anesthesia with precise titration of anesthesia levels. However, this presents with a risk of accidental dural puncture with CSE, post-dural puncture headache, and inadvertent drug errors with a spinal or epidural catheter. The judicious use of other adjuvants alongside local anesthetics offers advantages in extending the duration of anesthesia by a modest increment. The integration of spinal anesthesia with SIFI is a promising strategy to extend block duration, reduce peri-operative opioid requirements, and enhance patient outcomes. Overall, SIFI is a safe anesthetic technique for the peri-operative management of hip fracture patients and may present synergistic effects when combined with spinal anesthesia and may prolong the duration of regional anesthesia during unexpectedly prolonged surgery.

Effects of Mung Bean Water Supplementation on Modulating Lipid and Glucose Metabolism in a Diabetic Rat Model.

Type 2 diabetes mellitus (T2DM) is often associated with chronic inflammation exacerbated by hyperglycemia and dyslipidemia. Mung beans have a longstanding reputation in traditional medicine for their purported ability to lower blood glucose levels, prompting interest in their pharmacological properties. This study aimed to explore the impact of mung bean water (MBW) on carbohydrate and lipid metabolism in a T2DM rat model induced by nicotinamide/streptozotocin. Normal and DM rats were supplemented with a stock solution of MBW as drinking water ad libitum daily for 8 weeks. MBW supplementation led to significant reductions in plasma total cholesterol, HDL-C, and VLDL-C + LDL-C levels, and decreased malondialdehyde levels in plasma and liver samples, indicating reduced oxidative stress. MBW supplementation lowered plasma glucose levels and upregulated hepatic hexokinase activity, suggesting enhanced glucose utilization. Additionally, MBW decreased hepatic glucose-6-phosphate dehydrogenase and glutathione peroxidase activities, while hepatic levels of glutathione and glutathione disulfide remained unchanged. These findings underscore the potential of MBW to improve plasma glucose and lipid metabolism in DM rats, likely mediated by antioxidant effects and the modulation of hepatic enzyme activities. Further exploration of bioactive components of MBW and its mechanisms could unveil new therapeutic avenues for managing diabetes and its metabolic complications.

Integrative rehabilitation in the treatment of lumbosacral muscle strain in elite trampoline athletes: a pilot study.

Background: Lumbosacral muscle strain (LMS) is common in Chinese elite trampoline athletes. Advanced lumbar muscle activation is necessary for postural control before upper extremity voluntary movements, called anticipatory postural adjustment to reduce internal postural interference (IPI). The potential of delayed lumbar muscle activation has been reported in patients with non-specific LBP (NLBP) in response to IPI. However, it remains unknown whether this effect exists in elite trampoline athletes. There is also limited literature reporting the rehabilitation of LMS in this population. This study first aimed to explore whether elite trampoline athletes with LMS experience delayed activation of lumbar muscles under IPI. The secondary aim was to preliminarily evaluate an integrative rehabilitation program's effectiveness. Materials and methods: Ten elite trampoline athletes with LMS were recruited and received 10 sessions of integrative rehabilitation, including extracorporeal shock wave therapy, acupuncture, Tui-na, and spine function exercises. At baseline and after all sessions, the relative activation time of the lumbar muscles under IPI in a modified rapid arm-rise test was used as a primary outcome measure. The secondary measures included a visual analog scale (VAS) and a questionnaire to assess low back pain (LBP) and athletic training performance. Results: The relative activation time of the lumbar muscles under IPI was delayed at baseline, but significantly decreased after the intervention (P < 0.05). The VAS was significantly decreased after the intervention (P < 0.05). There was no significant correlation between the difference in VAS and in activation time of the lumbar muscles before and after the intervention (P > 0.05). Conclusions: Elite trampoline athletes with LMS had delayed activation in their lumbar muscles under IPI. Integrative rehabilitation was effective in LBP relief and neuromuscular control of the lumbar muscles, and impacted positively on training performance. Future studies with a larger sample size, a control group, and long-term follow-ups are needed to further examine the efficacy of integrative rehabilitation in elite trampoline athletes with LMS. Additionally, the application of this approach in athletes with LMS or LBP in other sports, particularly those involving IPI, should be explored.

Magnetic resonance imaging-based radiomics nomogram for the evaluation of therapeutic responses to neoadjuvant chemohormonal therapy in high-risk non-metastatic prostate cancer.

PURPOSE: The aim of this study was to assess the potential application of a radiomics features-based nomogram for predicting therapeutic responses to neoadjuvant chemohormonal therapy (NCHT) in patients with high-risk non-metastatic prostate cancer (PCa). METHODS: Clinicopathologic information was retrospectively collected from 162 patients with high-risk non-metastatic PCa receiving NCHT and radical prostatectomy at our center. The postoperative pathological findings were used as the gold standard for evaluating the efficacy of NCHT. The least absolute shrinkage and selection operator (LASSO) was conducted to develop radiomics signature. Multivariate logistic regression analyses were conducted to identify the predictors of a positive pathological response to NCHT, and a nomogram was constructed based on these predictors. RESULTS: Sixty-three patients (38.89%) experienced positive pathological response to NCHT. Receiver operating characteristic analyses showed that the area under the curve (AUC) of periprostatic fat (PPF) radiomics signature was 0.835 (95% CI, 0.754-0.898), while the AUC of intratumoral radiomics signature was 0.822 (95% CI, 0.739-0.888). Multivariate logistic regression analysis revealed that PSA level, PPF radiomics signature and intratumoral radiomics signature were independent predictors of positive pathological response. A nomogram based on these three predictors was constructed. The AUC was 0.908 (95% CI, 0.839-0.954). The Hosmer-Lemeshow goodness-of-fit test showed that the nomogram was well calibrated. Decision curve analysis revealed the favorable clinical practicability of the nomogram. The nomogram was successfully validated in the validation cohort. Kaplan-Meier analyses showed that nomogram and positive pathological response were significantly related with survival of PCa. CONCLUSION: The radiomics-clinical nomogram based on mpMRI radiomics features exhibited superior predictive ability for positive pathological response to NCHT in high-risk non-metastatic PCa.

The Influence of Climate Change on the Distribution of Hibiscus mutabilis in China: MaxEnt Model-Based Prediction.

Our study utilized 374 geographical distribution records of H. mutabilis and 19 bioclimatic factors, employing the MaxEnt model and the Geographic Information System (ArcGIS). The key environmental variables influencing the suitable distribution areas of H. mutabilis were analyzed through the comprehensive contribution rate, permutation importance, and Pearson correlation coefficient. Based on this analysis, the contemporary and future suitable distribution areas and their extents were predicted. The results indicate that the key limiting factor affecting the suitable distribution areas of H. mutabilis is the precipitation of the driest month (bio14), with secondary factors being annual precipitation (bio12), annual mean temperature (bio1), and annual temperature range (bio7). Under contemporary climate conditions, the total suitable area for H. mutabilis is approximately 2,076,600 km2, primarily concentrated in the tropical and subtropical regions of southeastern China. Under low-to-medium-emission scenarios (SSP1-2.6, SSP2-4.5), the total suitable area of H. mutabilis shows a trend of first decreasing and then increasing compared to the current scenario. In contrast, under high-emission scenarios (SSP5-8.5), it exhibits a trend of first increasing and then decreasing. The spatial pattern changes indicate that the retention rate of suitable areas for H. mutabilis ranges from 95.28% to 99.28%, with the distribution centers primarily located in Hunan and Guizhou provinces, showing an overall migration trend towards the west and north. These findings suggest that H. mutabilis possesses a certain level of adaptability to climate change. However, it is crucial to consider regional drought and sudden drought events in practical cultivation and introduction processes. The results of our study provide a scientific basis for the rational cultivation management, conservation, and utilization of germplasm resources of H. mutabilis.

Mitigating Ni and Cu ecotoxicity in the ecological restoration material and ornamental Primula forbesii Franch. with exogenous 24-epibrassinolide and melatonin.

Nickel (Ni) and copper (Cu) contamination have become major threats to plant survival worldwide. 24-epibrassinolide (24-EBR) and melatonin (MT) have emerged as valuable treatments to alleviate heavy metal-induced phytotoxicity. However, plants have not fully demonstrated the potential mechanisms by which these two hormones act under Ni and Cu stress. Herein, this study investigated the impact of individual and combined application of 24-EBR and MT on the growth and physiological traits of Primula forbesii Franch. subjected to stress (200 µmol L-1 Ni and Cu). The experiments compared the effects of different mitigation treatments on heavy metal (HM) stress and the scientific basis and practical reference for using these exogenous substances to improve HM resistance of P. forbesii in polluted environments. Nickel and Cu stress significantly hindered leaf photosynthesis and nutrient uptake, reducing plant growth and gas exchange. However, 24-EBR, MT, and 24-EBR + MT treatments alleviated the growth inhibition caused by Ni and Cu stress, improved the growth indexes of P. forbesii, and increased the gas exchange parameters. Exogenous MT effectively alleviated Ni stress, and 24-EBR + MT significantly alleviated the toxic effects of Cu stress. Unlike HM stress, MT and 24-EBR + MT activated the antioxidant enzyme activity (by increasing superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT)), significantly reduced reactive oxygen species (ROS) accumulation, and regulated ascorbate and glutathione cycle (AsA-GSH) efficiency. Besides, the treatments enhanced the ability of P. forbesii to accumulate HMs, shielding plants from harm. These findings conclusively illustrate the capability of 24-EBR and MT to significantly bolster the tolerance of P. forbesii to Ni and Cu stress.

Crystal structure and characterization of monascin from the extracts of Monascus purpureus-fermented rice.

We present a novel solid form of monascin, an azaphilonoid derivative extracted from Monascus purpureus-fermented rice. The crystal structure, C21H26O5, was characterized by single-crystal X-ray diffraction and belongs to the orthorhombic space group P212121. To gain insight into the electronic properties of the short contacts in the crystalline state of monascin, we utilized the Experimental Library of Multipolar Atom Model 2 (ELMAM2) database to transfer the electron density of monascin in its crystalline state. Hirshfeld surface analysis, fingerprint analysis, electronic properties and energetic characterization reveal that intermolecular C-H...O hydrogen bonds play a crucial role in the noncovalent bonding interactions by connecting molecules into two- and three-dimensional networks. The molecular electrostatic potential (MEP) map of the monascin molecule demonstrates that negatively charged regions located at four O atoms are favoured binding sites for more positively charged amino acid residues during molecular recognition. In addition, powder X-ray diffraction confirms that no transformation occurs during the crystallization of monascin.

Salinity influence correction for zinc ion seawater quality criteria and ecological risk assessment in Chinese seas.

The increasing prevalence of zinc pollution in marine ecosystems, primarily from industrial sources, has become a global environmental concern. This study addresses zinc toxicity in Chinese coastal waters, emphasizing the importance of considering environmental factors like salinity and temperature in establishing water quality criteria (WQC). Data collected from various marine regions underwent meticulous analysis, incorporating salinity corrections to derive more precise criteria values. The short-term criteria for the Bohai Sea, Yellow Sea, East China Sea, and South China Sea were 94.0, 77.6, 84.2, and 118 µg/L under the salinity correction, respectively, and the long-term criteria was 4.10 µg/L. Ecological risk assessments employing diverse methodologies revealed varying levels of risk across sea areas, underscoring the nuanced nature of zinc pollution's impact on marine ecosystems. Greater acute and chronic risk of zinc ions observed in the Yellow Sea region. These findings underscore the imperative need for tailored management strategies to protect local marine life from the environmental threats posed by zinc.

Recent Research on Iridium-Based Electrocatalysts for Acidic Oxygen Evolution Reaction from the Origin of Reaction Mechanism.

As the anode reaction of proton exchange membrane water electrolysis (PEMWE), the acidic oxygen evolution reaction (OER) is one of the main obstacles to the practical application of PEMWE due to its sluggish four-electron transfer process. The development of high-performance acidic OER electrocatalysts has become the key to improving the reaction kinetics. To date, although various excellent acidic OER electrocatalysts have been widely researched, Ir-based nanomaterials are still state-of-the-art electrocatalysts. Hence, a comprehensive and in-depth understanding of the reaction mechanism of Ir-based electrocatalysts is crucial for the precise optimization of catalytic performance. In this review, the origin and nature of the conventional adsorbate evolution mechanism (AEM) and the derived volcanic relationship on Ir-based electrocatalysts for acidic OER processes are summarized and some optimization strategies for Ir-based electrocatalysts based on the AEM are introduced. To further investigate the development strategy of high-performance Ir-based electrocatalysts, several unconventional OER mechanisms including dual-site mechanism and lattice oxygen mediated mechanism, and their applications are introduced in detail. Thereafter, the active species on Ir-based electrocatalysts at acidic OER are summarized and classified into surface Ir species and O species. Finally, the future development direction and prospect of Ir-based electrocatalysts for acidic OER are put forward.

Rationale Design for Anchoring Pendant Groups of Zwitterionic Polymeric Medical Coatings.

A biocompatible and antifouling polymeric medical coating was developed through rational design for anchoring pendant groups for the modification of stainless steel. Zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC) was copolymerized individually with three anchoring monomers of carboxyl acrylamides with different alkyl spacers, including acryloylglycine (2-AE), 6-acrylamidohexanoic acid (6-AH), and 11-acrylamidoundecanoic acid (11-AU). The carboxylic acid groups are responsible for the stable grafting of copolymers onto stainless steel via a coordinative interaction with metal oxides. Due to hydrophobic interaction and hydrogen bonding, the anchoring monomers enable the formation of self-assembling structures in solution and at a metallic interface, which can play an important role in the thin film formation and functionality of the coatings. Therefore, surface characterizations of anchoring monomers on stainless steel were conducted to analyze the packing density and strength of the intermolecular hydrogen bonds. The corresponding copolymers were synthesized, and their aggregate structures were assessed, showing micelle aggregation for copolymers with higher hydrophobic compositions. The synergistic effects of inter/intramolecular interactions and hydrophobicity of the anchoring monomers result in the diversity of the thickness, surface coverage, wettability, and friction of the polymeric coatings on stainless steel. More importantly, the antifouling properties of the coatings against bacteria and proteins were strongly correlated to thin film formation. Ultimately, the key lies in deciphering the molecular structure of the anchoring pendants in thin film formation and assessing the effectiveness of the coatings, which led to the development of medical coatings through the graft-onto approach.

Transcriptomics analyses reveal the key genes involved in stamen petaloid formation in Alcea rosea L.

Alcea rosea L. is a traditional flower with a long cultivation history. It is extensively cultivated in China and is widely planted in green belt parks or used as cut flowers and potted ornamental because of its rich colors and flower shapes. Double-petal A. rosea flowers have a higher aesthetic value compared to single-petal flowers, a phenomenon determined by stamen petaloid. However, the underlying molecular mechanism of this phenomenon is still very unclear. In this study, an RNA-based comparative transcriptomic analysis was performed between the normal petal and stamen petaloid petal of A. rosea. A total of 3,212 differential expressed genes (DEGs), including 2,620 up-regulated DEGs and 592 down-regulated DEGs, were identified from 206,188 unigenes. Numerous DEGs associated with stamen petaloid were identified through GO and KEGG enrichment analysis. Notably, there were 63 DEGs involved in the plant hormone synthesis and signal transduction, including auxin, cytokinin, gibberellin, abscisic acid, ethylene, brassinosteroid, jasmonic acid, and salicylic acid signaling pathway and 56 key transcription factors (TFs), such as MADS-box, bHLH, GRAS, and HSF. The identification of these DEGs provides an important clue for studying the regulation pathway and mechanism of stamen petaloid formation in A. rosea and provides valuable information for molecular plant breeding.

C-reactive protein is a predictor for lower-extremity deep venous thrombosis in patients with primary intracerebral hemorrhage.

OBJECTIVE: Our study aimed to determine whether there exists an association between low-grade systemic inflammation, as measured by serum C-reactive protein (CRP), and the risk of lower-extremity deep venous thrombosis (LEDVT) in patients with primary intracerebral hemorrhage (ICH). METHODS: This observational study was retrospectively conducted on patients with primary ICH who were presented to two tertiary medical centers between January 2021 and August 2022. The primary outcome was detecting LEDVT occurrence within 14 days from the onset of the acute ICH episode. Weighted logistic regression and restricted cubic spline models were employed to estimate the association between CRP and LEDVT following 1:1 propensity score matching (PSM). RESULTS: Of the 538 patients with primary ICH who met the inclusion criteria, 76 (14.13%) experienced LEDVT. Based on the cut-off levels of CRP measured upon admission from the receiver operating characteristic (ROC) curve, patients with primary ICH were categorized into two groups: (i) CRP < 1.59 mg/L and (ii) CRP ≥ 1.59 mg/L. After 1:1 PSM, the LEDVT events occurred in 24.6% of patients with CRP ≥ 1.59 mg/L and 4.1% of patients with CRP < 1.59 mg/L (P < 0.001). ROC curve revealed the area under the ROC curve of 0.717 [95% confidence interval (CI) 0.669-0.761, P < 0.001] for CRP to predict LEDVT with a sensitivity of 85.71% and specificity of 56.29%. After adjusting for all confounding variables, the occurrence of LEDVT in ICH patients with higher CRP levels (≥ 1.59 mg/L) was 10.8 times higher compared to those with lower CRP levels (95% CI 4.5-25.8, P < 0.001). A nonlinear association was observed between CRP and an increased risk of LEDVT in the fully adjusted model (P for overall < 0.001, P for nonlinear = 0.001). The subgroup results indicated a consistent positive link between CRP and LEDVT events following primary ICH. CONCLUSIONS: Higher initial CRP levels (CRP as a dichotomized variable) in patients with primary ICH are significantly associated with an increased risk of LEDVT and may help identify high-risk patients with LEDVT. Clinicians should be vigilant to enable early and effective intervention in patients at high risk of LEDVT.

Washed microbiota transplantation promotes homing of group 3 innate lymphoid cells to the liver via the CXCL16/CXCR6 axis: a potential treatment for metabolic-associated fatty liver disease.

Despite the observed decrease in liver fat associated with metabolic-associated fatty liver disease (MAFLD) in mice following fecal microbiota transplantation, the clinical effects and underlying mechanisms of washed microbiota transplantation (WMT), a refined method of fecal microbiota transplantation, for the treatment of MAFLD remain unclear. In this study, both patients and mice with MAFLD exhibit an altered gut microbiota composition. WMT increases the levels of beneficial bacteria, decreases the abundance of pathogenic bacteria, and reduces hepatic steatosis in MAFLD-affected patients and mice. Downregulation of the liver-homing chemokine receptor CXCR6 on ILC3s results in an atypical distribution of ILC3s in patients and mice with MAFLD, characterized by a significant reduction in ILC3s in the liver and an increase in ILC3s outside the liver. Moreover, disease severity is negatively correlated with the proportion of hepatic ILC3s. These hepatic ILC3s demonstrate a mitigating effect on hepatic steatosis through the release of IL-22. Mechanistically, WMT upregulates CXCR6 expression on ILC3s, thereby facilitating their migration to the liver of MAFLD mice via the CXCL16/CXCR6 axis, ultimately contributing to the amelioration of MAFLD. Overall, these findings highlight that WMT and targeting of liver-homing ILC3s could be promising strategies for the treatment of MAFLD.

Krause corpuscles are genital vibrotactile sensors for sexual behaviours.

Krause corpuscles, which were discovered in the 1850s, are specialized sensory structures found within the genitalia and other mucocutaneous tissues1-4. The physiological properties and functions of Krause corpuscles have remained unclear since their discovery. Here we report the anatomical and physiological properties of Krause corpuscles of the mouse clitoris and penis and their roles in sexual behaviour. We observed a high density of Krause corpuscles in the clitoris compared with the penis. Using mouse genetic tools, we identified two distinct somatosensory neuron subtypes that innervate Krause corpuscles of both the clitoris and penis and project to a unique sensory terminal region of the spinal cord. In vivo electrophysiology and calcium imaging experiments showed that both Krause corpuscle afferent types are A-fibre rapid-adapting low-threshold mechanoreceptors, optimally tuned to dynamic, light-touch and mechanical vibrations (40-80 Hz) applied to the clitoris or penis. Functionally, selective optogenetic activation of Krause corpuscle afferent terminals evoked penile erection in male mice and vaginal contraction in female mice, while genetic ablation of Krause corpuscles impaired intromission and ejaculation of males and reduced sexual receptivity of females. Thus, Krause corpuscles of the clitoris and penis are highly sensitive mechanical vibration detectors that mediate sexually dimorphic mating behaviours.

Experiences of individuals presenting to the emergency department for mental health reasons: A systematic mixed studies review.

OBJECTIVE: Emergency departments the world over have seen substantial increases in the number of individuals presenting for mental health reasons. However, we have a limited understanding of their experiences of care. The aim of this review was to systematically examine and synthesise literature relating to the experiences of individuals presenting to emergency department for mental health reasons. METHODS: We followed Pluye and Hong's seven-step approach to conducting a systematic mixed studies review. Studies were included if they investigated adult mental health experiences in emergency department from the users' perspective. Studies describing proxy, carer/family or care provider experiences were excluded. RESULTS: Sixteen studies were included. Thematic synthesis identified three themes and associated subthemes. Theme 1 - ED staff can make-or-break and ED experience - comprised: Feeling understood and heard; Engaging in judgement-free interactions; Receiving therapeutic support; Being actively and passively invalidated for presenting to the ED; and Once a psych patient, always a psych patient. Theme 2 - Being in the ED environment is counter-therapeutic - comprised: Waiting for an 'extremely' long time; and Lacking privacy. Theme 3 was Having nowhere else to go. CONCLUSIONS: The experiences described by individuals presenting to emergency department for mental health reasons were mostly poor. The results illustrate a need for increased mental health education and training for all emergency department staff. Employment of specialist and lived experience workers should also be prioritised to support more therapeutic relationships and emergency department environments. In addition, greater investment in mental health systems is required to manage the current crisis and ensure future sustainability.

Ventricular Netrin-1 deficiency leads to defective pyramidal decussation and mirror movement in mice.

The corticospinal tract (CST) is the principal neural pathway responsible for conducting voluntary movement in the vertebrate nervous system. Netrin-1 is a well-known guidance molecule for midline crossing of commissural axons during embryonic development. Families with inherited Netrin-1 mutations display congenital mirror movements (CMM), which are associated with malformations of pyramidal decussation in most cases. Here, we investigated the role of Netrin-1 in CST formation by generating conditional knockout (CKO) mice using a Gfap-driven Cre line. A large proportion of CST axons spread laterally in the ventral medulla oblongata, failed to decussate and descended in the ipsilateral spinal white matter of Ntn1Gfap CKO mice. Netrin-1 mRNA was expressed in the ventral ventricular zone (VZ) and midline, while Netrin-1 protein was transported by radial glial cells to the ventral medulla, through which CST axons pass. The level of transported Netrin-1 protein was significantly reduced in Ntn1Gfap CKO mice. In addition, Ntn1Gfap CKO mice displayed increased symmetric movements. Our findings indicate that VZ-derived Netrin-1 deletion leads to an abnormal trajectory of the CST in the spinal cord due to the failure of CST midline crossing and provides novel evidence supporting the idea that the Netrin-1 signalling pathway is involved in the pathogenesis of CMM.