MicroRNA-200c Release from Gelatin-Coated 3D-Printed PCL Scaffolds Enhances Bone Regeneration.

The fabrication of clinically relevant synthetic bone grafts relies on combining multiple biodegradable biomaterials to create a structure that supports the regeneration of defects while delivering osteogenic biomolecules that enhance regeneration. MicroRNA-200c (miR-200c) functions as a potent osteoinductive biomolecule to enhance osteogenic differentiation and bone formation; however, synthetic tissue-engineered bone grafts that sustain the delivery of miR-200c for bone regeneration have not yet been evaluated. In this study, we created novel, multimaterial, synthetic bone grafts from gelatin-coated 3D-printed polycaprolactone (PCL) scaffolds. We attempted to optimize the release of pDNA encoding miR-200c by varying gelatin types, concentrations, and polymer crosslinking materials to improve its functions for bone regeneration. We revealed that by modulating gelatin type, coating material concentration, and polymer crosslinking, we effectively altered the release rates of pDNA encoding miR-200c, which promoted osteogenic differentiation in vitro and bone regeneration in a critical-sized calvarial bone defect animal model. We also demonstrated that crosslinking the gelatin coatings on the PCL scaffolds with low-concentration glutaraldehyde was biocompatible and increased cell attachment. These results strongly indicate the potential use of gelatin-based systems for pDNA encoding microRNA delivery in gene therapy and further demonstrate the effectiveness of miR-200c for enhancing bone regeneration from synthetic bone grafts.

FKBP5 associated CD8 T cell infiltration is a novel prognostic biomarker in luminal B breast cancer.

OBJECTIVE: To investigate the relationship between FKBP prolyl isomerase 5 (FKBP5) gene expression and CD8 T cells in tumour progression and immunology of the luminal B subtype of breast cancer (LBBC) using bioinformatics analyses. METHODS: The Gene Expression Profiling Interactive Analysis 2, Human Protein Atlas and breast cancer gene-expression miner v4.5 databases were used for data mining and analysing FKBP5, its co-expressed genes and CD8 T cell-related markers. The Tumor IMmune Estimation Resource 2.0 database was used for analysing the correlation and prognosis of FKBP5 and CD8 T cell infiltration level in LBBC. RESULTS: Upregulated FKBP5 expression was correlated with improved survival in LBBC. Upregulated FKBP5-related CD8 T cell markers were also demonstrated to be significantly correlated with better survival in LBBC and might play a role in the biological activity of FKBP5. CONCLUSION: These findings suggest that FKBP5 and its associated CD8 T cell infiltration are potential benign prognostic indicators for LBBC.

CaCO 3 Nanoparticles Delivering MicroRNA-200c Suppress Oral Squamous Cell Carcinoma.

MicroRNA (miR)-200c suppresses the initiation and progression of oral squamous cell carcinoma (OSCC), the most prevalent head and neck cancer with high recurrence, metastasis, and mortality rates. However, miR-200c -based gene therapy to inhibit OSCC growth and metastasis has yet to be reported. To develop an miR-based gene therapy to improve the outcomes of OSCC treatment, this study investigates the feasibility of plasmid DNA encoding miR-200c delivered via non-viral CaCO 3 -based nanoparticles to inhibit OSCC tumor growth. CaCO 3 -based nanoparticles with various ratios of CaCO 3 and protamine sulfate (PS) were utilized to transfect pDNA encoding miR-200c into OSCC cells and the efficiency of these nanoparticles was evaluated. The proliferation, migration, and associated oncogene production, as well as in vivo tumor growth for OSCC cells overexpressing miR-200c were also quantified. It was observed that, while CaCO 3 -based nanoparticles improve transfection efficiencies of pDNA miR-200c , the ratio of CaCO 3 to PS significantly influences the transfection efficiency. Overexpression of miR-200c significantly reduced proliferation, migration, and oncogene expression of OSCC cells, as well as the tumor size of cell line-derived xenografts (CDX) in mice. In addition, a local administration of pDNA miR-200c using CaCO 3 delivery significantly enhanced miR-200c transfection and suppressed tumor growth of CDX in mice. These results strongly indicate that the nanocomplexes of CaCO 3 /pDNA miR-200c may potentially be used to reduce oral cancer recurrence and metastasis and improve clinical outcomes in OSCC treatment. (227 words).

Time-locked acute alpha-frequency stimulation of subthalamic nuclei during the evaluation of emotional stimuli and its effect on power modulation.

Introduction: Deep brain stimulation (DBS) studies in Parkinson's Disease (PD) targeting the subthalamic nucleus (STN) have characterized its spectral properties across cognitive processes. In emotional evaluation tasks, specific alpha frequency (8-12 Hz) event-related de-synchronization (ERD) (reduced power) has been demonstrated. The time-locked stimulation of STN relative to stimuli onset has shown subjective positive valence shifts with 10 Hz but not with 130 Hz. However, neurophysiological effects of stimulation on power modulation have not been investigated. We aim to investigate effects of acute stimulation of the right STN on concurrent power modulation in the contralateral STN and frontal scalp EEG. From our previous study, we had a strong a priori hypothesis that negative imagery without stimulation would be associated with alpha ERD; negative imagery with 130 Hz stimulation would be also associated with alpha ERD given the lack of its effect on subjective valence ratings; negative imagery with 10 Hz stimulation was to be associated with enhanced alpha power given the shift in behavioral valence ratings. Methods: Twenty-four subjects with STN DBS underwent emotional picture-viewing tasks comprising neutral and negative pictures. In a subset of these subjects, the negative images were associated with time-locked acute stimulation at either 10 or 130 Hz. Power of signals was estimated relative to the baseline and subjected to non-parametric statistical testing. Results: As hypothesized, in 130 Hz stimulation condition, we show a decrease in alpha power to negative vs. neutral images irrespective of stimulation. In contrast, this alpha power decrease was no longer evident in the negative 10 Hz stimulation condition consistent with a predicted increase in alpha power. Greater beta power in the 10 Hz stimulation condition along with correlations between beta power across the 10 Hz stimulation and unstimulated conditions suggest physiological and cognitive generalization effects. Conclusion: Acute alpha-specific frequency stimulation presumably was associated with a loss of this expected decrease or desynchronization in alpha power to negative images suggesting the capacity to facilitate the synchronization of alpha and enhance power. Acute time-locked stimulation has the potential to provide causal insights into the spectral frequencies and temporal dynamics of emotional processing.

A Medium Chain Fatty Acid, 6-hydroxyhexanoic acid (6-HHA), Protects Against Obesity and Insulin Resistance.

Obesity, a worldwide health problem, increases the risk for developing metabolic diseases such as insulin resistance and diabetes. It is well recognized that obesity-associated chronic inflammation plays a key role in the pathogenesis of systemic metabolic dysfunction. Previously, we revealed an anti-inflammatory role for spent culture supernatants isolated from the oral commensal bacterial species Streptococcus gordonii (Sg-SCS). Here, we identified that 6-hydroxyhexanoic acid (6-HHA), a medium chain fatty acid (MCFA), is the one of the key components of Sg-SCS . We found that treatment of 6-HHA in mice fed a high-fat diet (HFD) significantly reduced HFD-mediated weight gain which was largely attributed to a decrease in fat mass. Systemically, 6-HHA improves obesity-associated glucose intolerance and insulin resistance. Furthermore, administration of 6-HHA suppressed obesity-associated systemic inflammation and dyslipidemia. At the cellular level, treatment of 6-HHA ameliorated aberrant inflammatory and metabolic transcriptomic signatures in white adipose tissue of mice with diet-induced obesity (HFD). Mechanistically, we found that 6-HHA suppressed adipocyte-proinflammatory cytokine production and lipolysis, the latter through Gαi-mediated signaling. This work provides direct evidence for the anti-obesity effects of a novel MCFA, which could be a new therapeutic treatment for combating obesity. KEY POINTS: Hydroxyhexanoic medium chain fatty acids (MCFAs) are dietary and bacterial-derived energy sources, however, the outcomes of using MCFAs in treating metabolic disorders are diverse and complex. The MCFA 6-hydroxyhexanoic acid (6-HHA) is a metabolite secreted by the oral bacterial commensal species Streptococcus gordonii; here we investigated its role in modulating high-fat diet (HFD)-induced metabolic dysfunction. In a murine model of obesity, we found 6-HHA-mediated improvement of diet-mediated adiposity, insulin resistance and inflammation were in part due to actions on white adipose tissue (WAT).6-HHA suppressed proinflammatory cytokine production and lipolysis through Gi-mediated signaling in differentiated white adipocytes.

Evidence Accumulation and Neural Correlates of Uncertainty in Obsessive-Compulsive Disorder.

BACKGROUND: Decision making is frequently associated with risk taking under uncertainty. Elevated intolerance of uncertainty is suggested to be a critical feature of obsessive-compulsive disorder (OCD). However, impairments of latent constructs of uncertainty processing and its neural correlates remain unclear in OCD. METHODS: In 83 participants (24 OCD patients treated with capsulotomy, 28 OCD control participants, and 31 healthy control participants), we performed magnetic resonance imaging using a card gambling task in which participants made decisions whether to bet or not that the next card would be larger than the current one. A hierarchical drift diffusion model was used to dissociate speed and amount of evidence accumulated before a decisional threshold (i.e., betting or no betting) was reached. RESULTS: High uncertainty was characterized by a smaller amount of evidence accumulation (lower thresholds), thus dissociating uncertainty from conflict tasks and highlighting the specificity of this task to test value-based uncertainty. OCD patients exhibited greater caution with poor performance and greater evidence accumulation overall along with slower speed of accumulation, particularly under low uncertainty. Bilateral dorsal anterior cingulate and anterior insula distinguished high- and low-uncertainty decision processes in healthy control participants but not in the OCD groups, indicating impairments in anticipation of differences in outcome variance and salience network activity. There were no behavioral or imaging differences relating to capsulotomy despite improvements in OCD symptoms. CONCLUSIONS: Our findings highlight greater impairments particularly in more certain trials in the OCD groups along with impaired neural differentiation of high and low uncertainty and suggest uncertainty processing as a trait cognitive endophenotype rather than a state-specific factor.

Proteomic and physiological responses of contrasting two different heat-resistant orchardgrass genotypes to heat stress.

As an important forage crop worldwide, the growth and productivity of orchardgrass are greatly impacted by high temperatures. However, little information is known about how orchardgrass proteomic changes under heat conditions. Therefore, the present study investigated the proteomics and physiological changes in 667 [AKZ-NRGR667 (heat-tolerant)] and 7602 [PI237602 (heat-sensitive)] under heat stress (40/35 °C). In addition, the responses of translational regulating of heat stress in orchardgrass were analyzed through proteomic changes using the tandem mass tags (TMT) technique. Together, 410 differentially expressed proteins (DEPs) were identified from two orchardgrass genotypes under heat at 24 h. Proteomics analyses indicated that proteins related to substance metabolism, photosynthesis, and heat shock proteins (HSPs) were differentially expressed under heat stress and control conditions. Moreover, a large proportion of HSPs were expressed in the heat-tolerant genotype as compared to the heat-sensitive genotype. In conclusion, genotype 667 has higher adaptability and repairing capability due to stronger heat tolerance capacity that can make it more suited to sustaining its survival and growth than genotype 7602. These findings can provide the basis for genetic improvements in orchardgrass and other crops facing high-temperature stress or heat environment that may lead to heat resistance or tolerance.

Evaluation of the Antioxidant Activities and Phenolic Profile of Shennongjia Apis cerana Honey through a Comparison with Apis mellifera Honey in China.

This study evaluates the phenolic profile as well as the antioxidant properties of Shennongjia Apis cerana honey through a comparison with Apis mellifera honey in China. The total phenolic content (TPC) ranges from 263 ± 2 to 681 ± 36 mg gallic acid/kg. The total flavonoids content (TFC) ranges from 35.9 ± 0.4 to 102.2 ± 0.8 mg epicatechin/kg. The correlations between TPC or TFC and the antioxidant results (FRAP, DPPH, and ABTS) were found to be statistically significant (p < 0.01). Furthermore, the phenolic compounds are quantified and qualified by high performance liquid chromatography-high resolution mass spectrometry (HPLC-HRMS), and a total of 83 phenolic compounds were tentatively identified in this study. A metabolomics analysis based on the 83 polyphenols was carried out and subjected to principal component analysis and orthogonal partial least squares-discriminant analysis. The results showed that it was possible to distinguish Apis cerana honey from Apis mellifera honey based on the phenolic profile.

Mechanisms underlying capsulotomy for refractory obsessive-compulsive disorder: neural correlates of negative affect processing overlap with deep brain stimulation targets.

Ablative procedures such as anterior capsulotomy are potentially effective in refractory obsessive-compulsive disorder (OCD). Converging evidence suggests the ventral internal capsule white matter tracts traversing the rostral cingulate and ventrolateral prefrontal cortex and thalamus is the optimal target for clinical efficacy across multiple deep brain stimulation targets for OCD. Here we ask which prefrontal regions and underlying cognitive processes might be implicated in the effects of capsulotomy by using both task fMRI and neuropsychological tests assessing OCD-relevant cognitive mechanisms known to map across prefrontal regions connected to the tracts targeted in capsulotomy. We tested OCD patients at least 6 months post-capsulotomy (n = 27), OCD controls (n = 33) and healthy controls (n = 34). We used a modified aversive monetary incentive delay paradigm with negative imagery and a within session extinction trial. Post-capsulotomy OCD subjects showed improved OCD symptoms, disability and quality of life with no differences in mood or anxiety or cognitive task performance on executive, inhibition, memory and learning tasks. Task fMRI revealed post-capsulotomy decreases in the nucleus accumbens during negative anticipation, and in the left rostral cingulate and left inferior frontal cortex during negative feedback. Post-capsulotomy patients showed attenuated accumbens-rostral cingulate functional connectivity. Rostral cingulate activity mediated capsulotomy improvement on obsessions. These regions overlap with optimal white matter tracts observed across multiple stimulation targets for OCD and might provide insights into further optimizing neuromodulation approaches. Our findings also suggest that aversive processing theoretical mechanisms may link ablative, stimulation and psychological interventions.

Spent culture supernatant of Streptococcus gordonii mitigates inflammation of human periodontal cells and inhibits proliferation of pathogenic oral microbes.

BACKGROUND: The oral commensal bacterial species Streptococcus gordonii has been reported to regulate the inflammation of oral epithelial cells stimulated by the periodontal pathogen Porphyromonas gingivalis. This study investigated the activities of S. gordonii metabolites in S. gordonii spent culture supernatants (Sg-SCS) on periodontal-related bacterial growth and periodontitis-associated inflammatory cytokines. METHODS: Sg-SCS was collected from S. gordonii cultures grown in Dulbecco Modified Eagle Medium and added to the growth media of representative health- and disease-related oral species: S. gordonii, Streptococcus sanguinis, Streptococcus mitis, Streptococcus oralis, P. gingivalis, Tannerella forsythia, and Treponema denticola. The Sg-SCS was also tested for its ability to regulate the expression of proinflammatory cytokines by human macrophages, epithelial cells, and gingival fibroblasts upon stimulation with P. gingivalis-derived lipopolysaccharide (Pg-LPS). RESULTS: Sg-SCS significantly reduced transcript and protein levels of interleukin (IL)-1ß, 6, and 8 induced by Pg-LPS stimulation in multiple types of periodontal cells. mRNA sequencing and bioinformatics analyses indicated that Sg-SCS significantly affects 10 inflammatory pathways. Additionally, Sg-SCS exhibited suppression of the growth of periodontal disease-related bacteria, including T. denticola and P. gingivalis, along with the primary plaque-colonizing species S. oralis. At a low concentration, Sg-SCS also inhibits P. gingivalis adhesion. CONCLUSIONS: These results strongly suggest that S. gordonii-derived SCS contains metabolites that have anti-inflammatory properties and an ability to inhibit periodontitis-associated pathogenic bacteria. Further investigation will be needed to identify the individual metabolites within the Sg-SCS to develop a novel metabolite-based approach to treating and preventing periodontitis.

Risk and aversion coding in human habenula high gamma activity.

Neurons in the primate lateral habenula fire in response to punishments and are inhibited by rewards. Through its modulation of midbrain monoaminergic activity, the habenula is believed to play an important role in adaptive behavioural responses to punishment and underlie depressive symptoms and their alleviation with ketamine. However, its role in value-based decision-making in humans is poorly understood due to limitations with non-invasive imaging methods which measure metabolic, not neural, activity with poor temporal resolution. Here, we overcome these limitations to more closely bridge the gap between species by recording local field potentials directly from the habenula in 12 human patients receiving deep brain stimulation treatment for bipolar disorder (n = 4), chronic pain (n = 3), depression (n = 3) and schizophrenia (n = 2). This allowed us to record neural activity during value-based decision-making tasks involving monetary rewards and losses. High-frequency gamma (60-240 Hz) activity, a proxy for population-level spiking involved in cognitive computations, increased during the receipt of loss and decreased during receipt of reward. Furthermore, habenula high gamma also encoded risk during decision-making, being larger in amplitude for high compared to low risk. For both risk and aversion, differences between conditions peaked approximately between 400 and 750 ms after stimulus onset. The findings not only demonstrate homologies with the primate habenula but also extend its role to human decision-making, showing its temporal dynamics and suggesting revisions to current models. The findings suggest that habenula high gamma could be used to optimize real-time closed-loop deep brain stimulation treatment for mood disturbances and impulsivity in psychiatric disorders.

Association of Body Mass Index and Waist-to-Hip Ratio With Retinal Microvasculature in Healthy Chinese Adults: An Optical Coherence Tomography Angiography Study.

PURPOSE: To investigate the association of body mass index (BMI) and waist-to-hip ratio (WHR) with macular vessel density (VD) and foveal avascular zone (FAZ), using optical coherence tomography angiography (OCTA), in healthy Chinese adults. DESIGN: Cross-sectional study. METHODS: A total of 1555 Chinese adults aged ≥ 50 years with no history of ocular disease were recruited from communities in Guangzhou, China. The OCTA was performed with a 6 × 6 mm macular angiography model. The FAZ of the superficial capillary plexus (SCP), and VD of SCP and deep capillary plexus (DCP) were calculated. Univariable and multivariable linear regression analyses were used to evaluate the effect of BMI and WHR on VD and FAZ. RESULTS: The VD of the SCP increased as BMI increased, with average measurements of 39.30 ± 2.14 for normal, 39.52 ± 2.07 for overweight, and 39.76 ± 2.03 for obesity (P = .001). The VD of the DCP also increased with increasing BMI (P = .009). Multiple regression models confirmed a positive association between generalized obesity and superficial VD in the whole image (ß = 0.350, P = .008), inner circle (ß = 0.431, P = .032), and outer circle (ß = 0.368, P = .005). After adjusting for confounders, tertile 3 of the WHR level was positively associated with superficial VD (ß = 0.472, P = .033) and deep VD (ß = 0.422, P = .034) only in the inner circle. CONCLUSIONS: Generalized obesity was associated with increased superficial VD, while abdominal obesity was associated with increased superficial and deep VD only in the inner circle. Different manifestations of the retinal microvasculature may reflect distinct roles of body composition on macular vessel alterations and disease occurrence.

Association Between Lactate and 28-Day Mortality in Elderly Patients with Sepsis: Results from MIMIC-IV Database.

INTRODUCTION: This study aimed to explore the association of serum lactate with clinical outcomes in elderly patients with sepsis based on data from the MIMIC-IV database. METHODS: All elderly patients with sepsis (age ≥ 65 years) were included. Different models were constructed for exploring the relationships between lactate and 28-day mortality. A two-segment linear regression model was performed to verify the threshold effects of lactate on clinical outcomes and smooth curve fitting was performed. RESULTS: A total of 4199 elderly patients with sepsis were included. The 28-day mortality was 32.22% (n = 1395). After adjustment for all potential cofounders, for each 1 mmol/l increment in lactate, the odds ratio (OR) of 28-day mortality was 1.23 (95% CI 1.18-1.28, P < 0.0001). Smooth fitting curves indicated a non-linear positive relationship between lactate and 28-day mortality. The turning point of lactate level was 5.7 mmol/l: at ≤ 5.7 mmol/l, with each 1 mmol/l increment in lactate, the risk of 28-day mortality increased significantly (OR 1.32, 95% CI 1.25-1.38, P < 0.0001); the significantly positive relationship was still present at lactate > 5.7 mmol/l (OR 1.10, 95% CI 1.04-1.18, P = 0.0019). The area under the ROC curve (AUC) of lactate was 0.618 (95% CI 0.599-0.635) and the cutoff value of lactate was 2.4 mmol/l with a sensitivity of 0.483 and a specificity of 0.687. CONCLUSION: In elderly patients with sepsis, a non-linear positive relationship was discovered between serum lactate and 28-day mortality. Physicians should be alert to lactate assessment at admission and pay more attention to those patients with higher levels of lactate.

Subthalamic Oscillatory Activity of Reward and Loss Processing Using the Monetary Incentive Delay Task in Parkinson Disease.

BACKGROUND: The subthalamic nucleus (STN) is an effective deep brain stimulation target for Parkinson disease (PD) and obsessive-compulsive disorder and has been implicated in reward and motivational processing. In this study, we assessed the STN and prefrontal oscillatory dynamics in the anticipation and receipt of reward and loss using a task commonly used in imaging. MATERIALS AND METHODS: We recorded intracranial left subthalamic local field potentials from deep brain stimulation electrodes and prefrontal scalp electroencephalography in 17 patients with PD while they performed a monetary incentive delay task. RESULTS: During the expectation phase, enhanced left STN delta-theta activity was observed in both reward and loss vs neutral anticipation, with greater STN delta-theta activity associated with greater motivation specifically to reward. In the consummatory outcome phase, greater left STN delta activity was associated with a rewarding vs neutral outcome, particularly with more ventral contacts along with greater delta-theta coherence with the prefrontal cortex. We highlight a differential activity in the left STN to loss vs reward anticipation, demonstrating a distinct STN high gamma activity. Patients with addiction-like behaviors show lower left STN delta-theta activity to loss vs neutral outcomes, emphasizing impaired sensitivity to negative outcomes. CONCLUSIONS: Together, our findings highlight a role for the left STN in reward and loss processing and a potential role in addictive behaviors. These findings emphasize the cognitive-limbic function of the STN and its role as a physiologic target for neuropsychiatric disorders.

Plasmid encoding miRNA-200c delivered by CaCO3-based nanoparticles enhances rat alveolar bone formation.

Aim: miRNAs have been shown to improve the restoration of craniofacial bone defects. This work aimed to enhance transfection efficiency and miR-200c-induced bone formation in alveolar bone defects via plasmid DNA encoding miR-200c delivery from CaCO3 nanoparticles. Materials & methods: The CaCO3/miR-200c delivery system was evaluated in vitro (microscopy, transfection efficiency, biocompatibility) and miR-200c-induced in vivo alveolar bone formation was assessed via micro-computed tomography and histology. Results: CaCO3 nanoparticles significantly enhanced the transfection of plasmid DNA encoding miR-200c without inflammatory effects and sustained miR-200c expression. CaCO3/miR-200c treatment in vivo significantly increased bone formation in rat alveolar bone defects. Conclusion: CaCO3 nanoparticles enhance miR-200c delivery to accelerate alveolar bone formation, thereby demonstrating the application of CaCO3/miR-200c to craniofacial bone defects.

The restoration of craniofacial bone defects is surgically complex and requires the combined use of bone grafts and regenerative biomaterials. miRNAs are small biomolecules that have been shown to improve bone regeneration in large bone defects. The aim of this work was to develop a nanoparticle-based delivery system to sustain the release of miRNAs to improve the restoration of craniofacial bone defects. The results of this study demonstrated that CaCO₃ nanoparticles extend the delivery of miRNAs to enhance bone formation in a craniofacial bone defect animal model in a therapeutically safe manner that improves upon conventional nanoparticle materials for bone regeneration. The findings attest to the regenerative properties of miRNAs and further indicate the potential application of CaCO₃-based nanoparticles in restoring large bone defects.

A retrospective observational study of serum uric acid and in-hospital mortality in acute type A aortic dissection.

There is currently insufficient evidence of correlation between on-admission serum uric acid and in-hospital mortality of patients with acute type A aortic dissection. Thus, this study analysed the relation between serum uric acid and in-hospital deaths in patients with acute type A aortic dissection. A total of 1048 patients with acute type A aortic dissection participated in this study between January 2010 and December 2018. The independent variable was on-admission serum uric acid, whilst the dependent variable was in-hospital deaths. The covariates of the study included patient age, gender, body mass index, smoking status, hypertension, diabetes, Marfan syndrome, bicuspid aortic valve, chronic renal insufficiency, stroke, atherosclerosis, time to presentation, systolic blood pressure, diastolic blood pressure, aortic diameter, aortic regurgitation, abdominal vessel involvement, arch vessel involvement, ejection fraction value, laboratory parameters, symptom, coronary malperfusion, mesenteric malperfusion, cerebral malperfusion, hypotension/shock, cardiac tamponade and operation status. The mean age of the sample was 50.17 ± 11.47 years, with approximately 24.24% of the participants being female. After analysis, it was found that the admission serum uric acid of patients with acute type A aortic dissection was positively correlated with in-hospital death (OR = 1.04, 95% CI 1.02-1.06). Subsequently, a non-linear relationship was determined between admission serum uric acid (point 260 µmol/L) and in-hospital mortality for patients with acute type A aortic dissection. The effect sizes and confidence intervals of the right (serum uric acid > 260 µmol/L) and left (serum uric acid ≤ 260 µmol/L) aspects of the inflection point were 1.04 (1.02-1.05) and 1.00 (0.99-1.02), respectively. Furthermore, subgroup analysis indicated a stable relationship between serum uric acid and in-hospital mortality, whilst an insignificant difference was found for the interactions between different subgroups. Overall, a non-linear correlation was determined between admission serum uric acid and in-hospital mortality of patients with acute type A aortic dissection. When serum uric acid > 260 µmol/L, it showed a positive correlation with in-hospital mortality.

Red cell distribution width and in-hospital mortality in septic shock: A public database research.

OBJECTIVE: This study aimed to explore the relationship between red cell distribution width (RDW) and in-hospital mortality in septic shock based on a large-scale public database. METHODS: All patients with septic shock in MIMIC-IV were enrolled. Based on RDW values, the general characteristics of different groups were compared. Different models were constructed for exploring the association of RDW and in-hospital mortality. To assess the predictive value of RDW, receiver operator characteristic (ROC) curve analysis was applied. RESULTS: A total of 3006 patients with septic shock were included and in-hospital mortality was 32.27% (n = 970). The results of the fully adjusted model demonstrated that RDW was positively associated with in-hospital mortality in septic shock patients after adjusting all confounders (OR = 1.12, 95% CI:1.08-1.17, p < .001). A linear relationship between RDW and in-hospital mortality was found. For predicting in-hospital mortality, the area under the ROC curve (AUC) of RDW was .602 and the best threshold of RDW was 17.25%. CONCLUSION: RDW was associated with in-hospital mortality in septic shock. It could be a useful marker for predicting clinical outcomes in septic shock.

Power signatures of habenular neuronal signals in patients with bipolar or unipolar depressive disorders correlate with their disease severity.

The habenula is an epithalamic structure implicated in negative reward mechanisms and plays a downstream modulatory role in regulation of dopaminergic and serotonergic functions. Human and animal studies show its hyperactivity in depression which is curtailed by the antidepressant response of ketamine. Deep brain stimulation of habenula (DBS) for major depression have also shown promising results. However, direct neuronal activity of habenula in human studies have rarely been reported. Here, in a cross-sectional design, we acquired both spontaneous resting state and emotional task-induced neuronal recordings from habenula from treatment resistant depressed patients undergoing DBS surgery. We first characterise the aperiodic component (1/f slope) of the power spectrum, interpreted to signify excitation-inhibition balance, in resting and task state. This aperiodicity for left habenula correlated between rest and task and which was significantly positively correlated with depression severity. Time-frequency responses to the emotional picture viewing task show condition differences in beta and gamma frequencies for left habenula and alpha for right habenula. Notably, alpha activity for right habenula was negatively correlated with depression severity. Overall, from direct habenular recordings, we thus show findings convergent with depression models of aberrant excitatory glutamatergic output of the habenula driving inhibition of monoaminergic systems.

Cortical and Subcortical Structural Abnormalities in Patients With Idiopathic Cervical and Generalized Dystonia.

Objectives: In this study, we sought to investigate structural imaging alterations of patients with idiopathic dystonia at the cortical and subcortical levels. The common and specific changes in two subtypes of dystonia, cervical dystonia (CD) and generalized dystonia (GD), were intended to be explored. Additionally, we sought to identify the morphometric measurements which might be related to patients' clinical characteristics, thus providing more clues of specific brain regions involved in the mechanism of idiopathic dystonia. Methods: 3D T1-weighted MRI scans were acquired from 56 patients with idiopathic dystonia and 30 healthy controls (HC). Patients were classified as CD or GD, according to the distinct symptom distributions. Cortical thickness (CT) of 30 CD and 26 GD were estimated and compared to HCs using Computational Anatomy Toolbox (CAT12), while volumes of subcortical structures and their shape alterations (29 CD, 25 GD, and 27 HCs) were analyzed via FSL software. Further, we applied correlation analyses between the above imaging measurements with significant differences and patients' clinical characteristics. Results: The results of comparisons between the two patient groups and HCs were highly consistent, demonstrating increased CT of bilateral postcentral, superiorparietal, superiorfrontal/rostralmiddlefrontal, occipital gyrus, etc., and decreased CT of bilateral cingulate, insula, entorhinal, and fusiform gyrus (PFWE < 0.005 at the cluster level). In CD, trends of negative correlations were found between disease severity and CT alterations mostly located in pre/postcentral, rostralmiddlefrontal, superiorparietal, and supramarginal regions. Besides, volumes of bilateral putamen, caudate, and thalamus were significantly reduced in both patient groups, while pallidum volume reduction was also presented in GD compared to HCs. Caudate volume reduction had a trend of correlation to increasing disease severity in GD. Last, shape analysis directly demonstrated regional surface alterations in bilateral thalamus and caudate, where the atrophy located in the head of caudate had a trend of correlation to earlier ages of onset in GD. Conclusions: Our study demonstrates wide-spread morphometric changes of CT, subcortical volumes, and shapes in idiopathic dystonia. CD and GD presented similar patterns of morphometric abnormalities, indicating shared underlying mechanisms in two different disease forms. Especially, the clinical associations of CT of multiple brain regions with disease severity, and altered volume/shape of caudate with disease severity/age of onset separately in CD and GD might serve as potential biomarkers for further disease exploration.