Neutrophil extracellular traps-inspired DNA hydrogel for wound hemostatic adjuvant.

Severe traumatic bleeding may lead to extremely high mortality rates, and early intervention to stop bleeding plays as a critical role in saving lives. However, rapid hemostasis in deep non-compressible trauma using a highly water-absorbent hydrogel, combined with strong tissue adhesion and bionic procoagulant mechanism, remains a challenge. In this study, a DNA hydrogel (DNAgel) network composed of natural nucleic acids with rapid water absorption, high swelling and instant tissue adhesion is reported, like a band-aid to physically stop bleeding. The excellent swelling behavior and robust mechanical performance, meanwhile, enable the DNAgel band-aid to fill the defect cavity and exert pressure on the bleeding vessels, thereby achieving compression hemostasis for deep tissue bleeding sites. The neutrophil extracellular traps (NETs)-inspired DNAgel network also acts as an artificial DNA scaffold for erythrocytes to adhere and aggregate, and activates platelets, promoting coagulation cascade in a bionic way. The DNAgel achieves lower blood loss than commercial gelatin sponge (GS) in male rat trauma models. In vivo evaluation in a full-thickness skin incision model also demonstrates the ability of DNAgel for promoting wound healing. Overall, the DNAgel band-aid with great hemostatic capacity is a promising candidate for rapid hemostasis and wound healing.

Plasma metabolomics identifies key metabolites and improves prediction of diabetic retinopathy: development and validation across multi-national cohorts.

PURPOSE: To identify longitudinal metabolomic fingerprints of diabetic retinopathy (DR) and evaluate their utility in predicting DR development and progression. DESIGN: Multicenter, multi-ethnic cohort study. PARTICIPANTS: This study included 17,675 participants with baseline pre-diabetes/diabetes, in accordance with the 2021 American Diabetes Association guideline, and free of baseline DR from the UK Biobank (UKB); and an additional 638 diabetic participants from the Guangzhou Diabetic Eye Study (GDES) for external validation. METHODS: Longitudinal DR metabolomic fingerprints were identified through nuclear magnetic resonance assay in UKB participants. The predictive value of these fingerprints for predicting DR development were assessed in a fully withheld test set. External validation and extrapolation analyses of DR progression and microvascular damage were conducted in the GDES cohort. Model assessments included the C-statistic, net classification improvement (NRI), integrated discrimination improvement (IDI), calibration, and clinical utility in both cohorts. MAIN OUTCOME MEASURES: DR development, progression, and retinal microvascular damage. RESULTS: Of 168 metabolites, 118 were identified as candidate metabolomic fingerprints for future DR development. These fingerprints significantly improved the predictability for DR development beyond traditional indicators (C-statistic: 0.802, 95% CI, 0.760-0.843 vs. 0.751, 95% CI, 0.706-0.796; P = 5.56×10-4). Glucose, lactate, and citrate were among the fingerprints validated in the GDES cohort. Using these parsimonious and replicable fingerprints yielded similar improvements for predicting DR development (C-statistic: 0.807, 95% CI, 0.711-0.903 vs. 0.617, 95% CI, 0.494, 0.740; P = 1.68×10-4) and progression (C-statistic: 0.797, 95% CI, 0.712-0.882 vs. 0.665, 95% CI, 0.545-0.784; P = 0.003) in the external cohort. Improvements in NRIs, IDIs, and clinical utility were also evident in both cohorts (all P <0.05). In addition, lactate and citrate were associated to microvascular damage across macular and optic disc regions (all P <0.05). CONCLUSIONS: Metabolomic profiling has proven effective in identifying robust fingerprints for predicting future DR development and progression, providing novel insights into the early and advanced stages of DR pathophysiology.

FMOD Alleviates Depression-Like Behaviors by Targeting the PI3K/AKT/mTOR Signaling After Traumatic Brain Injury.

Depression frequently occurs following traumatic brain injury (TBI). However, the role of Fibromodulin (FMOD) in TBI-related depression is not yet clear. Previous studies have suggested FMOD as a potential key factor in TBI, yet its association with depression post-TBI and underlying mechanisms are not well understood. Serum levels of FMOD were measured in patients with traumatic brain injury using qPCR. The severity of depression was assessed using the self-depression scale (SDS). Neurological function, depressive state, and cognitive function in mice were assessed using the modified Neurological Severity Score (mNSS), forced swimming test (FST), tail suspension test (TST), Sucrose Preference Test (SPT), and morris water maze (MWM). The morphological features of mouse hippocampal synapses and neuronal dendritic spines were revealed through immunofluorescence, transmission electron microscopy, and Golgi-Cox staining. The protein expression levels of FMOD, MAP2, SYP, and PSD95, as well as the phosphorylation levels of the PI3K/AKT/mTOR signaling pathway, were detected through Western blotting. FMOD levels were decreased in TBI patients' serum. Overexpression of FMOD preserved neuronal function and alleviated depression-like behaviour, increased synaptic protein expression, and induced ultrastructural changes in hippocampal neurons. The increased phosphorylation of PI3K, AKT, and mTOR suggested the involvement of the PI3K/AKT/mTOR signaling pathway in FMOD's protective effects. FMOD exhibits potential as a therapeutic target for depression related to TBI, with its protective effects potentially mediated through the PI3K/AKT/mTOR signaling pathway.

A porous aromatic cage-based electrochemical sensor for enantioselective recognition of DOPA.

An electrochemical sensor based on porous aromatic cages was reported, which can achieve chiral sensing of DOPA enantiomers. The prepared sensor can achieve a recognition efficiency of up to 2.6 for DOPA enantiomers. The enhanced recognition efficiency could be attributed to the cooperation of intermolecular interactions, and the efficient charge transfer process.

Bibliometric Analysis of Cough Variant Asthma from 1993 to 2022.

Purpose: Cough variant asthma (CVA) is a chronic inflammatory disease characterized by recurrent coughing, a prevalent cause of chronic cough in children and adults. As a unique form of asthma, researchers have recently become increasingly interested in developing effective diagnostic and treatment methods. Currently, there has been no bibliometric analysis in CVA. Therefore, this study aims to enrich this knowledge network by examining the current development status, research focal points, and emerging trends in this field. Methods: Articles and reviews on CVA published between 1993 and 2022 were collected from the Web of Science Core Collection (WoSCC) database. Relevant data from the reports were extracted, and collaborative network analysis was performed using CiteSpace and VOSviewer software. Results: 772 articles were included in this study, indicating a significant increase since 2019. The countries with the highest output are China, Japan. The Journal of Asthma and Pulmonary Pharmacology Therapeutics emerged as the most prolific journals in this field. Keyword analysis revealed 22 clusters, highlighting airway inflammation, airway hyperresponsiveness, and eosinophil as the main focus and frontier of research on CVA. Conclusion: From the visual analysis results, the research of CVA is still in the development stage, and there is no unified definition of pathogenesis, diagnostic criteria and treatment strategies. Therefore, researchers and teams should actively carry out cross-institutional and cross-regional cooperation, expand cooperation areas, and carry out high-quality clinical research in the future.

Handgrip strength and risks of diabetic vascular complications: Evidence from Guangzhou Diabetic Eye Study and UK cohorts.

PURPOSE: The purpose is to investigate the association between handgrip strength (HGS) and the risk of future diabetic complications in multicountry cohorts. METHODS: The association between HGS and diabetic complications was evaluated using cox models among 84 453 patients with pre-diabetes and diabetes from the UK Biobank with a 12-year follow-up. The association between HGS and longitudinal microcirculatory damage rates was assessed among 819 patients with diabetes from the Guangzhou Diabetic Eye Study (GDES) with a 3-year follow-up. Participants were divided into three age groups (<56, 56-65 and ≥65 years), and each group was further subdivided into three HGS tertiles. RESULTS: A 5 kg reduction in HGS was associated with increased risk for all-cause mortality (women, HR=1.10, 95% CI: 1.05 to 1.14; p<0.001; men, HR=1.13, 95% CI: 1.11 to 1.15; p<0.001). Women and men in the lowest HGS group exhibited 1.6-times and 1.3-1.5-times higher risk of myocardial infarction and stroke compared with the highest HGS group. In men, there was a higher risk of developing end-stage renal disease (HR=1.83, 95% CI: 1.30 to 2.57; p=0.001), while this was not observed in women. Both sexes in the lowest HGS group had a 1.3-times higher risk of diabetic retinopathy compared with the highest HGS group. In the GDES group, individuals with the lowest HGS showed accelerated microcirculatory damage in retina (all p<0.05). CONCLUSIONS: Reduced HGS is significantly associated with a higher risk of diabetic complications and accelerated microvascular damage. HGS could serve as a practical indicator of vascular health in patients with pre-diabetes and diabetes.

6PPDQ induces cardiomyocyte senescence via AhR/ROS-mediated autophagic flux blockage.

Recently, attention has been drawn to the adverse outcomes of N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPDQ) on human health, but its cardiac toxicity has been relatively understudied. This work aims to investigate the effects of 6PPDQ on differentiated H9c2 cardiomyocytes. Our findings demonstrated that exposure to 6PPDQ altered cellular morphology and disrupted the expression of cardiac-specific markers. Significantly, 6PPDQ exposure led to cardiomyocyte senescence, characterized by elevated ß-Galactosidase activity, upregulation of cell cycle inhibitor, induction of DNA double-strand breaks, and remodeling of Lamin B1. Furthermore, 6PPDQ hindered autophagy flux by promoting the formation of autophagosomes while inhibiting the degradation of autolysosomes. Remarkably, restoration of autophagic flux using rapamycin counteracted 6PPDQ-induced cardiomyocyte senescence. Additionally, our study revealed that 6PPDQ significantly increased the ROS production. However, ROS scavenger effectively reduced the blockage of autophagic flux and cardiomyocyte senescence caused by 6PPDQ. Furthermore, we discovered that 6PPDQ activated the Aryl hydrocarbon receptor (AhR) signaling pathway. AhR antagonist was found to reverse the blockage of autophagy and alleviate cardiac senescence, while also reducing ROS levels in 6PPDQ-treated group. In conclusion, our research unveils that exposure to 6PPDQ induces ROS overproduction through AhR activation, leading to disruption of autophagy flux and ultimately contributing to cardiomyocyte senescence.

Dynamic simulation and experimental studies of molecularly imprinted label-free sensor for determination of milk quality marker.

Bovine serum albumin (BSA) has emerged as a biomarker for mammary gland health and cow quality, being recognized as a significant allergenic protein. In this study, a novel flexible molecular imprinted electrochemical sensor by surface electropolymerization using pyrrole (Py) as functional monomer, which can be better applied to the detection of milk quality marker BSA. Based on computational results, with regard to all polypyrrole (PPy) conformations and amino-acid positions within the protein, the BSA molecule remained firmly embedded into PPy polymers with no biological changes. The molecular imprinted electrochemical sensor displayed a broad linear detection range from 1.0 × 10-4 to 50 ng·mL-1 (R2 = 0.995) with a low detection limit (LOD) of 4.5 × 10-2 pg·mL-1. Additionally, the sensor was highly selective, reproducible, stable and recoverable, suggesting that it might be utilized for the evaluation of milk quality.

A Fully Integrated Handheld Electrochemical Sensing Platform for Point-of-Care Testing of Escherichia coli O157:H7.

Fully integrated devices that enable full functioning execution without or with minimum external accessories or equipment are deemed to be one of the most desirable and ultimate objectives for modern device design and construction. Escherichia coli O157:H7 (E. coli O157:H7) is often linked to outbreaks caused by contaminated water and food. However, the sensors that are currently used for point-of-care E. coli O157:H7 (E. coli O157:H7) detection are often large and cumbersome. Herein, we demonstrate the first example of a handheld and pump-free fully integrated electrochemical sensing platform with the capability to point-of-care test E. coli O157:H7 in the actual samples of E. coli O157:H7-spiked tap water and E. coli O157:H7-spiked watermelon juice. This platform was made possible by overcoming major engineering challenges in the seamless integration of a microfluidic module for pump-free liquid sample collection and transportation, a sensing module for efficient E. coli O157:H7 testing, and an electronic module for automatically converting and wirelessly transmitting signals into a single and compact electrochemical sensing platform that retains its inimitable stand-alone, handheld, pump-free, and cost-effective feature. Although our primary emphasis in this study is on detecting E. coli O157:H7, this pump-free fully integrated handheld electrochemical sensing platform may also be used to monitor other pathogens in food and water by including specific antipathogen antibodies.

Malignancy-associated ischemic stroke: Implications for diagnostic and therapeutic workup.

BACKGROUND: Patients with malignancies have an increased risk of suffering ischemic stroke via several mechanisms such as coagulation dysfunction and other malignancy-related effects as well as iatrogenic causes. Moreover, stroke can be the first sign of an occult malignancy, termed as malignancy-associated ischemic stroke (MAS). Therefore, timely diagnostic assessment and targeted management of this complex clinical situation are critical. FINDINGS: Patients with both stroke and malignancy have atypical ages, risk factors, and often exhibit malignancy-related symptoms and multiple lesions on neuroimaging. New biomarkers such as eicosapentaenoic acid and blood mRNA profiles may help in distinguishing MAS from other strokes. In terms of treatment, malignancy should not be considered a contraindication, given comparable rates of recanalization and complications between stroke patients with or without malignancies. CONCLUSION: In this review, we summarize the latest developments in diagnosing and managing MAS, especially stroke with occult malignancies, and provide new recommendations from recently emerged clinical evidence for diagnostic and therapeutic workup strategies.

An insular cortical circuit required for itch sensation and aversion.

Itch encompasses both sensory and emotional dimensions, with the two dimensions reciprocally exacerbating each other. However, whether a shared neural circuit mechanism governs both dimensions remains elusive. Here, we report that the anterior insular cortex (AIC) is activated by both histamine-dependent and -independent itch stimuli. The activation of AIC elicits aversive emotion and exacerbates pruritogen-induced itch sensation and aversion. Mechanistically, AIC excitatory neurons project to the GABAergic neurons in the dorsal bed nucleus of the stria terminalis (dBNST). Manipulating the activity of the AIC → dBNST pathway affects both itch sensation and itch-induced aversion. Our study discovers the shared neural circuit (AIC â†’ dBNST pathway) underlying the itch sensation and aversion, highlights the critical role of the AIC as a central hub for the itch processing, and provides a framework to understand the neural mechanisms underlying the sensation and emotion interaction.

Perioperative management of kidney transplantation in China: A national survey in 2021.

Perioperative anaesthesia management has an important significance for kidney transplantation; however, the related consensus remains limited. An electronic survey with 44 questions was developed and sent to the chief anaesthesiologist at 115 non-military medical centres performing kidney transplantation in China through WeChat. A response rate of 81.7% was achieved from 94 of 115 non-military medical centres, where 94.4% of kidney transplants (10404 /11026) were completed in 2021. The result showed an overview of perioperative practice for kidney transplantations in China, identify the heterogeneity, and provide evidence for improving perioperative management of kidney transplantation. Some controversial therapy, such as hydroxyethyl starch, are still widely used, while some recommended methods are not widely available. More efforts on fluid management, hemodynamical monitoring, perioperative anaesthetics, and postoperative pain control are needed to improve the outcomes. Evidence-based guidelines for standardizing clinical practice are needed.

Adaptive convolutional dictionary learning for denoising seismocardiogram to enhance the classification performance of aortic stenosis.

BACKGROUND: Aortic stenosis (AS) is the most prevalent type of valvular heart disease (VHD), traditionally diagnosed using echocardiogram or phonocardiogram. Seismocardiogram (SCG), an emerging wearable cardiac monitoring modality, is proved to be feasible in non-invasive and cost-effective AS diagnosis. However, SCG waveforms acquired from patients with heart diseases are typically weak, making them more susceptible to noise contamination. While most related researches focus on motion artifacts, sensor noise and quantization noise have been mostly overlooked. These noises pose additional challenges for extracting features from the SCG, especially impeding accurate AS classification. METHOD: To address this challenge, we present a convolutional dictionary learning-based method. Based on sparse modeling of SCG, the proposed method generates a personalized adaptive-size dictionary from noisy measurements. The dictionary is used for sparse coding of the noisy SCG into a transform domain. Reconstruction from the domain removes the noise while preserving the individual waveform pattern of SCG. RESULTS: Using two self-collected SCG datasets, we established optimal dictionary learning parameters and validated the denoising performance. Subsequently, the proposed method denoised SCG from 50 subjects (25 AS and 25 non-AS). Leave-one-subject-out cross-validation (LOOCV) was applied to 5 machine learning classifiers. Among the classifiers, a bi-layer neural network achieved a moderate accuracy of 90.2%, with an improvement of 13.8% from the denoising. CONCLUSIONS: The proposed sparsity-based denoising technique effectively removes stochastic sensor noise and quantization noise from SCG, consequently improving AS classification performance. This approach shows promise for overcoming instrumentation constraints of SCG-based diagnosis.

The Lateral Parabrachial Nucleus Inputs to the Lateral Hypothalamus Trigger Nocifensive Behaviors.

The lateral parabrachial nucleus (LPBN) is known to play a key role in relaying noxious information from the spinal cord to the brain. Different LPBN efferent mediate different aspects of the nocifensive response. However, the function of the LPBN â†’ lateral hypothalamus (LH) circuit in response to noxious stimuli has remained unknown. Here, we show that LPBN â†’ LH circuit is activated by noxious stimuli. Interestingly, either activation or inhibition of this circuit induced analgesia. Optogenetic activation of LPBN afferents in the LH elicited spontaneous jumping and induced place aversion. Optogenetic inhibition inhibited jumping behavior to noxious heat. Ablation of LH glutamatergic neurons could abolish light-evoked analgesia and jumping behavior. Our study revealed a role for the LPBN â†’ LH pathway in nocifensive behaviors.

Cortical and subcortical structural differences in psychostimulant-free ADHD youth with and without a family history of bipolar I disorder: a cross-sectional morphometric comparison.

Although attention-deficit/hyperactivity disorder (ADHD) and a family history of bipolar I disorder (BD) are associated with increased risk for developing BD, their neuroanatomical substrates remain poorly understood. This study compared cortical and subcortical gray matter morphology in psychostimulant-free ADHD youth with and without a first-degree relative with BD and typically developing healthy controls. ADHD youth (ages 10-18 years) with ('high-risk', HR) or without ('low-risk', LR) a first-degree relative with BD and healthy comparison youth (HC) were enrolled. High-resolution 3D T1-weighted images were acquired using a Philips 3.0 T MR scanner. The FreeSurfer image analysis suite was used to measure cortical thickness, surface area, and subcortical volumes. A general linear model evaluated group differences in MRI features with age and sex as covariates, and exploratory correlational analyses evaluated associations with symptom ratings. A total of n = 142 youth (mean age: 14.16 ± 2.54 years, 35.9% female) were included in the analysis (HC, n = 48; LR, n = 49; HR, n = 45). The HR group exhibited a more severe symptom profile, including higher mania and dysregulation scores, compared to the LR group. For subcortical volumes, the HR group exhibited smaller bilateral thalamic, hippocampal, and left caudate nucleus volumes compared to both LR and HC, and smaller right caudate nucleus compared with LR. No differences were found between LR and HC groups. For cortical surface area, the HR group exhibited lower parietal and temporal surface area compared with HC and LR, and lower orbitofrontal and superior frontal surface area compared to LR. The HR group exhibited lower left anterior cingulate surface area compared with HC. LR participants exhibited greater right pars opercularis surface area compared with the HC. Some cortical alterations correlated with symptom severity ratings. These findings suggest that ADHD in youth with a BD family history is associated with a more a severe symptom profile and a neuroanatomical phenotype that distinguishes it from ADHD without a BD family history.

The Current Situation of Anaesthesia for Hysteroscopy in Mainland China: A National Survey.

Purpose: The need for anaesthesia or analgesia for performing hysteroscopy remains debatable. This study aimed to conduct an overview of the situation of anaesthesia for hysteroscopy in mainland China. Methods: Two questionnaires were separately designed for anaesthesiologists and gynaecologists and distributed to every medical institution that performed hysteroscopic procedures on patients with infertility in mainland China. Electronic questionnaires were distributed via WeChat, and data on anaesthesia regimen, monitoring parameters, procedure number, and other information were collected. Results: Reproductive technology is conducted by 536 institutions in mainland China. The survey received 491 responses from anaesthetists (91.6%) and 436 from gynaecologists (81.3%). In 2021, 552,225 hysteroscopies were conducted in 268 medical centres. The average percentage of hysteroscopy under anaesthesia is 63.8% in 2021, wherein 47.3% of institutions have an anaesthesia percentage of >75%. Propofol and opioid analgesics, such as fentanyl and sufentanil, were the most commonly used intravenous anaesthetics. All sedations were performed by anaesthesiologists. Monitoring parameters included pulse oxygen saturation (98.9%), electrocardiogram (91.6%) and noninvasive blood pressure (91.3%). An anaesthesiologist-to-operating room ratio of <1 was observed in 31.3% of medical institutions. Surprisingly, 52.4% of medical institutions performing hysteroscopy had no postanaesthesia care unit (PACU). Most institutions with PACU were equipped with independent oxygen sources, suction and monitors. Both rigid and flexible hysteroscopes (rigid hysteroscope, 45.1%; flexible hysteroscope, 4.5%; both types, 50.4%) were used, and the hysteroscopic diameter was ≤5 mm in 60.3% of medical centres. Conclusions: China performs a large number of hysteroscopies, and sedation is the most frequently used anesthesia regimen. However, issues such as inadequate emergency support devices, insufficient personnel and weak resuscitation management after anaesthesia, have been observed.

Recent Advances in the Nanoshells Approach for Encapsulation of Single Probiotics.

The intestine, often referred to as the "second brain" of the human body, houses a vast microbial community that plays a crucial role in maintaining the host's balance and directly impacting overall health. Probiotics, a type of beneficial microorganism, offer various health benefits when consumed. However, probiotics face challenges such as acidic conditions in the stomach, bile acids, enzymes, and other adverse factors before they can colonize the intestinal tissues. At present, pills, dry powder, encapsulation, chemically modified bacteria, and genetically engineered bacteria have emerged as the preferred method for the stable and targeted delivery of probiotics. In particular, the use of nanoshells on the surface of single probiotics has shown promise in regulating their growth and differentiation. These nanoshells can detach from the probiotics' surface upon reaching the intestine, facilitating direct contact between the probiotics and intestinal mucosa. In this perspective, we provide an overview of the current developments in the formation of nanoshells mediated by single probiotics. We also discuss the advantages and disadvantages of different nanocoating strategies and explore future trends in probiotic protection.

Development and Validation of Tumor Marker Indices in Advanced Gastric Cancer Patients.

BACKGROUND: Tumor markers (TMs) are important for the prognosis of gastric cancer (GC). However, the prognostic importance of the tumor marker index (TMI) based on GC-specific TMs for advanced gastric cancer (AGC) still needs to be further explored. METHODS: We retrospectively examined patients who underwent radical gastric cancer surgery between February 2014 and June 2016 at the Department of Gastroenterological Surgery, Affiliated Cancer Hospital, Harbin Medical University. The patients were divided into training and validation groups. TMI was determined as the geometric mean of the standard cancer antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) levels. Patient overall survival was assessed using the Kaplan-Meier method. Independent prognosis-associated risk factors were identified using Cox hazard regression models. A nomogram model incorporating TMI and clinicopathological factors was developed, and its performance was evaluated using a decision curve analysis, concordance index, and calibration plots. RESULTS: In the TMI training cohort, the cutoff value was set at .439, categorizing patients into TMI-High and TMI-Low groups. The 5-year survival rate in the TMI-Low group significantly surpassed that in the TMI-High group (78.2% vs 58.1% and 49.7 vs 41.6, P < .001). TMI emerged as an independent prognostic factor. The nomogram accurately predicted patient prognosis by using TMI and clinicopathological characteristics. Validation of the TMI in the independent cohort yielded satisfactory results. CONCLUSION: The TMI constructed based on specific TMs associated with gastric cancer can offer a precise prognostic prediction for patients.

Brain network structural connectome abnormalities among youth with attention-deficit/hyperactivity disorder at varying risk for bipolar I disorder: a cross-sectional graph-based magnetic resonance imaging study.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is highly prevalent among youth with or at familial risk for bipolar-I disorder (BD-I), and ADHD symptoms commonly precede and may increase the risk for BD-I; however, associated neuropathophysiological mechanisms are not known. In this cross-sectional study, we sought to investigate brain structural network topology among youth with ADHD, with and without familial risk of BD-I. METHODS: We recruited 3 groups of psychostimulant-free youth (aged 10-18 yr), namely youth with ADHD and at least 1 biological parent or sibling with BD-I (high-risk group), youth with ADHD who did not have a first- or second-degree relative with a mood or psychotic disorder (low-risk group) and healthy controls. We used graph-based network analysis of structural magnetic resonance imaging data to investigate topological properties of brain networks. We also evaluated relationships between topological metrics and mood and ADHD symptom ratings. RESULTS: A total of 149 youth were included in the analysis (49 healthy controls, 50 low-risk youth, 50 high-risk youth). Low-risk and high-risk ADHD groups exhibited similar differences from healthy controls, mainly in the default mode network and central executive network. We found topological alterations in the salience network of the high-risk group, relative to both low-risk and control groups. We found significant abnormalities in global network properties in the high-risk group only, compared with healthy controls. Among both low-risk and high-risk ADHD groups, nodal metrics in the right triangular inferior frontal gyrus correlated positively with ADHD total and hyperactivity/impulsivity subscale scores. LIMITATIONS: The cross-sectional design of this study could not determine the relevance of these findings to BD-I risk progression. CONCLUSION: Youth with ADHD, with and without familial risk for BD-I, exhibit common regional abnormalities in the brain connectome compared with healthy youth, whereas alterations in the salience network distinguish these groups and may represent a prodromal feature relevant to BD-I risk.

Normal-weight central obesity and risk of cardiovascular and microvascular events in adults with prediabetes or diabetes: Chinese and British cohorts.

OBJECTIVE: To investigate the relationship between body fat distribution and risk of cardiometabolic and microvascular events among individuals with prediabetes or diabetes with normal body mass index (BMI). METHODS: A total of 17,232 participants with prediabetes or diabetes from UK Biobank (UKB) with 12-year follow-up and 499 diabetic participants from China with 2-year follow-up with normal BMI were included. Anthropometric measurements of waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR), and body fat composition assessment of trunk-to-leg fat ratio (TLFR) were obtained. Outcomes included incident all-cause and cardiovascular mortality and macrovascular and microvascular diseases. RESULTS: In British cohort, participants with central obesity defined by WHR had 27%-54% higher risk of incident all-cause mortality (hazard ratio (HR) 1.42, 95% confidence interval (CI): 1.23-1.64), cardiovascular mortality (HR 1.54 [1.15-2.07]), myocardial infarction (HR = 1.43 [1.15, 1.78]), stroke (HR 1.26 [0.90, 1.75]), heart failure (HR = 1.27 [1.00, 1.61]), diabetic nephropathy (HR 1.33 [1.07, 1.65]), and diabetic retinopathy (DR) (HR = 1.48 [1.12, 1.96]) than those without obesity. Central obesity defined by WC and WHtR was associated with 40%-44% and 23%-98% higher risks of developing diabetic events, respectively. In the Chinese cohort, individuals with abdominal obesity, defined by WC (HR 1.44) or WHtR (HR 1.43) but not by WHR, carried more than 40% higher risk of developing DR than those without it. Higher TLFR carried 1.30-2.85 times higher risk of CVD and microvascular diseases among the dysglycemic population. CONCLUSIONS: Body fat distribution diseases among individuals with prediabetes or diabetes are associated with an increased risk of cardiometabolic and microvascular diseases independent of BMI.