[Clinical and genetic characteristics of four children with Kabuki syndrome due to de novo variants of KMT2D gene].

OBJECTIVE: To explore the clinical and genetic characteristics of four children with Kabuki syndrome (KS) due to variants of KMT2D gene. METHODS: Four children with KS diagnosed at the Children's Hospital of Shanxi Province between January 2020 and December 2022 were selected as the study subjects. Whole exome sequencing was carried out for the children and their family members. Candidate variants were verified by Sanger sequencing and pathogenicity analysis. RESULTS: The KS phenotype scores for the four children were 7, 8, 6, and 6, respectively. Child 2 also presented with a rare solitary kidney malformation. Genetic testing revealed that all children had harbored novel de novo variants of the KMT2D gene, including c.16472_16473del, c.858dup, c.11899C>T, and c.12844C>T, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), all of the variants were classified as pathogenic. CONCLUSION: For children showing phenotypes such as distinctive facial features, intellectual disability, developmental delay, cardiac abnormalities, and urinary system anomalies, KS should be considered. Early diagnosis and intervention can be achieved through genetic testing, especially in the presence of KMT2D gene mutations.

DLP Fabrication of Multiple Hierarchical Biomimetic GelMA/SilMA/HAp Scaffolds for Enhancing Bone Regeneration.

Severe bone defects resulting from trauma and diseases remain a persistent clinical challenge. In this study, a hierarchical biomimetic microporous hydrogel composite scaffold was constructed by mimicking the hierarchical structure of bone. Initially, gelatin methacrylamide (GelMA) and methacrylic anhydride silk fibroin (SilMA) were synthesized, and GelMA/SilMA inks with suitable rheological and mechanical properties were prepared. Biomimetic micropores were then generated by using an aqueous two-phase emulsification method. Subsequently, biomimetic microporous GelMA/SilMA was mixed with hydroxyapatite (HAp) to prepare biomimetic microporous GelMA/SilMA/HAp ink. Hierarchical biomimetic microporous GelMA/SilMA/HAp (M-GSH) scaffolds were then fabricated through digital light processing (DLP) 3D printing. Finally, in vitro experiments were conducted to investigate cell adhesion, proliferation, and inward migration as well as osteogenic differentiation and vascular regeneration effects. In vivo experiments indicated that the biomimetic microporous scaffold significantly promoted tissue integration and bone regeneration after 12 weeks of implantation, achieving 42.39% bone volume fraction regeneration. In summary, this hierarchical biomimetic microporous scaffold provides a promising strategy for the repair and treatment of bone defects.

Exoskeleton Partial-Coated Stem Cells for Infarcted Myocardium Restoring.

The integration of abiotic materials with live cells has emerged as an exciting strategy for the control of cellular functions. Exoskeletons consisting ofmetal-organic frameworks are generated to produce partial-coated bone marrow stem cells (BMSCs) to overcome low cell survival leading to disappointing effects for cell-based cardiac therapy. Partially coated exoskeletons can promote the survival of suspended BMSCs by integrating the support of exoskeletons and unimpaired cellular properties. In addition, partial exoskeletons exhibit protective effects against detrimental environmental conditions, including reactive oxygen species, pH changes, and osmotic pressure. The partial-coated cells exhibit increased intercellular adhesion forces to aggregate and adhere, promoting cell survival and preventing cell escape during cell therapy. The exoskeletons interact with cell surface receptors integrin α5ß1, leading to augmented biological functions with profitable gene expression alteration, such as Vegfa, Cxcl12, and Adm. The partial-coated BMSCs display enhanced cell retention in infarcted myocardium through non-invasive intravenous injections. The repair of myocardial infarction has been achieved with improved cardiac function, myocardial angiogenesis, proliferation, and inhibition of cell apoptosis. This discovery advances the elucidation of potential molecular and cellular mechanisms for cell-exoskeleton interactions and benefits the rational design and manufacture of next-generation nanobiohybrids.

Regional homogeneity in patients with obsessive-compulsive disorder and depression: A resting state functional magnetic resonance imaging study.

OBJECTIVE: To explore the brain functional impairment of patients with obsessive-compulsive disorder (OCD) with and without depressive symptoms and analyze the correlation between the degree of impairment and the severity of symptoms. METHOD: Fourteen patients with OCD who met the ICD-10 diagnostic criteria for OCD were included. The group having OCD with depression (OCDd) consisted of 15 patients, and 17 healthy controls (HC) matched for age and education were also included. The Yale-Brown OCD Scale (Y-BOCS) and the 24-item Hamilton Assessment of Depression Scale (HAMD) were administered to the OCD and OCDd groups. Resting-state functional brain magnetic resonance imaging was performed in the three groups of participants. RESULT: The OCDd group had lower scores on the HAMD, Y-BOCS, and obsessive-compulsive thinking subscales compared with the OCD group (P < 0.05). The scores on the OCDd subscale were negatively correlated with the HAMD scores (R =  - 0.568, P = 0.027). The OCDd group had higher regional homogeneity (ReHo) values in the lingual gyrus than the OCD group. The OCDd group had higher ReHo values in the lingual gyrus than the HC group, and the OCDd group had higher ReHo values than the HC group. These differences were statistically significant (P < 0.05). After correction for multiple comparisons, significant difference was observed between the OCDd and HC groups (P＜0.05). In the OCD group, the ReHo value of the lingual gyrus was negatively correlated with the Y-BOCS total score and the compulsive behavior subscale score (R =  - 0.609, -0.552; P = 0.016, 0.033). CONCLUSION: Abnormal ReHo values in the lingual gyrus and right medial superior frontal gyrus were found in the patients with OCDd. In the OCDd group, the ReHo values of the lingual gyrus were negatively correlated with the scores on the Y-BOCS total and obsessive-compulsive subscales, suggesting that abnormal local coherence of the lingual gyrus may be related to the severity of OCD.

Tyrosine phosphorylation of band 3 impairs the storage quality of suspended red blood cells in the Tibetan high-altitude polycythemia population.

Due to environmental hypoxia on the Tibetan Plateau, local residents often exhibit a compensative increase in hemoglobin concentration to maintain the body's oxygen supply. However, increases in hemoglobin and hematocrit (Hct) pose a serious challenge to the quality of stored suspended red blood cells (SRBCs) prepared from the blood of high-hemoglobin populations, especially populations at high altitude with polycythemia in Tibet. To explore the difference in storage quality of SRBCs prepared from plateau residents with a high hemoglobin concentration, blood donors were recruited from Tibet (> 3600 m) and Chengdu (≈ 500 m) and divided into a high-altitude control (HAC) group, high-altitude polycythemia (HAPC) group and lowland control (LLC) group according to their hemoglobin concentration and altitude of residence. The extracellular acidification rate (ECAR), pyruvate kinase (PK) activity and band 3 tyrosine phosphorylation were analyzed on the day of blood collection. Then, whole-blood samples were processed into SRBCs, and storage quality parameters were analyzed aseptically on days 1, 14, 21 and 35 of storage. Overall, we found that tyrosine 21 phosphorylation activated glycolysis by releasing glycolytic enzymes from the cytosolic domain of band 3, thus increasing glucose consumption and lactate accumulation during storage, in the HAPC group. In addition, band 3 tyrosine phosphorylation impaired erythrocyte deformability, accompanied by the highest hemolysis rate in the HAPC group, during storage. We believe that these results will stimulate new ideas to further optimize current additive solutions for the high-hemoglobin population in Tibet and reveal new therapeutic targets for the treatment of HAPC populations.

Integrated biomarker profiling of the metabolome associated with type 2 diabetes mellitus among Tibetan in China.

INTRODUCTION: Metabolomic signatures of type 2 diabetes mellitus (T2DM) in Tibetan Chinese population, a group with high diabetes burden, remain largely unclear. Identifying the serum metabolite profile of Tibetan T2DM (T-T2DM) individuals may provide novel insights into early T2DM diagnosis and intervention. METHODS: Hence, we conducted untargeted metabolomics analysis of plasma samples from a retrospective cohort study with 100 healthy controls and 100 T-T2DM patients by using liquid chromatography-mass spectrometry. RESULTS: The T-T2DM group had significant metabolic alterations that are distinct from known diabetes risk indicators, such as body mass index, fasting plasma glucose, and glycosylated hemoglobin levels. The optimal metabolite panels for predicting T-T2DM were selected using a tenfold cross-validation random forest classification model. Compared with the clinical features, the metabolite prediction model provided a better predictive value. We also analyzed the correlation of metabolites with clinical indices and found 10 metabolites that were independently predictive of T-T2DM. CONCLUSION: By using the metabolites identified in this study, we may provide stable and accurate biomarkers for early T-T2DM warning and diagnosis. Our study also provides a rich and open-access data resource for optimizing T-T2DM management.

Age at menopause was not associated with microvascular complications in patients with type 2 diabetes mellitus.

This study aimed to determine whether there is an association between the age at menopause (AM) and diabetic microvascular complications. This cross-sectional study included 298 postmenopausal women with type 2 diabetes mellitus. They were divided into 3 groups according to AM (in years; group 1: AM < 45 years, n = 32; group 2:45 ≤ AM < 50 years, n = 102; group 3: AM ≥ 50 years, n = 164). Clinical data related to the duration of type 2 diabetes, body mass index, smoking status, hypertension status, AM, biochemical indices, and diabetic microvascular complications (retinopathy, nephropathy, and neuropathy) were collected. Logistic regression analysis was performed to identify the association between the AM and diabetic microvascular complications. No statistical differences were observed in the prevalence of diabetic retinopathy, chronic kidney disease, or diabetic peripheral neuropathy between the groups. After adjusting for possible confounders, AM did not correlate with the presence of diabetic retinopathy (ß = 1.03, 95% confidence interval [CI]: 0.94-1.14, P = .511), chronic kidney disease (ß = 1.04, 95% CI: 0.97-1.12, P = .280), and diabetic peripheral neuropathy (ß = 1.01, 95% CI: 0.93-1.09, P = .853). Our findings suggest that early menopause (age < 45 years) was not associated with microvascular diabetic complications. Further prospective studies are needed to clarify this issue.

Complementary and Alternative Medicine Use in Patients With Cancer and Immigration Background.

PURPOSE: Studies have shown that patients with cancer are more likely to use complementary and alternative medicine (CAM) than noncancer patients for symptom relief and hope. We aimed to evaluate factors of race, ethnic groups, and immigration status in attitude of patients with cancer in seeking out CAM. PATIENTS AND METHODS: This is a prospective questionnaire study where information on demographics, cancer information, race/ethnicity, immigration duration, and psychosocial factors was correlated with the CAM use in a community cancer center located in the borough of Brooklyn, at New York City. RESULTS: Among 658 patients, the prevalence of CAM use was 66.11%. CAM use was 71.98% in females and 54.34% in males (P = .113 × 10-4). Patients of African descent had higher CAM use (72.73%) than the White patients (63.53%; P = .0371). There was no difference of CAM use between the US born (68.77%) and the immigrants (63.98%, P = .199) as a whole; however, comparing with the US born (66.50%), Asian-born immigrants had lower CAM use (53.77%, P = .0161), whereas Latin-American born had a numerical trend toward higher CAM use (74.83%, P = .0608). The number of years of living in the United States was not associated with more CAM use. Prayer and spirituality was the most common CAM subtype used (25.91%). There was no difference in CAM use in the respective non-White ethnic groups whether they were US born or non-US born. CONCLUSION: In this cohort of patients with cancer enriched with immigration background, CAM use was the highest in African American patients. The use of CAM in the non-White patients was associated with their ethnic background, regardless whether they were US born or not. Cultural roots appeared to be a strong influencing factor for the usage of CAM.

The influence of childhood maltreatment on trait depression in patients with major depressive disorder: A moderated mediation model of rumination and mindful attention awareness.

Major depressive disorder (MDD) is one of the most prevalent psychiatric disorders. Individuals who were exposed to childhood maltreatment might be an especially vulnerable group and were more likely to meet the diagnostic criteria for depression than those who were not. Trait depression refers to a personality trait predisposition to depression, expressed as the frequency of symptoms rather than a transient depressive mood state. Clarifying the relationship between childhood maltreatment and trait depression in patients with MDD has therefore become an important field of research. Childhood Trauma Questionnaire-Short Form (CTQ-SF), Ruminative Responses Scale (RRS), State-Trait Depression Scale (ST-DEP), and Mindful Attention Awareness Scale (MAAS) were used as research instruments. SPSS 23.0 statistical software was used for statistical analysis and examined the moderated mediation models. A total of 288 patients with MDD were included in this study. After standardization of the variables, the model revealed childhood maltreatment was positively associated with trait depression (ß = 0.215, p < 0.001) and that rumination partially mediated the effect between childhood trauma and trait depression. Mindfulness moderated the association between rumination and trait depression in depressed patients (ß = 0.171, p < 0.001). Simple slope tests showed that rumination significantly predicted trait depression in patients with high levels of mindfulness (bsimple = 0.460, p < 0.001, 95%CI = [0.339, 0.581]), while this predictive effect was not significant in patients with low levels (bsimple = 0.119, p = 0.097, 95%CI = [-0.022, 0.261]). After adding mediating variables, we found that the negative impact of childhood maltreatment on trait depression was both directly and indirectly through the patients' own ruminative levels. However, mindfulness performed a critical moderating role in the overall mediating model, aggravating the negative impact of childhood maltreatment on trait depression. There are several limitations in this study: the history of childhood maltreatment was reviewed and reported; the MAAS was a single-dimensional questionnaire that fails to measure the content of other mindfulness factors; cross-sectional data could not be used to infer the causal relationship between variables.

Baseline Serum BCAAs are Related to the Improvement in Insulin Resistance in Obese People After a Weight Loss Intervention.

Background: Branched chain amino acids (BCAAs) have been revealed to be closely related to insulin resistance and obesity. This study aimed to investigate if BCAA levels at baseline are related to an improvement in insulin resistance after implementing a weight loss program intervention. Methods: Stored blood samples from participants in previous trials were used for BCAA evaluation. Linear regression was used to analyze the relationship between baseline amino acid levels and changes in the insulin resistance index (HOMA-IR) and blood glucose. Results: A total of 48 participants were enrolled. After the intervention, the body weight (78.29± 12.68 vs 72.06 ± 13.30 kg, p=0.020), fasting glucose (4.76 ± 0.43 vs 4.48 ± 0.39 mmol/L, p=0.001), fasting insulin (18.41±13.58 vs 12.87±10.88, p=0.028), and HOMA-IR (4.01±3.39 vs 2.62± 2.18, p=0.018) were improved significantly. BCAA levels were related to the improvement in HOMA-IR (ß=-0.006, p=0.039), and valine was found to be the most closely related to the improvement in HOMA-IR (ß=-0.013, p=0.017). Conclusion: The baseline BCAA is related to the improvement in insulin resistance among participants after a weight loss intervention.

The effectiveness of mindfulness-based interventions for ruminative thinking: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To systematically evaluate the effectiveness of mindfulness-based interventions for ruminative thinking. METHODS: Cochrane Library, Web of Science, Embase, EBSCO, PubMed and Science Direct databases were searched to include randomized controlled trials of mindfulness-based interventions for rumination that met the criteria. The Rumination scale was used as the primary outcome indicator, and the secondary outcome indicator included the Mindfulness scale. An evaluation of bias risk was conducted to identify possible sources of bias based on methodological and clinical factors. Stata 16.0 software was used to perform meta-analysis, subgroup analysis, sensitivity analysis, meta-regression analysis and publication bias detection of the extracted data. RESULTS: A total of 61 studies with 4229 patients were included. Meta-analysis results revealed a significant intervention effect on ruminative thinking (SMD = -0.534, 95 % CI = [-0.675, -0.394], z = -7.449, P < 0.001). However, there was no significant difference between mindfulness-based interventions and CBT (SMD = 0.009, 95%CI = [-0.239, 0.258], z = 0.073, P = 0.941). Meta-analysis showed that mindfulness-based interventions significantly enhanced the level of mindfulness (SMD = 0.495, 95 % CI = [0.343, 0.647], z = 6.388, P < 0.001), while it was not significant compared to CBT (SMD = 0.158, 95%CI = [-0.087, 0.403], z = 1.266, P = 0.205). The two subgroups with >65 % (SMD = -0.534, 95%CI = [-0.681, -0.386], z = -7.081, P < 0.001) and 80 % (SMD = -0.462, 95%CI = [-0.590, -0.334], z = -7.071, P < 0.001) of females showed significant improvement in ruminative thinking. There were significant intervention effects for depression, students, cancer, healthy adults, and clinical patients. Significant intervention effects were demonstrated for various participant ages and intervention periods. CONCLUSION: This study confirmed the feasibility of mindfulness-based interventions in improving ruminative thinking and enhancing the level of mindfulness. However, the effectiveness of mindfulness-based interventions was not significant compared to CBT. The two subgroups with a higher proportion of females showed a more significant improvement in ruminative thinking, whereas there were no significant differences in participant characteristics, age, and the duration of intervention.

Utility of plasma beta-hydroxybutyrate to define resolution of diabetic ketoacidosis.

BACKGROUND: Diabetic ketoacidosis (DKA) is a common, life-threatening complication of type 1 diabetes (T1D) characterized by unregulated ketogenesis caused by relative or absolute insulin deficiency. DKA management requires frequent biochemical monitoring. Plasma ß-hydroxybutyrate (BOHB) has not been included in traditional definitions of DKA resolution. OBJECTIVE: The aim of this study was to determine a cut-point level of BOHB to define DKA resolution in patients with T1D treated with intravenous (IV) insulin. SUBJECTS: We identified patients with T1D receiving IV insulin for DKA treatment at a quaternary children's hospital from January 1, 2017 through December 31, 2020 who had plasma measurements of BOHB after DKA onset and whose DKA resolved by traditional laboratory criteria (venous pH (vpH) ≥ 7.3, serum bicarbonate (HCO3 ) ≥ 15 mmol/L, and/or anion gap (AG) ≤ 14 mmol/L). METHODS: Associations between plasma BOHB and vpH, HCO3 , and AG were evaluated via scatterplots. Receiver operating characteristic (ROC) curves and area under the curve (AUC) were used to evaluate BOHB cut-points to predict DKA resolution. RESULTS: We analyzed 403 patients with 471 unique encounters. Plasma BOHB showed the most robust relationship with AG. The ROC curve comparing plasma BOHB to the accepted definition of DKA resolution, AG ≤14 mmol/L, had an AUC of 0.92. A BOHB value of <1.5 mmol/L had a sensitivity of 83% and specificity of 87%; this cut-point correctly classified 86% of the observations. CONCLUSIONS: A plasma BOHB value of <1.5 mmol/L can be used to define resolution of DKA.

Future orientation and perceived employability of chinese undergraduates: a moderated mediation model.

Although scholars and practitioners have highlighted the significance of students' attitudes for their future employment, few empirical examinations have attempted to determine the potential association between students' future orientation and their perceived employability. Thus, drawing on career construction theory, we test the positive effect of students' future orientation on their perceived employability by exploring the mediator of problem-based learning and the moderators of job market knowledge and proactive personality. Collecting our data via a time-lagged design (N = 368), we have found that the positive association between future orientation and employability is mediated by problem-based learning. Our moderation analyses further revealed that job market knowledge positively moderates the relationship between future orientation and problem-based learning and that students' proactive personality positively moderates the relationship between problem-based learning and perceived employability.

The effectiveness of exposure and response prevention combined with pharmacotherapy for obsessive-compulsive disorder: A systematic review and meta-analysis.

Objective: To systematically evaluate the effectiveness of exposure and response prevention (ERP) combined with medication on obsessive-compulsive disorder (OCD). Methods: PubMed, Web of Science, EBSCO, Cochrane, Embase, and Science Direct databases were searched to include randomized controlled trials of ERP combined with medication for OCD that met the criteria. The Yale Brown Obsessive Compulsive Scale was used as the primary outcome indicator, and Depression scales were used as secondary outcome indicators. An evaluation of bias risk was conducted to identify possible sources of bias based on methodological and clinical factors. Review Manager 5.3 and Stata 16.0 software was used to perform meta-analysis of the extracted data. Results: A total of 21 studies with 1113 patients were included. Meta-analysis showed that ERP combined with medication therapy was significantly better than medication therapy alone including selective serotonin reuptake inhibitors, clomipramine and risperidone (MD = -6.60, 95% CI: -8.35 to -4.84, P < 0.00001), but D-cycloserine (DCS) drugs do not enhance the effect of ERP intervention in patients with OCD (MD = 0.15, 95% CI: -0.87 to 1.17, P = 0.77). There is more significant maintenance by combined treatment method of medication plus ERP than medication treatment alone during the follow-up period (MD = -7.14, 95% CI: -9.17 to -5.10, P < 0.00001). DCS drugs did not enhance the effect of ERP intervention on depression in patients with OCD (SMD = -0.08, 95% CI: -0.31 to 0.15, P = 0.50). ERP combined with drug improved patients' depression levels significantly better than providing drug alone (SMD = -0.40, 95% CI: -0.68 to -0.11, P = 0.006). Conclusion: Patients with OCD have significant improvement in symptoms of obsessive-compulsive disorder and depression when ERP is combined with medication, however, not enough to prove that DCS can enhance ERP effectiveness.

Efficacy of Gamma Globulins in Children with Kawasaki Disease and Factors Influencing Children's Short-Term Prognosis.

Purpose: To explore and analyze the therapeutic effect of gamma globulins (GG) on Kawasaki disease (KD) in children and the influencing factors of short-term prognosis. Methods: First, 90 pediatric KD patients admitted between January 2019 and January 2021 were selected and divided into a control group (n = 40) and a research group (n = 50) according to the difference in treatment. In addition to routine treatment and nursing given to both groups, control group was given aspirin (ASA), based on which research group was supplemented with GG therapy. The treatment outcome and adverse events (AEs) of the two cohorts of patients were analyzed and compared, and the influencing factors of children's short-term prognosis were analyzed by logistics multivariate analysis. Results: Research group had a statistical higher overall response rate than control group, with significantly fewer cases suffering from AEs such as nausea and vomiting, diarrhea, rash, dizziness and headache, and coronary artery injury. On the other hand, logistics multivariate analysis identified that gender, body mass index (BMI), onset time, platelet (PLT), and treatment mode all independently influence the short-term prognosis of children with KD. Conclusions: GG therapy is effective in treating pediatric KD patients and can effectively prevent AEs. In addition, gender, BMI, onset-to-treatment time, PLT, C-reactive protein (CRP), and treatment methods are independent risk factors for short-term prognosis of children with KD.

DNA methylation plays an important role in iron-overloaded Tibetans.

The prevalence of iron overload in Tibetans in Tibet is higher than that in Han. DNA methylation (DNAm) is closely related to iron metabolism and iron level. Nevertheless, the epigenetic status of Tibetans with iron overload is unknown, and we therefore aimed to explore whether the phenomenon observed in the Tibetan population is regulated by epigenetics. The results showed that 2.26% of cytosine was methylated in the whole genome, and that the rate of CG cytosine methylation was higher in individuals in the iron overload (TH) group than in those in the iron normal (TL) group. We analyzed differentially methylated genes (DMGs) in whole-genome bisulfite sequencing data from the TH and TL groups of high-altitude Tibetans. Protein-protein interaction and pathway analyses of candidate DMGs related to iron uptake and transport showed that epigenetic changes in 10 candidate genes (ACO1, CYBRD1, FLVCR1, HFE, HMOX2, IREB2, NEDD8, SLC11A2, SLC40A1 and TFRC) are likely to relate to iron overload. This work reveals, for the first time, changes of DNAm in Tibetan people with iron overload, which suggest that DNAm is a mechanism underlying differences in iron content between individuals in the high-altitude Tibetan population. Our findings should contribute to the study of iron metabolism and the overall health status of Tibetans.

The Surprise Question as a Trigger for Primary Palliative Care Interventions for Children with Advanced Heart Disease.

There is significant uncertainty in describing prognosis and a lack of reliable entry criteria for palliative care studies in children with advanced heart disease (AHD). This study evaluates the utility of the surprise question-"Would you be surprised if this child died within the next year?"-to predict one-year mortality in children with AHD and assess its utility as entry criteria for future trials. This is a prospective cohort study of physicians and nurses caring for children (1 month-19 years) with AHD hospitalized ≥ 7 days. AHD was defined as single ventricle physiology, pulmonary vein stenosis or pulmonary hypertension, or any cardiac diagnosis with signs of advanced disease. Primary physicians were asked the surprise question and medical record review was performed. Forty-nine physicians responded to the surprise question for 152 patients. Physicians responded "No, I would not be surprised if this patient died" for 54 (36%) patients, 20 (37%) of whom died within 1 year, predicting one-year mortality with 77% sensitivity, 73% specificity, 37% positive predictive value, and 94% negative predictive value. Patients who received a "No" response had an increased 1-year risk of death (hazard ratio 7.25, p < 0.001). Physician years of experience, subspecialty, and self-rated competency were not associated with the accuracy of the surprise question. The surprise question offers promise as a bedside screening tool to identify children with AHD at high risk for mortality and help physicians identify patients who may benefit from palliative care and advance care planning discussions.

Impairments in intrinsic functional networks in type 2 diabetes: A meta-analysis of resting-state functional connectivity.

Type 2 diabetes mellitus (T2DM) is associated with abnormal communication among large-scale brain networks, revealed by resting-state functional connectivity (rsFC), with inconsistent results between studies. We performed a meta-analysis of seed-based rsFC studies to identify consistent network connectivity alterations. Thirty-three datasets from 30 studies (1014 T2DM patients and 902 healthy controls [HC]) were included. Seed coordinates and between-group effects were extracted, and the seeds were divided into networks based on their location. Compared to HC, T2DM patients showed hyperconnectivity and hypoconnectivity within the DMN, DMN hypoconnectivity with the affective network (AN), ventral attention network (VAN) and frontal parietal network, and DMN hyperconnectivity with the VAN and visual network. T2DM patients also showed AN hypoconnectivity with the somatomotor network and hyperconnectivity with the VAN. T2DM illness durations negatively correlated with within-DMN rsFC. These DMN-centered impairments in large-scale brain networks in T2DM patients may help to explain the cognitive deficits associated with T2DM.

Dopamine D2 receptors in the nucleus accumbens modulate erectile function in a rat model of nonorganic erectile dysfunction.

BACKGROUND: The central molecular mechanisms of nonorganic erectile dysfunction remains unknown. OBJECTIVE: This study aimed to investigate the association of dopaminergic neurons projecting to the nucleus accumbens of male rats with nonorganic erectile dysfunction. MATERIALS/METHODS: Nonorganic erectile dysfunction was induced by chronic mild stress. The sucrose consumption test, sexual behavior test, and apomorphine test were carried out to select depression-like rats with erectile dysfunction. These rats were considered as nonorganic erectile dysfunction model rats. Dopamine D1/D2 receptor agonist/antagonist was infused into the nucleus accumbens to observe the effect on sexual behavior. Dopaminergic projections to the nucleus accumbens were labeled with both the retrograde tracer FluoroGold injected into the nucleus accumbens and tyrosine hydroxylase. The expression level of tyrosine hydroxylase in dopaminergic neurons projecting to the nucleus accumbens in the ventral tegmental area was measured. The expression levels of dopamine D1/D2 receptors and tyrosine hydroxylase in the nucleus accumbens were also measured. RESULTS: Nonorganic erectile dysfunction was proved by the sucrose consumption test, sexual behavior test, and apomorphine test in model rats. After central infusion of the dopamine D2 receptor agonist into the nucleus accumbens, the recovery of erectile function, sexual arousal, and motivation were indicated by increased intromission ratio and decreased mount latency. Decreased expression levels of dopamine D2 receptors and tyrosine hydroxylase in the nucleus accumbens and decreased expression level of tyrosine hydroxylase in the dopaminergic neurons projecting to the nucleus accumbens were observed in model rats. DISCUSSION: These results suggest the impairment of dopaminergic neurons projecting to the nucleus accumbens and dopamine D2 signaling in the nucleus accumbens, causing the suppression of erectile function, sexual arousal, and motivation. CONCLUSION: These results suggest that the impaired dopamine D2 receptor pathway in the nucleus accumbens may be one of the main pathway involved in the development of nonorganic erectile dysfunction in the present model.

Internet-based platform for a low-calorie dietary intervention involving prepackaged food for weight loss in overweight and obese individuals in China: protocol for a randomised controlled trial.

INTRODUCTION: Obesity is a global health issue that impacts quality of life. A calorie-restricted diet with high-intensity consultation provided via the internet may be an effective way to lose weight. The objective of this study was to assess the effectiveness of a practitioner-guided, mobile internet-based low-energy dietary intervention in overweight and obese populations in China. METHODS AND ANALYSIS: This open-label randomised controlled trial enrolled 220 overweight and obese adults aged 18-70 years who met the inclusion criteria. Participants were assigned to the control group (n=110) or trial group (n=110). The trial group will be enrolled in the MetaWell programme, a weight loss programme using diet replacement products, wireless scales and a mobile phone app. Participants in the control group will receive paper material containing a sample diet for weight loss. The follow-up period will be 1 year, and measurements will occur at 3, 6 and 12 months. Dual-emission X-ray absorptiometry and abdominal quantitative CT will be performed to estimate the percentage of overall body fat and areas of visceral and subcutaneous fat, alongside several cardiometabolic measurements. The primary outcome of this study is the change in body mas index (BMI) at 6 months after enrolment. A mixed-effects model will be used to compare BMI and body fat changes between the two groups. ETHICS AND DISSEMINATION: This study was approved by the ethics committee of the Hospital of Chengdu Office of the People's Government of the Tibetan Autonomous Region. Advertisements for recruitment will be sent via official accounts using WeChat. The results will be disseminated via publications in academic journals and our clinic. Our study group will maintain contact with the participants to inform them of the study findings. TRIAL REGISTRATION NUMBER: ChiCTR1900021630.