Metabolic features of adolescent major depressive disorder: A comparative study between treatment-resistant depression and first-episode drug-naive depression.

Major depressive disorder (MDD) is a psychiatric illness that can jeopardize the normal growth and development of adolescents. Approximately 40% of adolescent patients with MDD exhibit resistance to conventional antidepressants, leading to the development of Treatment-Resistant Depression (TRD). TRD is associated with severe impairments in social functioning and learning ability and an elevated risk of suicide, thereby imposing an additional societal burden. In this study, we conducted plasma metabolomic analysis on 53 adolescents diagnosed with first-episode drug-naïve MDD (FEDN-MDD), 53 adolescents with TRD, and 56 healthy controls (HCs) using hydrophilic interaction liquid chromatography-mass spectrometry (HILIC-MS) and reversed-phase liquid chromatography-mass spectrometry (RPLC-MS). We established a diagnostic model by identifying differentially expressed metabolites and applying cluster analysis, metabolic pathway analysis, and multivariate linear support vector machine (SVM) algorithms. Our findings suggest that adolescent TRD shares similarities with FEDN-MDD in five amino acid metabolic pathways and exhibits distinct metabolic characteristics, particularly tyrosine and glycerophospholipid metabolism. Furthermore, through multivariate receiver operating characteristic (ROC) analysis, we optimized the area under the curve (AUC) and achieved the highest predictive accuracy, obtaining an AUC of 0.903 when comparing FEDN-MDD patients with HCs and an AUC of 0.968 when comparing TRD patients with HCs. This study provides new evidence for the identification of adolescent TRD and sheds light on different pathophysiologies by delineating the distinct plasma metabolic profiles of adolescent TRD and FEDN-MDD.

Correlation between cognitive impairment and serum markers in patients with obstructive sleep apnea-hypopnea syndrome.

BACKGROUND: Previous studies have revealed that sleep structure and hypoxemia are two important environmental factors for cognitive impairment in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). We hypothesized that the pathophysiological mechanisms between these two factors may also be involved in cognitive impairment in patients with OSAHS. Previous studies have suggested that alterations in serum glucose and lipid metabolism, inflammatory responses, and astrocyte markers not only contribute to sleep structural disorders in OSAHS but also affect the occurrence and development of this disease. Therefore, we hypothesized that alterations in the abovementioned indicators may be involved in cognitive impairment in OSAHS. Additionally, obesity is an important risk factor for OSAHS. This study therefore aimed to explore the correlation between serum indicators and cognitive impairment in patients with OSAHS. METHODS: Patients with OSAHS who underwent polysomnography in our hospital were recruited in this study. The overall cognitive function of patients were evaluated using the Mini mental State Examination (MMSE). Blood biochemical indicators such as glucose (GLU), triglycerides (TG), and triglyceride glucose (TyG) index were measured. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of serum glucagon-like peptide-1 receptor (GLP-1R), fibroblast growth factor 21 (FGF21), S100 calcium binding protein B (S100B), brain derived neurotrophic factor (BDNF), inflammatory factors such as C-reactive protein (CRP), tumor necrosis factor-α (TNFα), interleukin-4 (IL-4), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6). Spearman correlation analysis was used to determine if the indicator was related to cognitive function, and backward linear regression analysis was used to identify the main risk factors for cognitive impairment in non-obese and obese patients with OSAHS. RESULTS: Among 34 patients, 19 were non-obese and 15 were obese. Obese patients exhibited higher AHI compared to non-obese individuals, and the difference was statistically significant (p < 0.05). In non-obese patients, Spearman correlation analysis revealed a negative correlation between serum GLU, IL-4, and MMSE scores (p < 0.05); IL-6 was positively correlated with MMSE (p < 0.05). In addition, GLU and IL-6 were independently correlated with MMSE in non-obese patients (p < 0.05). In obese patients, serum TG and TyG were positively correlated with MMSE scores (p < 0.05); age, BMI, and IL-4 were negatively correlated with MMSE scores (p < 0.05). In addition, age and IL-4 were independently correlated with MMSE in obese patients (p < 0.05). CONCLUSIONS: Our data suggested that GLU and IL-6 were independently correlated with cognitive impairment in non-obese patients with OSAHS; age and IL-4 were independently correlated with cognitive impairment in obese patients. Early detection of this difference in heterogeneity may provide theoretical support for future investigations in prevention and treatment of cognitive impairment in patients with OSAHS.

Oxygen-carrying acid-responsive Cu/ZIF-8 for photodynamic antibacterial therapy against cariogenic Streptococcus mutans infection.

Caries as a result of acid demineralization is the most common oral microbial infectious disease. Due to the small and complex intraoral operating space, it is challenging to completely remove Streptococcus mutans (S. mutans) and other cariogenic bacteria. As an intelligent acid-responsive photosensitive nanomaterial, O2-Cu/ZIF-8@Ce6/ZIF-8@HA (OCZCH) was chosen to adapt to the anaerobic and acidic microenvironment for inactivating S. mutans. In this work, OCZCH not only exhibits a regular nanomorphology in SEM and TEM images but also shows intelligent acid responsiveness as evidenced by the release of Ce6 and oxygen. When excited by near-infrared light at 650 nm, Ce6 releases reactive oxygen species (ROS) that act synergistically with internal oxygen to significantly enhance the antimicrobial therapeutic effect of photodynamic therapy (PDT). In vitro antimicrobial experiments showed that OCZCH could achieve an impressive sterilization effect against S. mutans and biofilm. Notably, the acid-producing ability of the bacteria was also significantly inhibited. With its oxygen-carrying photosensitizing properties, excellent responsiveness to acidic environments, and antimicrobial capacity under anaerobic conditions, OCZCH is considered an innovative candidate for clinical application in treating dental caries.

Relationship between slow-wave sleep and serum γ-glutamine transaminase in non-obese men with obstructive sleep apnea-hypopnea syndrome.

BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a disease characterized with intermittent hypoxia and sleep fragmentation. Obesity and gender are major risk factors for the onset of OSAHS. Previous studies on obese men with OSAHS have been performed, while few studies on non-obese men with OSAHS have been carried out. The purpose of this study was to explore the clinical characteristics of polysomnography and blood biochemical indexes in non-obese men with OSAHS and to identify the possible influencing factors. METHODS: This retrospective study included patients with OSAHS who underwent polysomnography in our hospital. General clinical data such as overnight polysomnography and biochemical indicators were recorded. The patients were divided into two groups according to the apnea-hypopnea index (AHI): mild to moderate OSAHS and severe OSAHS. The differences in biochemical parameters such as the levels of γ-glutamine transaminase (GGT), triglyceride (TG), glucose (GLU), and sleep structure parameters such as N1, N2, slow-wave sleep (SWS), and rapid eye movement (REM) sleep were compared and analyzed. Spearman correlation analysis and logistic regression were used to identify the risk factors of non-obese men with OSAHS. ROC curves were used to evaluate the predictive ability of SWS and GGT on disease severity. RESULTS: Of 94 non-obese men with OSAHS, 49 had mild to moderate OSAHS and 45 had severe OSAHS. Our data suggested that the levels of low oxygen saturation (L-SaO2), mean oxygen saturation (M-SaO2), SWS, and GGT were significantly changed in the mild to moderate OSAHS group compared with the severe group (p < 0.05). For patients with OSAHS, the proportion of SWS in the group with severe OSAHS was higher than that in the mild to moderate group (p < 0.05), and the serum GGT enzyme levels were significantly elevated in the severe group compared to the mild to moderate group (p < 0.05). Using logistic regression analyses, our data revealed that both SWS and GGT enzyme levels were independent risk factors for AHI (p < 0.05). In addition, the results of correlation analysis indicated that SWS was related to triglyceride (TG), total cholesterol (TC), apolipoprotein E (APOE), and triglyceride glucose (TyG) index (p < 0.05); GGT was related to TG, TC, APOE, and TyG index (p < 0.05). Furthermore, SWS was independently associated with GGT (p < 0.05). The area under the ROC curve plotted with the combined coefficient of SWS and serum GGT was 0.728, which was predictive of the disease severity. CONCLUSIONS: These results suggest that SWS and GGT are independent associated factors of the severity of the disease. However, TyG index was not an independent associated factor of the severity of disease in non-obese men with OSAHS. In addition, SWS and GGT were negatively correlated. SWS combined with serum GGT may be predictive of the severity of the disease. This study may have added to our understanding of the pathogenesis of OSAHS in non-obese men.

Improved methods for estimating fraction of missing information in multiple imputation.

Multiple imputation (MI) has become the most popular approach in handling missing data. Closely associated with MI, the fraction of missing information (FMI) is an important parameter for diagnosing the impact of missing data. Currently γ m , the sample value of FMI estimated from MI of a limited m, is used as the estimate of γ0, the population value of FMI, where m is the number of imputations of the MI. This FMI estimation method, however, has never been adequately justified and evaluated. In this paper, we quantitatively demonstrated that E(γ m ) decreases with the increase of m so that E(γ m ) > γ0 for any finite m. As a result γ m would inevitably overestimate γ0. Three improved FMI estimation methods were proposed. The major conclusions were substantiated by the results of the MI trials using the data of the 2012 Physician Workflow Mail Survey of the National Ambulatory Medical Care Survey, USA.

Fraction of Missing Information (γ) at Different Missing Data Fractions in the 2012 NAMCS Physician Workflow Mail Survey.

In his 1987 classic book on multiple imputation (MI), Rubin used the fraction of missing information, γ, to define the relative efficiency (RE) of MI as RE = (1 + γ/m)-1/2, where m is the number of imputations, leading to the conclusion that a small m (≤5) would be sufficient for MI. However, evidence has been accumulating that many more imputations are needed. Why would the apparently sufficient m deduced from the RE be actually too small? The answer may lie with γ. In this research, γ was determined at the fractions of missing data (δ) of 4%, 10%, 20%, and 29% using the 2012 Physician Workflow Mail Survey of the National Ambulatory Medical Care Survey (NAMCS). The γ values were strikingly small, ranging in the order of 10-6 to 0.01. As δ increased, γ usually increased but sometimes decreased. How the data were analysed had the dominating effects on γ, overshadowing the effect of δ. The results suggest that it is impossible to predict γ using δ and that it may not be appropriate to use the γ-based RE to determine sufficient m.

Determining Sufficient Number of Imputations Using Variance of Imputation Variances: Data from 2012 NAMCS Physician Workflow Mail Survey.

How many imputations are sufficient in multiple imputations? The answer given by different researchers varies from as few as 2 - 3 to as many as hundreds. Perhaps no single number of imputations would fit all situations. In this study, η, the minimally sufficient number of imputations, was determined based on the relationship between m, the number of imputations, and ω, the standard error of imputation variances using the 2012 National Ambulatory Medical Care Survey (NAMCS) Physician Workflow mail survey. Five variables of various value ranges, variances, and missing data percentages were tested. For all variables tested, ω decreased as m increased. The m value above which the cost of further increase in m would outweigh the benefit of reducing ω was recognized as the η. This method has a potential to be used by anyone to determine η that fits his or her own data situation.

Consent for genetic research in a general population: an update on the National Health and Nutrition Examination Survey experience.

PURPOSE: The study determines the consent rates for storage of biologic samples for future research with and without genetic studies and describes trends in sociodemographic factors associated with consent. METHODS: We performed an analysis of the characteristics of consenting individuals participating in three data cycles of the National Health and Nutrition Examination Survey, a nationally representative survey of the U.S. population. RESULTS: In the 1999 to 2000 and the 2001 and 2002 surveys, 84.8% and 90.1% of eligible participants, respectively, consented to have their biologic samples including DNA stored in a national repository. Female and non-Hispanic black participants were least likely to consent when genetic studies and DNA were included. In the 2003 to 2004 survey, with the discontinuation of the DNA collection, 98.4% signed the consent document and these race/gender differences were no longer observed. CONCLUSION: Females and non-Hispanic blacks consistently had lower consent rates during the survey years when genetic studies were mentioned in the consent, but once DNA collection was discontinued these differences disappeared. These findings demonstrate wide acceptance among survey participants for allowing storage of specimens for future studies but indicate the need to explore race/gender issues with the collection and storage of DNA for genetic research.