Gut flora metagenomic analysis coupled with metabolic and deep immune profiling in chronic kidney disease.

BACKGROUND: Perturbation of gut microbiota has been linked to chronic kidney disease (CKD), which was correlated with a sophisticated milieu of metabolic and immune dysregulation. METHODS: To clarify the underlying host-microbe interaction in CKD, we performed multi-omics measurements, including systems-level gut microbiome, targeted serum metabolome and deep immunotyping, in a cohort of patients and non-CKD controls. RESULTS: Our analyses on functional profiles of the gut microbiome showed a decrease in the diversity and abundance of carbohydrate-active enzyme (CAZyme) genes but an increase in the abundance of antibiotic resistance, nitrogen cycling enzyme and virulence factor genes in CKD. Moreover, models generated using measurements of serum metabolites (amino acids, bile acids and short-chain fatty acids) or immunotypes were predictive of renal impairment but less so than many of the functional profiles derived from gut microbiota, with the CAZyme genes being the top-performing model to accurately predict the early stage of diseases. In addition, co-occurrence analyses revealed coordinated host-microbe relationships in CKD. Specifically, the highest fractions of significant correlations were identified with circulating metabolites by several taxonomic and functional profiles of gut microbiome, while immunotype features were moderately associated with the abundance of microbiome-encoded metabolic pathways and serum levels of amino acids (e.g. B cell cluster tryptophan and B cell cluster tryptophan metabolism). CONCLUSION: Overall, our multi-omics integration revealed several signatures of systems-level gut microbiome in robust associations with host-microbe co-metabolites and renal function, which may have aetiological and diagnostic implications in CKD.

Quality of life and clinical correlates in cognitively-able autistic adults: A special focus on sensory characteristics and perceived parental support.

BACKGROUND: Quality of life (QoL) has been suggested as an indicator of outcomes in autistic adults. Factors associated with QoL in autistic individuals remain unclear. This study aims to examine the subjective QoL for autistic adults in Taiwan and investigate the determinants for different domains of QoL. METHODS: The study comprised 90 autistic adults (aged 26.9, SD 7.3; males, 80.9%). We used Taiwanese version of World Health Organization Quality of Life-BREF to measure QoL. Four domains of QoL were compared with 61 non-autistic controls, including physical, psychological, social, and environment. To identify the correlates of QoL domains, we assessed IQ, personality trait, family support, anxiety/depressive symptoms, autistic severity, and sensory symptoms by various questionnaires, and assessed their association with QoL by correlation analyses and model selection. RESULTS: Our results showed that autistic adults reported lower QoL on the World Health Organization Quality of Life (WHOQOL)-BREF across all domains. QoL was significantly associated with autistic symptom severity, harm avoidance, family support, sensory symptoms, anxiety, and depression, but not intelligence. Model selections revealed male sex, poor paternal support, autism severity, depression, anxiety, and sensory symptoms were associated with specific QoL domains. CONCLUSION: Findings supported lower QoL in autistic adults. Modifying the QoL correlates may improve life quality in autistic adults. Furthermore, our findings revealed the importance of sensory symptoms and paternal support in QoL of autistic adults, which was a novel finding in this population.

The association between admission serum albumin and preoperative deep venous thrombosis in geriatrics hip fracture: a retrospective study of 1819 patients with age ≥ 65 years.

OBJECTIVE: This study evaluated the association between serum albumin levels and preoperative deep vein thrombosis (DVT) in geriatric hip fractures. METHODS: Older adult patients with hip fractures were screened between January 2015 and September 2019. The demographic and clinical characteristics of the patients were collected. Multivariate binary logistic regression and generalized additive model were used to identify the linear and nonlinear association between albumin levels and preoperative DVT. Analyses were performed using EmpowerStats and the R software. RESULTS: A total of 1819 patients were included in this study. The average age was 79.37 ± 6.88 years. There were 550 males and 1269 females. The preoperative albumin was 38.19 ± 4.07 g/L. There were 580 (31.89%) preoperative DVTs. Multivariate binary logistic regression showed that albumin level was associated with preoperative DVT (odds ratio [OR] = 0.94, 95% confidence interval [CI]: 0.91-0.97, P = 0.0002) after adjusting for confounding factors. The fully adjusted model showed a DVT risk decrease of 6% when albumin concentration increased by one g/L after controlling for confounding factors. In addition, the trend test and propensity score matching also showed a stable linear correlation between albumin level and preoperative DVT. CONCLUSION: Serum albumin is associated with preoperative DVT in geriatric patients with hip fractures, and it could be considered a predictor for the risk of DVT. REGISTRATION ID: ChiCTR2200057323.

Influence of fetal Leydig cells on the development of adult Leydig cell population in rats.

Leydig cells are the main endogenous testosterone synthesis cells in the body. Testosterone is an essential hormone in males that affects metabolism, emotion, and pubertal development. However, little is known about the development of Leydig cells and relationship between fetal Leydig cells (FLCs) and adult Leydig cells (ALCs). The aims of this study were to investigate the effect of (FLCs) on ALC development. Our study showed that FLCs in neonatal rat testis can be eliminated by 100 mg/kg ethane dimethane sulfonate (EDS) treatment without affecting the health of newborn rats. Immunohistological results showed that eliminating FLCs led to early re-generation of the ALC population (progenitor Leydig cells [PLCs] and ALCs) accompanied at first by increased and then by decreased serum testosterone, indicating that ALCs which appeared after neonatal EDS treatment were degenerated or had attenuated functions. Our results showed that FLCs were eliminated 4 days after EDS treatment, the ALC population regenerated by 21 days, and serum testosterone levels dramatically decreased at 56 days. Collectively, our results indicate that the ablation of FLCs in neonatal rat results in abnormal development of ALCs. Our study further indicates that abnormal development of Leydig cells in the fetal stage leads to steroid hormone disorders, such as testosterone deficiency, in the adult stage. Therefore, studies of Leydig cell development are important for understanding the pathogenesis of testosterone deficiency or pubertas praecox.

[Roles of sialic acids in sperm maturation and capacitation and sperm-egg recognition].

Sialic acids are a subset of nine-carbon alpha-keto aldonic acids involved in various biological functions. Sialic acid on the sperm surface is closely related to sperm maturation and capacitation and sperm-egg recognition, which makes sperm negatively charged to avoid accumulation and covers some antigenic determinants there to increase the survival rate of sperm in the female reproductive tract. The loss of sialic acids is an important factor mediating sperm capacitation. Moreover, the sialic acid at the extremity of the protein polymer is involved in signal identification in sperm-egg recognition. Here, we review the current understanding of sialic acids in sperm maturation and capacitation and sperm-egg recognition.

Deep immune profiling of patients with renal impairment unveils distinct immunotypes associated with disease severity.

Background: Chronic kidney disease (CKD) is pathologically correlated with a sophisticated milieu of innate and adaptive immune dysregulation, but the underlying immunological disturbances remain poorly understood. Methods: To address this, we comprehensively interrogated cellular and soluble elements of the immune system by using high-dimensional flow cytometry to analyze peripheral blood mononuclear cells and performing cytokine/chemokine profiling of serum samples, respectively, in a cohort of 69 patients and 19 non-CKD controls. Results: Altered serum levels of several cytokines/chemokines were identified, among which concentrations of stem cell factor (SCF) were found to be elevated with the progression of CKD and inversely correlated with estimated glomerular filtration rate (eGFR). Deep immunophenotyping analyses reveal a global change in immune modulation associated with CKD severity. Specifically, a decrease in the subsets of CD56dim natural killer (NK) cells (KLRG-1+CD38+CD64+CD15+CD197+) and monocytes (KLRG-1+CD38+PD-1+) was detected in severe CKD compared with controls and mild CKD. In addition, comparisons between mild and severe CKD demonstrated a loss of a mature B cell population (PD-1+CD197+IgD+HLA-DR+) in the advanced stages of disease. Further, we identified immunophenotypic markers to discriminate mild CKD from the controls, among which the portion of CD38+ monocytes was of particular value in early diagnosis. Conclusions: Our data unveil severity-specific immunological signatures perturbed in CKD patients.

Discovery of antipsychotic loxapine derivatives against intracellular multidrug-resistant bacteria.

The emergence and spread of multidrug-resistant bacteria highlight the need for new antibacterial interventions. A screening of 24 newly synthesized dibenzoxazepines identified a small molecule compound, SW14, with potent inhibitory activity against intracellular multidrug-resistant and fluoroquinolone-resistant strains of S. typhimurium in macrophages and epithelial cells. Moreover, intra-macrophagic Salmonella typhi, Yersinia enterocolitica, and Listeria monocytogenes and methicillin-resistant Staphylococcus aureus are also susceptible to SW14. Overall, our findings suggest that SW14 has a broad-spectrum activity against intracellular bacteria.

Two-dimensional taxonomy of internet addiction and assessment of smartphone addiction with diagnostic criteria and mobile apps.

A recent review by Montag et al. raised a taxonomical argument about internet addiction. We propose a two-dimensional taxonomy of internet addiction by both the device and the content as the solution. For the assessment of smartphone addiction, measurements should be based on functional impairment and validated by diagnostic criteria rather than solely on self-reported questionnaires. We detail the potential of mobile applications (apps) to improve the assessment of smartphone addiction. App-generated indicators could fulfill the unmet need of assessment of smartphone addiction and facilitate future assessment and treatment planning of smartphone addiction.

A Novel Dibenzoxazepine Attenuates Intracellular Salmonella Typhimurium Oxidative Stress Resistance.

Salmonella enterica serovar Typhimurium is the leading cause of invasive nontyphoidal salmonellosis. Additionally, the emergence of multidrug-resistant S. Typhimurium has further increased the difficulty of controlling its infection. Previously, we showed that an antipsychotic drug, loxapine, suppressed intracellular Salmonella in macrophages. To exploit loxapine's antibacterial activity, we simultaneously evaluated the anti-intracellular Salmonella activity and cytotoxicity of newly synthesized loxapine derivatives using an image-based high-content assay. We identified that SW14 exhibits potent suppressive effects on intramacrophagic S. Typhimurium with an 50% effective concentration (EC50) of 0.5 µM. SW14 also sensitized intracellular Salmonella to ciprofloxacin and cefixime and effectively controlled intracellular multidrug- and fluoroquinolone-resistant S. Typhimurium strains. However, SW14 did not affect bacterial growth in standard microbiological broth or minimal medium that mimics the phagosomal environment. Cellular autophagy blockade by 3-methyladenine (3-MA) or shATG7 elevated the susceptibility of intracellular Salmonella to SW14. Finally, reactive oxygen species (ROS) scavengers reduced the antibacterial efficacy of SW14, but the ROS levels in SW14-treated macrophages were not elevated. SW14 decreased the resistance of outer membrane-compromised S. Typhimurium to H2O2. Collectively, our data indicated that the structure of loxapine can be further optimized to develop new antibacterial agents by targeting bacterial resistance to host oxidative-stress defense. IMPORTANCE The incidence of diseases caused by pathogenic bacteria with resistance to common antibiotics is consistently increasing. In addition, Gram-negative bacteria are particularly difficult to treat with antibiotics, especially those that can invade and proliferate intracellularly. In order to find a new antibacterial compound against intracellular Salmonella, we established a cell-based high-content assay and identified SW14 from the derivatives of the antipsychotic drug loxapine. Our data indicate that SW14 has no effect on free bacteria in the medium but can suppress the intracellular proliferation of multidrug-resistant (MDR) S. Typhimurium in macrophages. We also found that SW14 can suppress the resistance of outer membrane compromised Salmonella to H2O2, and its anti-intracellular Salmonella activity can be reversed by reactive oxygen species (ROS) scavengers. Together, the findings suggest that SW14 might act via a virulence-targeted mechanism and that its structure has the potential to be further developed as a new therapeutic against MDR Salmonella.

Occupational safety training and education for needlestick injuries among nursing students in China: intervention study.

OBJECTIVES: To confirm the effect of occupational safety training and education programs (OSTEP) on needlestick injuries (NSIs) among nursing students in China. METHODS: Compare the rates and the nature of NSIs before and after OSTEP among the nursing students in China. Firstly, questionnaires were delivered to 248 randomly selected nursing students from seven training hospitals to obtain basic information concerning relevant occupational NSIs. Then regular intervention measures through OSTEP on 246 nursing students had been introduced for four years. And the resultant information concerning relevant occupational NSIs was obtained afterwards. Finally, the data analysis was performed using SPSS software, version 11.5. RESULTS: The rate of NSIs among these nursing students was relatively high before the OSTEP in China (average, 4.65 events/nurse). However, it decreased rapidly to 0.16 events/nurse average after the OSTEP. Occupational safety awareness and behavior in handling NSIs was improved in China. There was a significant difference in the results of Chi-square value (P<0.005). CONCLUSIONS: NSIs are common in nursing students in China. The OSTEP can reduce NSIs and change practical behavior markedly among nursing students in China. We should perform OSTEP on nurse students before and during the clinical practice. We must also provide effective preventive measures to reduce this kind of problem in future.