Comparative genomic analyses of Cutibacterium granulosum provide insights into genomic diversity.

Cutibacterium granulosum, a commensal bacterium found on human skin, formerly known as Propionibacterium granulosum, rarely causes infections and is generally considered non-pathogenic. Recent research has revealed the transferability of the multidrug-resistant plasmid pTZC1 between C. granulosum and Cutibacterium acnes, the latter being an opportunistic pathogen in surgical site infections. However, there is a noticeable lack of research on the genome of C. granulosum, and the genetic landscape of this species remains largely uncharted. We investigated the genomic features and evolutionary structure of C. granulosum by analyzing a total of 30 Metagenome-Assembled Genomes (MAGs) and isolate genomes retrieved from public databases, as well as those generated in this study. A pan-genome of 6,077 genes was identified for C. granulosum. Remarkably, the 'cloud genes' constituted 62.38% of the pan-genome. Genes associated with mobilome: prophages, transposons [X], defense mechanisms [V] and replication, recombination and repair [L] were enriched in the cloud genome. Phylogenomic analysis revealed two distinct mono-clades, highlighting the genomic diversity of C. granulosum. The genomic diversity was further confirmed by the distribution of Average Nucleotide Identity (ANI) values. The functional profiles analysis of C. granulosum unveiled a wide range of potential Antibiotic Resistance Genes (ARGs) and virulence factors, suggesting its potential tolerance to various environmental challenges. Subtype I-E of the CRISPR-Cas system was the most abundant in these genomes, a feature also detected in C. acnes genomes. Given the widespread distribution of C. granulosum strains within skin microbiome, our findings make a substantial contribution to our broader understanding of the genetic diversity, which may open new avenues for investigating the mechanisms and treatment of conditions such as acne vulgaris.

Prevalence and risk factors of non-tuberculous mycobacterial pulmonary isolates and infection in interstitial lung disease associated with systemic autoimmune disease.

OBJECTIVES: Non-tuberculous mycobacterial (NTM) lung disease (NTM-LD) prevalence is increasing worldwide. In this study, we aimed to evaluate the clinical significance of NTM pulmonary isolates (NTM-PI) and NTM-LD in patients with systemic autoimmune disease (SAD) who had a concurrent interstitial lung disease (ILD) diagnosis. METHODS: We retrospectively identified patients with SAD who had a concurrent ILD diagnosis (SAD-ILD) and from whom clinically indicated sputum specimens were collected for NTM culture between 2003 and 2018 at a tertiary referral hospital. We analysed the prevalence and risk factors of NTM pulmonary isolates (NTM-PI; ≥1 positive culture) and NTM-LD (≥2 positive cultures). RESULTS: This study included 258 patients. Rheumatoid arthritis and Sjögren's syndrome were the most common SADs (32.2% and 26.7%, respectively). The NTM-negative subgroup had 204 patients (79.1%) and the NTM-PI subgroup had 54 patients (20.9%). In the NTM-PI subgroup, 33 patients had one NTM positive set of specimens (NTM 1+, 12.8% of the entire sample) and 21 had NTM-LD (8.1% of the entire sample). In a multivariable analysis, chronic kidney disease (CKD; adjusted odds ratio [aOR]: 3.10 [1.53, 6.29]) and chronic obstructive pulmonary disease (COPD; aOR: 2.59 [1.16, 5.78]) were significantly associated with NTM-PI. For NTM-LD, CKD (aOR: 2.79 [1.00, 7.76]) and COPD (aOR: 3.70 [1.23, 10.72]) remained significant risk factors. CONCLUSIONS: In patients with SAD-ILD, the NTM-PI and NTM-LD prevalence rates were 20.9% and 8.1%, respectively. COPD and CKD were independent risk factors of both NTM-PI and NTM-LD. Previous use of biological agents was associated with NTM-PI.

The largest genome-wide association study for breast cancer in Taiwanese Han population.

PURPOSE: Breast cancer is a molecularly heterogeneous disease, and multiple genetic variants contribute to its development and prognosis. Most of previous genome-wide association studies (GWASs) and polygenic risk scores (PRSs) analyses focused on studying breast cancers of Caucasian populations, which may not be applicable to other population. Therefore, we conducted the largest breast cancer cohort of Taiwanese population to fill in the knowledge gap. METHODS: A total of 152,534 Participants recruited by China Medical University Hospital between 2003 and 2019 were filtered by several patient selection criteria and GWAS quality control steps, resulting in the inclusion of 2496 cases and 9984 controls for this study. We then conducted GWAS for all breast cancers and PRS analyses for all breast cancers and the four breast cancer subtypes, including luminal A, luminal B, basal-like, and HER2-enriched. RESULTS: The GWAS analyses identified 113 SNPs, 50 of which were novel. The PRS models for all breast cancers and the luminal A subtype showed positively correlated trends between the PRS and the risk of developing breast cancer. The odds ratios (95% confidence intervals) for the groups with the highest PRS in all breast cancers and the luminal A subtype were 5.33 (3.79-7.66) and 3.55 (2.13-6.14), respectively. CONCLUSION: In summary, we explored the association of genetic variants with breast cancer in the largest Taiwanese cohort and developed two PRS models that can predict the risk of developing any breast cancer and the luminal A subtype in Taiwanese women.

Integrated Human Skin Bacteria Genome Catalog Reveals Extensive Unexplored Habitat-Specific Microbiome Diversity and Function.

The skin is the largest organ in the human body. Various skin environments on its surface constitutes a complex ecosystem. One of the characteristics of the skin micro-ecosystem is low biomass, which greatly limits a comprehensive identification of the microbial species through sequencing. In this study, deep-shotgun sequencing (average 21.5 Gigabyte (Gb)) from 450 facial samples and publicly available skin metagenomic datasets of 2069 samples to assemble a Unified Human Skin Genome (UHSG) catalog is integrated. The UHSG encompasses 813 prokaryotic species derived from 5779 metagenome-assembled genomes, among which 470 are novel species covering 20 phyla with 1385 novel assembled genomes. Based on the UHSG, the core functions of the skin microbiome are described and the differences in amino acid metabolism, carbohydrate metabolism, and drug resistance functions among different phyla are identified. Furthermore, analysis of secondary metabolites of the near-complete genomes further find 1220 putative novel secondary metabolites, several of which are found in previously unknown genomes. Single nucleotide variant (SNV) reveals a possible skin protection mechanism: the negative selection process of the skin environment to conditional pathogens. UHSG offers a convenient reference database that will facilitate a more in-depth understanding of the role of skin microorganisms in the skin.

A method to protect the endometrium for microwave ablation treating types 1-3 uterine fibroids: a preliminary comparative study.

PURPOSE: To investigate the feasibility of percutaneous intrauterine instillation of chilled saline to protect the endometrium during microwave ablation (MWA) treating types 1-3 uterine fibroids. MATERIALS AND METHODS: Twenty-six patients with types 1-3 uterine fibroids were prospectively enrolled in an intrauterine saline instillation group (study group). The same number of patients with types 1-3 uterine fibroids who previously received MWA without endometrial protection were retrospectively included in a control group. Endometrial impairment was evaluated by hysteroscopy and magnetic resonance imaging (MRI). RESULTS: In the study group, hysteroscopy revealed an intact endometrium in 17 patients, congestion and reddening of the endometrium due to heat in 8 patients, and a burnt necrosis with a size < 1 cm on the functional layer of the endometrium in 1 patient. On MRI, in the study group, there were 17 (65.4%), 6 (23.1%), and 3 (11.5%) patients with grades 0, 1, and 2 endometrial impairment, respectively, but no grade 3 endometrial impairment. In the control group, there were 8 (30.8%), 8 (30.8%), 7 (26.9%), and 3 (11.5%) patients with grades 0, 1, 2, and 3 endometrial impairment, respectively. Endometrial impairment in the study group was significantly better than that in the control group (p = 0.006). One patient had puncture tunnel bleeding and no other complications occurred in the study group. CONCLUSION: Intraoperative percutaneous intrauterine instillation of chilled saline may be effective and safe in reducing the thermal damage to the endometrium caused by MWA for treating types 1-3 uterine fibroids.

Intraoperative Dexmedetomidine Decreases Postoperative Pain after Gastric Endoscopic Submucosal Dissection: A Prospective Randomized Controlled Trial.

BACKGROUND: Postoperative pain is one of the most common complications after gastric endoscopic submucosal dissection (ESD); however, there have been only a few studies assessing the efficacy of interventions on postoperative pain after gastric ESD. This prospective randomized controlled trial was designed to assess the effect of intraoperative dexmedetomidine (DEX) on postoperative pain after gastric ESD. MATERIALS AND METHODS: A total of 60 patients undergoing elective gastric ESD under general anesthesia were randomly divided into the DEX group receiving DEX with a loading dose of 1 µg/kg, followed by a maintenance dose of 0.6 µg/kg/h until 30 min before the end of the endoscopic procedure, and the control group receiving normal saline. The primary outcome was the visual analog scale (VAS) score of postoperative pain. Secondary outcomes were the dosage of morphine for postoperative pain control, hemodynamic changes during the observable period, the occurrence of adverse events, lengths of postanesthesia care unit (PACU) and hospital stays, and patient satisfaction. RESULTS: The incidence of postoperative moderate to severe pain was 27% and 53% in the DEX and control groups, respectively, with a significant difference. Compared to the control group, VAS pain scores at 1 h, 2 h, and 4 h postoperatively, the dosage of morphine in the PACU, and the total dosage of morphine within 24 h postoperatively were significantly decreased in the DEX group. Both incidences of hypotension and use of ephedrine in the DEX group were significantly decreased during surgery, but they were significantly increased in the postoperative period. Postoperative nausea and vomiting scores were decreased in the DEX group; however, the length of PACU stay, patient satisfaction, and duration of hospital stay were not significantly different between groups. CONCLUSION: Intraoperative DEX can significantly decrease postoperative pain level, with a slightly reduced dosage of morphine and a decreased severity of postoperative nausea and vomiting after gastric ESD.

Dexmedetomidine postconditioning attenuates myocardial ischemia/reperfusion injury by activating the Nrf2/Sirt3/SOD2 signaling pathway in the rats.

OBJECTIVES: To observe the protective effects of dexmedetomidine (Dex) postconditioning on myocardial ischemia/reperfusion injury (IRI) and to explore its potential molecular mechanisms. METHODS: One-hundred forty-seven male Sprague-Dawley rats were randomly divided into five groups receiving the different treatments: Sham, ischemia/reperfusion (I/R), Dex, Brusatol, Dex + Brusatol. By the in vivo rat model of myocardial IRI, cardioprotective effects of Dex postconditioning were evaluated by assessing serum CK-MB and cTnI levels, myocardial HE and Tunel staining and infarct size. Furthermore, the oxidative stress-related markers including intracellular ROS level, myocardial tissue MDA level, SOD and GSH-PX activities were determined. RESULTS: Dex postconditioning significantly alleviated myocardial IRI, decreased intracellular ROS and myocardial tissue MDA level, increased SOD and GSH-PX activities. Dex postconditioning significantly up-regulated myocardial expression of Bcl-2, down-regulated Bax and cleaved caspase-3 and decreased cardiomyocyte apoptosis rate. furthermores, Dex postconditioning promoted Nrf2 nuclear translocation, increased myocardial expression of Sirt3 and SOD2 and decreased Ac-SOD2. However, brusatol reversed cardioprotective benefits of Dex postconditioning, significantly decreased Dex-induced Nrf2 nuclear translocation and reduced myocardial expression of Sirt3 and SOD2. CONCLUSIONS: Dex postconditioning can alleviate myocardial IRI by suppressing oxidative stress and apoptosis, and these beneficial effects are at least partly mediated by activating the Nrf2/Sirt3/SOD2 signaling pathway.

Promoter methylation changes in the placenta involved in the relationship between prenatal depression and small for gestational age.

BACKGROUND: Recent studies suggest that the incidence of small for gestational age (SGA) birth related to maternal depression, but the mechanism is unclear. The aim of this study was to explore the changes of promoter methylation in the placenta which may be involved in the relationship between prenatal depression and SGA. METHODS: Three hundred forty-five pregnant women were enrolled in this prospective cohort study. Perinatal emotion and sleep quality in the second and third trimesters were assessed using self-rating depression scale, self-rating anxiety scale, and Pittsburgh sleep quality index. According to the exposure (depressed emotion of mother) and outcome (SGA), the placentas were divided into four groups. Methylation of the promoter regions of the placental CRH, HSD11ß2, SLA16A10, DIO3, and MTNR1B genes was determined using next generation sequencing based on bisulfite sequencing PCR. RESULTS: There were 97 (28.1%) and 95 (27.5%) pregnant women who had depression in the second trimester and third trimester, respectively. Thirty-five pregnant women had an SGA birth. The incidence of SGA births in this prospective cohort was 10.1%. The risk factors of SGA birth were low BMI of pregnancy women (RR = 0.71, 95%CI = 0.54 ~ 0.92), hypertensive disorder complicating pregnancy (HDCP, RR = 4.7, 95%CI = 1.18 ~ 18.72), and maternal depression in the second trimester (RR = 3.71, 95%CI = 1.31 ~ 12.16). We found that the CRH and HSD11ß2 methylation levels were higher in the depression group than those in the non-depression group. Methylation levels of DIO3 were higher in SGA group than that in the non-SGA group. Higher methylation levels of CRH correlated with higher methylation levels of DIO3 in the placenta. CONCLUSIONS: Maternal depression in the second trimester may lead to the changes of methylation levels in the promoter region of CRH and HSD11ß2 gene, while the changes of methylation of DIO3 in subsequent could related to SGA. This study suggests that maternal depressed emotion during pregnancy may result in SGA due to the epigenetic changes of placenta.

Association of poorly controlled HbA1c with increased risk of progression to end-stage kidney disease and all-cause mortality in patients with diabetes and chronic kidney disease.

Glycosylated hemoglobin (HbA1c) targets for patients with chronic kidney disease (CKD) and type 2 diabetes remain controversial. To evaluate whether baseline HbA1c and HbA1c trajectories are associated with the risk of end-stage kidney disease (ESKD) and all-cause mortality, we recruited adult patients with CKD and type 2 diabetes from a "Pre-ESKD Program" at a medical center in Taiwan from 2003 to 2017. Group-based trajectory modeling was performed to identify distinct patient groups that contained patients with similar longitudinal HbA1c patterns. Cox proportional hazard models were used to estimate hazard ratios (HRs) of ESKD and mortality associated with baseline HbA1c levels and HbA1c trajectories. In the analysis related to baseline HbA1c (n = 4543), the adjusted HRs [95% confidence interval (CI)] of all-cause mortality were 1.06 (0.95-1.18) and 1.25 (95% CI, 1.07-1.46) in patients with an HbA1c level of 7%-9% (53-75 mmol/mol) and >9% (>75 mmol/mol), respectively, as compared with those with an HbA1c level < 7% (<53 mmol/mol). In the trajectory analysis (n = 2692), three distinct longitudinal HbA1c trajectories were identified: nearly optimal (55.9%), moderate to stable (34.2%), and poor control (9.9%). Compared with the "nearly optimal" HbA1c trajectory group, the "moderate-to-stable" group did not have significantly higher mortality, but the "poorly controlled" group had 35% higher risk of mortality (adjusted HR = 1.35, 95% CI = 1.06-1.71). Neither baseline levels of HbA1c nor trajectories were associated with ESKD risk. In conclusion, in patients with CKD and type 2 diabetes, poor glycemic control was associated with an elevated risk of mortality but not associated with a risk of progression to ESKD.

High-Level Expression of Cell-Surface Signaling System Hxu Enhances Pseudomonas aeruginosa Bloodstream Infection.

Bloodstream infections (BSIs) caused by Pseudomonas aeruginosa are associated with a high mortality rate in the clinic. However, the fitness mechanisms responsible for the evolution of virulence factors that facilitate the dissemination of P. aeruginosa to the bloodstream are poorly understood. In this study, a transcriptomic analysis of the BSI-associated P. aeruginosa clinical isolates showed a high-level expression of cell-surface signaling (CSS) system Hxu. Whole-genome sequencing and comparative genomics of these isolates showed that a mutation in rnfE gene was responsible for the elevated expression of the Hxu-CSS pathway. Most importantly, deletion of the hxuIRA gene cluster in a laboratory strain PAO1 reduced its BSI capability while overexpression of the HxuIRA pathway promoted BSI in a murine sepsis model. We further demonstrated that multiple components in the blood plasma, including heme, hemoglobin, the heme-scavenging proteins haptoglobin, and hemopexin, as well as the iron-delivery protein transferrin, could activate the Hxu system. Together, these studies suggested that the Hxu-CSS system was an important signal transduction pathway contributing to the adaptive pathogenesis of P. aeruginosa in BSI.

Application of machine learning methods for the prediction of true fasting status in patients performing blood tests.

The fasting blood glucose (FBG) values extracted from electronic medical records (EMR) are assumed valid in existing research, which may cause diagnostic bias due to misclassification of fasting status. We proposed a machine learning (ML) algorithm to predict the fasting status of blood samples. This cross-sectional study was conducted using the EMR of a medical center from 2003 to 2018 and a total of 2,196,833 ontological FBGs from the outpatient service were enrolled. The theoretical true fasting status are identified by comparing the values of ontological FBG with average glucose levels derived from concomitant tested HbA1c based on multi-criteria. In addition to multiple logistic regression, we extracted 67 features to predict the fasting status by eXtreme Gradient Boosting (XGBoost). The discrimination and calibration of the prediction models were also assessed. Real-world performance was gauged by the prevalence of ineffective glucose measurement (IGM). Of the 784,340 ontologically labeled fasting samples, 77.1% were considered theoretical FBGs. The median (IQR) glucose and HbA1c level of ontological and theoretical fasting samples in patients without diabetes mellitus (DM) were 94.0 (87.0, 102.0) mg/dL and 5.6 (5.4, 5.9)%, and 92.0 (86.0, 99.0) mg/dL and 5.6 (5.4, 5.9)%, respectively. The XGBoost showed comparable calibration and AUROC of 0.887 than that of 0.868 in multiple logistic regression in the parsimonious approach and identified important predictors of glucose level, home-to-hospital distance, age, and concomitantly serum creatinine and lipid testing. The prevalence of IGM dropped from 27.8% based on ontological FBGs to 0.48% by using algorithm-verified FBGs. The proposed ML algorithm or multiple logistic regression model aids in verification of the fasting status.

Efficacy of dexmedetomidine on postoperative pain in patients undergoing gastric and esophageal endoscopic submucosal dissection: a study protocol for a randomized controlled prospective trial.

BACKGROUND: Endoscopic submucosal dissection (ESD) is widely used as an effective treatment of early gastric and esophageal tumors, as it is minimally invasive, safe, and convenient. Epigastric pain is a common complication of ESD. In the traditional cognition, the postoperative pain of ESD is not serious and does not attach too much attention. However, previous studies found that the incidence of moderate to severe pain after ESD can be as high as 44.9~62.8%. At present, there is no unified understanding of how to carry out good postoperative analgesia in patients undergoing ESD of stomach and esophagus. The purpose of present study is to investigate the efficacy of intraoperative dexmedetomidine (DEX) using on postoperative pain though observing the postoperative visual analog scale (VAS) score within 48 h after ESD surgery, so as to explore an effective analgesia and anesthetic method in patients undergoing gastric and esophagus ESD. METHODS/DESIGN: This study is a prospective, single-center, two-arm, randomized control trail. In total, 120 patients undergoing endoscopic submucosal dissection were stratified by type of surgery (i.e., gastric or esophagus ESD) and randomized into two treatment groups, DEX group (group D, n = 60) and control group (group C, n = 60). Patients in the experimental group (DEX group) will be administrated a loading dose of DEX at 1 µg/kg for 15 min and a continuous infusion at 0.6 µg/kg/h until 30 min before the end of operation. In control group, the same volume of normal saline was infused. The primary outcome is VAS at 2 h after ESD surgery. The secondary outcome will be VAS at 1 h, 4 h, 6 h,18 h, 24 h, and 48 h, the status of perioperative hemodynamics, the use of remedial analgesics, sedation score, shivering, postoperative nausea and vomiting (PONV), and satisfaction scores of patient and complication of ESD (such as bleeding, perforation, aspiration pneumonia). DISCUSSION: The results of this study will demonstrate that intraoperative application of DEX is beneficial for postoperative pain treatment in patients undergoing ESD. This study will not only confirm that postoperative pain treatment is necessary for patients undergoing ESD but also provides an effective anesthesia method for postoperative analgesia. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ID: ChiCTR2100043837 , registered on March 4, 2021, http://www.chictr.org.cn .

Insomnia and Poor Sleep in CKD: A Systematic Review and Meta-analysis.

Rationale & Objective: Poor sleep quality and insomnia are pervasive among patients with advanced chronic kidney disease (CKD); however, these health issues have not been systematically evaluated. Study Design: Systematic review and meta-analysis. Setting & Study Populations: Adult patients with CKD not receiving kidney replacement therapy (KRT), as well as adults receiving KRT, including hemodialysis, peritoneal dialysis, and kidney transplantation. Selection Criteria for Studies: A systematic literature search using PubMed, Embase, and PsycNET, was conducted for articles published between January 1, 1990, and September 28, 2018. Data Extraction: Data on the prevalences of poor sleep quality and insomnia in patients with CKD, including those receiving and not receiving KRT, were extracted. Analytical Approach: Pooled prevalences were estimated using a random-effects meta-analysis and were stratified according to age, CKD stage, World Health Organization region, risk of bias, Pittsburgh Sleep Quality Index score, and the different criteria for insomnia that were used at diagnosis. Results: Of 3,708 articles, 93 were selected, and significant methodological heterogeneity was present. The pooled prevalences of poor sleep quality for CKD without KRT, hemodialysis, peritoneal dialysis, and kidney transplantation were 59% (95% CI, 44%-73%), 68% (95% CI, 64%-73%), 67% (95% CI, 44%-86%), and 46% (95% CI, 34%-59%), respectively. The corresponding prevalences of insomnia were 48% (95% CI, 30%-67%), 46% (95% CI, 39%-54%), 61% (95% CI, 41%-79%), and 26% (95% CI, 9%-49%), respectively. Insomnia was significantly more prevalent among patients aged 51-60 years and those aged >60 years than among those aged <50 years. The prevalence of insomnia in the European region was the lowest of all World Health Organization regions. Limitations: High interstudy heterogeneity. Conclusions: Approximately half of the patients with advanced CKD had poor sleep quality or insomnia, and the prevalence was even higher among those who received KRT. Kidney transplantation may reduce the burden of poor sleep quality and insomnia.

How do maternal emotion and sleep conditions affect infant sleep: a prospective cohort study.

BACKGROUND: Recent studies suggest that the incidence of infant sleep disorder is related to maternal emotional and sleep conditions, but how they influence each other is not fully understood. METHODS: A total of 513 pairs of parents and infants were enrolled in this prospective cohort study. Maternal emotional and sleep conditions were assessed using a self-rating depression scale, self-rating anxiety scale, and Pittsburgh Sleep Quality Index at the third trimester and within 3 months after delivery. Infant sleep was assessed by the Brief Screening Questionnaire for Infant Sleep Problems within 3 months after birth. Expression of the glucocorticoid receptor (GR), melatonin receptors (MR), exchange proteins directly activated by cAMP (EPAC) receptors, and dopamine receptor (DR) in the placenta was detected by immunohistochemistry. Methylation of the promoter regions for the GR (NR3C1 and NR3C2), MR (MTNR1A and MTNR1B), EPAC (RASGRF1 and RASGRF2), and DR (DRD1 and DRD2) genes was assessed by next generation sequencing-based bisulfite sequencing PCR. RESULTS: The incidence of sleep disorders in infants 0-3 months of age in this cohort was 40.5%. Risk factors for infant sleep disorder were low education level of the father, depression of father, maternal postpartum depression, postpartum anxiety, postpartum sleep disorder, and maternal sleep disorder extend from the third trimester to postpartum. There was no difference in expression of placental DR, GR, MR, and EPAC between mothers whose infants were with and without sleep disorders. Methylation of MTNR1B was higher and expression of MR was lower in the placenta of mothers with sleep disorder in the third trimester than in mothers without sleep disorder. Level of NR3C2 methylation was lower and GR expression was higher in the placenta of mothers with sleep disorder extend from the third trimester to postpartum than in mothers without sleep disorder. CONCLUSION: Maternal sleep disorders in the third trimester could lead to decreased MR expression by up-regulating MTNR1B methylation, and then resulting in elevated cortisol and increased GR expression by down-regulating NR3C2 methylation, which could increase the incidence of maternal postpartum sleep disorders, finally, the maternal postpartum sleep disorder could result in the high incidence of infant sleep disorder.

The effect of a multidisciplinary lifestyle modification program for obese and overweight children.

BACKGROUND/PURPOSE: The increasing prevalence of overweight and obese children and adolescents has been recognized as a public health threat worldwide. This study aimed to assess the effect of a stepwise lifestyle intervention in children and adolescents. METHODS: We developed a multidisciplinary clinic aimed at providing lifestyle interventions for obese children and adolescents. The program comprised three stages with stepwise goals: knowledge building (the first 4 weeks), habit consolidation (5-12 weeks), and self-monitoring (13-20 weeks). RESULTS: Of the 63 participants (age 11.6 ± 3.2 years) who entered the first stage of the program, 48, 22, and 15 completed the first, second and third stages (4, 12, and 20 weeks), respectively. In the first stage, significant improvement was noted in body weight, body mass index (BMI), BMI z-score, and waist circumference. Improvements in physical fitness performance were observed at 4 weeks in 3/5 items and at 12 weeks in 4/5 items. The decreases in body weight, BMI and BMI z-score were most prominent in the first two stages. In the third stage, participants maintained a stable body weight. In the 15 subjects who completed the whole program, BMI decreased from 29.3 ± 6.9 to 27.8 ± 6.1 (P = 0.001), and BMI z-score decreased from 3.06 ± 0.96 to 2.69 ± 0.91(P = 0.001). CONCLUSION: We developed a feasible multidisciplinary program based on knowledge education and individualized training. BMI and physical fitness scores can be used as early indicators of lifestyle change for obese children and adolescents.

Over 50,000 Metagenomically Assembled Draft Genomes for the Human Oral Microbiome Reveal New Taxa.

The oral cavity of each person is home to hundreds of bacterial species. While taxa for oral diseases have been studied using culture-based characterization as well as amplicon sequencing, metagenomic and genomic information remains scarce compared to the fecal microbiome. Here, using metagenomic shotgun data for 3346 oral metagenomic samples together with 808 published samples, we obtain 56,213 metagenome-assembled genomes (MAGs), and more than 64% of the 3589 species-level genome bins (SGBs) contain no publicly available genomes. The resulting genome collection is representative of samples around the world and contains many genomes from candidate phyla radiation (CPR) that lack monoculture. Also, it enables the discovery of new taxa such as a genus Candidatus Bgiplasma within the family Acholeplasmataceae. Large-scale metagenomic data from massive samples also allow the assembly of strains from important oral taxa such as Porphyromonas and Neisseria. The oral microbes encode genes that could potentially metabolize drugs. Apart from these findings, a strongly male-enriched Campylobacter species was identified. Oral samples would be more user-friendly collected than fecal samples and have the potential for disease diagnosis. Thus, these data lay down a genomic framework for future inquiries of the human oral microbiome.