Global Genome Diversity and Recombination in Mycoplasma pneumoniae.

Genomic changes in Mycoplasma pneumoniae caused by adaptation to environmental or ecologic pressures are poorly understood. We collected M. pneumoniae from children who had confirmed pneumonia in Taiwan during 2017-2020. We used whole-genome sequencing to compare these isolates with a worldwide collection of current and historical clinical strains for characterizing population structures. A phylogenetic tree for 284 strains showed that all sequenced strains consisted of 5 clades: T1-1 (sequence type [ST]1), T1-2 (mainly ST3), T1-3 (ST17), T2-1 (mainly ST2), and T2-2 (mainly ST14). We identified a putative recombination block containing 6 genes (MPN366‒371). Macrolide resistance involving 23S rRNA mutations was detected for each clade. Clonal expansion of macrolide resistance occurred mostly within subtype 1 strains, of which clade T1-2 showed the highest recombination rate and genome diversity. Functional characterization of recombined regions provided clarification of the biologic role of these recombination events in the evolution of M. pneumoniae.

Prevalence of sleep disorders in children with chronic kidney disease: a meta-analysis.

BACKGROUND: The reported prevalence of sleep disorders in children with chronic kidney disease (CKD) varies greatly. A quantitative meta-analysis to estimate the prevalence of sleep disorders among pediatric CKD patients may provide further information. OBJECTIVES: The objective of this study is to estimate the prevalence of sleep disorders in children with CKD. The study protocol was registered on PROSPERO (registration number CRD42021268378). DATA SOURCES: Two authors independently searched the PubMed, MEDLINE, EMBASE, and Cochrane review databases up to June 2021. STUDY ELIGIBILITY CRITERIA: Eligible studies include data of prevalence of sleep disorders in children with CKD. STUDY APPRAISAL AND SYNTHESIS METHODS: The prevalence of restless legs syndrome, sleep-disordered breathing, pediatric obstructive sleep apnea (i.e., apnea-hypopnea index > 1 event/h in polysomnography), excessive daytime sleepiness, and insomnia/insufficient sleep was estimated using a random-effects model. Subgroup analyses were conducted to compare the prevalence of sleep disorders between children on dialysis and not on dialysis. This meta-analysis included 12 studies with 595 children (mean age: 12.9 years; gender ratio: 55.6% boys; mean sample size: 49.6 patients). RESULTS: The prevalence of restless legs syndrome in children with CKD was 21% (95% confidence interval [CI], 14-30%). The prevalence of sleep-disordered breathing, pediatric obstructive sleep apnea, excessive daytime sleepiness, and insomnia/insufficient sleep was 22% (95% CI, 12-36%), 34% (95% CI, 19-53%), 27% (95% CI, 17-41%), and 14% (95% CI, 7-27%), respectively. Subgroup analysis revealed the pooled prevalence of excessive daytime sleepiness was significantly higher in children on dialysis than in children not on dialysis (43.3% vs. 11.2%; P = 0.018). Children on dialysis also had a high prevalence of other sleeping disorders, although the differences did not reach statistical significance. Children with CKD exhibited a 3.9-fold (95% CI, 1.37 to 10.93) increased risk of restless legs syndrome and a 9.6-fold (95% CI, 3.57 to 25.76) increased risk of excessive daytime sleepiness compared with controls. LIMITATIONS: The selected papers are of small sample size, lack of a control group, and exhibit substantial heterogeneity. CONCLUSIONS: Sleep disorders are common in children with CKD. Our results indicate that while the prevalence rates of various sleep disorders were higher in children on dialysis than in children not on dialysis, the prevalence of excessive daytime sleepiness was statistically significant in children on dialysis. A higher resolution version of the Graphical abstract is available as Supplementary information.

Toxic Effects of Indoxyl Sulfate on Osteoclastogenesis and Osteoblastogenesis.

Uremic toxins, such as indoxyl sulfate (IS) and kynurenine, accumulate in the blood in the event of kidney failure and contribute to further bone damage. To maintain the homeostasis of the skeletal system, bone remodeling is a persistent process of bone formation and bone resorption that depends on a dynamic balance of osteoblasts and osteoclasts. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates the toxic effects of uremic toxins. IS is an endogenous AhR ligand and is metabolized from tryptophan. In osteoclastogenesis, IS affects the expression of the osteoclast precursor nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) through AhR signaling. It is possible to increase osteoclast differentiation with short-term and low-dose IS exposure and to decrease differentiation with long-term and/or high-dose IS exposure. Coincidentally, during osteoblastogenesis, through the AhR signaling pathway, IS inhibits the phosphorylation of ERK, and p38 reduces the expression of the transcription factor 2 (Runx2), disturbing osteoblastogenesis. The AhR antagonist resveratrol has a protective effect on the IS/AhR pathway. Therefore, it is necessary to understand the multifaceted role of AhR in CKD, as knowledge of these transcription signals could provide a safe and effective method to prevent and treat CKD mineral bone disease.

Association of Constipation with risk of end-stage renal disease in patients with chronic kidney disease.

BACKGROUND: Chronic Kidney Disease (CKD) is a growing public health problem. Many risk factors were identified and interventions were applied accordingly, but the incidence of end-stage renal disease continued increasing. Some other risk factors may be ignored. Gut microbiota has been recognized as an important endogenous organ. The kidney-gut axis would contribute to gut dysbiosis, which might worsen CKD. Constipation, commonly seen in CKD, was one of the clinical presentation of gut dysbiosis. The clinical impact of constipation to CKD remains unknown. Our study aimed at assessing the risk of ESRD between CKD patients with and without constipation in a nationwide database. METHODS: We identified newly diagnosed cases of CKD without constipation history before in 2000-2011 from the Taiwan National Health Insurance database. Subjects who developed constipation later formed constipation group. The others without constipation matched by propensity score formed non-constipation group. The incidence rates and hazards of ESRD in patients with and without constipation by the end of 2013 were compared by using Cox proportional hazard models with a time-dependent variable. RESULTS: The incidences of ESRD per 1000 person-years were 22.9 for constipation group and 12.2 for non-constipation group, respectively. Cox proportional hazard models with a time-dependent variable revealed an adjusted hazard ratio of 1.90 (95% CI, 1.60-2.27). Compared to the CKD patients without constipation, adjusted hazard ratio for the CKD patients with laxatives < 33, 33-197 and ≥ 198 days per year were 0.45 (0.31-0.63), 1.85 (1.47-2.31) and 4.41 (3.61-5.39) respectively. CONCLUSION: In a population of newly-diagnosed CKD patients, we observed that subjects with de novo constipation, as compared with non-constipation, have increased risk of developing ESRD. More severe constipation would increase the risk further.

Interspecific competition between Solenopsis invicta and two native ant species, Pheidole fervens and Monomorium chinense.

This study was designed to understand the effects of the interspecific competition between red imported fire ant, Solenopsis invicta Buren and two native ant species, Pheidole fervens Smith and Monomorium chinense Santschi, by conducting colony interference and individual confrontation tests under laboratory conditions. The colony interference test showed that both native ant species, owing to their numerical advantage, killed the Solenopsis invicta virus-1 (SINV-1)-infected or healthy queens of S. invicta. Significantly less time was required for M. chinense to kill all SINV-1-infected S. invicta compared with the time required to kill the healthy S. invicta. Compared with healthy S. invicta, SINV-1-infected S. invicta spent a longer time eliminating the P. fervens colonies. In confrontation tests, M. chinense killed a significantly higher number of infected S. invicta minors than they did healthy minors, but the number of S. invicta majors (either infected or healthy) killed was substantially less. This study found that the viral infection weakened the competitive ability of S. invicta and made them prone to be eliminated by M. chinense but not by P. fervens.

Development and application of a chronic kidney disease-specific health literacy, knowledge and disease awareness assessment tool for patients with chronic kidney disease in Taiwan.

OBJECTIVES: This study aims to develop an assessment tool for health literacy and knowledge specific to chronic kidney disease (CKD) for use in examining the associations between health literacy, disease-specific knowledge and disease awareness among patients with CKD in Taiwan. DESIGN: An assessment tool in Mandarin and Taiwanese was developed based on patient input, panel discussions with experts and a literature review, and checked for validity and reliability in a pilot test. Formal data were collected through population-based sampling with a set quota according to region and hospital accreditation level. Cross-sectional data were collected to confirm the reliability and validity of the assessment tool. Levels of health literacy, disease knowledge, and disease awareness were then reported and analysed. SETTING: Sample hospitals included 10 medical centres, 18 regional hospitals and 15 local hospitals in Taiwan. Researchers were granted Internal Review Board approval and obtained agreement to collect data in all study settings. PARTICIPANTS: Patients at least 20 years old who had been diagnosed with CKD of any stage were eligible to participate. The formal assessment collected 1155 valid questionnaires, yielding an 87.3% response rate. The mean age of participants was 67.48 years (SD=12.87, range 22-98), while 484 (41.95%) were female and 78% were aware they had CKD. RESULTS: The self-devised instrument proved to have excellent reliability and validity. Use of the instrument in the main study showed that CKD-specific health literacy was significantly associated with age (ß=-0.33, p<0.00), educational attainment and disease awareness (ß=0.13, p<0.00). CKD-specific knowledge was also significantly associated with age (ß=-0.18, p<0.00), educational attainment and disease awareness (ß=0.19, p<0.00). CONCLUSIONS: This CKD-specific health literacy and knowledge assessment tool developed for Mandarin and Taiwanese-speaking patients is reliable and well validated. Patients with CKD who are aware of and understand their disease performed better in the assessment.

An Outbreak of tet(X6)-Carrying Tigecycline-Resistant Acinetobacter baumannii Isolates with a New Capsular Type at a Hospital in Taiwan.

Dissemination of multidrug-resistant, particularly tigecycline-resistant, Acinetobacter baumannii is of critical importance, as tigecycline is considered a last-line antibiotic. Acquisition of tet(X), a tigecycline-inactivating enzyme mostly found in strains of animal origin, imparts tigecycline resistance to A. baumannii. Herein, we investigated the presence of tet(X) variants among 228 tigecycline-non-susceptible A. baumannii isolates from patients at a Taiwanese hospital via polymerase chain reaction using a newly designed universal primer pair. Seven strains (3%) carrying tet(X)-like genes were subjected to whole genome sequencing, revealing high DNA identity. Phylogenetic analysis based on the PFGE profile clustered the seven strains in a clade, which were thus considered outbreak strains. These strains, which were found to co-harbor the chromosome-encoded tet(X6) and the plasmid-encoded blaOXA-72 genes, showed a distinct genotype with an uncommon sequence type (Oxford ST793/Pasteur ST723) and a new capsular type (KL129). In conclusion, we identified an outbreak clone co-carrying tet(X6) and blaOXA-72 among a group of clinical A. baumannii isolates in Taiwan. To the best of our knowledge, this is the first description of tet(X6) in humans and the first report of a tet(X)-like gene in Taiwan. These findings identify the risk for the spread of tet(X6)-carrying tigecycline- and carbapenem-resistant A. baumannii in human healthcare settings.

Continuity of care: evaluating a multidisciplinary care model for people with early CKD via a nationwide population-based longitudinal study.

OBJECTIVES: To control and prevent the burdens associated with chronic kidney disease (CKD), Taiwan's National Health Insurance Administration (NHIA) launched the 'early-CKD programme' in 2011 to extend care and education to patients with CKD. This study aims to evaluate the effectiveness of the early-CKD programme in terms of continuity of care (COC). DESIGN AND PARTICIPANTS: This study used secondary data from 2010 to 2014 provided by the NHIA to identify 86 581 participants each for the intervention and control groups. Patients with CKD who participated in the early-CKD programme between 2011 and 2013 were defined as the intervention group. For the control group, propensity score matching was used to select patients with CKD who did not participate in the programme, but were seen by the same group of physicians. INTERVENTION: A multidisciplinary care model for patients with early CKD launched in 2011. PRIMARY OUTCOME MEASURES: Outcome variables included the continuity of care index (COCI), which measures a physician's COC; number of essential examinations; and resource utilisation. To better identify the difference between groups, we separated COCI into two groups based on mean: high (above mean) and low (below mean). A generalised estimating equation model was used to examine the effects of the early-CKD programme. RESULTS: The programme significantly increased the number of essential examinations/tests administered to patients (ß=0.61, p<0.001) and improved COCI between physicians and patients (OR=4.18, p<0.001). Medical expenses (ß=1.03, p<0.001) and medication expenses (ß=0.23, p<0.001) significantly increased after the programme was implemented, but patients' kidney-related hospitalisations and emergency department visits decreased (ß=-0.13, p<0.001). CONCLUSION: From the COC viewpoint, the programme in Taiwan showed a positive effect on COCI, number of essential examinations and resource utilisation.

Seven-year follow-up of peritoneal dialysis patients in Taiwan.

BACKGROUND: There are no Taiwanese publications and only a few Asian publications on the long-term outcome of peritoneal dialysis (PD) patients. The aim of this study was to evaluate the outcome of PD patients in Taiwan during a 7-year follow-up period. PATIENTS AND METHODS: This study enrolled 67 patients (23 males, mean age 46.2 +/- 14.5 years) on maintenance PD. We administered the Short-Form questionnaire on 30 September 1998 and recorded major events and outcomes until 30 September 2005. We compared differences in initial parameters between groups categorized by PD patient survival and PD technique survival. Causes of mortality and transfer to hemodialysis were determined. PD patient and PD technique survival rates were measured and risk factors for patient mortality and PD technique failure were analyzed. RESULTS: Those in patient survival or PD technique survival groups had lower mean age (p < 0.001 and 0.018 respectively) and higher serum albumin level (p = 0.015 and 0.041 respectively) compared to those that died or failed PD. The 7-year patient survival rate was 77% and the PD technique survival rate was 58%. The independent predictors for PD technique failure included lower Mental Component Summary scores [hazard ratio (HR) = 0.85, p = 0.031] and diabetes mellitus (HR = 4.63, p < 0.001), whereas lower serum albumin level (HR = 0.22, p = 0.031), lower Physical Component Summary scores (HR = 0.67, p = 0.047), and presence of diabetes mellitus (HR = 5.123, p = 0.009) were the independent predictors for patient mortality. CONCLUSION: For our PD patients, both patient and technique survival rates are good. Better glycemic control, adequate nutrition, and enhancement of health-related quality of life are all of potential prognostic benefit.

Glycosylated hemoglobin and albumin-corrected fructosamine are good indicators for glycemic control in peritoneal dialysis patients.

PURPOSE: Diabetes mellitus (DM) is the most common cause of end-stage renal disease and is an important risk factor for morbidity and mortality after dialysis. However, glycemic control among such patients is difficult to assess. The present study examined glycemic control parameters and observed glucose variation after refilling different kinds of fresh dialysate in peritoneal dialysis (PD) patients. METHODS: A total of 25 DM PD patients were recruited, and continuous glucose monitoring system (CGMS) was applied to measure interstitial fluid (ISF) glucose levels at 5-min intervals for 3 days. Patients filled out diet and PD fluid exchange diaries. The records measured with CGMS were analyzed and correlated with other glycemic control parameters such as fructosamine, albumin-corrected fructosamine (AlbF), glycosylated hemoglobin (HbA1c), and glycated albumin levels. RESULTS: There were significant correlations between mean ISF glucose and fructosamine (r = 0.45, P<0.05), AlbF (r = 0.54, P<0.01), and HbA1c (r = 0.51, P<0.01). The ISF glucose levels in glucose-containing dialysate increased from approximately 7-8 mg/dL within 1 hour of exchange in contrast to icodextrin dialysate which kept ISF glucose levels unchanged. CONCLUSION: HbA1c and AlbF significantly correlated with the mean ISF glucose levels, indicating that they are reliable indices of glycemic control in DM PD patients. Icodextrin dialysate seems to have a favorable glycemic control effect when compared to the other glucose-containing dialysates.