Health-related quality of life (HRQoL) measures serve as important indicators of pain-related physical and psychosocial function in youth with juvenile fibromyalgia syndrome (JFMS). While the administration of parent-proxy reported HRQoL measures in the assessment of JFMS is common, its added clinical value to patient self-reports is unclear. We aimed to determine the level of agreement on HRQoL among patients with JFMS as well as their parent-proxies and to determine factors associated with this agreement.We performed a retrospective, cross-sectional cohort study of children aged 8 to 17 years diagnosed with JFMS and presenting for initial evaluation to a pediatric rheumatology pain clinic between April 2017 and May 2018. All patients and proxies were administered the Pediatric Quality of Life Short Form 15 Generic Core Scales (PedsQL SF-15) as part of routine clinical care. We calculated absolute discrepancy scores  to describe the extent of difference in HRQoL scores between parent-proxies and patients. We examined agreement between parent-proxy report and patient self-report via intraclass correlation coefficients (ICCs), stratified by age and sex, as well as Bland-Altman plots. We also used multivariate regression models to determine factors associated with level of agreement.p < 0.05).A total of 65 patient-proxy pairs were included in this study. ICCs demonstrated good to excellent agreement between all parent-proxy and patient measures of HRQoL irrespective of the patient’s age or sex. The level of agreement was not associated with pain duration or pain severity but less agreement on psychosocial HRQoL was associated with older patient age (β = 1.30; This study in youth with JFMS demonstrated good to excellent patient-proxy agreement across all domains of the PedsQL SF-15 irrespective of patient’s age or sex. Our findings suggest that parent-proxy reports do not provide additional information beyond that obtained from the patient self-report of HRQoL according to the PedsQL SF-15. In order to facilitate children and adolescents with JFMS becoming partners in their own healthcare, and to decrease the burden of multiple questionnaires, we propose focusing on patients’ own perceptions of HRQoL in the clinical setting. Health-related quality of life (HRQoL) is a multidimensional concept reflecting the impact of disease and treatment on a patient’s subjective assessment of his or her functioning and emotional wellbeing . PatientJFMS is one of the most common pediatric chronic musculoskeletal pain conditions, affecting approximately 1 in 20 children  and predFor patient-reported outcome measures (PROs), patient self-report and parent-proxy report provide important perspectives on pain and health outcomes. The Pediatric Quality of Life Inventory, Version 4.0 Generic Core Scales (PedsQL) Short Form 15 (PedsQL SF-15), has been used widely in both healthy and non-healthy populations to assess HRQoL in children and adolescents. It has demonstrated good construct validity, predictive validity, and responsiveness. A number of studies evaluating agreement between patient and parent-proxy ratings of HRQoL using the PedsQL have found positive correlations in samples of children with medical problems –31. TherWhile the administration of parent-proxy reported HRQoL measures in the assessment of JFMS is common, its added clinical value to patient-reported measures is unclear. Our study aimed to characterize agreement between parent-proxy reports and patient self-reports of HRQoL in a population of children and adolescents with JFMS by 1) evaluating discrepancy between parent-proxy reports and patient self-reports of HRQoL, 2) determining concordance between parent-proxy reports and patient self-reports of HRQoL and 3) examining this concordance stratified by patient age and sex. We also aimed to examine potential factors influencing patient-proxy agreement. We hypothesized that there would be good agreement between parent-proxy reports and patient self-reports of HRQoL and that patient age, duration of pain, and pain severity would be associated with this agreement.We performed a retrospective, cross-sectional cohort study of children aged 8 to 17 years who presented for an initial evaluation to a pediatric rheumatology pain clinic at a tertiary care hospital from April 2017 to May 2018, and one of their parents or legal guardians. All patients and proxies were administered the PedsQL SF-15 as part of routine clinical care. This was only available in English. Online questionnaires were administered separately to patients and their proxies at the time of the clinic visit. For the purposes of this study, we utilized data (including PedsQL SF-15 responses) from the time of the initial clinic visit only (no follow-up data were utilized). Families were approached for consent (and/or assent) to enroll in an existing institutional review board (IRB)-approved registry of patients with chronic musculoskeletal pain, with approximately < 1% of new patients declining inclusion in this registry. We included patients meeting the following criteria: 1) enrolled in the patient registry, 2) completed the PedsQL SF-15, 3) had a parent-proxy complete the PedsQL SF-15 and, 4) fulfilled the 2010 American College of Rheumatology (ACR) criteria for fibromyalgia syndrome . AdditioClinical and demographic information for this study were abstracted and analyzed from an existing prospective patient registry, or research database, for the pediatric rheumatology pain clinic. This prospective patient registry includes data from the initial clinic visit and all subsequent follow-up visits for patients seen in the specialty pain clinic. It is periodically updated and maintained to include variables of interest by multiple research assistants staffed within the clinic. Demographics and clinical characteristics documented for each initial visit include age, race, ethnicity, sex, past medical, psychological and surgical history, past medications, social information, and educational information. All clinic visits  include information regarding physical exam findings, current medications, pain severity and quality, and diagnosis and treatment recommendations. Additionally, all visits include measures that are part of routine clinical care including the patient- and parent-proxy reported Functional Disability Inventory (FDI) , 33 scorPatients and one of their parents reported the child’s HRQoL using the PedsQL SF-15, which is a tool consisting of 15 items that assesses patients on 4 domains: physical functioning, emotional functioning, social functioning, and school functioning . ChildreWe calculated Cronbach’s alpha coefficients to estimate the internal consistency of the items in the HRQoL and assumed a minimum standard of 0.70 as adequate. We calculated absolute discrepancy scores  to describe the extent of difference in HRQoL scores between parent-proxies and patients. A greater discrepancy between parent-proxy report and self-report was indicated by higher scores. We created histograms of the raw differences between patient and parent-proxy scores to demonstrate the magnitude and direction of discrepancies between parent-proxies and patients.P-values less than 0.05 were considered statistically significant. All statistical analyses were performed using statistical software, StataCorp 15 .We first examined the agreement between parent-proxy report and patient self-report of HRQoL using intraclass correlation (ICC) and the 95% confidence interval (CI), which were calculated based on a mean-rating, absolute-agreement, 2-way mixed-effects model. ICC cutoffs were interpreted as previously defined: ≤0.4, poor to fair agreement; 0.41 to 0.60, moderate agreement; 0.60 to 0.80, good agreement; and 0.81 to 1.00, excellent agreement , 38. We n = 71) met the 2010 ACR criteria for fibromyalgia syndrome. Notably, 3 subjects had pain for less than 3 months and 2 were diagnosed with complex regional pain syndrome. There were 6 subjects with missing information for the PedsQL SF-15 . Thus, we had 65 evaluable subjects.During the study interval, 215 patients were evaluated in the pediatric rheumatology pain clinic and consented to enrollment in the patient registry. Of these, 7 were missing both the WPI and SSS and 2 subjects were missing the SSS. Of the remaining 206 subjects, 35.4% (n = 57) and non-Hispanic Caucasians . The median age of patients at presentation was 15 years  and the median reported duration of pain prior to clinic evaluation was 24 months . Patients had moderate pain at presentation according to both the verbal pain score ]) and pain visual analog scale  ) . The funTable Table p < 0.05) was independently associated with less agreement between patient self-report and parent-proxy report. Pain duration and pain severity were not significantly associated with the level of agreement between patients and parent-proxies.Regression coefficients for the absolute difference in patient-proxy scores were similar in models adjusting for age, sex, pain duration and pain severity for all domains of HRQoL except for psychosocial HRQoL. In this regression model, older age (β = 1.30; This study, examining the level of agreement on HRQoL among patients with JFMS and their proxies, demonstrated good to excellent agreement across all domains of the PedsQL SF-15 irrespective of patient’s age or sex. Furthermore, pain severity and pain duration did not influence patient-proxy agreement. Older patient age, however, was associated with less agreement between patient self-report and parent-proxy report for psychosocial HRQoL. Our findings suggest that parent-proxy reports serve as valid substitutions for patient self-reports but do not provide additional information beyond that obtained from the patient self-report of HRQoL according to the PedsQL SF-15. In order to facilitate children and adolescents with JFMS becoming partners in their own healthcare, and to decrease the burden of multiple questionnaires, we propose focusing on patient’s own perceptions of HRQoL in the clinical setting.Our study findings are in line with previous studies assessing agreement between patient and parent-proxy reports of HRQoL using the PedsQL SF-15 , 40, 41.This study has limitations. Our sample was restricted to children and adolescents seen in a specialized pediatric rheumatology pain clinic at a tertiary care hospital and therefore may not be reflective of the general pediatric population of patients with JFMS. However, our findings are similar to those previously reported in another sample of youth with JFMS  and measThis study has significant strengths. First, we leveraged the existence of a large patient registry reflecting real world data in a clinical setting. Second, this study is strengthened by the use of multiple statistical methods to characterize and assess patient-proxy agreement on HRQoL according to the PedsQL SF-15. All of our methods demonstrated good patient-proxy agreement, highlighting the robust nature of our findings. By using statistical tests of agreement with absolute discrepancy scores, histograms, ICCs and Bland-Altman plots, our study provides a comprehensive evaluation of patient-proxy agreement on HRQoL , 42. We In summary, we found good patient-proxy agreement on HRQoL in a population of children and adolescents with JFMS at time of initial presentation to a pediatric rheumatology pain clinic. These findings were consistent irrespective of patient age or sex and were not dependent on duration of symptoms or pain severity, highlighting that patients are goodreporters of their HRQoL and youth with JFMS communicate well with their caregivers. We recommend, when possible, administering the PedsQL SF-15 to patients only to minimize the burden of questionnaires in the clinical setting. Future research should explore whether patient-proxy agreement on HRQoL changes with time over the patient’s clinical course and in response to treatment.


Spontaneous coronary artery dissection (SCD) remains a rare and important cause of coronary artery disease (CAD). The purpose of this study was to describe the clinical and angiographic features in SCD and to evaluate the treatment and long-term prognosis of this condition in China.This retrospective cohort study included 118 Chinese patients with SCD confirmed by coronary angiography. Clinical and angiographic features, treatment modalities and outcomes of SCD were estimated.The overall prevalence of SCD was 0.15%. Age was 57 ± 10 years; 86% patients were men; 75% presented with acute coronary syndrome (ACS); 72% had concomitant atherosclerotic CAD. SCD often affected right coronary artery (RCA) and caused a short dissection (< 20mm). A conservative therapy was used in 28% of patients and revascularization in 72% . Only one patient died during hospitalization due to multiple organ failure after CABG. During a median follow-up of 43 months , 32 patients had a new-onset ACS, 9 received revascularization (7 PCI and 2 CABG), and 8 died. The Kaplan-Meier estimated 12-year rates of freedom from cardiac death and ACS were both higher in revascularization versus conservative therapy . No significant difference was found in freedom from revascularization between the two therapies.In China, SCD was usually associated with atherosclerosis and predominantly affected male population. SCD often affected RCA and caused a short dissection. In-hospital mortality rate was low regardless of therapeutic strategy. However, a significantly better long-term prognosis was observed in the revascularization compared with conservative therapy. Spontaneous coronary artery dissection (SCD), a separation of the arterial wall with the creation of a false lumen that is not related to medical instrumentation or trauma, remains an infrequent cause of acute coronary syndrome (ACS).Through January 2003 to December 2015, a total of 76,359 primary coronary angiographies were performed in our center. Of which, 531 potential patients were yielded by searching relevant key words in hospital database, including dissection, filling defect, intimal tear or intimal flap. The definition of SCD in this study was the presence of a longitudinal radiolucent linear image in at least two orthogonal projections proven on coronary angiography and confirmed by two experienced interventional cardiologists. Iatrogenic and traumatic SCD and previous coronary intervention were excluded. Finally, the diagnosis of SCD was identified in 118 patients. This retrospective cohort study was approved by the Ethics Committee of Wuhan Asia Heart Hospital and the need for individual patient consent was waived.Baseline risk factors, clinical presentation, treatment modality and in-hospital events were collected via medical records. Long-term outcomes were gained via clinical visits, telephone follow-up, or medical record review in the case of readmission. For deceased patients, information was obtained by telephone from the immediate family or contact with local police. The primary long-term end points included cardiac death, ACS  and revascularization.The National, Heart, Lung, and Blood Institute (NHLBI) classification and the Thrombolysis in Myocardial Infarction (TIMI) flow grade classification were used to characterize the SCD lesions.Successful percutaneous coronary intervention (PCI) was defined as TIMI flow grade = 3 after balloon angioplasty or stent implantation. Unsuccessful PCI was defined as TIMI flow grade < 3 or extension of dissection after PCI. Revascularization included PCI and coronary artery bypass grafting (CABG).Categorical data were presented as frequency and percentage and continuous data as mean ± SD. The chi-square or Fisher exact tests were performed for categorical data. The Kaplan-Meier curves were plotted by time-to-event data and compared by the log-rank tests. All analyses were performed with SPSS software. A two-side value of P < 0.05 was considered statistically significant.The overall prevalence of SCD in the present study was 0.15% (118 per 76359 subjects). The baseline of patients with SCD is described in The main coronary angiographic characteristics are reported in Most patients with SCD  underwent PCI or CABG during hospitalization . Five paClinical follow-up  was obtained in all 117 discharged patients. Overall, 32 (27.4%) of discharged patients had a new-onset ACS , 9 (7.7%) received revascularization (7 PCI and two CABG), and 8 (6.8%) had died at 12 years. Detail follow-up events and interventions based on therapeutic strategy are also showed in Repeated coronary angiography was performed in 12 of 32 patients with a new-onset ACS during follow-up. In four patients initially receiving conservative treatment, their six dissected vessels (2 single- and two double-vessel dissections) demonstrated persistent dissection. Two of them were treated with PCI. One PCI was successful and the other was unsuccessful due to balloon failing to cross the SCD lesion. Of 8 patients initially being treated with PCI treatment, seven had in-stent restenosis  and one had stent thrombosis at SCD lesion at follow-up. Five of 8 patients received re-PCI (four for dissection lesions and one for both dissection and atherosclerotic lesion) and all five PCIs were successful. Overall, Most of PCI procedures  had excellent results, without need for repeat revascularization. There was no follow-up coronary angiography in patients with CABG.Long-term outcomes of SCD patients are presented in To the best of our knowledge, this respectively cohort study reports the largest series of SCD patients and provides the longest clinical follow-up in China. In this study, we found that SCD was often associated with atherosclerosis and presented with an ACS, with a high prevalence of conventional cardiovascular risk factors. Moreover, SCD often affected RCA and proximal vessel segment and caused a short dissection. The technical success rate of revascularization was satisfactory. In-hospital mortality was low regardless of treatment strategy. During follow-up, a significantly better long-term outcome was observed in the revascularization versus conservative therapy.Previous series have reported the SCD detection in 0.07% to 1.1% of all coronary angiograms performed.There is a wide spectrum of clinical presentations of SCD due to a variety of extent and the flow limiting severity of dissection and the main presentation is ACS.Medical treatment of SCD in this study is similar to the treatment of ACS, including antiplatelet, anticoagulant and anti-ischemic therapy. Yet, the role of thrombolytic is debated. Previous NA-SCD studies suggested that thrombolytic drugs be avoided as their use has been reported to worse the clinical condition, presumably due to a further extension of dissection.Several series have reported poor technical success with PCI for NA-SCD. The PCI failure rate was reported 53% in the Mayo Clinic series and 36% in the Vancouver series.16In our study, SCD patients with LAD and/or triple-vessel lesions (including dissected and atherosclerotic lesions) tend to be treated with CABG. Follow-up results have showed that CABG as a treatment strategy for SCD is associated with excellent long-term outcomes. However, because of sample size limitation and possible selection bias, definite conclusions on effectiveness of CABG in this clinical setting cannot be drawn. Moreover, no CABG patient in the study receives repeated coronary angiography during follow-up, so the incidence of late bypasses graft occlusion is unclear.Many series of NA-SCD have a similar long-term prognosis between the revascularization and conservative therapy and a “watchful waiting” strategy is thus recommended for NA-SCD, unless with ongoing or recurrent ischemia.There are several limitations in the study. First, as most SCD patients had atherosclerosis, the results cannot be extended to NA-SCD patients. Second, as IVUS and OCT are not routine tests for ACS in our center, non-classic SCD  are inevitably missed. Third, this is a non-randomized retrospective research. Thus, selection bias and uncontrolled confounding limit the ability to assess SCD long-term outcome between different treatments.In China, SCD predominantly affects male population and has a relatively high prevalence of vascular risk factors and atherosclerosis. SCD often affects RCA and causes a short dissection. In-hospital mortality rate is low. The long-term prognosis of patients with SCD seems to be favorable in the revascularization versus conservative therapy.


Our population genetic results from five different reference datasets indicated that Shanxi Han shares a closer phylogenetic relationship with northern-neighbors and southern ethnically close groups than with Uyghur and Tibetan. Genome-wide variations revealed that modern northern-Han derived their ancestry from Yakut-related population (25.2%) and She-related population (74.8%). Summarily, the genetic mixing that led to the emergence of a Han Chinese ethnicity occurred at a very early period, probably in Neolithic times, and this mixing involved an ancient Tibeto-Burman population and a local pre-Sinitic population, which may have been linguistically Altaic.Modern East Asians derived from the admixture of aborigines and incoming farmers expanding from Yellow and Yangtze River Basins. Distinct genetic differentiation and subsequent admixture between Northeast Asians and Southeast Asians subsequently evidenced by the mitochondrial DNA, Y-chromosomal variations, and autosomal SNPs. Recently, population geneticists have paid more attention to the genetic polymorphisms and background of southern-Han Chinese and southern native populations. The genetic legacy of northern-Han remains uncharacterized. Thus, we performed this comprehensive population genetic analyses of modern and ancient genetic variations aiming to yield new insight into the formation of modern Han, and the genetic ancestry and phylogenetic relationship of the northern-Han Chinese population. We first genotyped 25 forensic associated markers in 3,089 northern-Han Chinese individuals using the new-generation of the Huaxia Platinum System. And then we performed the first meta-analysis focused on the genetic affinity between Asian Neolithic∼Iron Age ancients and modern northern-Han Chinese by combining mitochondrial variations in 417 ancient individuals from 13 different archeological sites and 812 modern individuals, as well as Y-chromosomal variations in 114 ancient individuals from 12 Neolithic∼Iron Age sites and 2,810 modern subjects. We finally genotyped 643,897 genome-wide nucleotide polymorphisms (SNPs) in 20 Shanxi Han individuals and combined with 1,927 modern humans and 40 Eurasian ancient genomes to explore the genetic structure and admixture of northern-Han Chinese. We addressed genetic legacy, population structure and phylogenetic relationship of northern-Han Chinese  Han Chinese, with a total population size circa 1.4 billion, is the world’s largest ethnic group and dominant ethnicity in China and Singapore. The origin of the Han Chinese population, genetic relationship with adjacent groups and past migratory pattern and admixture history have gained considerable attention from scientists working in the anthropology, linguistics, history, population and forensic genetics . ArchaeoPhysical anthropological investigation of somatometric and nonmetric features revealed that a significant difference exists between northern-Han Chinese and southern-Han Chinese . SubsequSTR, also called as microsatellite, is one of the extraordinary mutated genetic markers, is widely existed human autosomal, X-chromosome and Y-chromosome genomes . This levia high-density genetic markers are unclear. Thus, we genotyped and analyzed 23 autosomal STRs in 3,089 unrelated Han Chinese individuals and 643,897 SNPs in 20 Hans residing in Shanxi Province. Shanxi Province is between 34°34′-40°44′ north latitude and 110°14′-114°33′ east longitude, which stretches about a total area of 156,700 km2 from the Yellow River in the west and south to the Taihang Mountain in the east and the Great Wall in the north. This area is bounded by the Shaanxi, Inner Mongolia, Hebei, Henan, and other Provinces. Archaeological, anthropological and genetic evidence from Hengbei site consistently considered that Han Chinese is originated from Shanxi and neighboring regions, also called the Central Plain  from Yuncheng country in the Shanxi Province, northern China. A total of 20 EDTA anti-coagulated peripheral blood samples were collected for whole-genome SNPs genotyping. All self-declared Han Chinese indigenous subjects are needed to be no intermarriage with people of other ethnic groups and resided in here at least three generations. Human genomic DNA from male samples was extracted using the DNeasy blood and tissue kit (Qiagen) and measured utilizing the NanoDrop-2000  following the manufacturer’s instruction, and DNA from female samples was isolated using the Chelex-100 method. All our data used throughout this study are submitted in the 2O as negative in each batch of PCR amplification and electrophoresis. Infinium Global Screening Array BeadChip of Illumina WeGene V2 Arrays  covering approximately 700k SNPs was used to genotype autosomal SNPs based on the manufacturers’ introduction.We employed Huaxia Platinum Amplification System for multiallelic STR genotyping including 23-autosomal-STRs, two sex-linked inherited Y-InDel (rs2032678) and Amelogenin in a ProFlex PCR System (Thermo Fisher Scientific) in accordance with the manufacturer’s recommendation. A 10 μL reaction volume, which contains 4μL of primer set (the concentration of each locus is different), 4μL of master mix, 0.4 ng of template DNA as well as Prep-N-Go buffer was employed with the standard thermal cycling conditions which comprise an initial step at 95°C for 1 min; followed by 27 cycles of denaturation at 94°C for 3 s, anneal at 59°C for 16 s, and extension at 65°C for 29 s; and following a final extension at 60°C for 5 min and preservation at 10 °C. Applied Biosystems 3500 Genetic Analyzer (Thermo Fisher Scientific) was utilized to separate and detect the PCR products using the 36 cm capillary array and POP-4 polymer following the corresponding instruction. A 9.5 μL of deionized Hi-Di formamide and a 0.5 of μL GeneScan 600 LIZ Size Standard v2.0 (Thermo Fisher Scientific) were utilized to mix with the amplified products or allelic ladder before the capillary electrophoresis. Finally, we used the GeneMapper ID-X v.1.4 software to identify and analyze the corresponding allele. We employed the typical control DNA of 9947A human cell line sample (Thermo Fisher Scientific) as positive, and the ddHTo comprehensively dissect the genetic background of Shanxi northern-Han Chinese, we first integrated our raw genotyping data (23 STRs) with previously published genotype data from 11 Chinese populations from five Chinese ethnic groups  . To furtSTR Analysis for Forensics (STRAF) online software  was util3, outgroup-f3 , D admixture-f, qpWave and qpAdm to explore the population history of northern Han under the genetic variations of modern and ancient population using the ADMIXTOOLS . We employed 10-fold cross-validation with the predefined ancestry populations varying from 2 to 19. We conducted the MIXTOOLS . We finaMIXTOOLS .The 23 autosomal-STRs included in the Huaxia Platinum System were amplified from 3,089 northern-Han Chinese individuals residing in the Shanxi Province, which is considered as the origin place of the Han ethnic group . Pairwise Fst genetic distances between Shanxi Han and other eleven Chinese populations were listed in via the first three PCA components. The patterns of the genetic affinity of East Asian populations were in accordance with the linguistic classification. Southern-Han Chinese populations were well-positioned at the end of the tree and then clustered with Central-Han Chinese population, followed by clustering with northern-Han Chinese populations (Shanxi Han), finally followed by Japanese, Korean and other language family or continental populations  and other geographically adjacent populations  and then combined with modern data from 2,810 individuals. A total of 80.6% variance extracted from 38 populations showed population substructure existed among the modern Han Chinese population. And Hengbei, Jinggouzi, Dashanqian, Mogou, Taojiazhai, and Sanguan ancient populations showed a paternally close relationship with the modern Han Chinese populations f showed that the greater genetic affinity identified between Shanxi Han and Han Chinese populations, subsequently followed by the southern Tai-Kadai and Hmong-Mien speakers, and Western Trans-Himalayan and northern Altaic speakers , where X represents the worldwide populations and Y denotes the Chinese populations from different language families, to explore the status of allele sharing. Our results provided supporting evidence for more shared genetic drift between Shanxi Han and northern-Han or neighboring minorities  to find the potentially admixed ancestral populations. Two hundred sixty-four out of 2,016 pairs were observed with significant negative values  and East-Siberian-related population , like the two ancestry populations observed in Indian   .3f = −0.0018 and Z = −6.662) was observed in the form of f3, we then conducted the qpWave and qpAdm using the She and Yakut as source populations and using Yoruba, San, Papuan and Melanesian as outgroup populations. QpWave results (p = 0.052 for rank1) indicated that Shanxi Han was derived from two ancestral populations. The qpAdm analysis further suggested that Shanxi Han has derived 25.2% Yakut-related ancestry and 74.8% She-related ancestry.To further validate the minimum streams of ancestry populations and evaluate the corresponding admixture proportion, we first performed the TreeMix analyses among 65 worldwide populations  (qpWave to find that the minimum ancient ancestry streams modern northern-Han were 2 (rank1: p = 0.118). QpAdm further showed that DevilsGate Hunter-Gatherer-related population contributed 45% ancestry and Oakaie-related ancient population contributed 55% ancestry to modern northern-Han Chinese.Nineteen ancient populations from Eurasian were employed to explore the genetic admixture history between Shanxi Han. The shared genetic history of all pairs was presented in East Asia is occupied by anatomically modern human 50 kya when they migrated out of Africa. These regions are populated by the hunter–gatherer over 40 kya in the Paleolithic time . Under tA recent large-scale whole-genome variation study covering 11,670 Han Chinese individuals from 24 out of 33 administrative regions was carried out to explore the Han Chinese population genetic structure and genetic ancestry . Their vThe processes of ancient whole-genome DNA studies with the technological innovations of DNA hybridization enrichment and next-generation sequencing has revolutionized the phylogenetic relationship and population history reconstruction in the European, American, Oceanian and even southeast Asians . In EastOur present meta-analysis results from the Neolithic ancient people and modern Han Chinese on the basis of the combined genetic variations of mtDNA and Y-chromosome first showed that the ancient populations from West Liao River Valley sites (Dasanqian and Niuheliang) and Yellow River Valley sites  share considerable similar mitochondrial haplogroup with the modern northern-Han Chinese populations. For Y-chromosome variations, ancient people from the Hengbei site shared the more significant genetic similarity with modern northern-Han Chinese from Shanxi and Heilongjiang provinces, and Dashanqian and Mogou ancient people bear a similar genetic assemblage with modern Taiwan Han people. Mogou site in the Ganqing region adjacent to the central plain is the hometown of Di-Qiang people who are thought as the direct ancestral population of Han Chinese, which is genetically close to the Han Chinese population. Our results reveal a close genetic relationship among Hengbei, Mogou and modern northern-Han Chinese populations. Our findings combined with the archeological, historical and linguistic evidence consistently supported the admixed genetic origin of modern Han Chinese.via ancient DNA. Summarily, consistent with previous linguistic and archaeological evidence, the genetic mixing that led to the emergence of a Han Chinese ethnicity occurred at a very early period, probably in Neolithic times, and this mixing involved an ancient Tibeto-Burman population and a local pre-Sinitic population, which may have been linguistically Altaic. Fine-scale population history reconstruction of north Han from modern and ancient genomes consistently model their ancestral populations deriving from ancestral North East Asian and ancestral South East Asian.In summary, we genotyped 23-autosomal-STRs in 3,089 Shanxi northern-Han Chinese individuals and provided the first batch of allele frequency, forensic and population genetic parameters of northern Han Chinese. Comprehensive worldwide and nationwide population comparisons not only showed that Shanxi harbored a strong similar genetic assemblage with adjacent Han populations but also illustrated that there were apparent genetic distinctions between north-to-south Han Chinese as well as genetic differentiation between populations belonging to different language families, obviously differences observed between Tibetan, Uyghur, and others here. The first meta-analysis based on the mitochondrial and Y-chromosomal genetic variations among ancient and modern Asian populations showed a genetic affinity and genetic continuity between Mogou, Hengbei ancient population and present-day northern-Han Chinese. We also found Neolithic agriculture expansion related Dashanqian and Niuheliang ancient populations are genetically close to modern northern Han. The qpWave/qpAdm modeling further revealed that modern northern Han Chinese carried 74.8% She-related ancestry and 25.2% Yakut-related ancestry. Both Hengbei-associated and Tibetan-related uniparental lineage (D haplogroup) were observed in modern Northern Han Chinese. Besides, approximately 45% DevilsGate-like ancestry, one Tungusic-affiliated Neolithic population, was modeled This study was approved by the Ethics Committee of Zunyi Medical University and corresponding experiments have followed the recommendations of the World Medical Association Declaration of Helsinki. Informed consent was obtained before the sample collection from the participants.GH, PC, and FJ conceived the idea for the study. GH, PC, and FJ performed or supervised wet laboratory work. PC, JW, LL, HG, XZ, HL, LY, GH, MW, YH, GC, and YL analyzed the data. GH wrote and edited the manuscript.This work was supported by grants from the PhD Scientific Research Start-up Fund of Affiliated Hospital of Zunyi Medical University (No. 201501) and the National Natural Science Foundation of China (No. 81401562).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Higher hs-CRP was associated with poorer results in the 6MWT  and a lower HAP score . There were no other significant associations found. We conclude that inflammation may be a more important pathway to physical impediment than uremic toxemia. This suggests that there is a large physical rehabilitation potential in non-inflamed uremic patients.Association of higher serum levels of uremic toxins and inflammatory markers with poorer physical performance is understudied. We measured the six-minute walk test (6MWT), 10 repetition sit-to-stand test (STS-10), handgrip strength (HGS), and Human Activity Profile (HAP) questionnaire score in 90 prevalent hemodialysis patents, with low comorbidity to reduce the potential confounding of concomitant disease. Midweek pre-dialysis serum levels of asymmetric dimethyl-arginine (ADMA), β2-microglobulin (B2M), high-sensitivity C-reactive protein (hs-CRP), indoxyl sulfate (IS), insulin-like growth factor 1 (IGF-1), interleukin 6 (IL-6), myostatin, and urea were analyzed as predictor parameters of physical performance measures in adjusted models. Serum levels of most measured toxins were not significantly related to performance, except for ADMA, which was significantly related to poorer performance in the STS-10 test (B = 0.11 ± 0.03 s,  Poor physical performance and frailty predict a high risk of mortality, cardiovascular events, and hospitalizations in dialysis patients ,2. MotorUremia is defined by a state of elevated serum concentrations of various uremic toxins . Uremic In this work, we set out to analyze the association of serum uremic toxin levels with reduced physical performance of dialysis patients. We hypothesized that patients with higher concentrations of uremic toxins might suffer a greater loss of motor abilities. As patients with CKD have many comorbid diseases that may interfere with motor abilities, our study aimed to identify associations of five representative uremic toxins with physical performance measures in a sample of low-comorbid dialysis patients. We also analyzed two serum markers of inflammation—interleukin 6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP)—to account for the effect of inflammation, which is an important part of uremic milieu muscle catabolism . AdditioNinety prevalent hemodialysis patients fulfilled the inclusion criteria. They were all treated with high-flux dialyzers without reuse, and 52% of them were treated with on-line hemodiafiltration. The baseline demographic characteristics are shown in the The analysis of predictive parameters of the six-minute walk test (6MWT) test included age, sex, patient body height, fat tissue index, and serum levels of the selected uremic toxins. Certain anthropometric factors adjusted here—age, height, and fat tissue index (FTI)—were previously shown to be predictive for the results of the 6MWT . The estWe have previously shown that age, body height, and lean tissue index (LTI) predict 10-repetition sit-to-stand (STS-10) test performance . TherefoIt was previously shown that sex, age, body height, and wrist width are non-modifiable predictors of hand grip strength (HGS), whereas LTI and FTI are potentially modifiable predictors . Table 4Habitual daily physical activity, estimated with the HAP adjusted activity score (AAS) is known to be associated with age and LTI , so the Finally, in In this work, we examined the hypothesis that higher serum levels of uremic toxins predict worse physical performance in end-stage renal disease patients. We were able to recruit low-comorbid group of 90 prevalent hemodialysis patients, and assess four different measures of physical performance. We selected representative uremic toxins from three classes according to molecular weights and protein binding properties ,12. PrevADMA is a recognized toxin with a role in cardiovascular and renal disease, but exact mechanisms for its toxicity are unknown. It is an endogenous inhibitor of nitric oxide (NO) synthesis , and incChronic low-level inflammation is associated with poor cardiovascular outcomes ,19 and cOur study has some limitations. Since this was an observational study, we are unable to prove any causal relationship. We performed a number of statistical models, and therefore introduced the possibility for a raised alpha error. Also, if the number of participants was larger, we could perhaps confirm as significant more subtle associations; however, the number of participants was comparable to previous studies of motor performance in the dialysis population . There iIn conclusion, our analysis of selected uremic toxins in low-comorbidity hemodialysis patients revealed no consistent associations with physical performance in four major motor ability tests. We could only find a significant association of higher ADMA levels with poorer lower extremity function during the STS-10 test. More consistent was a predictive role of inflammation, expressed as elevated hs-CRP levels, for a loss of 6MWT distance and habitual activity in everyday life. This finding suggests that regular physical training and activity may have a large rehabilitation potential, possibly to the level of healthy controls in non-inflamed, low-comorbid, end-stage renal disease patients.This was a cross-sectional study recruiting a sample of prevalent hemodialysis patients from 10 outpatient dialysis units in Slovenia. Measurements were done in the period from July to December 2014. Main outcome measures were the results of key functional performance tests covering the motor abilities of the upper extremities (HGS), the lower extremities (STS-10), submaximal aerobic performance (6MWT), and the result of the Human Activity Profile questionnaire (HAP) to assess the level of physical abilities and activities in the home environment. Subjects were invited to participate if older than 18 years, able to walk with or without additional support, and if they voluntarily signed the informed consent for participation. Exclusion criteria contained acute disease in the last four weeks before the start of the study, active malignant disease or chronic infection, consequences of cerebrovascular accident, heart failure of New York Heart Association (NYHA) stage 3–4, symptomatic angina pectoris (Canadian Cardiovascular Society) stage 2–4, chronic obstructive pulmonary disease stage 3–4, decompensated liver cirrhosis, symptomatic peripheral arterial obstructive disease, painful degenerative or inflammatory arthropathy with current use of analgesic therapy, and symptomatic psychiatric disease. The study was approved by the Slovenian Medical Ethics Committee (document No. 125/05/14). Investigations were carried out following the rules of the Declaration of Helsinki of 1975, revised in 2008. All participants gave informed consent to inclusion in the study.2) to give the LTI and FTI. Then, physical performance tests were done. Additional medical information on comorbidities and most recent routine blood test laboratory values were obtained from dialysis centers and attending physicians. Concentrations of uremic toxins were measured from the serum midweek pre-dialysis samples taken at participating dialysis centers, and transported immediately to the central laboratory within the two-hour period in the week immediately subsequent to physical performance measurements.The exact description of the research protocol and measurements was given previously ,11,32. IThe 6MWT was performed on a 30 m track according to the guidelines , with thWe measured serum levels of urea, asymmetric-dimethylarginine (ADMA), β2-microglobulin (B2M), indoxyl sulfate (IS), myostatin, interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and insulin-like growth factor 1 (IGF-1). We used reagent kits based on ELISA or chemiluminescent technology, and routine laboratory methods for the measurement serum levels of hs-CRP. All procedures followed the instructions from manufacturers. With values above the linearity range, we diluted samples following instructions in the manufacturer kit. For the values below the detection limit, we expressed the results as a lower limit of detection divided by the square root of two. We present details for these methods in Urea is a prototype of small (60 Da) water-soluble uremic toxins, giving the name to the uremic syndrome. Because of a complex metabolism, it is not a reliable marker of kidney function loss. However, an indirect toxicity has been established, and some evidence supports direct toxicity of urea .ADMA is a small water-soluble molecule (202 Da), similar to urea. It belongs to a group of guanidines, known neurotoxins that have a significantly larger distribution volume than urea. This may result in decreased removal with conventional dialysis techniques. In-vitro studies show that guanidines have a pro-inflammatory effect at uremic concentrations. ADMA is an inhibitor of nitric oxide synthase, with a direct effect on cellular dysfunction . It was B2M is a middle-weight protein (11.8 kDa), included here as it is often used as a marker of other retention solutes of the same size class. It is implicated in the genesis of uremic amyloid disease  in chronIS is a protein-bound molecule (213 Da), and as such, it is representative of a group of relatively small protein-bound uremic toxins that are not easily removed with low- or high-flux dialysis membranes. It is suspected that IS conveys its in-vitro and in-vivo effect via a pro-oxidant mechanism, one of them being induction of ROS in endothelial cells . It has Myostatin is a member of the transforming growth factors beta superfamily, and is negatively associated with muscle growth and development. Its molecular mass is 25 kDa, and high-flux dialyzer membranes may partially remove it. Serum levels are increased in uremic patients and in patients with heart failure ,50. MyosIL-6 is a middle molecular weight protein of 24.5 kDa . It is pIGF-1 is a middle-weight protein 7.7 kDa). Its impairment by inflammatory factors is involved in muscle proteolysis , but the.7 kDa. IBaseline patient characteristics were calculated as means and their standard deviations for continuous variables, and frequencies for categorical variables. We performed a series of general linear models, with individual physical performance measures as dependent and uremic toxin levels as predictor variables. In each model, besides standard parameters, partial eta squared was calculated, which gives the proportion of variance in the dependent variable explained by each independent predictor variable. For each uremic toxin, a separate model—including selected demographic and non-modifiable anthropometric variables (such as height)—was calculated. We only adjusted for those case-mix and non-modifiable anthropometric variables that we previously showed to be significantly associated with physical performance test results analyzed here (1st model) ,4,11. ThWe performed adjusted analyses by entering all independent variables of interest simultaneously. No stepwise methods were executed. Probability levels of <0.05 were considered statistically significant. Analyses were conducted using the IBM SPSS statistics  and SAS Studio .


Escherichia coli and/or Klebsiella pneumoniae were the most common antibiotic-resistant bacteria recovered from all types of samples, followed by carbapenem-resistant E. coli and/or K. pneumoniae. Colistin-resistant Enterobacteriaceae, carbapenem-resistant Psuedomonas aeruginosa, carbapenem-resistant Acinetobacter baumannii, colistin-resistant Enterobacteriaceae, vancomycin-resistant Enterococci, and methicillin-resistant S. aureus were less common. These findings suggest extensive contamination by antibiotic-resistant bacteria in hospital and community environment in Thailand.This study determined the presence of important antibiotic-resistant bacteria in selected environments in Thailand, including wastewater samples from 60 hospitals; washed fluid, leachate, flies, cockroaches, and rats collected from five open markets; washed fluid from garbage trucks; and stabilized leachate from a landfill facility. At least one type of antibiotic-resistant bacteria was isolated from all samples of influent fluid before treatment in hospitals, from wastewater treatment tank content in hospitals, and from 15% of effluent fluid samples after treatment with chlorine prior to draining it into a public water source. Antibiotic-resistant bacteria were recovered from 80% of washed market fluid samples, 60% of market leachate samples, all fly samples, 80% of cockroach samples, and all samples of intestinal content of rats collected from the open markets. Antibiotic-resistant bacteria were recovered from all samples from the landfill. Extended-spectrum beta-lactamase (ESBL)-producing  Antimicrobial resistance (AMR) has enormous adverse impact on humans in terms of morbidity, mortality, and economic loss . The heaAcinetobacter baumannii, carbapenem-resistant Pseudomonas aeruginosa, colistin-resistant Enterobacteriaceae, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococci were common or important antibiotic-resistant bacteria in Thailand [The Thailand Antimicrobial Resistance Containment and Prevention Program was implemented as a One Health approach in 2012 . One of Thailand ,11,12,13Thailand , in flieThailand ,16, and Thailand  in ThailThe environment has been increasingly recognized for the role it might play in the global spread of clinically relevant antibiotic resistance . One of Accordingly, the aim of this study was to determine the magnitude of antibiotic-resistant bacteria contamination in selected environments in Thailand, including wastewater samples from hospitals; from washed fluid, leachate, flies, cockroaches, and rats collected from open markets, from washed fluid from a garbage truck that collected garbage from the five open markets; and, from stabilized leachate from a landfill facility.Sixty public hospitals were selected from a total of 959 public hospitals in Thailand by stratified random sampling to cover all geographical regions of Thailand, all sizes of hospitals, and the various types of hospital wastewater management systems. The study hospitals included 30 community hospitals, 20 general hospitals, and 10 regional hospitals. The wastewater management systems of the study hospitals included oxidation ditch , conventional activated sludge , sequential batch reactor , aerated lagoon , submerged aeration fixed film , construction wetland , stabilization pond , and anaerobic filter-submerged fixed-film aeration tank . A total of 186 samples collected from the wastewater management system of each hospital included 5 liters of influent fluid before treatment (60 samples), 5 liters of content in wastewater treatment tank (66 samples), and 5 liters of effluent fluid after treatment with chlorine prior to draining it into a public water source (60 samples). All samples were collected in sterile closed containers and kept at 4 °C until they were sent to a microbiological laboratory within 24 h after collection.Five open fresh markets in Nonthaburi Province, which is located near Bangkok, were selected.The samples collected from each market included 5 liters of washed market fluid (5 samples) and 5 liters of market leachate (5 samples). All samples were collected in sterile closed containers and kept at 4 °C until they were sent to microbiological laboratory within 24 h after collection.At least five flies per market (5 samples) and at least 5 cockroaches per market (5 samples) were collected in separate plastic bags. All samples were sent to microbiological laboratory within 24 h after collection.At least 2 rats caught from each market (5 samples) were sacrificed. The intestinal contents of the rats caught from the same market were collected with a swab in Cary-Blair transport medium, and the swabs were sent to microbiological laboratory within 24 h after collection.A landfill facility located in Nonthaburi Province, where the garbage from the 5 study open markets were disposed, was chosen. The samples collected from this landfill facility included 5 liters of washed fluid from a garbage truck that collected garbage from the markets in Nonthaburi Province (1 sample), and 5 liters of stabilized leachate from the landfill facility (1 sample). All samples were collected in sterile closed containers and kept at 4 °C until they were sent to microbiological laboratory within 24 h after collection.A. baumannii, carbapenem-resistant P. aeruginosa, colistin-resistant Enterobacteriaceae, vancomycin-resistant Enterococci (VRE), and methicillin-resistant S. aureus (MRSA).Cultures of all samples were performed at the microbiology laboratory of the Division of Infectious Diseases and Tropical Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. The targeted antibiotic-resistant bacteria to be isolated from the samples were extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant Tank Collected from Hospitals, Washed Market Fluid, Market Leachate, Washed Fluid from Garbage Truck, and Stabilized Leachate from Landfill Facility An undiluted sample of 0.1 mL was inoculated on MacConkey agar supplemented with ceftriaxone 2 µg/mL, on Enterococcosel agar  supplemented with vancomycin 6 µg/mL, and on mannitol salt agar supplemented with oxacillin 6 µg/mL. The inoculated agar plates were incubated at 35 °C for 18–24 h. A diluted sample with buffered peptone water supplemented with ceftriaxone 2 µg/mL at 1:10 was prepared. A diluted sample of 0.1 mL was also inoculated on all of the aforementioned agars and they were incubated at 35 °C for 18–24 h. Colony count of grown bacteria was performed on the plate inoculated with either undiluted or diluted sample. Each type of grown bacteria was inoculated on a blood agar plate and incubated at 35 °C for 18–24 h. The bacteria grown on blood agar plate were identified up to species level and were used for antibiotic susceptibility testing as described in An undiluted sample of 1 mL was inoculated on MacConkey agar supplemented with ceftriaxone 2 µg/mL, on Enterococcosel agar  supplemented with vancomycin 6 µg/mL, and on mannitol salt agar supplemented with oxacillin 6 µg/mL. The inoculated agar plates were incubated at 35 °C for 18–24 h. A diluted sample with buffered peptone water supplemented with ceftriaxone 2 µg/mL at 1:10 was prepared. A diluted sample of 0.1 mL was also inoculated on all of the aforementioned agars and they were incubated at 35 °C for 18–24 h. Colony count of grown bacteria was performed on the plate inoculated with either undiluted or diluted sample. Each type of grown bacteria was inoculated on blood agar plate and incubated at 35 °C for 18–24 h. The bacteria grown on a blood agar plate were identified up to species level and were used for antibiotic susceptibility testing as described in Tryptic Soy Broth (TSB) of 100 mL was added to each fly and cockroach sample and the mixture was blended in a food mixer device for one minute. The mixture was incubated at 35 °C for 18–24 h. Then, 0.1 mL of the incubated mixture was inoculated on MacConkey agar supplemented with ceftriaxone 2 µg/mL, on Enterococcosel agar  supplemented with vancomycin 6 µg/mL, and on mannitol salt agar supplemented with oxacillin 6 µg/mL. The swab containing intestinal content of rat was inoculated on the aforementioned agars and they were incubated at 35 °C for 18–24 h. Identification of the isolated bacteria and antibiotic susceptibility testing were performed as described in Acinetobacter baumannii or P. aeruginosa isolates were tested with imipenem, meropenem, colistin. Staphylococcus aureus isolate was tested with cefoxitin. Enterococcal isolate was tested with vancomycin.Identification of isolated bacteria was performed by MALDI-TOF (BRUKER) . AntibioThe prevalence of antibiotic-resistant bacteria isolated from influent fluid before treatment (INF), content in wastewater treatment tank (CWW), and effluent fluid after treatment with chlorine prior to draining it into a public water source (EFF) from 188 samples collected from 60 hospitals are shown in The amount of bacteria contained in the influent fluid before treatment (INF), in the content of the wastewater treatment tank (CWW), and in the effluent fluid after treatment with chlorine prior to draining it into a public water source (EFF) from 188 samples collected from 60 hospitals are shown in Escherichia coli and/or K. pneumoniae, and carbapenem-resistant E. coli and/or K. pneumoniae were commonly isolated from the influent fluid before treatment and from the content in the wastewater treatment tank, but the prevalence of such antibiotic-resistant bacteria was much lower in the effluent fluid after treatment with chlorine. Carbapenem-resistant P. aeruginosa and carbapenem-resistant A. baumannii were less frequently isolated from the influent fluid before treatment, from the content in the wastewater treatment tank, and even further decreased in the effluent fluid after treatment with chlorine. Colistin-resistant Enterobacteriaceae and VRE were isolated from some samples of the influent fluid before treatment and from the content in the wastewater treatment tank; however, they were absent in the effluent fluid after treatment with chlorine. The MRSA was recovered from only one sample of the content in the wastewater treatment tank. Among the effluent fluid samples after treatment with chlorine with a presence of antibiotic-resistant bacteria collected from 9 hospitals , from the content in the wastewater treatment tank (CWW), and from the effluent fluid after treatment with chlorine prior to draining it into a public water source (EFF) from 186 samples collected from 60 hospitals are shown in ospitals , seven sE. coli, whereas such samples from two markets (40%) contained carbapenem-resistant E. coli and/or K. pneumoniae. No colistin-resistant Enterobacteriaceae, MRSA, or VRE was recovered from any of these samples. The market leachate samples from three markets (60%) contained ESBL-producing E. coli, whereas none of these samples contained carbapenem-resistant E. coli and/or K. pneumoniae, colistin-resistant Enterobacteriaceae, MRSA, or VRE.The number of isolated bacteria and the prevalence and type of antibiotic-resistant bacteria isolated from the samples collected from markets are shown in E. coli. No carbapenem- or colistin-resistant Enterobacteriaceae, MRSA, or VRE was recovered from any of these samples. Cockroach samples from four markets (80%) contained ESBL-producing E. coli. No carbapenem- or colistin-resistant Enterobacteriaceae, MRSA, or VRE was recovered from any of these samples. All samples of intestinal content of rats contained ESBL-producing E. coli, and one such sample (20%) contained colistin-resistant E. coli. No carbapenem-resistant Enterobacteriaceae, MRSA, or VRE was recovered from any of these samples.All fly samples contained ESBL-producing E. coli, whereas none of these samples contained carbapenem-resistant E. coli and/or K. pneumoniae, carbapenem- or colistin-resistant Enterobacteriaceae, MRSA, or VRE.The number of isolated bacteria, and the prevalence and type of antibiotic-resistant bacteria isolated from samples collected from the landfill facility are shown in The study sites that were selected for this study included both healthcare facility and community. Healthcare facilities were selected to include hospitals of various sizes that were located in all geographical regions of Thailand and that have different wastewater management systems so that these hospitals would be accurate representatives of public hospitals in Thailand, and so that their study results could be generalized to all public hospitals in Thailand. The study sites in community were open fresh markets and a landfill facility located in the same area as the markets in a province located near Bangkok. Therefore, they should be representatives of urban community in Thailand, and their study results could be generalized to other urban areas of Thailand. The targeted antibiotic-resistant bacteria included those causing infection and colonization of hospitalized patients, people, and food animals in community. The ESBL-producing Enterobacteriaceae were found to be the most common and important resistant bacteria in healthcare settings and in community. Carbapenem-resistant bacteria, MRSA, and VRE, usually cause infection and colonization in hospitalized patient. Colistin-resistant Enterobacteriaceae could cause infection and colonization in hospitalized patients who received colistin, and in food animals on farms that used colistin for prevention, control, and treatment of infection in food animal. The sample collection, sample transportation, and microbiological procedures for isolation and identification of the aforementioned targeted antibiotic-resistant bacteria in this study were appropriate, and an attempt was made to isolate all types of targeted antibiotic-resistant bacteria from the collected samples. Therefore, culturing of samples that should have heavy contamination with many types of bacteria, such as influent fluid sample from hospital before treatment, was performed using both undiluted and diluted samples, whereas the samples that were most likely to contain a minimal amount of bacteria, such as effluent fluid sample from hospital after chlorine treatment, were cultured using a larger amount of sample in order to minimize the risk of a false-negative culture result.The abundant amount of bacteria and the presence of all kinds of common antibiotic-resistant bacteria causing infection in hospitalized patients in all samples of influent fluid before treatment and in the content of wastewater treatment tank observed in this study was expected because these samples were waste fluid drained from all areas of the hospitals, including the sinks and toilets from hospital wards. However, the samples of effluent fluid after treatment with chlorine prior to draining it into a public water source collected from nine hospitals  still contained antibiotic-resistant bacteria. This observation should not be related to the type of wastewater treatment system of such hospitals because these hospitals used five different wastewater treatment systems. Therefore, these positive finding should be associated with operational defects and shortcomings of the wastewater treatment system at these hospitals. The presence of antibiotic-resistant bacteria in effluent fluid from hospital is important since these antibiotic-resistant bacteria will contaminate the environment when they are drained into an open public water source, and hospital effluent was reported to be a reservoir for carbapenemase-producing bacteria . MoreoveE. coli from flies. This may be due to the fact that the flies in our study were caught in an urban area, whereas other studies were conducted in rural areas with animal farms where colistin-resistant bacteria were usually present. The ESBL-producing E. coli was also a predominant antibiotic-resistant bacterium isolated from cockroaches and rats in this study. Cockroaches and rats were also reported to be reservoirs for antibiotic-resistant bacteria in several countries [The finding that only 60% to 80% of washed market fluid samples and market leachate samples contained antibiotic-resistant bacteria instead of all samples may be explained by the fact that detergents or other antiseptic agents were used for cleaning the markets, and these agents could kill bacteria contaminating these markets. It is clear from the findings of this study that the environment in open fresh markets and the landfill facility were important reservoirs of antibiotic-resistant bacteria in community. Flies, cockroaches, and rats caught from the study markets were reservoirs of antibiotic-resistant bacteria and were also vectors for transmission of antibiotic-resistant bacteria in the community. Flies were postulated to be one of the important vectors for transmission of antibiotic-resistant bacteria in the community, including on animal farms . Althougountries ,27,28,29The findings from this study strongly suggest that there is an extensive amount of contamination by antibiotic-resistant bacteria in the environment in both hospital and communities in Thailand. Establishment of legislation and regulation for effective wastewater treatment system in hospital to avoid a presence of antibiotic-resistant bacteria in the treated effluent draining into public water sources is being considered based on the results of this study. However, it is much more difficult to minimize contamination by antibiotic-resistant bacteria in the environment that is caused by flies, cockroaches, and rats in community. Everyone has to comply with personal health sanitation and hygiene in order to avoid acquisition of antibiotic-resistant bacteria from the environment, and to prevent transmission of antibiotic-resistant bacteria to the environment while awaiting legislation and/or regulations to prevent contamination of the environment in community with antimicrobial-resistant bacteria. E. coli and/or K. pneumoniae, were recovered from wastewater samples from hospitals even after treatment; washed fluid, leachate, flies, cockroaches, and rats collected from open markets; washed fluid from garbage truck; and stabilized leachate from a landfill facility in the community. These findings strongly suggest that there is an extensive amount of contamination by antibiotic-resistant bacteria in the environment in both hospital and communities in Thailand.Antibiotic-resistant bacteria, especially ESBL-producing


To evaluate the incidence of post-interventional contrast staining (PICS) in acute ischemic stroke (AIS) Chinese patients who were treated with endovascular thrombectomy (ET) and investigate potential association of PICS with functional outcome and intracerebral hemorrhage (ICH). This observational study was based on a single-center prospective registry study. AIS patients who underwent ET from January 2013 to February 2017 were recruited into this study. All patients had dual-energy CT (DECT) scan of the head at 12 to 24 hours post-ET. The primary outcome was the incidence of PICS. Secondary outcomes were total ICH, symptomatic ICH (sICH), 3-month functional outcome, and long-term functional outcome. One hundred and eighty patients were enrolled in this study. PICS was detected in 50 patients (28%) based on the post-interventional CT scan. We first used basic statistical analyses, showing that the incidence of both total ICH  and sICH  were higher in patients with PICS than those without, and fewer patients achieved no disability (mRS≤1) in the PICS group compared to the control group at both 3-month and long-term follow-up (p<0.01 each). However, multivariate regression analysis further revealed that PICS only increased total  but not sICH risk. Furthermore, the logistic regression analyses did not show statistical difference in good clinical outcomes or mortality between the two groups. PICS is a common phenomenon in Chinese AIS patients. It is associated with total ICH after ET, but it seems to have no effect on functional outcome and sICH. Further large-scale studies are warranted to validate these results. Post-interventional contrast staining (PICS) is a common phenomenon in acute ischemic stroke (AIS) patients after endovascular thrombectomy (ET) and it usually resolves within 24-48 hrs , 2. HoweDifferent from Western countries, in which AIS is more commonly caused by cardioembolism, the etiology of most AIS patients in Eastern countries, like China, is large artery atherosclerosis (LAA), and approximately half of them have intracranial artery stenosis , 7. HoweIn this study, we aimed to evaluate the incidence of PICS in Chinese AIS patients treated with ET by post-operative DECT scan and investigate whether it is related to functional outcome and ICH.The Xuanwu Stroke Center program includes a prospective registry for the study of revascularization therapy (i.e. intravenous thrombolysis and endovascular treatment) for AIS. ET has been applied according to the national guidelines with the intention to start the therapy as soon as possible after symptoms onset. All potential patients were evaluated at admission by a stroke neurologist. Candidates for intravenous thrombolysis or ET underwent emergent non-contrast head CT. CT perfusion or head and neck CT angiography (CTA) was not mandatory. Twelve to 24 hours after ET, all patients underwent a follow-up head CT. For each patient, baseline characteristics, functional outcomes, complications, and follow-up outcomes were documented in the database.For the present study, all patients treated with ET in our neurovascular unit from January 2013 to February 2017 were selected. Eligibility criteria included 1) AIS patients treated with ET using a second-generation stent retriever device; 2) availability and accessibility of information on baseline data and at least 3-month follow-up outcome.The present study was approved by the Ethic Committee of Xuanwu Hospital of Capital Medical University. All patients or their legally authorized representative provided written informed consent at admission to our hospital.We used the following variables of patients from the database: age, sex, location of occluded artery, time from onset to puncture and recanalization, initial stroke severity assessed by the National Institutes of Health Stroke Scale (NIHSS), initial CT examination evaluated by Alberta Stroke Program Early CT Score (ASPECTS) and posterior circulation ASPECTS (pc-ASPECTS), bridging therapy utilization, risk factors for cerebrovascular diseases, etiology according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST), operation details, ICH, functional outcome at 3 months and long-term follow up assessed by modified Rankin Scale (mRS).DECT examination was performed for all patients at 12-24 hours after ET while a plain head CT was acquired at 72±6 hours post-treatment or whenever an ICH was indicated by clinical evidence. A 64-channel multidetector DECT equipment  was used for imaging at 90kV and 150kV respectively. A three-material decomposition algorithm was applied to differentiate normal brain parenchyma, hemorrhage, and iodine contrast through comparison with unenhanced, virtual images and iodine overlay images. Material with energy-dependent attenuation compatible with iodine was mapped on the iodine overlay image and not on virtual non-contrast (VNC) image, whereas material similar to water  was mapped on the virtual non-contrast image and not on the iodine overlay image , 9. In aThe primary outcome was the incidence of PICS. PICS was defined as the hyperattenuation areas only seen on the iodine overlay image but not on the virtual non-contrast image of DECT, which was confirmed by comparing plain CT scan at 72 hours post-treatment with the previous CT scan . SecondaAll patients were divided into two groups: PICS and non-PICS (control group) groups. Baseline characteristics and clinical outcomes were compared between the two groups. In multivariate analysis, ICH was adjusted for age, baseline NIHSS, pretreatment with antiplatelet or anticoagulation, hypertension, diabetes mellitus (DM), atrial fibrillation (AF), etiology of stroke, ASPECTS/pc-ASPECTS, time from onset to groin puncture, additional intra-arterial thrombolysis and treatment with intravenous alteplase. Functional outcomes were adjusted for age, baseline NIHSS, hypertension, DM, AF, etiology of stroke, ASPECTS/pc-ASPECTS, time from onset to groin puncture time, location of stroke (posterior or anterior circulation), symptomatic ICH (sICH), and thrombolysis in cerebral infarction (TICI) scores.Continuous variables were described by mean±SD or median . T-test for independent samples or Mann-Whitney U Tests were used to detect differences between the two groups. For binary data, frequency and percentage were used to summarize data, and between-group comparisons were performed via the Chi-square, Continuity Correction or Fisher’s exact test as appropriate. All data were analyzed using SPSS 19.0 (IBM Inc.) with the significance level of p<0.05 (two-sided).A total of 180 AIS patients treated with ET were eligible for this study, including 118 patients (65.6%) of anterior circulation stroke (ACS) and 62 patients (34.4%) of posterior circulation stroke (PCS).The baseline characteristics of all patients are summarized in PICS was detected in 50 patients (28%) : 8 of 62In total, ICH was detected in 63 patients (35%). While 30 of 50 patients (60%) experienced ICH in the PICS group, 33 of 130 patients (25%) in the control group experienced ICH, which was significantly different (p<0.001). The incidence of total ICH was also significantly higher in the PICS group than the control group in patients of ACS  and PCS  respectively .Nineteen of 180 (11%) patients suffered from sICH, including 10 patients (8%) in the control group and 9 patients (18%) in the PICS group (p=0.044). In patients with PCS, 3 of 8 patients (38%) with PICS suffered from sICH compared with 1 of 54 patients (2%) without PICS (p<0.001) .Forty-three of 180 patients (24%) had no disability at 3-months follow up, including 5 patients in the PICS group and 38 patients in the control group, which was significantly different  . A totalThe median length of follow up was 12 (3-26.5) months, and 161 patients finished the long-term follow up . For thoTo determine whether PICS was independently associated with ICH or clinical outcome, multivariate regression analysis was performed. The results revealed that PICS was only independently associated with total ICH . However, PICS did not have an impact on sICH, 3-months functional outcome or long-term functional outcome (p>0.1 each). Additionally, there was no correlation between PICS and mortality when controlling for other factors . All facIn this study, we found that PICS was detected in over one-fourth of AIS patients treated by ET, and it was an independent predicator for total ICH. However, PICS may not be associated with the functional outcome and sICH. Collectively, these results support the clinical relevance of DE-CT to identify early BBB disruption in patients with AIS receiving ET. These results also hint that PICS without final ICH may only require routine follow-up.The incidence of PICS in our cases was approximately 28%, which was lower than previous studies (31.2% and 60.3%) . This diInterestingly, we found that PICS was more frequently detected in patients with ACS than in patients with PCS. Several studies, focusing on the neuroanatomy and physiology, may provide insight into this finding. Firstly, previous studies showed that the incidence of PICS was associated with infarct volume , and theThirdly, PCS tend to have better collateral circulation, which is critical to rescue the ischemic penumbra. Finally, both vasoreactivity and autoregulation differ between the anterior and posterior circulations. The insensitivity to autoregulation in PCS may be a factor in limiting the amount of contrast extravasation into the parenchyma -20. Our Contrary to Arturo's study which demonstrated that PICS was associated with poor clinical outcomes , our stuLimitations of this study include small sample size which limits the utility of our conclusion. Additionally, this was an observational study and the outcome assessment was not blinded for either the baseline characteristics or treatment. Potential variables including additional use of intra-arterial thrombolysis and various etiologies of stroke might also have confounded out study results.PICS is a common phenomenon in Chinese AIS patients treated with ET. Even though PICS is associated with high incidence of ICH, no correlation to sICH or functional outcome was evident in our study. Additional, large-scale studies are needed to confirm our results and explore their influence on postoperative therapeutic guidelines.


Rotarix, as measured by laboratory-confirmed rotavirus infection after referral to hospital and/or emergency departments in children aged <5 years with gastroenteritis.Gastroenteritis caused by rotavirus accounts for considerable morbidity in young children. We aimed to assess the vaccine effectiveness (VE) of the oral rotavirus vaccine Rotarix VE, which was further discriminated through stratified analyses.We performed a systematic search for peer-reviewed studies conducted in real-life settings published between 2006 and 2016 and a meta-analysis to calculate the overall The overall VE estimate was 69% ; stratified analyses revealed a non-negligible impact of factors such as study design and socioeconomic status. Depending on the control group, VE ranged from 63%  to 81%  for unmatched and matched rotavirus test–negative controls. VE varied with socioeconomic status: 81%  in high-income countries, 54%  in upper-middle-income countries, and 63%  in lower-middle-income countries. Age, rotavirus strain, and disease severity were also shown to impact VE, but to a lesser extent.Rotarix is effective in helping to prevent hospitalizations and/or emergency department visits due to rotavirus infection.This meta-analysis of real-world studies showed that  Rotavirus (RV) is the major cause of severe gastroenteritis (GE) diseases, which amount to a considerable burden of disease in children younger than age 5 years . AlthougRotarix  was introduced in routine immunization programs as of 2006. In 2009, the World Health Organization recommended the global implementation of RV vaccination in infants [Vaccination is the best preventive approach against RV diseases . The ora infants . By June infants , 5.Rotarix is a 2-dose-shedule oral live-attenuated human RV vaccine, recommended for active immunization against GE due to RV infection (RVGE) in infants aged 6–24 weeks [Rotarix should be administered at least 4 weeks apart, and the vaccination course must be completed by 24 weeks of age [Rotarix was shown to have a favorable benefit/risk profile in infants and was efficacious against severe GE- or RV-associated hospitalization in several large clinical trials conducted worldwide [Rotarix was shown to provide broad protection against severe RVGE caused by nonvaccine RV strains; that is, efficacy or effectiveness has been demonstrated against 9 different strains [orldwide , with a orldwide , 14. Favorldwide . RotarixRotarix, as measured by laboratory-confirmed RV infection after referral to hospitals and/or the emergency department (ED), in children with GE diseases in real-world settings. We conducted a systematic literature review and a meta-analysis of the VE of 2- or 1-dose Rotarix vaccination data published between January 1, 2006, and July 7, 2016.This study evaluated the vaccine effectiveness (VE) of Rotarix . In addition, the reference list of meta-analyses or systematic reviews was checked for relevant articles that could have been missed. The quality of the selected articles was assessed using the Coordination of Cancer Clinical Practice Guidelines (CoCanCPG) .We extracted and summarized the following data as a minimum: study design, setting and period, study objectives, study country and its socioeconomic status , type oRotarix, as measured by laboratory-confirmed RV infection after referral to hospitals and/or EDs in children with GE under 5 years of age, as reported by observational studies identified by the systematic literature search . The secondary objectives of the meta-analysis were to assess the VE according to the number of Rotarix doses provided (1 or 2), type of controls used in the studies, the SES of the country, RV strain type, age (<1 or ≥1 year), and disease severity. Stratification analyses were carried out on 1 level  for 1 Rotarix dose and the complete schedule, whereas 2-level stratified analyses were conducted only for 2 doses of Rotarix (by age and SES and by strain and SES). A meta-analysis was performed only when at least 4 VE estimates could be included. To investigate the effect of specific study parameters on the VE, sensitivity analyses were conducted by excluding studies reporting on ED referrals only or primary health care centers, high-income countries and unmatched control groups, or unadjusted data.We estimated the overall VE in children receiving 2 doses of In performing the analyses, several considerations were predefined for each included study. If VE estimates were presented for multiple control groups, only 1 estimate was selected as follows: hospital controls were preferred above community controls; in case of multiple hospital controls, matched controls were used; and when nonmatched control groups were studied, test-negative controls were preferred. When both crude and covariate-adjusted VE were provided in studies, adjusted estimates were used for the meta-analysis.VE was defined as the percent reduction in the odds of referral to hospitals and/or EDs due to RVGE disease among vaccinated children compared with unvaccinated children. Meta-analyses were performed on odds ratios (ORs) and 95% confidence intervals (CIs); log(OR) and standard error of log(OR) were computed. If the ORs and 95% CIs were not available in the included studies, these were calculated from the estimates included in the articles using the formula OR = 1 – (VE/100) .I2 test, along with visual assessment of the funnel plots [I2 values of <25%, 25%–50%, 50%–75%, and >75% were considered very low, low, medium, and high heterogeneity, respectively [The random-effect model (using the DerSimonian-Laird approach)  was usedel plots . I2 valuectively .P value of <.10 considered significant [Publication bias was investigated for the overall 1- and 2-dose VE analyses, by visual assessment of funnel plots, and by Egger’s weighted regression test, with a 2-sided nificant .All analyses were performed without any adjustment for multiplicity using STATA v13.1.After removal of duplicates, the search strategy yielded 2890 unique records. Following the screening of titles and abstracts, we retained 261 articles for full-text review, from which 32 studies  were ideThe meta-analysis included 29 studies . For theAmong the 29 studies included in the meta-analysis, 6 were conducted in African countries , 2 in CeAll 29 studies included in the meta-analysis were case-control studies and fulfilled the quality criteria of the CoCanCPG checklist.Rotarix. Two [I2 = 67%; 95% CI, 50% to 78%) observed between studies  with an I2 of 34% , showing low between-study heterogeneity , 54% , and 63%  in high-, upper-middle-, and lower-middle-income countries, respectively. One-dose VE also varied slightly with the SES of the countries, from 48%  for upper-middle-income to 37%  for lower-middle-income countries  for matched and 63%  for unmatched RV test–negative controls , 72% , and 65%  for the G1P [When the analysis was performed by strain type, the estimated 2-dose VE of Stratified analyses on 2 levels performed for the 2-dose VE confirmed a higher VE in children aged <1 year than in those ≥1 year of age, in both upper-middle- and lower-middle-income countries .Rotarix were observed when excluding unmatched controls or studies where the matching process was not clear , sensitivity analyses yielded a 2-dose VE of 69% , similar to that obtained from the main analysis. When omitting data from high-income countries, VE estimates were found to be in the same ranges as those obtained for the main analysis . Higher VE estimates for both 2 doses and 1 dose of ot clear .P = .19), whereas significant asymmetry was shown by the coefficient for the 1-dose VE .Funnel plots assessing publication bias are presented in Rotarix vaccine includes peer-reviewed data publicly available on its use in real-world settings over a period of 10 years. Although several meta-analyses assessing Rotarix effectiveness against various end points have already been published [Rotarix against RVGE-related hospitalizations or ED visits. Our systematic review and meta-analysis showed that programmatic use of Rotarix prevents hospital admission or ED visits due to RVGE in children under 5 years of age.This meta-analysis of the VE of the ublished , 56–58, Rotarix is implemented in the NIP. Studies from Taiwan and Portugal, where the vaccine is only available on the private market, were also included.We analyzed data from 29 studies assessing postlicensure VE, conducted in various geographical regions, and covering the entire range of SES. Most of the studies included in the review were undertaken in countries where Rotarix provided considerable prevention of RV disease–related hospitalizations or referrals to ED, with a pooled VE estimate of 69%, but increasing to up to 81% in high-income countries. The estimated VE for 1 dose was 46%, indicating that partial reduction of hospitalization is also provided by 1 dose of Rotarix. However, our results highlight the importance of a full vaccination schedule.The meta-analysis showed that a 2-dose schedule of Overall VE values obtained from stratified analyses were the highest in high-income countries. This is consistent with results from clinical trials, showing lower vaccine efficacy in African countries  than in Rotarix than those with unmatched or neighborhood/community controls, with values varying from 81% to 63%. Furthermore, RV test–negative control types are highly specific for non-RV diseases and thereby increase the robustness of the estimate. The overall VE of 2 Rotarix doses obtained using matched RV test–negative controls was 81%, but only 4 studies could be included in the analysis.Because case-control study design is a widely used method to assess VE, only this type of study was included in our meta-analysis. In addition, to ensure high specificity of the outcome and avoid any potential misclassification, only studies with laboratory-confirmed RVGE diagnosis were considered when conducting the meta-analysis. The type of controls used was previously shown to impact VE to some extent, as observed in a review performed to assess VE of RV vaccines in Latin America . In our Rotarix VE was similar against disease of high and very high severity regardless of the number of doses but could not be estimated against mild and moderately severe disease due to the lack of data.Vaccine efficacy as assessed in clinical trials was previously shown to increase with the severity of the disease , a findiVE against RVGE-related hospitalizations or ED visits varied between 64% and 89% with the type of RV strain, in line with efficacy results observed in clinical trials that demonstrated broad protection against severe RVGE by different RV types , 14. TheA rigorous quality control procedure has been applied for both the systematic review and the meta-analysis. Additional analyses investigating the publication bias have been performed. The study’s main strength was the inclusion of robust case-control studies using laboratory confirmation of RV status. To minimize the risk of bias, adjusted results were preferentially included in the analysis. Nevertheless, although the case-control design allowed for stratified meta-analyses performed by type of control, this type of study also presents a certain risk of bias, as it relies on retrospectively assessed chart-based data and thorough documentation of vaccination history that might not have been correctly reported.The study also has several limitations. Although covering various geographical settings, the data used in the meta-analysis originated from only 21 countries, with a small amount of data from low-income countries. Similarly, a relatively small number of studies reported strain-specific data. For certain subgroups, only a limited number of studies could be included in the analyses, or no meta-analyses could be performed due to insufficient data. The funnel plots suggest publication bias for some small studies with high OR (or low VE). However, as these studies had very low weights, their impact on the overall estimates is low.Rotarix vaccination.Importantly, as previously discussed in relation with postlicensure studies , values Rotarix has a substantial preventive effect against hospitalizations and ED visits due to RVGE, further confirming the effectiveness of Rotarix in children younger than age 5 years across various geographic and economic settings.This meta-analysis provides strong evidence that vaccination with 2 doses of Open Forum Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.Supplementary materials are available at Supplementary DataClick here for additional data file.