Disease-Associated Streptococcus pneumoniae Genetic Variation.

Streptococcus pneumoniae is an opportunistic pathogen that causes substantial illness and death among children worldwide. The genetic backgrounds of pneumococci that cause infection versus asymptomatic carriage vary substantially. To determine the evolutionary mechanisms of opportunistic pathogenicity, we conducted a genomic surveillance study in China. We collected 783 S. pneumoniae isolates from infected and asymptomatic children. By using a 2-stage genomewide association study process, we compared genomic differences between infection and carriage isolates to address genomic variation associated with pathogenicity. We identified 8 consensus k-mers associated with adherence, antimicrobial resistance, and immune modulation, which were unevenly distributed in the infection isolates. Classification accuracy of the best k-mer predictor for S. pneumoniae infection was good, giving a simple target for predicting pathogenic isolates. Our findings suggest that S. pneumoniae pathogenicity is complex and multifactorial, and we provide genetic evidence for precise targeted interventions.

Pharmacokinetics, safety, and bioequivalence of apixaban tablets in healthy Chinese subjects under fasting and fed conditions.

OBJECTIVE: To evaluate the pharmacokinetics (PK), safety, and bioequivalence of two formulations of apixaban in healthy Chinese subjects under fasting and fed conditions. MATERIALS AND METHODS: A single-center, randomized, open, single-dose, two-period crossover PK study was carried out under fasting and fed conditions in 64 healthy subjects enrolled in either the fasting (36 subjects) or the fed (28 subjects) arms of the study. Subjects received a single oral dose of 2.5 mg apixaban tablets as test (T) or reference (R) formulation. The primary PK parameters determined were the area under the plasma concentration-time curve from zero to t and ∞ (AUC0-t and AUC0-∞) and the maximal plasma concentration (Cmax). Safety was assessed mainly from the occurrence of adverse events (AEs). RESULTS: A single drop-out in the fed arm of the trial was excluded from the statistical evaluation. The 90% confidence intervals (CIs) for the geometric mean ratio (GMR) for T/R using AUC0-t were 95.4 - 100.9% and 97.8 - 103.8%, and for AUC0-∞ were 95.3 - 100.6% and 98.3 - 104.3% under fasting (36 subjects) and fed (27 subjects) conditions, respectively. Similarly, the 90% CIs for Cmax were 94.6 - 103.1% and 88.8 - 102.0% under fasting (36 subjects) and the fed (27 subjects) conditions, respectively. Therefore, the 90% CIs for the T/R AUC and Cmax ratios were within the standard range for bioequivalence (80.0 - 125.0%). There were no serious adverse events (SAEs). CONCLUSION: The test and reference 2.5 mg apixaban tablets were bioequivalent and both showed good tolerability and safety.

[Dose-response relationship between age and Streptococcus pneumoniae vaccination coverage in kindergarten children]. / 幼儿园儿童年龄与肺炎链球菌疫苗覆盖率间的剂量-ååº”å ³ç³».

OBJECTIVES: To investigate the potential relationship between age and Streptococcus pneumoniae vaccination coverage in kindergarten children, and to provide a basis for guiding vaccination and developing new protein vaccines. METHODS: The stratified cluster random sampling method was used to select 1 830 healthy children from six kindergartens in Shunde District, Foshan City, China, and nasopharyngeal swabs were collected for the isolation and identification of Streptococcus pneumoniae. The logistic regression model based on restricted cubic spline was used to analyze the dose-response relationship between age and Streptococcus pneumoniae vaccination coverage. RESULTS: The rate of nasal Streptococcus pneumoniae carriage was 22.46% (411/1 830) among the kindergarten children, with the predominant serotypes of 6B, 19F, 15A, 23A, 34, and 23F. The coverage rates of 10-valent pneumococcal conjugate vaccine (PCV10) and 13-valent pneumococcal conjugate vaccine (PCV13) were 53.0% and 57.9%, respectively, and there was a significant non-linear dose-response relationship between age and the coverage rates of PCV10 and PCV13 (P<0.05), with a higher coverage rate of PCV10 (88.0%) and PCV13 (91.1%) in the children aged 2 years. There was a significant non-linear dose-response relationship between age and the coverage rates of pilus islet 1 (PI-1) and pilus islet 2 (PI-2) (P<0.05), with a lower vaccination coverage rate for PI-1 (37.7%) and PI-2 (16.1%). The coverage rates of PI-1 (13.0%-58.5%) and PI-2 (6.0%-29.4%) were lower in all age groups. The virulence genes lytA (99.5%) and ply (99.0%) associated with candidate protein vaccines showed higher vaccination coverage rates. CONCLUSIONS: There is a significant non-linear dose-response relationship between the age of kindergarten children and the coverage rates of PCV10 and PCV13 serotypes, and kindergarten children aged 2 years have a relatively high coverage rate of PCV. The high prevalence of the virulence genes lytA and ply shows that they are expected to become candidate virulence factors for the development of a new generation of recombinant protein vaccines.

[Screening of pathogenic molecular markers of Staphylococcus aureus in children based on whole genome sequencing technology]. / åŸºäºŽå ¨åŸºå› ç»„æµ‹åºæŠ€æœ¯ç­›é€‰å„¿ç«¥é‡‘é»„è‰²è‘¡è„çƒèŒçš„è‡´ç— ç›¸å ³åˆ†å­æ ‡å¿—ç‰©.

OBJECTIVES: To explore the molecular characteristics of Staphylococcus aureus (S. aureus) in children, and to compare the molecular characteristics of different types of strains (infection and colonization strains) so as to reveal pathogenic molecular markers of S. aureus. METHODS: A cross-sectional study design was used to conduct nasopharyngeal swab sampling from healthy children in the community and clinical samples from infected children in the hospital. Whole genome sequencing was used to detect antibiotic resistance genes and virulence genes. A random forest method to used to screen pathogenic markers. RESULTS: A total of 512 S. aureus strains were detected, including 272 infection strains and 240 colonization strains. For virulence genes, the carrying rates of enterotoxin genes (seb and sep), extracellular enzyme coding genes (splA, splB, splE and edinC), leukocytotoxin genes (lukD, lukE, lukF-PV and lukS-PV) and epidermal exfoliating genes (eta and etb) in infection strains were higher than those in colonization strains. But the carrying rates of enterotoxin genes (sec, sec3, seg, seh, sei, sel, sem, sen, seo and seu) were lower in infection strains than in colonization strains (P<0.05). For antibiotic resistance genes, the carrying rates of lnuA, lnuG, aadD, tetK and dfrG were significantly higher in infection strains than in colonization strains (P<0.05). The accuracy of cross-validation of the random forest model for screening pathogenic markers of S. aureus before and after screening was 69% and 68%, respectively, and the area under the curve was 0.75 and 0.70, respectively. The random forest model finally screened out 16 pathogenic markers (sem, etb, splE, sep, ser, mecA, lnuA, sea, blaZ, cat(pC233), blaTEm-1A, aph(3')-III, ermB, ermA, ant(9)-Ia and ant(6)-Ia). The top five variables in the variable importance ranking were sem (OR=0.40), etb (OR=3.95), splE (OR=1.68), sep (OR=3.97), and ser (OR=1.68). CONCLUSIONS: The random forest model can screen out pathogenic markers of S. aureus and exhibits a superior predictive performance, providing genetic evidence for tracing highly pathogenic S. aureus and conducting precise targeted interventions.

Spatiotemporal analysis of the morbidity of global Omicron from November 2021 to February 2022.

The Omicron variant was first reported to the World Health Organization (WHO) from South Africa on November 24, 2021; this variant is spreading rapidly worldwide. No study has conducted a spatiotemporal analysis of the morbidity of Omicron infection at the country level; hence, to explore the spatial transmission of the Omicron variant among the 220 countries worldwide, we aimed to the analyze its spatial autocorrelation and to conduct a multiple linear regression to investigate the underlying factors associated with the pandemic. This study was an ecological study. Data on the number of confirmed cases were extracted from the WHO website. The spatiotemporal characteristic was described in a thematic map. The Global Moran Index (Moran's I) was used to detect the spatial autocorrelation, while the local indicators of spatial association (LISA) were used to analyze the local spatial correlation characteristics. The joinpoint regression model was used to explore the change in the trend of the Omicron incidence over time. The association between the morbidity of Omicron and influencing factors were analyzed using multiple linear regression. This study was an ecological study. Data on the number of confirmed cases were extracted from the WHO website. The spatiotemporal characteristic was described in a thematic map. The Global Moran Index (Moran's I) was used to detect the spatial autocorrelation, while the LISA were used to analyze the local spatial correlation characteristics. The joinpoint regression model was used to explore the change in the trend of the Omicron incidence over time. The association between the morbidity of Omicron and influencing factors were analyzed using multiple linear regression. The value of Moran's I was positive (Moran's I = 0.061, Z-score = 3.772, p = 0.007), indicating a spatial correlation of the morbidity of Omicron at the country level. From November 26, 2021 to February 26, 2022; the morbidity showed obvious spatial clustering. Hotspot clustering was observed mostly in Europe (locations in High-High category: 24). Coldspot clustering was observed mostly in Africa and Asia (locations in Low-Low category: 32). The result of joinpoint regression showed an increasing trend from December 21, 2021 to January 26, 2022. Results of the multiple linear regression analysis demonstrated that the morbidity of Omicron was strongly positively correlated with income support (coefficient = 1.905, 95% confidence interval [CI]: 1.354-2.456, p < 0.001) and strongly negatively correlated with close public transport (coefficient = -1.591, 95% CI: -2.461 to -0.721, p = 0.001). Omicron outbreaks exhibited spatial clustering at the country level worldwide; the countries with higher disease morbidity could impact the other countries that are surrounded by and close to it. The locations with High-High clustering category, which referred to the countries with higher disease morbidity, were mainly observed in Europe, and its adjoining country also showed high spatial clustering. The morbidity of Omicron increased from December 21, 2021 to January 26, 2022. The higher morbidity of Omicron was associated with the economic and policy interventions implemented; hence, to deal with the epidemic, the prevention and control measures should be strengthened in all aspects.

Solvent-Free Thermal Synthesis of Extra-Large-Pore Aluminophosphate Zeotype via Self-Assembly of Double-Four-Ring Unit.

The use of Ge as framework atom to direct the formation of double-four-ring (d4r) unit is an effective way to prepare zeolite with extra-large pores, which however also brings about serious problems with regard to production cost and structure stability for their practical application. A new solvent-free thermal synthesis strategy is presented here for facile preparation and molecular-level mechanism study of extra-large-pore aluminophosphate zeotype DNL-1 with -CLO structure. For the first time, the formation of intermediate d4r in the induction period was successfully confirmed, and was correlated with the synthesis condition of low water content and quaternary ammonium template with suitable alkyl chain length. The self-assembly pathway via d4r to form lta, afterwards clo and super cages was further revealed. This work shed light on the rational synthesis of Ge-free extra-large-pore zeotypes based on d4r route.

Co-carriage of Streptococcus pneumoniae and Moraxella catarrhalis among preschool children and its influencing factors. / å­¦é¾„å‰å„¿ç«¥è‚ºç‚Žé“¾çƒèŒå’Œå¡ä»–èŽ«æ‹‰èŒæºå¸¦çŠ¶æ€åŠå½±å“å› ç´ åˆ†æž.

OBJECTIVES: To investigate the carriage status of Streptococcus pneumoniae (S.pneumoniae) and Moraxella catarrhalis (M. catarrhalis) in preschool children and the influencing factors for the carriage status. METHODS: The stratified cluster sampling method was used to select 2 031 healthy children from seven kindergartens in Shunde District of Foshan in Guangdong, China. Nasal swabs were collected from all children for the isolation and identification of S. pneumoniae and M. catarrhalis. The carriage status of S. pneumoniae and M. catarrhalis was analyzed in terms of its association with demographic features and hospital- and community-related factors. RESULTS: The carriage rates of S. pneumoniae and M. catarrhalis were 21.81% and 52.44%, respectively among the children. The co-carriage rate of S. pneumoniae and M. catarrhalis was 14.87%. The correspondence analysis showed that the factors such as lower grade, non-local registered residence, living in rural areas, small living area, history of respiratory tract infection but no history of antibiotic use, allergic skin diseases, and no hospital-related exposure history were significantly associated with the co-carriage of S. pneumoniae and M. catarrhalis among the children (P<0.05). CONCLUSIONS: Co-carriage of S. pneumoniae and M. catarrhalis can be observed in preschool children. Young age, poor living environment, a history of respiratory tract infection but no history of antibiotic use, allergic skin diseases, and no hospital-related exposure history are important risk factors for the co-carriage of S. pneumoniae and M. catarrhalis in preschool children.

Multidrug-resistant Staphylococcus aureus nasal carriage among HIV-positive outpatients in Guangzhou, China: Prevalence, risk factors, phenotypic and molecular characteristics.

INTRODUCTION: Data on comprehensive characterization of multidrug-resistant (MDR) Staphylococcus aureus (S. aureus) carriage in human immunodeficiency virus (HIV)-positive patients are limited. The objective of the present study is to determine the prevalence, risk factors, phenotypic and molecular characterization of MDR S. aureus isolated from HIV-positive population. METHODS: A cross-sectional study was conducted to determine the characteristics of MDR S. aureus nasal carriage among HIV-positive outpatients in an HIV clinic from June to August 2017. Nasal swabs and risk factor data of the enrolled HIV-positive outpatients were collected. Phenotypic and molecular characteristics of MDR and non-MDR S. aureus isolates were analyzed. Risk factors for nasal carriage with MDR S. aureus were estimated by logistic regression. The relationship between phenotypic and molecular characteristics of S. aureus isolates was assessed by the correspondence analysis. RESULTS: Overall, 1001 HIV-positive outpatients were included. The prevalence of MDR S. aureus nasal carriage was 15.18% (152/1001), and the proportion of multidrug resistance among S. aureus isolates was 60.08% (152/253). Having a history of respiratory tract infection was the risk factor for MDR S. aureus nasal carriage (adjusted odds ratio = 1.90, 95% confidence interval: 1.25-2.89). Multidrug resistance of S. aureus isolates was in good corresponding relationships with clonal complex (CC)5, CC15, CC59 and CC398. CONCLUSIONS: We found high burden of multidrug resistance among S. aureus isolated from HIV-positive outpatients, particularly in those who had upper respiratory tract infection. Moreover, CC59 and CC398 are highly related to multidrug resistance of S. aureus isolates.

Effects of exposure to low-dose ionizing radiation on changing platelets: a prospective cohort study.

BACKGROUND: Numerous studies have concentrated on high-dose radiation exposed accidentally or through therapy, and few involve low-dose occupational exposure, to investigate the correlation between low-dose ionizing radiation and changing hematological parameters among medical workers. METHODS: Using a prospective cohort study design, we collected health examination reports and personal dose monitoring data from medical workers and used Poisson regression and restricted cubic spline models to assess the correlation between changing hematological parameters and cumulative radiation dose and determine the dose-response relationship. RESULTS: We observed that changing platelet of 1265 medical workers followed up was statistically different among the cumulative dose groups (P = 0.010). Although the linear trend tested was not statistically significant (Ptrend = 0.258), the non-linear trend tested was statistically significant (Pnon-linear = 0.007). Overall, there was a correlation between changing platelets and cumulative radiation dose (a change of ßa 0.008 × 109/L during biennially after adjusting for gender, age at baseline, service at baseline, occupation, medical level, and smoking habits; 95% confidence interval [CI] = 0.003,0.014 × 109/L). Moreover, we also found positive first and then negative dose-response relationships between cumulative radiation dose and changing platelets by restricted cubic spline models, while there were negative patterns of the baseline service not less than 10 years (- 0.015 × 109/L, 95% CI = - 0.024, - 0.007 × 109/L) and radiation nurses(- 0.033 × 109/L, 95% CI = - 0.049, - 0.016 × 109/L). CONCLUSION: We concluded that although the exposure dose was below the limit, medical workers exposed to low-dose ionizing radiation for a short period of time might have increased first and then decreased platelets, and there was a dose-response relationship between the cumulative radiation dose and platelets changing.

Methicillin-Resistant Coagulase-Negative Staphylococci Carriage is a Protective Factor of Methicillin-Resistant Staphylococcus Aureus Nasal Colonization in HIV-Infected Patients: A Cross-Sectional Study.

BACKGROUND: Methicillin-resistant coagulase-negative Staphylococci (MRCoNS) is regarded as the repository of mecA gene for methicillin-resistant Staphylococcus aureus (MRSA) and may develop methicillin-susceptible Staphylococcus aureus (MSSA) to MRSA. Therefore, we aimed to explore whether MRCoNS carriage is a risk factor of MRSA colonization. Phenotypic characteristics were performed to further assess the associations between MRSA and MRCoNS. METHODS: This cross-sectional study was conducted in Guangzhou, China. Participants completed a questionnaire and provided a nasal swab for further analysis. The risk factors of MRSA colonization were analyzed using nonconditional logistic regression models. The phenotypic characteristics between MRSA and MRCoNS were compared by Chi-square test. RESULTS: Among the 1001 HIV-infected patients, a total of 119 (11.89%) participants were positive for MRSA, and 34.45% (41/119) of all MRSA carriers were positive for MRCoNS. We found MRCoNS carriage was a protective factor of MRSA colonization (adjusted odds ratio = 0.59, 95% confidence interval: 0.38-0.91). A significant difference in the proportions of antibiotic resistance between MRSA and MRCoNS isolates was found except for penicillin, clindamycin, tetracycline, and teicoplanin. The main STs and CC types of MRSA isolates in this population were ST188 (15.1%) and CC59 (17.6%), respectively. CONCLUSIONS: HIV-infected patients remain a highly vulnerable population for MRSA colonization. Though who carried MRCoNS is less likely to have MRSA colonization, similarity of some antibiotic resistance between MRSA and MRCoNS was found in this study. Regular surveillance on the colonization and antibiotic patterns of MRSA and MRCoNS is still necessary.

Group B streptococcus colonisation and associated risk factors among pregnant women: A hospital-based study and implications for primary care.

BACKGROUND: Group B streptococcus (GBS), which asymptomatically colonises the vaginal and rectal areas of women, is a leading cause of neonatal mortality and morbidity. This study aimed to determine the prevalence and factors associated with GBS colonisation among pregnant women in Shenzhen, China. METHODS: A hospital-based cross-sectional survey was conducted, using a multistage sampling method. Pregnant women at ≥28 weeks' gestation completed a questionnaire and vaginal swabs were obtained for GBS analysis. Data were analysed by chi-squared tests and logistic regression models. RESULTS: The colonisation rate of GBS among pregnant women was 4.9%. The influencing factors associated with GBS colonisation included body mass index before pregnancy (odds ratio [OR] = 3.79, 95% CI 1.28-11.26), gestational age (OR = 5.81, 95% CI 1.20-28.15), induced abortion (OR = 0.63, 95% CI 0.40-0.98) and lotion use before pregnancy (OR = 1.59, 95% CI 1.04-2.44). CONCLUSIONS: Our findings suggest that obesity, gestational age, induced abortion and lotion use were significantly associated with GBS colonisation. Further longitudinal research is needed to establish the causal relationship and its biological mechanisms.

A large meta-analysis of the global prevalence rates of S. aureus and MRSA contamination of milk.

Past reports have indicated a high prevalence of milk contaminated with Staphylococcus aureus (S. aureus) and methicillin-resistant Staphylococcus aureus (MRSA), but the pooled prevalence rates of S. aureus and MRSA in pasteurized and boiled cow's milk, raw cow's milk, and raw Caprinae milk (raw sheep's milk and raw goat's milk) and across different periods, continents, economic conditions and purchase locations remain inconsistent. We searched relevant articles published in PubMed, EMBASE, and Web of Science before July 2016. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement was used to evaluate the quality of 93 included studies. We observed that the pooled prevalence rates of S. aureus contamination in pasteurized and boiled cow's milk, raw cow's milk, and raw Caprinae milk were 15.4% (95% CI, 6.1-27.5%), 33.5% (95% CI, 29.5-37.7%) and 25.8% (95% CI, 17.5-35.0%), respectively. The pooled prevalence rates of MRSA contamination were 4.9% (95% CI, 0.0-15.7%), 2.3% (95% CI, 1.3-3.6%), and 1.1% (95% CI, 0.5-1.8%), respectively. The prevalence of S. aureus contamination in raw cow's milk increased over time. However, the pooled prevalence of raw cow's milk contaminated with S. aureus was lowest in European studies. These findings give an indication of the consequence of better milk regulation in Europe. High S. aureus prevalence rates in raw milk collected from farms and processing companies pose a potential threat to consumers. The implementation of good hygiene practices, appropriate health knowledge, and food safety principles at the farm level, as well as the prudent use of antibiotics in veterinary medicine and heat treatment before drinking, are necessary to reduce the potential risk of S. aureus and MRSA contamination.

TGF-ß Stimulates Endochondral Differentiation after Denervation.

Transforming growth factor beta (TGF-ß) is a multifunctional protein that induces gene expression of cartilage-specific molecules, but its exact role in the process of chondrogenesis is unclear. Because recent studies suggest that TGF-ß can facilitate chondrogenic precursor cells differentiating into chondrocytes, we sought to determine whether TGF-ß prevents denervation-induced reduction of endochondral bone formation in an experimental model. Mice were treated daily with recombinant human TGF-ß1 (rhTGF-ß1) for 3 weeks. We found that rhTGF-ß1 not only prevented denervation-induced reduction of gene expression of type II collagen, type X collagen, aggrecan, Indian hedgehog, and parathyroid hormone-related peptide, but also synergized endochondral differentiation. These results demonstrate that short-term systemic administration of TGF-ß substantially prevents denervation-induced reduction of endochondral bone formation via stimulating endochondral differentiation. Potential therapeutic applications will be pursued in further studies that address the molecular biological mechanism of TGF-ß on endochodral bone formation after denervation in animal models.

Prevalence, Influencing Factors, Antibiotic Resistance, Toxin and Molecular Characteristics of Staphylococcus aureus and MRSA Nasal Carriage among Diabetic Population in the United States, 2001-2004.

Diabetic population were reported more likely to suffer carriage and infection with Staphylococcus aureus (S. aureus) and methicillin-resistant Staphylococcus aureus (MRSA) than non-diabetic population. We aim to elucidate the prevalence and characteristics of S. aureus and MRSA nasal carriage among diabetic population in the United States National Health and Nutrition Examination Survey, 2001-2004. Univariate analyses were conducted using Chi-square test, Fisher's exact probability test or student t test, as appropriate. Multivariate analy¬sis using logistic regression was conducted to assess the association between influencing factors and S. aureus and MRSA nasal carriage. 1010 diabetic participants were included in the study. The prevalence of S. aureus and MRSA nasal carriage were 28.32% and 1.09%, respec¬tively. After the logistic regression, ever had a painful sensation or tingling in hands or feet past three months (Odds Ratio [OR] = 0.359, 95% Confidence Interval [CI], 0.146-0.882) was significant among S. aureus nasal carriage and gender (OR = 3.410, 95% CI, 1.091-10.653) was significant among MRSA nasal carriage. The proportions of staphylococcal enterotoxin (SE) A, SEB, SEC, SED, Toxic-shock syn¬drome toxin-1, and Panton Valentine Leukocidin toxin among S. aureus strains were 18.75%, 3.13%, 12.50%, 15.63%, 28.13%, and 9.38%, respectively. 63.63% of MRSA strains were community-acquired, 27.27% were hospital-acquired, and 9.09% were non-typeable. Diabetic patients might be more likely to carry S. aureus and MRSA in the United States. Improving hand hygiene compliance, reducing antibiotic overuse, screening for carriers, and decolonization are recommended to reduce the spread of S. aureus and MRSA, especially in community.

Genotypic and Phenotypic Markers of Livestock-Associated Methicillin-Resistant Staphylococcus aureus CC9 in Humans.

UNLABELLED: Use of antimicrobials in industrial food animal production is associated with the presence of multidrug-resistant Staphylococcus aureus among animals and humans. The livestock-associated (LA) methicillin-resistant S. aureus (MRSA) clonal complex 9 (CC9) is associated with animals and related workers in Asia. This study aimed to explore the genotypic and phenotypic markers of LA-MRSA CC9 in humans. We conducted a cross-sectional study of livestock workers and controls in Guangdong, China. The study participants responded to a questionnaire and provided a nasal swab for S. aureus analysis. The resulting isolates were assessed for antibiotic susceptibility, multilocus sequence type, and immune evasion cluster (IEC) genes. Livestock workers had significantly higher rates of S. aureus CC9 (odds ratio [OR] = 30.98; 95% confidence interval [CI], 4.06 to 236.39) and tetracycline-resistant S. aureus (OR = 3.26; 95% CI, 2.12 to 5.00) carriage than controls. All 19 S. aureus CC9 isolates from livestock workers were MRSA isolates and also exhibited the characteristics of resistance to several classes of antibiotics and absence of the IEC genes. Notably, the interaction analyses indicated phenotype-phenotype (OR = 525.7; 95% CI, 60.0 to 4,602.1) and gene-environment (OR = 232.3; 95% CI, 28.7 to 1,876.7) interactions associated with increased risk for livestock-associated S. aureus CC9 carriage. These findings suggest that livestock-associated S. aureus and MRSA (CC9, IEC negative, and tetracycline resistant) in humans are associated with occupational livestock contact, raising questions about the potential for occupational exposure to opportunistic S. aureus IMPORTANCE: This study adds to existing knowledge by giving insight into the genotypic and phenotypic markers of LA-MRSA. Our findings suggest that livestock-associated S. aureus and MRSA (CC9, IEC negative, and tetracycline resistant) in humans are associated with occupational livestock contact. Future studies should direct more attention to exploring the exact transmission routes and establishing measures to prevent the spread of LA-MRSA.

Non-hospital environment contamination with Staphylococcus aureus and methicillin-resistant Staphylococcus aureus: proportion meta-analysis and features of antibiotic resistance and molecular genetics.

BACKGROUND: Staphylococcus aureus (S. aureus), including methicillin-resistant Staphylococcus aureus (MRSA), survives in dry conditions and can persist for long periods on surfaces touched by humans. Studies that estimate the proportions and characteristics of S. aureus and MRSA contamination in non-hospital environments are lacking. Therefore, we conducted a proportion meta-analysis and reviewed the features of antibiotic resistance and molecular genetics. METHODS: Articles published between January 2005 and December 2015 that studied proportions of S. aureus and MRSA contamination in non-hospital environments were retrieved from the Medline database, Ovid database and Science Direct database. All statistics were analyzed by STATA 14.1. RESULTS: Twenty-nine articles were included. The overall proportions of S. aureus and MRSA contamination were 41.1% (95%CI 29-54%) and 8.6% (95%CI 5-13%), respectively. The proportion of MRSA contamination increased over time. From the articles, the proportion of Panton-Valentine Leukociden (PVL) genes among MRSA isolates was 54.5%, and the proportion of the qac gene was 100.0%. Distribution of the multilocus sequence type (MLST) and pulsed-field gel electrophoresis (PFGE) of MRSA indicated that MRSA strains were from both hospitals and communities. CONCLUSION: The overall proportions of S. aureus and MRSA contamination in non-hospital environments were high. The outcomes of antibiotic resistance and high proportions of PVL genes indicated that the antibiotic resistance of S. aureus and MRSA were notable. According to the different distributions of MLST and SCCmec of MRSA, we can infer that cross-circulation is within hospitals, communities, and livestock. The results also show that the risk from the MRSA strains was cross-transmitted among the population. High proportions of the qac gene of MRSA might indicate that current disinfection of MRSA has not been achieved, and it might be better to further identify the efficiency of the sterilization processes in a non-hospital environment so that relevant departments can take measures to improve disinfection of MRSA in non-hospital environments.

Smoking behaviors before and after implementation of a smoke-free legislation in Guangzhou, China.

BACKGROUND: According to the partial smoke-free legislation implemented on 1 September 2010 in Guangzhou, China, smoke-free did not cover all indoor areas. Some places have a full smoking ban (100 % smoke-free), other places have a partial smoking ban, and homes have no ban. This study aimed to compare the smoking behaviors before and after implementation of a smoke-free legislation. METHOD: A repeated cross-sectional survey was conducted on smoking-related behaviors with a total of 4,900 respondents before, and 5,135 respondents after the legislation was instituted. For each wave of the survey, a three-stage stratified sampling process was used to obtain a representative sample. Pearson's Chi-square test was used to determine differences of smoking prevalence and quit ratio between the two samples. Logistic regression models were used to examine the associations of a smoke-free legislation with smoking behaviors. RESULTS: The overall daily smoking rate declined significantly from 20.8 % to 18.2 % (p < 0.05), especially among those aged 15-24 years. The quit ratios increased significantly (from 14.5 % to 17.9 %), but remained low among 15-44 year olds. The overall self-reported smoking behaviors in locations with a full smoking ban decreased significantly from 36.4 % to 24.3 % with the greater drops occurring in cultural venues, public transport vehicles, and government offices. Smoking in places with partial smoking bans remained high (89.6 % vs. 90.4 %), although a slight decrease was observed in some of these areas. The implementation of a smoke-free legislation did not lead to more smoking in homes (91.0 % vs 89.4 %), but smoking in homes remained high. CONCLUSIONS: These findings highlight the urgent need for a comprehensive smoke-free legislation covering all public places in Guangzhou, simultaneously educational interventions and campaigns promoting voluntary changes in home smoking need to occur.

Pan-Genome-Wide Association Study of Serotype 19A Pneumococci Identifies Disease-Associated Genes.

Despite the widespread implementation of pneumococcal vaccines, hypervirulent Streptococcus pneumoniae serotype 19A is endemic worldwide. It is still unclear whether specific genetic elements contribute to complex pathogenicity of serotype 19A isolates. We performed a large-scale pan-genome-wide association study (pan-GWAS) of 1,292 serotype 19A isolates sampled from patients with invasive disease and asymptomatic carriers. To address the underlying disease-associated genotypes, a comprehensive analysis using three methods (Scoary, a linear mixed model, and random forest) was performed to compare disease and carriage isolates to identify genes consistently associated with disease phenotype. By using three pan-GWAS methods, we found consensus on statistically significant associations between genotypes and disease phenotypes (disease or carriage), with a subset of 30 consistently significant disease-associated genes. The results of functional annotation revealed that these disease-associated genes had diverse predicted functions, including those that participated in mobile genetic elements, antibiotic resistance, virulence, and cellular metabolism. Our findings suggest the multifactorial pathogenicity nature of this hypervirulent serotype and provide important evidence for the design of novel protein-based vaccines to prevent and control pneumococcal disease. IMPORTANCE It is important to understand the genetic and pathogenic characteristics of S. pneumoniae serotype 19A, which may provide important information for the prevention and treatment of pneumococcal disease. This global large-sample pan-GWAS study has identified a subset of 30 consistently significant disease-associated genes that are involved in mobile genetic elements, antibiotic resistance, virulence, and cellular metabolism. These findings suggest the multifactorial pathogenicity nature of hypervirulent S. pneumoniae serotype 19A isolates and provide implications for the design of novel protein-based vaccines.

Whole-genome sequencing analysis of Klebsiella aerogenes among men who have sex with men in Guangzhou, China.

Klebsiella aerogenes is a common infectious bacterium that poses a threat to human health. Nevertheless, there are limited data on the population structure, genetic diversity, and pathogenicity of K. aerogenes, especially among men who have sex with men (MSM). The present study aimed to clarify the sequence types (STs), clonal complexes (CCs), resistance genes, and virulence factors of popular strains. Multilocus sequence typing was used to describe the population structure of K. aerogenes. The Virulence Factor Database and Comprehensive Antibiotic Resistance Database were used to assess the virulence and resistance profiles. In this study, next-generation sequencing was performed on nasal swabs specimens collected in an HIV Voluntary Counseling Testing outpatient department in Guangzhou, China, from April to August 2019. The identification results showed that a total of 258 K. aerogenes isolates were collected from 911 participants. We found that the isolates were most resistant to furantoin (89.53%, 231/258) and ampicillin (89.15%, 230/258), followed by imipenem (24.81%, 64/258) and cefotaxime (18.22%, 47/258). The most common STs in carbapenem-resistant K. aerogenes were ST4, ST93, and ST14. The population has at least 14 CCs, including several novel ones identified in this study (CC11-CC16). The main mechanism of drug resistance genes was antibiotic efflux. Based on the presence of the iron carrier production genes irp and ybt, we identified two clusters according to virulence profiles. In cluster A, CC3 and CC4 carry the clb operator encoding the toxin. Increased monitoring is needed for the three main ST type strains carried by MSM. The main clone group CC4 has a large number of toxin genes, and it spreads among MSM. Caution is needed to prevent further spread of this clone group in this population. In sum, our results may provide a foundation for the development of new therapeutic and surveillance strategies for treating MSM.

Dose-Response Effects of Low-Dose Ionizing Radiation on Blood Parameters in Industrial Irradiation Workers.

While previous studies have focused on the health effects of occupational exposure of radiations on medical radiation workers, few have analyzed the dose-response relationship between low radiation doses and changes in blood parameters. Even fewer studies have been conducted on industrial worker populations. Using a prospective cohort study design, this study collected health examination reports and personal dose monitoring data from 705 industrial irradiation workers who underwent regular physical examinations at Dongguan Sixth People's Hospital. The dose-response effects of low-dose ionizing radiation on blood parameters were assessed using a generalized linear model and restricted cubic spline model. Red blood cell counts decreased then increased, before decreasing again with increasing ionizing radiation. This was in contrast to the curve of the total platelet count after irradiation. Additionally, a radiation dose of 2.904 mSv was the turning point for the nonlinear curve of hemoglobin count changes. In conclusion, long-term, low-dose ionizing radiation affects blood cell levels in industrial irradiation workers. There is a nonlinear dose-response relationship between red blood cell, platelet, and hemoglobin counts and the cumulative radiation dose. These findings should alert radiation workers to seek preventive medical treatment before the occurrence of any serious hematopoietic disease.