Social demographics determinants for resistome and microbiome variation of a multiethnic community in Southern Malaysia.

The prevalence of antibiotic-resistant bacteria in Southeast Asia is a significant concern, yet there is limited research on the gut resistome and its correlation with lifestyle and environmental factors in the region. This study aimed to profile the gut resistome of 200 individuals in Malaysia using shotgun metagenomic sequencing and investigate its association with questionnaire data comprising demographic and lifestyle variables. A total of 1038 antibiotic resistance genes from 26 classes were detected with a mean carriage rate of 1.74 ± 1.18 gene copies per cell per person. Correlation analysis identified 14 environmental factors, including hygiene habits, health parameters, and intestinal colonization, that were significantly associated with the resistome (adjusted multivariate PERMANOVA, p < 0.05). Notably, individuals with positive yeast cultures exhibited a reduced copy number of 15 antibiotic resistance genes. Network analysis highlighted Escherichia coli as a major resistome network hub, with a positive correlation to 36 antibiotic-resistance genes. Our findings suggest that E. coli may play a pivotal role in shaping the resistome dynamics in Segamat, Malaysia, and its abundance is strongly associated with the community's health and lifestyle habits. Furthermore, the presence of yeast appears to be associated with the suppression of antibiotic-resistance genes.

[Immunogenicity of group A+C meningococcal polysaccharide conjugate vaccine in infants: A phase â ¢ clinical trial study].

Objective: To evaluate the immunogenicity of group A+C meningococcal polysaccharide conjugate vaccine in infants under 2 years old. Methods: From March 2017 to June 2018, 1 932 healthy infants in Biyang County, Henan Province, who were not vaccinated with meningococcal meningitis vaccine and whose axillary temperature was ≤37.0 ℃, were recruited as participants. The 3 months and 6-11 months old infants were allocated to the experiment group and the control group in a ratio of 1∶1. Infants aged 12-23 months were allocated to the 1-dose group, the 2-dose group and the control group in a ratio of 1∶1∶1, with 276 infants in each group. The infants in the experiment group were intramuscularly injected with freeze-dried group A+C meningococcal polysaccharide conjugate vaccine to be evaluated, and infants in the control group received intramuscular injection of commercially available freeze-dried group A+C meningococcal conjugate vaccine. The venous blood of infants was collected 30 days before the first dose and after the last dose of inoculation, and the antibody seroconversion of each group was determined and compared. Results: The completion rate of immunogenicity study was 95.2% (1 839/1 932). Before inoculation, there was no statistical difference in the geometric mean titer and positive rate of group A+C antibodies between the experiment group and the control group in 3 months and 6-11 months old infants (all P values >0.05). The geometric mean titers and positive rate of group A antibodies in the 1-dose group were higher than those in the control group (all P values <0.05), but there was no statistical difference between the 2-dose group and the control group (all P values >0.05) in infants aged 12-23 months. After inoculation, the differences (95%CI) in the positive conversion rate of group A+C antibodies between the experiment group and the control group were -0.12% (-6.01%-5.77%) and 0.82% (-4.23%-5.86%) in the 3 months old infants. At the age of 6-11 months, the differences were 6.75% (1.71%-11.79%) and -4.32% (-8.73%-0.08%), respectively. At the age of 12-23 months, the differences were 1.02% (-3.80%-5.83%) and -4.40% (-7.79%- -1.01%) in the 2-dose group and -7.22% (-12.90%- -1.54%) and -18.61% (-23.75%- -13.46%) in the 1-dose group, respectively. The geometric mean titers of group A+C antibodies in the 3 months old infants were 48.50 and 63.12, respectively, which had no significant difference from the control group (43.02 and 57.99, respectively) (both P values <0.05). The geometric mean titers of group A+C antibodies in the 6-11 months and 12-23 months old infants were 84.09 and 92.51 (2-dose group), which were higher than those in the corresponding control group (43.10 and 61.83, respectively) (all P values <0.001). Conclusion: Group A+C meningococcal conjugate vaccine has good immunogenicity in infants under 2 years old.

[Boss mass index and mortality from cardiovascular disease in China: a prospective study in rural men].

Objective: To assess the relationship between body mass index (BMI) and death risk of cardiovascular disease (CVD) in rural male population. Methods: 22 282 men aged 40 years older in Tanghe county and Fenghuang county from the cohort of the "Prospective Study on Adult Behavior and Health Risk Factors in China" were selected as subjects of this study. Cox regression model was used to calculate the hazard ratios (HRs) of the death of CVD during the follow-up period with different BMI groups at baseline. Results: The average follow-up period in the two counties was (19.1±8.7) years and 10 828 (48.6%) people died during the follow-up period. 4 504 deaths were attributed to CVD. Among the deaths of CVD, 1 279 cases died of ischemic heart disease (IHD), ischemic stroke (IS) died in 1 201, cases died of died of 1 317 hemorrhagic stroke (HS), other 707 cases. Compared to population with BMI<18 kg/m(2), Cox regression model (adjusting factors of region, age, nationality, education level, occupation, smoking, drinking, blood pressure, blood pressure, etc.) showed that people with BMI between 20-22 kg/m(2) had the lowest risk of CVD death (HR=0.95, 95%CI: 0.83-1.09). But the difference was not statistically significant among each BMI group (P>0.05). The risk of IHD death was the lowest in the population with BMI between 20-22 kg/m(2) (P<0.05) (HR=0.64, 95%CI: 0.52-0.80). There was no statistically significant difference between the risk of IHD death in the population with BMI≥24 kg/m(2) and that in the population with BMI<18 kg/m(2) (P>0.05). There was no statistically significant difference between the risk of IS death and BMI (P>0.05). The death risk of HS in the population with BMI between 18-24 kg/m(2) was higher than that in the population with BMI<18 kg/m(2) (P<0.05). The death risk of the population with BMI between 26-28 kg/m(2) was the highest (HR=1.88, 95%CI:1.18-2.99). Conclusions: The mortality risk of CVD and IHD was the lowest in lean or normal weight group, and HS was higher in overweight group. Maintaining a reasonable weight can reduce the risk of death in patients with CVD.

[Epidemiological characteristics of fatal cases of hand, foot, and mouth disease in children under 5 years old in China, 2008-2018].

Objective: To understand the epidemiological characteristics and risk factors of fatal cases of hand, foot, and mouth disease (HFMD) in children under 5 years old in China from 2008 to 2018, and provide evidence for the development of targeted prevention and control measures and reduction of the incidence of fatal HFMD cases. Methods: The incidence data of reported HFMD cases in China during 2008-2018 were collected from the National Notifiable Disease Surveillance Reporting System of China for the analyses on the demographic characteristics, spatial distribution, diagnosis or reporting and pathogen spectrum of the HFMD cases. Then the risk factors causing deaths were analyzed by using logistic regression model. Results: From 2008 to 2018, a total of 3 646 fatal cases of HFMD in children under 5 years old were reported in China. There were more fatal HFMD cases in boys than in girls (1.82∶1), the death mainly occurred in age group 0 to 2 years (87.71%). Adjusted mortality rate of HFMD in children under 5 years old in China declined from 0.87 per 100 000 in 2010 to 0.11 per 100 000 in 2018 (APC=-23.20%). In the 2 523 laboratory-confirmed deaths, 2 323 (92.07%) were EV-A71 infections, but the constituents of CV-A16 and other enterovirus infections increased. The interval from onset to diagnosis M=2(P(25)-P(75):2-4)d. The interval from onset to death M=3(P(25)-P(75):2-4)d. Age between 0 and 1 years, EV-A71 infection, longer interval between onset and diagnosis, and living in rural area were the risk factors causing fatal HFMD cases. Conclusions: The number of the fatal cases, the rate of mortality and case fatality HFMD in China had shown downward trends since 2010. EV-A71 is still the main pathogen causing fatal cases, but we should pay more attention to gene pattern of the other enteroviruses except EV-A71 and CV-A16. To reduce the risk of the fatal cases we should strengthen the health education about the immunization of EV-A71 inactivated vaccines and reduce the interval from onset to diagnosis in young children in western provinces and rural areas.

Handrubbing with sprayed alcohol-based hand rub: an alternative method for effective hand hygiene.

BACKGROUND: Hand hygiene is crucial in infection prevention and control. It is unclear whether sprayed alcohol-based hand rub (ABHR) is non-inferior to the World Health Organization (WHO)-recommended method of handrubbing with poured ABHR. AIM: To test whether sprayed ABHR can be an alternative (non-inferior) method for effective hand hygiene with/without handrubbing. METHODS: A laboratory experiment was conducted with ABHR (isopropanol 60% v/v) according to European Norm 1500. Hand hygiene was performed by: (1) handrubbing with ABHR poured on to the palm of the hand; (2) handrubbing with sprayed ABHR; and (3) applying sprayed ABHR to hands without handrubbing. Hands were contaminated with Escherichia coli ATCC 10536, followed by hand hygiene and microbiological sampling. A generalized linear mixed model with a random intercept per subject was used to analyse the reduction in bacterial count following hand hygiene. FINDINGS: In total, 19 healthcare workers participated in the study. Handrubbing with sprayed ABHR was non-inferior [margin log10 0.6 colony-forming units (cfu)/mL] to the WHO-recommended method of handrubbing with poured ABHR; bacterial count reductions were log10 3.66 cfu/mL [95% confidence interval (CI) 1.68-5.64] and log10 3.46 cfu/mL (95% CI 1.27-5.65), respectively. Conversely, non-inferiority was not found for sprayed ABHR without handrubbing [bacterial count reduction log10 2.76 cfu/mL (95% CI 1.65-3.87)]. CONCLUSION: Handrubbing with sprayed ABHR was non-inferior to handrubbing with ABHR poured on to the palm of the hand to reduce bacterial counts on hands under experimental conditions. Handrubbing with sprayed ABHR may be an acceptable alternative hand hygiene method pending assessment in other settings and for other pathogens.

Bactericidal and cytotoxic activity of a diarylheptanoid (etlingerin) isolated from a ginger (Etlingera pubescens) endemic to Borneo.

AIMS: The aim of this study was to investigate the antimicrobial activities of Etlingera pubescens, and to isolate and identify the antimicrobial compound. METHODS AND RESULTS: The crude extracts of E. pubescens were obtained through methanol extraction, and evaluated for antimicrobial activities. From this extract, 1,7-bis(3,4-dihydroxyphenyl)heptan-3-yl acetate (etlingerin) was isolated. When compared to curcumin (a compound with a similar chemical structure), etlingerin showed twofold lower minimum inhibitory concentration values while also being bactericidal. Through time kill assay, etlingerin showed rapid killing effects (as fast as 60 min) against the Gram-positive bacteria (Staphylococcus aureus ATCC 43300 and Bacillus subtilis ATCC 8188). Further assessment revealed that etlingerin caused leakage of intracellular materials, therefore suggesting alteration in membrane permeability as its antimicrobial mechanism. Cytotoxicity study demonstrated that etlingerin exhibited approximately 5- to 12-fold higher IC50 values against several cell lines, as compared to curcumin. CONCLUSIONS: Etlingerin isolated from E. pubescens showed better antibacterial and cytotoxic activities when compared to curcumin. Etlingerin could be safe for human use, though further cytotoxicity study using animal models is needed. SIGNIFICANCE AND IMPACT OF THE STUDY: Etlingerin has a potential to be used in treating bacterial infections due to its good antimicrobial activity, while having potentially low cytotoxicity.

Investigation on the antimicrobial activities of gingers (Etlingera coccinea (Blume) S.Sakai & Nagam and Etlingera sessilanthera R.M.Sm.) endemic to Borneo.

AIMS: To investigate the antimicrobial properties of Etlingera coccinea and Etlingera sessilanthera and to isolate and identify the antimicrobial compounds. METHODS AND RESULTS: Extracts were obtained via sequential solvent extraction method using hexane, dichloromethane, ethyl acetate, methanol and water. Antimicrobial activity testing was done using broth microdilution assay against 17 strains of bacteria. The leaf hexane extract of E. coccinea and rhizome hexane extract of E. sessilanthera showed best antimicrobial activities, with minimum inhibitory concentration (MIC) values ranging from 0·016 to 1 mg ml-1 against Gram-positive bacteria. From these active extracts, two antimicrobials were isolated and identified as trans-2-dodecenal and 8(17),12-labdadiene-15,16-dial with MIC values ranging from 4 to 8 µg ml-1 against Bacillus cereus, Bacillus subtilis and Staphylococcus aureus. CONCLUSION: Etlingera coccinea and E. sessilanthera demonstrated good antimicrobial activities against clinically relevant bacteria strains. The antimicrobial compounds isolated showed low MIC values, hence suggesting their potential use as antimicrobial agents. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first to identify the potent antimicrobials from these gingers. The antimicrobials isolated could potentially be developed further for use in treatment of bacterial infections. Also, this study warrants further research into other Etlingera species in search for more antimicrobial compounds.

[Relationship between N-nitrosodimethylamine and risk of digestive tract cancers: a Meta analysis based on cohort studies].

OBJECTIVE: To analyze the relationship between N-nitrosodimethylamine(NDMA)and the risk of digestive tract cancers. METHODS: The papers about the relationship between NDMA and the risk of digestive tract cancers published from 1980 to 2012 were retrieved following databases: Chinese BioMedical Literature Database(CBM), the Chinese Journal Full-text Database(CNKI), Wanfang Database, PubMed and EBSCO. The fix and random effect model was used and statistical analyses were conducted by using RevMan 5.1 software. RESULTS: Thirteen papers were found, in which 7 about digestive tract cancers were used in this Meta analysis. The NDMA had significant positive effect on the incidence of digestive tract cancers(RR=1.12, 95% CI: 1.03-1.21). The relationship between NDMA and esophageal cancer was not significant(RR=1.18, 95%CI: 0.98-1.41)but NDMA could increase the risk of gastric cancer(RR=1.08, 95% CI: 1.00-1.18). For the subtypes of esophageal and gastric cancer, NDMA had positive relationship with esophageal squamous cell carcinoma(RR=1.72, 95% CI: 1.01-2.96), but had no significant relationship with esophageal adenocarcinoma, cardiac carcinoma and gastric adenocarcinoma. CONCLUSION: The population-based cohort studies have showed that the NDMA could significantly increase the risk of digestive tract cancers, but the effects differed with subtypes of esophageal and gastric cancer. However, it is necessary to collect more evidence due to the limited studies and obvious differences in the study design, sampling and exposure measurement of these cohort studies.

[Long-term effect of environmental cadmium exposure on human body's mineral metabolic balance].

OBJECTIVE: To investigate the effect of long-term exposure to environmental cadmium on eight mineral element's metabolic balance of human body. METHODS: To choose a high cadmium area polluted by smelting and mining north of Guangdong province and a cadmium-free area with a similar economic level, and living and eating habit of residents as a contrast from April 2011 to August 2012. Stratified random sampling and clustered sampling method were adopted to choose the non-occupationally cadmium-exposed respondents who have lived in local area for more than 15 years, older than 40 years, having local rice and vegetable as the main dietary source, with simple and relatively stable diet, and without diabetes, kidney disease, thyroid disease, liver disease or other history of chronic disease. This study included 298 respondents, of whom 155 were in cadmium exposure group and 143 in control group. Questionnaires was used to acquire their health status and their morning urine samples were collected. Electrolytically coupled plasma mass spectrometry (ICP-MS) was used to test the concentrations of sodium(Na), magnesium (Mg), phosphorus (P), potassium (K), calcium (Ca), copper (Cu), zinc (Zn) and iodine (I). The Mann-Whitney U test method was used to compare the differences of concentrations of urinary cadmium, Na, Mg, P, K, Ca, Cu, Zn, I, and the ratio of Na to K (Na/K), Ca to P (Ca/P) between exposed group and control group.χ(2) test was used to compare the abnormal rate of urinary cadmium between exposed group and control group. Pearson correlation and multiple regression method were used to investigate the relationship between urinary cadmium levels, gender, age, smoking, passive smoking, and minerals. RESULTS: The urinary cadmium level P50 (P25-P75) in exposed group was 5.45 (2.62-10.68) µg/g·cr, which was higher than that of the control group, which was 1.69 (1.22-2.36) µg/g·cr (Z=-10.49,P<0.001). The abnormal rate of urinary cadmium was 51.6% (80/155), which was higher than that of the control group (2.8 %(4/143)) (χ(2)= 87.56, P<0.001). The urinary Ca, Cu, Zn, and I level P50 (P25-P75) of exposed group were 173.80 (114.40-251.70), 20.55 (14.95-28.44), 520.23 (390.25-647.15), and 246.94 (203.65-342.97) µg/g·cr, which were higher than those in control group (142.42 (96.87-179.11), 15.44 (12.26-20.98), 430.09 (309.85-568.78) and 213.85 (156.70-281.63) µg/g·cr, respectively) (Z values were-4.33,-5.04,-3.47 and-4.24, all P values <0.001). The urinary P, K level P50 (P25-P75) of exposed group were 582.50 (463.20-742.8), 890.10(666.00-1 305.40) µg/g·cr, which were lower than control group (694.50 (546.20-851.17), 1 098.58(904.53-1 479.18) µg/g·cr) (Z values were-3.36,-4.02, all P values <0.001). on Based the results of Pearson correlation analysis, urinary cadmium was positively correlated with urinary Ca, Cu, Zn, and I, and the correlation coefficients were 0.31, 0.61, 0.38, and 0.25, respectively (all P values <0.05). Based on the results of multiple regression analysis, urinary cadmium levels contributed most to the metabolic balance of urinary Ca, Cu, Zn and I. The standardized regression coefficients were 0.31, 0.59, 0.39, and 0.24, respectively (all P values<0.001). CONCLUSION: Long-term environmental exposure to cadmium affected the metabolic balance of Ca, Cu, Zn and I in human body.

[Cadmium burden and renal dysfunction among residents in cadmium-polluted areas: A 3-year follow-up study].

OBJECTIVE: To investigate dynamic change of cadmium body burden and renal dysfunction among residents living in cadmium-polluted areas. METHODS: From April to July of 2011, the cadmium-polluted areas of northern Guangdong province in China was chosen as the study site. Based on the levels of cadmium pollution in soil and rice, the survey areas were divided into low exposed group (average concentration of cadmium was 0.15-0.40 mg/kg, 0.5-1.0 mg/kg in rice and soil, respectively) and high exposed group (average concentration of cadmium was >0.40 mg/kg, >1.0 mg/kg in rice and soil, respectively). Stratified random sampling and cluster sampling method of epidemiological investigations were carried out among 414 local residents who lived in cadmium exposure areas for more than 15 years, aged above 40, and without occupational cadmium exposure, including 168 and 246 residents in low and high exposed group, respectively. From March to June of 2014, 305 respondents of those who participated in 2011 were successfully traced, including 116 and 189 respondents in low and high exposed group, respectively. We used health questionnaires to acquire their health status. Home-harvested rice and vegetable samples were collected using quartering method for detection of cadmium level, including 190 rice samples, 161 vegetable samples in 2011 and 190 rice samples, 153 vegetable samples in 2014. Urine specimens of residents were collected for the detection of urinary cadmium and creatinine as well as renal dysfunction biomarkers, namely, N-acetyl-beta-D-glucosamidase (NAG) and ß2-microglobulin (ß2-MG), respectively. In 2011 and 2014, Chi-square test was used to investigate the differences of abnormality of cadmium concentration in rice, vegetables and urinary cadmium, ß2-MG, and NAG that were expressed as odds ratio(OR) and 95% confidence intervals (95%CI). RESULTS: In 2011 and 2014, cadmium concentration P50 (P25-P75) in rice was 0.43 (0.17-1.10) mg/kg, and 0.42 (0.20-1.14) mg/kg, respectively (Z=-0.77,P=0.440). In 2011 and 2014, cadmium concentrations P50 (P25-P75) in vegetables were 0.13 (0.07-0.34) mg/kg, and 0.25(0.12-0.59) mg/kg, respectively, with abnormal rates of 38.5%(62/161) and 60.8%(93/153), respectively. In 2014, both average concentration and abnormal rate of cadmium in vegetables were higher than those in 2011 (Z=-4.69, P<0.001 and χ(2)=15.58,P<0.001). Concentrations of urinary cadmium P50 (P25-P75) in high exposed group were 7.90 (3.96-14.91) µg/g creatinine, 8.64 (4.56-17.60) µg/g creatinine in 2011 and 2014, respectively. Contrary to that in 2011, urinary cadmium of high exposed group was significantly increased in 2014 (Z=-2.80, P=0.005). In 2011 and 2014, concentrations of ß2-MG, NAG P50 (P25-P75) were 0.15(0.07-0.29) µg/g creatinine, 0.15 (0.07-0.45) µg/g creatinine, and 7.12 (5.05-10.65) U/g creatinine, 13.55(9.1-19.84) U/g creatinine, respectively, with abnormal rates of 7.5% (23/305), 15.1% (46/305), 8.2% (25/305) , and 33.8% (103/305), respectively. Compared with baseline in 2011, average concentrations of ß2-MG, NAG significantly increased in 2014 (Z=-2.263, P=0.024 and Z=-12.52, P<0.001), and abnormal rates of ß2-MG, NAG were also higher in 2014 (χ(2)=15.61 , P<0.001 and χ(2)=64.72, P<0.001), with odds ratio(OR) of 2.00 (95%CI:1.23-3.24) and 4.12 (95%CI:2.87-5.92). CONCLUSION: Environmental cadmium pollution of crops such as rice and vegetables in survey areas continued to remain high. Body burden of cadmium might kept at sustainably high levels and renal dysfunction was worsened after continuous, long-term cadmium exposure. Our results suggested that NAG might be more sensitive than ß2-MG to serve as an indicator for an individual's future tubular function.

Effects of L-malate on physical stamina and activities of enzymes related to the malate-aspartate shuttle in liver of mice.

L-malate, a tricarboxylic acid cycle (TCA) intermediate, plays an important role in transporting NADH from cytosol to mitochondria for energy production and may be involved in the beneficial effects of improving physical stamina. In the present study, we investigated the effects of L-malate on the performance of forced swimming time and blood biochemical parameters related to fatigue - blood urea nitrogen (BUN), glucose (Glc), creatine kinase (CK),total protein (TP) and lactic acid (LA). To investigate the effects of L-malate on the malate-aspartate shuttle and energy metabolism in mice, the activities of enzymes related to the malate-aspartate shuttle were measured. L-malate was orally administered to mice continuously for 30 days using a feeding atraumatic needle. The swimming time was increased by 26.1 % and 28.5 %, respectively, in the 0.210 g/kg and 0.630 g/kg L-malate-treated group compared with the control group. There were no differences in the concentrations of Glc, BUN and TP between the L-malate-treated groups and the control groups. However, the levels of CK were significantly decreased in the L-malate-treated groups. The results predict a potential benefit of L-malate for improving physical stamina and minimizing muscle damage during swimming exercise. The activities of cytosolic and mitochondrial malate dehydrogenase were significantly elevated in the L-malate-treated group compared with the control group. These enzymatic activities may be useful indicators for evaluating changes affecting the malate-aspartate shuttle and energy metabolism in the liver of mice.

Notch signaling in development and disease.

Notch receptors and ligands were first identified in flies and worms, where they were shown to regulate cell proliferation, cell differentiation, and, in particular, binary cell fate decisions in a variety of developmental contexts. The first mammalian Notch homolog was discovered to be a partner in a chromosomal translocation in a subset of human T-cell leukemias. Subsequent studies in mice and humans have shown that Notch signaling plays essential roles at multiple stages of hematopoiesis, and also regulates the development or homeostasis of cells in many tissues and organs. Thus, it is not surprising that mutations which disrupt Notch signaling cause a wide range of cancers and developmental disorders. Perhaps because it is so widely used, Notch signaling is subject to many unusual forms of regulation. In this review, we will first outline key aspects of Notch signaling and its regulation by endocytosis, glycosylation, and ubiquitination. We will then overview recent literature elucidating how Notch regulates cell-lineage decisions in a variety of developmental contexts. Finally, we will describe the roles of dysregulated Notch signaling in causing several types of cancer and other pathologies.

Clam enterocystoplasty in general urological practice.

A series of 45 patients (31 female) underwent clam enterocystoplasty for urgency and incontinence. The majority had detrusor instability. Prolonged conservative treatment had failed in all cases. Improvement occurred in 71% and those younger than 30 years had better overall results; 29% remained incontinent, with 9% requiring a urinary diversion. Many patients did not achieve maximum benefit until 9 months post-operatively. Surgery had no statistically significant effect on any urodynamic parameter and post-operative complications were common. The operation was performed in either the coronal (19) or the sagittal plane (26); this did not influence results. In general, surgery was found to be technically simpler in the sagittal group and it is recommended that this becomes the standard procedure. We feel that this operation involves major surgery and should only be offered with reluctance.