Hospital-treated infectious diseases, genetic susceptibility and risk of type 2 diabetes: A population-based longitudinal study.

BACKGROUND: The longitudinal association between infectious diseases and the risk of type 2 diabetes (T2D) remains unclear. METHODS: Based on the UK Biobank, the prospective cohort study included a total of 396,080 participants without diabetes at baseline. We determined the types and sites of infectious diseases and incident T2D using the International Classification of Diseases 10th Revision codes (ICD-10). Time-varying Cox proportional hazard model was used to assess the association. Infection burden was defined as the number of infection episodes over time and the number of co-occurring infections. Genetic risk score (GRS) for T2D consisted of 424 single nucleotide polymorphisms. RESULTS: During a median of 9.04 [IQR, 8.3-9.7] years of follow-up, hospital-treated infectious diseases were associated with a greater risk of T2D (adjusted HR [aHR] 1.54 [95 % CI 1.46-1.61]), with risk difference per 10,000 individuals equal to 154.1 [95 % CI 140.7-168.2]. The heightened risk persisted after 5 years following the index infection. Bacterial infection with sepsis had the strongest risk of T2D (aHR 2.95 [95 % CI 2.53-3.44]) among different infection types. For site-specific analysis, bloodstream infections posed the greatest risk (3.01 [95 % CI 2.60-3.48]). A dose-response association was observed between infection burden and T2D risk within each GRS tertile (p-trend <0.001). High genetic risk and infection synergistically increased the T2D risk. CONCLUSION: Infectious diseases were associated with an increased risk of subsequent T2D. The risk showed specificity according to types, sites, severity of infection and the period since infection occurred. A potential accumulative effect of infection was revealed.

Hospital-treated infectious diseases, infection burden and risk of Parkinson disease: An observational and Mendelian randomization study.

BACKGROUND: Experimental and cross-sectional evidence has suggested a potential role of infection in the ethology of Parkinson's disease (PD). We aim to examine the longitudinal association of infections with the incidence of PD and to explore whether the increased risk is limited to specific infection type rather than infection burden. METHODS: Based on the UK Biobank, hospital-treated infectious diseases and incident PD were ascertained through record linkage to national hospital inpatient registers. Infection burden was defined as the sum of the number of infection episodes over time and the number of co-occurring infections. The polygenic risk score (PRS) for PD was calculated. The genome-wide association studies (GWAS) used in two-sample Mendelian Randomization (MR) were obtained from observational cohort participants of mostly European ancestry. RESULTS: Hospital-treated infectious diseases were associated with an increased risk of PD (adjusted HR [aHR] 1.35 [95 % CI 1.20-1.52]). This relationship persisted when analyzing new PD cases occurring more than 10 years post-infection (aHR 1.22 [95 % CI 1.04-1.43]). The greatest PD risk was observed in neurological/eye infection (aHR 1.72 [95 % CI 1.32-2.34]), with lower respiratory tract infection (aHR 1.43 [95 % CI 1.02-1.99]) ranked the second. A dose-response association was observed between infection burden and PD risk within each PD-PRS tertile (p-trend < 0.001). Multivariable MR showed that bacterial and viral infections increase the PD risk. CONCLUSIONS: Both observational and genetic analysis suggested a causal association between infections and the risk of developing PD. A dose-response relationship between infection burden and incident PD was revealed.

Organophosphate ester exposure among Chinese waste incinerator workers: Urinary levels, risk assessment and associations with oxidative stress.

Organophosphate esters (OPEs), which are frequently used as flame retardants and plasticizers in versatile products, are readily released to the external environment. Although workers at municipal waste incineration plants may be extensively exposed to OPEs, only scarce health monitoring and risk assessments have been conducted in this population. In this study, we investigated the levels of eight metabolites of organophosphate esters (mOPEs) and the oxidative stress marker 8-hydroxy-2-deoxyguanosine (8-OHdG) in urine samples from 73 waste incinerator workers and 97 general residents from Shenzhen, China between September 2016 and June 2017. The overall detection rate of mOPEs was 82.2 %-100 %, and higher concentrations of di-p-cresyl phosphate and chlorinated mOPEs [bis(2-chloroethyl) phosphate (BCEP), bis(1-chloro-2propyl) phosphate (BCIPP), bis(1,3-dichloro-2-propyl) phosphate) (BDCIPP)] were found among incinerator workers than among general residents. The incinerator workers also showed significantly higher levels of 8-OHdG than general residents, but the measured levels of most mOPEs were not significantly correlated with the level of 8-OHdG; this may be because co-exposure to multiple toxic compounds can lead to oxidative stress. Risk assessment using Monte Carlo simulations revealed that 95 % of the incinerator workers were free from non-carcinogenic effects due to OPEs exposure (hazard index = 0.27, 95 % CI: 0.09, 0.77). However, the carcinogenic risk of tris(2-chloroethyl) phosphate (TCEP) for incinerator workers was between 10-6 and 10-4. These results indicate that incinerator workers are extensively exposed to OPEs, and better protective measures need to be implemented.

Infant exposure to parabens, triclosan, and triclocarban via breastfeeding and formula supplementing in southern China.

Parabens, triclosan (TCS), and triclocarban (TCC) are antimicrobial additives that are widely used in personal care products (PCPs) and may dysregulate infant gut microbiota and induce a series of chronic diseases. Dietary intake may be an underestimated exposure route of such antimicrobial additives in infants, but relevant data remain scarce. Therefore, this study determined five common preservatives, including methyl- (MeP), ethyl- (EtP), propyl- (PrP), butyl- (BuP), and benzyl-paraben (BeP), and two antimicrobials TCS and TCC, in major infant food sources (breastmilk, milk-based infant formula [MIF], and cereal-based complementary food [CCF]) in southern China. The health risks associated with dietary exposure among infants across different months of age were also evaluated. The results demonstrated a high incidence of MeP, EtP, PrP, and BeP in processed infant food products, while TCS and TCC were mainly detected in maternal breastmilk. Notably, MeP and EtP were found in all of the MIFs tested, while MeP, EtP, and BeP were detected in 85.6 %-100 % of the CCFs. By incorporating the human equivalent dose and an additional 10-fold margin of safety for infants into the health risk assessment, the 95th percentile hazard quotient of PrP via the ingestion of breastmilk among neonates exceeded 1. For the first time, the results showed that exposure to PrP via breastmilk intake may pose a considerable health risk to urban neonates in southern China. The health risks caused by antimicrobial exposure via ingesting MIF and CCF among infants were negligible. Thus, we recommend breastfeeding women reduce their consumption of PCPs and processed food, especially during the first month after delivery.

Association between organophosphorus flame retardants exposure and cognitive impairment among elderly population in southern China.

The wide application of organophosphorus flame retardants (OPFRs) in consumer products leads to their ubiquitous occurrence. The neurotoxicity of OPFRs has been raised, whereas evidence from the elderly population were rather scarce. Hence, a case-control study was conducted based on the Shenzhen Aging-related Disorder Cohort. A total of 184 cases [Mini-mental State Examination (MMSE) < 24] and 795 participants as controls (MMSE ≥24) were recruited. Eight metabolites of OPFRs (m-OPFRs) in urine samples were measured, including bis(2-butoxyethyl) phosphate (BBOEP), bis(2-chloroethyl) phosphate (BCEP), bis(1-chloro-2-propyl) phosphate (BCIPP), bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), dibutyl phosphate (DBP), di-o-cresyl phosphate (DOCP), di-p-cresyl phosphate (DPCP) and diphenyl phosphate (DPHP). The detection frequencies of m-OPFRs ranged from 88.8 % to 95.4 %. BCEP had the highest median concentration (0.93 µg/L), followed by BCIPP (0.32 µg/L), DPHP (0.27 µg/L) and DBP (0.20 µg/L). Significant correlations were found between all pairs of urinary m-OPFRs with correlation coefficients ranging from 0.22 to 0.71 (p< 0.05). Logistic regression models showed that urinary concentrations of BDCIPP (adjusted odds ratio [OR]: 1.25, 95 % confidential interval [CI]: 1.04-1.50) and DBP (adjusted OR: 1.10, 95 % CI: 1.01-1.20) were positively associated with lower cognitive functions. Furthermore, a nonlinear dose-response relationship was found between urinary BDCIPP concentration and cognitive decline. To our knowledge, this is the first report on OPFR exposure and cognitive impairment among elderly population. Further toxicological tests of BDCIPP and DBP are needed to illustrate these results.

Antibiotics in urine from general adults in Shenzhen, China: Demographic-related difference in exposure levels.

Misuse or overuse of antibiotics can have a variety of detrimental microbial effects. However, the body burden of antibiotics in the general population is currently unclear. In this cross-sectional study, we determined four classes of widely-applied antibiotics (3 imidazoles, 2 sulfonamides, 5 quinolones, and 2 chloramphenicols) in urine samples from 1170 adult residents in Shenzhen, China. Antibiotics were detected in 30.8 % of all urine samples with concentrations ranging from

Exposure to polycyclic aromatic hydrocarbons and the associations with oxidative stress in waste incineration plant workers from South China.

Waste incineration is one of the most common emission sources of polycyclic aromatic hydrocarbons (PAHs), causing potential occupational exposure in waste incineration workers. However, relative investigations among waste incineration plant workers are still very limited, particularly in China. Therefore, we collected urine specimens from 77 workers in a waste incineration plant as the exposed group, and 101 residents as the control group in Shenzhen, China. Nine mono-hydroxylated PAH metabolites (OH-PAHs) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured, and their internal relationships were explored. The urinary levels of most OH-PAHs and 8-OHdG in the exposed group exhibited high levels versus another group (p < 0.05). We found negative associations between OH-PAHs and 8-OHdG in the control group (p < 0.05), while most of OH-PAHs were not associated with 8-OHdG in the exposed group, which indicated that the exposure to waste incineration could enlarge the level of individual oxidative stress damage. Nevertheless, PAHs were less likely to trigger obvious health risks in exposed workers through estimation of human intake and exposure risks. This study provides a reference for occupational PAH exposure and strengthen the need of health monitoring among incineration workers.

Increasing awareness of HIV pre-exposure prophylaxis (PrEP) and willingness to use HIV PrEP among men who have sex with men: a systematic review and meta-analysis of global data.

INTRODUCTION: Integrated knowledge regarding pre-exposure prophylaxis (PrEP) awareness and willingness to use PrEP can be useful for HIV prevention in high incidence groups. This review summarizes the awareness of PrEP and willingness to use PrEP among men who have sex with men (MSM). METHODS: Online electronic databases were searched before 31 August 2021. A meta-analysis was conducted to pool studies analysing PrEP awareness and willingness to use PrEP. LOESS regression and linear regression were applied to fit the trends over time for the proportion of MSM aware of PrEP and willing to use PrEP. Dose-response meta-analysis (DRMA) was conducted by a restricted cubic spline model to explore the relationship between willingness to use PrEP and selected factors. RESULTS AND DISCUSSION: A total of 156 articles involving 228,403 MSM were included. The pooled proportions of MSM aware of PrEP and willing to use PrEP were 50.0 (95% CI: 44.8-55.2) and 58.6% (95% CI: 54.8-62.4), respectively. PrEP awareness varied among countries with different economic status and different WHO regions, among different publication and research years, PrEP types and support policies. PrEP willingness differed among countries with different economic status and groups with different risks of HIV. The awareness of PrEP increased from 2007 to 2019 with a slope of 0.040260 (p<0.0001), while the proportion of MSM willing to use PrEP decreased from 2007 to 2014 (slope = -0.03647, p = 0.00390) but increased after 2014 (slope = 0.04187, p = 0.03895). The main facilitators of willingness to use PrEP were PrEP awareness, condomless sexual behaviours, high perceived risk of HIV infection and influence of social network. The main barriers were doubts about the efficacy and side effects of PrEP. DRMA results indicated that MSM with more sexual partners and lower level of education were more willing to use PrEP. No publication bias was observed. CONCLUSIONS: The proportions of PrEP awareness and willingness to use PrEP among MSM have increased since 2014, although the awareness was low and the willingness was moderate. Improving awareness of PrEP through increasing access to PrEP-related health education and enhancing risk perceptions of HIV infection could have positive effects on the willingness to use PrEP among MSM.