Effectiveness of the booster dose of inactivated COVID-19 vaccine against Omicron BA.5 infection: a matched cohort study of adult close contacts.

BACKGROUND: Although COVID-19 vaccines and their booster regimens protect against symptomatic infections and severe outcomes, there is limited evidence about their protection against asymptomatic and symptomatic infections in real-world settings, particularly when considering that the majority of SARS-CoV-2 Omicron infections were asymptomatic. We aimed to assess the effectiveness of the booster dose of inactivated vaccines in mainland China, i.e., Sinopharm (BBIBP-CorV) and Sinovac (CoronaVac), against Omicron infection in an Omicron BA.5 seeded epidemic. METHODS: Based on an infection-naive but highly vaccinated population in Urumqi, China, the study cohort comprised all 37,628 adults who had a contact history with individuals having SARS-CoV-2 infections, i.e., close contacts, between August 1 and September 7, 2022. To actively detect SARS-CoV-2 infections, RT-PCR tests were performed by local authorities on a daily basis for all close contacts, and a testing-positive status was considered a laboratory-confirmed outcome. The cohort of close contacts was matched at a ratio of 1:5 with the fully vaccinated (i.e., 2 doses) and booster vaccinated groups (i.e., 3 doses) according to sex, age strata, calendar date, and contact settings. Multivariate conditional logistic regression models were adopted to estimate the marginal effectiveness of the booster dose against Omicron BA.5 infection after adjusting for confounding variables. Subgroup analyses were performed to assess vaccine effectiveness (VE) in different strata of sex, age, the time lag from the last vaccine dose to exposure, and the vaccination status of the source case. Kaplan-Meier curves were employed to visualize the follow-up process and testing outcomes among different subgroups of the matched cohort. FINDINGS: Before matching, 37,099 adult close contacts were eligible for cohort enrolment. After matching, the 2-dose and 3-dose groups included 3317 and 16,051 contacts, and the proportions with Omicron infections were 1.03% and 0.62% among contacts in the 2-dose and 3-dose groups, respectively. We estimated that the adjusted effectiveness of the inactivated booster vaccine versus 2 doses against Omicron infection was 35.5% (95% CI 2.0, 57.5). The booster dose provided a higher level of protection, with an effectiveness of 60.2% (95% CI 22.8, 79.5) for 15-180 days after vaccination, but this VE decreased to 35.0% (95% CI 2.8, 56.5) after 180 days. Evidence for the protection of the booster dose was detected among young adults aged 18-39 years, but was not detected for those aged 40 years or older. INTERPRETATION: The receipt of the inactivated vaccine booster dose was associated with a significantly lower Omicron infection risk, and our findings confirmed the vaccine effectiveness (VE) of booster doses against Omicron BA.5 variants. Given the rapid evolution of SARS-CoV-2, we highlight the importance of continuously monitoring the protective performance of vaccines against the genetic variants of SARS-CoV-2, regardless of existing vaccine coverage.

The role of ambra1 in Pb-induced developmental neurotoxicity in zebrafish.

Lead is a highly toxic metal that displays developmental neurotoxicity. Ambra1 plays a crucial role in embryonic neural development. At present, the role of Ambra1 in lead-induced developmental neurotoxicity remains unknown. In this study, we investigated the mechanism of Ambra1 concerning its role in lead-induced neurotoxicity. Zebrafish (Danio rerio) embryos were exposed to 0.1, 1, or 10 µM Pb until 5 days post-fertilization, and their locomotor activity was significantly impaired by the 10 µM treatment. Meanwhile, Pb reduced the expression of ambra1a and ambra1b in the brain at 48 and 72 h post-fertilization. Overexpression of ambra1a or ambra1b reversed Pb-induced alterations in locomotor activity, and decreased the apoptotic cell numbers in the brains of Pb-treated zebrafish. Our data reveal a novel protective role of Ambra1 against Pb-induced neural damage in the developing zebrafish.

Joint effect between bisphenol A and alcohol consumption on benign prostatic hyperplasia: A case-control study in Hong Kong Chinese males.

BACKGROUND: Whether bisphenol A (BPA) exposure is a contributing factor to benign prostatic hyperplasia (BPH) remains unclear. This study evaluated the association between chronic BPA exposure and BPH risk, and explored whether this association was modified by alcohol drinking. METHODS: This study included a total of 650 BPH cases and 650 controls recruited from the same hospital in Hong Kong during 2011-2016. Chronic BPA exposure level was estimated by a validated cumulative BPA exposure index (CBPAI). We performed unconditional logistic regression model to examine the association of BPH risk with potential sources of BPA exposure via oral intake and CBPAI. We further tested the interactions between CBPAI and alcohol consumption habits on BPH risk. RESULTS: A positive exposure-response relationship was observed between CBPAI and BPH risk. Frequent BPA exposure via oral intake of foods heated in a plastic box/bag (odds ratio [OR] = 3.52, 95% confidence interval [CI]: 1.51-8.22), cooling water in a plastic bottle (OR = 2.65, 95% CI: 1.33-5.27), or using a plastic cup to contain hot water (OR = 4.14, 95% CI: 1.02-16.89), was significantly associated with increased BPH risk. Compared with nonalcohol drinkers, alcohol drinkers was insignificantly associated with BPH risk (OR = 1.10, 95% CI: 0.77-1.57), but it demonstrated a more remarkable positive gradient between CBPAI exposure and BPH risk among alcohol drinkers, indicating an additive interaction between CBPAI and alcohol on BPH risk (synergy index = 4.24, 95% CI: 1.21-14.94). CONCLUSIONS: Chronic oral BPA exposure increased BPH risk with a positive exposure-response relationship among Hong Kong Chinese, and alcohol drinking amplified the effect of BPA on BPH. Hence, minimizations of containing food or water/beverage in plastic containers and drinking alcohol are recommended in the community to mitigate BPH risk. Future larger and designated studies are warranted.

Changes in physical activity and rest-activity circadian rhythm among Hong Kong community aged population before and during COVID-19.

BACKGROUND: This study aims to determine the changes in physical activity and actigraphy-measured rest-activity circadian rhythm among Hong Kong community aged population before and during the outbreak of COVID-19. METHODS: This is a three repeated measure population-based cross-sectional study. We recruited community older men aged > 60 years in three periods of the COVID-19 outbreak in Hong Kong, i.e., before the COVID-19 outbreak (2 July 2019-8 January 2020), between the 2nd and 3rd waves of COVID-19 (23 June 2020-9 July 2020), and during the 3rd wave of COVID-19 (15 September 2020-29 September 2020). Participants reported detailed information on their physical activity habits using the International Physical Activity Questionnaire and wore actigraphs continuously for 7 days (168 h). The actigraph data were then transferred to four rest-activity circadian rhythm parameters: midline statistic of rhythm (MESOR), amplitude, acrophase and percent rhythm. Multivariate logistic regression was performed to estimate the association of period effect of COVID-19 on physical activity and rest-activity circadian rhythm parameters. RESULTS: Among the 242 community older men, 106 (43.8%) of them were recruited before the COVID-19 outbreak, 66 (27.3%) were recruited between the 2nd and 3rd waves of COVID-19, and 70 (28.9%) were recruited during the late phase of the 3rd wave of COVID-19. Compared with those recruited before COVID-19, participants recruited between the 2nd and 3rd waves of COVID-19 had lower physical activity (adjusted odds ratio (AOR) = 2.03, 95% confidence interval (95%CI) =1.05-3.93), MESOR (AOR = 2.05, 95%CI = 1.01-4.18), and amplitude (AOR = 1.91, 95%CI = 0.95-3.83). There was no difference in physical activity or circadian rhythm parameters between subjects recruited before and during the late phase of the 3rd wave. CONCLUSIONS: This study found that the effect of COVID-19 on physical activity and rest-activity circadian rhythm for the community people may be short-term, indicating strong resilience of the community population. Although maintaining physical activity are encouraged for the older adults to sustain good health, a rebound in their physical activity may be a sign for the next wave of outbreak if insufficient social distancing and population protection are facilitated.

Association of residential greenness with incident allergic rhinitis among adults: A prospective analysis of UK Biobank.

BACKGROUND: Limited studies have assessed the impact of residential greenness exposure on allergic rhinitis in adults, and its relationship with ambient air pollutants remains unknown. OBJECTIVE: To investigate the association of residential greenness with allergic rhinitis incidence and explore the mediation effects of ambient air pollutants in adults using data from a prospective cohort study in UK Biobank. METHODS: Greenness was defined as the area-weighted mean of greenness coverage based on the land used data from the Generalized Land Use Database for England (GLUD) 2005 in the UK Biobank. Multiple Cox proportional hazard models and a generalized additive model incorporating restricted cubic splines were used to model the potential nonlinear effect of residential greenness on allergic rhinitis incidence and the potential mediation effect of ambient air pollutants. RESULTS: Among the 281,699 subjects included in the analysis, 3260 allergic rhinitis incident cases occurred after a median follow-up of 14 years. With per 10% increase in residential greenness at a 300-m buffer, a 2.5% (95% CI: 1.0%, 4.0%) decreased risk of allergic rhinitis was observed. An L-shaped, non-linear dose-response relationship was indicated with a threshold of 54.9% greenness above which no excess allergic rhinitis risk was seen. PM10 partially mediated the relationship between greenness and allergic rhinitis incidence with a mediation effect of 26.9% (95% CI: 12.6%, 41.2%). A similar pattern of association was found at 1000-m buffer size. CONCLUSION: This study demonstrates a significant beneficial effect of residential greenness on reducing allergic rhinitis incidence. Greenness may erase air pollutants and mitigate the rhinitis risk from air pollution.

Estimated daily intake and cumulative risk assessment of organophosphate esters and associations with DNA damage among e-waste workers in Hong Kong.

Organophosphate esters (OPEs) are extensively used as additives in various products, including electronic equipment, which becomes e-waste when obsolete. Nevertheless, no study has evaluated OPEs exposure levels and the related health risks among e-waste workers in Hong Kong. Therefore, 201 first-spot morning urine samples were collected from 101 e-waste workers and 100 office workers to compare eight urinary OPE metabolites (mOPEs) levels in these groups. The concentrations of six mOPEs were similar in e-waste workers and office workers, except for significantly higher levels of diphenyl phosphate (DPHP) in e-waste workers and bis(1-chloro-2propyl) phosphate (BCIPP) in office workers. Spearman correlation analysis showed that most non-chlorinated mOPEs were correlated with each other in e-waste workers (i.e., nine out of ten pairs, including di-p-cresyl phosphate (DpCP) and di-o-cresyl phosphate (DoCP), DpCP and bis(2-butoxyethyl) phosphate (BBOEP), DpCP and DPHP, DpCP and dibutyl phosphate (DBP), DoCP and BBOEP, DoCP and DPHP, DoCP and DBP, BBOEP and DPHP, DPHP and DBP), indicating that handling e-waste could be the exposure source of specific OPEs. The median values of estimated daily intake (EDI) and hazard quotient (HQ) suggested that the health risks from OPEs exposures were under the recommended thresholds. However, linear regression models, Quantile g-computation, and Bayesian kernel machine regression found that urinary mOPEs elevated 8-hydroxy-2-deoxyguanosine (8-OhdG) levels individually or as a mixture, in which DPHP contributed prominently. In conclusion, although e-waste might not elevate the internal OPEs levels among the participating Hong Kong e-waste workers, attention should be paid to the potential DNA damage stimulated by OPEs under the currently recommended thresholds.

Assessing Neurobehavioral Alterations Among E-waste Recycling Workers in Hong Kong.

Background: E-waste workers in Hong Kong are handling an unprecedented amount of e-waste, which contains various neurotoxic chemicals. However, no study has been conducted to evaluate the neurological health status of e-waste workers in Hong Kong. This study aimed to evaluate the prevalence of neurobehavioral alterations and to identify the vulnerable groups among Hong Kong e-waste workers. Methods: We recruited 109 Hong Kong e-waste workers from June 2021 to September 2022. Participants completed standard questionnaires and wore a GENEActiv accelerometer for seven days. Pittsburgh Sleep Quality Index and Questionnaire 16/18 (Q16/18) were used to assess subjective neurobehavioral alterations. The GENEActiv data generated objective sleep and circadian rhythm variables. Workers were grouped based on job designation and entity type according to the presumed hazardous level. Unconditional logistic regression models measured the associations of occupational characteristics with neurobehavioral alterations after adjusting for confounders. Results: While dismantlers/repairers and the workers in entities not funded by the government were more likely to suffer from neurotoxic symptoms in Q18 (adjusted odds ratio: 3.18 [1.18-9.39] and 2.77 [1.10-7.46], respectively), the workers from self-sustained recycling facilities also have poor performances in circadian rhythm. Results also showed that the dismantlers/repairers working in entities not funded by the government had the highest risk of neurotoxic symptoms compared to the lowest-risk group (i.e., workers in government-funded companies with other job designations). Conclusion: This timely and valuable study emphasizes the importance of improving the working conditions for high-risk e-waste workers, especially the dismantlers or repairers working in facilities not funded by the government.

All cause and cause specific mortality associated with transition to daylight saving time in US: nationwide, time series, observational study.

Objectives: To estimate the association between the transition to daylight saving time and the risks of all cause and cause specific mortality in the US. Design: Nationwide time series observational study based on weekly data. Setting: US state level mortality data from the National Center for Health Statistics, with death counts from 50 US states and the District of Columbia, from the start of 2015 to the end of 2019. Population: 13 912 837 reported deaths in the US. Main outcome measures: Weekly counts of mortality for any cause, and for Alzheimer's disease, dementia, circulatory diseases, malignant neoplasms, and respiratory diseases. Results: During the study period, 13 912 837 deaths were reported. The analysis found no evidence of an association between the transition to spring daylight saving time (when clocks are set forward by one hour on the second Sunday of March) and the risk of all cause mortality during the first eight weeks after the transition (rate ratio 1.003, 95% confidence interval 0.987 to 1.020). Autumn daylight saving time is defined in this study as the time when the clocks are set back by one hour (ie, return to standard time) on the first Sunday of November. Evidence indicating a substantial decrease in the risk of all cause mortality during the first eight weeks after the transition to autumn daylight saving time (0.974, 0.958 to 0.990). Overall, when considering the transition to both spring and autumn daylight saving time, no evidence of any effect of daylight saving time on all cause mortality was found (0.988, 0.972 to 1.005). These patterns of changes in mortality rates associated with transition to daylight saving time were consistent for Alzheimer's disease, dementia, circulatory diseases, malignant neoplasms, and respiratory diseases. The protective effect of the transition to autumn daylight saving time on the risk of mortality was more pronounced in elderly people aged ≥75 years, in the non-Hispanic white population, and in those residing in the eastern time zone. Conclusions: In this study, transition to daylight saving time was found to affect mortality patterns in the US, but an association with additional deaths overall was not found. These findings might inform the ongoing debate on the policy of shifting daylight saving time.

Association of preserved ratio impaired spirometry with mortality: a systematic review and meta-analysis.

BACKGROUND: Preserved ratio impaired spirometry (PRISm) is prevalent within the general population. Increased mortality has been reported among subjects with PRISm, but the evidence has never been summarised. This systematic review aims to synthesise evidence on the association between PRISm and the risk of all-cause, cardiovascular and respiratory-related mortality. METHODS: We systematically searched MEDLINE, Embase and Web of Science for population-based cohort studies from inception to April 2023 using the terms related to impaired spirometry and mortality. Titles and abstracts were screened to identify eligible studies that reported mortality estimates for individuals with PRISm. We excluded studies that adopted other definitions of impaired spirometry, had a specific study setting (e.g. HIV patients), had an insufficient follow-up period (<1 year) or reported duplicated data. Random-effects meta-analysis was used to produce pooled hazard ratio (HR) with 95% confidence intervals. Between-study heterogeneity was assessed with I2. RESULTS: Eight studies met the inclusion criteria involving 40 699 individuals with PRISm. All included studies reported increased risk of all-cause mortality among adults with PRISm. Meta-analysis showed that PRISm was associated with an increased risk of all-cause mortality (pooled HR 1.71, 95% CI 1.51-1.93; I2=64%), cardiovascular mortality (pooled HR 1.57, 95% CI 1.44-1.72; I2=35%) and respiratory-related mortality (pooled HR 1.97, 95% CI 1.55-2.49; I2=0%). CONCLUSIONS: Individuals with PRISm have a significantly increased risk of mortality compared with those with normal spirometry.

Evaluation of the oxidative toxicity induced by lead, manganese, and cadmium using genetically modified nrf2a-mutant zebrafish.

Heavy metal pollution has become a serious environmental concern and a threat to public health. Three of the most common heavy metals are cadmium (Cd), lead (Pb), and manganese (Mn). Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important transcription factor activated in the response to oxidative stress. In this study, mutant zebrafish with an nrf2a deletion of 7 bp were constructed by the CRISPR/Cas9 system to investigate the oxidative toxicity of these three heavy metals. The results of general toxicity tests showed that Pb exposure did not cause significant damage to mutant zebrafish compared with wild-type (WT) zebrafish. However, high Mn exposure increased mortality and malformation rates in mutant zebrafish. Of concern, Cd exposure caused significant toxic damage, including increased mortality and malformation rates, apoptosis of brain neurons, and severe locomotor behavior aberration in mutant zebrafish. The results of qRT-PCR indicated that Cd exposure could induce the activation of genes related to oxidative stress resistance in WT zebrafish, while the expression of these genes was inhibited in mutant zebrafish. This study showed that of the three heavy metals, Cd had the strongest oxidative toxicity, Mn had medium toxicity, and Pb had the weakest toxicity.

Association between matched chronotype and poor mental health among shift workers: a systematic review and meta-analysis.

BACKGROUND: Nearly 0.7 billion workers are involved in the shift work system, leading to concerns about its potential impacts on the large-scale population mental health. This study aimed to synthesise evidence of the associations between matched chronotype and the risk of poor mental health among shift workers. METHODS: Six computerised databases were searched from inception to September 2022. Observational studies were selected if they reported any association between common mental health parameters and chronotype scores/types of shift workers. The Preferred Reporting Items for Systematic Reviews and Meta-analyses checklist was followed. We extracted adjusted risk estimates to calculate pooled effect sizes and explore sources of heterogeneity. The study was registered in PROSPERO: CRD42022357437. RESULTS: Fourteen studies including 49 909 workers were identified. Ever shift workers had a higher risk of poor mental health than the day workers (pooled OR 1.15, 95% CI 1.03 to 1.28; I2=14%, p=0.29), with the evening chronotype ever shift workers having a 1.47 times higher risk than those who worked during the day (pooled OR 1.47, 95% CI 1.13 to 1.91; I2=42%, p=0.16). Sensitivity analysis excluding studies with the highest risk of bias of each group demonstrated consistent findings. CONCLUSIONS: Evening chronotype ever shift workers have poorer mental health than shift workers with other chronotypes. Chronotype remains unrecognised in the contemporary rostering system, making it a hidden contributor to occupational mental health. Work-related physical and mental stresses may be prevented/mitigated with further investigation on optimising shift work schedule combined with individual chronotype preference.

Association of circadian rhythm with mild cognitive impairment among male pneumoconiosis workers in Hong Kong: a cross-sectional study.

Weakened circadian activity rhythms (CARs) were associated with mild cognitive impairment (MCI) in the general population. However, it remains unclear among pneumoconiosis patients. We aimed to address this knowledge gap. This cross-sectional study comprised 186 male pneumoconiosis patients (71.3 ± 7.8 years) and 208 healthy community men. Actigraphy was used to determine CARs parameters (percent rhythm, amplitude, MESOR, and acrophase). Values below the corresponding medians of the CARs parameters represented weakened CARs. The Cantonese version of Mini-Mental State Examination (CMMSE) was used to assess cognitive function, MCI, and the composite outcome of MCI plus cognitive impairment. Compared with the community referents, pneumoconiosis patients had worse cognition and dampened CARs. Compared with the community referents or pneumoconiosis patients with robust circadian rhythm, pneumoconiosis patients with weakened circadian rhythm were consistently associated with increased risk of MCI and the composite outcome. However, significant association was only observed between MESOR and the composite outcome (adjusted OR = 1.99, 95%: 1.04-3.81). A delayed phase of CARs was insignificantly associated with MCI and the composite outcome. Our findings showed that weakened CARs were associated with worse cognitive function among male pneumoconiosis workers. Intervention in improving CARs may mitigate cognitive deterioration in male pneumoconiosis workers.

Sex differences in the associations of sleep-wake characteristics and rest-activity circadian rhythm with specific obesity types among Hong Kong community-dwelling older adults.

BACKGROUND: Sex differences exist in sleep characteristics, circadian rhythm and body composition but the evidence on their associations with obesity risk remains unclear. We aimed to examine sex differences in the associations of sleep-wake cycle and rest-activity circadian rhythm with specific obesity types among aged Chinese population. METHODS: This report pooled data from 2 population-based surveys conducted during 4/2018-9/2018 and 7/2019-9/2020. All participants wore actigraphy on wrists for 7 days to measure their objective sleep patterns and rest-activity circadian rhythm. We measured participants' anthropometric data, and obtained their body weight, body fat percentage(fat%), visceral fat rating, muscle mass by calibrated bioelectrical impedance analysis device. Hand-grip strength was assessed by Jamar Hydraulic hand dynamometer. Multinomial logistic regression was performed to assess the odds ratio(OR) and 95% confidence intervals(95%CI). RESULTS: We recruited 206 male and 134 female older adults with complete actigraphy data, with obesity prevalence of 36.9% and 31.3%, respectively. Male participants who had delayed sleep-wake cycle(i.e.,sleep-onset-time and wake-up time) was associated with higher risk of obesity(late sleep-onset-time:OR=5.28, 95%CI=2.00-13.94), and the results remained consistent for different types of obesity. Males with late M10(i.e., most active 10-hours) onset had higher adipose outcomes with an adjusted OR of 2.92(fat%:95%CI=1.10-7.71; visceral fat:95%CI=1.12-7.61). Among female participants, those with lower relative amplitude were associated with higher BMI and lower hand-grip strength. CONCLUSIONS: This study revealed that circadian rhythm fragmentation was associated with obesity and muscle loss. Promoting good sleep quality and maintaining robust circadian rhythm and physical activity can prevent poor muscle strength among older adults.

Neurotoxicity and gene expression alterations in zebrafish larvae in response to manganese exposure.

Manganese (Mn) is an essential trace element, but excessive exposure can damage mental, cognitive, and motor functions. Although many studies have reported the toxicity of Mn, the underlying mechanism remains unclear. Here, wild-type and/or Tg(NBT:DsRed) zebrafish embryos/larvae were exposed to different dosages of Mn to determine the effects on mortality, malformation, and hatching rates. A video tracking system was used to analyze the locomotor activities of zebrafish larvae. The terminal deoxynucleotidyl transferase dUTP nick end labeling assay and acridine orange staining were performed to monitor cell apoptosis, while dopamine transporter and tyrosine hydroxylase (TH) expression were detected by immunohistochemical staining. Meanwhile, transcriptome sequencing of the head tissues of zebrafish larvae was performed to search for molecular targets of Mn neurotoxicity. The results showed that Mn exposure increased the mortality and malformation rates of zebrafish larvae, and significantly reduced swim distance and velocity. In addition, the proportion of apoptotic dopaminergic neurons increased, while TH expression significantly decreased. The results of transcriptome sequencing showed that a large number of differentially expressed genes associated with apoptosis and DNA damage repair were upregulated, consistent with the above results. Meanwhile, Western blot analysis showed that higher exposure level of Mn could induce activation of MAPK pathway. These data demonstrate that Mn exposure can damage dopaminergic neurons and cause apoptosis, which has detrimental effects on the motor abilities of zebrafish larvae.

Differences in Sleep Patterns and Mental Health Problems During Different Periods of COVID-19 Outbreak Among Community-Dwelling Older Men in Hong Kong.

Objectives: To determine the association of sleep with mental health among Hong Kong community-dwelling older men in the context of the COVID-19 pandemic. Methods: This additional analysis was derived from the community-dwelling men aged >60 recruited during three COVID-19 outbreaks (i.e., pre-outbreak, between the second and third wave, and during the third wave) in Hong Kong from July 2019 to September 2020. Sleep and mental health were measured by Pittsburgh Sleep Quality Index questionnaire and Hospital Anxiety and Depression Scale, respectively. Multivariate logistic regression models were performed for the associations between sleep and mental health after considering the outbreaks' impact. Results: Subjects enrolled between the second and third wave tended to have better sleep but worse mental health. Positive associations between poor sleep and depression (AOR = 3.27, 95% CI: 1.60-7.03) and anxiety (AOR = 2.40, 95% CI: 1.07-5.76) were observed. The period "between second and third wave" was positively associated with depression (AOR = 2.65, 95% CI: 1.22-5.83), showing an additive interaction with poor sleep. Conclusion: The positive association between poor sleep and depression was aggravated by the period "between the second and third wave" among community-dwelling older males in Hong Kong.

Joint toxicity of lead and cadmium on the behavior of zebrafish larvae: An antagonism.

Although the individual toxicity of lead (Pb) and cadmium (Cd) was intensively studied, little is known about their joint toxicity on the development of circadian behavioral rhythm. Therefore, we co-exposed zebrafish to Pb and Cd to investigate the alterations of behavioral rhythm and the potential mechanism. Inductively coupled plasma mass spectrometry analysis was used to detect the internal exposure level of heavy metals. The behavioral rhythm was monitored by a video-track tracking system. The changes of gene expression regarding melatonin-related molecules and clock genes were analyzed by quantitative polymerase chain reaction and JTK-Cycle analysis. The results showed that the level of Pb2+ and Cd2+ accumulated in the co-exposure group were significantly lower than that in the Pb or Cd group. Exposed to Pb reduced the locomotor activity; the behavioral rhythms were disrupted by Cd, while the pattern in the co-exposure group showed an antagonistic effect on locomotor activity and behavioral rhythm. The expression rhythm of aanat1 was disturbed and the expression levels of mtnr1aa and mtnr1bb were decreased by co-exposure treatment, but mtnr1c was increased in Pb and Cd group, respectively. Exposure to Cd caused the disruption of expression rhythm in clock genes, like clock1b, clock2, and cry1b, while only the rhythm of clock2 was disrupted in the co-exposure group. The results suggest that the behavioral rhythm disruption caused by Cd exposure is associated with the disturbance of certain circadian genes, whereas Pb exposure only abates the locomotor activity; an antagonistic effect on the behavioral pattern when co-exposed zebrafish larvae to Pb and Cd.

A protective role of autophagy in Pb-induced developmental neurotoxicity in zebrafish.

Lead (Pb) is one of the most toxic heavy metals and has aroused widespread concern as it can cause severe impairments in the developing nervous system. Autophagy has been proposed as an injury factor in Pb-induced neurotoxicity. In this study, we used zebrafish embryo as a model, measured the general toxic effects of Pb, and investigated the effect of Pb exposure on autophagy, and its role in Pb-induced developmental neurotoxicity. Zebrafish embryos were exposed to Pb at concentrations of 0, 0.1, 1 or 10 µM until 4 days post-fertilization. Our data showed that exposure to 10 µM Pb significantly reduced survival rates and impaired locomotor activity. Uptake of Pb was enhanced as the concentration and duration of exposure increased. Inhibition of lysosomal degradation with bafilomycin A1 treatment abolished the suppression of Lc3-II protein expression by Pb. Furthermore, autophagosome formation was inhibited by Pb in the brain. In addition, mRNA expression of beclin1, one of the critical genes in autophagy, were decreased in Pb exposure groups at 72 h post-fertilization. Whole-mount in situ hybridization assay showed that beclin1 gene expression in the brain was reduced by Pb. Rapamycin, an autophagy inducer, partly resolved developmental neurotoxicity induced by Pb exposure. Our results suggest that autophagy plays a protective role in the developmental neurotoxicity of Pb in zebrafish embryos and larvae.