Author: Nevin Manimala

J Environ Manage. 2021 Mar 24;288:112384. doi: 10.1016/j.jenvman.2021.112384. Online ahead of print.

ABSTRACT

Groundwater resources in South Asian cities are facing immense stress due to over-extraction leading to environmental, social and economic instabilities. The perennial mega rivers of Himalayas form the lifeline for South Asia, underpinning food and water security for a large population both directly and indirectly through exchange with groundwater systems. The present study delineates the spatio-temporal variation in patterns and processes of sub-hourly to annual-scale hydrological exchanges between the Ganges and its adjoining highly exploited aquifer in a urban-peri urban reach. Multivariate statistical analyses established river water-groundwater interaction in this region with ~40% loading of first principal component, i.e river water during monsoon on the shallow aquifer. The part of the aquifer detached from the main confined aquifer show an influence of precipitation (the second principal component) with loading of ~90%. Again the part of the aquifer suffering infiltration of local surface water bodies show effect of precipitation with a second principal loading of ~80%. Fourier transformation is used in the hydrograph to remove influence of heavy urbanization on the hydrographs. This study proves that the phenomenon of infiltrating river water during monsoon plays a primary role in controlling aquifer storage although contaminating the aquifer simultaneously. However, during pre and post-monsoon the flow path reversal helps in maintaining river baseflow. Cross-correlation between the river and piezometric series show increased delay of pressure head propagation of the infiltrating river waterfront, with increasing distance. These observations are also substantiated by stable isotope signatures. The present study provides an understanding of potential groundwater vulnerability resulting from waste water and irrigational contamination through river water intrusion which would eventually lead the government to implement proper water and environmental management policies towards availability of long-term sustainable water resources for the residents.

PMID:33773213 | DOI:10.1016/j.jenvman.2021.112384

J Environ Manage. 2021 Mar 24;288:112368. doi: 10.1016/j.jenvman.2021.112368. Online ahead of print.

ABSTRACT

A better knowledge of surface ozone variations and the relevant influential factors is of great significance for controlling frequent ozone pollution events. In this study, we first examined the primary variation patterns of surface ozone in space and time across China via a clustering analysis on the basis of daily maximum 8h average surface ozone (MDA8) between 2015 and 2018. Statistical models were then established between MDA8 and a set of influential factors to pinpoint dominant factors contributing to regional MDA8 variations. The clustering results revealed four typical variation patterns of MDA8 in China given distinct pollution levels, seasonality, and long-term trends. Statistical modeling results indicated that the seasonal variability of MDA8 was closely associated with UV radiation and meteorological factors like boundary layer height, temperature and relative humidity. In contrast, the long-term trends of MDA8 were largely linked to ozone precursors and meteorological variables including temperature, relative humidity, and total cloud cover. Moreover, the phenomenal increasing trends of MDA8 in North China were found to be statistically associated with the depletion of nitrogen dioxide (NO₂) and carbon monoxide (CO). Specifically, substantial increases in volatile organic compounds (VOCs) along with depletions in NO₂ and CO significantly boosted the photochemical ozone formation chain process in a VOC-limited regime like the North China plain. Overall, the inferred linkage in this study provides evidence and clues to help control increasing ozone pollution events in North China.

PMID:33773209 | DOI:10.1016/j.jenvman.2021.112368

Int Immunopharmacol. 2021 Mar 24;95:107575. doi: 10.1016/j.intimp.2021.107575. Online ahead of print.

ABSTRACT

BACKGROUND: Metformin (MET) may exert anti-rheumatic effects and reduce cartilage degradation through its immunomodulatory and anti-inflammatory actions.

METHODS: This was a double-blind placebo-controlled study, 120 adult patients with active rheumatoid arthritis (RA) were randomized to receive MET (1000 mg) or placebo daily with methotrexate (MTX, 7.5 mg/week) for 12 weeks. American College of Rheumatology (ACR)20, ACR50, and ACR70 response rates, Disease Activity Score in 28 joints (DAS-28), and drug safety were the efficacy endpoints. Serum levels of TNF-α, IL-1β, IL-6, IL-10, IL-17A, NF-κB, TGG-β1, MDA together with gene expression of AMPK and IGF-IR were assessed before and after the therapy.

RESULTS: A total of 80.8% of the patients in the MET group, compared with 54.7% in placebo group, met the criteria of ACR20 response after 12 weeks (P = 0.001). Statistically significant enhancements in the DAS28-3 (CRP) were observed after 4 and 8 weeks for the MET group compared with placebo and were sustained after 12 weeks. MET group showed statistically significant increase in percentage of patients achieving DAS remission after 12 weeks (P = 0.015). Significant improvements in ACR50, ACR70, Health Assessment Questionnaire Disability Index (HAQ-DI), and DAS28-3 (CRP) were also reported. MET was well-tolerated, and no serious adverse effects were reported in both groups. Furthermore, the MET group was superior in improving the measured parameters compared to the placebo.

CONCLUSIONS: MET improved the anti-rheumatic effect of MTX; suggesting it to be a beneficial adjuvant in patients with RA. Trial registration ID: NCT04068246.

PMID:33773207 | DOI:10.1016/j.intimp.2021.107575

Accid Anal Prev. 2021 Mar 24;154:106082. doi: 10.1016/j.aap.2021.106082. Online ahead of print.

ABSTRACT

Pedelecs (pedal electric cycles) have become increasingly popular in recent years. This increase may trigger many positive effects, but unfortunately it also results in an increase in accidents, especially single accidents, involving these vehicles. This investigation analyses 1738 free text descriptions of pedelec single accidents written by police officers on site. The accidents occurred in 2016 and 2017 in 14 federal German states. The aim is to evaluate whether pedelec single accidents have specific causes that have not yet been recorded in the official accident statistics. Results show that most cases can be assigned to categories addressing the user (60 %) or the road design (54 %, accidents can be assigned to several categories). With this dataset it is also possible to analyse the severity of injuries using ordered probit analysis. Of the nine categories where severe injuries are expected, most address the user. In addition, serious injuries are expected when problems are encountered on downhill slopes or involve technical faults. An additional ordered probit analysis with a second dataset, based on different sources but using the same categorisation, supports these results.

PMID:33773198 | DOI:10.1016/j.aap.2021.106082

Ecotoxicol Environ Saf. 2021 Mar 24;215:112149. doi: 10.1016/j.ecoenv.2021.112149. Online ahead of print.

ABSTRACT

The aim of present work was to evaluate the effects of titanium dioxide nanoparticles (TiO₂ NPs) on rice’s growth (Oryza sativa L.) and nutrient availability under different soil textures. Greenhouse experiment was carried out with three soil textures (sandy loam, silt loam and silty clay loam) and two concentrations of TiO₂ NPs (500, 750 mg kg^-1). Control (without TiO₂ NPs) was also maintained for the comparison. Growth parameters including chlorophyll content, root/shoot length, fresh/dry biomass and nutrients’ uptake including calcium (Ca), copper (Cu), iron (Fe), magnesium (Mg), phosphorous (P), potassium (K) and zinc (Zn) were determined. The results revealed that application of 500 mg kg^-1 TiO₂ NPs in silty clay loam soil increased the chlorophyll content (3.3-folds), root length (49%), shoot length (31%), root and shoot biomass (41% & 39%, respectively) as compared to other soil textures. The maximum plant growth was observed in silty clay loam > silt loam > sandy loam. Concentration of Cu, Fe, P and Zn in shoot was increased by 8 – , 2.3 – , 0.4 – , 0.05 -folds in silty clay loam upon 500 mg kg^-1 TiO₂ NPs application as compared to the control. Backward selection method to model the parameters (nutrients in soil) for the response variables (root/shoot length and biomass) showed that Ca, Fe, P are the main nutrients responsible for the increase in plant length and biomass. Overall, the growth of rice was better in silty clay loam at 500 mg kg^-1 of TiO₂ NPs.

PMID:33773153 | DOI:10.1016/j.ecoenv.2021.112149

Ecotoxicol Environ Saf. 2021 Mar 24;215:112160. doi: 10.1016/j.ecoenv.2021.112160. Online ahead of print.

ABSTRACT

BACKGROUND: The air pollution has become an important environmental health problem due to its adverse health effect. The objective of this study was to investigate the effects of ambient temperature and pollutants on mortality of respiratory diseases (RD) in Hefei, China, a typical inland city.

METHODS: Nonlinear exposure-response dependencies and delayed effects of urban daily mean temperature (DMT) and pollutants were evaluated by distributed lag non-linear models (DLNM). To further explore this effect, different genders and ages were also examined by stratified analysis.

RESULTS: A total of 12876 deaths from RD were collected from January 1, 2014 to December 31, 2018 in Hefei, China. There was a U-shaped correlation between DMT and RD mortality, and the RD mortality rised by 11.6% (95% CI: 2.2-22.0%) when the DMT was 35.8 °C (reference temperature is 20 °C). The results show that risk of death with short-term exposure to elevated concentrations of PM₁₀ and SO₂ was not significant. The maximum hysteresis and cumulative relative risk (RR) of RD mortality were 1.012 (95% CI: 1.003 ~ 1.021, lag 0 day) and 1.072 (95% CI: 1.014 ~1.133, lag 10 days) for each 10 μg/m³ augment in NO₂; 1.005 (95% CI: 1.001-1.009, lag 0 day) and 1.027 (95% CI: 1.004-1.051, lag 10 days) for each 10 μg/m³ augment in O_3; a negative association between CO exposure and the cumulative risk of death was observed (RR = 0.964, 95% CI: 0.935-0.993, lag 07 days). Subgroup analysis showed the effect of high temperatures, NO_2, O₃ and CO exposure was still statistically significant for the elderly and male.

CONCLUSION: The present study found that short-term exposure to high temperature, NO_2, O₃ and CO were significantly associated with the risk of RD mortality and male as well as elderly are more susceptible to these factors.

PMID:33773152 | DOI:10.1016/j.ecoenv.2021.112160

Ecotoxicol Environ Saf. 2021 Mar 24;215:112165. doi: 10.1016/j.ecoenv.2021.112165. Online ahead of print.

ABSTRACT

BACKGROUND: Exposure to metals/metalloids, including essential and nonessential elements, has been associated to male reproductive health in animals. However, findings from human studies are inconsistent.

OBJECTIVES: To investigate the impact of exposure to multiple metals/metalloids at environmental levels on the conventional human semen-quality parameters.

MATERIALS AND METHODS: Men living in rural or industrial areas were recruited by personalized letters. No exclusion criteria were applied. Each man provided one semen sample and one blood sample. We analyzed the semen sample both to determine conventional sperm parameters (concentration, progressive motility and normal forms) and to quantify lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As), nickel (Ni), vanadium (V) and selenium (Se) levels. The levels of these metals/metalloids were also quantified in venous blood and spermatozoa samples. Associations between the blood/seminal plasma metal/metalloid levels and semen quality parameters were assessed using confounder adjusted logistic regression models. Correlation and interactions between blood/seminal plasma and semen metal/metalloid levels were investigated using the Spearman’s correlation.

RESULTS: We found a positive association of seminal plasma cadmium level with lower Total count (OR = 4.48, 95%CI 0.25-80); whereas lead (OR = 4.51, 95%CI 0.86-23) and cadmium (OR = 3.45, 95%CI 0.77-16) seminal plasma levels had a positive association with progressive sperm motility. Overall, these associations remained suggestive after adjustment, though statistically unstable risks. Finally, we found weak interactions between beneficial effects of Se and detrimental ones only for Cd and Pb blood level on sperm concentration, total sperm count and progressive sperm motility.

CONCLUSIONS: Our findings suggest that environmental exposure to Pb and Cd contributes to a decline in human semen quality, whereas Se can have beneficial effects. Measurements of metals/metalloids in the seminal fluid may be more predictable of semen quality than conventional blood measurements.

PMID:33773149 | DOI:10.1016/j.ecoenv.2021.112165

Environ Int. 2021 Mar 19;153:106524. doi: 10.1016/j.envint.2021.106524. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: The growing impact of the COVID-19 pandemic has heightened the urgency of identifying individuals most at risk of infection. Per- and poly-fluoroalkyl substances (PFASs) are manufactured fluorinated chemicals widely used in many industrial and household products. The objective of this case-control study was to assess the association between PFASs exposure and COVID-19 susceptibility and to elucidate the metabolic dysregulation associated with PFASs exposure in COVID-19 patients.

METHODS: Total 160 subjects (80 COVID-19 patients and 80 symptom-free controls) were recruited from Shanxi and Shandong provinces, two regions heavily polluted by PFASs in China. Twelve common PFASs were quantified in both urine and serum. Urine metabolome profiling was performed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS).

RESULTS: In unadjusted models, the risk of COVID-19 infection was positively associated with urinary levels of perfluorooctanesulfonic acid (PFOS) (Odds ratio: 2.29 [95% CI: 1.52-3.22]), perfluorooctanoic acid (PFOA) (2.91, [1.95-4.83], and total PFASs (∑ (12) PFASs) (3.31, [2.05-4.65]). After controlling for age, sex, body mass index (BMI), comorbidities, and urine albumin-to-creatinine ratio (UACR), the associations remained statistically significant (Adjusted odds ratio of 1.94 [95% CI: 1.39-2.96] for PFOS, 2.73 [1.71-4.55] for PFOA, and 2.82 [1.97-3.51] for ∑ (12) PFASs). Urine metabolome-PFASs association analysis revealed that 59% of PFASs-associated urinary endogenous metabolites in COVID-19 patients were identified to be produced or largely regulated by mitochondrial function. In addition, the increase of PFASs exposure was associated with the accumulation of key metabolites in kynurenine metabolism, which are involved in immune responses (Combined β coefficient of 0.60 [95% CI: 0.25-0.95, P = 0.001]). Moreover, alternations in PFASs-associated metabolites in mitochondrial and kynurenine metabolism were also correlated with clinical lab biomarkers for mitochondrial function (serum growth/differentiation factor-15) and immune activity (lymphocyte percentage), respectively.

CONCLUSION: Elevated exposure to PFASs was independently associated with an increased risk of COVID-19 infection. PFASs-associated metabolites were implicated in mitochondrial function and immune activity. Larger studies are needed to confirm our findings and further understand the underlying mechanisms of PFASs exposure in the pathogenesis of SARS-CoV2 infection.

PMID:33773143 | DOI:10.1016/j.envint.2021.106524

Environ Int. 2021 Mar 24;153:106523. doi: 10.1016/j.envint.2021.106523. Online ahead of print.

ABSTRACT

BACKGROUND: Environmental exposures in early life influence the development of behavioral outcomes in children, but research has not considered multiple exposures. We therefore aimed to investigate the impact of a broad spectrum of pre- and postnatal environmental exposures on child behavior.

METHODS AND FINDINGS: We used data from the HELIX (Human Early Life Exposome) project, which was based on six longitudinal population-based birth cohorts in Europe. At 6-11 years, children underwent a follow-up to characterize their exposures and assess behavioral problems. We measured 88 prenatal and 123 childhood environmental factors, including outdoor, indoor, chemical, lifestyle and social exposures. Parent-reported behavioral problems included (1) internalizing, (2) externalizing scores, using the child behavior checklist (CBCL), and (3) the Conner’s Attention Deficit Hyperactivity Disorder (ADHD) index, all outcomes being discrete raw counts. We applied LASSO penalized negative binomial regression models to identify which exposures were associated with the outcomes, while adjusting for co-exposures. In the 1287 children (mean age 8.0 years), 7.3% had a neuropsychiatric medical diagnosis according to parent’s reports. During pregnancy, smoking and car traffic showing the strongest associations (e.g. smoking with ADHD index, aMR:1.31 [1.09; 1.59]) among the 13 exposures selected by LASSO, for at least one of the outcomes. During childhood, longer sleep duration, healthy diet and higher family social capital were associated with reduced scores whereas higher exposure to lead, copper, indoor air pollution, unhealthy diet were associated with increased scores. Unexpected decreases in behavioral scores were found with polychlorinated biphenyls (PCBs) and organophosphate (OP) pesticides.

CONCLUSIONS: Our systematic exposome approach identified several environmental contaminants and healthy lifestyle habits that may influence behavioral problems in children. Modifying environmental exposures early in life may limit lifetime mental health risk.

PMID:33773142 | DOI:10.1016/j.envint.2021.106523

Lancet Infect Dis. 2021 Mar 24:S1473-3099(21)00127-4. doi: 10.1016/S1473-3099(21)00127-4. Online ahead of print.

ABSTRACT

BACKGROUND: Although several COVID-19 vaccines have been developed so far, they will not be sufficient to meet the global demand. Development of a wider range of vaccines, with different mechanisms of action, could help control the spread of SARS-CoV-2 globally. We developed a protein subunit vaccine against COVID-19 using a dimeric form of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein as the antigen. We aimed to assess the safety and immunogenicity of this vaccine, ZF2001, and determine the appropriate dose and schedule for an efficacy study.

METHODS: We did two randomised, double-blind, placebo-controlled, phase 1 and phase 2 trials. Phase 1 was done at two university hospitals in Chongqing and Beijing, China, and phase 2 was done at the Hunan Provincial Center for Disease Control and Prevention in Xiangtan, China. Healthy adults aged 18-59 years, without a history of SARS-CoV or SARS-CoV-2 infection, an RT-PCR-positive test result for SARS-CoV-2, a history of contact with confirmed or suspected COVID-19 cases, and severe allergies to any component of the vaccine were eligible for enrolment. In phase 1, participants were randomly assigned (2:2:1) to receive three doses of the vaccine (25 μg or 50 μg) or placebo intramuscularly, 30 days apart. In phase 2, participants were randomly assigned (1:1:1:1:1:1) to receive the vaccine (25 μg or 50 μg) or placebo intramuscularly, 30 days apart, in either a two-dose schedule or a three-dose schedule. Investigators, participants, and the laboratory team were masked to group allocation. For phase 1, the primary outcome was safety, measured by the occurrence of adverse events and serious adverse events. For phase 2, the primary outcome was safety and immunogenicity (the seroconversion rate and the magnitude, in geometric mean titres [GMTs], of SARS-CoV-2-neutralising antibodies). Analyses were done on an intention-to-treat and per-protocol basis. These trials are registered with ClinicalTrials.gov (NCT04445194 and NCT04466085) and participant follow-up is ongoing.

FINDINGS: Between June 22 and July 3, 2020, 50 participants were enrolled into the phase 1 trial and randomly assigned to receive three doses of placebo (n=10), the 25 μg vaccine (n=20), or the 50 μg vaccine (n=20). The mean age of participants was 32·6 (SD 9·4) years. Between July 12 and July 17, 2020, 900 participants were enrolled into the phase 2 trial and randomly assigned to receive two doses of placebo (n=150), 25 μg vaccine (n=150), or 50 μg vaccine (n=150), or three doses of placebo (n=150), 25 μg vaccine (n=150), or 50 μg vaccine (n=150). The mean age of participants was 43·5 (SD 9·2) years. In both phase 1 and phase 2, adverse events reported within 30 days after vaccination were mild or moderate (grade 1 or 2) in most cases (phase 1: six [60%] of ten participants in the placebo group, 14 [70%] of 20 in the 25 μg group, and 18 [90%] of 20 in the 50 μg group; phase 2: 37 [25%] of 150 in the two-dose placebo group, 43 [29%] of 150 in the two-dose 25 μg group, 50 [33%] of 150 in the two-dose 50 μg group, 47 [31%] of 150 in the three-dose placebo group, 72 [48%] of 150 in the three-dose 25 μg group, and 65 [43%] of 150 in the three-dose 50 μg group). In phase 1, two (10%) grade 3 or worse adverse events were reported in the 50 μg group. In phase 2, grade 3 or worse adverse events were reported by 18 participants (four [3%] in the two-dose 25 μg vaccine group, two [1%] in the two-dose 50 μg vaccine group, two [1%] in the three-dose placebo group, four [3%] in the three-dose 25 μg vaccine group, and six [4%] in the three-dose 50 μg vaccine group), and 11 were considered vaccine related (two [1%] in the two-dose 25 μg vaccine group, one [1%] in the two-dose 50 μg vaccine group, one [1%] in the three-dose placebo group, two [1%] in the three-dose 25 μg vaccine group, and five [3%] in the three-dose 50 μg vaccine group); seven participants reported serious adverse events (one [1%] in the two-dose 25 μg vaccine group, one [1%] in the two-dose 50 μg vaccine group, two [1%] in the three-dose placebo group, one [1%] in the three-dose 25 μg vaccine group, and two [1%] in the three-dose 50 μg vaccine group), but none was considered vaccine related. In phase 2, on the two-dose schedule, seroconversion rates of neutralising antibodies 14 days after the second dose were 76% (114 of 150 participants) in the 25 μg group and 72% (108 of 150) in the 50 μg group; on the three-dose schedule, seroconversion rates of neutralising antibodies 14 days after the third dose were 97% (143 of 148 participants) in the 25 μg group and 93% (138 of 148) in the 50 μg group. In the two-dose groups in phase 2, the SARS-CoV-2-neutralising GMTs 14 days after the second dose were 17·7 (95% CI 13·6-23·1) in the 25 μg group and 14·1 (10·8-18·3) in the 50 μg group. In the three-dose groups in phase 2, the SARS-CoV-2-neutralising GMTs 14 days after the third dose were 102·5 (95% CI 81·8-128·5) in the 25 μg group and 69·1 (53·0-90·0) in the 50 μg group.

INTERPRETATION: The protein subunit vaccine ZF2001 appears to be well tolerated and immunogenic. The safety and immunogenicity data from the phase 1 and 2 trials support the use of the 25 μg dose in a three-dose schedule in an ongoing phase 3 trial for large-scale evaluation of ZF2001’s safety and efficacy.

FUNDING: National Program on Key Research Project of China, National Science and Technology Major Projects of Drug Discovery, Strategic Priority Research Program of the Chinese Academy of Sciences, and Anhui Zhifei Longcom Biopharmaceutical.

TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

PMID:33773111 | DOI:10.1016/S1473-3099(21)00127-4