Category: Statistics

Environ Sci Pollut Res Int. 2022 Apr 22. doi: 10.1007/s11356-022-20166-5. Online ahead of print.

ABSTRACT

Pethoxamid is chloroacetamide herbicide. Pethoxamid is commonly used to kill different weeds in various crops. Pethoxamid can leach in the water and soil and can cause toxic effects to other non-target species. Current study is therefore aimed to perform the investigation of the cytotoxic and genotoxic effects of pethoxamid on Allium cepa cells.The root growth, mitotic index (MI), chromosomal aberrations (CAs), and DNA damage were assessed through root growth inhibition, A. cepa ana-telophase, and alkaline comet assays, respectively. Furthermore, molecular docking was performed to evaluate binding affinity of pethoxamid on DNA and very-long-chain fatty acid (VLCFA) synthases. In root growth inhibition test, onion root length was statistically significantly decreased in a concentration dependent manner. Concentration- and time-dependent decreases in MI were observed, whereas increase in CAs such as disturbed ana-telophase, chromosome laggards, stickiness, anaphase bridges, and DNA damage was caused by the pethoxamid on A. cepa root cells. Molecular docking revealed that pethoxamid binds selectively to GC-rich regions in the minor groove of the DNA structure and showed remarkable binding affinity against all synthases taking part in the sequential biosynthesis of VLCFAs. It was concluded that the pethoxamid-induced genotoxicity and cytotoxicity may be through multiple binding ability of this herbicide with DNA and VLCFA synthases.

PMID:35449332 | DOI:10.1007/s11356-022-20166-5

Environ Sci Pollut Res Int. 2022 Apr 21. doi: 10.1007/s11356-022-20227-9. Online ahead of print.

ABSTRACT

The assessment of the generalization of the strict hypertension definition in the 2017 ACC/AHA Hypertension Guideline from environmental condition remains sparse. The aims of this study are to investigate and compare the associations of ambient air pollution and traffic-related pollution (TRP) with hypertension defined by the different criteria. A total of 32,135 participants were recruited from the baseline survey of the CHCN-BTH in 2017. We defined hypertension as SBP/DBP ≥ 140/90 mmHg according to the hypertension guidelines in China, Japan, Europe and ISH (traditional criteria) and defined as SBP/DBP ≥ 130/80 mmHg according to the 2017 ACC/AHA Hypertension Guideline (strict criteria). A two-level generalized linear mixed models were applied to investigate the associations of air pollutants (i.e. PM_2.5, SO₂, NO₂) and TRP with blood pressure (BP) measures and hypertension. Stratified analyses and two-pollutant models were also performed. The stronger associations of air pollutants were found in the hypertension defined by the strict criteria than that defined by the traditional criteria. The ORs per an IQR increase in PM_2.5 were 1.17 (95% CI: 1.09, 1.25) for the strict criteria and 1.14 (95% CI: 1.06, 1.23) for the traditional criteria. The similar conditions were also observed for TRP. The above results were robust in both stratified analyses and two-pollutant models. Our study assessed the significance of the hypertension defined by the strict criteria from environmental aspect and called attention to the more adverse effects of air pollution and TRP on the earlier stage of hypertension.

PMID:35449329 | DOI:10.1007/s11356-022-20227-9

Sci Rep. 2022 Apr 21;12(1):6574. doi: 10.1038/s41598-022-10250-8.

ABSTRACT

Acute spinal cord injury (SCI) leads to severe damage to the microvascular network. The process of spontaneous repair is accompanied by formation of new blood vessels; their functionality, however, presumably very important for functional recovery, has never been clearly established, as most studies so far used fixed tissues. Here, combining ultrafast Doppler imaging and ultrasound localization microscopy (ULM) on the same animals, we proceeded at a detailed analysis of structural and functional vascular alterations associated with the establishment of chronic SCI, both at macroscopic and microscopic scales. Using a standardized animal model of SCI, our results demonstrate striking hemodynamic alterations in several subparts of the spinal cord: a reduced blood velocity in the lesion site, and an asymmetrical hypoperfusion caudal but not rostral to the lesion. In addition, the worsening of many evaluated parameters at later time points suggests that the neoformed vascular network is not yet fully operational, and reveals ULM as an efficient in vivo readout for spinal cord vascular alterations. Finally, we show statistical correlations between the diverse biomarkers of vascular dysfunction and SCI severity. The imaging modality developed here will allow evaluating recovery of vascular function over time in pre-clinical models of SCI. Also, used on SCI patients in combination with other quantitative markers of neural tissue damage, it may help classifying lesion severity and predict possible treatment outcomes in patients.

PMID:35449222 | DOI:10.1038/s41598-022-10250-8

Sci Rep. 2022 Apr 21;12(1):6561. doi: 10.1038/s41598-022-10008-2.

ABSTRACT

The association between capecitabine efficacy and proton pump inhibitors (PPIs) is controversial. Here, we determined whether co-administration of PPIs affects the real-world effectiveness of capecitabine. This retrospective observational study included consecutive patients with stage II-III colorectal cancer (CRC) who received adjuvant capecitabine monotherapy or CapeOX (capecitabine and oxaliplatin) between January 2009 and December 2014 at nine participating institutions. The primary endpoint was the difference in relapse-free survival (RFS) between patients who received PPIs and those who did not and was estimated using the Kaplan-Meier method. Overall survival (OS) was the secondary endpoint. Multivariable analysis of RFS and OS was performed using a Cox proportional hazards model, propensity score adjustment, and inverse probability of treatment weighting (IPTW) analyses. Data from 606 patients were evaluated, 54 of whom had received a PPI. PPI-treated patients tended to have poorer RFS and OS than patients treated without PPIs. The hazard ratio for RFS with capecitabine monotherapy was 2.48 (95% confidence interval: 1.22-5.07). These results were consistent with sensitivity analyses performed using propensity score adjustment and IPTW methods. Co-administration of PPIs may reduce the effectiveness of capecitabine and negatively impact patients with stage II-III CRC.

PMID:35449143 | DOI:10.1038/s41598-022-10008-2

BMC Public Health. 2022 Apr 21;22(1):797. doi: 10.1186/s12889-022-13231-8.

ABSTRACT

INTRODUCTION: This study aimed to investigate sexual orientation disclosure and mental health among young men who have sex with men (YMSMs). To this end, we constructed a chained multimediator model of sexual minority stigma, sexual minority identity, social support, and resilience, with the moderator of sexual orientation disclosure.

METHODS: We conducted a cross-sectional survey of 345 YMSMs in Nanning, China. Bivariate analysis was used to evaluate factors associated with sexual orientation disclosure. Sexual minority stigma was used to predict identity, with social support as the step 1 mediator and resilience as the step 2 mediator. Sexual minority identity was analyzed using a chained moderated mediation model; sexual orientation disclosure was included as a moderator in all models to control its confounding effect.

RESULTS: The average age of YMSMs was 20.0 ± 1.3 years. Bivariate analysis indicated that YMSMs who disclosed sexual orientation may have experienced less stigma (15.49 ± 3.02 vs 16.21 ± 2.74), obtained more social support (65.98 ± 11.18 vs 63.19 ± 11.13), had strong psychological resilience (37.40 ± 8.57 vs 35.39 ± 7.73), and had a more positive self-identity (104.12 ± 21.10 vs 95.35 ± 16.67); differences between subgroups were statistically significant (p < 0.05). Sexual minority stigma, perceived stigma, and enacted stigma were significantly associated with social support and resilience. The association between sexual minority stigma and sexual minority identity was significantly mediated by social support (indirect effect [95% CI] = – 3.307 [- 4.782, – 1.907]). Resilience significantly mediated the same association for identity (- 2.544 [- 4.052, – 1.114]). The chained relationship from sexual minority stigma to social support, resilience, and identity was also significant, with an indirect effect of – 0.404 [- 0.621, – 0.249].

CONCLUSION: Among YMSMs in China, sexual minority stigma affects sexual minority identity through social support and resilience. Given the psychological effects of stigma, social support and resilience must be considered to better promote positive self-identity and mental health among YMSMs.

PMID:35449098 | DOI:10.1186/s12889-022-13231-8

BMC Res Notes. 2022 Apr 21;15(1):144. doi: 10.1186/s13104-022-06031-1.

ABSTRACT

OBJECTIVE: SARS-CoV-2 is the cause of COVID-19, the rapidly spreading pandemic. When SARS-CoV-2 enters the target cells in the respiratory system, the spike glycoprotein binds to a cellular receptor angiotensin converting enzyme 2 (ACE2). The susceptibility to infection in individuals under 20 years of age is approximately half that of adults aged over 20 years. In this study, we investigated the immunohistochemical protein expressions of ACE2 in mandibular salivary glands and tracheal glands from forensic autopsy specimens covering adults and children.

RESULTS: The ACE2 immunohistochemistry of autopsy specimens was performed, and the percentages of the immuno-positive areas in the cell layers of the glands were calculated. Our results demonstrate that the ACE2 positivity in mandibular salivary gland and tracheal glands showed the statistically significant decrease with the increase of age, which indicates that the susceptibility of aged individuals to SARS-CoV-2 may be due to various factors including but not limited to ACE2 protein expressions.

PMID:35449115 | DOI:10.1186/s13104-022-06031-1

BMC Surg. 2022 Apr 21;22(1):146. doi: 10.1186/s12893-022-01594-z.

ABSTRACT

INTRODUCTION: The effectiveness of hemorrhoidal artery ligation supplementation in reducing the incidence of post laser hemorrhoidoplasty bleeding has not been investigated.

METHODS: This was a double-blind, randomized controlled trial comparing post-operative bleeding incidence in patients undergoing laser hemorrhoidoplasty (LHP) only versus LHP with hemorrhoidal artery ligation (HAL). Outcome measures included post-operative bleeding and its severity (i.e. verbal rating scale and Clavien-Dindo classification), presence of perianal swelling and pain score (visual analog score) at 1-day, 1-week and 6-weeks post-operatively. Statistical tests were performed and a value of P < 0.05 was considered significant.

RESULTS: Seventy-six patients were randomized. There was no difference in median operating time. The bleeding incidence was highest at 1-week post-operatively (17.1%), and decreased to 1.3% at 6-weeks. There was no significant difference in bleeding incidence between both groups at any of the measured timepoints (P > 0.05). Severity of bleeding and incidence of post-operative perianal swelling were similar in both groups (P > 0.05). There was no difference in median pain scores.

CONCLUSION: Supplementation of HAL to LHP does not reduce the post-operative bleeding incidence. LHP is sufficient as a stand-alone procedure for treating haemorrhoids.

TRIAL REGISTRATION: National Registration Number is NMRR-15-1112-24065 (IIR). The trial start date was 1st January 2015 with the ClinicalTrials.gov identifier and registration number as NCT04667169.

PMID:35449097 | DOI:10.1186/s12893-022-01594-z

Genes Environ. 2022 Apr 22;44(1):13. doi: 10.1186/s41021-022-00242-5.

ABSTRACT

I will reflect on the role of genotoxicity in the regulation of chemical safety, summarizing the past and current situation, and giving personal views for the future. This includes how genotoxicity information has been, and is being, used in the evaluation of the safety of chemical substances including pharmaceuticals, pesticides, food additives and industrial chemicals before they are introduced into the market for sale.In Japan, the Industrial Safety and Health Act, enacted in 1972, assures workers’ safety by including safety assessment of chemicals to which workers may be exposed in the workplace. The law firstly included the bacterial gene mutation assay with rat liver microsome fraction (Ames test) for the evaluation of chemical mutagenicity to predict carcinogenic potential, which was the forerunner of requiring a genotoxicity test by law. Since then, genotoxicity, especially the Ames test and the in vitro chromosomal aberration test using cultured mammalian cells (especially Chinese hamster cells) have been incorporated into several laws to assess the safety of various chemicals. Many test systems for different endpoints have been developed, improved, and used in practice. The battery strategy, combining several test systems to detect as many genotoxic chemicals as possible, was implemented because no one test system can detect all genotoxic agents with different mechanisms of genetic damage. In general, the standard battery consists of the Ames test, in vitro chromosomal aberration test and the in vivo rodent erythrocyte micronucleus test as a representative in vivo assay. Many other test systems have been used for supplementary testing as well as for research studies. Important keywords for regulatory science include 1) guidelines, 2) Good Laboratory Practice, 3) evaluation and interpretation of test results. Here, I discuss on these key points, and give personal opinions for the future.

PMID:35449081 | DOI:10.1186/s41021-022-00242-5

Alzheimers Res Ther. 2022 Apr 21;14(1):57. doi: 10.1186/s13195-022-00998-6.

ABSTRACT

BACKGROUND: To evaluate a wide range of optical coherence tomography (OCT) parameters for possible application as a screening tool for cognitively healthy individuals at risk of Alzheimer’s disease (AD), assessing the potential relationship with established cerebrospinal fluid (CSF) core AD biomarkers and magnetic resonance imaging (MRI).

METHODS: We studied 99 participants from the Valdecilla Study for Memory and Brain Aging. This is a prospective cohort for multimodal biomarker discovery and validation that includes participants older than 55 years without dementia. Participants received a comprehensive neuropsychological battery and underwent structural 3-T brain MRI, lumbar puncture for CSF biomarkers (phosphorylated-181-Tau (pTau), total Tau (tTau), beta-amyloid 1-42 (Aβ 1-42), and beta-amyloid 1-40 (Aβ 1-40)). All individuals underwent OCT to measure the retinal ganglion cell layer (GCL), the retinal nerve fiber layer (RFNL), the Bruch’s membrane opening-minimum rim width (BMO-MRW), and choroidal thickness (CT). In the first stage, we performed a univariate analysis, using Student’s t-test. In the second stage, we performed a multivariate analysis including only those OCT parameters that discriminated at a nominal level, between positive/negative biomarkers in stage 1.

RESULTS: We found significant differences between the OCT measurements of pTau- and tTau-positive individuals compared with those who were negative for these markers, most notably that the GCL and the RNFL were thinner in the former. In stage 2, our dependent variables were the quantitative values of CSF markers and the hippocampal volume. The Aβ 1-42/40 ratio did not show a significant correlation with OCT measurements while the associations between pTau and tTau with GCL were statistically significant, especially in the temporal region of the macula. Besides, the multivariate analysis showed a significant correlation between hippocampal volume with GCL and RNFL. However, after false discovery rate correction, only the associations with hippocampal volume remained significant.

CONCLUSIONS: We found a significant correlation between Tau (pTau) and neurodegeneration biomarkers (tTau and hippocampus volume) with GCL degeneration and, to a lesser degree, with damage in RFNL. OCT analysis constitutes a non-invasive and unexpensive biomarker that allows the detection of neurodegeneration in cognitively asymptomatic individuals.

PMID:35449033 | DOI:10.1186/s13195-022-00998-6

Part Fibre Toxicol. 2022 Apr 22;19(1):30. doi: 10.1186/s12989-022-00469-8.

ABSTRACT

BACKGROUND: Considering the expanding industrial applications of carbon nanotubes (CNTs), safety assessment of these materials is far less than needed. Very few long-term in vivo studies have been carried out. This is the first 2-year in vivo study to assess the effects of double walled carbon nanotubes (DWCNTs) in the lung and pleura of rats after pulmonary exposure.

METHODS: Rats were divided into six groups: untreated, Vehicle, 3 DWCNT groups (0.12 mg/rat, 0.25 mg/rat and 0.5 mg/rat), and MWCNT-7 (0.5 mg/rat). The test materials were administrated by intratracheal-intrapulmonary spraying (TIPS) every other day for 15 days. Rats were observed without further treatment until sacrifice.

RESULTS: DWCNT were biopersistent in the rat lung and induced marked pulmonary inflammation with a significant increase in macrophage count and levels of the chemotactic cytokines CCL2 and CCL3. In addition, the 0.5 mg DWCNT treated rats had significantly higher pulmonary collagen deposition compared to the vehicle controls. The development of carcinomas in the lungs of rats treated with 0.5 mg DWCNT (4/24) was not quite statistically higher (p = 0.0502) than the vehicle control group (0/25), however, the overall incidence of lung tumor development, bronchiolo-alveolar adenoma and bronchiolo-alveolar carcinoma combined, in the lungs of rats treated with 0.5 mg DWCNT (7/24) was statistically higher (p < 0.05) than the vehicle control group (1/25). Notably, two of the rats treated with DWCNT, one in the 0.25 mg group and one in the 0.5 mg group, developed pleural mesotheliomas. However, both of these lesions developed in the visceral pleura, and unlike the rats administered MWCNT-7, rats administered DWCNT did not have elevated levels of HMGB1 in their pleural lavage fluids. This indicates that the mechanism by which the mesotheliomas that developed in the DWCNT treated rats is not relevant to humans.

CONCLUSIONS: Our results demonstrate that the DWCNT fibers we tested are biopersistent in the rat lung and induce chronic inflammation. Rats treated with 0.5 mg DWCNT developed pleural fibrosis and lung tumors. These findings demonstrate that the possibility that at least some types of DWCNTs are fibrogenic and tumorigenic cannot be ignored.

PMID:35449069 | DOI:10.1186/s12989-022-00469-8