Nevin Manimala

Environ Int. 2021 May 17;156:106640. doi: 10.1016/j.envint.2021.106640. Online ahead of print.

ABSTRACT

BACKGROUND: Increasing animal studies have indicated that organophosphate esters (OPEs) have endocrine-disruptive potential. However, human epidemiological evidence is limited, especially in susceptible populations, such as pregnant women and neonates. The purpose of this present study was to examine the trimester-specific relationships of prenatal exposure to OPEs with neonatal thyroid-stimulating hormone (TSH).

METHOD: A total of 102 mother-newborn pairs were recruited from a birth cohort study between April 2015 and September 2016 in Wuhan, China. Eight OPE metabolites were detectable in urine samples from pregnant women across the different three trimesters. Neonatal TSH levels were measured using time-resolved immunofluorescence assay. The associations between maternal urinary OPE metabolites and neonatal TSH and the critical exposure windows of fetal vulnerability were estimated using multiple informant models.

RESULTS: Seven OPE metabolites with detection frequency > 50% (52.9%-98.0%) were detected in repeated urine samples from different three trimesters, and the urinary OPE metabolites across pregnancy was of high variability (ICCs: 0.09-0.26). After adjusted for confounders (e.g., maternal age, prepregnancy BMI, passive smoking during pregnancy), some suggestive associations were observed between maternal urinary OPE metabolites and neonatal TSH in different trimesters. A doubling of second trimester di-o-cresyl phosphate & di-p-cresyl phosphate (DoCP & DpCP) was associated with a 7.82% increase in neonatal TSH level (95% CI: -0.70%, 17.06%, p-value = 0.07), a doubling of third trimester diphenyl phosphate (DPHP) was associated with a 4.71% decrease in neonatal TSH level (95% CI: -9.80%, 0.67%, p-value = 0.09), and a doubling of third trimester bis(2-butoxyethyl) phosphate (BBOEP) was associated with a 6.38% increase in neonatal TSH level (95% CI: -0.12%, 13.31%, p = 0.05). However, such associations did not differ materially across trimesters. When performing stratified analysis by infant sex, the associations were statistically significant and were sex-dependent.In females, maternal urinary DoCP & DpCP concentrations in each trimester were associated with increased neonatal TSH levels, and urinary DPHP concentration in the third trimester was associated with decreased neonatal TSH level. In males, maternal urinary BBOEP concentration in the first trimester was positively related to neonatal TSH level.

CONCLUSION: This prospective study demonstrated that prenatal exposure to OPEs can lead to a sex-dependent change in neonatal TSH levels. Although the sex-selective effect was differed among various urinary OPE metabolites, more evidence was supported that OPE exposure was related to increased TSH levels for both males and females.

PMID:34015666 | DOI:10.1016/j.envint.2021.106640

Environ Int. 2021 May 17;156:106641. doi: 10.1016/j.envint.2021.106641. Online ahead of print.

ABSTRACT

Conventional mechanical and biological wastewater treatment is unable to completely eliminate all pollutants, which can therefore enter surface water bodies together with treated wastewater. In addition, bioaerosols produced during wastewater treatment can pose a threat to the health of the wastewater treatment plant staff. In order to control the impact of a wastewater treatment plant (WWTP) on the surrounding environment, including its employees, samples of wastewater and water from a river which received treated wastewater were analysed in terms of their content of antibiotics and heavy metals, levels of selected physiochemical parameters, concentrations of antibiotic-resistance genes (ARGs) and genes of integrases. Furthermore, a quantitative analysis of ARGs in the metagenomic DNA from nasal and throat swabs collected from the WWPT employees was made. Both untreated and treated wastewater samples were dominated by genes of resistance to sulphonamides (sul1, sul2), MLS group of drugs (ermF, ermB) and beta-lactams (bla_OXA). A significant increase in the quantities of ARGs and concentrations of antibiotics was observed in the river following the discharge of treated wastewater in comparison to their amounts in the river water upstream from the point of discharge. Moreover, a higher concentration of ARGs was detected in the DNA from swabs obtained from the wastewater treatment plant employees than from ones collected from the control group. Many statistically significant (p < 0.05) correlations between the concentration of the gene of resistance to heavy metals cnrA versus ARGs, and between the ARGs content and the concentrations of heavy metals in both wastewater and river water samples were observed. The study has demonstrated that the mechanical and biological methods of wastewater treatment are not efficient and may affect the transmission of hazardous pollutants to the aquatic environment and to the atmospheric air. It has been shown that an activated sludge bioreactor can be a potential source of the presence of multi-drug resistant microorganisms in the air, which is a health risk to persons working in WWTPs. It has also been found that an environment polluted with heavy metals is where co-selection of antibiotic resistance may occur, in the development of which integrase genes play an essential role.

PMID:34015664 | DOI:10.1016/j.envint.2021.106641

J Trace Elem Med Biol. 2021 May 13;67:126785. doi: 10.1016/j.jtemb.2021.126785. Online ahead of print.

ABSTRACT

BACKGROUND & AIMS: Pervious epidemiological evidence on the associations of selenium, zinc with lipid profile and glycemic indices was contradictory. The aim of this study was to investigate whether selenium and zinc were casually associated with lipid profile and glycemic indices using mendelian randomization (MR) analysis.

METHOD: A two-sample MR was used to evaluate the causal-effect estimations. Summary statistics for selenium, zinc, lipids and glycemic indices were retrieved from previous large-scale genome-wide association study (GWAS). Single nucleotide polymorphisms (SNPs) that independently and strongly associated with the selenium and zinc were selected as the instrumental variables. The casual estimates were calculated using inverse variance weighted method (IVW), with weighted median, MR-Egger, and MR-PRESSO test as sensitivity analysis, respectively.

RESULTS: In the standard IVW analysis, per SD increment in selenium was associated with an 0.077 mmol/L decrease of TC (95 %CI: -0.102,-0.052) and 0.074 mmol/L of LDL-C (95 %CI: -0.1,-0.048). Suggestive casual associations were found between selenium and insulin or HbA1c. With IVW method, per SD increase in selenium was associated with an 0.023 mmol/L increase of insulin (95 %CI: 0.001,0.045), and an 0.013 mmol/L increase of HbA1c (95 %CI: 0.003,0.023). The results were robust in the sensitivity analysis. Zinc was not casually associated with any of lipid and glycemic markers.

CONCLUSION: Our MR analysis provides evidence of the potential causal effect of Se on beneficial lipid profile, including decreased TC and LDL-C. Furthermore, suggestive casual evidence was suggested between Se and increased serum HbA1c levels. Careful consideration is required for the protective effects of Se supplementation. No casual-effect association was found between Zn and any indices of the lipid and glucose parameters.

PMID:34015661 | DOI:10.1016/j.jtemb.2021.126785

Eur J Obstet Gynecol Reprod Biol. 2021 May 11;262:124-128. doi: 10.1016/j.ejogrb.2021.05.020. Online ahead of print.

ABSTRACT

OBJECTIVES: To assess the association between previous induced abortion and in vitro fertilization (IVF) outcomes among Chinese women.

STUDY DESIGN: In this retrospective cohort study, a total of 1436 infertility patients treated with IVF for the first time in the reproductive centre of Anhui Province Maternity and Child Health Hospital from February 2014 to April 2018 were selected as the study population, and 95 (6.6 %) had a history of induced abortion. Data were assessed from the hospital electronic database and medical records in the reproductive centre.

RESULTS: In total, 818 women (57.0 %) achieved clinical pregnancy, and 501 (34.9 %) achieved live birth. After adjustments for a series of potential confounding factors, women with a history of induced abortion had a significantly decreased probability of clinical pregnancy per transfer (OR: 0.71, 95 % CI: 0.53, 0.95, p = 0.037) and live birth per pregnancy (OR: 0.52, 95 % CI: 0.30, 0.90, p = 0.021) and a higher risk of miscarriage per pregnancy (OR: 1.89, 95 % CI: 1.24, 2.88, p = 0.009) than those without. Because relevant information was unavailable, the impacts of different types of previous induced abortion were not assessed.

CONCLUSIONS: Previous induced abortion may have an adverse effect on IVF outcomes among infertility patients.

PMID:34015639 | DOI:10.1016/j.ejogrb.2021.05.020

Virology. 2021 May 6;560:1-7. doi: 10.1016/j.virol.2021.04.011. Online ahead of print.

ABSTRACT

HLA polymorphism is one of the genetic factors that may be associated with variations in susceptibility to COVID-19 infection. In this study, the frequency of HLA alleles among Saudi patients infected with COVID-19 was examined. The association with infection susceptibility and mortality was evaluated. This study included 135 Saudi COVID-19-infected patients (106 recovered and 29 died) who were admitted to hospitals because of their symptoms, and 135 healthy controls. HLA class I (A, B, C) and class II (DRB1, DQB1) genotyping was performed using the molecular method (PCR-rSSO). In this study, there was a significant increase in the frequency of HLA-A*01, B*56 and C*01 among infected patients compared to the control group (12.1% vs. 5.2%, p = 0.004, 3.7% vs. 0%, p = 0.006, 4.4% vs. 1.5%, p = 0.042, respectively). Moreover, there was a significant increase in the frequency of HLA-A*03 and C*06 among fatal patients compared to infected patients (13.8% vs. 5.7%, p = 0.036, 32.8% vs. 17.5%, p = 0.011, respectively). In terms of HLA class II, HLA-DRB1*04 was significantly higher in the control group compared to infected patients (27.4% vs. 16.3%, p = 0.002), while HLA-DRB1*08 was significantly higher in the infected group compared to the control (4.8% vs. 0.7%, p = 0.004). After statistical correction of the p value, A*01, B*56, DRB1*04 and DRB1*08 remained statistically significant (p_c = 0.04, p_c = 0.03, p_c = 0.014 and p_c = 0.028). This initial data suggested that individual HLA genotypes might play a role in determining susceptibility to COVID-19 infection and infection outcome. However, examining a larger sample size from different populations is required to determine a powerful association for clinical application.

PMID:34015620 | DOI:10.1016/j.virol.2021.04.011

Accid Anal Prev. 2021 May 17;157:106185. doi: 10.1016/j.aap.2021.106185. Online ahead of print.

ABSTRACT

Advancements in data collection and processing methods have produced large databases containing high quality vehicular data. Despite this, conventional vehicle-vehicle collisions remain difficult to identify due to their rarity. Therefore, there is a need to identify potential collisions given the introduction of these new data collection methods. Surrogate indicators are a popular methods utilised to identify such events, however, the type of surrogate that can be used depends heavily on the type of data collection method. Though most surrogate indicators are used at different road geometries, there is evidence to suggest that some surrogate indicators may perform better than others at a given geometry. This review provides two key contributions to the body of literature. Firstly, a review of kinematic surrogates is put forward, along with a discussion on the whether these surrogates can be contextualised at different road geometries. Secondly, an extensive analysis and discussion of observer-based and video processed surrogate indicators, the collision types they aim to identify and the geometries they have been used at previously were analysed and advantages and disadvantages of the surrogates have been presented for future use. To do this, intersections, highways and roundabouts were selected and divided into geometry subtypes (i.e. three-legged and four-legged intersection) and segments (i.e. approaches to intersections and internal to the intersection) based on the likelihood of crash types and pre-crash manoeuvres occurring in that segment. Due to the lack of research around the use of kinematic triggers at road geometries, it is difficult to advocate for the use of any given trigger over another at a given geometry. Furthermore, it was found that kinematic triggers cannot accurately identify conflicts from naturalistic driving data and require the use of advanced statistical techniques such as machine learning to increase accuracy. A brief analysis of threshold identification techniques was also performed. Several future works have been put forward including the introduction of surrogates which capture conflict severity and the role of surrogate indicators in connected and automated vehicle environments.

PMID:34015605 | DOI:10.1016/j.aap.2021.106185

Eur J Oncol Nurs. 2021 May 13;52:101973. doi: 10.1016/j.ejon.2021.101973. Online ahead of print.

ABSTRACT

PURPOSE: The effects of burnout can have serious consequence for individual nurse’s, patients and healthcare organisations. The aim of this study was to assess prevalence and predictors of burnout and work-life balance amongst haemato-oncology nurses.

METHODS: This study employed a cross-sectional survey design. Haematology cancer nurses attending a 2-day conference in Ireland, during Oct 2019 were recruited. Anonymised data were collected on: 1) socio-demographics and occupational variables, 2) burnout using Maslach Burnout Inventory and 3) satisfaction with work-life balance.

RESULTS: There was an 80.4% survey completion rate (n = 78 of 97). One-third of haemato-oncology nurses reported high levels of emotional exhaustion, with an additional 46% experiencing moderate levels. Despite this, 64% of nurses highlighted a moderate or high level of personal accomplishment. Demographics such as <40yrs old, unmarried, working ≥25hrs per week and having 6-10 years’ experience in haemato-oncology, all showed trends towards increased burnout, although none reached statistical significance. Over half (58%) surveyed were dissatisfied with their work-life balance. Nurses with dependent children had statistically significant poorer work-life balance scores. In addition, one-third reported they did not receive adequate support or reasonable adjustments from their organisation, with inpatient nurses finding this particularly challenging.

RELEVANCE TO CLINICAL PRACTICE: Taking into consideration the high levels of burnout, healthcare organisations should have a responsibility to teach approaches of stress management, self-care and foster resilience within their workforce. Oncology nurses with dependent children, working in in-patient settings, have identified a need for greater flexibility with working conditions, to improve work-life balance.

PMID:34015591 | DOI:10.1016/j.ejon.2021.101973

Schizophr Res. 2021 May 17;232:45-53. doi: 10.1016/j.schres.2021.04.009. Online ahead of print.

ABSTRACT

AIM: A combination of olanzapine and samidorphan (OLZ/SAM) is in development for the treatment of patients with schizophrenia or bipolar I disorder and is intended to provide the efficacy of olanzapine while mitigating olanzapine-associated weight gain. This 52-week open-label extension (NCT02873208; ENLIGHTEN-2-EXT) assessed the long-term safety and tolerability of OLZ/SAM in patients with schizophrenia.

METHODS: Patients completing the 24-week randomized, double-blind, phase 3 ENLIGHTEN-2 study (NCT02694328) comparing weight change from baseline to week 24 with OLZ/SAM versus olanzapine were eligible to enroll in the 52-week ENLIGHTEN-2-EXT study. Assessments included adverse events (AEs; each visit), weight/waist circumference (every other week for the first 8 weeks, then every 4 weeks thereafter), metabolic laboratory parameters (weeks 4, 12, 24, 36, and 52), Positive and Negative Syndrome Scale (PANSS) scores (weeks 2, 4, 8, 12, 24, 36, and 52), and Clinical Global Impression-Severity (CGI-S) scores (weeks 2 and 4, then every 4 weeks thereafter through week 48, and at week 52). Analyses were based on observed results using descriptive statistics. Baseline was relative to the first OLZ/SAM dose in the extension study.

RESULTS: In total, 265 patients were enrolled and received at least 1 dose of OLZ/SAM; 167 (63.0%) completed the 52-week extension study. Common AEs (≥5%) were weight decreased (n = 23; 8.7%), extra dose administered (n = 21; 7.9%), headache (n = 18; 6.8%), and weight increased (n = 16; 6.0%). At week 52, the mean (SD) change from baseline for weight and waist circumference was -0.03 (6.17) kg and – 0.35 (6.12) cm, respectively. Changes in fasting lipid and glycemic parameters were generally small and remained stable over 52 weeks. During the extension, PANSS total scores remained stable, and at week 52, 81.3% of patients had CGI-S scores of 3 or less, reflecting mild illness severity.

CONCLUSIONS: OLZ/SAM was generally well tolerated over 52 weeks. Weight, waist circumference, metabolic laboratory parameters, and schizophrenia symptoms remained stable throughout the study.

PMID:34015555 | DOI:10.1016/j.schres.2021.04.009

Gait Posture. 2021 May 9;88:94-104. doi: 10.1016/j.gaitpost.2021.05.008. Online ahead of print.

ABSTRACT

BACKGROUND: Postural control requires the interaction of somatosensory, vestibular and visual systems to prevent disequilibrium. Children with strabismus have an impaired visual input which can lead to postural control deficits.

RESEARCH QUESTION: Does strabismus affect sensory organization for postural control in children?

METHODS: A systematic comprehensive search of multiple electronic databases for relevant articles was performed using a predetermined search strategy. Peer-reviewed journal publications that assessed sensory organization and postural performance in children with strabismus were included in this review. Methodological quality of the articles was evaluated using the modified Downs and Black quality assessment tool. A total of 10 articles were included in this review.

RESULTS: Eight of the 10 articles reviewed were included in the meta-analysis. Meta-analysis for Centre of Pressure CoP velocity (n = 3) (eyes open, stable support), was statistically significant (P = 0.01) in favor of controls over children with strabismus (MD, 3.08; 95 % CI -0.66, 5.51). Meta-analysis for CoP surface area (n = 5) (eyes open, stable support) was also statistically significant (P < 0.001) in favor of the control group (MD, 130.14; 95 % CI 70.01, 190.260). Meta-analysis with standardized mean difference (n = 6) for eyes open vs closed, stable support was statistically significant (P = 0.02) in favor of eyes open (MD, -0.94; 95 % CI, -1.74, -0.15). Overall, there was a high level of heterogeneity throughout the studies.

SIGNIFICANCE: This is the first systematic review of its kind to collate and synthesize evidence on the effect of strabismus on postural control in children. This review suggests that postural control performance in children with strabismus is inferior to that of age-matched control children. Further investigation is needed to understand the influence of the three sensory systems.

PMID:34015547 | DOI:10.1016/j.gaitpost.2021.05.008

Pract Radiat Oncol. 2021 May 17:S1879-8500(21)00121-1. doi: 10.1016/j.prro.2021.04.006. Online ahead of print.

ABSTRACT

OBJECTIVES: In patients with node-positive endometrial cancer, adjuvant radiotherapy with chemotherapy decreases local-regional recurrence compared to chemotherapy alone. However, optimal radiation field borders and extent of nodal coverage have not been well studied. In a multi-institutional cohort, survival outcomes and sites of failure were analyzed for patients with FIGO IIIC endometrioid endometrial cancer treated with pelvic (PRT) versus extended-field radiotherapy (EFRT), which encompassed high para-aortic lymph nodes.

METHODS: In a multi-institutional retrospective study, 143 patients with FIGO IIIC1 or IIIC2 endometrioid endometrial cancer treated with adjuvant radiotherapy from 2000-2016 were identified. Patient subgroups were classified by substage and radiation field extent: IIIC1 receiving EFRT, IIIC1 PRT, and IIIC2 EFRT. Recurrence-free (RFS), overall survival (OS) and out-of-field recurrence were calculated by Kaplan-Meier method. Multivariate analysis was performed by Cox proportional hazard. Sites of failure were categorized as within or outside the radiation field.

RESULTS: Median follow-up was 59 months; 87% received chemotherapy. Five-year RFS and OS rates were 73% and 87%, respectively. By subgroup, 5-year RFS rates were: 79% IIIC1 EFRT, 73% IIIC1 PRT and 69% IIIC2 EFRT (p=0.4). On MVA, recurrence risk was highest for IIIC2 EFRT, although not statistically significant (adjusted hazard ratio 2.0, p=0.4). In-field vaginal and nodal recurrences were observed in 2 (1%) and 4 (3%) patients, respectively. Of 78 stage IIIC1 patients treated with PRT, 5 (6%) had isolated para-aortic nodal relapse outside the radiation field; 3 were long-term survivors more than 6 years after salvage therapy. For patients with para-aortic recurrence, most had lymphovascular invasion (86%), ≥50% myometrial invasion (71%) and/or grade 3 disease (57%).

CONCLUSIONS: Adjuvant chemoradiotherapy results in excellent survival outcomes for patients with FIGO IIIC endometrioid endometrial cancer. For patients with positive pelvic nodes, isolated para-aortic relapse outside the PRT field was uncommon and amenable to salvage therapy.

PMID:34015544 | DOI:10.1016/j.prro.2021.04.006