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Frontiers in Endocrinology 2023We present a comprehensive overview of changes in thyroxine (T4) and thyroid stimulating hormone (TSH) serum concentrations after pre-gestational, gestational and/or...
We present a comprehensive overview of changes in thyroxine (T4) and thyroid stimulating hormone (TSH) serum concentrations after pre-gestational, gestational and/or lactation exposures of rodents to various chemicals that affect the thyroid hormone system. We show that T4 and TSH changes consistent with the idealized view of the hypothalamic-pituitary-thyroid (HPT) feedback loop (T4 decrements accompanied by TSH increases) are observed with only a relatively small set of chemicals. Most substances affect concentrations of various thyroid hormones without increasing TSH. Studies of altered T4 concentrations after gestational exposures are limited to a relatively small set of chemicals in which pesticides, pharmaceuticals and industrial chemicals are under-represented. Our risk-of-bias analysis exposed deficits in T4/TSH analytics as a problem area. By relating patterns of T4 - TSH changes to mode-of-action (MOA) information, we found that chemicals capable of disrupting the HPT feedback frequently affected thyroid hormone synthesis, while substances that produced T4 serum decrements without accompanying TSH increases lacked this ability, but often induced liver enzyme systems responsible for the elimination of TH by glucuronidation. Importantly, a multitude of MOA leads to decrements of serum T4. The current EU approaches for identifying thyroid hormone system-disrupting chemicals, with their reliance on altered TH serum levels as indicators of a hormonal mode of action and thyroid histopathological changes as indicators of adversity, will miss chemicals that produce T4/T3 serum decreases without accompanying TSH increases. This is of concern as it may lead to a disregard for chemicals that produce developmental neurotoxicity by disrupting adequate T4/T3 supply to the brain, but without increasing TSH.
Topics: Animals; Female; Rodentia; Thyroid Hormones; Thyroxine; Thyroid Gland; Thyrotropin
PubMed: 38352246
DOI: 10.3389/fendo.2023.1323284 -
Journal of Environmental Management Feb 2024Biofiltration utilizes natural mechanisms including biodegradation and biotransformation along with other physical processes for the removal of organic micropollutants... (Review)
Review
Biofiltration utilizes natural mechanisms including biodegradation and biotransformation along with other physical processes for the removal of organic micropollutants (OMPs) such as pharmaceuticals, personal care products, pesticides and industrial compounds found in (waste)water. In this systematic review, a total of 120 biofiltration studies from 25 countries were analyzed, considering various biofilter configurations, source water types, biofilter media and scales of operation. The study also provides a bibliometric analysis to identify the emerging research trends in the field. The results show that granular activated carbon (GAC) either alone or in combination with another biofiltration media can remove a broad range of OMPs efficiently. The impact of pre-oxidation on biofilter performance was investigated, revealing that pre-oxidation significantly improved OMP removal and reduced the empty bed contact time (EBCT) needed to achieve a consistently high OMP. Biofiltration with pre-oxidation had median removals ranging between 65% and >90% for various OMPs at 10-45 min EBCT with data variability drastically reducing beyond 20 min EBCT. Biofiltration without pre-oxidation had lower median removals with greater variability. The results demonstrate that pre-oxidation greatly enhances the removal of adsorptive and poorly biodegradable OMPs, while its impact on other OMPs varies. Only 19% of studies we reviewed included toxicity testing of treated effluent, and even fewer measured transformation products. Several studies have previously reported an increase in effluent toxicity because of oxidation, although it was successfully abated by subsequent biofiltration in most cases. Therefore, the efficacy of biofiltration treatment should be assessed by integrating toxicity testing into the assessment of overall removal.
Topics: Filtration; Water Purification; Water Pollutants, Chemical; Charcoal; Water
PubMed: 38325285
DOI: 10.1016/j.jenvman.2024.120203 -
Archives of Iranian Medicine Oct 2023Many human diseases such as cancer, neurological diseases, autism and diabetes are associated with exposure to pesticides, especially organochlorine pesticides. However,...
Many human diseases such as cancer, neurological diseases, autism and diabetes are associated with exposure to pesticides, especially organochlorine pesticides. However, pesticide exposure is also associated with cardiovascular disease (CVD) as the leading cause of death worldwide. In this systematic review, results on the link between organochlorine pesticide pollution and CVD were collected from databases (Medline (PubMed), Scopus and Science Direct) in May 2022 from studies published between 2010 and 2022. A total of 24 articles were selected for this systematic review. Sixteen articles were extracted by reviewers using a standardized form that included cross-sectional, cohort, and ecological studies that reported exposure to organochlorine pesticides in association with increased CVD risk. In addition, eight articles covering molecular mechanisms organochlorine pesticides and polychlorinated biphenyls (PCBs) on cardiovascular effects were retrieved for detailed evaluation. Based on the findings of the study, it seems elevated circulating levels of organochlorine pesticides and PCBs increase the risk of coronary heart disease, especially in early life exposure to these pesticides and especially in men. Changes in the regulatory function of peroxisome proliferator-activated γ receptor (PPARγ), reduction of paroxonase activity (PON1), epigenetic changes of histone through induction of reactive oxygen species, vascular endothelial inflammation with miR-expression 126 and miR-31, increased collagen synthesis enzymes in the extracellular matrix and left ventricular hypertrophy (LVH) and fibrosis are mechanisms by which PCBs increase the risk of CVD. According to this systematic review, organochlorine pesticide exposure is associated with increased risk of CVD and CVD mortality through the atherogenic and inflammatory molecular mechanism involving fatty acid and glucose metabolism.
Topics: Male; Humans; Polychlorinated Biphenyls; Environmental Pollutants; Cardiovascular Diseases; Cross-Sectional Studies; Hydrocarbons, Chlorinated; Pesticides; MicroRNAs; Aryldialkylphosphatase
PubMed: 38310416
DOI: 10.34172/aim.2023.86 -
BMC Cardiovascular Disorders Jan 2024Atrial fibrillation (AF) is the most frequently observed cardiac arrhythmia in clinical settings. Obesity can influence the efficacy of the treatment administered, which... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIM
Atrial fibrillation (AF) is the most frequently observed cardiac arrhythmia in clinical settings. Obesity can influence the efficacy of the treatment administered, which requires a larger dose and more time to accomplish therapeutic targets due to altered pathophysiology. Our study aimed to assess the overall efficacy and safety of nonvitamin K antagonist oral anticoagulants (NOACs) versus warfarin in AF patients with morbid obesity (BMI > 40 kg/m2 and/or weight > 120 kg) to prevent complications.
METHODS
We conducted a literature search on PubMed, Web of Science, the Cochrane Library, and Scopus till October 2022 for articles addressing the efficacy and safety of NOACs versus warfarin for the treatment of AF in morbidly obese patients. We performed the meta-analysis with RevMan software version 5.4 and Open Meta Analyst. The main outcomes assessed were stroke, major bleeding, and minor bleeding after anticoagulation, as did the history of comorbidities and risk factors in morbidly obese patients. Quality assessment was performed using Cochrane's ROB-2 tool and the Newcastle-Ottawa scale.
RESULTS
Regarding major bleeding events, pooled data showed that patients taking NOACs had a significantly lower risk than patients taking warfarin (OR = 0.54, 95% CI: [0.41-0.70]; p < 0.00001). However, for minor bleeding, there was a nonsignificant effect of NOACs on reducing the risk of bleeding (OR = 0.72, 95% CI = 0.47-1.09; p = 0.12), which became highly significant in favor of NOACs after sensitivity analysis (OR = 0.55, 95% CI = 0.49-0.61]; p < 0.00001). There was a significant difference in the incidence of stroke between the NOAC group and the warfarin group (OR = 0.69, 95% CI = 0.60-0.80]; p < 0.00001). According to the results of the single-arm study analysis, the overall effect of all the outcomes was associated with a high risk of disease development in patients receiving NOACs.
CONCLUSION
Our meta-analysis showed a favorable effect of NOACs vs warfarin in morbidly obese patients. Some outcomes were not significantly different, which calls for future research to better assess their safety and efficacy in this particular weight group.
TRIAL REGISTRATION
The study was registered with PROSPERO under registration number CRD42022362493 on October 2022.
Topics: Humans; Administration, Oral; Anticoagulants; Atrial Fibrillation; Hemorrhage; Obesity, Morbid; Stroke; Treatment Outcome; Warfarin
PubMed: 38279126
DOI: 10.1186/s12872-024-03731-3 -
Drug Safety May 2024Glucagon-like peptide 1 receptor agonists (GLP1RAs) are used in the treatment of diabetes and obesity. Their slowing effect of gastric emptying might change oral drug...
BACKGROUND
Glucagon-like peptide 1 receptor agonists (GLP1RAs) are used in the treatment of diabetes and obesity. Their slowing effect of gastric emptying might change oral drug absorption, potentially affecting pharmacokinetics, particularly in the case of medications with a narrow therapeutic index.
PURPOSE
The purpose of this systematic review is to summarize data on drug-drug interactions between GLP1RAs and oral drugs.
DATA SOURCES
The PubMed and EMBASE databases were searched up to November, 1st 2023.
STUDY SELECTION
We selected pharmacokinetic studies of any injectable GLP1RA given with an oral medication, and product prescribing sheets reporting data without access to the original study.
DATA EXTRACTION
Two authors independently extracted the data.
DATA SYNTHESIS
Twenty-two reports and six prescribing sheets were included. Treatment with GLP1RAs resulted in unaffected or reduced C and delayed t of drugs with high solubility and permeability (warfarin, contraceptive pills, acetaminophen), drugs with high solubility and low permeability (angiotensin converting enzyme inhibitors), drugs with low solubility and high permeability (statins) and drugs with low solubility and permeability (digoxin). However, the use of GLP1RAs did not exert clinically significant changes in the AUC or differences in clinically relevant endpoints.
LIMITATIONS
The major limitations of the studies that are included in this systematic review are the enrollment of healthy subjects and insufficient data in conditions that might affect pharmacokinetics (e.g., kidney dysfunction).
CONCLUSIONS
To conclude, reduced C and delayed t of drugs co-administered with GLP1RAs are consistent with the known delayed gastric output by the latter. Nevertheless, the overall drug exposure was not considered clinically significant. Dose adjustments are probably not required for simultaneous use of GLP1RAs with oral medications. Still, results should be carefully generalized to cases of background kidney dysfunction or when using drugs with narrow therapeutic index. The study is registered in PROSPERO: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022332339 .
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Digoxin; Drug Interactions; Glucagon-Like Peptide 1; Warfarin
PubMed: 38273155
DOI: 10.1007/s40264-023-01392-3 -
Alzheimer's & Dementia : the Journal of... Apr 2024The prevalence of cerebral smallvessel disease (SVD) and vascular dementia according to workplace or domestic exposure to hazardous substances is unclear. (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The prevalence of cerebral smallvessel disease (SVD) and vascular dementia according to workplace or domestic exposure to hazardous substances is unclear.
METHODS
We included studies assessing occupational and domestic hazards/at-risk occupations and SVD features. We pooled prevalence estimates using random-effects models where possible, or presented a narrative synthesis.
RESULTS
We included 85 studies (n = 47,743, mean age = 44·5 years). 52/85 reported poolable estimates. SVD prevalence in populations exposed to carbon monoxide was 81%(95% CI = 60-93%; n = 1373; results unchanged in meta-regression), carbon disulfide73% (95% CI = 54-87%; n = 131), 1,2-dichloroethane 88% (95% CI = 4-100%, n = 40), toluene 82% (95% CI = 3-100%, n = 64), high altitude 49% (95% CI = 38-60%; n = 164),and diving 24% (95% CI = 5-67%, n = 172). We narratively reviewed vascular dementia studies and contact sport, lead, military, pesticide, and solvent exposures as estimates were too few/varied to pool.
DISCUSSION
SVD and vascular dementia may be associated with occupational/domestic exposure to hazardous substances. CRD42021297800.
Topics: Humans; Adult; Dementia, Vascular; Cerebral Small Vessel Diseases; Hazardous Substances; Magnetic Resonance Imaging
PubMed: 38270898
DOI: 10.1002/alz.13647 -
The Science of the Total Environment Mar 2024Fipronil and imidacloprid have been widely detected in UK surface waters in recent years, often at concentrations that ecotoxicological studies have shown can harm...
Fipronil and imidacloprid have been widely detected in UK surface waters in recent years, often at concentrations that ecotoxicological studies have shown can harm aquatic life. Down-the-drain (DTD) passage of pet flea and tick treatments are being implicated as an important source, with many of the UK's 22 million cats and dogs receiving routine, year-round preventative doses containing these parasiticides. The UK Water Industry's 3rd Chemical Investigation Programme (UKWIR CIP3) has confirmed wastewater as a major entry pathway for these chemicals into surface waters, but the routes by which they enter the wastewater system remain unclear. We addressed this knowledge gap by conducting the first quantification of DTD emissions from 98 dogs treated with spot-on ectoparasiticides containing fipronil or imidacloprid, through bathing, bed washing and washing of owners' hands. Both chemicals were detected in 100 % of washoff samples, with bathing accounting for the largest emissions per event (up to 16.8 % of applied imidacloprid and 24.5 % of applied fipronil). Modelled to account for the frequency of emitting activities, owner handwashing was identified as the largest source of DTD emissions from the population overall, with handwash emissions occurring for at least 28 days following product application and an estimated 4.9 % of imidacloprid and 3.1 % of fipronil applied in dog spot-ons passing down-the-drain via this route. The normalised daily per capita emissions for all routes combined were 8.7 μg/person/day for imidacloprid and 2.1 μg/person/day for fipronil, equivalent to 20-40 % of the daily per capita load in wastewater, as estimated from UKWIR CIP3 data. Within the current international regulatory framework adhered to by the UK, the environmental exposure of veterinary medicines intended for use in small companion animals is assumed to be low, and DTD pathways are not considered. We recommend a systematic review of regulations and practices to address this overlooked pollution pathway.
Topics: Humans; Animals; Dogs; Cats; Insecticides; Antiparasitic Agents; Wastewater; Neonicotinoids; Nitro Compounds; Pyrazoles
PubMed: 38244617
DOI: 10.1016/j.scitotenv.2024.170175 -
PLoS Neglected Tropical Diseases Jan 2024Lymphatic filariasis (LF) is a neglected tropical disease (NTD) targeted by the World Health Organization for elimination as a public health problem (EPHP). Since 2000,...
BACKGROUND
Lymphatic filariasis (LF) is a neglected tropical disease (NTD) targeted by the World Health Organization for elimination as a public health problem (EPHP). Since 2000, more than 9 billion treatments of antifilarial medicines have been distributed through mass drug administration (MDA) programmes in 72 endemic countries and 17 countries have reached EPHP. Yet in 2021, nearly 900 million people still required MDA with combinations of albendazole, diethylcarbamazine and/or ivermectin. Despite the reliance on these drugs, there remain gaps in understanding of variation in responses to treatment. As demonstrated for other infectious diseases, some urgent questions could be addressed by conducting individual participant data (IPD) meta-analyses. Here, we present the results of a systematic literature review to estimate the abundance of IPD on pre- and post-intervention indicators of infection and/or morbidity and assess the feasibility of building a global data repository.
METHODOLOGY
We searched literature published between 1st January 2000 and 5th May 2023 in 15 databases to identify prospective studies assessing LF treatment and/or morbidity management and disease prevention (MMDP) approaches. We considered only studies where individual participants were diagnosed with LF infection or disease and were followed up on at least one occasion after receiving an intervention/treatment.
PRINCIPAL FINDINGS
We identified 138 eligible studies from 23 countries, having followed up an estimated 29,842 participants after intervention. We estimate 14,800 (49.6%) IPD on pre- and post-intervention infection indicators including microfilaraemia, circulating filarial antigen and/or ultrasound indicators measured before and after intervention using 8 drugs administered in various combinations. We identified 33 studies on MMDP, estimating 6,102 (20.4%) IPD on pre- and post-intervention clinical morbidity indicators only. A further 8,940 IPD cover a mixture of infection and morbidity outcomes measured with other diagnostics, from participants followed for adverse event outcomes only or recruited after initial intervention.
CONCLUSIONS
The LF treatment study landscape is heterogeneous, but the abundance of studies and related IPD suggest that establishing a global data repository to facilitate IPD meta-analyses would be feasible and useful to address unresolved questions on variation in treatment outcomes across geographies, demographics and in underrepresented groups. New studies using more standardized approaches should be initiated to address the scarcity and inconsistency of data on morbidity management.
Topics: Humans; Elephantiasis, Filarial; Prospective Studies; Filaricides; Diethylcarbamazine; Albendazole; Ivermectin
PubMed: 38227595
DOI: 10.1371/journal.pntd.0011882 -
PeerJ 2024Residues of pesticides on crops can result in mortality to foraging bees. Pesticide applicators in the U.S. encounter a statement on pesticide labels, which coarsely...
Residues of pesticides on crops can result in mortality to foraging bees. Pesticide applicators in the U.S. encounter a statement on pesticide labels, which coarsely indicate which products dissipate over the course of an evening. There is reason to suspect that these statements may not align with residual toxicity data, given previous findings. Without a complete database of residual toxicity estimates; however, it is not possible to determine whether the residual toxicity components of statements on pesticide labels similarly diverge from published studies. We compiled 50 studies on residual toxicity trials with formulated pesticides and calculated the residual time to 25% mortality (RT) of each assay for three different bee species (, and ). Our findings were compared to a U.S. Environmental Protection Agency (EPA) published database of RT values. Of the RT values that we could compare, we found that over 90% of the values support a similar conclusion to the EPA. Next, we compared our values and the EPA's values to the statements on 155 EPA registered pesticide product labels. Of these labels, a little less than a third presented their residual toxicity in a manner inconsistent with their calculated RT and current EPA labeling guidelines. Moreover, over a third of labels contained an active ingredient which was neither listed under the EPA's RT database nor had a published study to estimate this value. We provide the first evidence that many pesticide labels may convey residual toxicity information to applicators that is not correct and could lead to bees being exposed to toxic residues on plants.
Topics: United States; Animals; Bees; Biological Assay; Crops, Agricultural; Databases, Factual; Pesticides; Product Labeling
PubMed: 38188157
DOI: 10.7717/peerj.16672 -
The American Journal of Tropical... Apr 2024In the final stages of malaria elimination, interventions to reduce malaria transmission are often centered around a confirmed case of malaria, as cases tend to cluster...
In the final stages of malaria elimination, interventions to reduce malaria transmission are often centered around a confirmed case of malaria, as cases tend to cluster together at very low levels of transmission. The WHO commissioned a systematic review of the literature and synthesis of evidence for reactive indoor residual spraying (IRS) to develop official recommendations for countries. Several electronic databases were searched in November 2020. A total of 455 records were identified and screened; 20 full-text articles were assessed for eligibility. Two cluster-randomized trials met the inclusion criteria for epidemiological outcomes. Risk of bias was assessed using standard criteria. Because one study was a superiority trial in which the comparator included reactive case detection or mass drug administration and the other was a noninferiority trial in which the comparator was proactive, focal IRS, results could not be pooled. In the superiority trial, reactive IRS reduced malaria prevalence by 68% (risk ratio [RR]: 0.32; 95% CI: 0.13-0.80; certainty of evidence: HIGH) compared with no reactive IRS. No difference was observed for clinical malaria (RR: 0.65; 95% CI: 0.38-1.11; certainty of evidence: MODERATE). In the noninferiority study, the mean difference in incidence between reactive IRS and proactive IRS was 0.10 additional case per 1,000 person-years, which was within the prespecified noninferiority bound (95% CI: -0.38 to 0.58; certainty of evidence: MODERATE). The evidence indicates that reactive IRS may be a cost-effective tool for the prevention of malaria in elimination settings. As only two cluster-randomized controlled trials from sub-Saharan Africa were found, additional high-quality studies should be encouraged.
Topics: Humans; Malaria; Africa South of the Sahara; Insecticide-Treated Bednets; Mass Drug Administration; Incidence; Insecticides; Mosquito Control
PubMed: 38118168
DOI: 10.4269/ajtmh.22-0745