The Impact of Combined Sewer Overflows on Pharmaceutical and Illicit Drug Levels in New York/New Jersey Waterways.

Pharmaceuticals and drugs of abuse are organic micropollutants of emerging concern in both surface and groundwater worldwide. These compounds are considered to be pseudo-persistent because of their continuous release into water systems. The presence of these compounds in the environment at any concentration poses a potential risk to nontarget organisms. The main sources of these contaminants are wastewater treatment plants (WWTPs) and combined sewer overflows (CSOs). The primary goal of our study was to identify and quantify a panel of 28 commonly prescribed pharmaceuticals (mood-altering drugs, cardiovascular drugs, antacids, antibiotics) and high-prevalence drugs of abuse (cocaine, amphetamines, opioids, cannabis) in river water samples collected from 19 locations in the Hudson and East rivers in New York City. The second goal was to investigate the possible source (WWTP or CSOs) of these micropollutants. Samples were collected weekly from May to August 2021 (n = 224) and May to August 2022 (n = 232), and placed at -20 °C until analysis by liquid chromatography-tandem mass spectrometry. The most frequently detected analytes in 2021 were metoprolol (n = 206, 92%), benzoylecgonine (n = 151, 67%), atenolol (n = 142, 63%), and methamphetamine (n = 118, 53%), and in 2022 the most frequently detected were methamphetamine (n = 194, 84%), atenolol (n = 177, 76%), metoprolol (n = 177, 76%), and 2-ethylene-1,5-dimethyl-3,3-diphenylpyrrolidine (n = 159, 69%). Measured concentrations ranged from the limit of detection (0.50-5.00 ng/L) to 103 ng/L. More drugs and higher concentrations were detected in water contaminated by Enterococci (>60 most probably number) and after rainfall, indicating the influence of CSOs. The presence of drugs in samples with little to no Enterococci and after dry weather events indicates that WWTPs contribute to the presence of these substances in the river, probably due to a low removal rate. Environ Toxicol Chem 2024;43:1592-1603. © 2024 SETAC.

Women who decline blood during labour: Review of findings and lessons learnt from 52 years of Confidential Enquiries into maternal mortality in the United Kingdom (1962-2019).

OBJECTIVE: Patients who decline blood products because of their religious beliefs pose a unique challenge in the context of obstetric haemorrhage. Four large series assessing maternal outcomes in Jehovah's Witnesses from USA, UK, Netherlands and Japan estimate that maternal mortality is increased by between 44 and 160-fold. A review of maternal deaths from obstetric haemorrhage was undertaken in mothers who decline blood transfusion, using UK Confidential Enquiries into Maternal Deaths reports (1967-2019) in order to identify common trends and lessons learnt. DESIGN: Retrospective review using 18 triennial Confidential Enquiries in Maternal Deaths reports between 1967 and 2019. RESULTS: Fifteen maternal deaths from haemorrhage were reported in patients who declined blood products for religious beliefs in the 52 years reviewed. Common themes noted included delay in senior escalation, hesitation to perform life-saving hysterectomy and loss of situational awareness. Placental abruptions (3/15) and curettage for secondary postpartum haemorrhage (2/15) especially warrant senior input and cooperation with Jehovah's Witness Hospital Liaison Committees is recommended. CONCLUSIONS: Guidelines from the UK's Royal College of Obstetricians and Gynaecologists and Royal College of Surgeons highlight the need for collaborative, Montgomery-competent discussions during the antenatal period, as well as the engagement of local Jehovah's Witness Hospital Liaison committees. Consultant-led care, antenatal optimisation of haemoglobin and techniques to mitigate blood loss at delivery are paramount. We advocate using a lower threshold for hysterectomy than was used in the cases analysed, for example when the haemoglobin level drops below 8-9 g/l in the context of ongoing bleeding. As patients increasingly begin to decline blood products for non-religious reasons, the lessons learnt in the management of Jehovah's Witnesses are becoming ever more relevant.

Hormonal modulation of ESR1 mutant metastasis.

Estrogen receptor alpha gene (ESR1) mutations occur frequently in ER-positive metastatic breast cancer, and confer clinical resistance to aromatase inhibitors. Expression of the ESR1 Y537S mutation induced an epithelial-mesenchymal transition (EMT) with cells exhibiting enhanced migration and invasion potential in vitro. When small subpopulations of Y537S ESR1 mutant cells were injected along with WT parental cells, tumor growth was enhanced with mutant cells becoming the predominant population in distant metastases. Y537S mutant primary xenograft tumors were resistant to the antiestrogen tamoxifen (Tam) as well as to estradiol (E2) withdrawal. Y537S ESR1 mutant primary tumors metastasized efficiently in the absence of E2; however, Tam treatment significantly inhibited metastasis to distant sites. We identified a nine-gene expression signature, which predicted clinical outcomes of ER-positive breast cancer patients, as well as breast cancer metastasis to the lung. Androgen receptor (AR) protein levels were increased in mutant models, and the AR agonist dihydrotestosterone significantly inhibited estrogen-regulated gene expression, EMT, and distant metastasis in vivo, suggesting that AR may play a role in distant metastatic progression of ESR1 mutant tumors.

Hyperglycaemia is associated with impaired muscle signalling and aerobic adaptation to exercise.

Increased aerobic exercise capacity, as a result of exercise training, has important health benefits. However, some individuals are resistant to improvements in exercise capacity, probably due to undetermined genetic and environmental factors. Here, we show that exercise-induced improvements in aerobic capacity are blunted and aerobic remodelling of skeletal muscle is impaired in several animal models associated with chronic hyperglycaemia. Our data point to chronic hyperglycaemia as a potential negative regulator of aerobic adaptation, in part, via glucose-mediated modifications of the extracellular matrix, impaired vascularization and aberrant mechanical signalling in muscle. We also observe low exercise capacity and enhanced c-Jun N-terminal kinase activation in response to exercise in humans with impaired glucose tolerance. Our work indicates that current shifts in dietary and metabolic health, associated with increasing incidence of hyperglycaemia, might impair muscular and organismal adaptations to exercise training, including aerobic capacity as one of its key health outcomes.

Corrigendum to "Mouse Mesenchymal Progenitor Cells Expressing Adipogenic and Osteogenic Transcription Factors Suppress the Macrophage Inflammatory Response".

[This corrects the article DOI: 10.1155/2017/5846257.].

Getting to Know the Gut Microbial Diversity of Metropolitan Buenos Aires Inhabitants.

In recent years, the field of immunology has been revolutionized by the growing understanding of the fundamental role of microbiota in the immune system function. The immune system has evolved to maintain a symbiotic relationship with these microbes. The aim of our study was to know in depth the uncharacterized metagenome of the Buenos Aires (BA) city population and its metropolitan area, being the second most populated agglomeration in the southern hemisphere. For this purpose, we evaluated 30 individuals (age: 35.23 ± 8.26 years and BMI: 23.91 ± 3.4 kg/m2), from the general population of BA. The hypervariable regions V3-V4 of the bacterial 16S gene was sequenced by MiSeq-Illumina system, obtaining 47526 ± 4718 sequences/sample. The dominant phyla were Bacteroidetes, Firmicutes, Proteobacteria, Verrucomicrobia, and Actinobacteria. Additionally, we compared the microbiota of BA with other westernized populations (Santiago de Chile, Rosario-Argentina, United States-Human-microbiome-project, Bologna-Italy) and the Hadza population of hunter-gatherers. The unweighted UniFrac clustered together all westernized populations, leaving the hunter-gatherer population from Hadza out. In particular, Santiago de Chile's population turns out to be the closest to BA's, principally due to the presence of Verrucomicrobiales of the genus Akkermansia. These microorganisms have been proposed as a hallmark of a healthy gut. Finally, westernized populations showed more abundant metabolism related KEEG pathways than hunter-gatherers, including carbohydrate metabolism (amino sugar and nucleotide sugar metabolism), amino acid metabolism (alanine, aspartate and glutamate metabolism), lipid metabolism, biosynthesis of secondary metabolites, and sulfur metabolism. These findings contribute to promote research and comparison of the microbiome in different human populations, in order to develop more efficient therapeutic strategies for the restoration of a healthy dialogue between host and environment.

Mouse Mesenchymal Progenitor Cells Expressing Adipogenic and Osteogenic Transcription Factors Suppress the Macrophage Inflammatory Response.

Mesenchymal progenitor cell characteristics that can identify progenitor populations with specific functions in immunity are actively being investigated. Progenitors from bone marrow and adipose tissue regulate the macrophage (MΦ) inflammatory response by promoting the switch from an inflammatory to an anti-inflammatory phenotype. Conversely, mesenchymal progenitors from the mouse aorta (mAo) support and contribute to the MΦ response under inflammatory conditions. We used cell lines with purported opposing immune-regulatory function, a bone marrow derived mesenchymal progenitor cell line (D1) and a mouse aorta derived mesenchymal progenitor cell line (mAo). Their interaction and regulation of the MΦ cell response to the inflammatory mediator, lipopolysaccharide (LPS), was examined by coculture. As expected, D1 cells suppressed NO, TNF-α, and IL-12p70 production but MΦ phagocytic activity remained unchanged. The mAo cells enhanced NO and TNF-α production in coculture and enhanced MΦ phagocytic activity. Using flow cytometry and PCR array, we then sought to identify sets of MSC-associated genes and markers that are expressed by these progenitor populations. We have determined that immune-supportive mesenchymal progenitors highly express chondrogenic and tenogenic transcription factors while immunosuppressive mesenchymal progenitors highly express adipogenic and osteogenic transcription factors. These data will be useful for the isolation, purification, and modification of mesenchymal progenitors to be used in the treatment of inflammatory diseases.