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Journal of Environmental Management May 2024Drawing upon an extensive body of valuation literature focused on water quality, this paper performs a meta-analysis benefit transfer exercise aimed at quantifying...
Drawing upon an extensive body of valuation literature focused on water quality, this paper performs a meta-analysis benefit transfer exercise aimed at quantifying willingness to pay (WTP) for an enhancement in drinking water quality for households that have been directly exposed to Perfluoroalkyl Substances (PFAS) over recent decades in Italy. The analysis compiles metadata of 72 WTP estimates extracted from 40 previous valuation studies conducted in advanced economies. The benefit transfer is realized estimating a meta regression model (MRM) which includes both study design and socio-economic explanatory variables, according to the Weak Structural Utility Theoretic approach. To determine the most suitable MRM specification, a comparative evaluation of various model configurations is developed exploiting the Least Absolute Shrinkage and Selection Operator (LASSO) selection criterion, and assessing their predictive performances in terms of transfer error and explanatory power. The mean transfer error (MTE) and the adjusted R-squared of the preferred MRM are in line with past published meta-analyses (0.665 and 0.607, respectively). The parameters estimated in the model align with both economic theory and intuition. The benefit transfer process results in an estimated annual WTP of € 250.80 per household for improved drinking water quality in the PFAS-affected area and an aggregated value of social benefits from PFAS decontamination of around € 12 million.
PubMed: 38772240
DOI: 10.1016/j.jenvman.2024.121143 -
Microbiology Spectrum May 2024Probiotics refer to living microorganisms that exert a variety of beneficial effects on human health. On the contrary, they also can cause infection, produce toxins...
UNLABELLED
Probiotics refer to living microorganisms that exert a variety of beneficial effects on human health. On the contrary, they also can cause infection, produce toxins within the body, and transfer antibiotic-resistant genes to the other microorganisms in the digestive tract necessitating a comprehensive safety assessment. This study aimed to conduct functional genomic analysis and some relevant biochemical tests to uncover the probiotic potentials of subsp. TY-11 isolated from native yogurt in Bangladesh. We also performed transmission electron microscopic (TEM) analysis, comparative genomic study as well as phylogenetic tree construction with 332 core genes from 262 genomes. The strain TY-11 was identified as subsp. whose genome (1,916,674 bp) contained 1911 CDS, and no gene was identified for either antibiotic resistance or toxic metabolites. It carried genes for the degradation of toxic metabolites, treatment of lactose intolerance, toll-like receptor 2-dependent innate immune response, heat and cold shock, bile salts tolerance, and acidic pH tolerance. Genes were annotated for inhibiting pathogenic bacteria by inhibitory substances [bacteriocin: Helveticin-J (331 bp) and Enterolysin-A (275 bp), hydrogen peroxide, and acid]; blockage of adhesion sites; and competition for nutrients. The genes involved in its metabolic pathway were detected as suitable for digesting indigestible nutrients in the human gut. The TY-11 genome possessed an additional 37 core genes of subspecies which were deficient in the core genome of the most popular subsp. . During the phenotypic testing, the isolate TY-11 demonstrated high antagonistic activity (inhibition zone of 21.33 ± 1.53 mm) against ATCC 8739 and was not sensitive to any of the 10 tested antibiotics. This study was the first study to explore the molecular insights into probiotic roles, including antimicrobial activities and antibiotic sensitivity, of a representative strain (TY-11) of subsp. .
IMPORTANCE
This study aimed to conduct functional genomic analysis to uncover the probiotic potential of subsp. TY-11 isolated from native yogurt in Bangladesh. We also performed transmission electron microscopic (TEM) analysis, comparative genomic study as well as phylogenetic tree construction with 332 core genes from 262 genomes. In our current investigation, we revealed a number of common and unique excellences of the probiotic subsp. TY-11 that are likely to be important to illustrate its intestinal residence and probiotic roles. This is the first study to explore the molecular insights into intestinal residence and probiotic roles, including antimicrobial activities and antibiotic sensitivity, of a representative strain (TY-11) of subsp. .
PubMed: 38771133
DOI: 10.1128/spectrum.03470-23 -
Zoological Research May 2024Painful stimuli elicit first-line reflexive defensive reactions and, in many cases, also evoke second-line recuperative behaviors, the latter of which reflects the...
Painful stimuli elicit first-line reflexive defensive reactions and, in many cases, also evoke second-line recuperative behaviors, the latter of which reflects the sensing of tissue damage and the alleviation of suffering. The lateral parabrachial nucleus (lPBN), composed of external- (elPBN), dorsal- (dlPBN), and central/superior-subnuclei (jointly referred to as slPBN), receives sensory inputs from spinal projection neurons and plays important roles in processing affective information from external threats and body integrity disruption. However, the organizational rules of lPBN neurons that provoke diverse behaviors in response to different painful stimuli from cutaneous and deep tissues remain unclear. In this study, we used region-specific neuronal depletion or silencing approaches combined with a battery of behavioral assays to show that slPBN neurons expressing substance P receptor ( ) (lPBN ) are crucial for driving pain-associated self-care behaviors evoked by sustained noxious thermal and mechanical stimuli applied to skin or bone/muscle, while elPBN neurons are dispensable for driving such reactions. Notably, lPBN neurons are specifically required for forming sustained somatic pain-induced negative teaching signals and aversive memory but are not necessary for fear-learning or escape behaviors elicited by external threats. Lastly, both lPBN and elPBN neurons contribute to chemical irritant-induced nocifensive reactions. Our results reveal the functional organization of parabrachial substrates that drive distinct behavioral outcomes in response to sustained pain versus external danger under physiological conditions.
Topics: Animals; Parabrachial Nucleus; Mice; Nociception; Neurons; Pain; Male; Behavior, Animal
PubMed: 38766746
DOI: 10.24272/j.issn.2095-8137.2023.412 -
European Journal of Histochemistry : EJH May 2024Previous studies on the granular layer of the cerebellar cortex have revealed a wide distribution of different subpopulations of less-known large neuron types, called... (Review)
Review
Previous studies on the granular layer of the cerebellar cortex have revealed a wide distribution of different subpopulations of less-known large neuron types, called "non-traditional large neurons", which are distributed in three different zones of the granular layer. These neuron types are mainly involved in the formation of intrinsiccircuits inside the cerebellar cortex. A subpopulation of these neuron types is represented by the synarmotic neuron, which could play a projective role within the cerebellar circuitry. The synarmotic neuron cell body map within the internal zone of the granular layer or in the subjacent white substance. Furthermore, the axon crosses the granular layer and runs in the subcortical white substance, to reenter in an adjacent granular layer, associating two cortico-cerebellar regions of the same folium or of different folia, or could project to the intrinsic cerebellar nuclei. Therefore, along with the Purkinje neuron, the traditional projective neuron type of the cerebellar cortex, the synarmotic neuron is candidate to represent the second projective neuron type of the cerebellar cortex. Studies of chemical neuroanatomy evidenced a predominant inhibitory GABAergic nature of the synarmotic neuron, suggesting that it may mediate an inhibitory GABAergic output of cerebellar cortex within cortico-cortical interconnections or in projections towards intrinsic cerebellar nuclei. On this basis, the present minireview mainly focuses on the morphofunctional and neurochemical data of the synarmotic neuron, and explores its potential involvement in some forms of cerebellar ataxias.
Topics: Cerebellar Cortex; Animals; Humans; Neurons; GABAergic Neurons
PubMed: 38766720
DOI: 10.4081/ejh.2024.3954 -
ACS Omega May 2024Angiotensin receptor blockers (ARBs) are commonly used to treat hypertension that target the hormonal system (renin-angiotensin system (RAS)), which regulates various...
Novel Insights in the Hypertension Treatment & Type 2 Diabetics Induced by Angiotensin Receptor Blockers: MD Simulation Studies & Molecular Docking of Some Promising Natural Therapies.
Angiotensin receptor blockers (ARBs) are commonly used to treat hypertension that target the hormonal system (renin-angiotensin system (RAS)), which regulates various physiological functions in the body. ARBs work by blocking the binding of angiotensin II to its receptor, thereby preventing a rise in blood pressure. These drugs not only normalize the overactivation of RAS but also provide protective effects against cardiovascular, renal, and type 2 diabetic patients. Inappropriate RAS activity has been linked to insulin resistance of type 2 diabetes. Olmesartan, as an ARB, was found to have a beneficial role in reducing postprandial glucose levels in type 2 diabetes. However, ARBs can cause side effects, prompting a search for new compounds that have fewer adverse effects. This study explores the potential of natural metabolites, specifically eugenol, gallic acid, myricetin, -cymene, quercetin, and kaempferol, as ARB inhibitors compared to the current standard, olmesartan. Using in silico studies, the binding affinity of these natural substances to the ARB receptor was evaluated. The results showed that myricetin and kaempferol had affinities higher than those of olmesartan, suggesting that they could serve as promising ARB inhibitors for hypertension treatment. These natural compounds could provide an alternative approach to conventional antihypertensive drugs, which may have fewer side effects. However, more research is needed to validate the efficacy and safety of these natural compounds as antihypertensive drugs. Further in vitro and in vivo studies are needed to confirm their effectiveness and safety. This study provides a promising starting point for future investigations into the potential of natural metabolites as alternative treatments for hypertension. The findings also highlight the importance of exploring natural alternative treatments for hypertension and the protective effects of ARBs on early stage type-2 diabetics.
PubMed: 38764667
DOI: 10.1021/acsomega.4c01319 -
Signal Transduction and Targeted Therapy May 2024Tumor biomarkers, the substances which are produced by tumors or the body's responses to tumors during tumorigenesis and progression, have been demonstrated to possess... (Review)
Review
Tumor biomarkers, the substances which are produced by tumors or the body's responses to tumors during tumorigenesis and progression, have been demonstrated to possess critical and encouraging value in screening and early diagnosis, prognosis prediction, recurrence detection, and therapeutic efficacy monitoring of cancers. Over the past decades, continuous progress has been made in exploring and discovering novel, sensitive, specific, and accurate tumor biomarkers, which has significantly promoted personalized medicine and improved the outcomes of cancer patients, especially advances in molecular biology technologies developed for the detection of tumor biomarkers. Herein, we summarize the discovery and development of tumor biomarkers, including the history of tumor biomarkers, the conventional and innovative technologies used for biomarker discovery and detection, the classification of tumor biomarkers based on tissue origins, and the application of tumor biomarkers in clinical cancer management. In particular, we highlight the recent advancements in biomarker-based anticancer-targeted therapies which are emerging as breakthroughs and promising cancer therapeutic strategies. We also discuss limitations and challenges that need to be addressed and provide insights and perspectives to turn challenges into opportunities in this field. Collectively, the discovery and application of multiple tumor biomarkers emphasized in this review may provide guidance on improved precision medicine, broaden horizons in future research directions, and expedite the clinical classification of cancer patients according to their molecular biomarkers rather than organs of origin.
Topics: Humans; Biomarkers, Tumor; Neoplasms; Precision Medicine; Prognosis; Molecular Targeted Therapy
PubMed: 38763973
DOI: 10.1038/s41392-024-01823-2 -
Environment International May 2024Multiple lines of evidence suggest that exposure to per- and polyfluoroalkyl substances (PFAS) may alter glucose homeostasis, particularly during pregnancy, and may...
The effect of per and polyfluoroalkyl substance (PFAS) exposure on gestational diabetes mellitus and its subclinical risk factors: A systematic review and meta-analysis protocol.
BACKGROUND
Multiple lines of evidence suggest that exposure to per- and polyfluoroalkyl substances (PFAS) may alter glucose homeostasis, particularly during pregnancy, and may affect risk for developing gestational diabetes mellitus (GDM). While previous systematic reviews have been conducted on this topic, they did not assess internal validity of the included studies and their search strategies were narrowly focused.
OBJECTIVE
The objective of this study is to assess the effect of higher PFAS exposure (defined by individual compounds or mixtures measured before or during pregnancy) on GDM and subclinical measures of impaired glucose homeostasis (measured during pregnancy) compared to lower PFAS exposure in pregnant.
METHODS
We developed our systematic review protocol in accordance with the Navigation Guide. Peer-reviewed journal and grey literature searches were piloted in to identify relevant studies and refine our search terms and strategy. We also piloted the study screening criteria and data extraction form in DistillerSR, and refined our protocol accordingly. The risk of bias assessment protocol was adapted from Navigation Guide guidance and will be piloted and performed in DistillerSR. Pending the identification of comparable studies, quantitative meta-analyses will be performed where possible. Study results that cannot be quantitatively synthesized will be included in a narrative synthesis. The quality and strength of the body of evidence will be evaluated using Navigation Guide methodology, which is informed by guidance from the Cochrane Collaboration and Grading of Recommendations Assessment, Development and Evaluation (GRADE). We also made refinements to the quality of evidence considerations based on guidance from the National Institute of Environmental Health Sciences (NIEHS) Office of Health Assessment and Translation (OHAT).
FUNDING
This work was supported by the Systematizing Data on Per- and Polyfluoroalkyl Substances and Health Northeastern University TIER 1 Award.
PubMed: 38754246
DOI: 10.1016/j.envint.2024.108711 -
Journal of Nutrition and Metabolism 2024Growing evidence suggests that bioactive compounds in berry fruits may mitigate inflammation in patients with chronic kidney disease (CKD).
Effects of Cranberry Extract () Supplementation on Lipid Peroxidation and Inflammation in Patients with Chronic Kidney Disease (Stages 3-4): A Randomized Controlled Trial.
BACKGROUND
Growing evidence suggests that bioactive compounds in berry fruits may mitigate inflammation in patients with chronic kidney disease (CKD).
OBJECTIVES
To evaluate cranberry () supplementation effects on modulation of transcription factors involved in inflammation and oxidative stress in nondialysis (stages 3 and 4) patients with CKD. . A randomized, double-blind, placebo-controlled study was performed with 30 patients to receive capsules containing cranberry extract (1000 mg/day) or placebo (1000 mg/day of corn starch) for two months. . The mRNA expression of nuclear factor-erythroid 2-related factor-2 (Nrf2) and nuclear factor-kB (NF-kB) was evaluated in peripheral blood mononuclear cells (PBMCs) by quantitative real-time polymerase chain reaction. Thiobarbituric acid reactive substances (TBARS) were measured in the plasma to assess oxidative stress. Interleukin-6 (IL-6) plasma levels were assessed by enzyme-linked immunosorbent assay and C-reactive protein (CRP) by immunoturbidimetric method.
RESULTS
Twenty-five patients completed the study: 12 in the cranberry group (56.7 ± 7.5 years and body mass index (BMI) of 29.6 ± 5.5 kg/m) and 13 in the placebo group (58.8 ± 5.1 years and BMI 29.8 ± 5.4 kg/m). There were no differences in NF-kB or Nrf2 mRNA expressions ( = 0.99 and = 0.89) or TBARS, CRP, and IL-6 plasma levels after cranberry supplementation.
CONCLUSIONS
The cranberry extract administration (1000 mg/day) did not affect Nrf2 and NF-kB mRNA expression, oxidative stress, or inflammatory markers levels in nondialysis CKD patients. This trial is registered with NCT04377919.
PubMed: 38752013
DOI: 10.1155/2024/9590066 -
EFSA Journal. European Food Safety... May 2024The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of naringenin [FL-no: 16.132] as a new flavouring substance, in accordance...
The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of naringenin [FL-no: 16.132] as a new flavouring substance, in accordance with Regulation (EC) No 1331/2008. No other substances with sufficient structural similarity have been identified in existing FGEs that could be used to support a read-across approach. The information provided on the manufacturing process, the composition and the stability of [FL-no: 16.132] was considered sufficient. From studies carried out with naringenin, the Panel concluded that there is no concern with respect to genotoxicity. The use of naringenin as a flavouring substance at added portions exposure technique (APET) exposure levels is unlikely to pose a risk for drug interaction. For the toxicological evaluation of naringenin, the Panel requested an extended one-generation toxicity study on naringenin, in line with the requirements of the Procedure and to investigate the consequence of a possible endocrine-disrupting activity. The Panel considered that changes in thymus weight, litter size, post-implantation loss and a consistent reduced pup weight in the high-dose F2 generation could not be dismissed and selected therefore, the mid-dose of 1320 mg/kg body weight (bw) per day for the parental males as the no observed adverse effect level (NOAEL) of the study. The exposure estimates for [FL-no: 16.132] (31,500 and 50,000 μg/person per day for children and adults, respectively) were above the threshold of toxicological of concern (TTC) for its structural class (III). Using the NOAEL of 1320 mg/kg bw per day at step A4 of the procedure, margins of exposure (MoE) of 1590 and 630 could be calculated for adults and children, respectively. Based on the calculated MoEs, the Panel concluded that the use of naringenin as a flavouring substance does not raise a safety concern.
PubMed: 38751504
DOI: 10.2903/j.efsa.2024.8747 -
EFSA Journal. European Food Safety... May 2024Acetamiprid is a pesticide active substance with insecticidal action whose approval was renewed by Commission Implementing Regulation (EU) 2018/113. In January 2022, the...
Acetamiprid is a pesticide active substance with insecticidal action whose approval was renewed by Commission Implementing Regulation (EU) 2018/113. In January 2022, the EFSA PPR Panel published a statement following a request from the European Commission to advise on human health or the environment based on new scientific evidence presented by France during the decision-making phase. In July 2022, by means of a further mandate received from the European Commission, EFSA was requested to provide advice if new information and any other scientific evidence that has become available since the assessment conducted for the renewal in 2018 warrant re-evaluation of (i) toxicological parameters used for the risk assessment of acetamiprid during the renewal process, including toxicological endpoints; (ii) the residue definition for acetamiprid in products of plant origin; and (iii) the safety of existing maximum residue levels (MRLs). Meanwhile, the applicant of acetamiprid in the EU submitted new toxicology studies regarding the toxicological profile of the metabolite IM-2-1. Furthermore, the European Commission was made aware that several recent publications in scientific literature were made available after the literature searches conducted by EFSA. As the new data could affect the advice that EFSA was expected to deliver through the 2022 mandate, EFSA was further requested to consider this information by means of a revised mandate received in September 2023. As regards re-evaluation of point (i) in this statement, this was addressed by an EFSA Working Group integrating all the available evidence. The results of the weight of evidence indicated that there are major uncertainties in the body of evidence for the developmental neurotoxicity (DNT) properties of acetamiprid and further data are therefore needed to come to a more robust mechanistic understanding to enable appropriate hazard and risk assessment. In view of these uncertainties, the EFSA WG proposed to lower the acceptable daily intake (ADI) and acute reference dose (ARfD) from 0.025 to 0.005 mg/kg body weight (per day). A revised residue definition for risk assessment was proposed for leafy and fruit crops as sum of acetamiprid and N-desmethyl-acetamiprid (IM-2-1), expressed as acetamiprid. Regarding pulses/oilseeds, root crops and cereals, the new data received did not indicate a need to modify the existing residue definition for risk assessment, which therefore remains as parent acetamiprid. Regarding the residue definition for enforcement, the available data did not indicate a need to modify the existing definition because acetamiprid is still a sufficient marker of the residues in all crop groups. Considering the new health-based guidance values derived in the present statement, a risk for consumer has been identified for 38 MRLs currently in place in the EU Regulation. Consequently, EFSA recommended to lower the existing MRLs for 38 commodities based on the assessment of fall-back Good Agricultural Practices received within an ad hoc data call. Some fall-back MRLs proposals require further risk management considerations.
PubMed: 38751503
DOI: 10.2903/j.efsa.2024.8759