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Current Pollution Reports Sep 2023There is a growing interest in understanding the health effects of exposure to per- and polyfluoroalkyl substances (PFAS) through the study of the human metabolome. In...
PURPOSE OF REVIEW
There is a growing interest in understanding the health effects of exposure to per- and polyfluoroalkyl substances (PFAS) through the study of the human metabolome. In this systematic review, we aimed to identify consistent findings between PFAS and metabolomic signatures. We conducted a search matching specific keywords that was independently reviewed by two authors on two databases (EMBASE and PubMed) from their inception through July 19, 2022 following PRISMA guidelines.
RECENT FINDINGS
We identified a total of 28 eligible observational studies that evaluated the associations between 31 different PFAS exposures and metabolomics in humans. The most common exposure evaluated was legacy long-chain PFAS. Population sample sizes ranged from 40 to 1,105 participants at different stages across the lifespan. A total of 19 studies used a non-targeted metabolomics approach, 7 used targeted approaches, and 2 included both. The majority of studies were cross-sectional ( = 25), including four with prospective analyses of PFAS measured prior to metabolomics.
SUMMARY
Most frequently reported associations across studies were observed between PFAS and amino acids, fatty acids, glycerophospholipids, glycerolipids, phosphosphingolipids, bile acids, ceramides, purines, and acylcarnitines. Corresponding metabolic pathways were also altered, including lipid, amino acid, carbohydrate, nucleotide, energy metabolism, glycan biosynthesis and metabolism, and metabolism of cofactors and vitamins. We found consistent evidence across studies indicating PFAS-induced alterations in lipid and amino acid metabolites, which may be involved in energy and cell membrane disruption.
PubMed: 37753190
DOI: 10.1007/s40726-023-00269-4 -
Eye and Vision (London, England) Aug 2023This study aims to detect alterations in the spatio-chromatic pseudophakic vision produced by multifocal diffractive intraocular lenses (IOLs) and provides a physical...
BACKGROUND
This study aims to detect alterations in the spatio-chromatic pseudophakic vision produced by multifocal diffractive intraocular lenses (IOLs) and provides a physical interpretation.
METHODS
In vitro characterization of the imaging performance of two diffractive IOLs: AT LISA Tri (Zeiss) and FineVision (PhysIOL) in on-bench model eye illuminated with red (R, 625 nm), green (G, 530 nm) and blue (B, 455 nm) lights. We used the metrics: energy efficiency (EE), area under the modulation transfer function, longitudinal chromatic aberration (LCA), and halo intensity. Through-focus (TF) analysis and calculation of the expected defocus curve under white (W) daylight were included. In vivo visual acuity (VA) of 50 pseudophakics (60 eyes) was assessed under W, R, G, B lights at far and near. Two clinical experiments evaluated LCA and R, G, B TF-EE effects on pseudophakic vision and their relative importance.
RESULTS
Clinical mean VA values under W light agreed with the predicted values at far and near for both IOLs. LCA measurements and R, G, B TF-EE curves were consistent with their lens design based on the 0th and 1st diffraction orders operative for far and near vision, respectively. LCA effects were compensated at near but noticed at far (- 0.75 D under B light). We detected strong asymmetry in visual resolution depending on the object distance and the illuminating wavelength-red predominance at far, blue predominance at near-in consistency with the TF-EE measurements.
CONCLUSIONS
Diffractive multifocal IOL designs produce asymmetries in the spatio-chromatic vision of pseudophakics beyond the alterations strictly due to LCA. VA asymmetry for far/near object distance under R and B illumination is clinically detectable in subjects implanted with IOLs with 0th and 1st diffraction orders for far and near vision, respectively. Such VA asymmetry cannot be explained solely from the influence of defocus, as would be derived from a chromatic difference of power, but mainly from the wavelength dependence of the EE.
PubMed: 37525263
DOI: 10.1186/s40662-023-00350-5 -
The Role of Dietary Ingredients in Mental Energy - A Scoping Review of Randomized Controlled Trials.Journal of the American Nutrition... Feb 2024Low mental energy can contribute to decreased productivity, altered life balance, decreased physical performance, and ultimately affect quality of life. As such, there... (Review)
Review
Low mental energy can contribute to decreased productivity, altered life balance, decreased physical performance, and ultimately affect quality of life. As such, there is a great demand for food and beverage products that positively impact mental energy. Numerous products claim to alter mental energy making continued review of the scientific evidence critical. The objective of this study was to conduct a scoping review of randomized controlled trials to evaluate the effect of 18 dietary ingredients on mental energy outcomes in adults without severe disease. Methods: A literature search, completed using PubMed, resulted in the identification of 2261 articles, 190 of which met eligibility from initial abstract review. Full-text review was completed on the 190 studies which resulted in 101 articles that fully met eligibility for inclusion in this study. The search strategy for two ingredients did not yield any eligible studies, leaving studies for 16 ingredients that were extracted and summarized by reported significantly improved outcomes for cognition, mood and perceived feelings, and sleep assessments. The preliminary results for several dietary ingredients directionally suggested a mental energy benefit (≥20% of outcomes), including ashwagandha, chamomile, dark chocolate, ginseng, green tea, lavender, lion's mane mushroom, maca, tart cherries, turmeric, and valerian root. The results of this scoping review suggest that of the 16 dietary ingredients reviewed, 11 may be promising for further exploration on their potential benefits in supporting mental energy. Given consumer demand and market growth for food and beverage products that positively impact mental energy; continued efforts in assessment method alignment and additional evaluation in well-designed trials is warranted.KEY TEACHING POINTSOf the 16 dietary ingredients reviewed, 11 (ashwagandha, chamomile, dark chocolate, ginseng, green tea, lavender, lion's mane mushroom, maca, melatonin foods, turmeric, and valerian root) may be promising for further exploration on their potential mental energy benefits.Dark chocolate, ginseng, ashwagandha, and lion's mane mushroom were the most promising ingredients for further evaluation in the cognition domain of the ingredients evaluated.Turmeric, maca, lavendar, and ashwagandha were the most promising ingredients for further evaluation in the mood and perceived feelings domain of the ingredients evaluated.Ashwagandha, chamomile, green tea, melatonin foods, valerian root were the most promising ingredients for further evaluation in the sleep domain of the ingredients evaluated.Additional, well-designed, consistent, clinical trials and systematic reviews are warranted as the challenge of heterogeneity in mental energy study design remains.
Topics: Animals; Melatonin; Quality of Life; Lions; Randomized Controlled Trials as Topic; Tea
PubMed: 37561965
DOI: 10.1080/27697061.2023.2244031 -
Research Square Jul 2023This study on severe malarial anemia (SMA: Hb < 6.0 g/dL), a leading global cause of childhood morbidity and mortality, analyzed the entire expressed transcriptome in...
This study on severe malarial anemia (SMA: Hb < 6.0 g/dL), a leading global cause of childhood morbidity and mortality, analyzed the entire expressed transcriptome in whole blood from children with non-SMA (Hb ≥ 6.0 g/dL, n = 41) and SMA (n = 25). Analyses revealed 3,420 up-regulated and 3,442 down-regulated transcripts, signifying impairments in host inflammasome activation, cell death, innate immune responses, and cellular stress responses in SMA. Immune cell profiling showed a decreased antigenic and immune priming response in children with SMA, favoring polarization toward cellular proliferation and repair. Enrichment analysis further identified altered neutrophil and autophagy-related processes, consistent with neutrophil degranulation and altered ubiquitination and proteasome degradation. Pathway analyses highlighted SMA-related alterations in cellular homeostasis, signaling, response to environmental cues, and cellular and immune stress responses. Validation with a qRT-PCR array showed strong concordance with the sequencing data. These findings identify key molecular themes in SMA pathogenesis, providing potential targets for new malaria therapies.
PubMed: 37503086
DOI: 10.21203/rs.3.rs-3150748/v1 -
Neurogastroenterology and Motility Jul 2023The Chicago classification primarily utilizes ten 5 mL liquid swallows in a supine position as the standard high-resolution esophageal manometry (HRM) protocol. HRM...
BACKGROUND
The Chicago classification primarily utilizes ten 5 mL liquid swallows in a supine position as the standard high-resolution esophageal manometry (HRM) protocol. HRM can be performed with varying volumes and consistencies and in an upright position. We aimed to determine the impact on HRM results by (1) position, (2) swallows of differing volume and consistency, and (3) perception of bolus passage.
METHODS
HRM was performed in healthy volunteers (HV) with the following protocol of swallows: liquids 10 × 5 mL, 5 × 10 mL, and 3 × 10 mL multiple rapid swallows; applesauce 5 × 5 mL and 5 × 10 mL; and bread 5 × 2 × 2 cm and 5 × 4 × 4cm. HV rated difficulty of each swallow on a 5-point Likert scale. All HVs performed the protocol in supine position first and then in "semi-upright" (sitting 70 degrees in a bed) and "upright" (sitting in a chair) in a randomized order.
KEY RESULTS
Thirty-seven HVs, median age 27 years, 64% female completed this study. Median distal contractile integral (DCI) and integrated relaxation pressure 4 s (IRP4) of 5 mL liquid swallows significantly differed (all p < 0.01) between position performed. Large volume swallows resulted in higher DCI and lower IRP4. IRP4 results were significantly increased for 2 × 2 cm pieces of bread compared to 5 mL water swallows. DCI results were higher for 2 × 2 cm pieces of bread compared to 5 mL water swallows. Distal latency was shorter in more upright positions. Among this cohort of HV, perceived difficulty of bolus passage was more likely to occur with solid boluses.
CONCLUSIONS AND INFERENCES
The volume and consistency of a swallow and the position it is performed in, significantly alter HRM metrics. Interpretation of HRM studies should incorporate different normative values which are specific to the position and bolus type.
Topics: Humans; Female; Adult; Male; Deglutition; Esophagus; Manometry; Sitting Position; Water; Esophageal Motility Disorders
PubMed: 37036395
DOI: 10.1111/nmo.14593 -
Biomedicine & Pharmacotherapy =... Sep 2023Rivaroxaban is a direct inhibitor of factor Xa, a member of direct oral anticoagulant group of drugs (DOACs). Despite being a widely extended alternative to vitamin K...
Rivaroxaban is a direct inhibitor of factor Xa, a member of direct oral anticoagulant group of drugs (DOACs). Despite being a widely extended alternative to vitamin K antagonists (i.e., acenocoumarol, warfarin) the interindividual variability of DOACs is significant, and may be related to adverse drug reaction occurrence or drug inefficacy, namely hemorrhagic or thromboembolic events. Since there is not a consistent analytic practice to monitor the anticoagulant activity of DOACs, previously reported polymorphisms in genes coding for proteins responsible for the activation, transport, or metabolism of DOACs were studied. The study population comprised 60 healthy volunteers, who completed two randomized, crossover bioequivalence clinical trials between two different rivaroxaban formulations. The effect of food, sex, biogeographical origin and 55 variants (8 phenotypes and 47 single nucleotide polymorphisms) in drug metabolizing enzyme genes (such as CYP2D6, CYP2C9, NAT2) and transporters (namely, ABCB1, ABCG2) on rivaroxaban pharmacokinetics was tested. Individuals dosed under fasting conditions presented lower t (2.21 h vs 2.88 h, β = 1.19, R =0.342, p = 0.012) compared to fed volunteers. NAT2 slow acetylators presented higher AUC corrected by dose/weight (AUC/DW; 8243.90 vs 7698.20 and 7161.25 h*ng*mg /ml*kg, β = 0.154, R =0.250, p = 0.044), higher C/DW (1070.99 vs 834.81 and 803.36 ng*mg /ml*kg, β = 0.245, R =0.320, p = 0.002), and lower t (2.63 vs 3.19 and 4.15 h, β = -0.346, R =0.282, p = 0.047) than NAT2 rapid and intermediate acetylators. No other association was statistically significant. Thus, slow NAT2 appear to have altered rivaroxaban pharmacokinetics, increasing AUC and C. Nonetheless, further research should be conducted to verify NAT2 involvement on rivaroxaban pharmacokinetics and to determine its clinical significance.
Topics: Humans; Rivaroxaban; Healthy Volunteers; Anticoagulants; Polymorphism, Single Nucleotide; Phenotype; Arylamine N-Acetyltransferase
PubMed: 37385211
DOI: 10.1016/j.biopha.2023.115058 -
Biotechnology and Bioengineering Aug 2023Cancer cell lines play a crucial role as invaluable models in cancer research, facilitating the examination of cancer progression as well as the advancement of... (Review)
Review
Cancer cell lines play a crucial role as invaluable models in cancer research, facilitating the examination of cancer progression as well as the advancement of diagnostics and treatments. While they may not perfectly replicate the original tumor, they generally exhibit similar characteristics. Low-passage cancer cell lines are generally preferred due to their closer resemblance to the original tumor, as long-term culturing can alter the genetic and molecular profiles of a cell line thereby highlighting the importance of monitoring the passage number (PN). Variations in proliferation, migration, gene expression, and drug sensitivity can be linked to PN differences. PN can also influence DNA methylation levels, metabolic profiles, and the expression of genes/or proteins in cancer cell lines. When conducting research on cancer cell lines, it is crucial for researchers to carefully select the appropriate PN to maintain consistency and reliability of results. Moreover, to ensure dependability and replicability, scientists ought to actively track the growth, migration, and gene/or protein profiles of cancer cell lines at specific PNs. This approach enables the identification of the most suitable range of PNs for experiments, guaranteeing consistent and precise results. Additionally, such efforts serve to minimize disparities and uphold the integrity of research. In this review, we have laid out recommendations for laboratories to overcome these PN discrepancies when working with cancer cell lines.
Topics: Humans; Reproducibility of Results; Neoplasms; Cell Line; DNA Methylation; Cell Line, Tumor
PubMed: 37439093
DOI: 10.1002/bit.28496 -
Neuropharmacology Oct 2023The inbred mouse strain, BTBR TItpr3/J (BTBR), possesses neuronal and circuit abnormalities that underlie atypical behavioral profiles resembling the major symptoms of...
The inbred mouse strain, BTBR TItpr3/J (BTBR), possesses neuronal and circuit abnormalities that underlie atypical behavioral profiles resembling the major symptoms of human autism spectrum disorder (ASD). Forebrain serotonin (5-HT) transmission has been implicated in ASD-related behavioral alterations. In this study, we assessed 5-HT signals and the functional responsiveness in BTBR mice compared to standard C57BL/6J (B6) control mice to elucidate how 5-HT alterations contribute to behavioral abnormalities in BTBR mice. A lower number of 5-HT neurons in the median raphe, but not in the dorsal raphe, was observed in male and female BTBR mice. Acute systemic injection of buspirone, a 5-HT1A receptor agonist, induced c-Fos in several brain regions in both B6 and BTBR mice; however, blunted c-Fos induction in BTBR mice was documented in the cingulate cortex, basolateral amygdala (BLA), and ventral hippocampus (Hipp). Decreased c-Fos responses in these regions are associated with a lack of buspirone effects on anxiety-like behavior in BTBR mice. Analysis of mRNA expression following acute buspirone injection indicated that 5HTR1a gene downregulation (or upregulation) occurred in the BLA and Hipp of B6 mice, respectively, but not BTBR mice. The mRNA expression of factors associated with neurogenesis or the pro-inflammatory state was not consistently altered by acute buspirone injection. Therefore, 5-HT responsivity via 5-HT1A receptors in the BLA and Hipp are linked to anxiety-like behavior, in which circuits are disrupted in BTBR mice. Other distinct 5-HT circuits from the BLA and Hipp that regulate social behavior are restricted but preserved in BTBR mice.
Topics: Humans; Mice; Male; Female; Animals; Autistic Disorder; Autism Spectrum Disorder; Buspirone; Serotonin; Mice, Inbred C57BL; Mice, Inbred Strains; Social Behavior; Disease Models, Animal; Phenotype; RNA, Messenger
PubMed: 37301467
DOI: 10.1016/j.neuropharm.2023.109634 -
Biological Psychiatry. Cognitive... May 2024There has been renewed interest in the use of 3,4-methylenedioxy-methamphetamine (MDMA) and serotonergic psychedelics in the treatment of multiple psychiatric disorders.... (Review)
Review
There has been renewed interest in the use of 3,4-methylenedioxy-methamphetamine (MDMA) and serotonergic psychedelics in the treatment of multiple psychiatric disorders. Many of these compounds are known to produce prosocial effects, but how these effects relate to therapeutic efficacy and the extent to which prosocial effects are unique to a particular drug class is unknown. In this article, we present a narrative overview and compare evidence for the prosocial effects of MDMA and serotonergic psychedelics to elucidate shared mechanisms that may underlie the therapeutic process. We discuss 4 categories of prosocial effects: altered self-image, responses to social reward, responses to negative social input, and social neuroplasticity. While both categories of drugs alter self-perception, MDMA may do so in a way that is less related to the experience of mystical-type states than serotonergic psychedelics. In the case of social reward, evidence supports the ability of MDMA to enhance responses and suggests that serotonergic psychedelics may also do so, but more research is needed in this area. Both drug classes consistently dampen reactivity to negative social stimuli. Finally, preclinical evidence supports the ability of both drug classes to induce social neuroplasticity, promoting adaptive rewiring of neural circuits, which may be helpful in trauma processing. While both MDMA and serotonergic psychedelics produce prosocial effects, they differ in the mechanisms through which they do this. These differences affect the types of psychosocial interventions that may work best with each compound.
Topics: Humans; N-Methyl-3,4-methylenedioxyamphetamine; Hallucinogens; Social Behavior; Serotonin Agents; Reward; Neuronal Plasticity; Self Concept; Animals
PubMed: 38341085
DOI: 10.1016/j.bpsc.2024.02.001