Search Results (80)

Background: As more healthcare institutions consider providing preemptive pharmacogenomic (PGx) testing to greater numbers of their patients, it will be important to consider the potential concerns patients may have about the generation of preemptive PGx information. To date, few studies have examined the nature and incidence of patient concerns about preemptive PGx testing. Methods: We conducted a longitudinal survey study of 5000 patients receiving preemptive PGx testing in the Mayo Clinic RIGHT study. We assessed patient concerns regarding issues of data confidentiality, cost implications, comprehension of results, and potential disruption of pre-existing medication regimens. Participants were surveyed before and after they received PGx results from the RIGHT study. Results: We achieved 92.8% and 74.4% response rates on the pre- and post-results surveys, respectively. Participants had low levels of concern about PGx testing overall. However, 25.5% of participants were “quite/extremely concerned” about insurance implications, and 30.1% were “quite/extremely” concerned about increased out-of-pocket costs for prescription medications that might result from PGx testing. These same concerns were significantly reduced on the post-results survey. Patients who initially expressed concerns regarding their ability to understand PGx results were more likely to report having difficulty understanding results on the post-results survey. Conclusions: Our findings suggest that as healthcare institutions look to increase preemptive PGx screening, attention should be given to potential concerns patients may have around such testing. Educational interventions aimed at supporting patient understanding of PGx results and addressing potential concerns will be important elements of a successful PGx program. Full article

The accurate quantification of Campylobacter jejuni in poultry samples is critical for ensuring food safety and compliance with regulatory standards. This study evaluated the performance of three enrichment media—Mueller–Hinton Broth (MHB), Bolton’s Blood-Free Broth 2x (BFBB2x), and Buffered Peptone Water (BPW)—in supporting C. jejuni detection and quantification using the BAX^® Q7-RT PCR system and traditional plate count methods. Results demonstrated high reliability across all media types, with BFBB2x and MHB showing the strongest correlations (R² = 0.99) for the BAX^® system. BFBB2x exhibited the lowest RMSE (0.13), while MHB balanced precision (RMSE = 0.4) with sensitivity. For plate counts, MHB and BPW achieved the highest correlations (R² = 0.99) and precision (RMSE = 0.26), with MHB demonstrating the lowest detection limit (2.56 log₁₀ CFU/mL) compared to BFBB2x (2.93 log₁₀ CFU/mL) and BPW (3.31 log₁₀ CFU/mL). The findings underscore MHB’s robustness as an enrichment medium, offering consistent performance across both molecular and culture-based methods. The current study supports MHB as the more effective medium for the reliable and precise quantification of C. jejuni in poultry-associated matrices, highlighting its utility in minimizing contamination risks and enhancing food safety. Future research should explore its applicability in diverse poultry products and production environments. Full article

Background: Individuals diagnosed with autism spectrum disorder (ASD) commonly experience sensory processing that differs from general-population norms, and the autistic lived experience of eating includes preferences for routine, and sensory processing difficulty related to scents, tastes, temperatures, and textures of food. Meanwhile, research indicates that nutrients involved in one-carbon metabolism (OCM) may be related to sensory processing. Methods: This study enrolled 33 school-aged children with autism to assess whether OCM nutrient intake is associated with sensory processing. Parents completed two parent-report assessments: the youth and adult food frequency questionnaire (YAFFQ), and a sensory processing tool, Sensory Profile 2 (SP2). Results: Participant data showed generally good nutritional profiles mirroring those of general-population U.S. children. A group-binarized linear regression model showed the following relationships (p < 0.05): vitamin B12 consumption had a negative association with the SP2 Oral and Sensor domain scores. Choline intake had a positive association with the SP2 Avoider domain score. Vitamin B1 showed a positive association with the SP2 Visual domain score. Conclusions: These results support the possible existence of a relationship between sensory symptoms and OCM nutrient consumption levels in school-aged children diagnosed with autism. Future research is needed to confirm and explore the potential for causality. Full article

Background/Objectives: To identify and analyze what is known about the psychosocial factors affecting the wellbeing and sources of support of young adult (YA) cancer survivors. Methods: The search strategy included Neoplasms, young adults, psycho* or emotional well* or mental health. The OVID Medline and CINAHL databases were searched. Included were cancer survivors (YA) ages 18–39 at the time of the study. The studies included qualitative and quantitative designs, written in English, and published between January 2016 and October 2024. The results were recorded according to PRISMA-ScR guidelines. Results: Thirteen studies with 4992 participants found psychosocial factors to be the most important influence on life satisfaction with social support the most decisive factor. This expands the results of previous reviews by including a variety of study designs and data collection tools to provide a comprehensive understanding of the YA experience. Psychosocial concerns affecting wellbeing led to social isolation, low connectedness with family and friends, and significant distress. Consistent with previous reviews, the greatest challenges to wellbeing were psychosocial needs, which included seeking and delivering information that is easy to understand but detailed, which can decrease frustration and anger, and needs to be readily available and accessible. Unlike older adult cancer survivors, YA survivors are more likely to have reduced psychosocial functioning compared to their peers and suffer from higher distress than their adult peers and non-YA cancer survivors with anxiety as the most reported symptom. Conclusions: Interventions need to be developed that lessen the impact of a cancer diagnosis and cancer treatments. The specific needs of YAs must be further researched and evaluated to determine specific interventions and the support needed during this crucial stage of cancer survivorship. Future research must also increase the focus on the racial and ethnic diversity of participants as well as prioritizing underserved populations and the impact of the COVID-19 pandemic. Full article

Harsh acid oxidation of activated charcoal transforms an insoluble carbon-rich source into water-soluble, disc structures of graphene decorated with multiple oxygen-containing functionalities. We term these pleiotropic nano-enzymes as “pleozymes”. A broad redox potential spans many crucial redox reactions including the oxidation of hydrogen sulfide (H₂S) to polysulfides and thiosulfate, dismutation of the superoxide radical (O₂⁻*), and oxidation of NADH to NAD⁺. The oxidation of H₂S is predicted to enhance protein persulfidation—the attachment of sulfur to cysteine residues. Persulfidated proteins act as redox intermediates, and persulfidation protects proteins from irreversible oxidation and ubiquitination, providing an important means of signaling. Protein persulfidation is believed to decline in several neurological disorders and aging. Importantly, and consistent with the role of persulfidation in signaling, the master antioxidant transcription factor Nrf2 is regulated by Keap1’s persulfidation. Here, we demonstrate that pleozymes increased overall protein persulfidation in cells from apparently healthy individuals and from individuals with the mitochondrial protein mutation responsible for Friedreich’s ataxia. We further find that pleozymes specifically enhanced Keap1 persulfidation, with subsequent increased accumulation of Nrf2 and Nrf2’s antioxidant targets. Full article

Viral infections leading to inflammation have been implicated in several common diseases, such as Alzheimer’s disease (AD) and type 1 diabetes (T1D). Of note, herpes simplex virus 1 (HSV-1) has been reported to be associated with AD. We sought to identify the transcriptomic changes due to HSV-1 infection and anti-viral drug (acyclovir, ACV) treatment of HSV-1 infection in dissociated cells from human cerebral organoids (dcOrgs) versus stem cell-derived pancreatic islets (sc-islets) to gain potential biological insights into the relevance of HSV-1-induced inflammation in AD and T1D. We observed that differentially expressed genes (DEGs) in HSV-1-infected sc-islets were enriched for genes associated with several autoimmune diseases, most significantly, T1D, but also rheumatoid arthritis, psoriasis, Crohn’s disease, and multiple sclerosis, whereas DEGs in HSV-1-infected dcOrgs were exclusively enriched for genes associated with AD. The ACV treatment of sc-islets was not as effective in rescuing transcript perturbations of autoimmune disease-associated genes. Finally, we identified gene ontology categories that were enriched for DEGs that were in common across, or unique to, viral treatment of dcOrgs and sc-islets, such as categories involved in the transferase complex, mitochondrial, and autophagy function. In addition, we compared transcriptomic signatures from HSV-1-infected sc-islets with sc-islets that were infected with the coxsackie B virus (CVB) that had been associated with T1D pathogenesis. Collectively, this study provides tissue-specific insights into the molecular effects of inflammation in AD and T1D. Full article

Down syndrome (DS) is a multisystemic disorder that includes accelerated aging caused by trisomy 21. In particular, overexpression of cystathionine-β-synthase (CBS) is linked to excess intracellular hydrogen sulfide (H₂S), a mitochondrial toxin at higher concentrations, which impairs cellular viability. Concurrent overexpression of superoxide dismutase 1 (SOD1) may increase oxidative stress by generating excess hydrogen peroxide (H₂O₂) while also mitigating the toxic H₂S burden via a non-canonical sulfide-oxidizing mechanism. We investigated the phenotypic variability in basal H₂S levels in relation to DS B lymphocyte cell health and SOD1 in H₂S detoxification. The H₂S levels were negatively correlated with the DS B lymphocyte growth rates but not with CBS protein. Pharmacological inhibition of SOD1 using LCS-1 significantly increased the H₂S levels to a greater extent in DS cells while also decreasing the polysulfide products of H₂S oxidation. However, DS cells exhibited elevated H₂O₂ and lipid peroxidation, representing potential toxic consequences of SOD1 overexpression. Treatment of DS cells with a pleiotropic carbon nanozyme (pleozymes) decreased the total oxidative stress and reduced the levels of the H₂S-generating enzymes CBS and 3-mercaptopyruvate sulfurtransferase (MPST). Our results indicate that pleozymes may bridge the protective and deleterious effects of DS SOD1 overexpression on H₂S metabolism and oxidative stress, respectively, with cytoprotective benefits. Full article

Neuropathic pain resulting from spinal cord injury (SCI) is a significant secondary health issue affecting around 60% of individuals with SCI. After SCI, activation of microglia, the immune cells within the central nervous system, leads to neuroinflammation by producing pro-inflammatory cytokines and affects neuropathic pain. This interplay between inflammation and pain contributes to the persistent and intense pain experienced by many individuals with SCI. MicroRNAs (miRs) have been critical regulators of neuroinflammation. Previous research in our laboratory has revealed upregulation levels of circulating miR-19a and miR-19b in individuals with SCI with neuropathic pain compared to those without pain. In this study, we treated primary microglial cultures from mice with miR-19a and miR-19b for 24 h and conducted RNA sequencing analysis. Our results showed that miR-19a and miR-19b up- and downregulate different genes according to the volcano plots and the heatmaps. miR-19a and miR-19b regulate inflammation through distinct signaling pathways. The results showed that miR-19a promotes inflammation via toll-like receptor signaling, TNF signaling, and cytokine–cytokine receptor interactions, while miR-19b increases inflammatory responses through the PI3K-Akt signaling pathway, focal adhesion, and extracellular matrix receptor interactions. The protein–protein interaction (PPI) networks used the STRING database to identify transcription factors associated with genes up- or downregulated by miR-19a and miR-19b. Key transcription factors, such as STAT1, STAT2, and KLF4 for miR-19a, and Nr4a1, Nr4a2, and Nr4a3 for miR-19b, were identified and revealed their roles in regulating neuroinflammation. This study demonstrates that miR-19a and miR-19b modulate diverse patterns of gene expression, regulate inflammation, and induce inflammatory responses in microglia. Full article

Background: Less than 25% of gastric cancers (GC) are discovered early, leading to limited treatment options and poor outcomes (27.8% mortality, 3.7% 5-year survival). Screening programs have improved cure rates, yet post-diagnosis treatment guidelines remain unclear (systemic chemotherapy versus surgery). The optimal type of palliative surgery (palliative gastrectomy (PG), surgical bypass (SB), endoscopic stenting (ES)) for long-term outcomes is also debated. Methods: A literature review was conducted using PubMed, MEDLINE, and EMBASE databases along with Google Scholar with the search terms “gastric cancer” and “palliative surgery” for studies post-1985. From the initial 1018 articles, multiple screenings narrowed it to 92 articles meeting criteria such as “metastatic, stage IV GC”, and intervention (surgery or chemotherapy). Data regarding survival and other long-term outcomes were recorded. Results: Overall, there was significant variation between studies but there were similarities of the conclusions reached. ES provided quick symptom relief, while PG showed improved overall survival (OS) only with adjuvant chemotherapy in a selective population. PG had higher mortality rates compared to SB, with ES having a reported 0% mortality, but OS improved with chemotherapy across both SB and PG. Conclusions: Less frail patients may experience an improvement in OS with palliative resection under limited circumstances. However, operative intervention without systemic chemotherapy is unlikely to demonstrate a survival benefit. Further research is needed to explore any correlations. Full article

The Module-0 Demonstrator is a single-phase 600 kg liquid argon time projection chamber operated as a prototype for the DUNE liquid argon near detector. Based on the ArgonCube design concept, Module-0 features a novel 80k-channel pixelated charge readout and advanced high-coverage photon detection system. In this paper, we present an analysis of an eight-day data set consisting of 25 million cosmic ray events collected in the spring of 2021. We use this sample to demonstrate the imaging performance of the charge and light readout systems as well as the signal correlations between the two. We also report argon purity and detector uniformity measurements and provide comparisons to detector simulations. Full article

LCS-1, a putative selective inhibitor of SOD1, is a substituted pyridazinone with rudimentary similarity to quinones and naphthoquinones. As quinones catalytically oxidize H₂S to biologically active reactive sulfur species (RSS), we hypothesized LCS-1 might have similar attributes. Here, we examine LCS-1 reactions with H₂S and SOD1 using thiol-specific fluorophores, liquid chromatography–mass spectrometry, electron paramagnetic resonance (EPR), UV–vis spectrometry, and oxygen consumption. We show that LCS-1 catalytically oxidizes H₂S in buffer solutions to form RSS, namely per- and polyhydrosulfides (H₂S_n, n = 2–6). These reactions consume oxygen and produce hydrogen peroxide, but they do not have an EPR signature, nor do they affect the UV–vis spectrum. Surprisingly, LCS-1 synergizes with SOD1, but not SOD2, to oxidize H₂S to H₂S_3-6. LCS-1 forms monothiol adducts with H₂S, glutathione (GSH), and cysteine (Cys), but not with oxidized glutathione or cystine; both thiol adducts inhibit LCS-1-SOD1 synergism. We propose that LCS-1 forms an adduct with SOD1 that disrupts the intramolecular Cys⁵⁷-Cys¹⁴⁶ disulfide bond and transforms SOD1 from a dismutase to an oxidase. This would increase cellular ROS and polysulfides, the latter potentially affecting cellular signaling and/or cytoprotection. Full article

Success in large carnivore conservation often hinges on local residents’ tolerance towards those species. Feelings of powerlessness and frustration with wildlife policies can lead to intolerance of the species. In extreme cases, intolerance may manifest in poaching. Thus, changes in policy may influence the tolerance of wildlife. To examine the connections between policy and tolerance, we examined how policy scenarios influenced anticipated changes in tolerance to wolves Canis lupus. We administered a survey in 2015–2016 in the core wolf range within northern Wisconsin, USA. Using hierarchical cluster analysis, we clustered respondents into groups based on their current tolerance of wolves. We evaluated the behavioral intentions of the clusters and examined the influence of policy scenarios on respondents’ anticipated changes in tolerance. Finally, using an information-theoretic model selection framework, we assessed the effects of tolerance clusters and demographic factors. The respondents were clustered into three clusters relative to their current tolerance towards wolves: positive, ambivalent, and negative. Each cluster exhibited significantly different behavioral intentions and anticipated changes in tolerance for all scenarios. In all scenarios, respondents who already held positive attitudes towards wolves were significantly less likely to report expected changes in tolerance toward wolves following changes in wolf management. However, respondents who held ambivalent or negative attitudes towards wolves were significantly more likely to report expected changes in tolerance towards wolves following changes in wolf management. Regarding a regulated wolf hunting and trapping season, we observed a Simpson’s Paradox, wherein, when examined in aggregate, no clear pattern emerged, but when examined at the cluster level, important and intuitive patterns emerged. Our demographic model results suggest that policy changes resulting in greater state management authority over wolves, especially authority to implement certain forms of legal killing of wolves, could result in significant increases in tolerance for individuals who identify as hunters, have lost livestock to a predator, or are currently ambivalent or negative towards wolves. Our work elucidates the nuanced relationship between tolerance of wildlife and wildlife policy and identifies a potential ecological fallacy. Full article

Bacterial cytoplasmic organelles are diverse and serve many varied purposes. Here, we employed Rhodobacter sphaeroides to investigate the accumulation of carbon and inorganic phosphate in the storage organelles, polyhydroxybutyrate (PHB) and polyphosphate (PP), respectively. Using cryo-electron tomography (cryo-ET), these organelles were observed to increase in size and abundance when growth was arrested by chloramphenicol treatment. The accumulation of PHB and PP was quantified from three-dimensional (3D) segmentations in cryo-tomograms and the analysis of these 3D models. The quantification of PHB using both segmentation analysis and liquid chromatography and mass spectrometry (LCMS) each demonstrated an over 10- to 20-fold accumulation of PHB. The cytoplasmic location of PHB in cells was assessed with fluorescence light microscopy using a PhaP-mNeonGreen fusion-protein construct. The subcellular location and enumeration of these organelles were correlated by comparing the cryo-ET and fluorescence microscopy data. A potential link between PHB and PP localization and possible explanations for co-localization are discussed. Finally, the study of PHB and PP granules, and their accumulation, is discussed in the context of advancing fundamental knowledge about bacterial stress response, the study of renewable sources of bioplastics, and highly energetic compounds. Full article

1,4-naphthoquinones (NQs) catalytically oxidize H₂S to per- and polysufides and sulfoxides, reduce oxygen to superoxide and hydrogen peroxide, and can form NQ-SH adducts through Michael addition. Here, we measured oxygen consumption and used sulfur-specific fluorophores, liquid chromatography tandem mass spectrometry (LC-MS/MS), and UV-Vis spectrometry to examine H₂S oxidation by NQs with various substituent groups. In general, the order of H₂S oxidization was DCNQ ~ juglone > 1,4-NQ > plumbagin >DMNQ ~ 2-MNQ > menadione, although this order varied somewhat depending on the experimental conditions. DMNQ does not form adducts with GSH or cysteine (Cys), yet it readily oxidizes H₂S to polysulfides and sulfoxides. This suggests that H₂S oxidation occurs at the carbonyl moiety and not at the quinoid 2 or 3 carbons, although the latter cannot be ruled out. We found little evidence from oxygen consumption studies or LC-MS/MS that NQs directly oxidize H₂S_2–4, and we propose that apparent reactions of NQs with inorganic polysulfides are due to H₂S impurities in the polysulfides or an equilibrium between H₂S and H₂S_n. Collectively, NQ oxidation of H₂S forms a variety of products that include hydropersulfides, hydropolysulfides, sulfenylpolysulfides, sulfite, and thiosulfate, and some of these reactions may proceed until an insoluble S₈ colloid is formed. Full article

Current diagnostic and therapeutic approaches for gliomas have limitations hindering survival outcomes. We propose spectroscopic magnetic resonance imaging as an adjunct to standard MRI to bridge these gaps. Spectroscopic MRI is a volumetric MRI technique capable of identifying tumor infiltration based on its elevated choline (Cho) and decreased N-acetylaspartate (NAA). We present the clinical translatability of spectroscopic imaging with a Cho/NAA ≥ 5x threshold for delineating a biopsy target in a patient diagnosed with non-enhancing glioma. Then, we describe the relationship between the undertreated tumor detected with metabolite imaging and overall survival (OS) from a pilot study of newly diagnosed GBM patients treated with belinostat and chemoradiation. Each cohort (control and belinostat) were split into subgroups using the median difference between pre-radiotherapy Cho/NAA ≥ 2x and the treated T1-weighted contrast-enhanced (T1w-CE) volume. We used the Kaplan–Meier estimator to calculate median OS for each subgroup. The median OS was 14.4 months when the difference between Cho/NAA ≥ 2x and T1w-CE volumes was higher than the median compared with 34.3 months when this difference was lower than the median. The T1w-CE volumes were similar in both subgroups. We find that patients who had lower volumes of undertreated tumors detected via spectroscopy had better survival outcomes. Full article