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Adverse Human Health Effects of Chromium by Exposure Route: A Comprehensive Review Based on Toxicogenomic Approach.
Shin, DY, Lee, SM, Jang, Y, Lee, J, Lee, CM, Cho, EM, Seo, YR
International journal of molecular sciences. 2023;(4)
Abstract
Heavy metals are defined as metals with relatively high density and atomic weight, and their various applications have raised serious concerns about the environmental impacts and potential human health effects. Chromium is an important heavy metal that is involved in biological metabolism, but Cr exposure can induce a severe impact on occupational workers or public health. In this study, we explore the toxic effects of Cr exposure through three exposure routes: dermal contact, inhalation, and ingestion. We propose the underlying toxicity mechanisms of Cr exposure based on transcriptomic data and various bioinformatic tools. Our study provides a comprehensive understanding of the toxicity mechanisms of different Cr exposure routes by diverse bioinformatics analyses.
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Cost Effectiveness of Allogeneic Umbilical Cord Blood-Derived Mesenchymal Stem Cells in Patients with Knee Osteoarthritis.
Suh, K, Cole, BJ, Gomoll, A, Lee, SM, Choi, H, Ha, CW, Lim, HC, Kim, MK, Ha, GY, Suh, DC
Applied health economics and health policy. 2023;(1):141-152
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OBJECTIVES The aim of this study was to assess the cost effectiveness of allogeneic umbilical cord blood-derived mesenchymal stem cells with sodium hyaluronate (hUCB-MSC) compared with microfracture in patients with knee cartilage defects caused by osteoarthritis (OA) in South Korea. METHODS A partitioned survival model approach was taken consisting of five mutually exclusive health states: excellent, good, fair, poor, and death over a 20-year time horizon. Utility values were obtained from a randomized clinical trial. Cost data were extracted from a database provided by the Health Insurance Review & Assessment Service, and the utilization of healthcare services was estimated from an expert panel of orthopedic surgeons using a structured questionnaire. The incremental cost-effectiveness ratio (ICER) in terms of quality-adjusted life-years (QALY) was calculated. Deterministic and probabilistic sensitivity analyses were performed. RESULTS In the base case, the incremental costs of US$14,410 for hUCB-MSC therapy along with its associated QALY gain of 0.857 resulted in an ICER of US$16,812 (₩18,790,773) per QALY (95% confidence interval [CI] US$13,408-US$20,828) when compared with microfracture treatment from a healthcare payer perspective. From a societal perspective, the ICER was US$268 (₩299,255) per QALY (95% CI -US$2915 to US$3784). When using a willingness-to-pay threshold of US$22,367/QALY, the probability of hUCB being cost effectiveness compared with microfracture was 99% from the healthcare payer perspective and 100% from the societal perspective. CONCLUSIONS The study demonstrated that hUCB-MSC therapy was cost effective compared with microfracture when treating patients with knee OA. These findings should inform health policy decision makers about considerations for cost-effective therapy for treating knee OA to ultimately enhance population health.
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Renal protection CT protocol using low-dose and low-concentration iodine contrast medium in at-risk patients of HCC and with chronic kidney disease: a randomized controlled non-inferiority trial.
Yoon, JH, Park, JY, Lee, SM, Lee, ES, Kim, JH, Lee, JM
Cancer imaging : the official publication of the International Cancer Imaging Society. 2023;(1):100
Abstract
BACKGROUND Although efforts have been made to reduce the dose of Contrast Medium (CM) to improve patient safety, there are ongoing concerns regarding its potential effects on image quality and diagnostic performance. Moreover, research is lacking to establish a lower limit for safe and effective CM dose reduction. To determine whether the image quality of contrast-enhanced liver computed tomography (CT) using a reduced amount of iodinated CM was similar to that of standard liver CT. METHODS We enrolled participants at risk for hepatocellular carcinoma with decreased estimated glomerular filtration rates (< 60 mL/min/1.73m2). Participants were randomly assigned to the standard group or the renal protection protocol (RPP) group. In the standard group, images were reconstructed using hybrid iterative reconstruction (iDose), while in the RPP group, low monoenergetic (50-keV) images and deep learning (DL)-based iodine-boosting reconstruction were used. Four radiologists independently assessed image quality and lesion conspicuity. RESULTS Fifty-two participants were assigned to the standard (n = 25) or RPP (n = 27) groups. The iodine load was significantly lower in the RPP group than in the standard group (301.5 ± 1.71 vs. 524 ± 7.37 mgI/kg, P < 0.001). The 50-keV and DL-based iodine-boosting images from the RPP group exhibited higher image contrast than those from the standard group during arterial (3.60 ± 0.65, 3.75 ± 0.60, and 3.09 ± 0.43, respectively) and portal venous phases (4.01 ± 0.49, 3.86 ± 0.42, and 3.21 ± 0.31, respectively) (P < 0.05 for all). Overall image quality was superior in the RPP group (P < 0.05 for all). No significant difference in lesion conspicuity was observed (P > 0.017). CONCLUSIONS The reduction in image contrast and overall image quality caused by decreased CM can be restored using either low monoenergetic imaging or DL-based iodine-boosting reconstruction. TRIAL REGISTRATION clinicaltrials.gov, NCT04024514, Registered July 18, 2019, prospectively registered, https://classic. CLINICALTRIALS gov/ct2/show/NCT04024514 .
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Gastrointestinal tract involvement in systemic sclerosis: The roles of diet and the microbiome.
Nguyen, AD, Andréasson, K, McMahan, ZH, Bukiri, H, Howlett, N, Lagishetty, V, Lee, SM, Jacobs, JP, Volkmann, ER
Seminars in arthritis and rheumatism. 2023;:152185
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BACKGROUND Alterations in gastrointestinal (GI) microbial composition have been reported in patients with systemic sclerosis (SSc). However, it is unclear to what degree these alterations and/or dietary changes contribute to the SSc-GI phenotype. OBJECTIVES Our study aimed to 1) evaluate the relationship between GI microbial composition and SSc-GI symptoms, and 2) compare GI symptoms and GI microbial composition between SSc patients adhering to a low versus non-low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet. METHODS Adult SSc patients were consecutively recruited to provide stool specimens for bacterial 16S rRNA gene sequencing. Patients completed the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument (GIT 2.0) and the Diet History Questionnaire (DHQ) II and were classified as adhering to a low or non-low FODMAP diet. GI microbial differences were assessed using three metrics of alpha diversity (species richness, evenness, and phylogenetic diversity), as well as beta diversity (overall microbial composition). Differential abundance analysis was performed to identify specific genera associated with SSc-GI phenotype and low versus non-low FODMAP diet. RESULTS Of the 66 total SSc patients included, the majority were women (n = 56) with a mean disease duration of 9.6 years. Thirty-five participants completed the DHQ II. Increased severity of GI symptoms (total GIT 2.0 score) was associated with decreased species diversity and differences in GI microbial composition. Specifically, pathobiont genera (e.g., Klebsiella and Enterococcus) were significantly more abundant in patients with increased GI symptom severity. When comparing low (N = 19) versus non-low (N = 16) FODMAP groups, there were no significant differences in GI symptom severity or in alpha and beta diversity. Compared with the low FODMAP group, the non-low FODMAP group had greater abundance of the pathobiont Enterococcus. CONCLUSION SSc patients reporting more severe GI symptoms exhibited GI microbial dysbiosis characterized by less species diversity and alterations in microbial composition. A low FODMAP diet was not associated with significant alterations in GI microbial composition or reduced SSc-GI symptoms; however, randomized controlled trials are needed to evaluate the impact of specific diets on GI symptoms in SSc.
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Model-driven experimental design workflow expands understanding of regulatory role of Nac in Escherichia coli.
Park, JY, Lee, SM, Ebrahim, A, Scott-Nevros, ZK, Kim, J, Yang, L, Sastry, A, Seo, SW, Palsson, BO, Kim, D
NAR genomics and bioinformatics. 2023;(1):lqad006
Abstract
The establishment of experimental conditions for transcriptional regulator network (TRN) reconstruction in bacteria continues to be impeded by the limited knowledge of activating conditions for transcription factors (TFs). Here, we present a novel genome-scale model-driven workflow for designing experimental conditions, which optimally activate specific TFs. Our model-driven workflow was applied to elucidate transcriptional regulation under nitrogen limitation by Nac and NtrC, in Escherichia coli. We comprehensively predict alternative nitrogen sources, including cytosine and cytidine, which trigger differential activation of Nac using a model-driven workflow. In accordance with the prediction, genome-wide measurements with ChIP-exo and RNA-seq were performed. Integrative data analysis reveals that the Nac and NtrC regulons consist of 97 and 43 genes under alternative nitrogen conditions, respectively. Functional analysis of Nac at the transcriptional level showed that Nac directly down-regulates amino acid biosynthesis and restores expression of tricarboxylic acid (TCA) cycle genes to alleviate nitrogen-limiting stress. We also demonstrate that both TFs coherently modulate α-ketoglutarate accumulation stress due to nitrogen limitation by co-activating amino acid and diamine degradation pathways. A systems-biology approach provided a detailed and quantitative understanding of both TF's roles and how nitrogen and carbon metabolic networks respond complementarily to nitrogen-limiting stress.
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The Effect of Omega-3 Enriched Oral Nutrition Supplement on Nutritional Indices and Quality of Life in Gastrointestinal Cancer Patients: A Randomized Clinical Trial.
Sim, E, Kim, JM, Lee, SM, Chung, MJ, Song, SY, Kim, ES, Chun, HJ, Sung, MK
Asian Pacific journal of cancer prevention : APJCP. 2022;23(2):485-494
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Cancer cachexia is a multifactorial condition that reveals impairments in energy and protein balance leading to weight loss through the loss of skeletal muscle and body fat. Nutritional status of cancer patients affects therapeutic efficacy, and the disease survival is influenced by the degree of anorexia. The aim of this study was to evaluate the efficacy of omega-3 fatty acids fortified nutrition supplement intervention on nutritional status, quality of life (QOL) and pro-inflammatory cytokine concentrations of cancer patients. This study was a randomised controlled study. Participants (n = 58) included in the study were patients who were in stages between II to IV receiving one or more cancer therapies without taking any nutritional supplements. Both control and experimental groups received regular nutrition counselling and education, while only the experimental group was asked to take oral nutrition supplements (ONS) twice a day (400 ml, 400 kcal). Results show that ONS intervention: - alleviated symptoms of gastrointestinal symptoms including nausea, vomiting and constipation; - exerted improvements in many of QOL indices; and - did not improve (statistically significant) biochemical markers of nutritional status and concentration level of pro-inflammatory cytokines. Authors conclude that nutritional supplements can improve some of the QOL components which need evidence-based explanation in mechanistic aspects.
Abstract
OBJECTIVE Gastrointestinal (GI) cancer patients often experience severe malnutrition during cancer therapies due to gastrointestinal dysfunctions including poor digestion and absorption as well as tumor-associated anorexia. In this study, we performed a randomized clinical trial to determine the efficacy of oral nutrition supplement (ONS) enriched with omega-3 fatty acids on nutritional status, quality of life (QOL), and pro-inflammatory indices. METHODS Patients diagnosed with GI cancers were recruited and screened for eligibility. A total of 58 patients were randomly allocated to either the control group (n=27) or the experimental group (n=31). The intervention group received 200 ml ONS twice a day while the control group received routine care. Anthropometrics, Patient-Generated Subjective Global Assessment (PG-SGA) score, QOL score and nutrient intake data were collected at baseline, week 4 and week 8. Blood was drawn for biochemical assessments. Nine patients from each group dropped out of the study Forty patients (18 control patients and 22 intervention patients) completed the study. RESULTS This study showed that ONS intervention improved PG-SGA scores in the intervention group (p<0.01). Scores of physical functioning score and role functioning were declined only in the control group and the difference between week 8 and baseline for role functioning was significant (p<0.001). Fatigue score was steadily decreased in the experiment group, and the differences between week 8 and baseline was significant between two groups (p<0.02). However, no statistically significant improvement in biochemical markers of nutritional status and pro-inflammatory cytokine concentrations were found. These results suggests that ONS intervention for 8 weeks improves PG-SGA scores and QOL scores in patients undergoing cancer therapy.
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The intestinal microbiota as a predictor for antidepressant treatment outcome in geriatric depression: a prospective pilot study.
Lee, SM, Dong, TS, Krause-Sorio, B, Siddarth, P, Milillo, MM, Lagishetty, V, Datta, T, Aguilar-Faustino, Y, Jacobs, JP, Lavretsky, H
International psychogeriatrics. 2022;(1):33-45
Abstract
OBJECTIVES (1) To investigate if gut microbiota can be a predictor of remission in geriatric depression and to identify features of the gut microbiota that is associated with remission. (2) To determine if changes in gut microbiota occur with remission in geriatric depression. DESIGN Secondary analysis of a parent randomized placebo-controlled trial (NCT02466958). SETTING Los Angeles, CA, USA (2016-2018). PARTICIPANTS Seventeen subjects with major depressive disorder, over 60 years of age, 41.2% female. INTERVENTION Levomilacipran (LVM) or placebo. MEASUREMENTS Remission was defined by Hamilton Depression Rating Scale score of 6 or less at 12 weeks. 16S-ribosomal RNA sequencing based fecal microbiota composition and diversity were measured at baseline and 12 weeks. Differences in fecal microbiota were evaluated between remitters and non-remitters as well as between baseline and post-treatment samples. LVM and placebo groups were combined in all the analyses. RESULTS Baseline microbiota showed no community level α-diversity or β-diversity differences between remitters and non-remitters. At the individual taxa level, a random forest classifier created with nine genera from the baseline microbiota was highly accurate in predicting remission (AUC = .857). Of these, baseline enrichment of Faecalibacterium, Agathobacter and Roseburia relative to a reference frame was associated with treatment outcome of remission. Differential abundance analysis revealed significant genus level changes from baseline to post-treatment in remitters, but not in non-remitters. CONCLUSIONS This is the first study demonstrating fecal microbiota as a potential predictor of treatment response in geriatric depression. Our findings need to be confirmed in larger prospective studies.
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Nitric oxide: A core signaling molecule under elevated GHGs (CO2, CH4, N2O, O3)-mediated abiotic stress in plants.
Kabange, NR, Mun, BG, Lee, SM, Kwon, Y, Lee, D, Lee, GM, Yun, BW, Lee, JH
Frontiers in plant science. 2022;:994149
Abstract
Nitric oxide (NO), an ancient molecule with multiple roles in plants, has gained momentum and continues to govern plant biosciences-related research. NO, known to be involved in diverse physiological and biological processes, is a central molecule mediating cellular redox homeostasis under abiotic and biotic stresses. NO signaling interacts with various signaling networks to govern the adaptive response mechanism towards stress tolerance. Although diverging views question the role of plants in the current greenhouse gases (GHGs) budget, it is widely accepted that plants contribute, in one way or another, to the release of GHGs (carbon dioxide (CO2), methane (CH4), nitrous oxide (N2O) and ozone (O3)) to the atmosphere, with CH4 and N2O being the most abundant, and occur simultaneously. Studies support that elevated concentrations of GHGs trigger similar signaling pathways to that observed in commonly studied abiotic stresses. In the process, NO plays a forefront role, in which the nitrogen metabolism is tightly related. Regardless of their beneficial roles in plants at a certain level of accumulation, high concentrations of CO2, CH4, and N2O-mediating stress in plants exacerbate the production of reactive oxygen (ROS) and nitrogen (RNS) species. This review assesses and discusses the current knowledge of NO signaling and its interaction with other signaling pathways, here focusing on the reported calcium (Ca2+) and hormonal signaling, under elevated GHGs along with the associated mechanisms underlying GHGs-induced stress in plants.
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Interventions for ADHD in children & adolescents with epilepsy: A review and decision tree to guide clinicians.
Ono, KE, Bearden, DJ, Lee, SM, Moss, C, Kheder, A, Cernokova, I, Drane, DL, Gedela, S
Epilepsy & behavior : E&B. 2022;:108872
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Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common pediatric epilepsy comorbidities. Treating ADHD in the context of epilepsy can be overwhelming for parents and clinicians. Current frontline treatment for ADHD is stimulant medication. However, some parents of pediatric patients with epilepsy have concerns about adding additional medication to their child's epilepsy regimen and/or about adverse effects of stimulant medication. Non-medication ADHD treatments including psychosocial interventions and ketogenic diet have also shown success in improving ADHD symptoms. Our focused review provides an easy-to-use guide for clinicians on ADHD interventions and combinations of interventions for pediatric patients with epilepsy and ADHD. Our guide includes information from 8 electronic databases for peer-reviewed, English language studies of psychosocial treatments for youth with epilepsy and ADHD. One hundred eight studies were selected based on inclusion criteria (21 systematic reviews, 12 meta-analyses, 8 literature reviews, 6 population surveys, 31 clinical trials, 20 cross-sectional studies, and 10 retrospective reviews). Results indicated that stimulant medication is a frontline treatment for ADHD symptoms in youth with epilepsy, with important caveats and alternatives.
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Gut Microbiome Diversity and Abundance Correlate with Gray Matter Volume (GMV) in Older Adults with Depression.
Lee, SM, Milillo, MM, Krause-Sorio, B, Siddarth, P, Kilpatrick, L, Narr, KL, Jacobs, JP, Lavretsky, H
International journal of environmental research and public health. 2022;(4)
Abstract
Growing evidence supports the concept that bidirectional brain-gut microbiome interactions play an important mechanistic role in aging, as well as in various neuropsychiatric conditions including depression. Gray matter volume (GMV) deficits in limbic regions are widely observed in geriatric depression (GD). We therefore aimed to explore correlations between gut microbial measures and GMV within these regions in GD. Sixteen older adults (>60 years) with GD (37.5% female; mean age, 70.6 (SD = 5.7) years) were included in the study and underwent high-resolution T1-weighted structural MRI scanning and stool sample collection. GMV was extracted from bilateral regions of interest (ROI: hippocampus, amygdala, nucleus accumbens) and a control region (pericalcarine). Fecal microbiota composition and diversity were assessed by 16S ribosomal RNA gene sequencing. There were significant positive associations between alpha diversity measures and GMV in both hippocampus and nucleus accumbens. Additionally, significant positive associations were present between hippocampal GMV and the abundance of genera Family_XIII_AD3011_group, unclassified Ruminococcaceae, and Oscillibacter, as well as between amygdala GMV and the genera Lachnospiraceae_NK4A136_group and Oscillibacter. Gut microbiome may reflect brain health in geriatric depression. Future studies with larger samples and the experimental manipulation of gut microbiome may clarify the relationship between microbiome measures and neuroplasticity.