Epigenome-wide association study of lung cancer among never smokers in two prospective cohorts in Shanghai, China.

BACKGROUND: The aetiology of lung cancer among individuals who never smoked remains elusive, despite 15% of lung cancer cases in men and 53% in women worldwide being unrelated to smoking. Epigenetic alterations, particularly DNA methylation (DNAm) changes, have emerged as potential drivers. Yet, few prospective epigenome-wide association studies (EWAS), primarily focusing on peripheral blood DNAm with limited representation of never smokers, have been conducted. METHODS: We conducted a nested case-control study of 80 never-smoking incident lung cancer cases and 83 never-smoking controls within the Shanghai Women's Health Study and Shanghai Men's Health Study. DNAm was measured in prediagnostic oral rinse samples using Illumina MethylationEPIC array. Initially, we conducted an EWAS to identify differentially methylated positions (DMPs) associated with lung cancer in the discovery sample of 101 subjects. The top 50 DMPs were further evaluated in a replication sample of 62 subjects, and results were pooled using fixed-effect meta-analysis. RESULTS: Our study identified three DMPs significantly associated with lung cancer at the epigenome-wide significance level of p<8.22×10-8. These DMPs were identified as cg09198866 (MYH9; TXN2), cg01411366 (SLC9A10) and cg12787323. Furthermore, examination of the top 1000 DMPs indicated significant enrichment in epithelial regulatory regions and their involvement in small GTPase-mediated signal transduction pathways. Additionally, GrimAge acceleration was identified as a risk factor for lung cancer (OR=1.19 per year; 95% CI 1.06 to 1.34). CONCLUSIONS: While replication in a larger sample size is necessary, our findings suggest that DNAm patterns in prediagnostic oral rinse samples could provide novel insights into the underlying mechanisms of lung cancer in never smokers.

Evaluation of Microbiological Susceptibility and Long-term Adhesive Properties to Dentin of Primers with Terminalia catappa Linn.

PURPOSE: To investigate the antibacterial effects of Terminalia catappa Linn (TCL) leaf extracts at different concentrations and the effects of these extracts used as primers on the long-term adhesive properties of two universal adhesives. MATERIALS AND METHODS: After extract preparation, the antimicrobial and antibacterial activities of TCL against Streptococcus mutans (UA 159) were assessed in microdilution assays to provide the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). Additionally, to provide quantitative data on the ability of TCL extract to reduce cell viability, colony forming units (CFU) were counted. To examine adhesive properties, 288 human molars were randomly assigned to 32 experimental conditions (n = 9) according to the following variables: (1) treatment agent: negative control (untreated surface), and primers at concentrations of 1xMIC, 5xMIC, and 10xMIC; (2) adhesives: Scotchbond Universal (SBU) and Futurabond Universal (FBU); (3) adhesive strategy: etch-and-rinse (ER) or self-etch (SE); and (4) storage time: 24 h or after 2 years. Primers were applied for 60 s, upon which the teeth were incrementally restored and sectioned into adhesive-dentin bonded sticks. These were tested for microtensile bond strength (µTBS) and nanoleakage (NL) after 24-h and 2-year water storage, as well as in-situ degree of conversion (DC) at 24 h. The chemical profile of the hybrid layer was determined via micro-Raman spectroscopy. Biofilm assay data were analyzed using the Kruskal-Wallis test; the pH of culture media and the chemical profile were analyzed by one-way ANOVA. The adhesive properties (µTBS, NL, DC) were evaluated using a four-way ANOVA and Tukey's test. Significance was set at 5%. RESULTS: Similar values of MIC and MBC were observed (2 mg/ml), showing bactericidal potential. CFU analysis demonstrated that concentrations of 5xMIC and 10xMIC significantly inhibited biofilm formation (p < 0.001). The application of the TCL primer at all concentrations significantly increased the immediate µTBS and DC, and decreased the immediate NL values when compared to the control group (p < 0.05), regardless of the adhesive and adhesive strategies. Despite an increase in the NL values for all groups after 2 years (p > 0.05), in groups where the TCL primer was applied, the µTBS remained constant after 2 years for both adhesives, while a decrease in the µTBS was observed in the control groups (p < 0.05). Usually, 10xMIC showed better results than 1xMIC and 5xMIC (p < 0.05). The application of TCL promoted cross-linking; cross-linking rates increased proportionally to the concentration of TCL (p < 0.05). CONCLUSION: Primers containing TCL promoted bactericidal and bacteriostatic action, as well as cross-linking with dentin, while maintaining the adhesive properties of the adhesive-dentin interface after 2 years of water storage.

Air pollution mixture associated with oxidative stress exacerbation and symptoms deterioration in allergic rhinitis patients: Evidence from a panel study.

With allergic rhinitis (AR) on the rise globally, there has been a growing focus on the role of environmental pollutants in the onset of AR. However, the potential mechanisms by how and which these pollutants exacerbate AR conditions remain unknown. This panel study of 49 patients diagnosed with AR over one year aimed to assess the individual and combined effects of short-term exposure to multiple ambient pollutants on oxidative stress, symptoms, and quality of life among patients with AR. All participants underwent four repeated assessments of health conditions and personal environmental exposures (PM2.5, O3, SO2, and NO2) over warm and cold seasons during 2017-2018. We evaluated two oxidative stress biomarkers (malondialdehyde [MDA], and superoxide dismutase [SOD]) via nasal lavage. We collected information on self-reported symptoms and quality of life using the Rhinitis Symptom Scale (SRS), the Visual Analog Scale (VAS), and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) through in-person interviews. Bayesian kernel machine regression (BKMR) was used to evaluate the joint effects of pollutant mixture and identify key contributors. The results revealed a significant association of the pollutant mixture when all four pollutants were at or above their median levels, with increased oxidative stress. This was evidenced by elevated MDA and reduced SOD. We found a joint detrimental effect of the pollutant mixture on AR symptoms with a strong association with increased SRS scores, but a non-significant positive association with VAS and RQLQ scores. PM2.5, O3, and SO2 presented as the potentially primary contributors to the adverse health effects associated with the pollutant mixture in Taiyuan city. Patients with AR exposed to short-term air pollutant mixture are more likely to have greater nasal symptoms and worse quality of life from increased oxidative stress and reduced antioxidant capacity. Further research is warranted to better elucidate the underlying mechanisms.

Influence of silver fluoride plus potassium iodine on adhesive properties of primary carious dentin-resin interface: An in vitro study.

This paper evaluated the influence of different protocols of silver fluoride (SF) pretreatment of artificial carious lesions on the adhesive interface of composite resin restorations and remineralization of deciduous dentin compared to silver diamine fluoride (SDF). Sixty-four deciduous molar teeth were randomly divided into 8 groups (n = 8) according to the restoration time (immediately - IM; 30 days after SDF/SF treatment - 30 D) and treatment before restoration (SDF 38 %; SDF 38 % + potassium iodide - KI; SF 38 %; SF 38 % +KI). After SDF/SF application, teeth in the IM group were restored with self-etch universal adhesive system/composite resin. Samples in the 30D groups were stored in artificial saliva (37 °C) for 30 days before receiving the same restoring protocol. Beams were obtained from all groups and subjected to bond strength tests (µTBS), ultrastructural qualitative analysis (FEG) and mineral analysis (SEM/EDX; Micro-Raman spectroscopy). The µTBS data were subjected to three-factor ANOVA and multiple comparisons (Holm-Sidak method). Bond strength values (MPa) for IM groups were 16.9 ± 2.7 (SDF); 17.6 ± 3.5 (SDF + KI); 16.8 ± 5.5 (SF); 18.4 ± 4.1 (SF + KI); and 14.9 ± 4.2 (SDF); 16.0 ± 5.4 (SDF + KI); 14.1 ± 3.6(SF); 16.4 ± 5.4 (SF + KI) for 30D groups. Bond strength wasn't influenced by the moment of restoration (IM or 30D); the use of KI didn't alter adhesion characteristics; SDF/SF solutions resulted in similar adhesive strength; calcium and phosphate expressions were identified at the interfaces on IM and 30D moments. However, 30D presented qualitative increase in these ions, compatible with remineralization. It was concluded that the adhesion of composite resin restorations in artificial caries lesions of deciduous teeth treated with SDF (38 %) and SF (38 %) had similar effects in vitro; the use of KI or the moment when restorations were accomplished did not influence the adhesion and all tested protocols promoted remineralization of carious dentin.

Associations of prenatal one-carbon metabolism nutrients and metals with epigenetic aging biomarkers at birth and in childhood in a US cohort.

Epigenetic gestational age acceleration (EGAA) at birth and epigenetic age acceleration (EAA) in childhood may be biomarkers of the intrauterine environment. We investigated the extent to which first-trimester folate, B12, 5 essential, and 7 non-essential metals in maternal circulation are associated with EGAA and EAA in early life. Bohlin EGAA and Horvath pan-tissue and skin and blood EAA were calculated using DNA methylation measured in cord blood (N=351) and mid-childhood blood (N=326; median age = 7.7 years) in the Project Viva pre-birth cohort. A one standard deviation increase in individual essential metals (copper, manganese, and zinc) was associated with 0.94-1.2 weeks lower Horvath EAA at birth, and patterns of exposures identified by exploratory factor analysis suggested that a common source of essential metals was associated with Horvath EAA. We also observed evidence nonlinear associations of zinc with Bohlin EGAA, magnesium and lead with Horvath EAA, and cesium with skin and blood EAA at birth. Overall, associations at birth did not persist in mid-childhood; however, arsenic was associated with greater EAA at birth and in childhood. Prenatal metals, including essential metals and arsenic, are associated with epigenetic aging in early life, which might be associated with future health.

Experimental studies testing interventions to promote cultural safety, interculturality or antiracism in healthcare: protocol for a systematic review.

INTRODUCTION: Cultural safety, interculturality and antiracism are crucial concepts in addressing health disparities of minority and diverse groups. Measuring them is challenging, however, due to overlapping meanings and their highly contextual nature. Community engagement is essential for evaluating these concepts, yet the methods for social inclusion and protocols for participation remain unclear. This review identifies experimental studies that measure changes resulting from culturally safe, intercultural or antiracist healthcare. The review will describe outcomes and additional factors addressed in these studies. METHODS AND ANALYSIS: The study focuses on epidemiological experiments with counterfactual comparisons and explicit interventions involving culturally safe, intercultural or antiracist healthcare. The search strategy covers PubMed, CINAHL, Scopus, Web of Science, ProQuest, LILACS and WHO IRIS databases. We will use critical appraisal tools from the Joanna Briggs Institute to assess the quality of randomised and non-randomised experimental studies. Two researchers will screen references, select studies and extract data to summarise the main characteristics of the studies, their approach to the three concepts under study and the reported effect measures. We will use fuzzy cognitive mapping models based on the causal relationships reported in the literature. We will consider the strength of the relationships depicted in the maps as a function of the effect measure reported in the study. Measures of centrality will identify factors with higher contributions to the outcomes of interest. Illustrative intervention modelling will use what-if scenarios based on the maps. ETHICS AND DISSEMINATION: This review of published literature does not require ethical approval. We will publish the results in a peer-reviewed journal and present them at conferences. The maps emerging from the process will serve as evidence-based models to facilitate discussions with Indigenous communities to further the dialogue on the contributing factors and assessment of cultural safety, interculturality and antiracism. PROSPERO REGISTRATION NUMBER: CRD42023418459.

Maternal prenatal social experiences and offspring epigenetic age acceleration from birth to mid-childhood.

PURPOSE: Investigate associations of maternal social experiences with offspring epigenetic age acceleration (EAA) from birth through mid-childhood among 205 mother-offspring dyads of minoritized racial and ethnic groups. METHODS: We used linear regression to examine associations of maternal experiences of racial bias or discrimination (0 = none, 1-2 = intermediate, or 3+ = high), social support (tertile 1 = low, 2 = intermediate, 3 = high), and socioeconomic status index (tertile 1 = low, 2 = intermediate, 3 = high) during the prenatal period with offspring EAA according to Horvath's Pan-Tissue, Horvath's Skin and Blood, and Intrinsic EAA clocks at birth, 3 years, and 7 years. RESULTS: In comparison to children of women who did not experience any racial bias or discrimination, those whose mothers reported highest levels of racial bias or discrimination had lower Pan-Tissue clock EAA in early (-0.50 years; 90% CI: -0.91, -0.09) and mid-childhood (-0.75 years; -1.41, -0.08). We observed similar associations for the Skin and Blood clock and Intrinsic EAA. Maternal experiences of discrimination were not associated with Pan-Tissue EAA at birth. Neither maternal social support nor socioeconomic status predicted offspring EAA. CONCLUSIONS: Children whose mothers experienced higher racial bias or discrimination exhibited slower EAA. Future studies are warranted to confirm these findings and establish associations of early-life EAA with long-term health outcomes.

Endoscopic procedures in hepatology: Current trends and new developments.

Gastrointestinal endoscopy has long been a reliable backbone in the diagnosis and management of hepatobilary disorders and their complications. However, with evolving non-invasive testing, personalised medicine has reframed the utility and necessity of endoscopic screening. Conversely, the growing interest and use of endoscopic ultrasound (EUS) and advanced endoscopy within gastrointestinal units has also opened novel diagnostic and therapeutic avenues for patients with various hepatobiliary diseases. The integration of "advanced endoscopy" within the practice of hepatology is nowadays referred to as "endo-hepatology". In essence, endo-hepatology consists of two pillars: one focusing primarily on disorders of the liver parenchyma, vascular disorders, and portal hypertension, which is mainly captured via EUS, while the other targets the hepatobiliary tract via endoscopic retrograde cholangiopancreatography and advanced imaging. Applications under the umbrella of endo-hepatology include, amongst others, EUS-guided liver biopsy, EUS-guided portal pressure gradient measurement, coil and glue embolisation of gastric varices as well as cholangioscopy. As such endo-hepatology could become an attractive concept wherein advanced endoscopy might reinforce the medical management of patients with hepatobiliary disorders and their complications after initial basic work-up. In this review, we discuss current trends and future developments within endo-hepatology and the remaining hurdles to overcome.

A practical approach to the endoscopic management of biliary strictures after liver transplantation.

Biliary tract complications are an important cause of morbidity and mortality after liver transplantation (LT) occurring in 5% to 25% of patients. The most common biliary complication in LT recipients are strictures representing approximately half of these biliary adverse events. Bile duct strictures can be divided into anastomotic biliary strictures (ABS) and non-anastomotic biliary strictures (NABS) depending on their location in the biliary tree, being ABS the most encountered type. Several risk factors identified in previous studies can predispose to the development of ABS and NABS, especially those related to surgical techniques and donor characteristics. Magnetic resonance cholangiopancreatography (MRCP) is the recommended noninvasive imaging test for detecting post-LT biliary strictures, given its high sensitivity and specificity. Once the diagnosis of a biliary stricture after LT has been made, endoscopic retrograde cholangiopancreatography (ERCP) is the preferred initial therapy with good short and long-term results. Biliary sphincterotomy plus balloon dilation (BD) with placement of multiple plastic stents (MPS) has been the classic endoscopic approach for treating ABS, although fully-covered metallic stents (FCSEMS) have emerged as an alternative thanks to shorter total duration of stenting and fewer endoscopic procedures compared to MPS. In this review, we provide a practical update on the management of biliary strictures after LT, focusing our attention on the available evidence in the endoscopic therapy.

Behavioral Modification of Leucauge mariana Induced by an Ichneumonid Spider-Parasitoid, Hymenoepimecis castilloi, in the Colombian Andes.

Hymenoepimecis is a genus of Darwin wasps in the Polysphincta group of genera (Hymenoptera: Ichneumonidae: Pimplinae) known as ectoparasitoids of a broad spectrum of spiders. The parasitoid induces production of a web known as cocoon web, which provides shelter and support for the wasp pupa. In this study, we describe for the first time the interaction between Hymenoepimecis castilloi Pádua & Sääksjärvi (Hymenoptera: Ichneumonidae) and its host spider Leucauge mariana (Taczanowski) (Araneae: Tetragnathidae) in the Colombian Andes, provide new records of wasp genus distribution, and described the behavioral modifications induced in the spider. Web modifications occurred in the webs of both solitary and aggregated individuals. Adhesive spirals were lacking, and webs were connected to vegetation by multiple threads in all cocoon webs, which was not seen attached to webs of non-parasitized spiders. All parasitoid cocoons were observed hanging on a vertical line in the hub of the cocoon web. As previously described for other species, we believe that this modified web design results in increased web strength and favors parasitoid development during the pupal stage.

Cross-sectional and prospective associations of early childhood circulating metals with early and mid-childhood cognition in the Project Viva cohort.

BACKGROUND: Relatively little is known about the immediate and prospective neurodevelopmental impacts of joint exposure to multiple metals (i.e., metal mixtures) in early childhood. OBJECTIVES: To estimate associations of early childhood (∼3 years of age) blood metal concentrations with cognitive test scores at early and mid-childhood (∼8 years of age). METHODS: We studied children from the Project Viva cohort. We measured erythrocyte concentrations of seven essential (Co, Cu, Mg, Mn, Mo, Se, and Zn) and eight non-essential metals (As, Ba, Cd, Cs, Hg, Pb, Sn, and Sr) in early childhood blood samples. Trained research assistants administered cognitive tests assessing vocabulary, visual-motor ability, memory, and general intelligence (standard deviations: ∼10 points), in early and mid-childhood. We employed multivariable linear regression to examine associations of individual metals with test scores adjusting for confounders, other concurrently measured metals, and first-trimester maternal blood metals. We also estimated joint associations and explored interaction between metals in mixture analyses. RESULTS: We analyzed 349 children (median whole blood Pb ∼1 µg/dL). In cross-sectional analyses, each doubling of Pb was associated with lower visual-motor function (mean difference: -2.43 points, 95% confidence interval (CI): -4.01, -0.86) and receptive vocabulary, i.e., words understood (-1.45 points, 95% CI: -3.26, 0.36). Associations of Pb with mid-childhood cognition were weaker and less precise by comparison. Mg was positively associated with cognition in cross-sectional but not prospective analyses, and cross-sectional associations were attenuated in a sensitivity analysis removing adjustment for concurrent metals. We did not observe joint associations nor interactions. DISCUSSION: In this cohort with low blood Pb levels, increased blood Pb was robustly associated with lower cognitive ability in cross-sectional analyses, even after adjustment for prenatal Pb exposure, and regardless of adjustment for metal co-exposures. However, associations with mid-childhood cognition were attenuated and imprecise, suggesting some buffering of Pb neurotoxicity in early life. WHAT THIS STUDY ADDS: Relatively few studies have comprehensively separated the effects of neurotoxic metals such as lead (Pb) from pre- and postnatal co-occurring metals, nor examined persistence of associations across childhood. In a cohort of middle-class children, we found higher early childhood (∼3 y) blood Pb was associated with lower scores on cognitive tests, independent of other metals and prenatal blood Pb. However, early childhood Pb was only weakly associated with cognition in mid-childhood (∼8 y). Our results suggest the effects of low-level Pb exposure may attenuate over time in some populations, implying the presence of factors that may buffer Pb neurotoxicity in early life.

Infant Feeding Practices and Metal Concentrations in Children's Blood.

This cohort study assesses the association between 4 infant feeding practices and concentrations of 8 nonessential and 7 essential metals in red blood cells.

Long-term Evaluation of Dentin Bonding Properties of the Photoinitiator System Contained in Universal Adhesives Used in Fiber-Post Luting Procedures.

PURPOSE: This study evaluated the long-term push-out bond strength (PBS) and nanoleakage (NL) of universal adhesives with different photo-initiator systems in the root canals of teeth in which fiber posts were luted. MATERIALS AND METHODS: One-hundred twenty endodontically treated human premolars were randomly divided into 12 groups based on the following factors: adhesives (Scotchbond Universal [SBU], Ambar Universal [AMB], and Ambar Universal APS [AMB-APS]); adhesive strategy (etch-and-rinse and self-etch), and time of testing (immediately vs after 2 years). The posts were cemented, sectioned into slices, tested for PBS at 0.5 mm/min, and examined for NL using scanning electron microscopy immediately thereafter or after 2 years of water storage. Data were evaluated using a four-way ANOVA (root thirds vs time vs universal adhesive vs adhesive strategies) and Tukey's test (α = 5%). RESULTS: For both evaluation times, AMB-APS demonstrated no significant difference in the PBS or NL when different radicular thirds were compared (p > 0.05). However, for SBU and AMB, the cervical third demonstrated higher PBS and lower NL than those of the apical third at both time points (p < 0.0001). AMB-APS exhibited higher PBS and lower NL in the apical third in comparison with SBU and AMB (p < 0.0001). SBU and AMB displayed a significant decrease in the PBS and increased NL after 2 years (p < 0.0001), whereas AMB-APS demonstrated no significant signs of degradation even after 2 years of water storage (p > 0.05). CONCLUSION: Independent of the root third evaluated, the universal adhesive containing APS photo-initiator system demonstrated bonding stability at the adhesive interface between the root canal and fiber posts, even after 2 years of water storage.

Environmental tobacco smoke and children's health: a bibliometric and altmetric analysis of 100 most cited articles.

BACKGROUND: Exposure to environmental tobacco smoke (ETS) is arguably the most ubiquitous and hazardous, even at very low levels, starting in early life. The objective of this study was to describe the state of research and future trends on ETS exposure and Children's Health (CH) topics with bibliometrics and altmetrics. METHODS: An electronic search was performed in Scopus database on January 31, 2023. Consensus was arrived on 100 most-cited articles by two reviewers. These papers were then cross matched with citations harvested from Web of Science (WoS) and Google Scholar. Altmetric Attention Score (AAS) and Dimension counts were also collected. Analysis and network visualization of authors, countries, and keywords were generated using VOSviewer software. RESULTS: Among a total of 1107 articles published on ETS and CH, the 100 top-cited articles appeared in 54 journals, with Pediatrics (n = 12) contributing a maximum number of articles. The time period between 2000 and 2009 accounted for 44% of all publications. With respect to the research design employed across these studies, cross-sectional design took precedence over others accounting for approximately 40%. Predominantly, articles focused on childhood asthma; however, current research trends have shifted towards emerging fields such as children's oral health and DNA methylation. Twitter, policy documents, and news outlets were the main platforms where outputs were discussed. The AAS was not associated with journal impact factor or access type. Weak correlations were observed between AAS and citation count in Scopus, WoS, and Google Scholar (r = 0.17 to 0.27) while a positive association existed between dimension count and the number of citations across all three databases (r = 0.84 to 0.98). CONCLUSION: This study demonstrates the evolution, digital dissemination and research hotspots in the field of ETS and CH, predicting the possible future research directions. High-quality studies with more specific exposure classification are warranted to better understand the relationship between ETS and CH.

Associations Between Epigenetic Age Acceleration and microRNA Expression Among U.S. Firefighters.

Epigenetic changes may be biomarkers of health. Epigenetic age acceleration (EAA), the discrepancy between epigenetic age measured via epigenetic clocks and chronological age, is associated with morbidity and mortality. However, the intersection of epigenetic clocks with microRNAs (miRNAs) and corresponding miRNA-based health implications have not been evaluated. We analyzed DNA methylation and miRNA profiles from blood sampled among 332 individuals enrolled across 2 U.S.-based firefighter occupational studies (2015-2018 and 2018-2020). We considered 7 measures of EAA in leukocytes (PhenoAge, GrimAge, Horvath, skin-blood, and Hannum epigenetic clocks, and extrinsic and intrinsic epigenetic age acceleration). We identified miRNAs associated with EAA using individual linear regression models, adjusted for sex, race/ethnicity, chronological age, and cell type estimates, and investigated downstream effects of associated miRNAs with miRNA enrichment analyses and genomic annotations. On average, participants were 38 years old, 88% male, and 75% non-Hispanic white. We identified 183 of 798 miRNAs associated with EAA (FDR q < 0.05); 126 with PhenoAge, 59 with GrimAge, 1 with Horvath, and 1 with the skin-blood clock. Among miRNAs associated with Horvath and GrimAge, there were 61 significantly enriched disease annotations including age-related metabolic and cardiovascular conditions and several cancers. Enriched pathways included those related to proteins and protein modification. We identified miRNAs associated with EAA of multiple epigenetic clocks. PhenoAge had more associations with individual miRNAs, but GrimAge and Horvath had greater implications for miRNA-associated pathways. Understanding the relationship between these epigenetic markers could contribute to our understanding of the molecular underpinnings of aging and aging-related diseases.

Securing the diagnosis of HRS-AKI: implications for current therapies.

INTRODUCTION: Hepatorenal syndrome (HRS)-acute kidney injury (HRS-AKI) is a specific type of kidney injury seen in patients with cirrhosis and ascites and is associated with high mortality and morbidity. It is characterized by rapid deterioration of renal function due to reduced renal blood flow secondary to portal hypertensive splanchnic and systemic vasodilation. Early diagnosis and treatment of HRS-AKI are associated with greater likelihood of improvement in renal function, lower need for dialysis, and better post-transplant outcomes. AREAS COVERED: This review discusses the diagnostic criteria for HRS-AKI, which has undergone several key changes over the last decade, with an aim to secure an early diagnosis and aid swift treatment initiation. Additionally, this review outlines the current treatment paradigms for HRS-AKI. EXPERT OPINION: In the last 20 years, there have been several advances in understanding the pathophysiology and natural course of HRS-AKI. These have led to critical changes in its definition and diagnostic algorithm. However, prognosis of HRS-AKI remains dismal with no significant improvement in HRS-AKI reversal or HRS-related mortality over this time. We discuss several gaps in the current understanding and management of HRS-AKI that will benefit from further research.

Maternal adverse childhood experiences (ACEs) and DNA methylation of newborns in cord blood.

BACKGROUND: Adverse childhood experiences (ACEs) increase the risk of poor health outcomes later in life. Psychosocial stressors may also have intergenerational health effects by which parental ACEs are associated with mental and physical health of children. Epigenetic programming may be one mechanism linking parental ACEs to child health. This study aimed to investigate epigenome-wide associations of maternal preconception ACEs with DNA methylation patterns of children. In the Center for the Health Assessment of Mothers and Children of Salinas study, cord blood DNA methylation was measured using the Illumina HumanMethylation450 BeadChip. Preconception ACEs, which occurred during the mothers' childhoods, were collected using a standard ACE questionnaire including 10 ACE indicators. Maternal ACE exposures were defined in this study as (1) the total number of ACEs; (2) the total number of ACEs categorized as 0, 1-3, and > 4; and (3) individual ACEs. Associations of ACE exposures with differential methylated positions, regions, and CpG modules determined using weighted gene co-expression network analysis were evaluated adjusting for covariates. RESULTS: Data on maternal ACEs and cord blood DNA methylation were available for 196 mother/newborn pairs. One differential methylated position was associated with maternal experience of emotional abuse (cg05486260/FAM135B gene; q value < 0.05). Five differential methylated regions were significantly associated with the total number of ACEs, and 36 unique differential methylated regions were associated with individual ACEs (Sidák p value < 0.05). Fifteen CpG modules were significantly correlated with the total number of ACEs or individual ACEs, of which 8 remained significant in fully adjusted models (p value < 0.05). Significant modules were enriched for pathways related to neurological and immune development and function. CONCLUSIONS: Maternal ACEs prior to conception were associated with cord blood DNA methylation of offspring at birth. Although there was limited overlap between differential methylated regions and CpGs in modules associated with ACE exposures, statistically significant regions and networks were related to genes involved in neurological and immune function. Findings may provide insights to pathways linking psychosocial stressors to health. Further research is needed to understand the relationship between changes in DNA methylation and child health.