Thyroid hormone action and liver disease, a complex interplay.

Thyroid hormone action is involved in virtually all physiological processes. It is well known that the liver and thyroid are intimately linked, with thyroid hormone playing important roles in de novo lipogenesis, beta-oxidation (fatty acid oxidation), cholesterol metabolism, and carbohydrate metabolism. Clinical and mechanistic research studies have shown that thyroid hormone can be involved in chronic liver diseases, including alcohol-associated or NAFLD and HCC. Thyroid hormone action and synthetic thyroid hormone analogs can exert beneficial actions in terms of lowering lipids, preventing chronic liver disease and as liver anticancer agents. More recently, preclinical and clinical studies have indicated that some analogs of thyroid hormone could also play a role in the treatment of liver disease. These synthetic molecules, thyromimetics, can modulate lipid metabolism, particularly in NAFLD/NASH. In this review, we first summarize the thyroid hormone signaling axis in the context of liver biology, then we describe the changes in thyroid hormone signaling in liver disease and how liver diseases affect the thyroid hormone homeostasis, and finally we discuss the use of thyroid hormone-analog for the treatment of liver disease.

Altered anti-viral immune responses in monocytes in overweight heavy drinkers.

Alcohol abuse causes increased susceptibility to respiratory syndromes like bacterial pneumonia and viral infections like SARS-CoV-2. Heavy drinkers (HD) are at higher risk of severe COVID-19 if they are also overweight, yet the molecular mechanisms are unexplored. Single-cell RNA-sequencing (scRNA-seq) was performed on peripheral blood mononuclear cells from lean or overweight HD and healthy controls (HC) after challenge with a dsRNA homopolymer (PolyI:C) to mimic a viral infection and/or with lipopolysaccharide (LPS). All monocyte populations responded to both PolyI:C and LPS with pro-inflammatory gene expression. However, the expression of interferon-stimulated genes, essential for inhibiting viral pathogenesis, was greatly reduced in overweight patients. Interestingly, the number of upregulated genes in response to the PolyI:C challenge was far greater in monocytes from HD compared to HC, including much stronger pro-inflammatory cytokine and interferon-γ signaling responses. These results suggest that increased body weight reduced anti-viral responses while heavy drinking increased pro-inflammatory cytokines.

5S rRNA pseudogene transcripts are associated with interferon production and inflammatory responses in alcohol-associated hepatitis.

BACKGROUND AND AIMS: Interferon (IFN) signaling is critical to the pathogenesis of alcohol-associated hepatitis (AH), yet the mechanisms for activation of this system are elusive. We hypothesize that host-derived 5S rRNA pseudogene (RNA5SP) transcripts regulate IFN production and modify immunity in AH. APPROACH AND RESULTS: Mining of transcriptomic datasets revealed that in patients with severe alcohol-associated hepatitis (sAH), hepatic expression of genes regulated by IFNs was perturbed and gene sets involved in IFN production were enriched. RNA5SP transcripts were also increased and correlated with expression of type I IFNs. Interestingly, inflammatory mediators upregulated in sAH, but not in other liver diseases, were positively correlated with certain RNA5SP transcripts. Real-time quantitative PCR demonstrated that RNA5SP transcripts were upregulated in peripheral blood mononuclear cells (PBMCs) from patients with sAH. In sAH livers, increased 5S rRNA and reduced nuclear MAF1 (MAF1 homolog, negative regulator of RNA polymerase III) protein suggested a higher activity of RNA polymerase III (Pol III); inhibition of Pol III reduced RNA5SP expression in monocytic THP-1 cells. Expression of several RNA5SP transcript-interacting proteins was downregulated in sAH, potentially unmasking transcripts to immunosensors. Indeed, siRNA knockdown of interacting proteins potentiated the immunostimulatory activity of RNA5SP transcripts. Molecular interaction and cell viability assays demonstrated that RNA5SP transcripts adopted Z-conformation and contributed to ZBP1-mediated caspase-independent cell death. CONCLUSIONS: Increased expression and binding availability of RNA5SP transcripts was associated with hepatic IFN production and inflammation in sAH. These data identify RNA5SP transcripts as a potential target to mitigate inflammation and hepatocellular injury in AH.

Navigating puberty, identity, and race among transnationally, transracially adopted Korean American adolescents.

This exploratory study examined the relation between pubertal timing and dimensions of ethnic-racial identity among adopted Korean Americans raised transracially in White families. The study also examined whether internalized racism moderated the association between pubertal timing and ethnic-racial identity. Adopted Korean American adolescents (N = 202; 108 females; ages 13-19 years) completed measures of pubertal development, ethnic-racial identity, and internalized racism in 2007. There was no significant main effect of pubertal timing for either male or female adolescents. Internalized racism moderated the relation between pubertal timing and ethnic-racial identity clarity (B = -.16, p = .015) among male adolescents. Specifically, earlier pubertal timing was significantly associated with lower ethnic-racial identity clarity for male adolescents with higher levels of internalized racism.

A critical review of recent knowledge of alcohol's effects on the immunological response in different tissues.

Alcohol misuse contributes to the dysregulation of immune responses and multiorgan dysfunction across various tissues, which are associated with higher risk of morbidity and mortality in people with alcohol use disorders. Organ-specific immune cells, including microglia in the brain, alveolar macrophages in the lungs, and Kupffer cells in the liver, play vital functions in host immune defense through tissue repair and maintenance of homeostasis. However, binge drinking and chronic alcohol misuse impair these immune cells' abilities to regulate inflammatory signaling and metabolism, thus contributing to multiorgan dysfunction. Further complicating these delicate systems, immune cell dysfunction associated with alcohol misuse is exacerbated by aging and gut barrier leakage. This critical review describes recent advances in elucidating the potential mechanisms by which alcohol misuse leads to derangements in host immunity and highlights current gaps in knowledge that may be the focus of future investigations.

Macrophage-derived MLKL in alcohol-associated liver disease: Regulation of phagocytosis.

BACKGROUND AND AIMS: Mixed lineage kinase domain-like pseudokinase (MLKL), a key terminal effector of necroptosis, also plays a role in intracellular vesicle trafficking that is critical for regulating liver inflammation and injury in alcohol-associated liver disease (ALD). Although receptor interacting protein kinase 3 (Rip3)-/- mice are completely protected from ethanol-induced liver injury, Mlkl-/- mice are only partially protected. Therefore, we hypothesized that cell-specific functions of MLKL may contribute to ethanol-induced injury. APPROACH AND RESULTS: Bone marrow transplants between Mlkl-/- mice and littermates were conducted to distinguish the role of myeloid versus nonmyeloid Mlkl in the Gao-binge model of ALD. Ethanol-induced hepatic injury, steatosis, and inflammation were exacerbated in Mlkl-/- →wild-type (WT) mice, whereas Mlkl deficiency in nonmyeloid cells (WT→ Mlkl-/- ) had no effect on Gao-binge ethanol-induced injury. Importantly, Mlkl deficiency in myeloid cells exacerbated ethanol-mediated bacterial burden and accumulation of immune cells in livers. Mechanistically, challenging macrophages with lipopolysaccharide (LPS) induced signal transducer and activator of transcription 1-mediated expression and phosphorylation of MLKL, as well as translocation and oligomerization of MLKL to intracellular compartments, including phagosomes and lysosomes but not plasma membrane. Importantly, pharmacological or genetic inhibition of MLKL suppressed the phagocytic capability of primary mouse Kupffer cells (KCs) at baseline and in response to LPS with/without ethanol as well as peripheral monocytes isolated from both healthy controls and patients with alcohol-associated hepatitis. Further, in vivo studies revealed that KCs of Mlkl-/- mice phagocytosed fewer bioparticles than KCs of WT mice. CONCLUSION: Together, these data indicate that myeloid MLKL restricts ethanol-induced liver inflammation and injury by regulating hepatic immune cell homeostasis and macrophage phagocytosis.

Recent Advances in Understanding of Pathogenesis of Alcohol-Associated Liver Disease.

Alcohol-associated liver disease (ALD) is one of the major diseases arising from chronic alcohol consumption and is one of the most common causes of liver-related morbidity and mortality. ALD includes asymptomatic liver steatosis, fibrosis, cirrhosis, and alcohol-associated hepatitis and its complications. The progression of ALD involves complex cell-cell and organ-organ interactions. We focus on the impact of alcohol on dysregulation of homeostatic mechanisms and regulation of injury and repair in the liver. In particular, we discuss recent advances in understanding the disruption of balance between programmed cell death and prosurvival pathways, such as autophagy and membrane trafficking, in the pathogenesis of ALD. We also summarize current understanding of innate immune responses, liver sinusoidal endothelial cell dysfunction and hepatic stellate cell activation, and gut-liver and adipose-liver cross talk in response to ethanol. In addition,we describe the current potential therapeutic targets and clinical trials aimed at alleviating hepatocyte injury, reducing inflammatory responses, and targeting gut microbiota, for the treatment of ALD.

New insights into the mechanism of alcohol-mediated organ damage via its impact on immunity, metabolism, and repair pathways: A summary of the 2021 Alcohol and Immunology Research Interest Group (AIRIG) meeting.

On November 19th, 2021, the annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held at Loyola University Chicago Health Sciences Campus in Maywood, Illinois. The 2021 meeting focused on how alcohol misuse is linked to immune system derangements, leading to tissue and organ damage, and how this research can be translated into improving treatment of alcohol-related disease. This meeting was divided into three plenary sessions: the first session focused on how alcohol misuse affects different parts of the immune system, the second session presented research on mechanisms of organ damage from alcohol misuse, and the final session highlighted research on potential therapeutic targets for treating alcohol-mediated tissue damage. Diverse areas of alcohol research were covered during the meeting, from alcohol's effect on pulmonary systems and neuroinflammation to epigenetic changes, senescence markers, and microvesicle particles. These presentations yielded a thoughtful discussion on how the findings can lead to therapeutic treatments for people suffering from alcohol-related diseases.

Gut microbial trimethylamine is elevated in alcohol-associated hepatitis and contributes to ethanol-induced liver injury in mice.

There is mounting evidence that microbes residing in the human intestine contribute to diverse alcohol-associated liver diseases (ALD) including the most deadly form known as alcohol-associated hepatitis (AH). However, mechanisms by which gut microbes synergize with excessive alcohol intake to promote liver injury are poorly understood. Furthermore, whether drugs that selectively target gut microbial metabolism can improve ALD has never been tested. We used liquid chromatography tandem mass spectrometry to quantify the levels of microbe and host choline co-metabolites in healthy controls and AH patients, finding elevated levels of the microbial metabolite trimethylamine (TMA) in AH. In subsequent studies, we treated mice with non-lethal bacterial choline TMA lyase (CutC/D) inhibitors to blunt gut microbe-dependent production of TMA in the context of chronic ethanol administration. Indices of liver injury were quantified by complementary RNA sequencing, biochemical, and histological approaches. In addition, we examined the impact of ethanol consumption and TMA lyase inhibition on gut microbiome structure via 16S rRNA sequencing. We show the gut microbial choline metabolite TMA is elevated in AH patients and correlates with reduced hepatic expression of the TMA oxygenase flavin-containing monooxygenase 3 (FMO3). Provocatively, we find that small molecule inhibition of gut microbial CutC/D activity protects mice from ethanol-induced liver injury. CutC/D inhibitor-driven improvement in ethanol-induced liver injury is associated with distinct reorganization of the gut microbiome and host liver transcriptome. The microbial metabolite TMA is elevated in patients with AH, and inhibition of TMA production from gut microbes can protect mice from ethanol-induced liver injury.

Sessile Serrated Adenoma With Dysplasia of the Colon.

OBJECTIVES: Sessile serrated adenomas with dysplasia (SSADs) of the colon are transitional lesions between sessile serrated adenomas (SSAs) and a subset of colorectal adenocarcinomas. We wished to gain insight into the relative percentages and significance of SSAD subtypes. METHODS: Retrospective (2007-2012) clinicopathologic review of colorectal polyps initially regarded as having mixed serrated and dysplastic elements. SSADs were subdivided into those with cap-like adenomatous dysplasia (ad1), non-cap-like adenomatous dysplasia (ad2), serrated dysplasia (ser), minimal dysplasia (min), and dysplasia not otherwise specified (nos). MLH1 immunostaining was performed on many. RESULTS: SSADser (7.7%) had a greater propensity for right colon, women, and MLH1 loss vs the entire cohort. SSAad1 (11.6%) had the least female preponderance, was least likely to have MLH1 loss, and was most likely to affect the left colorectum. SSAD with MLH1 loss was associated with an increased burden of SSAs in the background colon (P = .0003) but not tubular adenomas or hyperplastic polyps. Most SSADs (ad2 and nos groups, 80% combined) showed difficult-to-classify dysplasia, intermediate MLH1 loss rates, and intermediate clinical features. CONCLUSIONS: While some trends exist, morphologically subclassifying SSADs is probably not justified in routine clinical practice. MLH1 loss portends a greater burden of SSAs in the background colon.

Identification of a MicroRNA-E3 Ubiquitin Ligase Regulatory Network for Hepatocyte Death in Alcohol-Associated Hepatitis.

We aimed to identify a microRNA (miRNA)-E3 ubiquitin ligase regulatory network for protein substrates enriched in cell death pathways and investigate the underlying molecular mechanisms in alcohol-associated hepatitis (AH). An miRNA-E3 ubiquitin ligase regulatory network for protein substrates enriched in cell death pathways was constructed using integrated bioinformatics analysis. Differentially expressed hub miRNAs (GSE59492) and their validated miRNA target genes (GSE28619) were identified in the liver of patients with AH compared with healthy controls. Liver samples from patients with AH and healthy individuals and mice exposed to Gao-binge (acute on chronic) ethanol were used for experimental validation. Using hub miRNAs identified by weighted correlation network analysis, a miRNA-E3 ubiquitin ligase regulatory network was established based on 17 miRNAs and 7 E3 ligase genes targeted by these miRNAs that were down-regulated in AH. Among the miRNAs in this regulatory network, miR-150-5p was the only miRNA regulating the E3 ligase cytokine-inducible SH2 containing protein (CISH), the E3 ligase that regulates the largest number of substrates among all E3 ligase family members. Therefore, the CISH regulatory pathway for ubiquitinated substrates was selected for subsequent experimental validation. Consistent with the bioinformatics analysis results, expression of miR-150-5p was markedly increased, while CISH was decreased, in the livers of patients with AH and mice exposed to Gao-binge ethanol. Moreover, ubiquitination of Fas-associated protein with death domain, a predicted CISH substrate involved in the regulation of programmed cell death, was reduced in livers from mice after Gao-binge ethanol. Conclusion: Identification of the miRNA-E3 ubiquitin ligase regulatory network for protein substrates enriched in the cell death pathways provides insights into the molecular mechanisms contributing to hepatocyte death in AH.

Gene Deconvolution Reveals Aberrant Liver Regeneration and Immune Cell Infiltration in Alcohol-Associated Hepatitis.

BACKGROUND AND AIMS: Acute liver damage causes hepatocyte stress and death, but in chronic liver disease impaired hepatocyte regeneration and immune cell infiltration prevents recovery. While the roles of both impaired liver regeneration and immune infiltration have been studied extensively in chronic liver diseases, the differential contribution of these factors is difficult to assess. APPROACH AND RESULTS: We combined single-cell RNA-sequencing (RNA-seq) data from healthy livers and peripheral immune cells to measure cell proportions in chronic liver diseases. Using bulk RNA-seq data from patients with early alcohol-associated hepatitis, severe AH (sAH), HCV, HCV with cirrhosis, and NAFLD, we performed gene deconvolution to predict the contribution of different cell types in each disease. Patients with sAH had the greatest change in cell composition, with increases in both periportal hepatocytes and cholangiocyte populations. Interestingly, while central vein hepatocytes were decreased, central vein endothelial cells were expanded. Endothelial cells are thought to regulate liver regeneration through WNT signaling. WNT2, important in central vein hepatocyte development, was down in sAH, while multiple other WNTs and WNT receptors were up-regulated. Immunohistochemistry revealed up-regulation of FZD6, a noncanonical WNT receptor, in hepatocytes in sAH. Immune cell populations also differed in disease. In sAH, a specific group of inflammatory macrophages was increased and distinct from the macrophage population in patients with HCV. Network and correlation analyses revealed that changes in the cell types in the liver were highly correlated with clinical liver function tests. CONCLUSIONS: These results identify distinct changes in the liver cell populations in chronic liver disease and illustrate the power of using single-cell RNA-seq data from a limited number of samples in understanding multiple different diseases.

Diagnostic and Prognostic Significance of Complement in Patients With Alcohol-Associated Hepatitis.

BACKGROUND AND AIMS: Given the lack of effective therapies and high mortality in acute alcohol-associated hepatitis (AH), it is important to develop rationally designed biomarkers for effective disease management. Complement, a critical component of the innate immune system, contributes to uncontrolled inflammatory responses leading to liver injury, but is also involved in hepatic regeneration. Here, we investigated whether a panel of complement proteins and activation products would provide useful biomarkers for severity of AH and aid in predicting 90-day mortality. APPROACH AND RESULTS: Plasma samples collected at time of diagnosis from 254 patients with moderate and severe AH recruited from four medical centers and 31 healthy persons were used to quantify complement proteins by enzyme-linked immunosorbent assay and Luminex arrays. Components of the classical and lectin pathways, including complement factors C2, C4b, and C4d, as well as complement factor I (CFI) and C5, were reduced in AH patients compared to healthy persons. In contrast, components of the alternative pathway, including complement factor Ba (CFBa) and factor D (CFD), were increased. Markers of complement activation were also differentially evident, with C5a increased and the soluble terminal complement complex (sC5b9) decreased in AH. Mannose-binding lectin, C4b, CFI, C5, and sC5b9 were negatively correlated with Model for End-Stage Liver Disease score, whereas CFBa and CFD were positively associated with disease severity. Lower CFI and sC5b9 were associated with increased 90-day mortality in AH. CONCLUSIONS: Taken together, these data indicate that AH is associated with a profound disruption of complement. Inclusion of complement, especially CFI and sC5b9, along with other laboratory indicators, could improve diagnostic and prognostic indications of disease severity and risk of mortality for AH patients.

Hepatobiliary malignancies have distinct peripheral myeloid-derived suppressor cell signatures and tumor myeloid cell profiles.

Myeloid-derived suppressor cells (MDSCs) are immunosuppressive cells that are increased in patients with numerous malignancies including viral-derived hepatocellular carcinoma (HCC). Here, we report an elevation of MDSCs in the peripheral blood of patients with other hepatobiliary malignancies including non-viral HCC, neuroendocrine tumors (NET), and colorectal carcinoma with liver metastases (CRLM), but not cholangiocarcinoma (CCA). The investigation of myeloid cell infiltration in HCC, NET and intrahepatic CCA tumors further established that the frequency of antigen-presenting cells was limited compared to benign lesions, suggesting that primary and metastatic hepatobiliary cancers have distinct peripheral and tumoral myeloid signatures. Bioinformatics analysis of The Cancer Genome Atlas dataset demonstrated that a high MDSC score in HCC patients is associated with poor disease outcome. Given our observation that MDSCs are increased in non-CCA malignant liver cancers, these cells may represent suitable targets for effective immunotherapy approaches.

Adenomas per colonoscopy and adenoma per positive participant as quality indicators for screening colonoscopy.

Background and study aims Adenomas per colonoscopy (APC) and adenomas per positive patient (APP) have been proposed as additional quality indicators but their association with adenoma detection rate (ADR) is not well studied. The aim of our study was to evaluate the variability in APC and APP, their association with ADR, and associated risk factors in screening colonoscopies from a community practice. Patients and methods We calculated the APC, APP, and ADR from all screening colonoscopies performed over 5 years. We used adjusted hierarchical logistic regression to assess the association of factors with APC, APP, and ADR. Results There were 80,915 screening colonoscopies by 60 gastroenterologists. The median (Q1-Q3) APC, APP, and ADR were 0.41 (0.36 - 0.53), 1.33 (1.23 - 1.40), and 0.32 (0.28 - 0.38), respectively. Despite the high correlation between APC and ADR, 47.6 % of endoscopists with the lowest APC had a higher ADR, and no endoscopists with the highest APC had a lower ADR. Of endoscopists with the lowest APP, 74.3 % had a higher ADR and 5.6 % of endoscopists with the highest APP had a lower ADR. Factors associated with higher APC after multivariable adjustment included: older patients age (OR 1.003; 95 % CI 1.002 - 1.005), male patients (OR 1.123; 95 % CI 1.090 - 1.156), younger endoscopist age (OR 0.943; 95 % CI 0.941 - 0.945), and longer withdrawal time (OR 3.434; 95 % CI 2.941 - 4.010). Factors associated with higher APP were male sex, younger endoscopist age, and longer withdrawal time. Conclusion APC and APP provides additional information about endoscopist performance. Younger endoscopist age and longer withdrawal time are associated with colonoscopy quality.

Functionally Diverse Inflammatory Responses in Peripheral and Liver Monocytes in Alcohol-Associated Hepatitis.

Alcohol-associated hepatitis (AH) is an acute inflammatory disease in which gut-microbial byproducts enter circulation and peripheral immune cells infiltrate the liver, leading to nonresolving inflammation and injury. Single-cell RNA sequencing of peripheral blood mononuclear cells isolated from patients with AH and healthy controls paired with lipopolysaccharide (LPS) challenge revealed how diverse monocyte responses are divided among individual cells and change in disease. After LPS challenge, one monocyte subtype expressed pro-inflammatory genes in both disease and healthy controls, while another monocyte subtype was anti-inflammatory in healthy controls but switched to pro-inflammatory in AH. Numerous immune genes are clustered within genomic cassettes, including chemokines and C-type lectin receptors (CTRs). CTRs sense byproducts of diverse microbial and host origin. Single-cell data revealed correlated expression of genes within cassettes, thus further diversifying different monocyte responses to individual cells. Monocyte up-regulation of CTRs in response to LPS caused hypersensitivity to diverse microbial and host-derived byproducts, indicating a secondary immune surveillance pathway up-regulated in a subset of cells by a closely associated genomic cassette. Finally, expression of CTR genes was higher in livers of patients with severe AH, but not other chronic liver diseases, implicating secondary immune surveillance in nonresolving inflammation in severe AH.

Evaluation of a Deep Neural Network for Automated Classification of Colorectal Polyps on Histopathologic Slides.

Importance: Histologic classification of colorectal polyps plays a critical role in screening for colorectal cancer and care of affected patients. An accurate and automated algorithm for the classification of colorectal polyps on digitized histopathologic slides could benefit practitioners and patients. Objective: To evaluate the performance and generalizability of a deep neural network for colorectal polyp classification on histopathologic slide images using a multi-institutional data set. Design, Setting, and Participants: This prognostic study used histopathologic slides collected from January 1, 2016, to June 31, 2016, from Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, with 326 slides used for training, 157 slides for an internal data set, and 25 for a validation set. For the external data set, 238 slides for 179 distinct patients were obtained from 24 institutions across 13 US states. Data analysis was performed from April 9 to November 23, 2019. Main Outcomes and Measures: Accuracy, sensitivity, and specificity of the model to classify 4 major colorectal polyp types: tubular adenoma, tubulovillous or villous adenoma, hyperplastic polyp, and sessile serrated adenoma. Performance was compared with that of local pathologists' at the point of care identified from corresponding pathology laboratories. Results: For the internal evaluation on the 157 slides with ground truth labels from 5 pathologists, the deep neural network had a mean accuracy of 93.5% (95% CI, 89.6%-97.4%) compared with local pathologists' accuracy of 91.4% (95% CI, 87.0%-95.8%). On the external test set of 238 slides with ground truth labels from 5 pathologists, the deep neural network achieved an accuracy of 87.0% (95% CI, 82.7%-91.3%), which was comparable with local pathologists' accuracy of 86.6% (95% CI, 82.3%-90.9%). Conclusions and Relevance: The findings suggest that this model may assist pathologists by improving the diagnostic efficiency, reproducibility, and accuracy of colorectal cancer screenings.

Psychological correlates of interest in genetic testing among Korean American adoptees and their parents.

Adopted persons increasingly have turned to genetic testing to obtain health information or to search for birth family. The present study investigated psychological factors that may contribute to interest among adoptees and their parents in genetic testing for the adoptee, including adoptees' ethnic identity development, their thoughts or curiosity about birth family (birth family thoughts), and the interaction of these two factors. Data were drawn from the second wave of a longitudinal study, conducted in 2014, on transracially, transnationally adopted Korean American adolescents and their adoptive parents. In a sample of 106 adolescent-parent dyads, 2 adolescents (1.89%) had undergone genetic testing. Among the dyads in which adolescents had not sought genetic testing, 47.12% of adolescents and 43.27% of parents indicated interest in genetic testing for the adolescent adoptee. Adolescents' interest in genetic testing was independent from parents' interest. Neither adolescent psychological adjustment nor physical health was related to interest in genetic testing in either adolescents or parents. Adolescents' birth family thoughts were related to adolescents' interest in genetic testing, but not to parents' interest in genetic testing for their child. This study showed ethnic identity exploration and resolution moderated the relationship between birth family thoughts and adolescents' interest in genetic testing. Results point to the relevance of birth family thoughts and identity development to genetic testing in transnational and transracial adolescent adoptees.

Conceptualization and measurement of birth family thoughts for adolescents and adults adopted transnationally.

For adopted individuals, understanding the role of birth family is an important part of developing a coherent life narrative. However, there is limited empirical research on this aspect of the adoption experience. We introduce a new construct, birth family thoughts, that captures a sense of curiosity about birth family, and describe the development of an accompanying brief self-report measure, the Birth Family Thoughts Scale (BFTS). Across 4 studies of transnationally adopted Korean American adolescents, emerging adults, and adults who were adopted before the age of 3 (ncombined = 546), we found strong support for a 1-factor structure using exploratory and confirmatory factor analyses, and good internal consistency and test-retest reliability. Convergent validity was generally supported. The BFTS was positively related to measures of adoption- and ethnicity-related constructs, although there were a few inconsistencies between studies and measures. Discriminant validity also was generally supported. We found no evidence for the BFTS being related to a poor adoptive family situation or an indication of psychopathology. We did find some evidence of the BFTS relating to internalizing and externalizing symptoms. Furthermore, while the BFTS was unrelated to travel to Korea, it was correlated with visiting an orphanage in Korea. It was also related to initiating a birth family search in Study 1, but not in Studies 2 or 3. We discuss the importance of considering birth family thoughts across the life span and with other populations, as well as the limitations of the current study including sampling issues inherent in working with hard-to-reach populations. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Younger Physicians and Longer Withdrawal Times Are Associated With Detection of Advanced Neoplasia in a Large Community Practice.

Studies assessing colonoscopic practice have demonstrated variation in adenoma detection rate,1 detection rates of advanced adenomas,2,3 and detection rates of sessile serrated lesions (SSLs).4,5 Our aims were to study the patient-, provider-, and procedure-level variables associated with detection rates of adenoma, SSLs, and advanced neoplasia in screening colonoscopies performed in large community practice.