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The Journal of Adolescent Health :... Jun 2021To synthesize the diverse body of literature on sexual and gender minority youth (SGMY) and sexual health education. (Review)
Review
PURPOSE
To synthesize the diverse body of literature on sexual and gender minority youth (SGMY) and sexual health education.
METHODS
We conducted a systematic search of the literature on SGMY and sexual health education, including SGMY perspectives on sexual health education, the acceptability or effectiveness of programs designed for SGMY, and SGMY-specific results of sexual health education programs delivered to general youth populations.
RESULTS
A total of 32 articles were included. Sixteen qualitative studies with SGMY highlight key perspectives underscoring how youth gained inadequate knowledge from sexual health education experiences and received content that excluded their identities and behaviors. Thirteen studies examined the acceptability or effectiveness of sexual health interventions designed for SGMY from which key characteristics of inclusive sexual health education relating to development, content, and delivery emerged. One study found a sexual health education program delivered to a general population of youth was also acceptable for a subsample of sexual minority girls.
CONCLUSIONS
Future research on SGMY experiences should incorporate populations understudied, including younger adolescents, sexual minority girls, and transgender persons. Further, the effectiveness of inclusive sexual health education in general population settings requires further study.
Topics: Adolescent; Female; Humans; Sex Education; Sexual Behavior; Sexual Health; Sexual and Gender Minorities; Transgender Persons
PubMed: 33162290
DOI: 10.1016/j.jadohealth.2020.09.032 -
Experimental and Molecular Pathology Dec 2020Mallory-Denk Bodies (MDBs) are prevalent in a variety of liver diseases including alcoholic hepatitis (AH) and are formed in mice livers by feeding DDC. Long noncoding...
Mallory-Denk Bodies (MDBs) are prevalent in a variety of liver diseases including alcoholic hepatitis (AH) and are formed in mice livers by feeding DDC. Long noncoding RNAs (lncRNAs) are considered as emerging new gene regulators, which participates in many functional activities through diverse mechanisms. We previously reported the mechanisms involved in the formation of liver MDBs in mouse model and in AH livers where MDBs had formed. To investigate the regulation of mRNAs expression and the probable role of lncRNAs in AH livers with MDBs, RNA-Seq analyses was further conducted to determine the mRNA and lncRNA expression profiles of the AH livers compared with the normal livers. It showed that different lncRNAs have different information contribution degrees by principal component analysis, and the integrated analysis of lncRNA-mRNA co-expression networks were linked to endocytosis, cell cycle, p53 signaling pathways in the human. Based on the co-expression networks, we identify 36 mRNAs that could be as potential biomarkers of alcoholic liver disease (ALD) and hepatocellular carcinoma (HCC). To our knowledge, this is the first report on the regulatory network of lncRNAs associated with liver MDB formation in human, and these results might offer new insights into the molecular mechanisms of liver MDB formation and the progression of AH to HCC.
Topics: Animals; Carcinoma, Hepatocellular; Cell Cycle; Disease Models, Animal; Endocytosis; Gene Expression Regulation; Gene Regulatory Networks; Hepatitis, Alcoholic; Hepatocytes; Humans; Liver; Liver Neoplasms; Mallory Bodies; Mice; RNA, Long Noncoding; RNA, Messenger; Sequence Analysis, RNA; Signal Transduction; Tumor Suppressor Protein p53
PubMed: 33121977
DOI: 10.1016/j.yexmp.2020.104559 -
Cureus Aug 2020Alcoholic hepatitis results from excessive alcohol consumption in patients with or without underlying chronic liver disease. Leukemoid reactions have been associated...
Alcoholic hepatitis results from excessive alcohol consumption in patients with or without underlying chronic liver disease. Leukemoid reactions have been associated with poor outcomes in severe alcoholic hepatitis. There are only a handful of reported cases describing this relationship, and the striking similarity in these cases was a high short-term mortality rate. We believe that these patients represent a unique subgroup of patients with alcoholic hepatitis and that leukemoid reaction is a poor prognostic indicator in this condition. Here, we describe a case of 55-year-old male with severe alcoholic hepatitis with superimposed candida esophagitis who was found to have leukemoid reaction during diagnostic workup.
PubMed: 32944462
DOI: 10.7759/cureus.9747 -
Molecular & Cellular Proteomics : MCP Dec 2020Mallory-Denk-bodies (MDBs) are hepatic protein aggregates associated with inflammation both clinically and in MDB-inducing models. Similar protein aggregation in...
Mallory-Denk-bodies (MDBs) are hepatic protein aggregates associated with inflammation both clinically and in MDB-inducing models. Similar protein aggregation in neurodegenerative diseases also triggers inflammation and NF-κB activation. However, the precise mechanism that links protein aggregation to NF-κB-activation and inflammatory response remains unclear. Herein we find that treating primary hepatocytes with MDB-inducing agents (N-methylprotoporphyrin (NMPP), protoporphyrin IX (PPIX), or Zinc-protoporphyrin IX (ZnPP)) elicited an IκBα-loss with consequent NF-κB activation. Four known mechanisms of IκBα-loss the canonical ubiquitin-dependent proteasomal degradation (UPD), autophagic-lysosomal degradation, calpain degradation and translational inhibition, were all probed and excluded. Immunofluorescence analyses of ZnPP-treated cells coupled with 8 M urea/CHAPS-extraction revealed that this IκBα-loss was due to its sequestration along with IκBβ into insoluble aggregates, thereby releasing NF-κB. Through affinity pulldown, proximity biotinylation by antibody recognition, and other proteomic analyses, we verified that NF-κB subunit p65, which stably interacts with IκBα under normal conditions, no longer binds to it upon ZnPP-treatment. Additionally, we identified 10 proteins that interact with IκBα under baseline conditions, aggregate upon ZnPP-treatment, and maintain the interaction with IκBα after ZnPP-treatment, either by cosequestering into insoluble aggregates or through a different mechanism. Of these 10 proteins, the nucleoporins Nup153 and Nup358/RanBP2 were identified through RNA-interference, as mediators of IκBα-nuclear import. The concurrent aggregation of IκBα, NUP153, and RanBP2 upon ZnPP-treatment, synergistically precluded the nuclear entry of IκBα and its consequent binding and termination of NF-κB activation. This novel mechanism may account for the protein aggregate-induced inflammation observed in liver diseases, thus identifying novel targets for therapeutic intervention. Because of inherent commonalities this MDB cell model is a protoporphyric model, making these findings equally relevant to the liver inflammation associated with clinical protoporphyria.
Topics: Active Transport, Cell Nucleus; Animals; Autophagy; Cell Nucleus; HEK293 Cells; HeLa Cells; Hep G2 Cells; Hepatocytes; Humans; I-kappa B Proteins; Inflammation; Liver; Male; Mice, Inbred C57BL; Mice, Knockout; NF-kappa B; Nuclear Pore Complex Proteins; Protein Aggregates; Protein Binding; Protein Multimerization; Protoporphyrins; RNA, Small Interfering; Sequestosome-1 Protein; Solubility
PubMed: 32912968
DOI: 10.1074/mcp.RA120.002316 -
Scientific Reports Aug 2020The current study investigated telocytes (TCs) in the intestinal bulb of Grass carp using light microscopy (LM), Transmission electron microscopy (TEM), scanning...
The current study investigated telocytes (TCs) in the intestinal bulb of Grass carp using light microscopy (LM), Transmission electron microscopy (TEM), scanning electron microscopy, and immunohistochemistry (IHC). By LM, TCs were distinguished by the typical morphological features that had a cell body and telopodes using HE, toluidine blue, methylene blue, Marsland silver stain, Grimelius's silver nitrate, Giemsa, PAS, combined AB pH2,5/PAS, Crossmon's and Mallory triple trichrome, Van Gieson stains, Verhoeff's stain, Sudan black, osmic acid, performic acid with methylene blue and bromophenol blue. TCs were identified under the epithelium as an individual cell or formed a TCs sheath. They detected in the lamina propria, between muscle fibers, around the myenteric plexus and fibrous tissue. TCs acquired immunological features of endocrine cells that exhibited high affinity for silver stain, performic acid with methylene blue, Marsland stain, and immunohistochemical staining using chromogranin A. Sub epithelial TCs were closely related to the endocrine cells. TCs and their secretory activities were recognized using acridine orange. TCs were identified by IHC using CD34, CD117, S100-protein, desmin. TCs formed a3D network that established contact with macrophage, mast cells, dendritic cells, lymphocytes, smooth muscle fibers, fibroblast, Schwann cells and nerve fibers. In conclusion, the localization of TCs in relation to different types of immune cells indicated their potential role in the maintenance of intestinal immunity.
Topics: Animals; Carps; Immunohistochemistry; Intestines; Microscopy, Electron, Transmission; Paraffin Embedding; Telocytes; Telopodes
PubMed: 32820212
DOI: 10.1038/s41598-020-70032-y -
Biomedicines Jul 2020FAT10 expression is highly up-regulated by pro-inflammatory cytokines IFNγ and TNFα in all cell types and tissues. Increased FAT10 expression may induce increasing... (Review)
Review
FAT10 expression is highly up-regulated by pro-inflammatory cytokines IFNγ and TNFα in all cell types and tissues. Increased FAT10 expression may induce increasing mitotic non-disjunction and chromosome instability, leading to tumorigenesis. In this review, we summarized others' and our work on FAT10 expression in liver biopsy samples from patients with alcoholic hepatitis (AH). FAT10 is essential to maintain the function of liver cell protein quality control and Mallory-Denk body (MDB) formation. FAT10 overexpression in AH leads to balloon degeneration and MDB aggregation formation, all of which is prevented in fat10-/- mice. FAT10 causes the proteins' accumulation, overexpression, and forming MDBs through modulating 26s proteasome's proteases. The pathway that increases FAT10 expression includes TNFα/IFNγ and the interferon sequence response element (ISRE), followed by NFκB and STAT3, which were all up-regulated in AH. FAT10 was only reported in human and mouse specimens but plays critical role for the development of alcoholic hepatitis. Flavanone derivatives of milk thistle inhibit TNFα/IFNγ, NFκB, and STAT3, then inhibit the expression of FAT10. NFκB is the key nodal hub of the IFNα/TNFα-response genes. Studies on Silibinin and other milk thistle derivatives to treat AH confirms that overexpressed FAT10 is the major key molecule in these networks.
PubMed: 32630199
DOI: 10.3390/biomedicines8070189 -
The American Journal of Pathology Jun 2020Hepatocellular carcinoma (HCC) is the most common form of liver tumors. Although HCC is associated with chronic viral infections, alcoholic cirrhosis, and nonalcoholic...
Hepatocellular carcinoma (HCC) is the most common form of liver tumors. Although HCC is associated with chronic viral infections, alcoholic cirrhosis, and nonalcoholic fatty liver disease, genetic factors that contribute to the HCC risk remain unknown. The BRCA2 DNA repair associated (BRCA2) and cyclin-dependent kinase inhibitor 1A (CDKN1A) interacting protein, known as BCCIP, are essential for cell viability and maintenance of genomic stability. In this study, we established a new genetically engineered mouse model with Bccip deficiency. Mosaic or heterozygous Bccip deletion conferred an increased risk of spontaneous liver tumorigenesis and B-cell lymphoma development at old age. These abnormalities are accompanied with chronic inflammation, histologic features of nonalcoholic steatohepatitis, keratin and ubiquitin aggregates within cytoplasmic Mallory-Denk bodies, and changes of the intracellular distribution of high-mobility group box 1 protein. Our study suggests BCCIP dysregulation as a risk factor for HCC and offers a novel mouse model for future investigations of nonviral or nonalcoholic causes of HCC development.
Topics: Animals; BRCA2 Protein; Carcinoma, Hepatocellular; Cell Cycle Proteins; Heterozygote; Liver Neoplasms; Lymphoma, B-Cell; Mice; Mice, Knockout; Mosaicism
PubMed: 32201259
DOI: 10.1016/j.ajpath.2020.01.020 -
Archives of Medical Science : AMS Oct 2019Liver biopsy is a well-known method for the diagnosis and evaluation of chronic diffuse liver diseases, especially among patients with "hepatopathy of unknown origin".
INTRODUCTION
Liver biopsy is a well-known method for the diagnosis and evaluation of chronic diffuse liver diseases, especially among patients with "hepatopathy of unknown origin".
MATERIAL AND METHODS
In the years 2014-2015 we performed 259 liver biopsies in 28 patients (22 females, 6 males, aged 18-65 years, mean: 45 years) with an initial diagnosis of "hepatopathy of unknown origin". The liver biopsies of these 28 patients were revised by two independent pathologists.
RESULTS
Histopathological features of autoimmune conditions were found in 11 cases, steatohepatitis with/without Mallory bodies in 7, simple steatosis without inflammation in 2 cases. In the other 8 cases the histopathological features were non-specific but pointed to vanishing bile duct syndrome, hemochromatosis, acute inflammation or fibrosis without inflammation. Surprisingly, only mild fibrosis without inflammatory infiltrates was present in one patient with a high titer of antinuclear antibodies (ANA > 1 : 3200). Mild cholestasis with bilirubinostasis was found in 4 cases. One patient had prominent lobular iron deposits and is now under observation for hemochromatosis. Vanishing bile duct syndrome as ductopenia without any signs of inflammation was found in one patient with suspicion of primary biliary cirrhosis. In one liver biopsy specimen we found normal liver architecture without inflammation or steatosis in a patient with elevated ALT and GGT, negative for viral antibodies and autoantibodies.
CONCLUSIONS
Liver biopsy - despite the increasing access to new, non-invasive methods - remains a useful method in the differential diagnosis of liver diseases.
PubMed: 31749874
DOI: 10.5114/aoms.2019.82637 -
Cureus Sep 2019Intramural esophageal hematoma (IEH) is a rare cause of submucosal esophageal bleeding and it is on the spectrum of esophageal wall injury along with mucosal tears...
Intramural esophageal hematoma (IEH) is a rare cause of submucosal esophageal bleeding and it is on the spectrum of esophageal wall injury along with mucosal tears (Mallory-Weiss syndrome) and full thickness perforation (Boerhaave's syndrome). Its risk factors include coagulopathy, trauma (foreign body ingestion or esophageal instrumentation) or it can happen spontaneously. It presents with a triad of chest pain, dysphagia, and hematemesis; however, the triad is only present in 35% of patients. We are presenting a case of IEH secondary to food ingestion that was managed successfully by conservative measures.
PubMed: 31696016
DOI: 10.7759/cureus.5623 -
Alimentary Pharmacology & Therapeutics Nov 2019There is substantial variation in how histologic definitions and scoring systems of non-alcoholic fatty liver disease (NAFLD) are operationalised.
BACKGROUND
There is substantial variation in how histologic definitions and scoring systems of non-alcoholic fatty liver disease (NAFLD) are operationalised.
AIM
To develop a consensus-based framework for standardising histologic assessment of liver biopsies in clinical trials of NAFLD.
METHODS
An expert panel of 14 liver pathologists and three hepatologists was assembled. Using modified RAND/University of California Los Angeles appropriateness methodology, 130 items derived from literature review and expert opinion were rated by each panel member on a 1-9 scale. Disagreement was defined as ≥5 ratings in the lowest (1-3) and highest (7-9) categories. Items were classified as inappropriate (median 1-3.5 without disagreement), uncertain (median 3.5-6.5 or any median with disagreement) or appropriate (median 6.5-9 without disagreement). Survey results were discussed as a group before voting.
RESULTS
Current measures of disease activity and fibrosis may not fully capture important features of non-alcoholic steatohepatitis (NASH). Alternative methods to evaluate ballooning degeneration are needed. Panellists were uncertain whether portal inflammation, degree of steatosis and Mallory-Denk bodies are important measures of disease activity. Furthermore, it was felt that current staging systems do not capture the full spectrum of fibrosis in NASH. A consensus definition and sub-stages for bridging fibrosis are needed. The severity of perisinusoidal fibrosis should be captured at all stages. Lastly, a method to evaluate features of fibrosis regression should be developed.
CONCLUSION
The operating properties of the modifications proposed should be evaluated prospectively to determine reliability and responsiveness.
Topics: Biopsy; Humans; Image Interpretation, Computer-Assisted; Liver; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; Practice Patterns, Physicians'; Randomized Controlled Trials as Topic; Reference Standards; Reproducibility of Results; Research Design; Retrospective Studies; Surveys and Questionnaires
PubMed: 31583739
DOI: 10.1111/apt.15503