Miracle-dz/UniFAR-FTUs huggingface dataset:
Appearance of sinusoidal inclusion‐containing endothelia cells in liver disease

Sinusoidal “inclusion‐containing endothelial cells” were studied histopathologically and immunohistochemically in various liver diseases, and their clinical importance was investigated. A total of 498 needle liver biopsies were examined. Endothelial inclusions inside the cells were recognized as eosinophilic granules in hematoxylin‐eosin‐stained sections. Electron microscopy showed that these inclusions corresponded to round cytoplasmic dense bodies with a single limiting membrane. The contents of these bodies were generally homogeneous, but sometimes heterogeneous. The inclusions appeared to contain protein, but were resistant to trypsin digestion, and immunohistochemistry failed to identify any immunoglobulins or hepatocyte‐derived proteins. These endothelial cells also contained an increased number of micropinocytotic vesicles when compared with ordinary cells. The inclusion‐containing endothelial cells appeared frequently in chronic hepatitis, but were relatively rare in other liver diseases. The incidence was higher in chronic aggressive hepatitis than in chronic persistent hepatitis or inactive cirrhosis. Although the density of these cells varied considerably even among patients with the same histological diagnosis and the phenotypical changes of these endothelial cells, assessed by monoclonal antibodies, were not apparent, the serum γ globulin level tended to increase in relation to the density of inclusion‐containing endothelial cells and the correlation was significant in hepatitis C. (HEPATOLOGY 1994;20:604–610).
Can Probiotics Reduce Inflammation and Enhance Gut Immune Health in People Living with HIV: Study Designs for the Probiotic Visbiome for Inflammation and Translocation (PROOV IT) Pilot Trials

Objectives: Despite substantial improvements in HIV outcomes with combination antiretroviral therapy (cART), morbidity and mortality remain above population norms. The gut mucosal immune system is not completely restored by cART, and the resultant microbial translocation may contribute to chronic inflammation, inadequate CD4 T-cell recovery, and increased rates of serious non-AIDS events. Since the microbial environment surrounding a CD4 T cell may influence its development and function, we hypothesize that probiotics provided during cART might reduce inflammation and improve gut immune health in HIV-positive treatment-naïve individuals (PROOV IT I) and individuals with suboptimal CD4 recovery on cART (PROOV IT II). Methods: These prospective, double-blinded, randomized, placebo-controlled, multicenter pilot studies will assess the impact of the probiotic Visbiome at 900 billion bacteria daily. Forty HIV positive cART-naïve men will be randomized in the PROOV IT I study, coincident with antiretroviral initiation, and be followed for 24 weeks. In PROOV IT II, 36 men on cART, but with a CD4 T-cell count below 350 cells/mm3 will be followed for 48 weeks. The primary outcome for both studies is the comparison of blood CD8 T-cell immune activation. Secondary analyses will include comparison of blood inflammatory biomarkers, microbial translocation, blood and gut immunology and HIV levels, the bacterial community composition, diet, intestinal permeability, and the safety, adherence and tolerability of the study product. Discussion: These studies will evaluate the ability of probiotics as a safe and tolerable therapeutic intervention to reduce systemic immune activation and to accelerate gut immune restoration in people living with HIV.
Experiences of working from a freestanding position as a case manager when supporting clients in the Swedish welfare system

The Swedish state uses a case management function known as Personligt Ombud (PO). The role as PO differs from the traditional professional roles. It has a freestanding position in the welfare system. The aim of this study was to investigate POs’ experiences of working from a freestanding position when supporting clients. Telephone interviews were conducted with 22 POs across Sweden. The interviews were recorded, transcribed, and analyzed by latent qualitative content analysis. The findings were reflected in three categories – freedom-promoted flexibility, surfing through a complex welfare system, and working for legitimacy. POs developed a holistic view to both the client as well as to the welfare system. POs experienced solely representing the client, which is a positive feature because part of the POs’ role is advocating for the clients rights. The PO service differs from the PO service from other existing case management models and may need to develop strategies for decision-making and support in their own role. For example, they may use group supervision teams or ‘reflective teams’. The freestanding position may also entail problems in terms of lack of legitimacy. It is important for POs to develop good platforms with the surrounding actors among others things to improve the co-ordination process. It could be interesting if the PO model would be tested in other countries that have a fragmented welfare system. The PO model may also be useful to other ‘target groups’ who are in need of co-ordinated rehabilitation services.
Low circulating levels of dehydroepiandrosterone in histologically advanced nonalcoholic fatty liver disease

The biological basis of variability in histological progression of nonalcoholic fatty liver disease (NAFLD) is unknown. Dehydroepiandrosterone (DHEA) is the most abundant steroid hormone and has been shown to influence sensitivity to oxidative stress, insulin sensitivity, and expression of peroxisome proliferator‐activated receptor alpha and procollagen messenger RNA. Our aim was to determine whether more histologically advanced NAFLD is associated with low circulating levels of DHEA. Serum samples were obtained prospectively at the time of liver biopsy in 439 patients with NAFLD (78 in an initial and 361 in validation cohorts) and in controls with cholestatic liver disease (n = 44). NAFLD was characterized as mild [simple steatosis or nonalcoholic steatohepatitis (NASH) with fibrosis stage 0‐2] or advanced (NASH with fibrosis stage 3‐4). Serum levels of sulfated DHEA (DHEA‐S) were measured by enzyme‐linked immunosorbent assay. Patients with advanced NAFLD had lower plasma levels of DHEA‐S than patients with mild NAFLD in both the initial (0.25 ± 0.07 versus 1.1 ± 0.09 μg/mL, P < 0.001) and validation cohorts (0.47 ± 0.06 versus 0.99 ± 0.04 μg/mL, P < 0.001). A “dose effect” of decreasing DHEA‐S and incremental fibrosis stage was observed with a mean DHEA‐S of 1.03 ± 0.05, 0.96 ± 0.07, 0.83 ± 0.11, 0.66 ± 0.11, and 0.35 ± 0.06 μg/mL for fibrosis stages 0, 1, 2, 3, and 4, respectively. All patients in both cohorts in the advanced NAFLD group had low DHEA‐S levels, with the majority in the hypoadrenal range. The association between DHEA‐S and severity of NAFLD persisted after adjusting for age. A relationship between disease/fibrosis severity and DHEA‐S levels was not seen in patients with cholestatic liver diseases. Conclusion: More advanced NAFLD, as indicated by the presence of NASH with advanced fibrosis stage, is strongly associated with low circulating DHEA‐S. These data provide novel evidence for relative DHEA‐S deficiency in patients with histologically advanced NASH. (HEPATOLOGY 2008;47:484–492.)
Comprehensive and quantitative proteome profiling of the mouse liver and plasma

We report a comprehensive and quantitative analysis of the mouse liver and plasma proteomes. The method used is based on extensive fractionation of intact proteins, further separation of proteins based on their abundance and size, and high‐accuracy mass spectrometry. This analysis reached a depth in proteomic profiling not reported to date for a mammalian tissue or a biological fluid, with 7099 and 4727 proteins identified with high confidence in the liver and in the corresponding plasma, respectively. This method allowed for the identification in both compartments of low‐abundance proteins such as cytokines, chemokines, and receptors and for the detection in plasma of proteins in the pg/mL concentration range. This method also allowed for semiquantitation of all identified proteins. The calculated abundance scores correlated with the abundance of the corresponding transcripts for the large majority of the proteins identified in the liver. Finally, comparison of the liver and plasma datasets demonstrated that a significant number of proteins identified in the liver can be detected in plasma. These included proteins involved in complement and coagulation, in fatty acid, purine and pyruvate metabolism, in gluconeogenesis and glycolysis, in protein ubiquitination, and in insulin, interleukin‐4, epidermal growth factor, and platelet‐derived growth factor signaling. Conclusion: This in‐depth analysis of the mouse liver and corresponding plasma proteomes provides a strong basis for investigations of liver pathobiology and biology that employ mouse models of hepatic diseases in an effort to better understand, diagnose, treat, and prevent human hepatic diseases. (HEPATOLOGY 2008.)
Evaluation of the Effectiveness of a Water Lift System in the Sinus Membrane-Lifting Operation as a Sinus Surgical

Purpose: The effectiveness of a Water Lift System in the sinus membrane-lifting operation was examined. This investigation focused on the capability of this equipment to reduce the risk of Schneiderian membrane perforation. Materials and Methods: A preliminary clinical study on the use of the Water Lift System in sinus membrane elevation to place implants through the sinus floor was conducted. A total of 70 sinus membrane-lifting operations were performed on patients with various bone heights ranging from 1.2 to 9.9 mm (most commonly in the range of 4–6 mm) through the lateral approach (four cases) or the crestal approach (66 cases). Results: In all of the cases performed using the lateral approach, sinus membrane perforation did not occur. In the 66 cases performed using the crestal approach, Schneiderian membrane tearing occurred in two cases. The membrane tearing occurred during elevation of the Schneiderian membrane but not when a hole was drilled to access the Schneiderian membrane. One case of membrane tearing resulted from previous inflammation in the maxillary sinus, and the other case of membrane tearing was caused by application of excessive hydraulic pressure. In addition, similar outcomes were obtained and no microbial infections were observed in a total of 68 successful cases. Conclusions: In this study, the Water Lift System was confirmed to effectively reduce the risk of Schneiderian membrane perforation during the sinus membrane-lifting operation. We conclude that the Water Lift System deserves to be considered as a sinus surgical instrument, which ensures safety in the sinus membrane-lifting operation.
The Better Life Program: Effects of group skills training for persons with severe mental illness and substance use disorders

Objectives: Despite the widespread use of group interventions for treating dual disorders, few standardized programs have been empirically validated. This study evaluated a manualized group skills training intervention for clients with dual disorders, the Better Life Program, in order to determine its feasibility and changes in substance abuse and mental health outcomes. Method: Patients with dual disorders at nine centres in Norway participated in a pilot study using a within-subjects pre- and post test design. The program required an average of 37 sessions to complete and was provided as a supplement to standard mental health care. The aim of the program is to reduce substance misuse through providing information, motivational enhancement, skills training to develop rewarding relationships, relapse prevention, and establishing healthy leisure activities. Results: Among the 82 patients who began treatment, 63 (83%) completed it. Treatment completers showed significant reductions in substance misuse and improvement in global functioning, but did not change in general symptom distress. Conclusions: This pilot study supports the feasibility of the Better Life Program, and suggests that it may improve substance misuse and mental health outcomes. Further research is warranted to evaluate the effects of this program using controlled research designs. Conflicts of interest: None.
Blocking transforming growth factor–beta up‐regulates E‐cadherin and reduces migration and invasion of hepatocellular carcinoma cells

Hepatocellular carcinoma (HCC) treatment is challenging because the mechanisms underlying tumor progression are still largely unknown. Transforming growth factor (TGF)–β1 is considered a crucial molecule in HCC tumorigenesis because increased levels of patients' serum and urine are associated with disease progression. The aim of the present study was to investigate the inhibition of TGF‐β signaling and its impact on HCC progression. Human HCC cell lines were treated with a TGF‐β receptor kinase inhibitor (LY2109761) whose selectivity was determined in a kinase assay. Exogenous TGF‐β1 phosphorylates the TGF‐β receptor, consequently activating Smad‐2, whereas the drug selectively blocks this effect and dephosphorylates autocrine p‐Smad‐2 at concentrations ranging from 0.001 to 0.1 μM. A cytotoxic effect documented by 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyltetrazolium bromide (MTT), trypan blue, and propidium iodide staining assays was observed at 10μM, whereas the drug inhibits (P < 0.001) the migration of HCC cells on fibronectin, laminin‐5, and vitronectin and invasion through Matrigel (P < 0.001) at concentrations up to 0.1 μM. LY2109761 up‐regulates (P < 0.001) E‐cadherin mRNA and protein levels. This increase was localized at the cellular membrane where E‐cadherin mediates anchorage that is cell–cell dependent. Consistently, a functional monoclonal antibody that inhibits E‐cadherin–dependent cell–cell contact restores the migratory and invasive activity. Finally, nonmetastatic HCC tissues from 7 patients were cultured with TGF‐β1 in the presence or absence of LY2109761. E‐cadherin expression was reduced by TGF‐β1 and was significantly (P < 0.0001) increased by LY2109761 treatment, measured by quantitative real‐time PCR on microdissected tissues and by immunohistochemistry on serial sections. In 72 patients, E‐cadherin tissue expression was more weakly expressed in metastatic than in nonmetastatic HCC (P < 0.0001). Conclusion: LY2109761 blocks migration and invasion of HCC cells by up‐regulating E‐cadherin, suggesting that there could be a mechanistic use for this molecule in clinical trials. (HEPATOLOGY 2008.)
Turkish adaptation of Spinal Cord Independence Measure — version III

Various rating scales have been used to assess ability in individuals with spinal cord injury. There is no specific functional assessment scale for Turkish patients with spinal cord injury. The Spinal Cord Independence Measure (SCIM) is a specific test, which has become popular in the last decade. A study was conducted to validate and evaluate the Turkish adaptation of the SCIM III (T-SCIM III). The SCIM III was translated into Turkish. Reliability, (internal consistency, interrater reliability, and test–retest reliability), validity (with Functional Independence Measurement), and sensitivity (changes in 8-week exercise program) were studied. Internal consistency for total score was sufficient (Cronbach &agr;=0.79). The interrater reliability was moderate to high (Cohen &kgr; between 0.72 and 1). Convergent validity was high (r=0.89, P<0.01). The T-SCIM III was found to be more sensitive than the Functional Independence Measurement to changes in function. Hence, we recommend the use of T-SCIM III in clinical practice as a reliable, valid, and easy-to-use tool.
Safety first? The impact of domestic abuse on women's treatment experience

This paper presents the findings of an exploratory study designed to investigate what is known about women's experiences of domestic abuse and their impact on treatment outcomes. Aims: To explore whether domestic abuse has an impact on women's access to treatment, retention, relapse, or increase in their substance use. Design: A literature review and key informant interviews. Participants: Thirteen key informants were drawn from a range of agencies working with women using alcohol or drugs in England. Measurement: The empirical research was read using set criteria including: type of treatment setting, single or mixed gender treatment, number in the sample, methods used, and key findings. The key themes were then extracted from the literature. The interviews were recorded, transcribed, and analysed using thematic coding. Findings: Practice‐based evidence suggests women's engagement with and retention in treatment is negatively affected by domestic abuse. Literature‐based evidence is equivocal and limited in scope, quality and quantity. Conclusions: While further research is required to substantiate the practice‐based evidence, it appears that treatment service providers are failing to recognize and address the issue of domestic abuse among their service users, leaving women and their children at risk.
Evaluation of a Partial Hospitalization Mental Health Program for Older Adults

Abstract This article reports the program evaluation of a Partial Hospitalization Mental Health Program for Older Adults at a suburban, Midwestern community-based hospital. Most patients in the Partial Hospitalization Program (PHP) presented with depressive disorders, especially late-life depression. A short review of the literature about PHPs and a description of the specific program being evaluated are presented. The evaluation itself provides a detailed description of the demographic and clinical characteristics of the patients, evaluates the clinical and statistical effectiveness of the program, and attempts to provide a predictive model for positive outcome. The program was found to be highly effective. Eighty percent of patients demonstrated a clinically and statistically significant positive change in functional level, and 66% of patients demonstrated a similar positive change in depressive symptoms. A predictive model for positive outcome in functional level (as measured by the Global Assessment of Functioning) included level of education and number of individual therapy sessions, and accounted for 28% of the variance. No variables were found to predict positive change in the depressive symptoms (as measured by the Geriatric Depression Scale). Implications for treatment as well as limitations of the study are discussed.
The significance of lumbosacral transitional vertebræ

MAN’S assumption of the erect posture has necessitated many skeletal modifications and these are nowhere more apparent than about the lumbosacral junction. Finality in structure has not yet been attained and developmental abnormalities are abundant, a fact of practical importance, as some anomalies strengthen the spine while others weaken it. The presence of an enlarged transverse process on one or both sides of the last lumbar vertebra is one of the best known of these anomalies, and it is interesting both from the anatomical and clinical view-points. The condition is usually referred to as sacralization or lumbarization, and its occurrence is puzzling unless one possesses a knowledge of the anatomy and morphology of the spinal column.
Evaluation of Okadaic Acid-Induced Genotoxicity in Human Cells Using the Micronucleus Test and γH2AX Analysis

Marine algal blooms have become a public health concern due to increasing frequency in the environment and severity of exposure consequences. Human intoxications produced by phycotoxins occur globally through consumption of marine fish products containing bioaccumulated toxins. Okadaic acid (OA) is the main representative of diarrheic shellfish poisoning (DSP) toxin. OA was found to inhibit protein phosphatases and to produce oxidative damage, as well as to disturb different cellular functions including cell cycle, gene expression, and DNA repair mechanisms. The aim of this study was to determine whether OA induced genotoxicity by using a micronucleus (MN) test and γH2AX analysis, and to elucidate the underlying mechanisms. Human peripheral blood leukocytes, neuroblastoma cells (SHSY5Y), and hepatoma cells (HepG2) were treated with a range of OA concentrations in the presence and absence of S9 fraction. MN induction was observed in leukocytes at all concentrations tested, and in SHSY5Y and HepG2 cells only at the highest concentration (1000 nM). In contrast, γH2AX analysis was only positive for HepG2 cells. Taking together these data, in addition to the comet assay results obtained in a previous study in this issue, OA was found to exert a either a clastogenic or aneugenic effect dependent upon the cell types examined.
Circulating miR-155 Expression in Plasma: A Potential Biomarker for Early Diagnosis of Esophageal Cancer in Humans

MicroRNAs (miRNAs) are postulated to play important roles in oncogenesis. Recently, extracellular miRNAs were detected in plasma or serum of diseased subjects. However, the role of circulating miRNAs in plasma/serum remains to be elucidated. In this study, the relative expressions of miR-155, miR-183, and miR-20a in esophageal tissue were found to be significantly associated with increased risk for esophageal cancer. The relative expressions of circulating miR-155 and miR-183 were significantly reduced in cancer patients. Circulating miR-155 showed significantly higher risk for esophageal cancer when adjusted by smoking status and alcohol use. Circulating miR-155 was found to have significant diagnostic value for esophageal cancer as evidenced by a receiver operating characteristic curve area of 66%. However, Pearson analysis showed no statistical correlation in the relative miRNAs expression between plasma and esophageal tissues, which suggested different origins of circulating miRNAs distinct from tumor cell miRNAs. In conclusion, results suggest that circulating miR-155 in plasma may serve as a reliable, novel, noninvasive biomarker for early diagnosis and detection of esophageal cancer.
Monitoring of Alcohol Use and Attributable Harm from an International Perspective

Alcohol consumption was shown to cause about 4% of the global burden of disease in 2000; about the same size of burden as due to tobacco smoking. In addition, alcohol has been linked to considerable social harm. The high public health relevance of alcohol has triggered considerable efforts to reduce alcohol-attributable harm. As part of these efforts, monitoring systems have been planned and in part implemented to serve as means of early warning and to measure success or failure of different interventions. The present article gives an overview of systems currently in place or planned for monitoring alcohol use and related harm from a global perspective, and makes recommendations concerning optimal indicators.