Miracle-dz/UniFAR-FTUs huggingface dataset:
Digital image analysis of liver collagen predicts clinical outcome of recurrent hepatitis C Virus 1 year after liver transplantation

Clinical outcomes of recurrent hepatitis C virus after liver transplantation are difficult to predict. We evaluated collagen proportionate area (CPA), a quantitative histological index, at 1 year with respect to the first episode of clinical decompensation. Patients with biopsies at 1 year after liver transplantation were evaluated by Ishak stage/grade, and biopsy samples stained with Sirius red for digital image analysis were evaluated for CPA. Cox regression was used to evaluate variables associated with first appearance of clinical decompensation. Receiver operating characteristic (ROC) curves were also used. A total of 135 patients with median follow‐up of 76 months were evaluated. At 1 year, median CPA was 4.6% (0.2%‐36%) and Ishak stage was 0‐2 in 101 patients, 3‐4 in 23 patients, and 5‐6 in 11 patients. Decompensation occurred in 26 (19.3%) at a median of 61 months (15‐138). Univariately, CPA, tacrolimus monotherapy, and Ishak stage/grade at 1 year were associated with decompensation; upon multivariate analysis, only CPA was associated with decompensation (P = 0.010; Exp(B) = 1.169; 95%CI, 1.037‐1.317). Area under the ROC curve was 0.97 (95%CI, 0.94‐0.99). A cutoff value of 6% of CPA had 82% sensitivity and 95% specificity for decompensation. In the 89 patients with hepatic venous pressure gradient (HVPG) measurement, similar results were obtained. When both cutoffs of CPA > 6% and HVPG ≥ 6 mm Hg were used, all patients decompensated. Thus, CPA at 1‐year biopsy after liver transplantation was highly predictive of clinical outcome in patients infected with hepatitis C virus who underwent transplantation, better than Ishak stage or HVPG. Liver Transpl 17:178–188, 2011. © 2011 AASLD.
Substance Use and the Police: An International Workplace Experience

Policing is an occupation shaped by local norms involving high levels of public authority, accountability, and responsibility. Moreover, police forces are exposed to situations that are dangerous or hazardous to themselves and members of the public. Furthermore, police action may require fast reflexes and quick thinking. This paper reviews the international empirical reports of the prevalence of substance abuse (mainly alcohol) among the police forces surveyed. The relevance of demographic variables and the impact of job content and job context related factors is analyzed. Police forces provide an interesting comparison group with the experience of health professionals often faced with similar stressors in the workplace, and the relative importance of personal and environmental variables.
Physical dating violence victimization in college women in Chile.

OBJECTIVES There are no published studies on physical dating violence in college students in Chile, and campuses across the country currently lack systematized programs to prevent or respond to this public health problem. This is the first study to examine prevalence and predictors of physical dating violence victimization with a sample of female college students in Chile. METHODS A closed-ended questionnaire was administered to students enrolled in general education courses at a major public university. The prevalence of women's physical dating violence victimization was calculated, and generalized ordered logit models were used to estimate risk factors for such victimization (n = 441). Ancillary analyses examined associations of dating violence victimization with experiences of unwanted sexual contact and forced condom nonuse. RESULTS Approximately 21% of subjects reported one or more incidents of physical dating violence not involving physical injury since age 14, and another 5% reported at least one incident resulting in physical injury during this time period. Risk factors identified in five sequential models were sexual abuse and witnessing of domestic violence in childhood, low parental education, residence away from the parental home, urban residence, and having had sexual intercourse. Maternal employment and religious participation had protective effects. Dating violence victimization was found to be significantly associated with experiences of unwanted sexual contact and forced condom nonuse. CONCLUSIONS The study findings show a high prevalence of physical dating violence, strong associations between several sociodemographic factors and dating violence, and links between dating violence and sexual/reproductive risk. Our results indicate a need to expand attention to this public health problem in Chile as well as other developing countries, where research and prevention/response initiatives have generally been similarly limited. The findings also have important implications for the content of dating violence, HIV/sexually transmitted infection (STI), and pregnancy prevention programs for adolescents and young adults.
Is cytomegalovirus infection dangerous in cytomegalovirus‐seropositive recipients after liver transplantation?

Cytomegalovirus (CMV) infections contracted after liver transplantation put patients at an increased risk of morbidity and mortality. We analyzed the effects of CMV infection by time of onset, mortality, and graft failure risk factors in liver recipients who were CMV donor‐positive/recipient‐positive (D+/R+). We reviewed 618 medical records for consecutive adult liver transplant cases. CMV pp65 antigenemia assays to determine patient CMV status were administered monthly. The incidences of CMV infection and disease were 55.7% (344 of 618 records) and 5.5% (34 of 618 records), respectively. The differences in patient survival and graft failure rates for CMV‐infected and CMV‐uninfected patients were not significant (P = 0.707 and P = 0.973), but the rates were lower in patients with CMV disease than in CMV‐uninfected patients (P = 0.005 and P = 0.030, respectively). The recurrence of hepatitis B virus and hepatocellular carcinoma, hepatic dysfunction, infection, numerous pp65‐staining cells, and CMV disease were found to be the risk factors for mortality and graft failure in CMV D+/R+ adult liver transplant patients. In conclusion, the occurrence of CMV disease, and not asymptomatic CMV infection, was a risk factor for mortality and graft failure in adult liver transplant recipients with CMV D+/R+. Liver Transpl, 2011. © 2011 AASLD.
Incidence and Causes of Strokes Associated With Pregnancy and Puerperium A Study in Public Hospitals of Ile de France

Background and Purpose The incidence, causes, and prognosis of nonhemorrhagic strokes and intraparenchymal hemorrhages occurring in association with pregnancy or puerperium are poorly understood. Methods We carried out a retrospective (1989 through 1991) and prospective (1992) study in 63 public maternities (348 295 deliveries) of the region of Ile de France (10 660 554 inhabitants) and in the neurology, neurosurgery, and intensive care units of the same geographic area. Records of women who suffered a cerebrovascular event during pregnancy or the first 2 weeks postpartum were reviewed by two study neurologists. Stroke was defined according to the criteria of the World Health Organization. Results Thirty-one cases of strokes were identified, including 15 nonhemorrhagic strokes (including strokelike deficits associated with eclampsia) and 16 intraparenchymal hemorrhages, assessed in all cases by CT scan and/or MRI. The incidence of nonhemorrhagic strokes in women who delivered in public maternities of Ile de France was 4.3 per 100 000 deliveries (95% confidence interval, 2.4 to 7.1) and that of intraparenchymal hemorrhage was 4.6 per 100 000 deliveries (95% confidence interval, 2.6 to 7.5). Eclampsia accounted for 47% of cases of nonhemorrhagic strokes. The other causes were extracranial vertebral artery dissection, postpartum cerebral angiopathy, inherited protein S deficiency, and disseminated intravascular coagulation associated with amniotic fluid embolism. The cause remained undetermined in four cases despite extensive investigations. Eclampsia accounted for 44% of intraparenchymal hemorrhages. Another 37% were due to rupture of a vascular malformation. The cause remained undetermined in three cases. There were four maternal deaths (all associated with intraparenchymal hemorrhage), three of them in eclamptic women. Fetal mortality and prematurity were associated with eclampsia. Conclusions The incidence of nonhemorrhagic stroke does not seem to be much increased during pregnancy and early puerperium. In contrast to that in the nonpregnant state, the frequency of intraparenchymal hemorrhage in pregnancy appears to be similar to that of nonhemorrhagic strokes, suggesting that pregnancy may increase the risk of cerebral hemorrhage. Eclampsia is the main cause of both nonhemorrhagic stroke and intraparenchymal hemorrhage. Intraparenchymal hemorrhage associated with eclampsia carries a poor prognosis.
Feasibility and safety of percutaneous coronary intervention in patients with end‐stage liver disease referred for liver transplantation

Percutaneous coronary intervention (PCI) has traditionally not been an option for patients with end‐stage liver disease (ESLD) and coronary artery disease (CAD). This retrospective study was designed to demonstrate the feasibility and safety of PCI in liver transplant candidates. Patients with ESLD and hemodynamically significant CAD who were otherwise deemed to be acceptable candidates for liver transplantation underwent PCI. The procedural success rates, mortality and myocardial infarction rates, and bleeding outcomes were examined. Sixteen patients with ESLD underwent PCI: 15 with bare‐metal stents (1.3 stents per patient on average) and 1 with balloon angioplasty alone. The median diameter stenosis per lesion was 80%, the median platelet count was 68 × 109/L, the median international normalized ratio was 1.3, and the median Model for End‐Stage Liver Disease score was 13. PCI was successful in 94% of the patients. One patient had a suboptimal residual stenosis of 50% after stenting. There were no in‐hospital or 30‐day deaths or myocardial infarctions, and no patients developed hematomas. One patient required a 1‐U platelet transfusion, and another required 1 U of packed red blood cells. All patients remained clinically stable 1 month after PCI. Nine of the 16 patients were listed for liver transplantation, and 3 patients underwent liver transplantation. In conclusion, we have demonstrated the safety and feasibility of PCI in a small cohort of patients with ESLD and hemodynamically significant CAD, the majority of whom had significant thrombocytopenia. Larger studies are required to determine whether PCI is an effective treatment strategy for patients with ESLD and hemodynamically significant CAD who otherwise would not be candidates for liver transplantation. Liver Transpl 17:809‐813, 2011. © 2011 AASLD.
Non-targeted lipidomics of CSF and frontal cortex grey and white matter in control, mild cognitive impairment, and Alzheimer’s disease subjects

Objective We undertook a non-targeted lipidomics analysis of post-mortem cerebrospinal fluid (CSF), frontal cortex grey matter, and subjacent white matter to define potential biomarkers that distinguish cognitively intact subjects from those with incipient or established dementia. Our objective was to increase our understanding of the role of brain lipids in pathophysiology of aging and age-related cognitive impairment. Methods Levels of 650 individual lipids, across 26 lipid subclasses, were measured utilising a high-resolution mass spectrometric analysis platform. Results Monoacylglycerols (MAG), diacylglycerols (DAG), and the very-long-chain fatty acid 26:0 were elevated in the grey matter of the mild cognitive impairment (MCI) and old dementia (OD) cohorts. Ethanolamine plasmalogens (PlsEtn) were decreased in the grey matter of the young dementia (YD) and OD cohorts while and phosphatidylethanolamines (PtdEth) were lower in the MCI, YD and OD cohorts. In the white matter, decrements in sulphatide levels were detected in the YD group, DAG levels were elevated in the MCI group, and MAG levels were increased in the YD and OD groups. Conclusion The parallel changes in grey matter MAGs and DAGs in the MCI and OD groups suggest that these two cohorts may have a similar underlying pathophysiology; consistent with this, MCI subjects were more similar in age to OD than to YD subjects. While PlsEtn and phosphatidylethanolamine were decreased in the YD and OD groups they were unaltered in the MCI group indicating that alterations in plasmalogen synthesis are unlikely to represent an initiating event in the transition from MCI to dementia.
Efficient human fetal liver cell isolation protocol based on vascular perfusion for liver cell–based therapy and case report on cell transplantation

Although hepatic cell transplantation (CT) holds the promise of bridging patients with end‐stage chronic liver failure to whole liver transplantation, suitable cell populations are under debate. In addition to hepatic cells, mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) are being considered as alternative cell sources for initial clinical cell work. Fetal liver (FL) tissue contains potential progenitors for all these cell lineages. Based on the collagenase incubation of tissue fragments, traditional isolation techniques yield only a fraction of the number of available cells. We report a 5‐step method in which a portal vein in situ perfusion technique is used for tissue from the late second trimester. This method results in the high viabilities known for adult liver vascular perfusion, addresses the low cell yields of conventional digestion methods, and reduces the exposure of the tissue to collagenase 4‐fold. We used donated tissue from gestational weeks 18 to 22, which yielded 1.8 ± 0.7 × 109 cells with an average viability of 78%. Because HSC transplantation and MSC transplantation are of interest for the treatment of hepatic failure, we phenotypically confirmed that in addition to hepatic progenitors, the resulting cell preparation contained cells expressing typical MSC and HSC markers. The percentage of FL cells expressing proliferation markers was 45 times greater than the percentage of adult hepatocytes expressing these markers and was comparable to the percentage of immortalized HepG2 liver hepatocellular carcinoma cells; this indicated the strong proliferative capacity of fetal cells. We report a case of human FL CT with the described liver cell population for clinical end‐stage chronic liver failure. The patient's Model for End‐Stage Liver Disease (MELD) score improved from 15 to 10 within the first 18 months of observation. In conclusion, this human FL cell isolation protocol may be of interest for further clinical translation work on the development of liver cell–based therapies. Liver Transpl 18:226–237, 2012. © 2011 AASLD.
Substance use by liver transplant candidates: An anonymous urinalysis study

Toxicological urinalysis is a highly sensitive and specific test that detects recent substance use. It has been established for substance misuse treatment but has not been routinely used at liver transplantation (LT) centers. Patients with a history of substance misuse are required to be abstinent from alcohol and illicit drugs before they are listed for LT. In this cross‐sectional study, we sought to determine the prevalence of recent substance use in LT candidates via toxicological urinalysis. One hundred nine adults who were admitted for an LT assessment provided data, and they were categorized by the etiology of their liver disease [alcohol‐related liver disease (ALD), hepatitis C virus (HCV), or other liver diseases]. Urine was toxicologically screened for drugs and their metabolites as well as the urinary alcohol metabolites ethyl glucuronide and ethyl sulfate. The prevalence of alcohol metabolites in patients with ALD was 20%. Licit and illicit substances together provided a positive toxicological result in 30% of the patients. Positive results were more common among patients with HCV (40%) and ALD (38%) versus patients with other liver diseases (18%). During the clinical assessment, 4% of the patients with ALD or HCV self‐reported current alcohol or illicit drug use. These results correspond to the findings of other studies and emphasize the uncertainty of self‐reported substance use data for LT candidates. Liver Transpl 17:1200–1204, 2011. © 2011 AASLD.
Sirolimus‐based immunosuppression in liver transplantation for hepatocellular carcinoma: A meta‐analysis

Sirolimus (SRL) is a novel immunosuppressant with antitumor properties. We performed a meta‐analysis to determine whether SRL can improve patient survival and decrease the risks of tumor recurrence in patients with a pretransplant diagnosis of hepatocellular carcinoma (HCC). We searched databases for controlled clinical trials assessing the survival and oncological benefits of SRL for liver transplant recipients with pretransplant HCC. Five studies with a total of 2950 participants were included in this study. In comparison with SRL‐free regimens, SRL‐based regimens improved overall survival at 1 [odds ratio (OR) = 4.53, 95% confidence interval (95% CI) = 2.31‐8.89], 3 (OR = 1.97, 95% CI = 1.29‐3.00), and 5 years (OR = 2.47, 95% CI = 1.72‐3.55). The pooled results showed that in comparison with SRL‐free regimens, SRL‐based regimens decreased tumor recurrence (OR = 0.42, 95% CI = 0.21‐0.83). No significant differences in the frequencies of episodes of major posttransplant complications were observed between the groups. In conclusion, SRL is generally safe and prolongs patient survival in liver transplant recipients with pretransplant HCC. Liver Transpl 18:62–69, 2012. © 2011 AASLD.
Inhibition of p38 mitogen-activated protein kinase pathway as prophylaxis of postoperative ileus in mice.

BACKGROUND & AIMS Postoperative ileus, an iatrogenic complication of abdominal surgery, is mediated by severe inflammation of the tunica muscularis. Macrophages that reside in the muscularis have important roles in initiating the inflammation. We investigated whether activation of the p38 mitogen-activated protein kinase (MAPK) and stress-activated protein kinase is involved in the genesis of postoperative ileus, and whether p38-MAPK inhibition by the macrophage-specific inhibitor semapimod prevents intestinal dysmotility. METHODS Postoperative ileus was induced by intestinal manipulation of the small bowel in mice. Protein kinase phosphorylation was assessed by immunoblotting of muscularis externa preparations. Proinflammatory gene expression was quantified by real-time polymerase chain reaction. Myeloperoxidase histochemistry for neutrophils was performed in jejunal segments. Nitric oxide production was measured by Griess reaction in smooth-muscle organ culture supernatants. Jejunal contractility was assessed within an organ bath setup. Intestinal motility was analyzed by gastrointestinal and colonic transit measurements. RESULTS High levels of p38-MAPK and stress-activated protein kinase phosphorylation were observed immediately after intestinal manipulation. Semapimod treatment led to a significant decrease of p38-MAPK phosphorylation in macrophages; proinflammatory gene expression of macrophage inflammatory protein-1alpha, interleukin-6, monocyte chemoattractant protein-1, and intercellular adhesion molecule-1; and neutrophil infiltration. Furthermore, semapimod completely abrogated nitric oxide production within the tunica muscularis. Subsequently, semapimod prevented the suppression of smooth muscle contractility and small intestinal and colonic motility after intestinal manipulation. CONCLUSION A single preoperative semapimod administration prevents intestinal macrophage activation and subsequent gastrointestinal dysmotility induced by abdominal surgery. Semapimod inhibits p38-MAPK and nitric oxide production in macrophages, making it a promising strategy for prophylaxis of postoperative ileus.
Reduced growth and integrin expression of prostate cells cultured with lycopene, vitamin E and fish oil in vitro

Integrins are transmembrane proteins that facilitate the interaction of cells with the extracellular environment. They have also been implicated in cancer progression. The effects of nutrients thought to be involved in the prevention of prostate cancer on integrin expression have not been determined. Prostate cancer cell lines representing a range of malignancy from normal (RWPE-1) to highly invasive phenotypes (22Rv1 < LNCaP < PC-3) were cultured with or without lycopene (10 nm), vitamin E (5 μm) or fish oil (100 μm) for 48 h. Growth and integrin (α2β1, αvβ3 and αvβ5) expression were assessed using Trypan Blue exclusion and monoclonal antibodies combined with flow cytometry. Vitamin E enhanced (P < 0·001) whereas fish oil reduced the growth of all the cell lines tested (P < 0·001). Lycopene had no effect on growth. All the malignant cell lines exhibited lower expression of α2β1 with the addition of lycopene to culture media. Supplemental fish oil reduced α2β1 in most invasive cell lines (LNCaP and PC-3). Each nutrient at physiological levels reduced integrins αvβ3 and αvβ5 in most invasive cell lines (PC-3). The results suggest that integrins may represent an additional target of bioactive nutrients and that the effects of nutrients may be dependent on the type of cell line used.
A comparison of the effects of soya isoflavonoids and fish oil on cell proliferation, apoptosis and the expression of oestrogen receptors α and β in the mammary gland and colon of the rat

Isoflavonoids and fish oil may be protective against colorectal cancer, but the evidence in relation to breast cancer risk is ambiguous. In the present study, we have investigated the impact of soya-derived isoflavonoids and n-3 fatty acids from fish oil, both individually and in combination, on apoptosis, cell proliferation and oestrogen receptor (ER) expression in the colon and mammary gland of the rat. Female rats were fed diets high in n-3 fatty acids (80 g/kg diet) or soya protein (765 mg/kg diet isoflavones) for 2 weeks, and then killed before the removal of the colon and mammary glands. Cell proliferation and apoptosis were quantified morphologically in whole crypts and terminal end buds. The expressions of ERα and ERβ were measured in colon tissue scrapes and the mammary gland. Fish oil significantly increased apoptosis and decreased mitosis in both tissues, an effect associated with a decrease in the expressions of ERα and ERβ. Soya had no effect on apoptosis in either tissue, but reduced mitosis in the colon (P < 0·001) while increasing it in the mammary gland (P = 0·001). The changes in proliferation were associated with contrasting changes in the ER expression such that fish oil significantly decreased both ERβ and ERα, while soya increased ERα and decreased ERβ. The results may provide a novel mechanism by which n-3 fatty acids could reduce cancer risk, but the interpretation of the results in relation to soya consumption and breast cancer risk requires further investigation.