Miracle-dz/UniFAR-FTUs huggingface dataset:
Obeticholic acid, a farnesoid X receptor agonist, improves portal hypertension by two distinct pathways in cirrhotic rats

The farnesoid X receptor (FXR) is a nuclear bile acid receptor involved in bile acid homeostasis, hepatic and intestinal inflammation, liver fibrosis, and cardiovascular disease. We studied the effect of short‐term treatment with obeticholic acid (INT‐747), a potent selective FXR agonist, on intrahepatic hemodynamic dysfunction and signaling pathways in different rat models of cirrhotic portal hypertension (PHT). For this, thioacetamide (TAA)‐intoxicated and bile‐duct–ligated (BDL) rats were used as models. After gavage of two doses of 30 mg/kg of INT‐747 or vehicle within 24 hours, in vivo hemodynamics were assessed. Additionally, we evaluated the direct effect of INT‐747 on total intrahepatic vascular resistance (IHVR) and intrahepatic vascular tone (endothelial dysfunction and hyperresponsiveness to methoxamine) by means of an in situ liver perfusion system and on hepatic stellate cell contraction in vitro. FXR expression and involved intrahepatic vasoactive pathways (e.g., endothelial nitric oxide synthase [eNOS], Rho‐kinase, and dimethylarginine dimethylaminohydrolase [DDAH]) were analyzed by immunohistochemistry, reverse‐transcriptase polymerase chain reaction, or western blotting. In both cirrhotic models, FXR expression was decreased. Treatment with INT‐747 in TAA and BDL reactivated the FXR downstream signaling pathway and decreased portal pressure by lowering total IHVR without deleterious systemic hypotension. In the perfused TAA and BDL cirrhotic liver, INT‐747 improved endothelial vasorelaxation capacity, but not hyperresponsiveness. In both groups, this was associated with an increased eNOS activity, which, in TAA, related to down‐regulation of Rho‐kinase and in BDL to up‐regulation of DDAH‐2. Conclusion: FXR agonist INT‐747 improves PHT in two different rat models of cirrhosis by decreasing IHVR. This hemodynamic effect relates to increased intrahepatic eNOS activity by pathways that differ depending on the etiology of cirrhosis. (Hepatology 2014;59:2286–2298)
Development of a Sampling Patch to Measure Dermal Exposures to Monomeric and Polymeric 1,6-Hexamethylene Diisocyanate: A Pilot Study

The purpose of this study was to develop and evaluate a patch sampler to monitor dermal exposures to monomeric and polymeric 1,6-hexamethylene diisocyanate (HDI) in the automotive refinishing industry. Different patch materials were used to construct the patches, and patches impregnated with a derivatizing solution were compared with those that were not impregnated. We observed that impregnated felt patches measured significantly more HDI monomer (p = 0.04) than non-impregnated patches in a controlled experiment. Both impregnated and non-impregnated patches were compared with the tape-strip method by monitoring three spray painters’ dermal exposure to monomeric and polymeric HDI. Isocyanurate was the predominant species measured by all three sampler types with detectable levels in >86% of samples. Overall, tape-strips of exposed skin measured lower levels of monomeric and polymeric HDI than impregnated patch samplers at the same sampling site on the skin. Unlike tape-strips, impregnated patches are not as prone to evaporative or reactive losses or losses due to rapid penetration into the skin. Further investigations are warranted to evaluate these and other methods to measure dermal exposure to workers under occupational conditions to better understand the relationship between dermal exposure and internal dose.
Is there Still Enough Diagnostic Confidence with Bone Spect Scintigraphy Alone: A Retrospective Evaluation and Extended Review of the Literature

Aim: Single photon emission computed tomography (SPECT) dramatically increases the sensitivity of bone scanning for detection of spinal abnormalities. However, the level of specificity obtained by SPECT remains controversial and increased diagnostic confidence can be obtained with new imaging modalities such as fused PET/CT and SPECT/CT. Patients and Methods: Between 7/2005 and 7/2007 ninety one patients with different malignant primary tumors were in- vestigated. Following injection of 555 MBq 99m Tc - MDP planar and SPECT images were performed in all patients. Re- sults: Out of a total of 145 spinal lesions was confirmed by radiography, SPECT detected 133 (91%). In contrast, planar scintigraphy detected only 99/145 (68%) lesions. SPECT uptake pattern including the vertebral body and an adjacent pedicle was seen in 9/28 (32%) of metastatic lesions and in 1/2 (50%) cases of spondylitis. SPECT uptake pattern includ- ing the pedicle alone was seen in 45/115 (39%) of degenerative alterations. Focal lesions limited to the lateral part of the vertebral body, especially to the pars interarticularis (n=8), facet joints (n=14) and costotransversal joints (n=6), were cor- rectly diagnosed as spondylarthrosis and costotransversalarthrosis in all cases. Furthermore, SPECT uptake pattern of spondylitis was biconcave, whereas metastatic lesions showed focal or linear uptakes. Conclusion: SPECT without image fusion still gives sufficient diagnostic confidence for the differentiation of benign and malignant spine lesions. Uptake pat- terns localized at the facet joints or localized at the pedicles are indicative for benign lesions, whereas continuous uptake patterns of the vertebral body and adjacent pedicle remain suspicious for malignancy.
Reduced adiponectin signaling due to weight gain results in nonalcoholic steatohepatitis through impaired mitochondrial biogenesis

Obesity and adiponectin depletion have been associated with the occurrence of nonalcoholic fatty liver disease (NAFLD). The goal of this study was to identify the relationship between weight gain, adiponectin signaling, and development of nonalcoholic steatohepatitis (NASH) in an obese, diabetic mouse model. Leptin‐receptor deficient (Leprdb/db) and C57BL/6 mice were administered a diet high in unsaturated fat (HF) (61%) or normal chow for 5 or 10 weeks. Liver histology was evaluated using steatosis, inflammation, and ballooning scores. Serum, adipose tissue, and liver were analyzed for changes in metabolic parameters, messenger RNA (mRNA), and protein levels. Leprdb/db HF mice developed marked obesity, hepatic steatosis, and more than 50% progressed to NASH at each timepoint. Serum adiponectin level demonstrated a strong inverse relationship with body mass (r = −0.82; P < 0.0001) and adiponectin level was an independent predictor of NASH (13.6 μg/mL; P < 0.05; area under the receiver operating curve (AUROC) = 0.84). White adipose tissue of NASH mice was characterized by increased expression of genes linked to oxidative stress, macrophage infiltration, reduced adiponectin, and impaired lipid metabolism. HF lepr db/db NASH mice exhibited diminished hepatic adiponectin signaling evidenced by reduced levels of adiponectin receptor‐2, inactivation of adenosine monophosphate activated protein kinase (AMPK), and decreased expression of genes involved in mitochondrial biogenesis and β‐oxidation (Cox4, Nrf1, Pgc1α, Pgc1β and Tfam). In contrast, recombinant adiponectin administration up‐regulated the expression of mitochondrial genes in AML‐12 hepatocytes, with or without lipid‐loading. Conclusion: Leprdb/db mice fed a diet high in unsaturated fat develop weight gain and NASH through adiponectin depletion, which is associated with adipose tissue inflammation and hepatic mitochondrial dysfunction. We propose that this murine model of NASH may provide novel insights into the mechanism for development of human NASH. (Hepatology 2014;60:133–145)
Asphalt Fume Exposure Levels in North American Asphalt Production and Roofing Manufacturing Operations

This study extends by 8 years (1998–2005) a previous survey of asphalt fume exposures within North American asphalt processing and roofing product manufacturing workers. It focuses on characterizing personal, full-shift samples and seeks to address several limitations of the previous survey. Five major roofing manufacturers with established occupational health programs submitted workplace asphalt fume sampling results to a central repository for review and analysis. A certified industrial hygienist-led quality assurance team oversaw the data collection, consolidation, and analysis efforts. The analysis dataset consisted of 1261 personal exposure samples analyzed for total particulate (TP) and benzene soluble fraction (BSF) using existing NIOSH methods. For BSF, the survey's arithmetic (0.25 mg/m3, SD = 0.62) and geometric (0.12 mg/m3, GSD = 2.88) means indicate that the industry has sustained the control levels achieved in the late 1980s, early 1990s. Similar results were found for TP. The survey-wide summary statistics are consistent with other post-1990 multi-company exposure studies. Although these findings indicate that currently available controls are capable of achieving substantial (95%) compliance with the current threshold limit value in asphalt processing and inorganic shingle and roll plants, they also show that the majority of plants are not achieving this level of exposure control, and that exposures are significantly higher in plants making other product lines, particularly organic felt products. The current retrospective survey of existing company exposure data, like its predecessor, has several important limitations. These include lack of data on smaller manufacturers and on several commercially important product lines; insufficient information on the prevalence and effectiveness of engineering controls; no standard criteria by which to define and assess exposures in non-routine operations; and a paucity of exposure data collected as part of a random sampling strategy. To improve efforts to characterize exposures and potential health risks in roofing plants, a prospective program is currently being developed and piloted with the aim of building a more complete, higher-quality database based on a common industrial hygiene protocol.
Acceptability of a Guided Imagery Intervention for Persons Undergoing a Total Knee Replacement

BACKGROUND: Guided imagery (GI) has been recommended as a mind–body therapy for pain relief following orthopaedic surgery, but little is known about the acceptability of the intervention. PURPOSE: Describe the perceptions of patients undergoing total knee replacement (TKR) surgery regarding the acceptability of a customized GI intervention to promote TKR outcomes. METHODS: Narrative and survey data collected during a randomized controlled trial of the GI intervention were analyzed to assess the acceptability of the intervention. RESULTS: Most participants were satisfied with and actively engaged in the intervention, and they perceived it to be helpful. For the smaller group of participants who did not find the intervention to be acceptable, reasons for dissatisfaction and barriers to engagement were identified. CONCLUSIONS: Guided imagery is an acceptable intervention for many persons undergoing TKR surgery. The results of this study can provide information to further develop a targeted and customized GI intervention for this population.
A Randomized Controlled Trial of an Individualized Preoperative Education Intervention for Symptom Management After Total Knee Arthroplasty

Pain and nausea limit recovery after total knee arthroplasty (TKA) patients. The aim of this study was to determine the effect of a preoperative educational intervention on postsurgical pain-related interference in activities, pain, and nausea. Participants (n = 143) were randomized to intervention or standard care. The standard care group received the usual teaching. The intervention group received the usual teaching, a booklet containing symptom management after TKA, an individual teaching session, and a follow-up support call. Outcome measures assessed pain, pain interference, and nausea. There were no differences between groups in patient outcomes. There were no group differences for pain at any time point. Respondents had severe postoperative pain and nausea and received inadequate doses of analgesia and antiemetics. Individualizing education content was insufficient to produce a change in symptoms for patients. Further research involving the modification of system factors affecting the provision of symptom management interventions is warranted.
Disruption of negative feedback loop between vasohibin‐1 and vascular endothelial growth factor decreases portal pressure, angiogenesis, and fibrosis in cirrhotic rats

Pathological angiogenesis represents a critical hallmark for chronic liver diseases. Understanding the mechanisms regulating angiogenesis is essential to develop new therapeutic strategies that specifically target pathological angiogenesis without affecting physiological angiogenesis. Here we investigated the contribution and therapeutic impact of the endogenous angioinhibitor vasohibin‐1 in portal hypertension and cirrhosis. The spatiotemporal expression profiling of vasohibin‐1 and its relationship with vascular endothelial growth factor (VEGF), angiogenesis, and fibrogenesis was determined through the analysis of human cirrhotic liver specimens, widely accepted in vivo animal models of portal hypertension and cirrhosis, and in vitro angiogenesis assays. Effects of vasohibin‐1 overexpression by adenoviral‐mediated gene transfer on angiogenesis, fibrogenesis, and portal hypertension‐associated hemodynamic alterations were also studied in rats. We found that vasohibin‐1 and VEGF are up‐regulated, in mesentery and liver, in cirrhotic and precirrhotic portal hypertensive rats and cirrhosis patients. Our results are consistent with vasohibin‐1/VEGF cascades being spatially and temporally coordinated through a negative‐feedback loop driving pathological angiogenesis. Paradoxically, further overexpression of vasohibin‐1 by adenoviral gene transfer exerts multifold beneficial effects in portal hypertension and cirrhosis: reduction of pathologic angiogenesis, attenuation of liver fibrogenesis partly mediated through inhibition of hepatic stellate cell activation, and significant decreases in portocollateralization, splanchnic blood flow, portohepatic resistance, and portal pressure. The explanation for this apparent contradiction is that, unlike endogenous vasohibin‐1, the ectopic overexpression is not regulated by VEGF and therefore disrupts the negative‐feedback loop, thus generating constant, but lower levels of VEGF synthesis sufficient to maintain vascular homeostasis but not pathological angiogenesis. Conclusion: Our study provides evidence that vasohibin‐1 regulates portal hypertension‐associated pathological angiogenesis and highlights that increasing vasohibin‐1 might be a promising novel therapeutic strategy for portal hypertension and cirrhosis. (Hepatology 2014;60:633–647)
Unmet Need of Emergency Contraceptives: The Curious Scenario of Female Undergraduates in the Niger Delta.

Background: The high morbidity and mortality among young women from unsafe abortions resulting from unwanted pregnancy and teenage pregnancy are mostly as a result of low contraceptive usage especially emergency contraceptives (EC). This is often due to restricted availability, limited knowledge, worries about side effects and future fertility, underestimation of pregnancy risk, high cost, religious and cultural barriers. Objectives: This study aimed to assess the knowledge, use and unmet need of emergency contraceptives among female undergraduates of the Niger Delta University. Methods: This is a cross sectional study conducted in July 2013 among 450 female students who were randomly selected using the multi-stage sampling technique. Data were collected with the aid of a pre-tested, structured self-administered questionnaire. Epi-Info 3.5. 3 was used for data entry
Cadaveric surgery: a novel approach to teaching clinical anatomy

Introduction: Anatomy is an essential basic science for safe and effective medical practice. In 2006 the UK Anatomy Act was changed to allow the use of surgical procedures on cadavers. This has unlocked opportunities for new methods of teaching clinically relevant anatomy. This study explores how surgical procedures may provide a purposeful and memorable way for undergraduates to learn anatomy, compared with conventional teaching methods.
Transcriptional profiling of pure fibrolamellar hepatocellular carcinoma reveals an endocrine signature

Fibrolamellar hepatocellular carcinoma (FLC) is a rare subtype of liver cancer occurring mostly in children and young adults. We have shown that FLC comprises two separate entities: pure (p‐FLC) and mixed‐FLC (m‐FLC), differing in clinical presentation and course. We show that p‐FLCs have a distinct gene expression signature different from that of m‐FLCs, which have a signature similar to that of classical hepatocellular carcinomas. We found p‐FLC profiles to be unique among 263 profiles related to diverse tumoral and nontumoral liver samples. We identified two distinct molecular subgroups of p‐FLCs with different outcomes. Pathway analysis of p‐FLCs revealed ERBB2 overexpression and an up‐regulation of glycolysis, possibly leading to compensatory mitochondrial hyperplasia and oncocytic differentiation. Four of the sixteen genes most significantly overexpressed in p‐FLCs were neuroendocrine genes: prohormone convertase 1 (PCSK1); neurotensin; delta/notch‐like EGF repeat containing; and calcitonin. PCSK1 overexpression was validated by immunohistochemistry, yielding specific, diffuse staining of the protein throughout the cytoplasm, possibly corresponding to a functional form of this convertase. Conclusion: p‐FLCs have a unique transcriptomic signature characterized by the strong expression of specific neuroendocrine genes, suggesting that these tumors may have a cellular origin different from that of HCC. Our data have implications for the use of genomic profiling for diagnosis and selection of targeted therapies in patients with p‐FLC. (Hepatology 2014;59:2228–2237)
Sorafenib use in hepatocellular carcinoma: More questions than answers

A lmost 2 years ago, an article with the title “Field-Practice Study of Sorafenib Therapy for Hepatocellular Carcinoma: A Prospective Multicenter Study in Italy” by Iavarone et al. was published in this journal. To date, the conclusions of this article continue to stimulate discussion. In their attempt to better identify the role of sorafenib in the setting of broad nonclinical trial use, Iavarone et al. conducted an observational study right after the phase III randomized study of sorafenib versus placebo (SHARP trial) reported an improved median overall survival (OS) outcome of 10.7 versus 7.9 months in favor of sorafenib. The key outcomes of this observational study conducted by Iavarone et al. were a similar median survival of 10.5 months and a toxicity profile analagous to the SHARP trial. The key issues under question are the correlation of improved outcome in association with a lower dose of sorafenib; the prediction of outcome based on side effects; and the use of the modified Response Evaluation Criteria in Solid Tumors (mRECIST). The intent of this editorial is to help elucidate those points and draw some practical conclusions that apply to the use of sorafenib in the clinical setting.
Temporal Variation of Size-Fractionated Particulate Matter and Carbon Monoxide in Selected Microenvironments of the Milan Urban Area

This article focuses on air pollution in specific urban microenvironments and conditions characterized by high relative concentration levels and by possible risk to human health. For this reason, monitoring of particle number concentration (PNC) with a wide, size-resolved particle-size range, and CO (an indicator of combustion sources, e.g., traffic), was performed in a variety of microenvironments. Concentrations of ultrafine particles (UFPs), size-fractionated particulate matter (PM), and carbon monoxide (CO) were measured in the central area of Milan over three-week-long periods, one each during summer, autumn, and winter, with three monitoring sessions per day. Experimental data were collected continuously during each monitoring period along an established urban pathway. To assess the relevance of time and spatial factors affecting atmospheric concentrations of UFPs, PM, and CO data were collected while walking or moving by different private and public means of transport. Measurements were divided on the basis of different microenvironments (MEs), seasons, days of the week, and periods of the day. Data analysis shows statistically significant differences across MEs and monitoring periods. The highest measured median concentrations and data variability were observed for busy streets, walking or moving by motorized vehicle (CO, UFP) and in metro trains (PM); the lowest concentrations were observed in park areas and in indoor environments. The highest concentrations were measured during working day morning monitoring sessions. Regarding seasonal variation, UFP, PM, and CO showed different patterns: the highest median concentrations were observed in summer for CO, and in autumn and winter for the UFP and PM. Appreciable differences among all MEs and monitoring periods were observed: concentration patterns and variations appear related to typical sources of urban pollutants (traffic), proximity to sources, and time of day. [Supplementary materials are available for this article. Go to the publisher's online edition of Journal of Occupational and Environmental Hygiene for the following free supplemental resource: a file containing Table VI: Tau b (Kendall) index for non–parametric correlation tau test. ]
Respirable Dust and Respirable Silica Exposure in Ontario Gold Mines

A comprehensive survey of respirable dust and respirable silica in Ontario gold mines was conducted by the Ontario Ministry of Labor during 1978–1979. The aim was to assess the feasibility of introducing gravimetric sampling to replace the assessment method which used konimeters, a device which gave results in terms of number of particles per cubic centimeter (ppcc) of air. The study involved both laboratory and field assessments. The field assessment involved measurement of airborne respirable dust and respirable silica at all eight operating gold mines of the time. This article describes the details of the field assessment. A total of 288 long-term (7–8 hr) personal respirable dust air samples were collected from seven occupational categories in eight gold mines. The respirable silica (α-quartz) was determined by x-ray diffraction method. The results show that during 1978–1979, the industry wide mean respirable dust was about 1 mg/m3, and the mean respirable silica was 0.08 mg/m3.The mean% silica in respirable dust was 7.5%. The data set would be useful in future epidemiological and health studies, as well as in assessment of workers’ compensation claims for occupational diseases such as silicosis, chronic obstructive pulmonary disease (COPD), and autoimmune diseases such as renal disease and rheumatoid arthritis.