Miracle-dz/UniFAR-FTUs huggingface dataset:
Adenosine‐dependent activation of hypoxia‐inducible factor‐1 induces late preconditioning in liver cells

The cellular mechanisms by which ischemic preconditioning increases liver tolerance to ischemia/reperfusion injury are still poorly understood. This study investigated the role of the hypoxia‐inducible factor‐1 (HIF‐1) in the protection associated with the late phase of liver preconditioning. Late preconditioning was induced in primary cultured rat hepatocytes by a transient (10 minute) hypoxic stress or by 15 minutes incubation with the adenosine A2A receptors agonist CGS21680 24 hours before exposure to 90 minutes of hypoxia in a serum‐free medium. Late preconditioning induced the nuclear translocation of HIF‐1 and the expression of carbonic anhydrase IX (CAIX), a HIF‐1–regulated transmembrane enzyme that catalyzes bicarbonate production. Such effects were associated with prevention of hepatocyte killing by hypoxia and the amelioration of intracellular acidosis and Na+ accumulation. The inhibition of PKC‐mediated and PI3‐kinase–mediated signals with, respectively, chelerythrine and wortmannin abolished HIF‐1 activation and blocked both CAIX expression and the protective action of late preconditioning. CAIX expression was also prevented by interfering with the transcriptional activity of HIF‐1 using a dominant negative HIF‐1β subunit. The inhibition of CAIX with acetazolamide or the block of bicarbonate influx with disodium‐4‐acetamido‐4′‐isothiocyanato‐stilben‐2,2′‐disulfonate also reverted the protective effects of late preconditioning on intracellular acidosis and Na+ accumulation. Conclusion: The stimulation of adenosine A2A receptors induced late preconditioning in liver cells through the activation of HIF‐1. HIF‐1–induced expression of CAIX increases hepatocyte tolerance to ischemia by maintaining intracellular Na+ homeostasis. These observations along with the importance of HIF‐1 in regulating cell survival indicates HIF‐1 activation as a possible key event in liver protection by late preconditioning. (HEPATOLOGY 2008.)
Proton Therapy for Local-regionally Advanced Breast Cancer Maximizes Cardiac Sparing

Abstract Purpose: To evaluate the potential of proton therapy in sparing cardiac/coronary structures when compared with 3-dimensional conformal radiation therapy (3DCRT), helical tomotherapy (HT), and intensity-modulated radiation therapy using volumetric modulated arc therapy (VMAT). Materials and Methods: Comparative treatment planning was performed using computed tomography scans of 10 patients with left-sided stage III breast cancer after mastectomy, targeting the chest wall, axilla levels I to III, and the supraclavicular and internal mammary nodes (IMN) to 50.4 Gy (radiobiologic equivalent [RBE]) in 28 fractions. Organs at risk were heart, lungs, contralateral breast, unspecified healthy tissues, and coronary arteries. Plans were also compared that included IMNs for protons, but not for photons. Results: Mean heart dose of 1.2 Gy (RBE) was lowest with protons when compared with 6.8, 10.2, and 8.2 Gy for 3DCRT, HT, and VMAT, respectively (P < .05). The mean left anterior descending artery (LAD) dose .
The Subjective Value of "Home" to Older Homeowners

Older individuals generally report a high level of housing satisfaction with their current homes and seldom wish to move, yet most objective measures of the physical quality of their housing suggest that their residential situation is often far from desirable or adequate. The purpose of the present study was to investigate whether a group of subjective values could be identified which might provide a better understanding of the meaning of "home" to older persons. Using factor analytical procedures, four factors were found: (1) traditional family orientation; (2) cost vs. comfort trade-off; (3) status value of homeownership; and (4) competence in familiar environment. Results are discussed in regard to the implications of these subjective-value factors for both public housing and relocation counseling.
Air Pollution and Hospital Admissions for Myocardial Infarction in a Subtropical City: Taipei, Taiwan

This study was undertaken to determine whether there was a correlation between air pollutant levels and hospital admissions for myocardial infarction (MI) in Taipei, Taiwan. Hospital admissions for MI and ambient air pollution data for Taipei were obtained for the period 1996–2006. The relative risk of hospital admissions was estimated using a case-crossover approach, controlling for weather variables, day of the week, seasonality, and long-term time trends. In the single-pollutant models, on warm days (>23°C) statistically significant positive associations were found for all pollutants except sulfur dioxide (SO2). On cool days (<23°C), all pollutants were significantly associated with increased MI admissions except SO2. For the two-pollutant model, ozone (O3) and nitrogen dioxide (NO2) were significant in combination with each of the other four pollutants both on warm and cool days for higher admissions for MI. This study provides evidence that higher levels of ambient air pollutants increase the risk of hospital admissions for MI.
Nitrates in Drinking Water and the Risk of Death from Rectal Cancer: Does Hardness in Drinking Water Matter?

The objectives of this study were to (1) examine the relationship between nitrate levels in public water supplies and increased risk of death from rectal cancer and (2) determine whether calcium (Ca) and magnesium (Mg) levels in drinking water might modify the effects of nitrate on development of rectal cancer. A matched case-control study was used to investigate the relationship between the risk of death from rectal cancer and exposure to nitrate in drinking water in Taiwan. All rectal cancer deaths of Taiwan residents from 2003 through 2007 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cases by gender, year of birth, and year of death. Information on the levels of nitrate-nitrogen (NO3-N), Ca, and Mg in drinking water was collected from Taiwan Water Supply Corporation (TWSC). The municipality of residence for cancer cases and controls was presumed to be the source of the subject's NO3-N, Ca, and Mg exposure via drinking water. Relative to individuals whose NO3-N exposure level was <0.38 ppm, the adjusted odds ratio (OR) (95% CI) for rectal cancer occurrence was 1.15 (1.01–1.32) for individuals who resided in municipalities served by drinking water with a NO3-N exposure ≥0.38 ppm. There was no apparent evidence of an interaction between drinking water NO3-N levels with low Mg intake via drinking water. However, evidence of a significant interaction was noted between drinking-water NO3-N concentrations and Ca intake via drinking water. Our findings showed that the correlation between NO3-N exposure and risk of rectal cancer development was influenced by Ca in drinking water. This is the first study to report effect modification by Ca intake from drinking water on the association between NO3-N exposure and risk of rectal cancer occurrence. Increased knowledge of the mechanistic interaction between Ca and NO3-N in reducing rectal cancer risk will aid in public policymaking and setting threshold standards.
Obesity and steatosis influence serum and hepatic inflammatory markers in chronic hepatitis C

Obesity and fatty liver are commonly observed among patients with chronic hepatitis C virus (HCV) and are risk factors for increased hepatic fibrosis. Obesity is accompanied by a low‐grade, chronic inflammatory response that may contribute to pathogenesis of obesity‐related comorbidities. To assess whether obesity and steatosis potentiate expression of inflammatory markers in chronic HCV, serum protein and hepatic messenger RNA (mRNA) levels of c‐reactive protein (CRP), interleukin‐6 (IL‐6), and tumor necrosis factor‐alpha (TNF‐α) were measured in 171 patients with chronic HCV. The relationships of body mass index, steatosis, histological features of inflammation and fibrosis with serum and hepatic levels of these factors were determined. In comparison with lean patients, overweight and obese subjects had increased circulating (P < 0.001) and hepatic (P = 0.003) CRP, and there was a significant correlation between serum protein and hepatic CRP mRNA levels (rs= 0.51, P < 0.001). Obesity (P = 0.001) and steatosis (P < 0.001) were associated with increased circulating but not hepatic IL‐6, and a weak correlation was seen between serum protein and hepatic IL‐6 mRNA levels (rs= 0.29, P = 0.003). An independent relationship was seen between hepatic TNF‐α mRNA levels and higher total inflammatory score (P < 0.001) and stage of fibrosis (P = 0.037). Subjects with HCV genotype 3 had lower hepatic TNF‐α mRNA levels compared with subjects with genotype 1 (P = 0.017), but there was no relationship between serum TNF‐α protein and hepatic TNF‐α mRNA levels. Conclusion: In patients with chronic HCV, obesity and steatosis are associated with increased expression of selected inflammatory markers; however, circulating levels of IL‐6 and TNF‐α do not reflect hepatic expression. Hepatic TNF‐α was associated with both increased inflammatory activity and hepatic fibrosis, providing support for the key role of this pro‐inflammatory cytokine in liver injury in chronic HCV. (HEPATOLOGY 2008;48:80–87.)
Granulocyte‐colony stimulating factor induces proliferation of hepatic progenitors in alcoholic steatohepatitis: A randomized trial

Liver failure is the major cause of death in alcoholic steatohepatitis (ASH). In experimental hepatitis, granulocyte‐colony stimulating factor (G‐CSF) mobilizes hematopoietic stem cells, induces liver regeneration, and improves survival. We studied the short‐term effects of G‐CSF on CD34+ stem cell mobilization, liver cell proliferation, and liver function in patients with ASH. Twenty‐four patients (mean age 54 years) with alcoholic cirrhosis [Child‐Turcotte‐Pugh score 10 (7–12)] and concomitant biopsy‐proven ASH [Maddrey score 36 (21‐60)] were randomized to standard care associated with 5 days of G‐CSF (10 μg/kg/day, group A, n = 13) or standard care alone (group B, n = 11). Serial measurement of CD34+ cells, liver tests, cytokines [hepatocyte growth factor (HGF); tumor necrosis factor α; tumor necrosis factor‐R1; interleukin‐6; alfa‐fetoprotein], and 13C‐aminopyrine breath tests were performed. Proliferating hepatic progenitor cells [HPC; double immunostaining (Ki67/cytokeratin 7)], histology, and neutrophils were assessed on baseline and day 7 biopsies. Abstinent alcoholic patients with cirrhosis served as controls for immunohistochemistry. G‐CSF was well tolerated. At day 7, both CD34+ cells (+747% versus −6%, P < 0.003), and HGF (+212% versus −7%, P < 0.03) increased in group A but not in group B. Cytokines and aminopyrine breath test changes were similar between groups. On repeat biopsy, a >50% increase in proliferating HPC was more frequent in group A than in group B (11 versus 2, P < 0.003). Changes in Ki67+/cytokeratin 7+ cells correlated with changes in CD34+ cells (r = 0.65, P < 0.03). Neutrophils and histological changes were similar in both groups. Conclusion: G‐CSF mobilizes CD34+ cells, increases HGF, and induces HPC to proliferate within 7 days of administration. Larger trials would be required to determine whether these changes translate into improved liver function. (HEPATOLOGY 2008.)
Rhinitis Associated with Pesticide Use Among Private Pesticide Applicators in the Agricultural Health Study

Farmers commonly experience rhinitis but the risk factors are not well characterized. The aim of this study was to analyze cross-sectional data on rhinitis in the past year and pesticide use from 21,958 Iowa and North Carolina farmers in the Agricultural Health Study, enrolled 1993–1997, to evaluate pesticide predictors of rhinitis. Polytomous and logistic regression models were used to assess association between pesticide use and rhinitis while controlling for demographics and farm-related exposures. Sixty-seven percent of farmers reported current rhinitis and 39% reported 3 or more rhinitis episodes. The herbicides glyphosate [odds ratio (OR) = 1.09, 95% confidence interval (95% CI) = 1.05–1.13] and petroleum oil (OR = 1.12, 95% CI = 1.05–1.19) were associated with current rhinitis and increased rhinitis episodes. Of the insecticides, four organophosphates (chlorpyrifos, diazinon, dichlorvos, and malathion), carbaryl, and use of permethrin on animals were predictors of current rhinitis. Diazinon was significant in the overall polytomous model and was associated with an elevated OR of 13+ rhinitis episodes (13+ episodes OR = 1.23, 95% CI = 1.09–1.38). The fungicide captan was also a significant predictor of rhinitis. Use of petroleum oil, use of malathion, use of permethrin, and use of the herbicide metolachlor were significant in exposure-response polytomous models. Specific pesticides may contribute to rhinitis in farmers; agricultural activities did not explain these findings.
Oral Parenteral Antimicrobial Therapy Administration in a Homeless Population

Outpatient parenteral antimicrobial therapy (OPAT) is increasingly used to treat serious infections. Patients who identify themselves as homeless may receive OPAT less often, and little is known about their treatment outcomes. The purpose of this study was to describe challenges, treatment completion rates, and cost savings of OPAT in homeless patients discharged from a public safety-net hospital.
Peripheral Infiltration and Extravasation Injury Methodology: A Retrospective Study

Peripheral infiltration is defined as the inadvertent delivery of nonvesicant fluid or medication into surrounding tissue that has the potential to harm the patient. Vesicant fluid that has leaked into the tissue space is called extravasation. At present, there is no agreement in the literature on the best practice for managing these injuries in pediatric patients. The purpose of this study was to identify occurrences of peripheral infiltration injuries and examine treatment modalities used to treat pediatric patients who suffered such an injury.
Occlusion Reduction and Heparin Elimination Trial Using an Antireflux Device on Peripheral and Central Venous Catheters

Catheter occlusion and thrombosis are common problems associated with central venous catheters, peripherally inserted central catheters, and peripheral intravenous catheters. A prospective study was performed at a community hospital to determine whether an antireflux valve device would reduce the frequency of complications in these catheters and safely allow the elimination of heparin flushes for central venous catheters and peripherally inserted central catheters. The study compared complications with current intravenous practice to complication rates for the antireflux valve device. The study used evidence obtained during this trial to institute the best clinical practice.
Visceral fat: A key mediator of steatohepatitis in metabolic liver disease

Visceral obesity is intimately associated with metabolic disease and adverse health outcomes. However, a direct association between increasing amounts of visceral fat and end‐organ inflammation and scarring has not been demonstrated. We examined the association between visceral fat and liver inflammation in patients with nonalcoholic fatty liver disease (NAFLD) to delineate the importance of visceral fat to progressive steatohepatitis and hence the inflammatory pathogenesis of the metabolic syndrome. We undertook a cross‐sectional, proof of concept study in 38 consecutive adults with NAFLD at a tertiary liver clinic. All subjects had a complete physical examination, anthropometric assessment, and fasting blood tests on the day of liver biopsy. Abdominal fat volumes were assessed by magnetic resonance imaging within 2 weeks of liver biopsy. The extent of hepatic inflammation and fibrosis augmented incrementally with increases in visceral fat (P < 0.01). For each 1% increase in visceral fat, the odds ratio for increasing liver inflammation and fibrosis was 2.4 (confidence interval [CI]: 1.3‐4.2) and 3.5 (CI: 1.7‐7.1), respectively. Visceral fat remained an independent predictor of advanced steatohepatitis (odds ratio [OR] 2.1, CI: 1.1‐4.2, P = 0.05) and fibrosis (OR 2.9, CI: 1.4‐6.3, P = 0.006) even when controlled for insulin resistance and hepatic steatosis. Interleukin‐6 (IL‐6) levels, which correlated with visceral fat, also independently predicted increasing liver inflammation. Visceral fat was associated with all components of the metabolic syndrome. Conclusion: Visceral fat is directly associated with liver inflammation and fibrosis independent of insulin resistance and hepatic steatosis. Visceral fat should therefore be a central target for future interventions in nonalcoholic steatohepatitis and indeed all metabolic disease. (HEPATOLOGY 2008.)
Nitrates in Drinking Water and the Risk of Death from Childhood Brain Tumors in Taiwan

The objective of this study was to (1) examine the relationship between nitrate (NO3-N) levels in public water supplies and risk of death from childhood brain tumors (CBT) and (2) determine whether calcium (Ca) and magnesium (Mg) levels in drinking water might modify the effects of NO3-N on development of CBT. A matched cancer case-control study was used to investigate the relationship between the risk of death attributed to CBT and exposure to NO3-N in drinking water in Taiwan. All CBT deaths of Taiwan residents from 1999 through 2008 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cases by gender, year of birth, and year of death. Information on the levels of nitrate-nitrogen (NO3-N), Ca, and Mg in drinking water were collected from Taiwan Water Supply Corporation. The municipality of residence for CBT cases and controls was presumed to be the source of the subject's NO3-N, Ca, and Mg exposure via drinking water. Relative to individuals whose NO3-N exposure level was ≤0.31 ppm, and the adjusted odds ration (OR) (95% confidence interval [CI]) for CBT occurrence was 1.4 (1.07–1.84) for individuals who resided in municipalities served by drinking water with a NO3-N exposure >0.31 ppm. No significant effect modification was observed by Ca and Mg intake via drinking water. Data suggest that exposure to NO3-N in drinking water is associated with a higher risk of CBT development in Taiwan.
Geno- and Immunotoxic Effects on Populations Living Near a Mine: A Case Study of Panasqueira Mine in Portugal

Mining industry is a vital economic sector for many countries but it is also one of the most hazardous activities, both occupationally and environmentally. Existing studies point to several adverse effects on communities' health living near mines, effects such as mesothelioma and respiratory illnesses. Results achieved in a geochemical sampling campaign undertaken in the vicinity of São Francisco de Assis village showed an anomalous distribution of some heavy metals in soils and waters. To evaluate the effects of mining activities on human health produced by these conditions, a group of 28 individuals from São Francisco de Assis village was examined for some biological endpoints. A nonexposed group (30 individuals) with the same demographic characteristics without exposure to genotoxic compounds was also studied and data obtained from both groups compared. Results of the T-cell receptor mutation assay and micronucleus (MN) test showed significant increases in the frequencies of both mutations and MN in exposed subjects compared to controls. Data obtained in the analysis of the different lymphocyte subsets demonstrated significant decreases in percentages of CD3+ and CD4+ cells, and a significant increase in percentage of CD16/56+ cells, in exposed individuals. The results of the present study indicate an elevated risk of human environmental contamination resulting from mining activities, emphasizing the need to implement preventive measures, remediation, and rehabilitation plans. This would lead to a reduction in cancer risk not only for this particular population but for all populations exposed under similar conditions.
Long-Term Response of Rats to Single Intratracheal Exposure of Libby Amphibole or Amosite

In former mine workers and residents of Libby, Montana, exposure to amphibole-contaminated vermiculite has been associated with increased incidences of asbestosis and mesothelioma. In this study, long-term effects of Libby amphibole (LA) exposure were investigated relative to the well-characterized amosite asbestos in a rat model. Rat-respirable fractions of LA and amosite (aerodynamic diameter ≤2.5 μm) were prepared by water elutriation. Male F344 rats were exposed to a single dose of either saline, amosite (0.65 mg/rat), or LA (0.65 or 6.5 mg/rat) by intratracheal (IT) instillation. One year after exposure, asbestos-exposed rats displayed chronic pulmonary inflammation and fibrosis. Two years postexposure, lung inflammation and fibrosis progressed in a time- and dose-dependent manner in LA-exposed rats, although the severity of inflammation and fibrosis was smaller in magnitude than in animals exposed to amosite. In contrast, gene expression of the fibrosis markers Col 1A2 and Col 3A1 was significantly greater in LA-exposed compared to amosite-exposed rats. There was no apparent evidence of preneoplastic changes in any of the asbestos-exposed groups. However, all asbestos-exposed rats demonstrated a significant increase in the expression of epidermal growth factor receptor (EGFR) 2 yr after instillation. In addition, only LA-exposed rats showed significant elevation in mesothelin (Msln) and Wilms' tumor gene (WT1) expression, suggesting possible induction of tumor pathways. These results demonstrate that a single IT exposure to LA is sufficient to induce significant fibrogenic, but not carcinogenic, effects up to 2 yr after exposure that differ both in quality and magnitude from those elicited by amosite administration at the same mass dose in F344 rats. Data showed that LA was on a mass basis less potent than amosite.
Natural killer T cell dysfunction in CD39‐null mice protects against concanavalin A–induced hepatitis

Concanavalin A (Con A)–induced injury is an established natural killer T (NKT) cell–mediated model of inflammation that has been used in studies of immune liver disease. Extracellular nucleotides, such as adenosine triphosphate, are released by Con A–stimulated cells and bind to specific purinergic type 2 receptors to modulate immune activation responses. Levels of extracellular nucleotides are in turn closely regulated by ectonucleotidases, such as CD39/NTPDase1. Effects of extracellular nucleotides and CD39 on NKT cell activation and upon hepatic inflammation have been largely unexplored to date. Here, we show that NKT cells express both CD39 and CD73/ecto‐5′‐nucleotidase and can therefore generate adenosine from extracellular nucleotides, whereas natural killer cells do not express CD73. In vivo, mice null for CD39 are protected from Con A–induced liver injury and show substantively lower serum levels of interleukin‐4 and interferon‐γ when compared with matched wild‐type mice. Numbers of hepatic NKT cells are significantly decreased in CD39 null mice after Con A administration. Hepatic NKT cells express most P2X and P2Y receptors; exceptions include P2X3 and P2Y11. Heightened levels of apoptosis of CD39 null NKT cells in vivo and in vitro appear to be driven by unimpeded activation of the P2X7 receptor. Conclusion: CD39 and CD73 are novel phenotypic markers of NKT cells. Deletion of CD39 modulates nucleotide‐mediated cytokine production by, and limits apoptosis of, hepatic NKT cells providing protection against Con A–induced hepatitis. This study illustrates a further role for purinergic signaling in NKT‐mediated mechanisms that result in liver immune injury. (HEPATOLOGY 2008.)