Miracle-dz/UniFAR-FTUs huggingface dataset:
Miners Compensated for Pneumoconiosis and Glutathione S-Transferases M1 and T1 Genotypes

Chronic inhalation of quartz-containing dust produces reversible inflammatory changes in lungs resulting in irreversible fibrotic changes termed pneumoconiosis. Due to the inflammatory process in the lungs, highly reactive substances are released that may be detoxified by glutathione S-transferases. Therefore, 90 hard coal miners with pneumoconiosis as a recognized occupational disease (in Germany: Berufskrankheit BK 4101) were genotyped for glutathione S-transferases M1 (GSTM1) and T1 (GSTT1) according to standard methods. Furthermore, occupational exposure and smoking habits were assessed by questionnaire. Changes in a chest x-ray were classified according to ILO classification 2000. Of the investigated hard coal miners 43% were GSTM1 negative whereas 57% were GSTM1 positive. The arithmetic mean of the age at time of investigation was 74.2 yr (range: 42–87 yr). Seventy-four percent of the hard coal miners reported being ever smokers, while 26% denied smoking. All hard coal miners provided pneumoconiosis-related changes in the chest x-ray. The observed frequency of GSTM1 negative hard coal miners was not different from frequencies reported for general Caucasian populations and in agreement with findings reported for Chinese coal miners. In contrast, in a former study, 16 of 19 German hard coal miners (84%) with urinary bladder cancer displayed a GSTM1 negative genotype. The outcome of this study provides evidence that severely occupationally exposed Caucasian hard coal miners do not present an elevated level of GSTM1 negative individuals.
In Vivo Molecular Imaging Characterizes Pulmonary Gene Expression During Experimental Lung Transplantation

Experimental gene therapy is a promising strategy to prevent ischemia‐reperfusion (I/R) injury and allograft rejection after lung transplantation, and methods will eventually be needed to characterize pulmonary transgene expression in vivo in humans. Therefore, we studied positron emission tomography (PET) as a means of performing in vivo molecular imaging in rodent models of lung transplantation. Rats were transfected endotracheally with adenovirus encoding a fusion gene of a mutant Herpes simplex virus‐1 thymidine kinase and the green fluorescent protein gene (the former serving as an imaging reporter gene). Twenty‐four hours after transfection, lungs were transplanted in groups representing normal transplantation, I/R injury and acute allograft rejection. Imaging was obtained either 24 h after transplantation to study reperfusion injury or 4 days after transplantation to study graft rejection. After imaging, lungs were excised and analyzed for thymidine kinase activity. Imaging detected transgene expression in transplanted lungs even in the presence of acute rejection or I/R injury. The PET imaging signal correlated with in vitro lung tissue assays of thymidine kinase activity (r2= 0.534). Thus, noninvasive molecular imaging with PET is a feasible, sensitive and quantitative method for characterizing pulmonary transgene expression in experimental lung transplantation.
Inflammatory stress exacerbates lipid accumulation in hepatic cells and fatty livers of apolipoprotein E knockout mice

The prevailing theory in non‐alcoholic fatty liver disease (NAFLD) is the “two‐hit” hypothesis. The first hit mainly consists of lipid accumulation, and the second is subsequent systemic inflammation. The current study was undertaken to investigate whether inflammatory stress exacerbates lipid accumulation in liver and its underlying mechanisms. We used interleukin‐1β (IL‐1β) and tumor necrosis factor alpha (TNF‐α) stimulation in human hepatoblastoma cell line (HepG2) cells and primary hepatocytes in vitro, and casein injection in apolipoprotein E knockout mice in vivo to induce inflammatory stress. The effects of inflammatory stress on cholesterol accumulation were examined by histochemical staining and a quantitative intracellular cholesterol assay. The gene and protein expressions of molecules involved in cholesterol trafficking were examined by real‐time polymerase chain reaction (PCR) and western blot. Cytokine production in the plasma of apolipoprotein E knockout mice was measured by enzyme‐linked immunosorbent assay. Our results showed that inflammatory stress increased cholesterol accumulation in hepatic cells and in the livers of apolipoprotein E knockout mice. Further analysis showed that inflammatory stress increased the expression of low‐density lipoprotein (LDL) receptor (LDLr), sterol regulatory element–binding protein (SREBP) cleavage activating protein (SCAP), and SREBP‐2. Confocal microscopy showed that IL‐1β increased the translocation of SCAP/SREBP‐2 complex from endoplasmic reticulum (ER) to Golgi in HepG2 cells, thereby activating LDLr gene transcription. IL‐1β, TNF‐α, and systemic inflammation induced by casein injection also inhibited expression of adenosine triphosphate–binding cassette transporter A1 (ABCA1), peroxisome proliferator‐activated receptor‐α (PPAR‐α), and liver X receptor‐α (LXRα). This inhibitory effect may cause cholesterol efflux reduction. Conclusion: Inflammatory stress up‐regulates LDLr‐mediated cholesterol influx and down‐regulates ABCA1‐mediated cholesterol efflux in vivo and in vitro. This may exacerbate the progression of NAFLD by disrupting cholesterol trafficking control, especially during the second hit phase of liver damage. (HEPATOLOGY 2008.)
Occurrence of Cryptosporidium in a Wastewater Treatment Plant in North Germany

Cryptosporidium parvum is one of the most common human parasitic protozoa and is responsible for many waterborne outbreaks in several industrialized countries. The oocyst, which is the infective form, is known to be highly resistant to wastewater treatment procedures and represents a potential hazard to human populations through contaminated raw or treated wastewater. In this investigation, the occurrence of Cryptosporidium in wastewater samples was monitored and removal efficiency was assessed. Treated (effluent) and untreated (influent) wastewater samples were collected seasonally over a period of 2 years. Oocysts were repeatedly detected in influent and effluent samples collected from the treatment plant during all sampling seasons, with a mean concentration of 782 oocysts/L. The seasonal distribution showed that oocysts are predominant during autumn and winter. Molecular analyses via the small (18S) subunit of rRNA amplification and subsequent sequencing with an objective of characterizing the oocysts revealed that Cryptosporidium parvum was the dominant Cryptosporidium parasite present in wastewater.
A Phase II Multicenter Study of Two Different Dosages of Pemetrexed Given in Combination With Cyclophosphamide as First-Line Treatment in Patients With Locally Advanced or Metastatic Breast Cancer

Pemetrexed/cyclophosphamide was evaluated as first-line treatment for patients with locally advanced/metastatic breast cancer. In this randomized phase II study (NCT00190671), therapy consisted of either 600 mg/m2 (P600) or 1,800 mg/m2 (P1800) pemetrexed, followed by 600 mg/m2 cyclophosphamide, every 21 days; 103 females (42 P600; 61 P1800) were enrolled. P600 was discontinued, as response rate (19.1%) was lower than targeted. In the P1800 arm, 20 patients had partial response (32.8%; 95% CI: 21.0–44.6) and 26 (42.6%) had stable disease. Median progression-free survival was 6.3 months (range: 0.3–31.1). P1800 plus cyclophosphamide 600 represents a regimen of reasonable efficacy and acceptable tolerability.
Age-Specific Absolute and Relative Organ Weight Distributions for Fischer 344 Rats

The Fischer 344 (F344) rat has been the standard rat strain used in toxicology studies conducted by the National Cancer Institute (NCI) and the National Toxicology Program (NTP). However, the numerous reports published to date on growth, survival, and tumor incidence have not included an overall compilation of organ weight data. Notably, dose-related organ weight effects are endpoints used by regulatory agencies to develop toxicity reference values (TRVs) for use in human health risk assessments. In addition, physiologically-based pharmacokinetic (PBPK) models, which utilize relative organ weights, are increasingly being used to develop TRVs. Because a compilation of organ weights for F344 rats could prove beneficial for TRV development and PBPK modeling, all available absolute and relative organ weight data for untreated control F344 rats were collected from NCI/NTP feed, drinking-water, and inhalation studies in order to develop age-specific distributions. Results showed that organ weights were collected more frequently at 2-wk (59 studies), 3-mo (148 studies), and 15-mo (38 studies) intervals than at other intervals and more frequently from feeding and inhalation than from drinking-water studies. Liver, right kidney, lung, heart, thymus, and brain weights were most frequently collected. From the collected data, the mean and standard deviation for absolute and relative organ weights were calculated. Findings showed age-related increases in absolute weights and decreases in relative weights for brain, liver, right kidney, lung, heart, thyroid, and right testis. The results suggest a general variability trend in absolute organ weights of brain < right testis < heart < right kidney < liver < lung < thymus < thyroid.
Antigenotoxic Properties of Chlorophyll b Against Cisplatin-Induced DNA Damage and its Relationship with Distribution of Platinum and Magnesium In Vivo

The chemotherapeutic agent cisplatin (cDDP) is widely used to treat a variety of solid and hematological tumors. However, cDDP exerts severe side effects, such as nephrotoxicity, neurotoxicity, and bone-marrow suppression. The use of some dietary compounds to protect organs that are not targets in association with chemotherapy has been encouraged. This study evaluated the protective effects of chlorophyll b (CLb) on DNA damage induced by cDDP by use of single-cell gel electrophoresis (SCGE) assays. Further, this investigation also determined platinum (Pt) and magnesium (Mg) bioaccumulation in mice tissues after treatment with CLb alone and/or in association of cDDP (simultaneous treatment) by inductively coupled plasma–mass spectroscopy (ICP-MS). All parameters were studied in peripheral blood cells (PBC), kidneys, and liver of mice after administration of CLb (0.2 or 0.5 mg/kg of body weight [b.w.]), cDDP (6 mg/kg b.w.), and the combination CLb 0.2 plus cDDP or CLb 0.5 plus cDDP. Pt accumulation in liver and kidneys was higher than that found in PBC, while DNA damage was higher in kidneys and liver than in PBC. Further, treatment with CLb alone did not induce DNA damage. Evidence indicates that genotoxic effects produced by cDDP may not be related to Pt accumulation and distribution. In combined treatments, CLb decreased DNA damage in tissues, but the PT contents did not change and these treatments also showed that CLb may be an important source of Mg. Thus, our results indicate that consumption of CLb-rich foods may diminish the adverse health effects induced by cDDP exposure. We are grateful to Joana D'Arc Castania Darin and Mara Ribeiro de Almeida (FCFRP-USP) for their technical assistance. The authors would like to thank São Paulo Foundation Research (FAPESP 2005/59552-6, 2008/06793-4, and 2010/05096-8), the National Council of Technological and Scientific Development (CNPq), and Coordination for the Improvement of Higher Level Education Personnel (CAPES) for financial support.
Prevalence and risk correlates of hypertension among adult rural population in Bihar

Background: Cardiovascular diseases will be prime cause of morbidity by 2020 in India. Objective: To determine prevalence and correlates of hypertension in an adult rural community. Materials and Methods: A cross-sectional study was carried out in the field practice area of the Department of Community Medicine of tertiary care teaching institute of Bihar among adult population to find out the prevalence of hypertension with the sociodemographic correlates from October 2009 to September 2010. A pretested predesigned questionnaire was used to collect sociodemographics data by interview technique from 997 study participants. The blood pressure was assessed and classified using recent JNC 7 and WHO criteria to grade hypertension. Results: Majority of the study participants were Muslims (89%) and in 40-49 age group (21.26%). In males and females, the overweight and obese combined were, respectively, 13%. In the dietary habit, 85.36% were non-vegetarian; 8.83% consumed salt more than 10 grams per day; 26.78% reported themselves as alcoholics; tobacco smokers were 58.28%, highest in 40-49 age group (23.58%). Overall, 11.43% were hypertensive and 16% were prehypertensive. Among hypertensive, majority were male (61%); and in 60-69 age group (27.27%), overweight and obese (56.14%), smokers (75.44%), non-vegetarian (67.54%). There was a significant linear trend between age and salt intake with prevalence of hypertension (P<0.0001). Conclusions: Hypertension in the rural population of Bihar was lower than previous estimates.
A randomized trial of combination hepatitis B therapy in HIV/HBV coinfected antiretroviral naïve individuals in Thailand

Coinfection with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) is associated with considerable liver disease morbidity and mortality. Emerging HIV epidemics in areas of high HBV endemicity such as Asia are expanding the population with HIV/HBV coinfection. Limited randomized trial data exist to support current guidelines for HBV combination therapy in HIV/HBV coinfection. The objective of this prospective randomized clinical trial was to compare the strategy of HBV monotherapy with lamivudine (LAM) or tenofovir disoproxil fumarate (TDF) versus HBV combination therapy with LAM/TDF in antiretroviral‐naïve HIV/HBV‐coinfected subjects in Thailand. Thirty‐six HIV/HBV‐coinfected subjects initiating highly active antiretroviral therapy (HAART) were randomized to either LAM (arm 1), TDF (arm 2), or LAM/TDF (arm 3) as HBV‐active drugs within HAART. At week 48, time‐weighted area under the curve analysis revealed that the median HBV DNA reduction from baseline was 4.07 log10 c/mL in arm 1, 4.57 log10 c/mL in arm 2, and 4.73 log10 c/mL in arm 3 (P = 0.70). HBV DNA suppressed to <3 log10 c/mL in 46% in arm 1, 92% in arm 2, and 91% in arm 3 (P = 0.013, intent‐to‐treat analysis). HBV‐resistant changes were detected in two subjects, both in arm 1. Hepatitis B e antigen (HBeAg) loss was observed in 33% of HBeAg‐positive subjects, and 8% experienced hepatitis B surface antigen loss. Hepatic flare was observed in 25% of subjects. Conclusion: LAM monotherapy resulted in a greater proportion of subjects with HBV DNA >3 log10 c/mL at week 48 and in early resistance development. This study confirms current treatment guidelines that recommend a TDF‐based regimen as the treatment of choice for HIV/HBV coinfection, but does not demonstrate any advantage of HBV combination therapy in this short‐term setting. (HEPATOLOGY 2008.)
Evaluation of repatriation parameters: does medical history matter?

BACKGROUND Aeromedical repatriation of patients is an expanding service due to the growing number of travelers worldwide. Of these repatriated patients, a small number require specialized transportation due to severe medical complications. We evaluated the medical in-flight records of Dutch patients with severe disease or polytrauma who were repatriated by air from 1998 to 2002 via one of the largest Dutch alarm centers. We questioned how this Dutch population of repatriated patients is demographically distributed and whether this population is a priori at high risk for acute medical complications that need specialized medical attention. RESULTS Seventy-seven of 115 repatriated patients were 50 years and older, of which most were male (73%). Fifty patients had no significant medical history, whereas the remaining 65 patients suffered from comorbidities such as cardiovascular disease or cancer. In patients aged 18 to 49 years, one third of all patients were repatriated due to traumatic fractures. In the older age category, the main reasons for repatriation were cardiopulmonary incidents. There was an equal distribution in the primary medical reason for repatriation as defined by need for trauma/neurological support and ventilation or circulatory support. Of note, 82% of the 65 patients who traveled with a chronic disease condition were repatriated due to worsening of this particular condition. CONCLUSIONS The present study shows that an aeromedical repatriation service is frequently employed by travelers with a history of chronic disease who develop medical complications. The growing number of repatriated elderly patients and/or patients with preexisting comorbidities requires development of secure pretravel risk assessment and adaptation of the medical service level in foreign countries.
Outside the Box: Dear Ofcare . . .

I was pleased to hear that you're going to start levying fines on naughty NHS organisations that don't keep up standards. I've always been a believer that the punishment should fit the crime, so I herewith enclose some suggestions. Firstly, I'd like you to pop into Seddle ward in St Fritters' Hospital (take the lift to the top floor, end of the corridor, first right) and set about that slovenly sister with the red hair. She wouldn't know a care protocol from the 263 bus timetable. And according to the woman I met in surgical outpatients, she's got a fancy man from Supplies whom she meets in the sluice while the student nurses are doing the drugs round. I'd respectfully suggest a two-year compulsory secondment to that nunnery at the top of the hill. While you're at St Fritters, you should pay a visit to Catering. When my next-door neighbour was in having her gallbladder out, they kept sending up those cook-chill dinners (cooked on the outside, chilled on the inside, according to Gloria). And she found a human hair in the casserole. Personally, I'd make the head chef go on one of those Jamie Oliver courses and put up “five a day” posters in every ward at his own expense. I don't really want to complain about the little cottage hospital as it's so convenient for my hip physio, but I'll do my duty. My nephew went to the A&E with a rugby injury (somewhere near the groin—I didn't like to ask). Apparently, the doctor's tie dragged right across the lad's pubes when he was examining him. Five minutes later, he was bending over a cot and the kiddy grabbed his tie and stuffed it in its mouth. It's a difficult one this, because I think they're all as bad as each other, so I recommend all the male doctors in that hospital should wear bow-ties for 12 months. One final tip-off. The GP surgery on the corner of the High St has got a receptionist with a loose tongue. I was in the queue behind her in Asda the other day and she was spilling the beans about Mrs Connors' biopsy. What she needs in my view is for her smutty little diary to be scanned in and put on the practice website so the rest of us can poke our noses into her private business. I do hope these suggestions help. Good luck with the new regulator. Mildred Trotterby
The Role of Iron Impurities in the Toxic Effects Exerted by Short Multiwalled Carbon Nanotubes (MWCNT) in Murine Alveolar Macrophages

Lung toxicity mediated by multiwalled carbon nanotubes (MWCNT) has been widely demonstrated and recently associated with induction of carcinogenic asbestos-like effects, but the chemical features that drive this toxic effect have still not been well elucidated. The presence of metals as trace contaminants during MWCNT preparation, in particular iron (Fe) impurities, plays an important role in determining a different cellular response to MWCNT. Our goal was to clarify the mechanisms underlying MWCNT-induced toxicity with correlation to the presence of Fe impurities by exposing murine alveolar macrophages to two different MWCNT samples, which differed only in the presence or absence of Fe. Data showed that only Fe-rich MWCNT were significantly cytotoxic and genotoxic and induced a potent cellular oxidative stress, while Fe-free MWCNT did not exert any of these adverse effects. These results confirm that Fe content represents an important key constituent in promoting MWCNT-induced toxicity, and this needs to be taken into consideration when planning new, safer preparation routes.
Certolizumab pegol therapy of rheumatoid arthritis: Overview

First‐line treatment for moderate to severe rheumatoid arthritis (RA) has been the use of disease‐modifying anti‐rheumatic drugs (DMARDs), e.g., methotrexate. Because of the cases of failure reported to respond to available treatments, newer RA drugs including tumor necrosis factor (TNF‐α) blockers have emerged. Certolizumab pegol (CZP) is a unique polyethylene glycolated (PEG) humanized monoclonal antibody designed specifically to target TNF‐α pro‐inflammatory cytokine. Given that its properties closely reflect its PEG fragment, CZP has demonstrated a clear efficiency. Pharmacokinetics and pharmacodynamics of CZP are described together with Phase II and III CZP clinical studies focused on CZP efficiency and safety. We also discuss the future of CZP and new clinical studies that might help physicians in their choice of CZP among available TNF‐α blockers. Drug Dev Res 72:603–614, 2011. © 2011 Wiley Periodicals, Inc.
31-Day Study of Cobalt(II) Chloride Ingestion in Humans: Pharmacokinetics and Clinical Effects

The United Kingdom Expert Group on Vitamins and Minerals concluded that ingesting cobalt (Co)-containing supplements up to 1400 μg Co/d is unlikely to produce adverse health effects. However, the associated blood Co concentrations and safety of Co-containing dietary supplements have not been fully characterized. Thus, blood Co kinetics and a toxicological assessment of hematological and biochemical parameters were evaluated following Co dietary supplementation in 5 male and 5 female volunteers who ingested approximately 1000 μg Co/d (10-19 μg Co/kg-d) as cobalt(II) chloride for a period of 31 d. Supplement intake was not associated with significant overt adverse events, alterations in clinical chemistries including blood counts and indicators of thyroid, cardiac, liver, or kidney functions, or metal sensitization. A non-clinically significant (<5%) increase in hemoglobin, hematocrit, and red blood cell (RBC) counts were observed in males but not females 1 wk after dose termination. Mean Co concentrations in whole blood/serum after 31 d of dosing were approximately two-fold higher in females (33/53 μg/L) than in males (16/21 μg/L). In general, steady-state concentrations of Co were achieved in whole blood and/or red blood cells (RBC) within 14–24 d. Temporal patterns of whole blood and serum Co concentrations indicated metal sequestration in RBC accompanied by slower whole blood clearance compared to serum. Data also indicated that peak whole blood Co concentrations up to 91.4 μg/L were not associated with clinically significant changes in clinical chemistries. In addition, Co blood concentrations and systemic uptake via ingestion were generally higher in females.